Summary

In this week’s issue,

• Leon Tang summarizes and reflects on his week-long trip in Shanghai for the popular Evercore China Biotech Summit and iSWT Community’s Shanghai Reception.

• moderated iSWTC Boston panel and captured how three panelists — from VC, law, and biotech — pushed the conversation past “China speed” as a novelty toward the harder question of whether that speed can be paired with patient capital, institutional trust, and durable science to make China a genuine global innovation engine. (Paid Content)

Dispatch from Shanghai: Inside the Booming China Biotech Ecosystem

Greetings from China! As I wrap up my two-week China workation trip, I find myself energized by the sheer velocity of innovation happening here (and by a few days vacation in Inner Mongolia). The pulse of cross-border collaboration is beating faster than ever. From high-table discussions outside presentation rooms to private dinners running late into the night, the energy in China’s biotech sector is palpable—and the global industry is paying close attention.

Highlights of the 2nd Evercore China Biotech Summit

Walking through the halls of the Summit, the sheer scale of the ecosystem was on full display with nearly 60 local biotechs presenting. What struck me most wasn’t just the numbers, but the velocity.

Take VelaVigo, a company founded in November 2021 and a former client, for example, they have managed to sprint from a preclinical company at the 1st Evercore Summit to a clinical company with 4 clinical assets in just one year.

Between sessions, the chatter among Western investors and execs was a mix of genuine awe and strategic caution. There is a deep respect for the R&D and capital efficiency here—the “China speed” is real. However, we also discussed the elephant in the room: market crowding. It feels like every table has a GLP-1 candidate or a KRAS inhibitor, and the oncological space is getting tight with PD-1 multi-specifics. Innovation is high, but the race to the same finish lines is creating a unique kind of pressure.

Outside the presentation room, attendees also dove into the shifting regulatory landscape, specifically the “brake” being applied to the Investigator-Initiated Trial (IIT) system. The shadow of Degree 818 and recent safety concerns due to the three deaths from IIT trials led to a period of intense self-regulation. One CEO mentioned that while we saw about a thousand applications in 2026, we have slowed to a trickle since May, with only about ten new IIT trial approvals. It’s a necessary maturation phase, but for those of us on the ground, the contrast to the previous breakneck pace is startling.

iSWT Community/BioKatalyst Shanghai Reception

Beyond the summit, community building remains at the heart of what we do. On behalf of the iSWT Community, Joyce Zhang and I were thrilled to co-organize a special reception alongside BioKatalyst for our members who were in Shanghai IFC this week.

It turned out to be a wonderfully intimate and deeply insightful event where almost 70 guests showed up. A special thanks goes to Seamus (Yonghua) Jiang from BioKatalyst for co-hosting, and to Lu Han from Imviva, Daniel Rosan from Ascidian Therapeutics, Ying Yang from Sanofi, Ahmed Mousa from Vicore Pharma, and Chengfei Yuan for sharing such incredible, on-the-ground insights with the community.

As Ying Yang from Sanofi aptly summarized, the impact of the rise of China’s biotech sector on the global pharmaceutical industry is evolving, disruptive, and inevitable. It is evolving as China increasingly leads in specific modalities and best-in-class therapies while first-in-class innovations continue to emerge. The sector is proving disruptive by fundamentally influencing the R&D models and global pricing strategies of big pharma. Finally, this shift is inevitable because the deep knowledge and technical skills accumulated within China’s biotech ecosystem cannot be unlearned, nor can the established infrastructure be unwound.

Reflections from My Shanghai Biotech Trip

My conversations with executives from both hemispheres confirmed several strategic shifts that are redefining the cross-border landscape.

Western biopharma companies are increasingly embracing China’s R&D infrastructure, driven by looming patent cliffs and mounting US drug pricing pressures. During my trip, I observed Western biotech CEOs actively hunting for opportunities to access China’s competitive R&D, either by in-licensing or forming strategic collaborations. This trend is further supported by major investment funds—such as RA Capital, OrbiMed, Vivo Capital, Venrock, TCGx, MPM Bioimpact, and more—which are establishing local incubators, while smaller funds explore novel ways to leverage China’s ecosystem. Additionally, many seasoned serial entrepreneurs are now choosing to build their next companies here, drawn by the competitive early-stage R&D and vast talent pool.

The strategic pull is reinforced by undeniable economics: with per-capita healthcare costs approximately ten times lower than in the US, China offers a vastly more efficient clinical trial ecosystem without sacrificing quality in a meaningful way.

To put a human face on these macro trends, a long-time friend recently shared that she is relocating to China to launch her next company. She is the quintessential US biotech success story: an immigrant with a PhD degree, years of big pharma R&D experience, and successful launch of 2 Boston-based startups. That she has decided her third act belongs not in Kendall Square, but in a Chinese biotech hub, speaks volumes about where the center of gravity is shifting.

My friend’s move serves as a reminder to the global community: to succeed in this new era of biotech, we must “Stay Hungry, Stay Foolish.”

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

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Summary

In this week’s issue,

• gives a postmortem of a potential AstraZeneca-Bristol Myers Squibb merger, which now appears to be dead.

• examines the US biopharma ROI crisis, shifting clinical trial regulations in China caused by recent IIT scandals, and the severe moral risks of US-China biotech decoupling.

• revisits Forte Biosciences’ little-known proxy war to show how boardroom decisions—not just laboratory discoveries—helped transform a failed single-asset biotech into a $2.2 billion acquisition by Argenx.

iSWTC Boston Chapter will hold an in-person panel discussion "From China Speed to Global Value: How China-Origin Innovation Is Reshaping Global Biopharma." Our paid subscriber can attend the event at Lexington on Aug 22nd for free. Please find the free code at the paid content area.

About 100 life sciences executives have joined our Shanghai Conference Hangout 2026 networking group on WeChat. Many of our readers are going to healthcare conferences or visiting China biotech in Yangtze River Delta area this summer. Scan the QR code to join the group.Please include your name, affiliation, and title when requesting to join. Contact for any questions.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

In July and August, our newsletter is published every two weeks. We will come back to weekly schedule in September.

A Postmortem of AZ-BMS

A merger between AstraZeneca and Bristol Myers Squibb is likely not to be. The two companies do not have any ongoing discussions about a potential deal, Reuters reported this week, citing a senior source close to the matter. But examining the case is still a valuable exercise.

When the Financial Times broke the news that the two had held talks and described the discussions as ongoing by using a present tense, I wrote an editorial on Fierce Pharma laying out how their combination would be a bad idea.

“Combining the two drugmakers would trigger severe regulatory concerns and significant pipeline disruptions, not to mention cost numerous jobs, all while damaging the broader biopharma ecosystem and hurting patients,” I wrote in that article.

My arguments were mainly as follows. Unlike Takeda with Shire, AstraZeneca does not need a large acquisition to buy commercial scale in the U.S. With a robust—and growing—U.S. business already, AZ can simply expand its U.S. presence organically, even though it takes a bit longer than one big scoop.

The firms have major overlaps in their therapeutic interest (immune checkpoint inhibitors, ADCs, cell therapies), which will inevitably trigger significant antitrust investigations, which in itself would be a big distraction. Whether the final entity will be based in the U.S. or the U.K. would also be subject to intense scrutiny from the other country.

Besides, integrating the two massive R&D engines would cause another distraction, potentially delaying development timelines. In a LinkedIn post, John LaMattina, a senior partner at PureTech Health, who was formerly president of Pfizer global R&D, said a merger would put the two firms’ R&D organizations in “turmoil for at least 18 months.”

To make the deal math work, the combined firm would undergo major organizational and pipeline overhauls, potentially cost thousands of jobs while leading to fewer therapies for patients.

The challenge of large pharma M&A was “always that R&D productivity appeared to fall further during the merger period as employees understandably focused on job risks during integration,” UBS analysts, who described themselves as “surprised” by the merger reports, wrote in a note on Aug. 3.

More broadly, such a megadeal would dampen the biotech M&A sentiment because it would signal a retreat to financial engineering versus targeted pursuit of biotech innovation. In exchange for buying global commercial scale and rare disease diversification with Shire, Takeda was weighed down by debt for a long time, limiting its ability to pursue other business development opportunities. In a widely circulated note, Jefferies’ analysts argued that AZ is the last company that needs financial engineering.

Following my editorial, I got some interesting feedback—and some vicious Trump-styled attacks.

One venture capitalist argued that some molecules could be spun off to biotechs, where they may get an acceleration. However, even if that turned out to be the case, I suspect that its scale would be too limited to compensate for the damage.

For one thing, Big Pharma is way more inclined to kill or shelve assets than out-licensing or spinning them out. Negotiating deals requires additional resources and is therefore way more complicated. Some assets may even be direct competitors to the seller’s internal pipeline and are chopped mainly for business reasons.

Alternatively, in a sale enforced by antitrust authorities, the fact that the portfolio/asset has caught the attention of regulators means its scale could be too big for a biotech to handle. In this case, a transfer of ownership would pose another distraction rather than acceleration.

A medicinal chemist then pointed out that Big Pharma doesn’t have a flawless track record in divesting assets. BMS’ Cobenfy, bought from its $14 billion acquisition of Karuna, was originally developed and shelved by Eli Lilly. There’s also Roche’s famous $7.1 billion-upfront deal for Telavant and its anti-TL1A drug RVT-3101, which was spun off by Pfizer.

I don’t have a complete understanding tracking projects spun out of Big Pharma, so I acknowledge it’s possible biotechs could strike gold from the aftermath of an AZ-BMS merger, but I’d also caution about survivorship bias.

On the financial side, as UBS analysts noted, large pharma M&A was a feature of the previous industry patent cliffs. Larger bolt-on transactions such as AZ-Alexion have been successful “as they have added an additional new adjacency to the acquirer rather than overlapping operations,” they wrote.

Buying revenue could solve near-term patent cliffs but they rarely add much underlying value. Just five years after buying Wyeth in 2009 to fill its Lipitor patent cliff, Pfizer would find it necessary to try absorbing AZ.

Whether BMS’ Celgene deal is worth it is also up for debate. From a pure return-on-capital perspective, the sale of Otezla to Amgen and the massive Revlimid revenues have likely made it up to BMS and allowed the New Jersey pharma to pursue subsequent bolt-on deals like Karuna. But Revlimid’s patent cliff hit BMS hard, contributing to its current unstable position ahead of the expected losses of exclusivity of its two biggest products, Eliquis and Opdivo, around 2028.

AZ faces its own patent cliff. Its timeline—early 2030s for Imfinzi, Tagrisso and Calquence—appears complementary to BMS’. But on the flip side, BMS’ portfolio will mute AZ’s growth toward 2030, and the combined firm will have to deal with LOEs for an even longer period.

Word of the talks has rattled AZ investors, and its stock has struggled to regain ground since the FT report.

, Deputy Editor of Fierce Pharma and iSWTC volunteer

Why “Biotech Walls” Will Fail Patients (and Markets)

In the past few weeks, policymakers are scrambling to erect legislative barriers to contain the rise of China biotech—like the Outbound Investment Regulations and the Biotech Investment National Security Act (BINSA)—but these “Biotech Walls” are being outpaced by a market-driven reality. For the US biopharma industry, US-China cross-border collaboration isn’t just another strategy but an essential mechanism to survive the current ROI crisis caused by some self-inflicted policy headwinds.

The “Trans-Pacific Biotech Relay” Overcomes “Biotech Walls”

This month, public and private capital markets delivered an undeniable validation of what I call the “Trans-Pacific Biotech Relay”—a model where China’s hyper-efficient early R&D engine handles the early sprint of discovery, passing the baton to Western biotechs for late-stage registrational trials and global commercialization, a concept shared in my joint ThinkChina article published last week, co-authored with Prof Xiangming Chen.

Two recent capital market successes highlight the value of collaboration - San Francisco-based Braveheart Bio raised $382.5 million via IPO to advance BHB-1893—a cardiac candidate licensed from Hengrui Pharmaceuticals; while Avere Therapeutics secured $320 million post-reverse merger to develop AVR-001, an IL-23 inhibitor licensed from Hansoh Pharmaceutical for $120 million upfront. Both deals exemplify how US firms accelerate development by integrating Chinese-discovered assets.

This public market momentum is mirrored by spectacular Chinese assets-backed M&A exits in 2026. San Diego-based Candid Therapeutics leveraged China’s clinical trial speed to generate a robust human data package, resulting in a $2.2 billion acquisition by European pharma UCB just 20 months after inception. This follows the lucrative M&A exits of $2.2 billion acquisition of RAPT Therapeutics and ~$1.7 billion acquisition of Ouro Medicines earlier this year, reinforcing that one of the fastest paths to venture-scale returns in 2026 lies in a trans-Pacific collaboration.

The Boston Debate: Internal Bottlenecks vs. Foreign Bogeyman

At the recent Live from Boston live event by Endpoints news, leading biopharma minds confronted the structural ROI crisis in US drug development.

Strand Therapeutics CEO Jake Becraft noted that because promising scientific discoveries are now copied and raced into trials almost instantly, pure science is no longer a durable differentiator. Instead, Becraft argued that the US must radically reform its clinical infrastructure to improve the ROI of the US biotech industry, rather than relying on technological protectionism.

Meanwhile, Pfizer’s Andrew Baum took aim at the domestic policy decisions that are truly depressing biopharma returns, calling out the industry’s use of China as a political scapegoat:

“So if you look at the bulk of the damage to industry returns, it’s not created by China, it’s created by actions that we are taking ourselves.… China is a nice bogeyman to go after. But really it’s taking the heat away from what should be the focus of those two factors [IRA and MFN]”

The Inflation Reduction Act (IRA) and the Most Favored Nation (MFN) pricing policies—which tie US drug prices to lower international benchmarks—represent a far more existential threat to US biopharma ROI than China biotech.

By the way, many went to the event to watch the debate between Peter Kolchinsky and Jason Kelly - they certainly did not disappoint.

The IIT Safety Reckoning: Normalizing the “China Speed” Advantage

For years, China’s physician-led Investigator-Initiated Trials (IITs) served as a major competitive advantage, bypassing traditional regulatory sign-offs to run rapid, low-cost first-in-human studies. However, a series of safety and transparency crises are actively reshaping this landscape.

A monthslong STAT investigation recently revealed that a young boy died of acute respiratory distress syndrome (ARDS) during a high-dose study in HuidaGene’s CRISPR gene-editing trial for Duchenne muscular dystrophy in Shanghai in August 2025. This tragedy follows a report by Science that a 6-year-old girl with a rare autism-like disorder died in an IIT in Shanghai in March 2025. In that case, researchers undisclosed the death, publishing mouse data in Nature with no mention of the human fatality. The latest investigative report by 南方周末 provides a lot more details.

In response to these incidents, China’s regulatory agencies are tightening oversight. Under the recently enacted Order 818, IITs are now restricted exclusively to top-tier “3A hospitals” and require rigorous non-clinical evaluations and institutional ethics board approvals.

This regulatory tightening will likely slow down the IIT pace and normalize China’s first-in-human clinical trial advantages. While this reduces the raw speed advantage, it will elevate the quality, GCP compliance, and international credibility of Chinese clinical data—a net positive for long-term global licensing.

The Moral Cost of Decoupling

As outlined in our recent ThinkChina analysis, “Why China’s biotech rise is harder to contain than AI,” biotech is not like semiconductors. It is a physical, deeply interconnected global value chain. The US biopharma sector remains heavily dependent on China for critical active pharmaceutical ingredients (APIs), including 95% of imported ibuprofen, 70% of acetaminophen, and 40–45% of penicillin. Meanwhile, China produces 40% of the world’s new drug candidates entering clinical trials.

Decoupling is no longer just an economic risk but a clinical and moral hazard. US healthcare spending per capita is approximately nine times that of China. If US patients—who are already paying so much more than Chinese patients for healthcare—get the next generation of miraculous cancer or genetic therapies much later than Chinese patients because of political friction, it will represent a catastrophic failure of our industry, our policy makers, and the United States government.

As I concluded in the article: Disease has no borders; neither should we.

Invitation to Executive Shanghai Networking Group

Are you a Western biopharma executive planning a business trip to China or attending healthcare conferences in Shanghai this Summer?

We invite you to apply to join our selective WeChat networking group that currently have ~100 members consisting of cross-border VCs, biopharma BD professionals, and biotech executives sharing on-the-ground intelligence and coordination. Please scan the WeChat QR code below to join.

Note: Please include your name, affiliation, and title in your application request. Please message me on WeChat (ID: LeonTangBiotech) if you request is not approved in time.

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

The Boardroom Was as Important as the Laboratory

How Forte Biosciences survived a shareholder revolt, absorbed its critics, and turned governance reform into a $2.2 billion exit

When a biotech loses its lead asset, everyone immediately focuses on the science. Yet the first crisis is often not scientific — it is in the boardroom. Forte Biosciences’ path to a $2.2 billion acquisition by Argenx this July (Fierce News) looked, in hindsight, like a clean story of scientific conviction rewarded. It wasn’t. Before FB102 ever reached a patient who mattered to the outcome, Forte spent two years fighting for its own survival in proxy statements, SEC filings, and a Delaware courtroom. That boardroom battle may not have determined whether FB102 worked—but it helped determine whether Forte survived long enough to find it out.

A Company Trading Below Its Own Cash

In September 2021, Forte’s only clinical asset, FB-401 — a topical biologic for atopic dermatitis — missed its primary endpoint in Phase 2. For a single-asset biotech, that is close to an existential event. The company had cash, but no story. FB-102, the compound that would eventually justify a $2.2 billion valuation, surfaced almost invisibly — a line item in a 10-K filed the following spring, with little accompanying narrative about why it deserved the company’s remaining capital (Forte 10K 2022).

That vacuum is what activist investors are built to exploit, and one moved quickly. Braden Leonard’s BML Investment Partners began accumulating Forte stock in March 2022, paying roughly $1.55 per share. Within two months it was Forte’s largest shareholder, at nearly 9%. The math behind BML’s public letter to CEO Paul Wagner in May 2022 was simple and, on its face, hard to dispute: Forte’s cash alone was worth an estimated $2.50–$2.60 per share in an orderly liquidation — roughly 40% above where the stock was trading (Fierce News). BML wasn’t proposing a bet on FB-102’s science. It was proposing to close a straightforward valuation gap between market price and cash in the bank, and it said so plainly: absent a liquidation plan, it wanted a tender offer or a large dividend so skeptical holders could recoup their cash. BML’s thesis wasn’t built on immunology. It was built on balance-sheet arithmetic.

Forte’s response was defensive rather than explanatory. In July 2022 the board adopted a stockholder rights plan — a poison pill — engineered with specific thresholds: 10% ownership would trigger it for most investors, 20% for passive institutional holders filing the lighter-touch Schedule 13G. BML was already at 8.9%. In practice, the pill capped BML roughly where it stood, without stopping it from writing letters, nominating directors, or running a future proxy contest. It was a scalpel, not a wall — but it was still a wall built around one activist’s specific position. Whether the poison pill bought management the time needed to execute its strategy—or unnecessarily delayed shareholder scrutiny—became one of the central questions of the governance debate.

The Proxy War

Camac Partners entered a few months later, in August 2022, buying into a thesis BML had already made public — Forte trading at roughly a 40% discount to its own cash. By 2023, Camac and its allies at ATG Capital Management had built an 8.5% stake and were preparing something more serious than a letter: a full proxy contest, with their own director nominees, Michael Hacke and Chris McIntyre, running against incumbents Paul Wagner and Lawrence Eichenfield ahead of the September 2023 annual meeting.

What followed is worth reading in the companies’ and investors’ own words, because both sides made real arguments rather than simply trading insults.

Camac’s core complaint was that Forte’s board had become bloated and insulated relative to its actual operations — the company (Camac letter to stock holder, Rebuttal to Forte). Camac pointed out, “only six employees – yet has an eight-member Board of Directors”, burning roughly $7 million a quarter. Camac also flagged that Forte’s share count had grown from under 15 million to over 36 million shares in fourteen months, with new stock consistently priced below net cash per share — and, most pointedly, that a large private placement had closed on July 28, 2023, just weeks before an annual meeting the board had already delayed by 110 days, with the shareholder record date falling after the raise. The practical effect, Camac argued, was that newly issued shares — sold to investors sympathetic to management — would be eligible to vote in a contest about whether management should stay.

Forte’s rebuttal was substantive, not merely defensive (Forte rebuttal). Management noted that roughly 90% of clinical-stage biotech programs fail industry-wide, and that a single Phase 2 miss was not evidence of managerial failure — pointing to other companies, like Human Genome Sciences, that rebounded from early setbacks. It disclosed that its own C-suite and board had personally invested $1.2 million alongside outside investors in the same financings Camac was criticizing. It presented preclinical data it said supported FB-102’s potential. And it turned Camac’s own conduct into a counter-argument, noting that Camac had sold nearly 500,000 shares into illiquid markets around the time of its public campaign, while ATG had sold call options on Forte stock — positions Forte argued gave the activists a financial interest in depressing, not recovering, the share price.

The vote, held September 19, 2023, was not close in the sense of nearly flipping, but it was far from a mandate. CEO Wagner won roughly 61% to 39%; Eichenfield roughly 60% to 40% — this despite both major proxy advisory firms, ISS and Glass Lewis, recommending against Eichenfield’s reelection. Roughly four in ten voting shares wanted the incumbents out. And because the newly placed shares from the July 2023 raise were large enough, relative to the final margins, to plausibly have been decisive, the win came with an asterisk that Camac was not willing to let go.

The Reckoning, and the Real Concession

Camac took that asterisk to the Delaware Court of Chancery, arguing breach of fiduciary duty tied to the placement’s timing. The litigation dragged into 2024. In June, the parties reached a proposed settlement — which the Delaware court itself declined to approve as insufficient. Forte went further. By September 2024, Lawrence Eichenfield and fellow director Donald Williams had resigned; two new independent directors, Richard Vincent (an active biotech CFO) and Shiv Kapoor, joined the board; the poison pill was allowed to lapse without renewal; Forte paid $1.5 million toward Camac’s legal fees; and — the detail that matters most for this story — Forte formally established a Strategic Committee composed of independent directors, tasked with evaluating the company’s capital allocation and strategic options going forward (8-K Sep 2024). The court dismissed the case as moot. Camac, notably, went on record acknowledging the resolution’s benefit to all shareholders.

This is the pivot point worth sitting with. Forte never adopted Camac’s implicit endgame — liquidation, or ceding board seats to Camac’s own nominees. Neither Hacke nor McIntyre ever joined the board. But the company also didn’t simply outlast its critics. It absorbed the parts of the critique that were structurally sound — a board with genuine capital-markets expertise, a formal mechanism to evaluate strategic options, the removal of a defensive tool that had outlived its purpose — while keeping its scientific bet intact. That is a harder and less satisfying story than “management was right” or “activists were right.” It is closer to: an adversarial, self-interested process forced a genuinely better-governed company into existence, without forcing it to abandon its underlying conviction.

Why the Governance Fix Mattered More Than the Fight Itself

The more important point is what the settlement made possible next, not the settlement itself. The governance settlement did not create clinical data. But it may have removed an important governance overhang. Within two months of the board refresh and resolution of the litigation, Forte completed an oversubscribed $53 million private placement led by respected healthcare investors including OrbiMed, Janus Henderson, Tybourne, Ikarian Capital, BVF, Fred Alger and Red Hook. A further $71.6 million offering followed in mid-2025, funding the clinical trials in vitiligo and celiac disease that would ultimately produce the data behind the Argenx deal.

No investor has publicly stated that governance reform drove its investment decision. Nevertheless, the timing raises an intriguing possibility: resolving the governance dispute may have made the company substantially easier for sophisticated institutional investors to finance.

The Lesson

Forte’s near-death and eventual $2.2 billion exit is not a story about management being vindicated over activists, or the reverse. Both sides in this fight had a point, and both had self-interest baked into their positions — BML and Camac were buying a cash discount as much as they were buying a governance thesis; Forte’s board was defending real scientific conviction as much as it was defending its own seats. What separated Forte from a company that simply gets liquidated, or one that entrenches itself into irrelevance, was its willingness to let an adversarial process actually change something — a more balanced board, a formal capital-allocation review, the end of a defensive tool once its purpose had passed — without letting that process dictate the company’s core bet.

For biotech operators watching from the outside, that is the transferable lesson. A failed lead asset is a scientific event. What happens next is very often a governance event first. The laboratory ultimately determined whether FB102 worked. The boardroom determined whether Forte survived long enough to find out. That may be the least appreciated lesson behind one of biotech’s most remarkable turnarounds.

iSWT Community CoFounder

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Image credit, Science

Summary

In this week’s issue,

• reflects on the tragic death of a 6-year girl from a rogue first-in-human clinical trial uncovered by an investigation report by Science and Retraction Watch.

• recaps jaw-dropping efficacy data from J&J’s multiple myeloma bispecifics and their implication for CAR-T.

• argues that China’s new PIONEER program could expand the regulatory use of human-relevant NAMs, potentially accelerating drug development through China’s strong CRO ecosystem and offering particular value for CGT and other therapies poorly served by traditional animal models.

Many of our members are attending The 2nd Evercore China Biotech Summit August 17 to 19 in Shanghai. We created a networking group for the confirmed in-person attendees of this invitation-only conference. Almost 80 members have joined our networking group, which you can join via the QR code below.

We strictly enforce the “in-person confirmed attendees only” rule for this networking event. Please contact , who is the group admin, to learn more.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

In July and August, our newsletter is published every two weeks. We will come back to weekly schedule in September.

Thoughts on “A Fatal Reaction” That is Preventable

On July 23, 2026, Science and Retraction Watch exposed the previously undisclosed death of a 6-year-old girl in an investigator-initiated trial (IIT) for brain gene editing at Xinhua Hospital in Shanghai. The child died in March 2025, yet the fatality was concealed for over a year and deliberately omitted from a proof-of-concept paper published in Nature in February 2026. Acting as de facto sponsors, the family paid approximately $860,000 for the unapproved therapy, assuming all financial and commercial risks. The intervention—the first human-brain base-editing procedure—was applied to a child with a relatively mild, non-life-threatening phenotype of Snijders Blok-Campeau syndrome.

Event Timeline & Core Controversies

Mei’s (a pseudonym) diagnosis was confirmed in March 2023, and the family initiated contact with the lead investigator, Qiu Zilong, in July 2023. By late 2024, Qiu’s laboratory reported successful behavioral rescue in mouse models of the mutation using base editing.

I have summarized the clinical trial timeline and subsequent events in the chart below (assisted by Noah AI).

The primary governance failure was the sequencing of approvals. Granting ethical clearance prior to the completion of non-human primate (NHP) toxicology studies—and subsequently failing to reassess the trial or adjust dosing after severe toxicity signals emerged—represents a catastrophic breakdown in clinical safeguards.

Other irregularities included a $130,000 payment from the family to Kan Yang, a member of Qiu’s team and lead author of the Nature paper. Furthermore, the inadequate disciplinary actions taken against Qiu Zilong and Xinhua Hospital, combined with the active omission of the patient’s death in the Nature publication, highlight profound ethical breaches.

Stakeholder & Community Reactions in China

Major Chinese outlets, including Caixin, Economic Observer, and Guokr, have uniformly condemned these governance failures. There is a dark irony in the fact that Principal Investigator Qiu Zilong had previously denounced the 2018 “gene-edited baby” scandal for its ethical disregard. Following initial, lenient penalties, the involved institutions (Shanghai Jiao Tong University and Xinhua Hospital) are facing intense public and media pressure to conduct a thorough investigation.

On July 26, 2026, China’s Xinhua News reported that the SJTU School of Medicine has initiated a new inquiry into the event. Industry professionals, including members of the iSWT Community, have expressed outrage, characterizing the failure to report adverse events and the manipulation of scientific publications as a severe threat to the field’s credibility.

A Tragedy Preventable by Decree 818

This incident occurred in early 2025, prior to the implementation of State Council Decree No. 818 on May 1, 2026. Decree 818 establishes a rigorous, state-level regulatory framework for “New Biomedical Technologies” like gene editing, mandates strict ethical reviews, and explicitly prohibits institutions from charging subjects for clinical research.

It is important to remember while this strategy was unraveling in 2025, successful stories such as the first-in-human in vivo CAR-T trial from EsoBiotec and impressive data from Legend Biotech were taking place in the same year. Decree 818 now provides a robust enforcement mechanism to balance the risk-benefit profiles of high-stakes, first-in-human (FIH) trials and curb financially motivated “pay-to-play” models.

Isolated Incident or Systemic Failure?

While this case exposed horrific individual breaches—such as advancing trials without NHP toxicology data and researchers accepting personal payments—it has sparked debate regarding the stability of China’s IIT system.

Having advised on multiple FIH trials in China, including ultra-rare pediatric gene therapies, I view this as an isolated case of rogue behavior rather than a systemic norm. Our interactions with hospital PIs consistently demonstrate a demand for high-standard preclinical efficacy and comprehensive NHP toxicity data packages. Peer feedback indicates that most municipalities enforce stringent, standardized review processes, standing in stark contrast to the reckless governance observed in this instance.

Trust Needs to Be Earned

While we cannot bring Mei back, a tragedy of this magnitude becomes even more consequential if we fail to reflect, learn, and implement necessary reforms. Our path to redemption lies in unwavering transparency—a commitment to ensuring such heartbreak is never repeated. By doing so, we honor our shared mission: to deliver lifesaving therapies for devastating diseases, accelerating progress while safeguarding the families and patients who entrust us with their lives.

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

J&J’s bispecific combo posts massive benefits in earlier myeloma

Johnson & Johnson dropped some jaw-dropping data for its multiple myeloma (MM) bispecifics this week.

Combining BCMA-directed Tecvayli (teclistamab) and GPRC5D-targeted Talvey (talquetamab) led to an 89% progression-free survival improvement and 62% overall survival advantage over traditional standard treatments in second- to fifth-line MM, J&J reported from the phase 3 MonumenTAL-6 study. The comparator arm used pomalidomide and dexamethasone with either elotuzumab (EPd) or bortezomib (PVd).

Efficacy of this magnitude is very rare among phase 3 oncology trials. Tagrisso pulled off a 84% PFS benefit for stage 3 EGFR-mutated non-small cell lung cancer in the LAURA trial, and Revolution Medicines’ daraxonrasib recently delivered a 60% reduction in the risk of death for metastatic pancreatic cancer patients in the RASolute 302 trial. In both cases, the data received standing ovation when presented at ASCO.

The MonumenTAL-6 readout adds to a growing body of evidence supporting the use of T-cell engagers in earlier myeloma treatment, threatening the market potential of CAR-T therapies like J&J and Legend Biotech’s Carvykti. The trial enrolled CD38-exposed patients, as did the MajesTEC-9 trial for Tecvayli monotherapy. In contrast, the MajesTEC-3 study for Tecvayli-Darzalex (recent FDA approval) and MonumenTAL-3 for Talvey-Darzalex enrolled predominantly CD38-naiive populations.

However, at least for this one, J&J doesn’t think the bispecific duo would pose a big threat to the BCMA CAR-T in the second-line setting, despite its massive efficacy showing.

In an interview with Fierce, J&J’s oncology therapeutic area head, Dr. Yusri Elsayed, suggested that in earlier-line settings, BCMA-directed therapies—be it TCE or CAR-T—will be the mainstay treatment options. For GPRC5D agents, either alone or in combination, doctors will mostly use them in later lines, and the Tecvayli-Talvey regimen will therefore likely be reserved for a very small group of high-risk patients being treated at large academic centers, he said.

Using a GPRC5D TCE after prior BCMA treatment represents a popular sequencing strategy for relapsed or refractory MM. Combining the two mechanisms up front risks depriving doctors of a later-line salvage option. Besides, GPRC5D-related toxicities such as dysgeusia (taste distortion) may significantly impact quality of life.

That said, potential pressure from Tecvayli (MajesTEC-3 and -9) could be more damaging to Carvykti.

Between the two, the MajesTEC-3 regimen is expected to be less of a threat because anti-CD38 antibodies like Darzalex have increasingly been used in the front-line, leaving a dwindling pool of CD38-naïve patients in later lines. Nevertheless, during J&J’s second-quarter earnings call last week, Jennifer Taubert, worldwide chair of innovative medicine, stated that the Tecvayli-Darzalex combo holds “the potential for cure” in second-line MM.

The description likely rattled Legend investors who were already concerned about Carvykti’s position and J&J’s commercial priorities. Shares of Legend dropped 10% that day despite another record quarter for Carvykti sales that roughly met analysts’ expectations.

A quick recap:

• MajesTEC-3, only 5% of patients were CD38-exposed, Tecvayli-Darzalex posted an 83% PFS improvement versus DPd or DVd. No OS hazard ratio has been given but favored the experimental arm.

• MajesTEC-9, 85% of patients were CD38-refractory (100% exposed), Tecvayli monotherapy delivered 71% PFS and 40% OS benefits versus PVd or Kd (carfilzomib + dexamethasone).

In both MajesTEC trials, patients were required to have taken lenalidomide, and eventually about 80% were len-refractory.

• In Carvykti’s Cartitude-4 study, all patients were len-refractory, about 26% were CD38-exposed, and 23% were CD38-refractory. PFS improvement in the overall population was 59% at primary analysis, later expanding to 71%, at which point a 45% OS advantage met statistical significance.

During a discussion at ASCO 2026, Dr. Ajai Chari from the University of California, San Francisco, offered his considerations for choosing between TCEs versus CAR-Ts in relapsed or refractory MM (graph below).

(Dr. Ajai Chari/ASCO 2026)

Panelist Dr. Saurabh Chhabra from Mayo Clinic Arizona said his preference is to use CAR-T first before bispecific.

“That’s mainly because with the constant pressure from the bispecific antibody, we worry about development of the BCMA gene mutations […] which can impair the activity of the T cells when we collect them for CAR-T,” he said, adding that more data are needed to see if finite duration of TCE treatment could solve that problem.

, Deputy Editor of Fierce Pharma and iSWTC volunteer

China’s PIONEER Program: Could NAMs Become Another Accelerator for China Biopharma?

China’s drug-development ecosystem is already known for speed and scale. A new CDE initiative could add another tool—especially for cell and gene therapies and other modalities where traditional animal models have clear limitations.

In July 2026, China’s Center for Drug Evaluation (CDE) released draft documents for the PIONEER Program — “Propel Innovation and Operation of NAMs to Enhance Efficiency in R&D.” The pilot aims to promote the research, validation and regulatory use of New Approach Methodologies (NAMs), including organoids, organ-on-chip systems, computational models, ex vivo approaches and combinations of these methods. The proposal remains under public consultation. (CDE/PIONEER announcement)

Why NAMs, and why now?

China and the U.S. are responding to essentially the same scientific problem:

Animal models do not always translate well to humans.

CDE highlights species differences, long timelines, high costs and low throughput as limitations of traditional animal testing. Its definition of NAMs is broad and emphasizes approaches with greater human biological relevance, potentially reducing, refining or replacing conventional animal studies. (CDE PIONEER implementation framework)

FDA is moving in the same direction. Its roadmap covers human-derived in vitro systems, organoids and microphysiological systems, computational modeling, PBPK/QSP, AI/ML and other approaches. FDA envisions progressively reducing animal testing when validated alternatives can provide sufficiently relevant evidence. (FDA Roadmap to Reducing Animal Testing)

The underlying question is gradually shifting from:

“Which animal study is required?”

to:

“What evidence best predicts the human response?”

Same destination, different regulatory approaches

FDA currently has the more developed regulatory framework.

Its 2026 draft guidance emphasizes four concepts for regulatory use of NAMs:

Context of Use → Human Biological Relevance → Technical Characterization → Fit-for-Purpose

Importantly, FDA focuses on validating a NAM for a specific regulatory question, rather than treating a technology as universally validated for all purposes. (FDA draft NAM validation guidance)

China’s PIONEER program looks somewhat more like a regulatory sandbox.

Drug developers may apply when they want to use NAM data to support a specific drug-development program. Importantly, NAM technology developers can also apply directly and work with CDE on methodological validation.

For accepted projects, CDE proposes “early intervention, timely communication and full-process tracking.” CDE may work with applicants to establish validation plans, and a methodology that successfully passes review could subsequently be used by that applicant for the defined application scenario without repeating the full validation process.

The draft also proposes no numerical enrollment cap and a five-year application window after formal launch. (CDE PIONEER application guide)

Put simply:

FDA: Build validation standards and progressively identify where animal studies can be reduced or replaced.

China: Bring forward the technology and development problem, validate the use case with CDE, and accumulate regulatory precedents.

FDA currently provides greater regulatory clarity. PIONEER may provide greater flexibility for experimenting with new approaches.

Could NAMs add another layer of speed to China drug development?

This is particularly interesting because PIONEER does not arrive in isolation.

China already has a dense CRO/CDMO ecosystem and highly parallelized R&D model. McKinsey estimates that early discovery-to-IND cycles in China can be 50%–70% faster than global benchmarks, with CRO density, parallel workflows and execution intensity among the drivers. (McKinsey: Asia’s role in biopharma’s future)

NAMs could potentially plug directly into this infrastructure.

When a conventional animal model has limited translational value, developers could have another option: engage CDE earlier around a package combining:

human-cell systems + organoids/organ chips + computational modeling + selected traditional studies.

The benefit may extend beyond eliminating an animal study.

Human-relevant models could help:

identify problems earlier → compare candidates more efficiently → address questions that translate poorly across species → potentially shorten development timelines.

China’s CRO network could make these technologies easier to industrialize. Providers that already integrate discovery chemistry, DMPK, pharmacology and IND-enabling toxicology could increasingly add organoids, microphysiological systems, computational toxicology and quantitative modeling.

NAMs could therefore become another component of China’s broader drug-development infrastructure rather than remaining mainly an academic or specialized technology.

Potentially greater impact for CGT and novel modalities

The PIONEER documents are particularly notable for therapies where traditional animal models are inherently limited.

CDE identifies advanced therapy products and rare-disease drugs as potential application areas. The framework also contemplates using NAMs for selected toxicity and PK endpoints, replacing some conventional animal efficacy models, supporting waivers of longer-duration repeat-dose toxicity studies for antibodies, and contributing to weight-of-evidence assessments. (CDE PIONEER technical considerations)

This could be particularly relevant for:

Cell therapy • Gene therapy • Gene editing • RNA medicines • Species-specific antibodies • Bispecifics and other immune-modulating therapies

For these modalities, activity can depend heavily on human-specific targets, immune biology or cellular interactions.

Animal studies may therefore require surrogate molecules or species that reproduce only part of the intended human biology.

Human-derived systems could provide another way to investigate questions such as:

immune activation • gene-editing specificity • cell trafficking • tissue toxicity • target-dependent effects

—alongside appropriately selected in vivo studies.

More options could become available to biopharma

In the near term, PIONEER is unlikely to mean “no more animal studies.”

A more realistic outcome is a broader menu of nonclinical strategies:

Traditional animal studies

Animal studies + human-relevant NAMs

or, in selected circumstances,

NAM evidence supporting reduction or replacement of a particular animal study.

For global programs, an important limitation remains: acceptance by CDE cannot automatically be assumed to translate into acceptance by FDA, EMA or other regulators.

Still, FDA and CDE are increasingly converging around similar scientific principles:

human relevance + defined context of use + reproducibility + fit-for-purpose validation.

PIONEER is still a draft pilot, so its practical impact will depend on which projects enter the program and what regulatory precedents emerge.

But it could give drug developers—particularly those working on CGT and other novel modalities—more choices for answering questions that traditional animal models do not address well.

And within China’s already fast and CRO-intensive development ecosystem, that additional flexibility could become another contributor to development speed.

iSWT Community CoFounder

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🎙️ Meet the Speakers:

• Anna French, D.Phil. – Managing Partner, Qiming Venture Partners USA

• Andreas Penk – CEO, European Biopharma Therapeutics

• Dan Zhang – Professor, Fudan University & Chief Scientist, PUMC

• Leon Tang (host) – Co-Founder,

Enter the Global Biotech Relay

In BioVerse #33, our expert panel unpacks this complementary, cross-border model designed to accelerate breakthroughs and bring affordable, innovative therapies to patients faster. We explore how bridging the East and West plays to the unique strengths of each global ecosystem:

🔬 The West (US & Europe): Continuing to lead the charge in “zero-to-one” basic science discovery and initial company creation.

⚡ The East (China): Powering rapid translational execution, early clinical development, and highly cost-efficient proof of concept.

📈 Global Markets: Leveraging Western capital and commercial infrastructure to support late-stage registrational studies and successful market launches.

Catch the full video to see how this West-East synergy is actively reshaping the future of biotech R&D!

Free registration to China Pharmaceutical Innovation Conference (CPIC)

Email contact@iswtc.org to receive the free registration of the CPIC conference. Paid iSWT Community subscribers can access the free registration code behind the paywall.

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Summary

In this week’s issue,

• highlights the widening divergence between US biotech’s dominance in M&A and China biotech’s increasing share in BD&L. These results may reflect the evolving formula for biotech R&D.

• walks through the biggest clinical surprise this year.

• Our summer intern Ella Charen summarized the first China BioPioneers/BioVerse webinar: China’s ADC rise over the past decade reflects a perfect convergence of timing, talent, and infrastructure that let Chinese biotechs iterate faster than the West on payload innovation and manufacturing — but closing the gap on global commercialization and drug delivery will require continued cross-Pacific collaboration.

BioVerse #33, in collaboration with Tonacea, will take place on July 14th at 9AM ET. This webinar is a pre-conference discussion for the first China Pharmaceutical Innovation Conference (CPIC) in Shanghai, July 22-24.

Anna French from Qiming Venture Partners USA, Andreas Penk from European Biopharma Therapeutics, and Dan Zhang from Fudan University will talk about the new West-East Biotech Relay model. Register for the webinar on Zoom here.

CPIC offers complimentary registrations to our newsletter subscribers. Learn more in the paid subscribers’ session.

We’re pleased to share a special benefit for our paid members. TellMed Strategies — a life sciences communications agency and past contributor to previous issue’s communication guidebook for Asian Biotechies — is offering:

• A free one-hour consultation

• 10% off their standard fees for one year

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

The Great Biotech Rebalancing: Why the Trans-Pacific Relay Model is the Future of Biotech R&D

The first half of 2026 biotech deal-making has signaled a golden age of biotech deal-making and the start of a new biotech R&D model. This resurgence represents a fundamental pivot in market confidence. The sheer volume of capital deployment in H1 2026 underscores this shift:

• M&A Resurgence: Total M&A transaction value reached $117 billion, a staggering 111% increase over H1 2025, according to a recent Oppenheimer report. At the current M&A cadence, 2026 is on track of setting a new annual M&A record.

• BD&L Velocity and China’s Dominance: Strategic licensing and business development reached $8 billion in total global upfront payments, a 16% year-over-year increase. In a landmark shift, China has become the primary engine of this landscape, with assets originated there securing nearly $5 billion—~60% of all global upfront payments—and commanding an overwhelming 60% of total global BD&L deal value ($99.7 billion out of $166.4 billion), according to PharmCube database (Contact me for H1’ 26 China-originated BD&L analysis).

Chinese assets or platforms accounted for six of the top ten largest licensing upfronts in 1H’26. China has become the primary source of the global BD&L. To navigate this new reality, strategists must look beyond the figures to the distinct roles now played by US and Chinese biotech ecosystems.

The Dichotomy of Dominance: M&A vs. BD&L

The biotech ecosystem has bifurcated into two distinct engines of value: US-driven M&A exits and China-driven early-stage innovation sourcing via BD&L. This split is fueled by a critical scarcity of late-stage opportunities, a reality highlighted in recent Oppenheimer analysis that is forcing Big Pharma to look upstream toward earlier-stage Chinese assets.

• US Biotechs, The M&A Exit Engine: The US biotechs remains the undisputed leader in M&A exits. The market continues to reward US firms for their ability to bring assets to global clinical development and the commercial threshold, with median upfront M&A payments hovering above $1 billion for the sixth consecutive quarter. Big Pharma remains the dominant acquirer, accounting for roughly 75% of total M&A transaction value.

• China Biotechs, The Early Innovation Powerhouse: Conversely, China biotechs have become the indispensable source for BD&L. Rather than outright acquisitions, the market is turning to China for early-stage innovations and R&D capabilities.

The strategic implication is clear: while the market rewards the US for late-stage clinical development and commercial execution, it is increasingly looking to China for the arbitrage of preclinical and early-stage clinical efficiencies.

The McKinsey Thesis: Structural Efficiencies of China Biotech’s Early R&D

I recently proposed the “Trans-Pacific Biotech Relay” model—designed to capture the synergistic strengths of the US and Chinese biotech sectors—, which is validated by a recent McKinsey report titled Biopharma R&D: The evolving formula for discovery and development.

McKinsey’s structural analysis provides the essential framework to understand why different stages of the drug development lifecycle are migrating to specific geographic hubs, confirming the theoretical underpinnings of my hypothesis.

• The China Advantage: China has established a significant lead in the efficiency of drug discovery and Phase 1 clinical development. These stages prioritize speed and the rapid iteration of First-in-Human (FIH) data—areas where Chinese hubs utilize specialized scientific talent pools to move faster than Western counterparts.

• The US Advantage: The US maintains its dominance in high-risk, capital-intensive global Phase 2/3 development and commercialization. These stages require sophisticated market access expertise, a deep understanding of complex international regulatory landscapes, and a deep pool of venture capital that only the US investors are willing to deploy.

This finding justifies the “relay” model: China handles the early “sprint” of discovery and initial clinical proof-of-concept, before passing the baton to US-based expertise for the “marathon” of late-stage clinical trials and commercialization.

The Geopolitical Crossroads: Protection vs. Collaboration

As China’s biotech R&D prowess becomes undeniable, the US biotech sector finds itself at a psychological and strategic crossroads. The reaction to this rise is increasingly polarized.

• The Protectionist View: Some segments of the industry are succumbing to “paranoia,” attempting to hide themselves from Chinese competition. This stance often cites China’s weak IP protection and China biotechs’ dominant reliance on “fast-follow” strategies that free ride on the US biotechs’ hard-won first-in-class innovations.

• The Collaborative View: In contrast, some leading-edge firms are choosing to embrace China’s R&D speed and efficiency. These firms recognize that in an environment defined by a scarcity of late-stage assets, ignoring a region that controls over 60% of current BD&L transaction value is more than a missed opportunity—it is a structural disadvantage.

The “relay” is a structural necessity, not a political choice. Biotechs and investors that adopt the collaborative view are leveraging Trans-Pacific synergies to accelerate their pipeline R&D, while those who pull back risk higher costs and unfavorable market positioning.

Evidence Supportive of the “Trans-Pacific Relay” Model

The “Trans-Pacific Relay” is the industry’s most efficient path for value creation, optimizing the R&D process by utilizing China for discovery/FIH and the US for global clinical development/commercialization.

• Strategic Case Study: Candid Therapeutics: The $2.2 billion exit of Candid Therapeutics, announced in May 2026, serves as an excellent “Proof-of-concept” case study. By leveraging China’s advantages in generating early First-in-Human data, Candid achieved an impressive exit, proving early proof-of-concept clinical data generated in China can be tremendously “de-risking” for biotech acquisition exit.

• The BD&L Shift: Renting vs. Buying: Data from the 1H’26 period reveals a significant trend: 5 of the top 6 major China-originated deals include R&D collaborations (highlighted in yellow). This represents a shift in risk profile; Big Pharma is no longer just “buying a drug,” they are “renting an R&D engine.” This “relay” ensures that global capital is deployed where it is most efficient at every stage of the R&D.

Conclusion: The Competitive Mandate

The integration of China into the global R&D ecosystem is a fundamental structural shift that transcends quarterly financial metrics. For biotech leaders, acknowledging this reality is no longer optional—it is a competitive mandate.

The “Trans-Pacific Relay” represents a responsible path forward for the industry. Embracing this integration is the only way to bring innovative drugs to patients more cost-effectively by leveraging global strengths, and to maximize ROI to fulfill our fiduciary duty when allocating our capital.

In a globalized R&D market, the leaders of the next decade will be those who move past geopolitical friction to embrace cross-border biotech R&D synergy. The relay is already in motion; those who refuse the baton will find themselves unable to compete.

, Co-Founder of iSWT Community & Founder of InScienceWeTrust BioAdvisory

AZ, Ionis’ shock failure

In probably the biggest clinical disappointment so far this year, AstraZeneca and Ionis’ Cardio-TTRansform trial for Wainua (eplontersen) in transthyretin amyloid cardiomyopathy (ATTR-CM) failed to meet its primary endpoint, as the antisense drug didn’t outperform placebo on the composite outcome of cardiovascular mortality and recurrent CV events.

The outright failure of the study shocked investors. In the two days following Thursday’s announcement, AZ’s shares fell more than 9%, a pretty dramatic reaction for a Big Pharma company.

Ionis suffered even more badly. On the same day, words came out that Roche has halted development of two Huntington’s disease prospects. One of them was Ionis-partnered tominersen, which had failed in a phase 3 before. Ionis’ stock plummeted about 31% during the two days.

ATTR-CM carries blockbuster sales expectations for Wainua, which was thought to be a potential market disruptor.

Of the two approaches to ATTR treatment, Wainua and Alnylam’s siRNA therapy Amvuttra are gene silencers designed to block the production of the TTR protein. Pfizer’s Vyndamax (tafamidis) and BridgeBio’s Attruby (acoramidis) are TTR stabilizers which work by preventing TTR proteins from dissociating to stop the buildup of toxic amyloid fibrils.

Expectations were high heading into the Cardio-TTRansform (C-T) readout because Amvuttra had succeeded in the Helios-B trial, in which CV risk reductions were also observed in patients taking background tafamidis. AZ and Ionis had previously adjusted C-T to make it the largest ATTR-CM trial (1,432 patients) to date and extended its events follow-up time to 140 weeks.

The hope was once that C-T could offer a more definitive answer to the appropriateness of a silencer-stabilizer combination. After all, Helios-B was not statistically powered to prove a definitive clinical advantage within patients who were already taking tafamidis, and it imposed an artificial 40% cap on stabilizer uses at baseline. By comparison, C-T had unrestricted use of background stabilizer—eventually, 57% of patients in each arm got a stabilizer at baseline, and another 24% initiated a stabilizer during the study.

Now, C-T’s failure is being hailed as an undoubtful win for Alnylam and BridgeBio, as reflected in the gains of their share prices. However, I have a few reservations about its long-term implications for the ATTR-CM market.

First, C-T has been viewed as much a competitor to Alnylam as a potential confidence boost to the silencer class and a boon to the overall ATTR field.

ATTR-CM is an emerging disease category. Experts have suggested that it could be more prevalent than originally estimated. But its growth potential hinges on increased awareness and diagnosis. More players, especially someone like AZ, which boasts a large CV presence (Crestor, Farxiga), could help with that.

The C-T fail risks undermining doctors’ perception of silencers as a class, although some have immediately argued that siRNAs are simply better than ASOs. (If you have any hypothesis on whether ASO didn’t work here from a mechanism perspective, I’d love to hear: aliu@questex.com).

In a prespecified subgroup analysis of Wainua monotherapy in C-T, a nominally significant improvement of 29% was observed over placebo on the compositive CV outcomes endpoint. In Helios-B, this number was 33%. Not materially different, right? In the combo subgroup (on stabilizer at baseline), C-T reported “no treatment effect,” while Helios-B got a 21.5% benefit (nominal p-value 0.2701).

During a call after the announcement, Ionis management laid the blame in large part on tafamidis outperforming expectations in a relatively less severe population compared with Pfizer’s original ATTR-ACT study, according to Citi.

It naturally makes one wonder if Amvuttra got lucky. As patients are identified earlier in the disease course due to better diagnosis in the real world, does Amvuttra still hold value on top of stabilizer? That is one big question hanging over Alnylam.

C-T’s primary endpoint was assessed over 140 weeks, whereas Helios-B was across 156 weeks. The notion that longer follow-up could allow for a more noticeable benefit doesn’t work here, according to Ionis management, as cited by William Blair. That’s because more patients started taking tafamidis throughout the study.

Full data from C-T will be presented late August during ESC Congress 2026. Detailed results could “better illuminate the relative benefit of silencer monotherapy vs stabilizer monotherapy in as close to a head-to-head comparison as the clinical community might hope to see,” Citi analysts said in a July 9 note.

In addition, researchers are working on meta-analyses comparing results from C-T to Helios-B and other TTR studies to be highlighted at ESC, according to Citi.

Meanwhile, analysts have now grown increasingly cautious about Alnylam’s next-generation silencer, nucresiran, which is likely dealing with the same stabilizer-heavy population with very low event rates in its own trial. In their note, Evercore ISI analysts suspected Alnylam will amend its trial protocol.

For AZ, the C-T fail is poised to erase a big sales opportunity. But Jefferies analysts still argued that investors overreacted to the news. If anything, the stakes are now even higher for AZ and partner Daiichi Sankyo’s Avanzar trial for their TROP2 ADC, Datroway, in first-line non-small cell lung cancer.

— , Deputy Editor of Fierce Pharma and iSWT Community volunteer

China BioPioneers · International Edition Launches: Inside the ADC Conversation Reshaping Global Oncology

A recap of the inaugural episode, aired July 1, 2026

Moderated by our editor , the inaugural webinar featured:

• Jiaqiang (JQ) Cai — Co-founder, CSO & Co-CEO, MediLink Therapeutics

• Ziye Sui — CEO & Executive Director, Lepu Biopharma

• Alexandra Snyder — SVP, Discovery Oncology and Translational Medicine, Merck (MSD)

• Greg Dwyer — SVP, Business Development, Orum Therapeutics

• Anshu Goyal — CEO & Co-Founder, XYone Therapeutics

Background: Why an International Edition, and Why iSWT

China BioPioneers has spent five years and over 100 conversations documenting the arc of China’s pharmaceutical innovation, hosting founders and CEOs from companies including Hengrui, Fosun, Innovent, and Ascentage. The International Edition — a collaboration between Healthcare Executive, Weijieyao, Asymchem, and iSWT Community — represents a natural evolution of that mission.

As China’s biopharma innovation has become increasingly integrated into the global landscape, cumulative license-out deal value has now exceeded $100 billion, and China is shifting from pipeline source to genuine co-creator in global drug development. Yet a communication gap persists: many Western observers still frame Chinese innovation primarily around cost and speed, while Chinese executives increasingly seek direct, substantive dialogue with global peers rather than one-way scrutiny. iSWT — built to bridge Eastern and Western biopharma ecosystems — was a natural partner to help close that gap, giving the series a platform for equal dialogue rather than a one-sided narrative.

Why ADCs: The First Episode’s Topic

The inaugural episode’s focus on antibody-drug conjugates (ADCs) was a deliberate choice — few modalities better exemplify the rise of Chinese biopharma innovation.

China’s ADC pipeline now exceeds 800 candidates, the largest regional ADC pipeline globally. Out-licensing activity tells an equally striking story: a handful of deals in 2019–2020 gave way to explosive growth in 2022–2023, with cumulative reported ADC deal value approaching $40 billion by 2025.

Key Questions Discussed:

1. Why Did China Succeed in ADCs?

The Perfect Storm — Right Time, Right People, Right Place. MediLink’s JQ Cai traced the inflection point to 2016: major Western pharma companies were pulling back from ADC programs amid clinical difficulties, just as novel Topo1-based payloads began to emerge as a real alternative to first-generation linker-payload systems (Immunomedics, Daiichi Sankyo). Even so, Chinese investment kept flowing — Lepu Biopharma’s 2018 acquisition of Miracogen being a case in point, made in pursuit of a synergistic IO + ADC combination strategy that has since become a standard-of-care paradigm across oncology. Simultaneously, highly trained chemists were returning to China from the West, investor capital was flooding into oncology to meet local demand, and China’s CRO ecosystem was scaling rapidly. As JQ put it, nothing mattered more than timing.

The “Triathlon” Modality Fit. ADCs are unusually complex, demanding seamless coordination across antibody engineering, linker-payload chemistry, and advanced CMC. China may not lead the world in any single discipline, but it holds strong, mature capabilities across all three simultaneously — a balanced strength that makes ADCs uniquely suited to the Chinese biotech ecosystem, even without being the single best “swimmer” or “runner” in the field.

Unrivaled Clinical Infrastructure. China’s clinical trial infrastructure allows companies to enroll large patient populations and generate human proof-of-concept data remarkably fast, dramatically accelerating the research-to-clinic iteration loop that underpins everything above.

2. Development Strategy: East vs. West

The Chinese Strategy — Speed, Scale, and Iteration. MediLink is a case study in operating under intense pressure to deliver quickly. JQ described starting the company with no cash and no validated linker-payload system — yet already committed to 60 monkeys for GLP toxicology studies and a secondhand 200-liter reactor. The strategy: design a highly stable, extracellularly-cleaving linker-payload platform, then source antibodies from a range of external partners to rapidly assemble roughly 10 clinical assets. Early BD deals — some licensing assets for startlingly low upfront fees, in one case around $1.5M — let partners fund and de-risk early clinical trials, generating the human readouts MediLink needed to prune its pipeline and scale to 14 clinical-stage assets today. It is a high-pressure-cooker model, but one that China’s clinical infrastructure makes viable.

The Western & Global Strategy — Targeted Risk and Depth. Orum Therapeutics’ Greg Dwyer described a different calculus. Rather than pursuing stepwise improvements on already-validated technology at scale, Orum placed a concentrated, high-risk/high-reward bet on molecular glue degraders (GSPT1) as an entirely new payload class — degrader-antibody conjugates, or DACs — rather than standard cytotoxics. Leveraging Korean funding alongside Cambridge/Lexington-based drug development talent, Orum built the translational depth to move a novel mechanism efficiently from concept into the clinic. The emphasis throughout: fully understand a small number of proprietary technologies rather than advance dozens of assets in parallel.

3. CMC and the Critical Role of CDMOs

Manufacturing emerged as one of the most consequential — and most expensive — parts of ADC development for any early-stage biotech. The panel agreed that integrated, end-to-end CDMOs have become genuine strategic game-changers, and that China’s CDMO ecosystem now leads the global market on this dimension.

Greg Dwyer offered useful historical context: in ADCs’ early days, companies had to build their own manufacturing facilities because third-party manufacturers were unwilling to handle highly potent toxins. Today, Chinese CDMOs lead precisely by offering integrated, end-to-end services — a single partner managing antibody production, linker-payload synthesis, and final conjugation, which dramatically reduces timeline risk when any one step inevitably slips.

Merck’s Alex Snyder emphasized that quality is the absolute priority, followed by flexibility (the ability to absorb clinical timeline shifts) and phase-appropriate capacity. Ziye Sui added color from Lepu’s own experience navigating China’s newly piloted segmented-manufacturing policy across multiple provincial regulators (Hubei and Jiangsu) for its EGFR ADC — complex, but a sign of a maturing regulatory system. Compounding the pressure, the push to reach approval within roughly five years of entering the clinic — versus seven to ten years a decade ago — places unprecedented demands on manufacturing readiness. JQ noted that once a biotech has multiple successful assets, building internal manufacturing capacity becomes essential for supply chain security, though it only makes economic sense at that scale.

4. Challenges and the Road Ahead

China still lacks global commercialization capability. Both Ziye Sui and JQ agreed that while Chinese biotechs excel at early-stage development, the largest and most profitable markets — the U.S. and Europe — remain firmly controlled by multinational pharma. For now, Chinese biotechs have little choice but to partner with MNCs for global commercialization; Lepu, for instance, has no near-term plan to sell beyond China independently. Building independent global sales infrastructure remains a massive, largely unmet hurdle.

The Topo1 payload war. With hundreds of Topo1-based ADCs now in clinical development, the field faces intensifying competition — and, JQ cautioned, real risk of drug resistance emerging across patients treated with mechanistically similar agents.

The delivery problem: less than 2% of active drug reaches the tumor. XYone’s Anshu Goyal offered the panel’s most sobering data point: even the most successful, approved ADCs on the market today deliver less than 2% of active drug to the tumor, with the remaining 98% wasted or contributing to toxicity. By his framing, the field remains in its infancy — and closing that gap will require sustained, global collaboration on delivery and therapeutic index, not incremental payload swaps alone.

5. Extra Advice for Small Biotechs Seeking Big Pharma Collaboration

Merck’s Alex Snyder closed with advice distilled from what she and her team look for when evaluating potential biotech partners:

1. Address a clear unmet need. Partnership conversations start from the clinical gap you’re closing — not the platform you’ve built. Big pharma is evaluating whether your asset solves a problem patients and physicians actually have today, not just a technically interesting mechanism.

2. Clarify the problem — and the tangible benefit. Be precise about the specific scientific or clinical problem your technology is trying to solve, and know exactly what data will prove you’ve solved it. What is the concrete, differentiated benefit your tech or drug brings to the table relative to what’s already in development or approved? Vague differentiation claims don’t survive diligence.

3. Anticipate the future treatment landscape. Don’t design for today’s market. By the time your asset reaches Phase 3, the standard of care may look very different — new combinations, new lines of therapy, new competitors. Understand where your molecule will actually sit in the treatment sequence years down the road, not just where it fits now. It may sound like reading a crystal ball, but every serious partner in this field is trying to anticipate that future and position their therapy as the next advance within it.

At the end of the day, disease has no borders. With substantial ADC work still ahead — on delivery, resistance, and global access alike — continuous, cross-Pacific collaboration remains the fastest path to getting life-saving treatments to patients.

China BioPioneers · International Edition is a collaboration between Healthcare Executive, Weijieyao, Asymchem, and iSWT Community.

by Ella Charen, iSWT Summer Intern.

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We are proud to announce our collaboration with Healthcare Executive, Weijieyao and sponsor Asymchem Group on the inaugural episode of China BioPionners International Edition — a milestone that sits at the heart of our community's mission: bridging the Eastern and Western biopharma worlds to foster deeper understanding and meaningful collaboration.

In this first episode, our co-founder moderates a conversation with an outstanding panel — Jiaqiang Cai, Ziye Sui, Alexandra Snyder, MD, Greg Dwyer, Anshu Goyal — exploring the theme:
"Innovation, Globalization, and the Next Wave of ADC Development: China–West Perspectives."

Why ADCs — and why now?
ADCs represent perhaps the most compelling example of China's emergence as a global biopharma innovator. With cumulative license-out transactions surpassing $100 billion USD, Chinese innovation is no longer just a pipeline source — it is becoming a co-creator in the global pharmaceutical value chain. Yet a real communication gap remains. This first episode exists to close it.

[Update: a typo in an earlier version was corrected]

Summary

In this week’s issue,

• , inspired by his 8-day trip for BIO2026 Conference and SITC Biotech Strategic Meeting, believes a Trans-Pacific biotech replay model is the only path forward to curing diseases and strengthening the US biotech industry.

• went from a Pfizer ADC’s phase 3 flop to an emerging debate that’s poised to become the next frontier in the U.S.-China geopolitical discussions.

• We invited Tara DiMilia, the CEO of TellMed Strategies, to discuss how Asian biotech companies can navigate the nuances of U.S. communications — from regulatory compliance and patient advocacy to media relations and social media — and what it really takes to get your science heard in one of the world’s most competitive markets.

On July 1st, an ADC expert panel that consists of Jiaqiang Cai from MediLink, Ziye Sui from Lepu Biopharma, Alexandra Snyder from Merck & Co, Greg Dwyer from Orum Therapeutics, Anshu Goyal from XYone Therapeutics, and our very own from EMD Serono will converge at BioVerse #32 to share their thoughts on the current landscape of this exciting field. Sign up for the webinar here.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

The US-China Biotech Collaboration is the Only Path Forward - Reflection on BIO 2026 and SITC Biotech Meeting

The past eight days have been nothing short of a whirlwind. From the sun-drenched, jam-packed BIO 2026 “Speed Dating Marathon” in San Diego to ringing the bell of reality at the Society for Immunotherapy of Cancer (SITC) Biotech Strategic Meeting at the New York Stock Exchange, I had the privilege of speaking with literally hundreds of industry leaders. We’ve spoken on panels, shared boat parties on the San Diego Bay, and strategized in the boardrooms.

Across these meetings, a unifying theme emerged that is reshaping how we think about drug discovery, clinical development, and global dealmaking. The geopolitical landscape may be fraught with tension, and the dialogue surrounding decoupling grows louder by the day. But when you step away from the political rhetoric and look strictly at the data, the science, and the economics of capital efficiency, a clear, undeniable truth surfaces:

Here is a deep dive into the data-driven realities, the case studies, and the winning formulas that will define the next decade of biopharma.

1. The Data-Driven Reality: The U.S. Discovery Edge vs. The China Development Engine

A recent, highly illuminating report by the Cure Innovation Index perfectly captured a dynamic that those of us in cross-border biotech venture capital and business development have been witnessing play out in real-time

The U.S. and China are no longer running the same race; they are running highly complementary legs of a global relay.

The U.S. Lead in Basic Science and Discovery: The United States remains the undisputed heavyweight champion of basic science, frontier discovery, and commercial depth. Fueled by unparalleled academic institutions, robust NIH funding, and a risk-tolerant venture capital ecosystem, the US is the birthplace of revolutionary modalities. Whether we are discussing next-generation CRISPR applications, novel RNA therapeutics, or advanced in-vivo CAR-T cell therapies, the fundamental “zero-to-one” innovations predominantly originate in American labs. The U.S. ecosystem excels at asking the biggest biological questions and inventing the tools to answer them.

China’s Structural Advantage in Speed and Cost: However, the Cure Innovation Index also highlights a profound shift in the ecosystem: China has built an undeniable, world-class engine for clinical development. Once a fundamental discovery is made, it must survive the grueling transition into human trials—a phase fraught with operational bottlenecks.

This is where China’s structural advantages become glaringly apparent. According to the data, China is currently executing the discovery-to-IND (Investigational New Drug) phase 50% to 70% faster than the rest of the world. Furthermore, they are running Phase 1 clinical trials at a staggering 50% to 60% less cost. This is not merely a byproduct of cheaper labor; it is a structural, deeply ingrained advantage built on immense patient populations, highly concentrated medical centers, streamlined regulatory pathways for First-In-Human trials, and an aggressive, highly optimized CRO/CDMO infrastructure.

2. The Pragmatic Imperative: Compete, Don’t Disengage

In today’s macroeconomic environment, the cost of capital is punishingly high. Biotech companies are under immense pressure to stretch their funding further and deliver clinical proof-of-concept faster than ever before. Yet, the U.S. currently faces a severe clinical translation bottleneck. The “Valley of Death” between a brilliant laboratory discovery and a successful Phase 1/2 trial is widening, choked by exorbitant costs and agonizingly slow patient recruitment timelines.

Because China’s structural advantages in development speed and cost-effectiveness are durable, deeply embedded, and supported by massive infrastructure investments, they are not going to simply vanish due to geopolitical headwinds. In this sense, the proposed BINSA and COINS acts would be rhetoric at best and tremendous self-damaging at worst.

Why? Because most tier-1 China biotech companies (think of HengRui, Innovent, Hansoh etc) have sufficient capital to support their R&D for at least 5 years.

For the U.S. biopharma industry, this presents a stark choice: leverage this global efficiency, or lose out to competitors, particularly those from Europe and Japan. As the Cure Innovation Index implicitly suggests, turning our backs on a system that can cut development time and costs in half is not a viable strategy for survival, let alone leadership. We must navigate the material risks of dependency with eyes wide open, but ignoring the operational leverage that China provides will cause self-inflicted damages to the US biotech industry.

3. The Candid Therapeutics Masterclass: Execution at the “China Speed”

If you want a real-world validation of this thesis, you need look no further than Candid Therapeutics. During the BIOCHINA Global Forum in San Diego, I had the privilege of connecting with Ken Song, the visionary behind Candid, and a few days later listened to his sharing the incredible story during our China biotech panel at the SITC event at the NYSE.

Candid Therapeutics offers a masterclass in modern biotech execution. In a breathtaking 20-month sprint, the company successfully in-licensed five China-originated assets, heavily leveraging China’s drug discovery quality and clinical trial advantages. This strategic maneuvering culminated in a massive $2.2 billion acquisition—creating tremendous value for their shareholders in record time.

The secret sauce to Candid’s success was their mastery of first-in-human clinical trials in China. During our panel, Ken shared a jaw-dropping statistic that perfectly encapsulates the East-West dynamic: by tapping into the Chinese clinical ecosystem, they were able to recruit approximately 70 patients in 2025 alone while a Western competitor took two full years to enroll many fold fewer patients outside China.

Presentation by Ken Song at BIOCHINA, Jun 21, 2026, San Diego

In the high-stakes, hyper-competitive arenas of T-cell engagers for autoimmune diseases, that delta in recruitment speed is the difference between leading the market and becoming irrelevant.

M&A, as panelist Kristen Hege rightly pointed out, is a business of “the right time, right place, and right people.” By leveraging China’s clinical speed, Candid drastically compressed their timelines, ensuring they were in the right place at exactly the right time for an impressive $2.2-billion exit.

4. The Winning Formula: A Trans-Pacific Relay

Looking back at the blur of the past eight days, a highly effective, repeatable blueprint for bringing innovation to patients has clearly emerged. I call it the Trans-Pacific Relay

This is the exact model that Mianus Accelerator and InScienceWeTrust BioAdvisory are championing. Partnering meetings that fall into this model are the vast majority of my meetings. The industry’s dealmaking appetite right now centers squarely on three distinct archetypes:

• China-focused Development of Early-Stage West-Originated Assets: Western biotechs with brilliant innovations (such as next-gen in vivo CAR-T, novel payload ADCs, or first-in-class gene therapies) are partnering with Chinese firms to conduct rapid, cost-effective early stage clinical trials. This generates the critical early clinical data needed to secure subsequent funding rounds or trigger M&A interest back in the U.S..

• Out-Licensing of Clinically De-risked or Truly Innovative Early-Stage China-Originated Assets: Western pharma companies, hungry for pipeline replenishment but wary of early-stage biological risk, are aggressively in-licensing assets that have already been clinically de-risked in China. China has a massive surplus of these highly optimized, Phase 1/2 ready assets looking for Western late-stage development and commercial partners.

  True innovations still have buyers - As SITC keynote speaker Andrew Baum noted, the buyer’s lens right now is heavily focused on novel payload ADCs and the return of agonists (like PD-1/IL-2). But the buyers are not always from the West. Daina Graybosch noted that her ASCO note on Graywolf, a first-in-class innovator, received no interest from Western investors except for one biotech company - Innovent Biologics, the Chinese biotech powerhouse.

• Aggressive Drug Discovery Campaigns for European/Western Companies: European and U.S. companies are increasingly utilizing China’s vast CRO network not just for chemistry and manufacturing, but for sophisticated, end-to-end drug discovery campaigns, turning capital into clinical candidates at “China Speed”.

This relay race allows each ecosystem to do what it does best. It pairs the audacious creativity of Western basic science with the ruthless operational efficiency of Eastern preclinical CROs and clinical development infrastructures, ultimately delivering the de-risked asset back to the West for registrational trials and global commercialization.

5. Conclusion: The Art of Biotech Crosstalk

During my panel at the SITC Biotech Strategic Meeting at the NYSE, I was asked about the future of China on the global stage. Many in the West look at China’s rapid ascent in biotechnology with apprehension, fearing it will inevitably take center stage and push others aside.

However, I view this through a distinctly different cultural lens. In Western culture, stand-up comedy is traditionally a one-man show—a solitary figure on stage holding the microphone. But in traditional Chinese culture, the equivalent art form is 相声 (Crosstalk). Crosstalk requires two performers: a lead speaker and a highly skilled supporting partner bouncing off one another in perfect rhythm and harmony to deliver a masterpiece.

Will the future of global biotech be a one-man comedy show, dominated by a single superpower? Or will it be a deeply collaborative, perfectly synchronized two-performer 相声?

Given the economic realities of drug development, the widening Valley of Death, and the undeniable complementary strengths of the U.S. and China, I believe we have no choice but to master the art of crosstalk. We have brilliant innovation, and we have the high-octane engines required to accelerate it.

At the end of the day, our ultimate adversary is not each other but cancer, autoimmune disorders, and rare genetic diseases.

Disease has no borders—and if we want to cure it, neither should we.

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

From Pfizer ADC’s Phase 3 flop to heated debate over a gene editing NewCo

Pfizer’s first phase 3 readout from a pipeline ADC inherited from its $43 billion Seagen acquisition was a dud.

Sigvotatug vedotin (SV), designed to target integrin beta-6 (IB6), failed to beat docetaxel on overall survival in previously treated nonsquamous NSCLC, according to the phase 3 SigVie-002 (Be6A Lung-01) trial. No IB6 expression-response relationship was observed.

Pfizer, pointing to a stronger positive trend in second-line patients and phase 1 data, expressed confidence in an ongoing phase 3 trial, Be6A Lung-02, combining SV with Keytruda in first-line NSCLC with high PD-L1 expressions.

But the reality is, with PD-(L)1xVEGF and TROP2 ADCs, the first-line NSCLC space is looking very competitive. The ORR for SV+Keytruda reached 50% among all 46 patients and 86% in 7 patients with PD-L1-high (TPS >=50%) tumor, according to phase 1 results updated at ASCO 2026.

In the Chinese phase 3 OptiTROP-Lung05 study that triggered some buzzes at ASCO 2026, Merck and Kelun’s TROP2 ADC, sac-TMT, used together with Keytruda, recorded a 70% ORR in all patients and 81% in the PD-L1-high subgroup.

Pfizer’s phase 3 failure once again speaks to how much the field still doesn’t understand about ADCs, and the difficulty in finding the next Enhertu or Padcev. The news followed Pfizer’s decisions in the past year or so to axe three ADCs programs targeting B7-H4, CD228 and PD-L1 (TLR7 immune-stimulating payload), as well as significantly reducing efforts around RemeGen-partnered HER2 ADC, disitamab vedotin.

In an interview with Pfizer’s Chief Oncology Officer Dr. Jeff Legos earlier this year, I asked what his plan was to avoid repeating Gilead’s lessons with Immunomedics (multiple Trodelvy phase 3 flops and no sign of new ADC six years after $21B acquisition). Besides the now-failed Be6A Lung-01, he pointed to Pfizer’s work in profiling novel antigens and “a variety of permutations” involving new antibody constructs (multi-specifics) and payloads (protein degraders, molecular glue). For example, rather than SV’s MMAE vedotin payload, Pfizer is working on another IB6 ADC with a Topo1 payload.

Similarly, Daiichi Sankyo’s new R&D chief, Dr. John Tsai, is tasked with developing the next DXd (a platform technology that can yield multiple products) as part of the company’s plan to become a global top 5 oncology company by 2035. And Daiichi is also exploring novel payloads and tumor-selective antibody engineering. In a recent interview, he told Fierce that Daiichi is taking a rigorous approach to biology. One focus is on treatment resistance and cancer escape pathways to consider how to combine or sequence drugs with different payloads.

Rather than following verified targets (HER2/Enhertu and TROP2/Datroway), Daiichi’s strategy now is to be first-in-class to outcompete the 200-some Chinese ADC players, Tsai said.

“We think about unique targets first, and we will be there first, because it’s novel approaches that we take,” he said. “It’s not repeating the sequencing of combinations of PD-1/VEGF.

For competitive reasons, Tsai wouldn’t disclose specific targets because he knows, once that’s out there, Daiichi will have to move faster to outrun followers.

This consideration brings us to the second topic. This week, Serapha Bio emerged through a reverse merger with Boundless Bio with $230 million in funding commitments from a group led by RA Capital and RTW Investments. The company’s lead asset is an in vivo base editing candidate licensed from China’s YolTech Therapeutics. It targets the PiZZ mutation to treat alpha-1-antitrypsin deficiency (AATD).

What would have been just another China-to-West NewCo sparked heated debate on biotwitter. The deal struck a nerve because before co-founding YolTech, the company’s Chief Development and Technical Officer, Dr. Emma Wang, worked at Beam Therapeutics, which is developing a clinically more advanced base editing therapy, BEAM-302.

Some people immediately cried foul, accusing YolTech of stealing trade secrets. While no concrete evidence has emerged, the optic does not look good on YolTech. Robert Nelsen, co-founder of ARCH Venture Partners, which counts Beam among its key investments, tweeted on June 23:

“They should have named it Beam Prime. Or Me Too. Or USA Innovation. Or You Invent, We Take.”

In response, RA’s Peter Kolchinsky tweeted:

“Bob, let’s let the teams compete on the quality of their results. Beam is ahead. If anyone else merely the same, they won’t win. But if they are better, then innovation is working as it should, with competition driving improvement. Every company builds on work of others.”

The debate on BioTwitter quickly merged with the ongoing discussion about whether the U.S. should license from Chinese biotechs, while also veering into complaints about American VCs’ seemingly deteriorating tolerance for risk that’s inherent in the development of groundbreaking new technologies.

Underlying these debates is IP, which I think is poised to become the next frontier of geopolitical tension between the U.S. and China in the biopharma industry. Disputes over gene editing technologies are nothing new, but the involvement of a Chinese company has clearly amplified the backlash.

This case holds potential of becoming a watershed event that will reshape how U.S. capital and biopharma engage with Chinese biotechs. Depending on how U.S. stakeholders respond, this case could either elevate the U.S. ecosystem or pull it back further.

I’m going to quote Dr. Lucas Harrington, who co-founded Mammoth Biosciences from the Doudna Lab. In this June 25 tweet, he wrote:

“This is the point that has been missed in the Chinese biotech debate. The real reason these Chinese assets make sense is largely due to the erosion of the US patent system’s ability to protect biotech discoveries. Investment in Chinese companies (that eg @jrkelly is pushing for regulations of) is a consequence not the cause. Adding in financial regulations for an intellectual property problem will only make things worse. Gene editing is one of the clearest embodiments of this issue and why the RA deal for a base editor has been such a flashpoint. US companies were the first to try to exploit this and the Chinese companies are just doing it better and faster.”

However, under the current political environment, as this recent article by The Economist stated, “China can be a useful bogeyman in American politics.” Any serious policy discussions about complex issues in the U.S. risk being reduced to a simple ban.

— , Deputy Editor of Fierce Pharma and iSWT Community volunteer

From Research to Recognition: Bringing Visibility to Life Science Innovation in the U.S. Market

Science Can’t Sell Itself

Science can’t sell itself. The brilliance of your innovation may have the ability to significantly improve, or even save, lives — but potential partners, investors, and the medical community need to hear about it and understand its importance for it to succeed. Effective communication is the bridge between breakthroughs and real-world impact.

A good example of ineffective communication is the rollout of the microwave oven. While the technology was ready in 1945, it took until the 1980s for most Americans to buy one, and many other countries didn’t see them until the 2000s. That 30-plus-year delay happened because the early marketing used scary terms like “high-frequency radiation,” which caused panic as people confused it with nuclear weapons. Even when the science and its promise are clear, you need to get your voice heard amid an increasingly crowded healthcare landscape.

This is especially true in the U.S. market. Many companies are surprised to find that a strong data package and polished presentation aren’t sufficient. Americans expect directness, personalization, and clarity. Investors want to see not only the data but also how others are responding to your progress. Successful communications require understanding the nuances of language, preferred channels, and the regulatory environment — and creating branding that aligns with U.S. culture and regulatory parameters.

Taking a Step Beyond AI

While AI can be valuable for translations and identifying cultural differences, it often misses important nuances. In life sciences communications, those nuances matter.

For example, some companies have used the word “novelty” as a substitute for “innovation” or “new.” While technically correct, Americans commonly associate “novelty” with a trinket or gimmick, making it inappropriate for medically focused materials. Even technical terminology may be translated inaccurately or fail to meet expectations for clarity and accessibility.

Beyond word choices, translations can overlook tone and language preferences of U.S. investors, investigators, and patients. Failing to appropriately acknowledge patients in materials such as data press releases causes a company to appear disconnected from healthcare’s broad mission. This release demonstrates these subtleties — the subhead points to the assessment of the treatment “in patients with T1D” rather than the disease itself, and the quote also refers to patients. This nuanced language demonstrates commitment to patient care while remaining within regulatory compliance.

Communications strategies must also account for complex U.S. legal and regulatory requirements, and building authentic relationships across media and social platforms is critical to creating a brand that resonates. Knowing which tactics best align with a company’s stage, goals, and audience still requires strategic human input — and the right approach can look very different from one company to the next.

Two companies recently took very different approaches to increasing clinical trial enrollment. One was a gene therapy company with more than 1,000 employees preparing to launch a study, while the other was a startup oncology biotech with an active trial underway. Differences in company stage, trial status, audience needs, and regulatory considerations resulted in two very different communications approaches. One program centered on thought leader engagement and conference activities, while the other relied primarily on targeted social media outreach, curated content, and a study-specific webpage.

AI can help generate ideas and accelerate execution, but successful programs still require human insight, strategic judgement, and relationship-building. Ultimately, it all begins with a strong brand.

Branding: Defining Who You Are

A strong U.S. presence begins with a clear, compelling brand. This includes:

• A differentiated company identity, mission and values

• Human-centered storytelling that resonates with future employees, investors, patients and other key stakeholders

• Visible company leadership with authentic, relatable personal brands

• Authentic engagement with patient communities

• Clear articulation of your product, its purpose and its relation to your identity, mission, and values

As an example, Modifi Bio’s use of imagery successfully illustrated how strategic branding can elevate scientific complexity into accessible, memorable messaging. Their tagline, “Modifying DNA to eradicate cancer,” paired with visual metaphors such as chameleon imagery, transformed intricate molecular science into a story people could easily understand. Creativity is important, but must remain within legal and regulatory parameters and keep patients at the center.

Setting the Framework

Regulatory Considerations

The U.S. regulatory environment demands precision and discipline. Companies that do not adhere to FDA requirements can face regulatory, legal, and financial consequences — including warning letters, product sales restrictions, and damage to investor confidence. A few core principles to keep in mind:

• Investigational products must be clearly and constantly defined as such

• All statements must comply with research/product labels

• Safety information must be shared when naming a product, even on social media

• Language should be at a third-grade reading level

The Power of Patient Advocacy

Patient advocacy is a cornerstone of U.S. healthcare communication. Unlike in many other markets, U.S. patient groups increasingly expect a seat at the table on trial design, and FDA advisory committees consider patient perspectives when evaluating therapies. These relationships need to be two-way: companies should both gain input from patient advocates and provide information to them.

Engagement can start as early as clinical trial planning, helping ensure that outcomes data matches patient needs — particularly for diseases affecting mobility and quality of life, where patient and physician perspectives on success can differ greatly.

One very successful patient campaign created by TellMed Strategies was for a client developing a radiopharmaceutical treatment for a rare cancer. TellMed produced pinwheels imprinted with a zebra design — the symbol of rare diseases, aligning with the saying “when you hear hoof beats, don’t just think horses; it could be a zebra.” The pinwheels carried another metaphor too: one doctor stated that “hope is like air for this community of patients,” and pinwheels are powered by air. Distributed to patient advocacy groups across the globe, photos of the pinwheels in Times Square, in front of the Eiffel Tower, and at other international monuments were broadly shared on social media, bringing a sense of hope and unity to the community and significantly raising disease awareness.

Tactics to Raise Visibility

Owned Materials

Branding and messaging should be consistently reflected across all materials, particularly your website and company presentation. These “owned media” tools give you full control over content. A U.S.-facing website — even a simple one-page site — is essential, as it is often the first point of contact for investors, potential employees, and partners, and serves as the foundation for validating information found through news and social media.

Company presentations should clearly lay out the problem you are solving and how you are solving it. Your website — whether a simple one-pager or a more elaborate multi-page site — should reflect your stage and budget, and remember that for many investors, potential employees, and partners, it will be their first interaction with your brand.

Working with U.S. News Media

The U.S. media ecosystem is vast, ranging from national networks to niche trade publications. Working well with media requires honesty, authenticity, and an understanding of each outlet’s audience, deadlines, and methods. Press release distribution services support searchability, but generating genuine journalist interest amplifies both visibility and brand credibility.

While the Wall Street Journal typically focuses on public companies, a reporter decided to lead the piece “New Blood Thinners Will Prevent Blood Clots Without Causing Bleeding” with a privately held emerging biotech only because TellMed was able to offer the reporter a broad view of the company’s role within the ecosystem. Initial discussions grew into a top-of-the-fold story based on TellMed’s continued information-sharing with the reporter — prompting investor attention and social media engagement well beyond the initial publication.

Prepare spokespeople thoroughly: they should know the reporter’s background, anticipate questions, and understand the importance of speaking succinctly on the record.

Social Media: Humanizing Your Company and Your Science

Investors, potential hires, and patients all turn to social media to assess a company’s reputation and culture. Experience across life science companies suggests it is often the first point of exposure — one company found that two-thirds of new hires cited social media as their initial introduction to the firm. In the U.S., the key platforms serve distinct roles:

• LinkedIn: Reaches industry, employees, investors, and future talent. Weekly cadence, thought leadership, and human-centered posts perform best.

• Facebook: A critical platform for patient engagement. Supports live events, community building, and cross-promotion with Instagram.

• Instagram: Highly visual and effective for patient communities. Reels, Stories, and Live sessions help humanize the company.

• YouTube: A home for video content that can be shared across platforms.

• Bluesky: An emerging platform gaining traction among researchers and academics, requiring frequent posting.

Across all platforms, the goal is to humanize the company, offer personal perspectives, and provide patient-centric information.

Launching a U.S. Communications Program

Bringing scientific innovation to the U.S. market requires more than data — it requires cultural understanding, regulatory fluency, patient partnership, and strategic storytelling. Start by defining your current goals, build a milestone roadmap for consistent visibility, and tailor your messaging to U.S. language and culture. Thoughtful implementation and relationship-building will transform these activities into meaningful visibility and measurable results. When executed well, communications become a growth engine, a trust builder and a catalyst for recognition, shaping perception, and unlocking strategic opportunities.

Your scientific successes can change lives, but you need to make sure your story is heard and understood.

Tara DiMilia, CEO of TellMed Strategies, a healthcare communications agency with experience helping companies create a footprint in the U.S.

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Summary

In this week’s issue,

• Steve Yang from , inspired by a recent China IIT strategy from an early-stage US biotech, shares a framework for western biotechs to choose CRO partners for China first-in-human or proof-of-concept clinical studies.

• saw a (perhaps temperary) return to normalcy at the FDA.

• moderated a lively and wide-ranging BD panel at the SAPA-NE Annual Conference on June 13th, bringing together voices from global pharma, Chinese biotech, venture capital, and transaction law to examine how China is evolving from a pipeline source into a true co-creator in the global drug development ecosystem (see its summary by Jia Guo in paid content).

On July 1st, an ADC expert panel that consists of Jiaqiang Cai from MediLink, Ziye Sui from Lepu Biopharma, Alexandra Snyder from Merck & Co, Greg Dwyer from Orum Therapeutics, Anshu Goyal from XYone Therapeutics, and our very own from EMD Serono will converge at BioVerse #32 to share their thoughts on the current landscape of this exciting field. Sign up for the webinar here.

Hundreds of iSWT Community members are heading for San Diego for BIO and its Satellite events from Jun 21 to 25, and 200+ iSWTC members have joined our IN-PERSON attendees-ONLY networking group. Please contact Feng Pan, Ting Yi, or to join this exciting and curated networking group.

Paid members please check the events from the paid members’ session to learn about the events organized by iSWT Community members and access discount codes.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

A Framework for Western Biotechs Choosing a CRO Partner for China FIH/POC Studies

A $9.1M seed-funded startup just announced plans for an IIT study in China.

Kopra Bio, a UCSF spinout working on virus therapy for brain cancer, is the latest western biotech to head to China for early clinical data. As Endpoints News put it:

“Increasingly, US companies are looking to conduct their own IITs in China and to get their first clinical data for a fraction of the cost of a traditional Phase 1 study in the US.”

It is a pattern that is hard to ignore — and the numbers back it up. Pfizer’s CEO has described Chinese biotech firms conducting clinical research at “half the cost and three times the speed” of their western counterparts. For an early-stage company burning through a $9M seed round, that math is existential. FIH and POC data are what separate fundable from un-fundable, and China’s world-class hospitals, deep patient pools, and regulatory pathway that often moves faster than the FDA make it a compelling venue to get there.

Western biotechs no longer need convincing. They get it.

The harder question is how. And the hardest part of “how to Pick the right CRO?”

Why CRO Selection in China Is Different

FIH and IIT programs are not smaller versions of late-stage trials — they are structurally different. These are focused studies of 2 to 50 subjects, asking specific questions about safety, target engagement, and dose response. They require iterative protocol design, close PI collaboration, and rapid mobilization, and they demand a CRO with genuine scientific depth — real endpoint and biomarker expertise — not just logistical capacity.

Layer cross-border complexity on top — timezone gaps of 12 to 16 hours, differences in how issues escalate, the challenge of managing a China program while keeping investors and board members informed — and the right partner needs to be more than a China operator. They need a western-facing point of contact who bridges the gap between what is happening in the clinic and what the sponsor needs to know.

Know the Landscape

China’s CRO market presents three broad categories of partners:

Small/Mid-Sized China CRO. Locally rooted with a predominantly domestic client base. Western-facing infrastructure is almost nonexistent, cross-border track records are thin, and many suffered significant staff attrition during the domestic funding downturn — with downstream implications for study continuity and data quality.

Large China-Based CRO. Scaled operators with broad hospital networks and growing global ambitions, but built around late-stage, large-trial execution. International contracting structures are still maturing, and whether a small western sponsor’s program receives genuine priority attention deserves scrutiny.

Large Global CRO. Strong institutional credibility and global reach, but infrastructure and pricing calibrated for pivotal, late-stage programs. The overhead of their operating model may not suit the agile demands of a first-in-human study.

Four Dimensions That Determine Fit

Clinical Trial Focus. Look for a CRO for whom early-stage work is a primary focus, not a niche grafted onto a late-stage engine. The signals: dedicated early-phase teams with genuine endpoint expertise; a track record of supporting protocol amendments without re-negotiating scope; and staff continuity from initiation through data readout. Ask directly — what share of this CRO’s active portfolio is FIH and IIT work, and who specifically will run your program?

Client Base. A small biotech with a single program needs to be a priority client, not a secondary account. A 2022 McKinsey analysis documented the pattern[LT1] : small companies are routinely assigned less experienced teams, receive less proactive communication, and face higher personnel turnover than large pharma clients at the same CRO. Watch for the “bait-and-switch” — a polished senior team wins the contract, then hands off to a less experienced operational team once the ink is dry. Insist on meeting — and contractually naming — the individuals who will manage the study before signing.

Counterparty Credibility. A CRO with active master service agreements across leading global pharmaceutical companies has already passed rigorous legal, financial, and data governance due diligence by sophisticated procurement organizations. That externally validated baseline of accountability is meaningfully different from a CRO signing its first western client — and it reduces the due diligence burden on a lean early-stage team.

Competitive Positioning. The right question is not which CRO owns the most China infrastructure. It is which one takes full accountability for the outcome while assembling best-of-breed capabilities around the program. The same McKinsey analysis identified this integrator model as the necessary evolution for CROs serving innovation-driven biotech — and AI is accelerating the shift by reducing the cross-border coordination costs that once made such orchestration impractical.

The Legal Layer Most Sponsors Underweight

Before signing any CRO agreement for a China study, three questions demand explicit answers.

Jurisdiction. What law governs the contract? A contract governed by Chinese law operates under a fundamentally different framework than one governed by U.S. or English law. For a company funded by U.S. or European investors, this is not a technicality.

Counterparty substance. Is the entity you are signing with the real accountable party? Some CROs establish overseas offices primarily as contracting interfaces, with execution occurring through separate domestic entities. Understanding whether the counterparty has meaningful staff, assets, and direct accountability for delivery is essential due diligence.

Ownership and conflicts. Who owns the CRO? China’s biotech ecosystem is highly interconnected, with investors frequently holding stakes across CROs, CDMOs, and the biotech companies they fund — sometimes including competing programs. Ask directly: do any investors in the CRO hold positions in competing pipelines?

The Bottom Line

Each CRO category has genuine strengths — local clinical networks, global reach, or institutional scale. The challenge for early-stage biotech is that none was designed with your program in mind. What you need is a partner who can draw on those strengths selectively while taking full accountability for the outcome.

McKinsey’s 2022 analysis points to exactly this model — the “integrator” CRO whose competitive advantage is coordination and accountability across best-fit capabilities, not the breadth of its own internal infrastructure. For a cross-border FIH or POC study, that means a partner fluent in both Chinese clinical operations and western sponsor expectations, with the institutional standing to hold all parties to the same standard.

The CRO selection decision is, in effect, a decision about where accountability sits. The four dimensions in this framework are simply a structured way to find the partner who has earned it.

Steve Yang — Co-Founder and CEO of , Board Member and CFO of MERIT CRO, Inc.

Steve publishes regularly on early-stage biotech development strategy and the evolving China clinical landscape. Contact: syang@mianuscapital.com

Some good news at the FDA

The FDA is showing some signs of returning to normal, although probably only temporarily.

This week, uniQure announced that the FDA, in a U-turn, agreed that a three-year analysis from a phase 1/2 trial of the company’s Huntington’s disease gene therapy, AMT-130, would be enough to support a filing for accelerated approval.

Before uniQure’s planned BLA submission in the third quarter, the company and the agency plan to align on the confirmatory study design, “including consideration of concurrent control on standard-of-care therapy instead of a sham procedure,” uniQure said.

As we covered in Issue 116 and Issue 130, the FDA’s previous sudden rejection of uniQure’s accelerated approval plan—and the agency’s demand for a sham-controlled study—was part of a high-profile drama that led to complaints from the rare disease community and stirred up concerns within the biopharma industry around regulatory consistency. Along with several other negative opinions from the FDA (e.g. Moderna and Replimune, more on those later), it fed into a campaign to bring down former CBER director Dr. Vinay Prasad and then-FDA chief Dr. Marty Makary. Both have since left the FDA.

The announcement follows a June 3 meeting between rare disease advocacy groups and the current FDA leadership, including Commissioner Kyle Diamantas, CDER Director Dr. Mike Davis, CDER Director Karim Mikhail—all serving in acting capacity. No specific applications were discussed, but participants described the meeting as constructive, according to Endpoints News.

“Two things really resounded from the discussion – we need to improve the infrastructure for gathering evidence in rare diseases and also work in the here and now, meeting science where it is and using the tools we have to discern treatment effect even when populations are small and heterogenous. I believe FDA heard that we cannot afford to choose between those goals,” Kara Berasi, CEO of the Haystack Project, said, as quoted by Endpoints.

In another good sign for the industry, the FDA’s internal review of Moderna’s mRNA flu vaccine, mFlusiva, was less critical than what Dr. Prasad raised in a surprise “refusal to file” (RTF) letter back in February.

In briefing documents prepared for an advisory committee meeting this past week, the FDA still raised the issue of the standard-dose control in Moderna’s phase 3, flagging that the preference for individuals ages 65 years and older is a high-dose version. But the agency also said that “no major deficiencies were identified.”

After the RTF, Moderna has adjusted its regulatory plan. For the 65 and above group, the company instead is seeking an accelerated approval while committing to a confirmatory study.

During Thursday’s adcomm, members voted 9-to-0 supporting the flu shot in both those 50 to 64 and 65 and above.

Meanwhile, Replimune said in late May that it and the FDA are “aligned on a path forward” for the agency to reconsider the company’s twice-rejected melanoma cancer vaccine RP1 (vusolimogene oderparepvec). The third chance afforded to Replimune follows endorsement from The Wall Street Journal’s editorial board in tandem with the newspaper’s open salvo against Dr. Makary’s leadership.

Last week, the FDA also granted accelerated approval to Sanofi’s Tzield for stage 3 Type 1 diabetes to delay the progression of disease, confirming the use of decline in C-peptide levels as an approvable endpoint. This application recently hit a hiccup, as Sanofi at one point asked to be removed from the controversial Commissioner’s National Priority Voucher program.

An FDA memo (PDF) now shows that during CNPV review meetings, then-CDER director Dr. Tracy Beth Høeg tried to overrule the review team’s recommendation for approval, causing the agency to miss its original PDUFA date in April.

All these new events suggest that the FDA is gaining stability after last month’s regime change. As a lawyer who had no prior experience in drug development, Diamantas didn’t come in with a preset agenda on how he wants to run the FDA’s drug departments. So, he’s been leaning on the expertise of career scientists, earning their trust while bringing back some level of regulatory certainty.

During the June 3 meeting, Diamantas reportedly told the rare disease advocates that he would prevent political interference in the decision-making of career staff. In his (probably) no-more-than-3-month tenure as commissioner, maybe; but it’s quite impossible for a permanent appointee, as we discussed in Issue 139 about Dr. Makary’s ouster, because political loyalty to President Trump—not science—is a requirement to serve in this administration.

So folks, enjoy it while it lasts.

— , Deputy Editor at Fierce Pharma and iSWTC volunteer

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Summary

In this week’s issue,

• examines two data sets from Eli Lilly’s recent acquisitions of Ajax and Kelonia, laying out the company’s BD strategy from his conversation with Jake Van Naarden.

• recaps the biotech deal-making panel at SAPA 2026 Investment Forum last Friday in New York City where the panelists helped the audience demystify AI and embrace China.

• Our guest contributor, Anran Chen, argues that Tango’s recent 92% ORR data in MTAP-deleted pancreatic cancer validates MTA-cooperative PRMT5 inhibition as a synthetic-lethal strategy — succeeding where first-generation inhibitors failed by building molecular selectivity into the drug itself, with broader implications across the full MTAP-deletion landscape.

On July 1st, ADC experts will converge at BioVerse #32 to share their thoughts on the current landscape of this exciting field. Sign up for the webinar here.

At BioVerse #31, David Dai, Ethan Xu, Viraj Parekh, and highlighted recap ASCO and ADA 2026 on June 10th. Watch the replay on Substack or YouTube here, and paid subscribers can download the presentation from the paid-member-only session.

Hundreds of iSWT Community members are heading for San Diego for BIO and its Satellite events from Jun 21 to 25. San the QR code below to join our in-person networking group that now has 180+ members.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

How Kelonia, Ajax reflect Lilly’s BD strategy

Eli Lilly has been on an M&A spree. Fierce Biotech has counted 10 acquisitions announced so far this year. For a Fierce article, I talked to Lilly’s Jake Van Naarden, who has been the company’s oncology chief by way of its 2019 acquisition of Loxo Oncology. He added the head of corporate business development title toward the end of 2025.

At the 2026 European Hematology Association (EHA) annual meeting, Lilly unveiled the first clinical data from AJ1-11095, a novel JAK inhibitor that it just obtained from an up-to-$2.3 billion acquisition of Ajax Therapeutics.

Unlike existing JAK inhibitors like Incyte’s Jakafi that target the Type I (active) conformation of the JAK2 kinase, Lilly’s candidate goes after the Type II (inactive) conformation. By stabilizing JAK2 in its inactive state, the drug could prevent JAK2 heterodimerization with JAK1/TYK2 and hence disease persistence. Ultimately, the goal is to achieve better efficacy and reduce mutant JAK2 allele burden that drives myeloproliferative neoplasms (MPNs) such as myelofibrosis.

Early results in the dose escalation phase of a phase 1 trial in post-JAK myelofibrosis are very impressive: 70% (16/23) of patients achieved a best response of at least a 35% reduction in spleen volume (SVR35). At week 12, 70% (16/23) achieved a 50% or greater reduction in their total symptom score (TSS50), or 65% (15/23) at week 24 or 96% (22/23) best TSS50.

No dose-limiting toxicities. Five treatment discontinuations included two non-responses but none due to drug-related toxicity.

The results are impressive because historically, in the post-JAK setting, SVR35 response rates ranged from 0% to 32%.

By cross-trial comparison, Lilly’s data look to be on another level than Incyte’s INCA033989, an antibody targeting CALR mutations, which account for about 1/4 or 1/3 of all myelofibrosis cases.

Updated data from Incyte’s phase 1 trial that included dose expansion cohort reported a best SVR35 of 39% (27/69). At week 24, SVR35 was 47% (8/17) among JAK-ineligible (i.e. JAK-naïve) patients and 20% (9/45) among JAK-relapsed/refractory/intolerant patients.

Best TSS50 rate was 53% (37/70). At week 24, 32% (18/56) achieved TSS50.

These data are largely similar to what Incyte presented in December at ASH 2025 with data only from the dose escalation phase. At the time, best SVR35 was 31.3% and best TSS50 was 60%.

Back then, William Blair analysts put the Incyte drug’s peak sales at $1.9 billion. Remember, INCA033989 is designed to target mutCALR, while Lilly’s AJ1-11095 is gunning for a more inclusive population of other mutation types.

Revelation of Lilly’s first Ajax results came shortly after promising early data unveiled at ASCO 2026 for its in vivo CAR-T obtained from its $3.25 billion-upfront buyout of Kelonia Therapeutics.

All 18 patients with previously treated multiple myeloma who got Kelonia’s BCMA-targeted KLN-1010 achieved minimal residual disease negativity. The patient with the longest follow-up—beyond 10 months—also remained in deep remission.

Among the 18 patients, 16 experienced cytokine release syndrome, but all are classified as grade 1 or 2.

These results—again—look favorable compared with AstraZeneca’s initial data from its EsoBiotec buyout. Early results from ESO-T01 in multiple myeloma included only 3 (of 5) stringent complete remission by day 60. All patients developed grade 3 or higher adverse events, and 3 had grade 3 CRS. There was also one death that was not directly attributed to the treatment, although its timing invites questions of an indirect effect.

In both Ajax and Kelonia, Lilly saw very strong early clinical data and made the move.

Van Naarden said he’s running two strategies in dealmaking at Lilly these days.

• One model is about spreading the net—those high-volume, early-stage deals, most of which are too small to be press released. In 2025, Lilly did roughly 40 deals but only spent $4 billion in total.

  “The strategy there is, most of these things won’t work,” Van Naarden explained. “But we haven’t spent that much money in total, so if one or two work, it easily pays for the entire endeavor.”

• Ajax and Kelonia represent the second approach. Van Naarden cited an unprecedented amount of capital (from the incretin franchise), increased certainty on the macroenvironment (drug pricing deals), and the inevitable pharma life cycle as impetuses to pursue this second model more recently.

  Here, Lilly is investing in candidates that “at the time of the deal, you know are real,” he said. Meaning, these assets are more validated with early proof-of-concept clinical data. At the same time, Lilly doesn’t need something to “generate revenue tomorrow.” (Translation: Forget about GSK/Nuvalent type of deals).

“On the balance of 2026 but also going forward, we’re not done with either of these two strategies,” Van Naarden said.

, Deputy Editor at Fierce Pharma and iSWTC volunteer

Demystifying AI and Embracing China: Key Insights from the 2026 SAPA Investment Forum Biotech Deal-Making Panel

Last Friday, I had the privilege of moderating a panel discussion featuring Fernando Salles (Prolalix Biotherapeutics), Allan Shaw (Evecxia Therapeutics), Carla Lema Tome (Otsuka Therapeutics), David Dai (UBS), and Blair Bu (IntelliPro) at the 2026 SAPA Investment Forum.

The following summary outlines the critical takeaways and strategic insights shared by these industry leaders.

2026 Biotech Deal-making is On Track for a Record Year

As of June 12, 2026, the biotech sector is demonstrating unprecedented momentum. Global M&A transactions have already exceeded $108 billion, while licensing deals have totaled over $153 billion, encompassing approximately $12.5 billion in upfront payments. Notably, China-originated licensing deals represent a significant portion of this activity, contributing $94.5 billion in total value with $4.9 billion in upfront payments. Across M&A and licensing, these indicators suggest that 2026 is poised to be a record-breaking year in biotech history.

More details are in the analyses here:

Sapa Ifnr 2026 Panel 2 Bd And M&a

798KB ∙ PDF file

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Hot Trends in the Current Biotech Transactions Landscape

The panel identified in vivo CAR-T, T-cell engagers for autoimmune diseases, siRNA, and protein degraders as the most prominent modalities currently driving deal flow. From a therapeutic perspective, cardiometabolic diseases, immunology, and oncology remain the primary areas of focus.

Following the recent ASCO meeting, David Dai highlighted the surge in the RAS-targeting space, boosted by the impressive phase 3 data from daraxonrasib that received standing ovation in Chicago. While David characterized daraxonrasib as revolutionary, he noted that next-generation (K)RAS-targeting molecules are already demonstrating even more promising clinical profiles.

Actionable Strategies for Effective Deal-making

The panel reached a consensus that experienced BD consultants and investment bankers are indispensable for navigating complex transactions. Allan and Fernando drew upon decades of experience from both the buy-side and sell-side to underscore this point, while Carla highlighted the value of maintaining collaborative, long-term relationships with financial advisors.

To secure optimal terms, top-tier biotech investment banks often manage pricing discovery by running competitive, auction-like processes. This efficacy is rooted in their unique ability to foster trust and facilitate access among key biopharma stakeholders at the same time.

Navigating Regulatory Uncertainty and Macroeconomic Pressures

Regarding Most Favored Nation (MFN) policies, executives like Carla are increasingly integrating mitigation strategies into their deal structures. Paradoxically, while MFN was designed to lower U.S. drug prices, the policy may lead companies to prioritize U.S.-only launches or delay entry into reference countries to manage pricing risks.

Opinions on FDA uncertainty were divided: some panelists reported minimal impact on their current programs, while others argued that the regulator’s stringent approach to certain cell and gene therapies (CGT) has significantly cooled investment in those specific sectors.

Furthermore, the prevailing high interest rate environment remains a significant overhang for the industry at large, and the influx of capital to the AI space could complicate the biotech capital market.

AI and China - The Two Major Themes in Global Biotech

Industry leaders, including Pfizer CEO Albert Bourla, have identified AI and China as the two critical themes dominating their strategic outlook. Regarding AI, while generalist investors have heavily capitalized AI-driven companies, the panel noted that its long-term benefits to biotech’s fundamental business models are still being proven. As one panelist observed: “AI is very good at “in the box” thinking, yet humans are still much better at “out of the box” innovation.”

On the topic of China, Blair and I discussed the 20-month journey of Candid Therapeutics, which culminated in a $2.2 billion acquisition driven by an unprecedented clinical development campaign in China. This serves as a powerful example of why engaging with the Chinese ecosystem is now a strategic imperative, rather than an optional pursuit, for maintaining a competitive edge.

Human Connection as the Ultimate Differentiator

The discussion concluded with a resounding consensus: deal-making remains a people-driven business. In a market saturated with AI-generated reports and generic marketing materials, decision-makers are often overwhelmed. A polished, AI-generated pitch deck sent to a general contact is far less effective than a personalized communication featuring targeted insights sent to a disease area head with whom the sender has an established relationship.

In an era of information abundance, high-quality human connection and trust remain the true differentiators that separate a handful of successful deal-makers from the rest.

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

Tango's 92% ORR and the PRMT5 Revival: What the Data Does and Doesn't Settle

On Monday, Tango Therapeutics (TNGX) posted one of the highest early response rates metastatic Pancreatic Ductal Adenocarcinoma (PDAC) has produced: a 92% objective response rate for its PRMT5 inhibitor vopimetostat added to Revolution Medicines’ daraxonrasib. The cohort is tiny (11 of 12) but it’s the best Phase 1 ORR PDAC has shown.

The market took it seriously. TNGX closed up about 53% at an all-time high of $30.93, a roughly $4.6B company, with the year-to-date gain now around 254%. That afternoon Tango launched a $500M equity raise; the next day it priced at roughly $600M gross, $30.00 a share. The market treated it as the first clinical proof of concept for PRMT5 + pan-RAS, with a strong bias on PRMT5: daraxonrasib’s owner, Revolution Medicines, barely moved.

Two things are worth holding apart from the start. The result signals a continuing revival of a target the field had nearly written off — and the move ran well ahead of 12 patients. The more durable story isn’t the pancreas number; it’s what it says about PRMT5.

The most clinically advanced synthetic-lethal idea since PARP

PRMT5 was a marquee oncology target a decade ago, and then a graveyard. The first-generation inhibitors — GSK’s pemrametostat (GSK3326595), J&J’s onametostat (JNJ-64619178), Pfizer’s PF-06939999 — all hit the same wall. They blocked PRMT5 in every cell indiscriminately, and because PRMT5 is essential to blood-cell production, dose-limiting anemia and thrombocytopenia capped exposure below the level needed to kill tumors. Responses were modest and scattered, and the enrichment hypotheses that were tried — broad solid-tumor activity, then splicing-factor-mutant myeloid disease — never delivered a consistent signal. GSK ran pemrametostat through nearly 300 patients and had to cut the dose for toxicity; Pfizer terminated its program in 2022. By the early 2020s, PRMT5 looked like a cautionary tale about an essential enzyme with no therapeutic window.

The vulnerability that would eventually matter was already on the table. In 2016 (Kryukov et al., Science), cancers that delete MTAP were shown to become selectively dependent on PRMT5 — and the mechanism is unusually clean. MTAP sits on chromosome 9p21.3, immediately next to CDKN2A, one of the most frequently deleted tumor suppressors in cancer; when a tumor drops CDKN2A it usually takes MTAP with it as a passenger. The cell loses an enzyme it never meant to lose, MTA (methylthioadenosine) accumulates, and that MTA partially jams PRMT5 — but only in the cancer cell. However, the MTAP-PRMT5 story did not end well for the first-generation drugs. Being SAM-competitive, they inhibited PRMT5 the same whether or not MTA was elevated. Due to toxicity, the therapeutic window is extremely narrow.

The second generation was built to exploit exactly the MTA gradient. These agents are MTA-cooperative, which is more inhibitory in MTA-high cells. This strategy provides two levels of selectivity: biologically, the high MTA in MTAP-deleted cells already sensitizes them to PRMT5 inhibition; chemically, the MTA-cooperative design makes the inhibitor selectively more potent in those same MTA-high cells. The toxicity that sank the first generation is, in principle, designed out. Vopimetostat is one of these, other examples include Mirati-then-BMS’s MRTX1719 (BMS-986504), Amgen’s AMG 193, AstraZeneca’s AZD3470, Bayer’s BAY3372.

The population is large. Roughly 10–15% of all cancers carry the deletion, concentrated in the hardest tumors: ~40% of PDAC, ~15% of NSCLC, ~45% of glioblastoma. Tango frames it as ~60,000 MTAP-deleted metastatic cases a year in the US, ~20,000 of them pancreatic.

All of which makes MTAP deletion the most advanced synthetic-lethal vulnerability oncology has found since BRCA/PARP — the pairing whose approval, more than a decade ago, defined the idea, and whose lack of successors let the enthusiasm fade. It also sharpens what synthetic lethality actually requires. A genetic dependency on its own rarely delivers a usable therapeutic window: the first-generation inhibitors had the right target and the right patients and still failed, because genetic selectivity doesn’t translate into selective drug action. Opening the therapeutic window took a second layer of selectivity, built into the molecule rather than the patient — a chemotype that reads the consequence of the lesion (elevated MTA), not just the lesion itself. Genetic selectivity defines who to treat; molecular selectivity is what actually widens the window.

Combination partners

On combination partners, two ideas dominate. In NSCLC and PDAC, KRAS is the natural pairing, given the overlap between MTAP deletion and KRAS mutation — though not in GBM, where KRAS mutation is rare. The other is MAT2A, which sits in the same SAM/MTA pathway and shows synergy in preclinical models

What Tango actually showed

The 28 May cut is a Phase 1 escalation with two arms in MTAP-deleted, 2/3L disease: vopimetostat plus daraxonrasib (any RAS), and plus zoldonrasib (G12D-only). The headline is the daraxonrasib arm — 92% ORR, 11 of 12, 100% DCR, 90% six-month PFS, median PFS not reached. The larger G12D zoldonrasib arm read 52% in 27. Pooled, 2/3L pancreas is 64% in 39.

Two caveats sit under the 92%. First, n=12: the confidence interval on six-month PFS runs 47–99%, and dropping one responder takes the ORR to 83% (10 of 12). This is a real signal in a disease that concedes nothing — and it’s a twelve-patient single-arm cohort. The honest read is the pooled 64% on about six months of follow-up. Second, the headline arm is the smaller, broader one; the G12D-restricted arm, with more than twice the patients, reads 52%.

That 40-point spread is one of the most interesting things in the dataset, and Tango offered both readings without resolving them. The attractive explanation, supported preclinically: PRMT5 inhibition upregulates wild-type RAS activity, which a pan-RAS agent suppresses and a strictly G12D-selective one cannot. The duller one, probably also true: these are non-randomized arms with small numbers, the zoldonrasib patients had worse ECOG, and other baseline differences likely run the same direction. The current data can’t apportion the two, and the reasonable guesses remain guesses.

The dose detail

The other eye-catching differentiator is dosing. Daraxonrasib runs here at 100 mg — versus 300 mg in RASolute 302 and 200 mg in Revolution’s own gem/nab-paclitaxel combination, on paper the deepest RAS dose cut in development. But it isn’t less drug: vopimetostat raises daraxonrasib exposure roughly 3×, so 100 mg here matches the AUC of 300 mg alone — an interaction Tango predicted before the trial. The mechanism is well-grounded. Published PK work shows daraxonrasib is cleared substantially by CYP3A4 and taken into the liver by OATP1B, so inhibiting those routes lifts its exposure two ways at once — higher oral bioavailability and slower clearance. The one unconfirmed link is that vopimetostat is the inhibitor doing it; that is not a disclosed fact.

When taking a closer look, this model faced several caveats. The PK story cannot explain the reduced RAS-associated toxicity. Also Building a regimen on a boosting interaction imports a real liability: daraxonrasib exposure now depends on CYP3A4/OATP activity, which varies with genetics, food, and concomitant CYP3A inhibitors/inducers. It is also worth noticing that the match comes off a small PK sample, so the PK statement is at best directional, not settled.

Who gets the pan-RAS backbone in MTAP-deleted PDAC

Daraxonrasib is at the center of the stage; the question is who can dance with it. Mechanistic orthogonality is the easy bar — PRMT5, MAT2A, and chemo all clear it. And in PDAC, MTAP deletion mostly co-occurs with KRAS mutation, so the RAS backbone fits the biomarker population.

So the endgame in MTAP-deleted pancreas most likely resolves into three backbones competing to pair with pan-RAS — PRMT5, MAT2A, chemo — not a comfortable three-drug stack. The contribution-of-components problem haunts every doublet of two active agents: vopimetostat has real monotherapy activity (27% across histologies, 49% histology-selective) and daraxonrasib carries pancreas on its own, so proving the combination beats each component — and, in front line, beats FOLFIRINOX and gem/nab-paclitaxel on survival — is the bar. It sits far above any response rate.

Beyond pancreas, the RAS pairing falls away

The RAS backbone is mostly a pancreas story, and pancreas is the smaller half of the prize. The real franchise is the whole MTAP-deletion footprint, where KRAS is not necessarily the most important player. PDAC (~20,000 cases a year) is the easy case precisely because KRAS is near-universal there — an MTAP-deleted pancreatic tumor is almost by definition also a RAS-combination candidate. That co-occurrence doesn’t hold elsewhere. In NSCLC — the largest slice, ~22,000 MTAP-deleted cases — only about a quarter of tumors carry a KRAS mutation, and MTAP loss has no statistical co-occurrence with it; most MTAP-deleted lung cancer is simply not a RAS-doublet population. In glioblastoma (~7,000), KRAS mutation is rare to begin with. Strip out the KRAS-driven tumors and the RAS partner carrying this week’s narrative falls away, leaving the bulk of the MTAP footprint as a contest fought on the PRMT5 (or MAT2A) molecule itself.

Cytopenia is the gating property. Anemia and thrombocytopenia are the on-target, dose-limiting toxicity of PRMT5 inhibition — the same toxicity that sank the first generation — and across the rest of the MTAP map, mostly monotherapy or non-RAS combinations, the selectivity window that lets a drug reach efficacy without crashing blood counts is what separates the molecules. The other differentiator is CNS penetrance, since glioblastoma and the brain metastases NSCLC throws off are unreachable by a systemic-only drug. Only Tango’s purpose-built TNG456 and Amgen’s AMG 193 are reported brain-penetrant; vopimetostat is not — which quietly makes Amgen, already in pancreas with chemo, the one competitor in both halves of the franchise. This is the field where a drug’s own properties, far more than the pancreas ORR, start to decide things.

PRMT5 spent a decade as proof that an essential enzyme is hard to drug. The MTA-cooperative generation is the bet that a biomarker fixed that. Tango just delivered the strongest evidence so far that the bet is good — and the first clear view of how many companies are about to be fighting over the same map.

Anran Chen , Guest Contributor, Oncology researcher at Bayer

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• ASCO: PD-1/VEGF drug class, especially ivonescimab from Akeso and Summit Therapeutics; ADC; and other targeted therapies.

• ASCO: Daraxonsarib from RevMed, next-gen immuno-oncology assets, and other interesting assets.

• ADA: Triple-agonist retatrutide’s phase 3 data; Pfizer’s one-month long-circulating GLP-1 injectable; and the mixed results from the muscle-preserving space.

• Tidbits of the US-China biotech “coopetition” from ASCO and ADA.

Free subscribers can watch the video on our YouTube channel here.

Paid subscribers can download the PDF of the presentation (behind the paywall).

Please email contact@iswtc.org for any questions.

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Summary

In this week’s issue,

• shares his thoughts on the divergent market reactions to the positive China-only clinical data from Akeso/Summit’s HARMONi-6 and Legend Biotech’s first-in-human in vivo CAR-T.

• Anran Chen, an oncology research at Bayer, assesses the landmark RASolute 302 P3 results for daraxonrasib in 2L metastatic pancreatic cancer, then uses that milestone to reframe the competitive dynamics across mutation-selective, pan-KRAS, and pan-RAS programs going forward.

At BioVerse #31, David Dai, Ethan Xu, Viraj Parekh, and will recap ASCO and ADA 2026 on June 10th. You can register for the webinar here. Many iSWT Community members are in New Orleans for ADA 2026 conference. Scan the WeChat QR Code below and join our networking group to meet other members at the conference. Both in-person and virtual attendees are encouraged to join.

SAPA Healthcare Investment Forum & Roadshow is this Friday, where many iSWTC members will speak and attend. Scan the QR code to join the networking WeChat group for speakers and in-person attendees. This group is ONLY open for in-person attendees.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

Thoughts on Divergent Market Reactions to Akeso and Legend’s China-Only Data

Recent positive clinical data releases from Akeso and Legend Biotech have triggered very different capital market outcomes - Legend enjoyed up to 40% stock jump throughout the week whereas Akeso / Summit suffered 10%+ decline.

Although both China-only datasets were deemed positive, investor sentiment diverged significantly, reflecting nuanced skepticism toward clinical data reproducibility and market positioning.

LB2501 First-in-Human Results Impressed

Legend Biotech’s China-only first-in-human (FIH) trial for LB2501, an in vivo CD19/CD20 dual-targeting CAR-T, was exceptionally well received. Investors drove the stock up significantly following data showing a 100% Objective Response Rate (ORR) at the second dose level of 6 patients. Furthermore, the toxicity profile was favorable, with no ICANS reported and all adverse events limited to Grade 1 or 2, establishing a strong foundation for in vivo CAR-T as a potential successor to autologous therapies.

HARMONI-6 OS Hit Received Mixed Reactions

In contrast, Akeso’s HARMONI-6 data, presented at ASCO, received a lukewarm reception despite demonstrating meaningful overall survival (OS) benefits with an OS hazard ratio of 0.66. The market responded with a combined valuation decline of over $3.5 billion for Akeso and Summit. Skepticism centered on the China-only patient population, with Dr. Julie Brahmer highlights the lack of global diversity as a primary limitation. Yet some analysts like Evercore’s Cory Kasimov maintain confidence in the upcoming global HARMONi-3 trial expected to read out in H2 2026.

Overall, the immediate reaction underscored a lack of “benefit of the doubt” regarding the reproducibility of these results in Western populations.

Comparative Market Dynamics of Akeso and Legend

In my opinion, the disparity in market reactions is rooted in competitive intensity and corporate track records. Akeso/Summit operates in the crowded PD-1/VEGF space, facing significant pressure from major players like BMS/BioNTech, Pfizer, AbbVie, and Merck.

Conversely, Legend benefits from its proven ability to reproduce Chinese IIT data globally, ability to secure FDA approval, and its established commercial infrastructure in Western markets. The recent ASCO presentation by Kelonia, which was acquired by Eli Lilly recently,, read through very well to the lentiviral in vivo CAR-T technology used by Legend’s program.

Quality Standards as a Differentiator

Despite the speed of the Chinese clinical system, data quality is not uniform. The primary differentiator for successful global integration is rigorous oversight.

According to my colleague Jimmy Ren, who oversaw the Legend / J&J partnership for 4 years, the partnership utilized a functional service provider (FSP) CRO model that ensured J&J to retain full control over clinical operations and data integrity by directly managing the full-time employees of clinical CRO as FSPs.

The China country head from a leading global CRO, based on our recent meeting, stated that Legend’s stringent internal requirements for investigator-initiate trials (IIT) often exceed the industry standard for the industry-sponsored trials (IST), reinforcing that while China offers unprecedented speed, it is the quality of execution that ultimately determines global value.

China’s Essential Role in Global Clinical Development

China remains an essential hub for global clinical recruitment. According to an ASCO presentation by Jeff Legos, Pfizer’s Chief Oncology Officer, 100% of Pfizer’s late-stage oncology trials and 62% of early-stage trials recruited patients from China in 2025. The large number of important presentations at ASCO 2026 is another example, as reported by .

More importantly, the region’s flexible early-stage trial ecosystem has become a default strategic component for biopharma and biotech - China’s flexible early-stage trial infrastructure has generated high-quality first-in-human datasets that powered acquisition of biotechs like Candid Therapeutics and EsoBiotec, as well as market successes like Legend Biotech.

Bottom Line

The clinical development ecosystem in China has solidified its standing as a vital node for international medical breakthroughs, increasingly serving as a strategic cornerstone for biopharma through its unmatched reach and adaptability.

In my view, the recent legislative attempts in the US to restrict this collaborative framework are profoundly shortsighted. By blocking access to such a primary driver of robust infrastructure to generate first-in-human clinical data and unmatched source of patient resources, these measures pose a direct threat to the welfare of American patients awaiting the next generation of curative treatments.

, Founder of ISWT BioAdvisory & BD head of Mianus Accelerator

After the Ovation: A Post-Daraxonrasib world of KRAS landscape

When the RASolute 302 data finished on the plenary screen, the room stood. It is worth pausing on that before any discussion of mechanism, sequencing, or competitive position, because a standing ovation at ASCO is not given for a hazard ratio. It is given when a disease that has outlasted the field for decades finally gives ground.

Metastatic pancreatic cancer is about as hard as oncology gets. Roughly half of patients are diagnosed after the disease has spread, five-year survival in the metastatic setting sits near 3%, and second-line chemotherapy has offered only six to seven months of median survival. For patients and the clinicians who treat them, this is the first time a RAS-directed therapy has changed the trajectory of this disease in a randomized phase 3.

For chemical biology, the meaning is just as large. KRAS was the canonical “undruggable” target for forty years. The achievement should be named as such before anything else.

A close look at RASolute-302 trial

While the topline had been public since April, the plenary’s job was to show the texture beneath the headline. The intent-to-treat and the RAS G12 co-primary populations told nearly the same story: OS 13.2 vs 6.6–6.7 months (HR 0.40), PFS 7.2–7.3 vs 3.5–3.6 months (HR 0.45–0.49), confirmed response 31.6–33.2% vs 11.2–11.8%. The efficacy is not carried by a single endpoint or a single analysis population.

The genuine surprise was tolerability. A drug that hits wild-type RAS was widely expected to pay for breadth in toxicity, and against chemotherapy it did the opposite: fewer grade ≥3 treatment-related events (43.6% vs 57.5%), far fewer discontinuations (1.2% vs 11.2%), and fewer dose reductions (36.1% vs 57.5%). The discontinuation gap deserves a caveat — chemotherapy toxicity forces patients off treatment while responders on an oral agent stay on, so some of that spread is structural. But the dose-reduction comparison does not have that confound: it is a within-treatment event, and daraxonrasib patients were on drug far longer (median 6.2 vs 1.5–3.2 months), with more time to accumulate toxicity, and still required fewer reductions. What reductions they did need were driven by on-target, manageable effects — rash, stomatitis, diarrhea, largely grade 1–2 — rather than the myelosuppression and neuropathy that define chemotherapy.

One honest limitation belongs here too. At the February data cut, median follow-up was only about 8.5 months while median OS reads 13.2 months, with an upper confidence bound not yet estimable. The direction and magnitude of benefit are clear but the precise survival tail will firm up only with longer follow-up. This is a strong result still maturing.

One of most quoted lines recently about daraxonrasib is that it works “regardless of RAS mutation status”. That framing is true in the sense the trial was designed to show, but looking deep into the NEJM recent release showed more nuances.

RAS G12 mutation accounts for roughly 80–85% of metastatic PDAC in the real world; RASolute 302 enrolled an even higher share, about 92%. The whole-population benefit is, therefore, substantially a G12 benefit wearing a pan-RAS label — and within G12 it is overwhelmingly G12D/G12V (OS HR 0.38).

Step outside G12D/V and the evidence thins quickly. The “other G12” subgroup crosses 1.0 on both survival and progression. And in the non-G12 subgroup — G13, Q61, or no RAS mutation identified, only about twenty patients per arm — overall survival is nominally favorable (HR 0.37) while progression-free survival actually favors chemotherapy (HR 1.38, with most progression events on daraxonrasib), both with wide 95% CIs.

The “regardless of mutation” story is best read as a reasonable bet supported mainly in G12D/V, not an established fact across RAS — consistent with where the FDA placed the Breakthrough and Orphan designations: G12-mutant, previously treated disease. The benefit outside G12D/V remains inconclusive.

For all the debate it draws, the G12-only-versus-all-comers label question is a small one commercially. It swings perhaps 15–20% of the second-line population, a minor uncertainty next to the bigger questions.

The bigger commercial questions that actually decide the platform’s value is not 2L mPDAC. Second-line pancreatic cancer is a meaningful achievement on its own, but it is not where the weight of the opportunity sits. There are other fields that matter more:

• 1L PDAC. The treated first-line pool is roughly two to two-and-a-half times the second-line pool, with longer treatment duration earlier in disease, and RASolute 303 is the trial that addresses it (daraxonrasib alone, daraxonrasib plus gemcitabine/nab-paclitaxel, or gemcitabine/nab-paclitaxel alone; co-primary PFS and OS). RASolute 302 has de-risked the biology and the safety assumptions, but 303 carries risks 302 did not: a first-line comparator far tougher than second-line chemotherapy, harder recruitment into a more competitive landscape, and a three-arm design that dilutes statistical power. The early first-line signals are encouraging (combination response ~55–58%, monotherapy ~47%), but they are early.

• Lung and colon. A pan-RAS mechanism logically reaches KRAS-mutant NSCLC and RAS-mutant colorectal cancer, both larger than PDAC and both in trials, and the bars are higher in each. NSCLC is G12C’s home, with established selective agents and IO-combination strategies, so a broad agent has to justify why more pathway inhibition beats a clean mutant-selective drug. Colorectal is harder still: EGFR-mediated feedback blunts RAS monotherapy, and the pancreatic effect size should not be assumed to transfer. The pancreatic result is the proof of concept, not a forecast for the other two.

RAS landsacpe post RASolute-302

Last year I discussed the pan-RAS and pan-KRAS programs against mutation-selective G12C and G12D agents (here issue 115). RASolute 302 begins to answer the toxicity question that hung over the pan-RAS approach, and in doing so shifts the bar each class is measured against. The pancreatic readout does not land evenly across the RAS landscape. It pressures mutant-selective, pan-KRAS, and pan-RAS programs to different degrees, and worth reading those effects separately.

Mutation-selective inhibitors keep their core biological argument: a G12C- or G12D-selective drug spares H- and N-RAS and wild-type KRAS, and that selectivity should translate into a narrower, lower-grade toxicity profile than an agent that inhibits the active state across all of RAS. Daraxonrasib’s registrational grade ≥3 treatment-related rate of 43.6% — favorable against chemotherapy — is the relevant anchor here, and the cross-comparison with the early profiles of selective agents such as zoldonrasib and ASP3082 (setidegrasib) is exactly the trade-off this implies. The changing factor is that the benchmark for the selective agents has moved. For G12D in particular, the comparator is no longer chemotherapy; it is daraxonrasib. A G12D-selective drug now has to demonstrate a survival readout in the same neighborhood and win on tolerability, which is a narrower path than competing against chemo. G12C, meanwhile, still contends with the first-generation incumbents in NSCLC — and daraxonrasib, not yet read out in lung cancer, will soon press there too.

Pan-KRAS relies on a Goldilocks position: a larger addressable population than any single mutant-selective drug, with less wild-type-RAS exposure than full pan-RAS. But daraxonrasib’s better-than-feared safety has compressed precisely the advantage pan-KRAS was meant to monetize — the room to be “broad but gentler” is thinner than it looked. The needle is still threadable; the eye is smaller.

A combination is where the threads most plausibly converge. A switch-II-pocket binder is mechanistically orthogonal to a tri-complex, which gives pan-KRAS and mutant selective SII-P binders a coherent rationale to pair with a pan-RAS(ON) backbone rather than simply compete with it. On the other hand, Revolution Medicines, with its own selective tri-complexes toolkit alongside daraxonrasib — has the operational advantage of building those combinations in-house, without the friction a cross-company pairing would require.

Pan-RAS is the toughest game for any fast-follower. Every credible competitor shares the same tri-complex, cyclophilin-A-mediated design, so the first-in-class advantage is large and durable. Absent a demonstrated edge in DMPK or potency, a second pan-RAS(ON) agent will struggle to differentiate on concept alone.

Exhibit — the RAS-targeting landscape, by target and modality

It is possible to hold two things at once. RASolute 302 is a landmark — the first targeted therapy to bend the survival curve in metastatic pancreatic cancer, and the clinical validation of an approach the field spent decades believing was impossible. It earned its ovation.

What it did not do is to settle anything downstream: whether the benefit extends cleanly beyond G12D/V, whether first line converts, whether a pan-RAS mechanism travels to lung and colon, and how mutant selective, pan-KRAS, and pan-RAS strategies divide the work.

The ovation marked the end of the hard part of the science. It marked the beginning of the hard part of the strategy — for RevMed and its competitors alike.

Anran Chen , Guest Contributor, Oncology researcher at Bayer

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Summary

In this week’s issue,

• comments on the $10.5-billion Pfizer/Innovent Co-Co deal and the highlights of China biotech at ASCO, including our another robust Asian Biotechies In A Bar, LITERALLY gathering.

• Xueting Jiang, a former buy-side analyst who followed Kelun for nearly a decade, traces how a Chinese IV-fluid company’s industrial discipline, capital patience, and messy but persistent R&D buildup quietly produced one of the most competitive TROP2 ADC platforms in global oncology.

BioVerse #31 will have David Dai, Chandler Park, , and additional speakers to conduct a deep-dive recap of ASCO and ADA during BioVerse #10 on June 10th. You can register for the session here.

Our ISWT Community Boston Chapter organizes a panel to brings together experienced biopharma leaders to offer something beyond the usual job search advice: honest, hard-won perspectives on building a resilient career — not just landing the next role.

The event is scheduled on June 06 and more details about can be found at the registration page.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

The $10.5B Pfizer-Innovent Mega-Deal & China’s Spotlight at ASCO 2026

The global biopharma landscape is shifting rapidly, and if this year’s ASCO in Chicago has proven anything, it’s that the bridge between East and West is stronger—and more lucrative—than ever.

The $10.5 Billion Elephant in the Room

The headline dominating conversations this week is Pfizer’s massive $10.5 billion oncology deal with China’s Innovent Biologics, encompassing a sweeping portfolio of 12 assets. This isn’t just a massive financial commitment; it’s a powerful validation of China’s early-stage R&D capabilities and a clear signal of where Big Pharma is looking to replenish its pipelines.

As highlighted by my post on LinkedIn, this mega-deal underscores several major industry trends:

• Accelerating Partnerships: This marks the fifth major Big Pharma/China biotech mega co-development deal in just 12 months.

• Recognition of China Speed and Efficiency: To quote Pfizer CEO Albert Bourla, Chinese biotechs are “doing everything half the cost, three times the speed.”

• Evolving Deal Structures: We are seeing a massive shift toward sophisticated, collaborative structures—including Co-Development, Co-Commercialization, and “Reverse BD”—rivaling the total deal value of traditional East-to-West licensing.

• R&D Competitiveness Trumps Geopolitics: Despite ongoing congressional debates regarding the containment of China’s biotech sector, the market is speaking for itself. Innovation and the sheer need for clinical proof-of-concept are overriding geopolitical friction.

When I asked a panel of deal-makers at the AHEA event last Friday night if more deals like this would be announced in 2026, I got a resounding “Yes”.

The Power of Personal Connections

While the financial figures make the headlines, the speed and success of these cross-border deals often come down to the people behind them.

As noted in a LinkedIn post by Blair Bu regarding the AHEA Cross-Border Collaboration Executive Forum at ASCO, personal connections among key deal-makers are the true catalysts. The close-knit network of leaders—from Hengrui and BMS to Innovent and Pfizer—demonstrates that integrating a global strategy relies heavily on relationships.

On a personal note, , , and I finally met at ASCO, and we made friend our great friend Ivy!

The third Chicago installment of the Asian Biotechies In A Bar, LITERALLY event hosted at the BIG Bar was another very robust gathering. Just as the success of major cross-border deals relies on personal connections, this event demonstrates how we at continue to foster that critical network, helping our members to connect, to collaborate, and succeed, TOGETHER.

China-Originated Clinical Innovation: Rising Prominence & Scientific Hurdles

Outside the sphere of high-value deal-making, the spotlight at ASCO is shining intensely on clinical data born in China. With the scientific community tracking results from the plenary presentation of Harmoni-6 trial (an article by ), new Sac-TMT readouts ( again :p), and HER2 biparatopic mAB anbenitamab phase 3 hit, there is palpable excitement regarding the therapeutic efficacy and novel R&D now streaming from the East.

Yet, a critical perspective is essential. Even as momentum builds, Western partners and regulatory bodies remain cautious of notable disparities in China-originated datasets, specifically focusing on:

• Gaps in Control Arm Standards: Comparators in several studies frequently fail to align with the contemporary standard of care expected in US or European markets.

• Enrollment and Demographic Nuance: Distinctive patient selection criteria and demographic profiles present ongoing challenges for bridging this data to a global clinical context.

Connecting the Dots Post-Conference

On a final note, David Dai, Chandler Park, and I will be joined by a panel of industry experts for a deep-dive recap of ASCO and ADA during BioVerse #10 on June 10th. You can register for the session here.

, Founder of ISWT BioAdvisory

From IV Bags to Sac-TMT: How Kelun Built a Top TROP2 ADC the China Way

About the Writer: Xueting Jiang is a Boston-based former buy-side healthcare analyst who has followed China’s pharmaceutical industry for more than a decade, with a focus on cross-border healthcare innovation and China-origin assets entering the global market.

When sacituzumab tirumotecan — MK-2870, or sac-TMT — became one of the most closely watched TROP2 ADCs in global oncology, most investors naturally traced the story back to Merck. The latest ASCO 2026 data only strengthened that instinct. In the Phase 3 OptiTROP-Lung05 study in first-line PD-L1–positive advanced NSCLC, sac-TMT plus Keytruda reduced the risk of progression or death by 65% versus Keytruda alone, with median PFS not reached versus 5.7 months and ORR rising to 70.2% from 42.0%. Overall survival was still immature, but the early trend favored the combination. By the investigators’ framing, this was the first Phase 3 study to show a significant PFS benefit for an ADC plus pembrolizumab regimen in this setting.

Yet the more revealing story begins further upstream. Before sac-TMT became MK-2870, it came out of Kelun — a Chengdu, China-based pharmaceutical company better known for IV fluids than for global oncology innovation.

For Western investors and business development teams, Kelun is a case study in how an older industrial pharma company can turn manufacturing discipline, capital patience, and organizational pressure into a globally relevant innovation platform.

Two Companies, One Origin Story

Before going further, a structural point matters. This article traces the history of Kelun Pharmaceutical, the parent company whose capital, culture, and industrial history made the ADC platform possible. The platform itself now sits inside Kelun-Biotech, a separately listed subsidiary that completed its Hong Kong IPO in 2023.

That separation was deliberate. For the parent company, it carved the innovation business out of a lower-margin industrial P&L. For Kelun-Biotech, it created an independent identity, its own valuation framework, a dedicated financing channel, and the infrastructure to engage global partners.

Kelun Pharmaceutical is the origin story. Kelun-Biotech is where that story is now being tested against global biotech standards.

Industrial DNA

My first visit to Kelun Pharmaceutical’s Chengdu headquarters was long before anyone was talking about its ADC pipeline.

A detail from that visit stayed with me. Employees were expected not to use the elevators — cost discipline rendered literal in a building’s daily routines. The company also maintained a formal emphasis on employee weight management. At the time, that detail was easy to dismiss as a corporate idiosyncrasy. In retrospect, they revealed something more durable: a belief that the habits required to survive in China’s brutally competitive IV-fluid market — cost control, physical discipline, operational rigor, and process consistency — were not sector-specific. They were organizational values.

That same culture, transposed into drug development, begins to look surprisingly relevant to ADCs.

ADCs are often described as a scientific modality, but in practice they are also an industrial one. Chemistry, antibody biology, linker-payload design, toxicology, CMC, payload handling, manufacturing scale-up, and clinical execution all have to work together. A company trained for years in the margins of large-volume infusion was not obviously training for ADCs. But it was training in discipline, scale, process, and execution — capabilities that later became unexpectedly important.

The Xinjiang Detour

Kelun’s 2010 IPO raised roughly RMB 5 billion and was meant to support a broader “Three-Drive” strategy across infusion, APIs, formulations, and R&D. But the company’s first major capital deployment went in a very different direction.

In late 2010, Kelun established Chuanning Bio in Xinjiang as a large antibiotic-intermediate manufacturing base. The project eventually required close to RMB 6 billion of investment — roughly the size of the entire IPO proceeds — and exposed Kelun to exactly the kind of burden traditional pharma companies often underestimate: heavy capex, long payback cycles, commodity pricing, environmental complexity, and balance-sheet pressure.

This matters because Kelun’s R&D transformation was never a clean story of excess cash being redeployed into innovation. Unlike global pharma companies investing ahead of a patent cliff, Kelun was trying to reinvent itself while still carrying the financial and operational weight of its old industrial bets.

Innovation Under Pressure

At the same time, China’s capital markets were starting to reward a new pharma narrative. Hengrui became the reference point: a traditional Chinese drug company re-rated for sustained investment in innovation. For Kelun, the contrast was uncomfortable. It had scale, manufacturing depth, and cash flow, but it was not yet seen as an innovation company.

Its R&D transformation therefore began less as a clean master plan than as a pressured catch-up effort. Kelun built research institutes, recruited external talent, and invested across biosimilars, biologics, small molecules, and manufacturing platforms before any single program looked globally meaningful.

The ADC platform came later — not from a perfectly designed roadmap, but from years of scattered, expensive, and persistent capability-building that eventually converged.

Organized Chaos as a Feature

There is always a temptation, with the benefit of hindsight, to turn Kelun’s story into a deliberate platform-building narrative. That would be too neat.

Kelun did not have the markers Western investors often associate with biotech innovation. There was no Nobel-pedigreed founder, no Silicon Valley formation story, no venture-backed origin, and no clean scientific thesis from day one. The company came from large-volume infusion — a business defined by scale, thin margins, quality control, manufacturing discipline, and the daily pressure of cost survival.

As an analyst who followed the company for nearly a decade, I watched the early R&D phase in real time. It was genuinely hard to narrate. Kelun was building research institutes, running biosimilar programs, exploring small molecules, investing in biologics manufacturing, and still managing the complexity of Xinjiang. The individual projects were often less important than the fact that the company was building an R&D organization at all.

It looked like a company running hard in several directions at once — held together by capital, family control, manufacturing cash flow, and institutional stubbornness.

Kelun’s path was more organization-led than a technology-led platform evolution. Its capabilities accumulated across antibody biology, medicinal chemistry, payload intuition, toxicology, CMC, clinical development, and manufacturing before ADCs became the place where those capabilities could express themselves most clearly.

In many modalities, that kind of scattered path would be a weakness. In ADCs, it can become an advantage. ADCs reward accumulated, cross-functional capability. No single function is sufficient. A good antibody is not enough. A potent payload is not enough. Manufacturing alone is not enough. The platform only works when chemistry, biology, toxicology, CMC, clinical strategy, and execution are integrated tightly enough to move real products forward.

Kelun did not arrive at sac-TMT because it had a single guiding thesis from day one. It arrived there because it stayed in the game long enough for dispersed investments to become institutional muscle.

The People Behind the Platform

Kelun’s ADC story is also a story of people — though it should not be reduced to any single executive or scientist.

Wang Jingyi represented an earlier phase of Kelun’s innovation buildout: the effort to create R&D infrastructure inside a company that had no prior identity as an innovator. At that stage, the goal was not necessarily one specific molecule or modality. It was organizational capability itself.

Xue Tongtong came to represent a later phase, when biologics, small-molecule chemistry, CMC, clinical development, and global business development began to converge more specifically around ADCs. After departing Kelun, she founded MediLink Therapeutics, which quickly attracted international partnerships of its own.

The subsequent legal dispute between Kelun-Biotech and MediLink is easy to read as corporate drama. But it also reflects something more structural: China’s ADC sector had become valuable enough for talent mobility, platform know-how, and trade-secret boundaries to genuinely matter. That is a sign of maturity rather than tension.

The Broader Lesson for China Pharma

Understanding Kelun requires resisting the search for a single genius, a single perfect molecule, or a perfectly designed strategy.

Kelun is not alone. It represents a broader strand of China’s pharmaceutical industry: companies that began with manufacturing, generics, hospital channels, and industrial execution, then gradually accumulated the capabilities needed for more complex innovation. Their strength is often not speed in one dimension, but coordination across many — more decathlon than 100-meter sprint.

Kelun’s path was not cleaner than its peers. It was burdened by legacy businesses, heavy capex, organizational complexity, and years of uncertain R&D spending. But industrial discipline, capital patience, family conviction, manufacturing cash flow, and tolerance for disorder can sometimes create capabilities that look, in hindsight, as if they were planned all along.

For investors and Western BD teams, the lesson is broader than sac-TMT. China’s next wave of globally relevant assets may not always come from textbook venture-backed biotechs. Some may come from older industrial pharma organizations whose capabilities were built slowly, messily, and almost invisibly — until a modality like ADCs suddenly made them visible.

Kelun-Biotech’s global test is still ongoing. Sac-TMT’s final value will depend on data, competition, execution, and market adoption. But the industrial story is already instructive: a Chinese IV-fluid giant did not become an ADC platform overnight. It carried its old discipline into a new modality — and found that the habits of industrial survival could become a foundation for global innovation.

XueTing Jiang , Guest Contributor, former buy-side healthcare analyst covering China Biopharma industry

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Our newsletter writers will take a break during the long Memorial Day weekend. As our readers unwind or prep your travel itinerary for Chicago, we highly recommend adding these insightful podcast episodes and long-read to your playlist. All offer incredible perspectives on the extremely turbulent biotech industry at the moment:

• Pfizer CEO: Transforming Drug Discovery, Lessons from China and Leading with Optimism: Albert Bourla joins In Good Company with Nicolai Tangen to discuss navigating Pfizer through the COVID-19 breakthrough, the growing importance of China and AI.

• Jeremy Levin on Biotech in the Balance: Jeremy Levin joins The Long Run with Luke Timmerman for a deep dive into the ethics of biotech, the necessity of regulatory transparency, incentivizing patient capital, and China’s strategic position in the industry.

• RA Capital’s Peter Kolchinsky and Tess Cameron argue a China biotech ban weakens America: A proposed US ban on Chinese biotech collaborations risks shifting global pharmaceutical leadership and profits to European competitors. While securing drug manufacturing outside of China is critical, blocking access to their efficient early-stage clinical trials will only harm American innovation. Ultimately, this protectionist approach would inflate costs and slow down US patient access to vital new medicines.

Boston Chapter In-Person Panel Discussion

Beyond the Job Search: Career Strategy in a Challenging Biopharma Market

The biopharma industry is going through one of its most turbulent periods in recent memory. Layoffs, pipeline cuts, and a difficult hiring market have left many talented professionals navigating prolonged job searches — often in isolation, and without a clear roadmap.

Our ISWT Community Boston Chapter organizes a panel to brings together experienced biopharma leaders to offer something beyond the usual job search advice: honest, hard-won perspectives on building a resilient career — not just landing the next role.

The event is scheduled on June 06 and more details about can be found at the registration page.

Note: This event is Free to Paid ISWTC Newsletter Subscribers. Please check the latest Newsletter Paid content for the free access code

🤝Heading to Chicago for ASCO 2026?

If you are joining the many subscribers traveling to ASCO this year, we want to help you connect! We have set up an exclusive ASCO2026 by iSWT Community WeChat group for our members from Asia, the US, and Europe to mingle, share insights, and coordinate in-person networking in Chicago during the ASCO week.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

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Summary

In this week’s issue,

• argues that Neurona’s $1.15B exit is less a success story than a testament to surviving CGT’s brutal translational death valley — six years from launch to first patient, across multiple financing rounds, before the science finally had to prove itself in humans.

• reflects on the China biotech panel discussion at the 11th UChicago China Forum in the context of the $15.2-billion HengRui-BMS deal and impressive METiS Techbio IPO on HKEX last week.

• shares a pessimistic view of the next FDA leadership as both CDER and CBER now have new acting directors following the departure of Dr. Marty Makary.

Last week, gave a short presentation titled “The Current Trends of West-China Biotech Collaborations” in University of Chicago. Paid subscribers can download the presentation in the paid subscribers’ session.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

From Academic Curiosity to a $1.15B Exit: The Real Lesson Behind Neurona’s Long Journey

For years, CNS cell therapy occupied one of biotech’s most difficult and least trusted corners. The underlying science was compelling, but the field had accumulated decades of disappointment — poor translational reproducibility, unclear mechanisms, manufacturing uncertainty, invasive delivery, and repeated clinical failures.

Against that backdrop, UCB’s agreement to acquire Neurona Therapeutics for up to $1.15 billion may represent more than a successful exit (Press Release). It may be the clearest demonstration yet that CNS regenerative medicine can become a real therapeutic modality — but only through an extraordinarily long and disciplined translational process.

We have been following Neurona closely since its earliest clinical data releases, including in prior newsletter issues such as (Apr 2025).

The most important lesson from Neurona is not simply that cell therapy for epilepsy can work. It is how long it took, how narrowly the company remained focused, and how much unglamorous work was required to get there.

One Disease. One Cell Type. One Hypothesis.

Neurona emerged from more than two decades of neuroscience research at UCSF centered on medial ganglionic eminence (MGE)-derived inhibitory interneurons — GABAergic neurons capable of suppressing pathological neural hyperexcitability. Critically, the company did not launch with a broad “programmable cell platform” ambition. Its 2015 founding announcement already framed the mission around repairing damaged neural circuits in epilepsy using precisely defined neuronal populations.

That focus sharpened over time into a single coherent hypothesis: replacing inhibitory signaling in hyperexcitable neural networks could durably rebalance epileptic circuitry. The target was drug-resistant mesial temporal lobe epilepsy (MTLE) — the most common form of focal epilepsy and a condition that has historically required tissue-destructive interventions like brain resection or laser ablation. The cell type, the disease, the delivery approach, and the clinical endpoint were all defined early and never substantially deviated from.

In hindsight, that discipline may have been one of the company’s most durable competitive advantages.

A Timeline That Tells a Harder Story

The CGT sector tends to compress success stories into a tidy arc: great science → financing → trial → acquisition. Neurona’s actual history tells a much harder story.

The company formally launched in 2015 with a $23.5 million Series A led by The Column Group — at a stage with no IND, no clinical data, and very limited precedent for successful CNS regenerative medicine. What followed was not a rapid sprint to the clinic. By 2017, Neurona received early-stage funding from the California Institute for Regenerative Medicine (CIRM), and in 2019, a $4.8 million CIRM translational grant to advance the epilepsy program toward the pre-IND stage. Even with the scientific thesis established and a committed investor, the company spent those years solving problems that rarely generate external excitement: differentiation reproducibility, cell characterization, biodistribution, long-term safety, seizure modeling, and regulatory alignment.

This is the hidden reality of CGT. The distance between an elegant academic paper and a clinically usable therapeutic product is enormous.

It took until 2021 — six years after launch — for Neurona to receive FDA IND clearance. The company then raised an additional $41.5 million specifically to support the Phase 1/2 trial launch, illustrating just how capital-intensive the “clinical barrier crossing” phase remains for CGT companies, even after the science appears convincing. The first patient was dosed in 2022.

When the Data Finally Arrived

Only then did Neurona confront the defining question of the entire CGT field: can the biology reproduce meaningful benefit in humans?

For CNS cell therapy, that question is particularly difficult. Transplanted cells must survive, integrate into functional circuitry, remain localized, maintain long-term activity, and avoid neurological toxicity. The early clinical results were therefore highly consequential.

At the 2023 AAN meeting, the first two treated patients showed greater than 90% seizure reduction at nine and five months post-treatment, respectively. By late 2023 and into 2024, updated data across the full five-patient low-dose cohort showed a 92% median reduction in disabling seizures during the primary efficacy window of 7–12 months post-treatment, with the earliest patients sustaining greater than 95% seizure reduction at 16–21 months from a single administration. No adverse events were attributed to the cell therapy, and no clinically significant neurocognitive impairments were detected.

At that point, the narrative changed rapidly. RMAT designation followed in June 2024. EMA PRIME designation, crossover financing, and pivotal trial alignment followed. The UCB acquisition agreement was announced in April 2026.

The lesson is direct: human efficacy data remains the true inflection point for value creation in CGT — not platform breadth, not scientific elegance, not theoretical optionality. Clinical validation is what transforms “interesting biology” into a real therapeutic modality.

What Neurona Suggests About the Future of CGT

Neurona’s journey also exposes a structural tension across the field. Research-driven spinouts naturally emerge with broad platform ambitions — multiple cell types, multiple tissues, multiple indications, expansive regenerative narratives. That breadth is scientifically understandable; academic discoveries often appear highly versatile before translational constraints emerge.

But Neurona’s history suggests the industrial reality of CGT may reward the opposite. A company that spent more than a decade advancing a single tightly defined therapeutic concept — inhibitory interneuron replacement for drug-resistant MTLE — still found the path extraordinarily difficult. The implication is uncomfortable: if a highly focused CNS program required roughly twenty years from foundational science, a decade from company formation, multiple financing rounds, years of translational optimization, and prolonged clinical follow-up simply to achieve initial validation, then broad multi-program CGT ambitions may substantially underestimate the true operational burden of therapeutic translation.

This is especially true in CNS, where biology is complex, delivery is invasive, endpoints require extended follow-up, and regulatory tolerability thresholds are exceptionally high.

The Deeper Achievement

The $1.15 billion headline — $650 million upfront plus up to $500 million in milestones — will understandably capture attention. But the deeper achievement was something less visible: Neurona successfully crossed the long and painful translational valley between academic neuroscience and validated human therapeutic biology.

That crossing required focused execution across multiple financing rounds, incremental technical progress through years of regulatory uncertainty, and tolerance for scientific ambiguity with no guarantee of a clinical payoff. Much of the work was operational rather than glamorous, and the company remained remarkably disciplined throughout — one disease, one biologically matched cell type, one coherent clinical strategy.

Regenerative medicine rarely progresses through sudden technological breakthroughs. More often, it advances through long periods of patient, highly focused translational execution — until one day the clinical data become undeniable. For the broader CGT industry, and for CNS-focused programs in particular, that may be the most valuable lesson of all.

, Co-Founder of iSWT Community

Reflections from the UChicago China Forum: Reverse BD, Major TechBio IPO, and the New Era for Chinese American Talents

After co-authoring and hosting more than 140 Asian Biotechies In A Bar newsletters and BioVerse webinars together, and I finally participated in an in-person event together, at the 11th University of Chicago China Forum last week. We are grateful to Chloe Xu, Clarence Li, and August Yu for the invitation.

Leading up to our discussion, two major news stories broke: the $15.2 billion licensing/co-development deal between HengRui and BMS, and the IPO of six-year-old METiS Techbio which reached over $3 billion market cap. These occurred against the backdrop of an uneventful Trump-Xi Summit, providing the US-China biotech community with a collective sense of relief.

The HengRui-BMS Deal Validates the “Reverse BD” Trend

Last week, HengRui and BMS announced a 13-asset licensing and co-development agreement that garnered significant attention for several reasons:

• First, it is the largest deal by asset count, involving 13 distinct products. It is also unique in its structure, featuring four HengRui assets out-licensed to BMS, four BMS assets to be developed by HengRui in China, and an option to co-develop five additional assets.

• Furthermore, it highlights a new trend where BMS will leverage HengRui’s speed and cost-efficiency in R&D to advance these assets to clinical proof of concept.

• Finally, it stands as the second-largest China-outbound deal by total value, surpassed only by the $18.5 billion AstraZeneca/CSPC agreement.

This deal serves as a major validation of the “West-to-East” innovation flow, often labeled as “reverse BD” (business development) or “reverse Newcos.” Major biopharmas like Gilead, Eli Lilly, AstraZeneca, and BMS have announced similar arrangements, as have biotechs such as Rapport Therapeutics and Crescent Biopharma.

China’s advantages in preclinical and early-stage clinical R&D are undeniable; instead of simply licensing Chinese innovations, Western firms are utilizing China to expedite their own R&D to remain competitive. Industry insiders suggest that more deals similar to the HengRui/BMS and Kelun/Crescent agreements will be announced throughout 2026.

AI-Powered METiS Makes an IPO Splash on the HKEX

METiS Techbio raised approximately $269 million in the largest TechBio IPO in China for 2026. The stock has performed exceptionally well, closing last week with a market capitalization of over $3 billion.

Self-described as the “SpaceX of pharmaceuticals,” this six-year-old company has hit several impressive milestones: an innovative nanotechnology platform that has fostered nearly 30 global partnerships; a diverse pipeline of over 10 assets, including a Pre-NDA candidate; and a dual-track strategy that generates predictable revenue as an R&D enabler while pursuing high-reward developments through its own pipeline.

The fusion of nanotechnology innovation and efficient execution exemplifies a new generation of Chinese biotech. These companies fully capitalize on China’s strengths in AI, biotech R&D infrastructures, and an improving capital market.

Their cornerstone investors include prominent generalist firms like BlackRock, UBS, and Mirae, alongside healthcare specialists like Deerfield, RTW, and Lake Bleu. This prestigious lineup reflects strong confidence from international institutional investors.

Opportunities for Chinese Americans in the New Biotech Era

The China Forum took place following a largely uneventful Trump-Xi Summit. Although the CEO of Illumina joined the presidential delegation, the biotech sector was largely excluded from the official agenda. The absence of major pharmaceutical CEOs suggests that US-China biotech competition may currently be a low priority for top government officials.

In the realm of US-China biotech “coopetition”, no news is the best news.

At the China Forum, our panel—including Erica Wang, Gui-Dong Zhu, Qiusong Tang, , and myself—addressed a room of MBA students. We concluded that the cultural intelligence and language skills of Chinese American students will be indispensable in the growing wave of US-China biotech collaboration.

A prime example is METiS CEO Chris Lai. Born in East Asia, educated at MIT, and trained in Western corporations, Chris co-founded METiS in Beijing in 2020. In just over six years, he has led the company to the HKEX and built a techbio firm valued at over $3 billion.

Similarly, many young professionals with roots in both the East and West are playing vital roles as entrepreneurs, executives, and investors. While “sea turtles” with decades of US biopharma experience founded the industry almost 2 decades ago, a new generation of young “Asian biotechies” is now elevating China biotech to a new level with a native global vision that extends far beyond just the US and China.

Our panelists enthusiastically encouraged students with East Asian backgrounds to seize their incredible unique advantages and dive into this booming industry!

There has never been a more thrilling time to be an Asian biotechie!

, Co-Founder of iSWT Community & Founder of ISWT BioAdvisory

A clean slate of FDA leadership

Following the resignation of Dr. Marty Makary as FDA commissioner this week amid reports of a White House plan to fire him, acting director of the FDA’s Center for Drug Evaluation and Research Dr. Tracy Beth Høeg and acting director of the Center for Biologics Evaluation and Research Dr. Katherine Szarama have both stepped down from their posts. On X, Dr. Høeg said she was fired.

According to the FDA’s website, Dr. Michael Daivs, mostly recently deputy CDER director, has become the acting CDER head. Dr. Davis was previously chief medical officer of the Usona Institute, which was one of three recipients of the national priority vouchers (CNPVs) tied to the Trump administration’s executive order over psychedelics.

Karim Mikhail, formerly Amarin CEO who joined the FDA in 2025 as a senior advisor in the Office of The Commissioner, is now the acting CBER director. Meanwhile, earlier this month, Dr. Angelo de Claro shed the “acting” in his title to become the permanent director of the Oncology Center of Excellence.

That means, the FDA will have a clean slate of leadership on the drugs side, leaving more uncertainty for an agency that has already weathered a tumultuous year. The Trump administration hopes to name a new nominee for permanent commissioner in the next few weeks, a senior administration official told CNBC.

The search for Dr. Makary’s replacement is reportedly being led by Chris Klomp, the director of Medicare and senior advisor to HHS Secretary Robert F. Kennedy Jr. The search will prioritize candidates who have proven leadership experience, particularly within large organizations, and can command the respect of FDA officials and Americans, The Washington Post reported, citing a person familiar with the search process. They also hope to find a leader who will carry on some policy changes initiated under Makary, such as expediting some drug approvals.

In an open letter to Trump, a number of biopharma leaders (incl. RA’s Peter Kolchinsky, Seaport’s Daphne Zohar, Nkarta CEO and former BIO Chair Paul Hastings) have thrown their support behind Dr. Richard Pazdur as the new FDA commissioner. However, I view this more as a call for stability at the agency because, in my opinion, the chance of a Pazdur commandership is almost zero.

Like former CBER director Dr. Peter Marks, Dr. Pazdur left the agency in such a high-profile way, and he has since been critical of the agency for politicizing drug decisions. He has publicly questioned the legality of CNPV when the Trump administration is clearly fond of the program and, as mentioned above, is looking for someone who will keep advancing policies to speed some drug approvals.

Dr. Pazdur was also reportedly behind the FDA’s rejection of Replimune’s oncolytic immunotherapy RP1, a case that The Wall Street Journal’s editorial board zeroed in on in its unusually relentless anti-Makary campaign, which apparently played a role in Trump’s decision to fire him.

The FDA commissioner role has effectively become an impossible job, which led me to this pessimistic view that whoever comes after Dr. Makary won’t last long and that the stability and predictability that the biopharma industry longs for will continue to be out of reach.

Career scientists at the agency and the biopharma world would want the agency to stick to science. But that’s basically a pipe dream under the current administration, which favors political interventions and can easily get upset if someone isn’t a “team player.” Dr. Marks was pushed out because of a clash with the administration on vaccine safety, his successor Dr. Vinay Prasad got on the wrong side of the administration over restrictions on Sarepta’s gene therapy Elevidys, and Dr. Makary reached the end of the road after Trump reportedly grew frustrated with him for slow walking approvals of flavored vapes.

— , Deputy Editor at Fierce Pharma and iSWT Community volunteer

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Summary

In this week’s issue,

• reveals Candid Therapeutics’ highly successful clinical operations campaign in China that enabled its impressive 20-month journey from launch to a $2.2-Billion acquisition.

• discusses the reported firing of Dr. Marty Makary as the FDA commissioner after a year of turmoil.

• surveys three next-generation CDK inhibitor strategies converging at ASCO 2026 — selective CDK4 inhibition for improved tolerability, CDK2 inhibition to tackle resistance biology, and China’s triple CDK2/4/6 approach to preemptively suppress resistance.

Last week, gave a presentation about the current M&A and BD&L trends in Biotech at the AtPhilly conference. Paid subscribers can download this informative presentation in the paid subscribers’ session.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

How Candid Therapeutics Leveraged China’s Clinical Trial Infrastructure for a $2.2 Billion Exit

Last Sunday, Candid Therapeutics was acquired by UCB for up to $2.2 billion, a move that coincided with the withdrawal of their planned IPO. This transaction underscores the significant appetite among big pharma for T-cell engagers (TCE) in the autoimmunity space, following Ouro Medicines’s $2.2 billion acquisition by Gilead, Antigen’s licensing agreement with UCB, Kali Therapeutics’ deal with Sanofi, Chimagen’s deal with GSK (issue 69, 2024-11-03), and Curon’s asset acquisition by Merck & Co (issue 53, 2024-08-11), as well as many other smaller and undisclosed deals.

While several TCE-based deals for autoimmune diseases have surfaced recently, the Candid-UCB acquisition stands out due to its unique development trajectory.

An Unprecedented 20-Month “Biotech Dash”

The initial TCE clinical data from IGM Biosciences, presented at ACR 2023, sparked industry-wide interest in utilizing T-cell engagers as a scalable alternative to autologous CAR-T therapies for autoimmune indications. Capitalizing on this momentum, our firm secured several advisory mandates in the space.

The seminal Nature Medicine publication by Georg Schett and Ricardo Grieshaber-Bouyer, evaluating a CD19 TCE, followed by their NEJM paper on BCMA-TCE, further validated the modality’s potential.

I published a strategic analysis of BCMA-targeted TCEs just days prior to Candid Therapeutics’ official launch, which featured a substantial $370 million Series A. Since that milestone, I have closely monitored Candid’s progress through my networks in both the US and China.

Candid’s public trajectory has been remarkable: launching in September 2024 with a $370 million series A along with 2 clinical-stage assets, closing multiple R&D partnerships, and establishing cross-border teams. After announcing plans for a $505 million crossover financing in March 2026, the company opted for a $2.2 billion exit this May—completing an extraordinary 20-month cycle from inception to acquisition.

Several investors and collaborators have discussed Candid’s strategic model on BioVerse (BioVerse #13 and #17), and a recent The Long Run podcast interview with Ken Song provides extensive operational details.

By any metric, this journey represents one of the most efficient and impressive value-creation stories in our industry.

Clinical Execution: Leveraging the “China Speed” in Clinical Trials

Biotech insiders recognized early on that Candid’s success was predicated on a sophisticated and impressive clinical operations campaign in China. The first public disclosure of this strategy came in June 2025, when the company announced the “strategic establishment of China operations.”

Caidya served as their primary clinical CRO for the company in China. According to Shen Jinye, Head of Business Development at Caidya and an iSWT Community member, the firm assisted Candid in initiating about 10 trials in China across diverse indications.

This deep engagement with China early-stage clinical trial space even led Ken Song to co-author a Nature Biotechnology commentary on China’s innovative translational medicine ecosystem. Utilizing China’s efficient early-stage trial system, Candid launched multiple investigator-initiated trials (IITs) for their lead BCMA-targeting candidate, cizutamig.

The decision to prioritize China was pragmatic. While Song initially sought to conduct signal-finding trials in the US, the regulatory requirements and preparatory timelines proved prohibitive, according to his The Long Run interview. By pivoting to China and Europe, Candid achieved rapid generation of proof-of-concept clinical data.

Ultimately, the China-based data identified the optimal indications for global Phase 2 development, providing the clinical validation required for the UCB acquisition. While China-originated assets provided the foundation, China’s world-class clinical infrastructure facilitated the $2.2 billion exit.

Insights from the Frontlines of China’s IIT Ecosystem

In my role as fractional BD head of Mianus Accelerator, I have observed the distinct competitive advantages of China’s early-stage development landscape. At the recent AtPhilly conference in Philadelphia, the dedicated China IIT session chaired by Bo Liang highlighted the system’s ability to de-risk innovative therapies through rapid first-in-human studies. Furthermore, the enactment of Decree 818 on May 1st (issue 138) has enhanced R&D efficiency, further solidifying China’s position in global early-stage clinical R&D.

During the panel discussion, perspectives from global pharma executives, biotech leaders, China-based physicians, and CROs suggest that China is building a “first-in-class” clinical trial infrastructure. This system is becoming a core competitive advantage in the global race for biotech innovation.

Operational metrics are impressive: according to one CRO presentation, the timeline from initial discussion to first-patient-in can be as short as four to five months.

Following the success of Legend Biotech, EsoBiotec, and Candid Therapeutics, 173 IITs were initiated by international companies in 2025 in China. We expect this trend to accelerate as global sponsors seek faster paths to clinical data.

Regulatory Reform: A Strategic Imperative for the US

Jake Becraft, who recently testified before Congress regarding biotech competitiveness, recently sat down with our editor for a thought-provoking interview. He emphasized the urgent need for US regulatory and infrastructural reform to maintain leadership in clinical development.

“The defining competitive metric in modern biotechnology is no longer who discovers a promising therapy first. It is who can turn that discovery into first-in-human clinical data the fastest.”, said Jake Becraft.

I can’t agree more.

, Co-Founder of iSWT Community & Founder of ISWT BioAdvisory

Dr. Makary to be fired after months of turmoil: report

President Trump has approved a plan to fire FDA Commissioner Dr. Marty Makary, The Wall Street Journal reported Friday, citing people familiar with the matter.

The decision isn’t yet final and could change, according to WSJ. When asked about Makary’s firing, Trump said: “I know nothing about it.”

Makary was sworn in as FDA commissioner on April 1, 2025. His yearlong tenure has been dogged by turmoil from massive DOGE-led layoffs, endless senior leadership turnover, complaints from the biopharma industry over inconsistent regulatory decisions and protests from antiabortion activists who wanted him to restrict the abortion pill mifepristone.

His pending firing appears to be the result of a combination of factors piling up into a bigger problem that points to him as what WSJ described as “a rogue agent” within the administration. The last straw seems to be Trump’s frustration with him not moving fast enough to approve fruit-flavored vapes. But according to an anonymous White House official cited by Politico, his ouster has been championed by senior leadership at the Department of Health and Human Services rather than the White House.

Dr. Makary’s leadership has indeed been marred by turbulence. But his departure does not restore stability at the agency on the biopharma side.

For one thing, both CDER and CBER are currently under acting leadership following high-profile departures.

Second, what the Trump administration wants in an ideal FDA commissioner and what the industry longs for in a consistent drug regulator are simply mutually exclusive.

What Trump and Robert F. Kennedy, Jr., want is a political servant who will strike on vaccines and endorse unproven peptides at their beck and call. But that kind of political intervention is the very source of uncertainty that the biopharma industry desperately seeks to steer clear of.

This tightrope that Makary was walking was doomed to snap. When Dr. Vinay Prasad held vaccines to an overly high bar as Kennedy wanted, claiming without evidence that at least 10 children had died due to COVID vaccinations, an outcry from the scientific community followed. When he tried to apply the same scrutiny to drug approval, suddenly the right wing called him a socialist. The biopharma industry can handle tight regulatory standards, but they must be predictable and consistent.

After Dr. Prasad was pushed out, the target apparently shifted to Dr. Makary.

Dr. Makary’s pending ouster could confirm a possibility, like the exit of Dr. Prasad before him, that this FDA leadership position has less to do with scientific acumen and more to do with political obedience. Without science-based leadership, all that the biopharma industry is left with is political favoritism and the rest is just uncertainty.

The wry positive side is, I think the industry has already learned to speak the language of the Trump administration. Whenever someone sees an unfavorable policy or decision from the FDA, it warns that China is winning or accuses political disloyalty.

Now, assuming Makary has been fired. What will happen to some of the FDA’s new policies?

First, the controversial Commissioner’s National Priority Review Voucher pilot. That will probably stay because it opens a channel for involvement by political leadership.

Plausible mechanism pathway. This isn’t exactly a new regulatory concept, but it’s being applied to personalized therapies for the first time. Given Kennedy’s public endorsement of CRISPR and an eagerness to chalk up baby KJ as a regulatory win, this will likely stay on as well.

Clinical trial reforms such as real-time review of clinical data and expedited IND, these will likely be kept as well, given broad endorsement and the fact they’re not Dr. Makary’s own pet project.

Potential crackdown on Chinese data and companies? That’s the trend no matter who’s leading the FDA. The question is in what form and to what extent?

Without an official announcement, Dr. Makary is still technically the commissioner. But the White House is already mulling over his potential replacement. Kyle Diamantas, the FDA’s top food regulator who does not have a medical background, is the frontrunner, Politico reported, citing a former HHS official. But Reuters reported that Diamantas is only being considered as acting commissioner, citing three sources.

Former FDA commissioner Dr. Stephen Hahn and former acting FDA commissioner Dr. Brett Giroir are being considered as permanent replacement, according to Reuters. But Politico reported the two as potential interim leaders of the agency.

Hahn’s name was notably missing among the authors of a Dec. 3 NEJM article, in which 12 former FDA leaders—including Dr. Giroir—criticized Dr. Prasad’s vaccine policy and his unverified safety claims against COVID vaccines.

, Deputy Editor of Fierce Pharma and iSWT Community volunteer

The Next Wave of CDK Inhibition: ASCO 2026 Signals a New Competitive Era in HR+/HER2- Breast Cancer

The CDK inhibitor market is entering its second competitive cycle. After nearly a decade in which palbociclib, ribociclib, and abemaciclib reshaped HR+/HER2- breast cancer, the field is fragmenting into distinct next-generation strategies — each targeting a different limitation of the first generation. Upcoming ASCO 2026 may be the meeting where this transition becomes impossible to ignore.

Why the First Generation Is No Longer Enough

CDK4/6 inhibitors remain global first-line standard of care in metastatic HR+/HER2- breast cancer, and their OS and PFS benefits are not in dispute. But two persistent liabilities have opened the door for successors: hematologic toxicity — primarily neutropenia driven by CDK6 inhibition in bone marrow — and resistance that is virtually universal, with roughly 20% of patients showing primary resistance and most others progressing after two to three years.

Three strategic responses are now advancing in parallel:

1. highly selective CDK4 inhibition to reduce toxicity,

2. CDK2 inhibition to address resistance biology,

3. combined CDK2/4/6 inhibition to preemptively suppress resistance emergence.

Selective CDK4 Inhibition: The Front-Running Race

The underlying rationale is straightforward. HR+/HER2- tumors appear more dependent on CDK4 than CDK6, and CDK6 inhibition in hematopoietic cells drives most of the class’s dose-limiting toxicities. A CDK4-selective agent could, in principle, preserve antitumor efficacy while materially improving tolerability.

Pfizer’s atirmociclib is currently the benchmark. In March 2026, Pfizer announced positive topline results from FOURLIGHT-1, a randomized Phase 2 study in second-line HR+/HER2- metastatic breast cancer after prior CDK4/6i therapy. The study met its primary PFS endpoint with a hazard ratio of 0.60 versus fulvestrant or everolimus plus exemestane. OS remains immature. This is among the first meaningful randomized signals that a next-generation CDK4-selective agent can retain efficacy after CDK4/6i progression — a biologically important result given that CDK2-driven resistance is common in this population.

The company is also running FOURLIGHT-3, a head-to-head Phase 3 against investigator’s choice of CDK4/6 inhibitor in first-line disease. That study may become one of the defining competitive trials in the category because it directly tests whether selective CDK4 inhibition can improve efficacy and safety versus established CDK4/6i.

At ASCO 2026, Pfizer will expand the atirmociclib dataset in two directions. FOURLIGHT-2 will report Phase 2 neoadjuvant data pairing atirmociclib with letrozole versus letrozole alone — a setting where no CDK4/6 inhibitor is yet broadly established, making a positive result strategically significant.

FOURLIGHT-2 ASCO Abstract

Pfizer will also present early combination data for atirmociclib with vepdegestrant (Veppanu), the recently FDA-approved PROTAC ER degrader co-developed with Arvinas, pairing two novel mechanisms in a post-CDK4/6i population.

Atirmociclib + Vepdegestrant ASCO Abstract

BeOne Medicines is the nearest competitor with BGB-43395. At ASCO 2026, BeOne will present first-line metastatic data for BGB-43395 for the first time. According to management commentary, BGB-43395 may demonstrate even greater CDK4 selectivity than atirmociclib, which could translate into a particularly clean hematologic profile, though some GI toxicity appears elevated. BeOne is also preparing a Phase 3 head-to-head trial against CDK4/6i in first-line disease, mirroring Pfizer’s FOURLIGHT-3 approach. The atirmociclib versus BGB-43395 race is now one of the most closely watched competitive dynamics in HR+/HER2- oncology.

ASCO abstract link here:

BGB-43395 ASCO Abstract

CDK2 Inhibition: Targeting Resistance Biology

While selective CDK4 inhibition is primarily about improving therapeutic index, CDK2 inhibitors take a different approach: directly attacking the most common resistance escape mechanism. Cyclin E1 (CCNE1) overexpression or amplification activates CDK2 signaling and allows tumor cells to bypass CDK4/6 blockade altogether. CCNE1 dysregulation is also prevalent across ovarian, endometrial, gastric, and other solid tumors, which means CDK2 inhibition has the potential to evolve into a biomarker-driven, pan-solid tumor strategy.

Avenzo Therapeutics is advancing AVZO-021 and will present updated Phase 1 data at ASCO 2026 covering both HR+/HER2- breast cancer and CCNE1-amplified solid tumors. The breadth of the tumor-type inclusion reflects how developers increasingly frame CDK2 inhibition as a platform rather than a breast cancer-only play.

AVZO-021 ASCO Abstract

Incyte may be furthest along in CDK2. Its selective CDK2 inhibitor INCB123667 has entered the Maestra-2 Phase 3 trial in CCNE1-overexpressing, platinum-resistant ovarian cancer — the first pivotal CDK2 program to reach this stage. The indication choice is deliberate: it targets a population with high unmet need, clear CCNE1 biology, and limited competitive overlap with breast cancer. Phase 1 data presented at ASCO 2025 showed a 33% ORR at the 100 mg daily dose in platinum-resistant ovarian cancer, with most responders having CCNE1 overexpression.

INCB123667 ASCO Abstract

China’s Contrarian Bet: CDK2/4/6 Triple Inhibition

While Western developers pursue selective inhibition, Sino Biopharmaceutical’s culmerciclib takes the opposite approach — simultaneous CDK2, CDK4, and CDK6 inhibition, with preferential CDK4 activity, designed to preemptively block the resistance escape route rather than address it after the fact.

Culmerciclib has now received two NMPA approvals: the original indication (post-endocrine therapy progression, in combination with fulvestrant, approved December 2025) and a new first-line indication (in combination with fulvestrant, approved May 2026). The first-line approval is based on CULMINATE-2 Phase 3 data, which reportedly showed a median PFS not reached in the culmerciclib arm versus 20.2 months in the control arm, an ORR of 59.3%, Grade ≥3 neutropenia of 20.3%, and a low 3.5% treatment discontinuation rate. At ASCO 2026, Sino will present a small Phase 2 data in Chinese patients who have progressed on prior CDK4/6i therapy

Culmerciclib ASCO Abstract

The central unresolved question for culmerciclib is global competitiveness. No direct head-to-head data versus a Western CDK4/6 standard exist, and the broader CDK2/4/6 approach is being tested against an increasingly sophisticated selective-inhibitor field. Whether three-target breadth ultimately proves superior to mechanistically cleaner selective strategies — in terms of resistance control, safety, and combinability — remains to be seen.

The Bigger Picture

The first decade of CDK therapy established CDK4/6 inhibition as one of oncology’s most commercially successful targeted therapy classes. The next decade will be defined by a more fragmented competitive landscape: selective CDK4 inhibitors competing on tolerability and first-line replacement potential; CDK2 inhibitors creating a new biomarker-selected category across tumor types; and CDK2/4/6 agents testing whether upfront resistance suppression can outperform sequential selective approaches.

ASCO 2026 will not resolve these questions — but it could make the shape of the answer start to become more visible.

, Co-Founder of iSWT Community

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Summary

In this week’s issue,

• examines Sun Pharma’s $11.75B Organon acquisition as a strategic inflection point—unpacking the deal’s rationale, execution risks, and what it signals for India’s pharma ambitions on the world stage

• rounds up a series of setbacks for Chinese assets, including a pan-RAS candidate, a J&J collaboration, Summit Therapeutics and Akeso’s high-profile PD-1/VEGF, and a concerning Congressional report.

• opines on the diverging attitudes of the US and European countries in the era of rising China biotech, given the latest Congressional anti-China biotech bill proposal.

Replay of BioVerse #30 is now on Substack and YouTube channel. Our paid subscribers can download the 52-slide presentation behind the paywall.

This week, many iSWT Community members will speak and attend 2026 @Philly Cell & Gene Therapy Annual Conference. Join our conference networking group by scanning the WeChat group QR code below. Our paid subscribers will enjoy 50% discount for the conference registration.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

Beyond Generics: Sun Pharma’s $11.75B Organon Acquisition and Its Bid to Redefine Indian Pharma on the World

On April 26, 2026, Sun Pharmaceutical Industries announced a definitive agreement to acquire Organon & Co. in an all-cash transaction valued at $11.75 billion—the largest cross-border pharmaceutical acquisition ever executed by an Indian company (Press Release). Under the terms of the deal, Sun Pharma will pay $14.00 per share for all outstanding Organon stock, representing a 24% premium to Organon’s closing price the prior Friday and more than a 100% premium to where the stock traded at the start of April.

At its core, this transaction brings together two companies with complementary strategic needs: a capital-efficient generics leader seeking to accelerate its pivot into specialty and innovative medicines, and a cash-generative but strategically constrained commercial platform searching for a stronger owner. The combination is more than a scale play. It is a potential inflection point for Sun Pharma—and a signal of the broader maturation of the Asian pharmaceutical industry.

Sun Pharma: From Generics Powerhouse to Global Specialty Player

Sun Pharma is India’s most valuable pharmaceutical company and one of the few truly globalized players to emerge from the country. Built on cost-efficient manufacturing and generics dominance across the U.S., India, and emerging markets, the company has consistently generated strong free cash flow while maintaining a clean balance sheet. As of FY2025, Sun Pharma held more than $3.1 billion in cash and carried minimal debt—providing the financial capacity to fund a transaction of this scale through a combination of internal resources and committed bank financing.

Over the past decade, Sun has deliberately reshaped its business mix toward specialty and innovative medicines—particularly in dermatology and oncology, which has scaled to a global annualized run rate exceeding $500 million for Ilumya alone. In Q2 FY2026, for the first time, U.S. innovative medicine sales surpassed generics, underscoring the trajectory of this transition. As of FY2025, innovative medicines accounted for approximately 21% of Sun’s total consolidated revenue.

Despite this progress, several structural gaps remained. Sun had no biosimilars business, limited exposure to women’s health, and continued reliance on the inherent volatility of the U.S. generics market. The Organon acquisition is designed to close all three gaps simultaneously.

Organon: Solid Assets, Significant Constraints

Organon was spun off from Merck & Co. in 2021 as a standalone global commercial platform focused on women’s health, biosimilars, and established (off-patent branded) medicines. The company reported full-year 2025 revenue of $6.2 billion and adjusted EBITDA of $1.9 billion (approximately 30% margin), with operations spanning approximately 140 countries and a portfolio of over 70 marketed products.

Its business is structured around three pillars:

– Women’s Health (~33% of revenue): Led by Nexplanon, the subdermal contraceptive implant, and complementary fertility and contraception products. This is Organon’s primary growth engine and the anchor of its commercial identity.

– Biosimilars (fastest-growing segment): Developed and commercialized in partnership with Samsung Bioepis. This segment delivered 23% as-reported revenue growth in Q1 2026, driven by an existing portfolio of eight marketed biosimilars.

– Established Brands (~remainder of revenue): Largely legacy Merck cardiovascular, respiratory, and pain management assets. These provide steady cash flow, though growth has been limited.

Organon’s challenges are equally material. The company carried $8.6 billion in debt at year-end 2025—a direct consequence of its leveraged spin-off structure—against a cash balance of only $574 million, leaving limited capacity to invest in pipeline expansion or transformative deals. Revenue growth has been modest to negative, and the looming expiration of Nexplanon’s U.S. rod patent in 2027 poses a significant structural headwind to its most profitable franchise.

Compounding these structural pressures, Organon experienced a serious governance failure in late 2025.An audit committee investigation found that U.S. wholesalers were pressured to purchase excess Nexplanon inventory across multiple quarters between 2022 and 2025 to meet revenue guidance—practices the board deemed improper. CEO Kevin Ali resigned in October 2025 without severance. Organon subsequently raised $440 million through a product divestiture in November 2025

In aggregate, Organon became a classic post-spin entity: operationally solid and commercially scaled, but strategically constrained by leverage, governance overhang, and a maturing portfolio with limited reinvestment capacity.

Strategic Rationale: Why This Deal Makes Sense

Immediate and Substantial Scale

The combined entity is projected to generate approximately $12.4 billion in annual revenue, placing Sun Pharma among the top 25 global pharmaceutical companies. More importantly, the deal expands Sun’s commercial footprint to over 150 countries, with 18 individual markets each generating over $100 million in revenue and a combined front-end commercial team of roughly 24,000 employees. Critically, it reduces Sun’s historical concentration in the Indian and U.S. generics markets, which have been susceptible to pricing pressure and regulatory volatility.

One underappreciated dimension is geographic optionality. Organon currently generates approximately $800 million in revenue from China—a ready-made commercial infrastructure that Sun Pharma could leverage to launch its own specialty pipeline into a market it has historically struggled to access at scale.

Portfolio Transformation

The acquisition substantially upgrades Sun’s portfolio composition across three areas.

1) Organon’s Women’s Health franchise positions the combined company as a top-three global player in contraception and fertility—introducing a high-barrier therapeutic pillar that Sun had no previous presence in. The share of innovative medicines in Sun’s total revenue mix is expected to rise from approximately 21% to 27% post-close.

2) The deal gives Sun an immediate, scaled entry into biosimilars, with eight marketed products and an established partnership with Samsung Bioepis. Sun Pharma estimates this will make it the seventh-largest biosimilar company globally—bypassing years of capability-building and capital investment that an organic entry would have required.

3) Organon’s $3+ billion Established Brands portfolio offers Sun the opportunity to apply its proven branded-generics playbook—particularly its commercial engine in India and other emerging markets—to reinvigorate volume-led growth in legacy cardiovascular, respiratory, and pain management assets.

Financial Profile

Organon’s $1.9 billion adjusted EBITDA provides an attractive earnings base from day one. Sun has identified over $350 million in cost synergies expected to be realized within two to four years of closing. The combined entity’s adjusted EBITDA is projected at approximately $3.7 billion, with post-transaction net leverage targeted at 2.3x net debt/EBITDA. At the $11.75 billion enterprise value, Sun is paying approximately 6.1x NTM EV/EBITDA—a meaningful discount to comparable companies such as Viatris, which trades at roughly 7.0x. Sun is funding the acquisition through internal cash resources and committed bank financing.

Execution Reality: Where the Risk Lives

The strategic logic is sound, but the execution risk is real and multi-dimensional.

Leverage transition

Sun moves from a net-cash position to carrying combined net debt at 2.3x EBITDA. While manageable by industry standards, disciplined capital allocation and rapid deleveraging will be essential priorities in the first two to three years post-close. There is limited margin for error if integration proves slower or more costly than anticipated.

Portfolio quality mismatch

The fundamental tension in this deal is that Organon’s portfolio is largely composed of mature, slow-growth or declining assets, while Sun’s long-term ambition is to build a specialty innovation engine. Without deliberate reinvestment of free cash into earlier-stage R&D or pipeline acquisitions, the combined company risks becoming a sophisticated cash-flow aggregator rather than a genuine growth-oriented biopharma.

Integration complexity

Sun has operated principally as an emerging-market and generics business; Organon is a Western commercial organization with different processes, incentive structures, compliance standards, and cultural norms. Questions around talent retention—particularly in Organon’s Women’s Health and biosimilars commercial teams—and cross-cultural alignment will require sustained management attention.

Biosimilars execution gap

Acquiring Organon’s biosimilars portfolio provides assets and a Samsung Bioepis partnership, but Sun has not yet demonstrated the biologics manufacturing and clinical development capabilities required to compete at scale in this category. The upside is real; it is not automatic.

Governance overhang

Organon enters the transaction under interim leadership and with unresolved reputational damage from the Nexplanon channel stuffing investigation. While the immediate crisis appears contained, integration under unstable leadership introduces additional organizational and compliance risk that Sun will need to manage carefully.

The bottom line on achievability: near-term value creation (0–3 years) looks highly probable—cost synergies, cash flow harvesting, and earnings accretion are achievable and well-defined. Long-term success (3–10 years) is more uncertain and will depend on whether Sun chooses to reinvest cash into innovation or consolidates into a mature-asset portfolio company.

Broader Implications: A Coming-of-Age Moment for India and Asia Pharma

Beyond Sun Pharma’s own strategic trajectory, this deal carries meaningful industry-level implications.

For India, it represents a coming-of-age moment. Long positioned as the “pharmacy of the world” for generics exports, India is now producing companies capable of executing large-scale, outbound acquisitions of branded global assets. The industry’s value-chain progression—from bulk API manufacturing to generics to specialty and now to global commercial platform ownership—is unmistakable. Peers such as Dr. Reddy’s and Cipla will face strategic pressure to respond, whether through their own acquisitions, biosimilars investment, or accelerated specialty pipelines.

For the broader Asian pharmaceutical landscape, the transaction defines a new competitive archetype: emerging-market operators acquiring and optimizing global branded assets. This model—combining cost efficiency, scale, and commercial diversification—positions companies like Sun to compete more directly with established Western multinationals, as well as with Korean biosimilar leaders (including Samsung Bioepis itself) and Chinese biopharmas pursuing their own international expansion strategies.

Final Assessment

This is a bold but fundamentally logical deal. Strategically, it fills genuine and material gaps in Sun Pharma’s portfolio and geographic reach. Financially, it is attractively structured, with a below-peer entry multiple, clearly identified synergies, and a manageable leverage outcome. Operationally, it is demanding—and will test the limits of Sun’s integration discipline and long-term strategic clarity.

The near-term question is not whether the deal creates value—it almost certainly will, at least in the short run. The more consequential question is whether Sun Pharma uses this platform to complete its transformation into a truly global, innovation-driven pharmaceutical company, or allows the combined entity to drift toward managed decline of a large, diversified portfolio of maturing assets.

If Sun gets the integration right and reinvests wisely, this deal will be remembered as the defining moment in India’s pharmaceutical industry evolution. If execution falters, it risks becoming a cautionary tale about the gap between strategic ambition and operational reality.

, iSWT Community Co-founder

A terrible, horrible, no good, very bad week for Chinese biotech assets

I’ll admit: the situation isn’t quite as dire as this headline—borrowed from a classic children’s book—might suggest. However, a string of negative updates for Chinese biotech assets this week serves as a reminder that multibillion-dollar deals cannot erase the inherent risks of drug development or the shadow of geopolitics.

This week, Erasca’s pan-RAS molecular glue (mentioned in our recent newsletter Issue 135), licensed from China’s Joyo Pharmatech, reported a patient death, sending the San Diego biotech’s shares down by almost 50%.

Johnson & Johnson axed a pair of CAR-T therapies it got from Sino-American firm AbelZeta Pharma (previously Cellular Biomedicine).

Summit Therapeutics’ high-stakes HARMONi-3 trial of Akeso-partnered PD-1xVEGF bispecific ivonescimab in first-line non-small cell lung cancer surprisingly missed statistical significance on progression-free survival at a recently added interim analysis of the squamous cohort.

The U.S. House Appropriations Committee sent a draft spending bill report that would bar the FDA from “accepting, reviewing, or considering” clinical data generated in China to support an investigational new drug (IND) application.

Going into these in more detail one by one.

Erasca

Erasca pooled ERAS-0015’s early-phase data from two studies in the U.S. and China and reported a 40% overall response rate in 20 patients with KRAS G12X-mutated pancreatic cancer in the second line. By cross-trial comparison, the ORR was 10 percentage points better than Revolution Medicines’ daraxonrasib, which recently made waves with a near-doubling of overall survival in this hard-to-treat tumor type. (see ISWTC newsletter Issue 135; 2026-04-12).

In second-line KRAS G12X-mutated non-small cell lung cancer, ERAS-0015’s ORR was reported at 62% among 37 patients. Again, notably better than daraxonrasib’s historical showing of 37.5%.

Evercore ISI analysts called the readouts a “home run profile,” and it met Erasca’s own bar of requiring at least 10 percentage points to be differentiated from daraxonrasib. Yet Erasca’s share price dropped nearly 50% in what appears to be reaction to the death of a patient.

The 66-year-old pancreatic cancer patients died after developing a grade 3 pneumonitis. Erasca explained this lung inflammation as a very rare side effect associated with RAS inhibition. The patient died after requesting the withdrawal of supportive care.

In addition to the death case, Erasca disclosed on April 27 that it had received a letter, in which RevMed alleged that ERAS-0015 infringed on its U.S. patent No. 12,409,225 and that the Erasca med was developed with RevMed’s trade secrets. Erasca said it “believes the assertions in the letter are without merit and intends to contest the allegations vigorously.”

J&J

J&J discontinued a CD20 CAR-T candidate, JNJ-9530, and a CD19/CD20 bispecific CAR-T, JNJ-4496 (prizloncabtagene autoleucel, or prizlo-cel), citing “the evolving large B-cell lymphoma treatment landscape.”

J&J paid Cellular Biomedicine (later changed name to AbelZeta) $245 million upfront in 2023 to get its hands on the two candidates. J&J later added CD20 CAR-T among novel therapies that hold $5 billion in peak-year sales potential, drawing comparisons to its Legend Biotech partnership on Carvykti.

At EHA 2025, J&J released the first JNJ-4496 data from a phase 1b trial, reporting 100% ORR and 80% CRR in 10 second-line large B-cell lymphoma patients who got the recommended phase 2 dose, or 92% ORR and 75% CRR in 12 third-line-plus patients.

An update at ASH 2025 showed 100% ORR and 90% CRR in 31 patients with both CD20 and CD19 high/medium expressions, or 82% ORR and 63% CRR in 11 patients with at least one low antigen. At that time, a J&J presentation noted that, “High CR rates were observed even in immunosuppressive TME archetypes, when compared to approved CD19 CAR-Ts,” and that this dual-targeting CAR-T “may overcome limitations of single-antigen targeting CAR-T cells, with a potential to improve clinical outcomes.”

Elsewhere, Gilead’s KITE-363 and KITE-753 and JW Therapeutics’ JWCAR201 are CD19/CD20 CAR-Ts

Summit

Summit’s stock price suffered a 25% blood bath Friday after its first-quarter report suggested that the squamous cohort of the closely watched global HARMONi-3 trial has apparently missed statistical significance in an interim analysis. The trial’s independent data monitoring committee recommended the study remain blinded and continue as planned.

Missing stat sig at interim is not catastrophic, but given the plenary placement of HARMONi-6 at the upcoming ASCO 2026 (see ISWTC newsletter Issue 137; 2026-04-26), this readout was a big disappointment to investors.

HARMONi-3 is evaluating ivonescimab plus chemo against Keytruda and chemo in first-line NSCLC. H-6 is like the Chinese counterpart of H-3’s squamous cohort, although the comparator is BeOne’s Tevimbra and chemo.

Summit only added this interim analysis recently and framed it as an opportunity to start speaking with regulators early about a potential submission while final PFS and interim OS are expected later this year. Expectations of success were high because two Chinese trials, H-6 and the landmark H-2 (ivonescimab vs. Keytruda monotherapy in 1L PD-L1-positive NSCLC) met PFS at interim analysis.

According to Summit, it didn’t spend a lot of alpha on this analysis, meaning the bar is higher to achieve statistical significance than the final PFS analysis.

Analysts did their guesswork without knowing the exact statistical plan or enrollment speed. Leerink Partners analysts’ base-case scenario suggests the PFS effect size is about 10 percentage points lower than the 40% seen in H-6.

Jefferies analysts also said PFS was “likely tangibly worth than” H-6. If alpha split was 0.002 to 0.003, the interim had about 80% power to detect a PFS improvement of about 35%, in which case the miss would suggest a PFS of 30% or worse, the team said.

Citi modeled a “minimal (~0.001)” alpha spend and suspected that the total PFS events were fewer than expected. Jefferies argued against the possibility of this small alpha allocation because Summit had planned to leverage this data for potential earlier market entry.

Both Leerink and Evercore suggested the stakes are even higher now for the Chinese H-6 overall survival update at ASCO 2026 because investors are now expecting a degradation in benefit from the Chinese to global data.

Congress

The House Appropriations Subcommittee on Agriculture, Rural Development and FDA, added to its spending bill report this week directing the FDA to prohibit the use of clinical trial data generated in China, Russia, Iran, or North Korea in IND applications.

“The Committee is deeply concerned about the growing influence of the People’s Republic of China (PRC) over the U.S. pharmaceutical supply chain and drug development ecosystem,” the report says, while comparing doing early-phase trials in Chinas “transferring know-how to our adversary.”

The report is non-binding and as BioCentury’s story rightfully pointed out, “The bill must still pass the full House, then the Senate, and be reconciled in conference. It is unlikely that the report language will survive to final enactment.” But such reports are typically used by spending committee to send strong signals of how they think Congressional funding should be spent.

This proposal adds to other initiatives such as the Biosecure Act and the ban of shipping American citizens’ living cells to China for therapeutic engineering. It continues to reflect a broader, more hawkish posture toward China’s biotech rise.

I have repeatedly said, even when the Biosecure Act appeared to have failed in its original form, that Washington’s hawkish position against Chinese biotechs and their assets will not go away in the foreseeable future and will likely only get worse. Such is the reality of geopolitics, which unfortunately takes precedence over the advancement of science these days.

So, I do not want to scare people and overstate the meaningfulness of this specific proposal, but I also hope our readers do not underestimate this bigger anti-China trend that has been playing out for some time in DC. I think while it is unlikely that the exact language of the latest report will pass, some form of restrictions is very possible in the future. When that day comes, I hope, for U.S. patients’ sake, the U.S. has significantly improved its own IND process.

Before that, to quote from MassBio CEO Kendalle Burlin O’Connell: “Many MassBio members are licensing or originating molecules from China-based partners as a way to bring novel science to patients faster and at lower cost. An outright ban could complicate pipeline strategy without necessarily strengthening U.S. competitiveness. This is a conversation we’ll have with members in the months ahead.

— , Deputy Editor at Fierce Pharma and iSWT Community volunteer

The Great Biotech Divide: US Restriction vs. European Collaboration in the Era of Rising China Biotech

Last week, the US House Appropriation Committee proposed to “prohibit the FDA from accepting, reviewing, or considering any covered clinical data generated by a clinical investigation site located in [China]”. This represents the latest attempt by D.C. hawks to contain China’s biotech industry and protect the US one.

In a sharp contrast, the UK drug regulator will accept more Chinese clinical data to speed approvals, following the EMA’s recent label extension for China-originated PD-1 inhibitor serplulimab. These diverging attitudes highlight the complex US-China biotech coopetition.

US Industry: China’s Clinical Capability is Essential

The US biotech industry increasingly relies on China to improve R&D efficiency and produce innovative medicines for American patients. Blockbuster drugs like Legend Biotech’s Carvykti and BeOne Medicine’s Brukinsa have saved tens of thousands of American lives. The China-originated clinical data played a pivotal role for those medicines’ speedy approvals in the US.

Today, American biotech companies like Candid Therapeutics and Summit Therapeutics continue this trend, spearheading the development of the future medicines for American patients by leveraging China’s efficient clinical study system, while creating wealth for US investors and employees.

The efficiency gains are so significant that major funds like RA Capital and MPM Bioimpact are expanding clinical capabilities in China.

European Perspective: Strategic Collaboration

In Europe, serplulimab has achieved swift success by utilizing data from Chinese trials, a sharp contrast to the protracted regulatory timeline it still faces in the United States. This move toward partnership is underscored by AstraZeneca’s commitment to invest $15 billion and build a workforce of more than 20,000 in China by 2030, demonstrating that strategic collaboration is being prioritized over geopolitical friction by Europeans.

The growing synergy between European and Chinese entities is particularly evident in the field of in vivo CAR-T therapy. For example, a pioneering first-in-human study in China facilitated the acquisition of the Belgian company EsoBiotec (see issue 87). Furthermore, a joint Chinese-German team recently published a significant paper in the New England Journal of Medicine after successfully testing mRNA-based in vivo CAR-T for autoimmune conditions.

As these Europe-China partnerships strengthen, legislative efforts in the U.S. to restrict the transfer of “know-how” to China may fail to impede the progress of the Chinese biotech sector.

The Chinese Strategy: Positioning R&D as Essential While Expanding Its Commercial Market

On May 1, 2026, China codified its innovative dual-track regulatory system into law. Key features of this new framework include:

• Dual-Track Regulatory System: This establishes an accelerated “technology translation” pathway for sophisticated, highly personalized innovations, bypassing the traditionally lengthy drug and device registration processes.

• Early Commercialization: Medical institutions are now legally permitted to charge fees for approved clinical applications, providing a revenue stream prior to obtaining full market authorization.

• Streamlined Approvals: The system expedites reviews for therapies addressing rare diseases or unmet clinical needs, incorporating mechanisms for priority and emergency use.

• Risk-Based Rollout: A “safety observation period” of one to five years—determined by the technology’s risk level—restricts use to original trial hospitals before broader expansion to other qualified facilities.

• Data Synergy: Data collected during the clinical translation phase may serve as real-world evidence to support subsequent traditional registration for drugs or devices.

China’s unique dual-track system has no international equivalent and appears highly compelling for Western biotech and biopharma firms seeking to conduct clinical development in specialized fields.

While the U.S. remains the primary source of revenue and profit for innovative medicine, China is actively working to narrow the commercial market gap (see issue 137). Although this transformation will take time, it may be achievable in the future.

My Takeaway

Let’s be clear: the attempt to sever China from US clinical trials and R&D ‘know-how’ would cause self-inflicted damages. This kind of hostile policy risks increasing our drug development costs, driving up prices for American patients, and potentially blocking access to cutting-edge medicines. Meanwhile, Europe is strategically deepening its ties with the Chinese biotech sector, making this proposed US anti-China bill ineffective even if it passes. China is not standing still; it is actively innovating its regulatory frameworks—like the new dual-track system—to boost its R&D competitiveness while simultaneously expanding its domestic commercial market.

The US-China biotech coopetition is the defining theme for the coming years, and while policy friction is inevitable, this particular Congress draft bill seems ill-advised. It won’t achieve its stated goals of protecting the US biotech industry or safeguarding American patients.

, Co-Founder of iSWT Community & Founder of ISWT BioAdvisory

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Summary

In this week’s issue,

• examines China's landmark Apr 2026 drug pricing reform — arguing that by finally creating a domestic market capable of rewarding innovation at scale, it may prove to be the policy inflection point that transforms China's biopharma sector.

• previews the showdown between PD-1xVEGF and TROP2 at the upcoming ASCO 2026 annual meeting. It is unprecedented for a pair of China-only phase 3 trials to command such attention at a major medical conference.

• tells Kelonia’s $7-billion acquisition’s backstory that includes a 3 near-deaths and one potential 70-time return for its early investor.

We co-hosted an AACR recap event with BioPlus Partners in San Diego last week, and more than 100 of our members attended this over-subscribed event.

BioVerse #30 will be our third AACR conference recap. We will hear the insights and discussion from Anu Connor from Ipsen, Zhen Su from Marengo Therapeutics, Elizabeth McKenna from Cancer Discovery, and Dennis Chang from Lumanity. Book your calendar on April 29th, register for the webinar here, and network with other attendees here.

Many members are also going to ChinaBio or other satellite events in Shanghai this week. Join our in-person networking WeChat group to mingle with other members there.

@Philly conference will take place on May 8 and 9 in King of Prussia in Pennsylvania. Our paid subscribers will enjoy 50% discount for the conference registration.

, , and have been writing for the newsletter since 2023.

China’s Drug Pricing Reform: The Starting Point for a Bipolar Biopharma World

1. What Happened: An Inflection Point, Not a Starting Gun

On April 14, 2026, China’s State Council Office released Opinions on Improving the Drug Price Formation Mechanism (国办发〔2026〕9号), outlining a comprehensive framework for reforming drug price formation across the healthcare system. An analyst at Citigroup described the document as the “most significant” drug pricing guidelines in a decade. The framework spans 14 measures covering launch pricing, reimbursement standards, retail pricing, supply management, raw material oversight, and traceability.

This is not a new initiative, and it is not arriving in a vacuum. It formalizes a direction first signaled in a February 2025 draft consultation, building on years of incremental steps toward more market-oriented pricing. The 2026 document represents an inflection point in a trajectory that has been building — a moment where policy intent becomes institutional commitment. Full implementation will take years, but the direction is clear and the institutional will behind it is credible.

China is the world’s second-largest economy by nominal GDP and the largest by purchasing power parity. Its biopharma industry has developed rapidly, with globally competitive capabilities in biologics, ADCs, and multispecific antibodies. This pricing reform reflects a government that has consistently followed through on major healthcare system commitments — and that now has the economic weight and industrial base to back a genuine upgrade of its drug market.

2. Key Themes in the Reform

Theme 1: A Tiered Framework That Finally Rewards Innovation

The reform establishes a tiered pricing framework distinguishing three categories: high-level innovative drugs, improved new drugs, and generics.

For high-level innovative drugs — those with significant clinical value and high R&D risk — the policy supports premium launch pricing aligned with investment intensity, alongside a period of relative price stability. This is a meaningful structural departure from historical practice, where reimbursement price cuts frequently exceeded 70 percent under the prior negotiation system, and where pricing uncertainty systematically compressed returns on innovative therapies.

For improved new drugs, pricing is calibrated to the magnitude of incremental patient benefit.

Generics are guided toward reference-based pricing anchored to comparable therapies. The framework reinforces a consistent signal: genuine innovation will be differentiated and protected; me-too drugs will compete on price.

A particularly significant provision: negotiated reimbursement drugs may now be sold outside designated medical insurance channels at prices not constrained by the insurance payment standard. This allows companies to charge higher prices in private channels — including private hospitals, retail pharmacies, and online platforms. Private channels today represent a modest share of total drug sales, but their growth trajectory is strong, and this provision creates the commercial infrastructure for a meaningful parallel market over time.

The policy also calls for commercial insurance to play a bigger role in funding innovative drugs. China’s supplementary insurance market is underdeveloped relative to its public payer system today, but the policy direction — combined with rising household incomes and a growing middle class — points toward a multi-payer ecosystem that can support premium-priced therapies at meaningful scale.

Theme 2: Real-World Evidence as a Dynamic Pricing Mechanism

The policy creates a formal pathway for pharmaceutical companies to adjust prices post-launch based on real-world research results and clinical outcomes. This moves China away from static, cost-based pricing toward an evidence-driven model more consistent with leading global health technology assessment frameworks.

Akeso, one of the leading Chinese biotech, captured the shift well: “Pricing is no longer solely the outcome of reimbursement negotiation, but increasingly incorporates the market’s assessment of clinical value.” The infrastructure for systematic real-world evidence collection and assessment in China is still maturing, but the policy commitment to building it is explicit — and China has demonstrated it can build institutional capacity at scale when it chooses to.

Theme 3: Signals Toward Global Pricing Integration

The reform references a China drug price registration system and regional platforms including a China-ASEAN medical trade and procurement platform. These are early-stage initiatives, but they point consistently in one direction: China is not content to remain a price-taker in global pharmaceutical markets. Over time, a China pricing infrastructure with international connectivity has the potential to reshape how multinationals think about global launch sequencing and reference pricing exposure.

3. How This Compares to Western Pricing Approaches

China’s emerging model sits between the world’s two dominant frameworks: the U.S. system, where companies retain significant control over launch prices, and the European model, where governments anchor prices to clinical value through formal health technology assessments. The blend — market autonomy at launch, regulatory oversight through reimbursement and procurement — is a pragmatic design for a system of China’s scale and complexity.

The contrast with the U.S. trajectory is sharpening. While China is actively building infrastructure to reward innovative drug pricing, U.S. policy discussions increasingly center on importing lower international reference prices. For multinationals navigating both markets, this divergence is becoming a genuine strategic variable. China’s track record on major healthcare system commitments — volume-based procurement, the NRDL expansion, hospital payment reform — suggests that when the State Council commits at this level, implementation follows.

4. What This Means for China’s Biopharma Industry

China’s biopharma sector has spent the past decade proving it can discover and develop innovative drugs. The science, talent, and clinical infrastructure are now globally competitive. What has been missing is a domestic commercial model that allows companies to earn back their investment at home—and that gap has shaped the entire industry.

The missing piece: a market that funds innovation

Under the prior system, the economics were unforgiving. Reimbursement negotiations often drove price cuts exceeding 70%, leaving even successful drugs struggling to generate enough return to sustain the next wave of R&D. The consequence was structural: companies licensed out assets early and often, frequently on terms that undervalued the underlying science. This was less a strategic choice than a financial necessity. China generated innovation, but much of the value was realized elsewhere.

What changes under the new framework

The new policy directly addresses this imbalance. By allowing premium pricing for high-value innovation and creating commercial pathways outside the traditional reimbursement cycle, it introduces a credible route toward sustainable domestic businesses.

• Domestic revenues become more viable. Companies with truly differentiated therapies can expect pricing that better reflects clinical value—particularly in the early phases of commercialization—rather than facing immediate and steep price compression.

• Licensing out becomes a choice rather than a necessity. Much of the recent surge in outbound licensing—over 150 deals last year—has been driven by the need to secure returns outside China. As the domestic market improves, companies gain the option to hold onto assets longer, negotiate from a position of strength, and capture more value.

• The ecosystem begins to reinforce itself. When innovative drugs can generate meaningful returns locally, companies can reinvest in R&D, retain talent, and build commercial capabilities on their own terms. Over time, reliance on external capital and early licensing to fund innovation should diminish, allowing a more balanced and sustainable industry structure to emerge.

5. What This Means for the Global Biopharma Industry

China as a Tier-1 Innovative Drug Market

The most consequential long-term implication of this reform is that China becomes a tier-1 market for innovative drugs — one where premium pricing, early price stability, and diversified payment channels make it commercially comparable to the U.S. and leading European markets. Given China’s population, disease burden, and rising per capita healthcare spend, that would represent one of the most significant market expansions the industry has seen. The conditions are now being built. The trajectory is credible, even if the destination is years away.

Rethinking Global Launch Sequencing

One structural barrier to early China launches has long been the risk that low negotiated prices create downward reference pricing pressure in other markets, leading multinationals to deprioritize or delay China entry. The new framework reduces that risk by protecting early-stage pricing and enabling differentiated pricing across channels. Over time, this could bring China earlier into global development and launch planning — included in pivotal trial design, regulatory strategy, and first-wave commercial forecasting alongside the U.S., EU, and Japan rather than as a deferred market. That shift in sequencing, if it materializes, would itself be a significant structural change in how global drug development is organized.

A More Competitive Global Landscape

The U.S. has anchored global biopharma for decades not just because of its science, but because of its commercial engine: a large, high-price domestic market that funds the risk economics of drug development at scale. China now has the scientific base, the manufacturing capability, and the clinical infrastructure. This reform is an explicit attempt to add the missing commercial engine. If it succeeds, the global biopharma landscape shifts toward a genuinely bipolar structure — one where the two largest economies are also the two anchors of pharmaceutical innovation and value creation. That outcome is years away, and meaningful uncertainty remains. But today may be the starting point.

Bottom Line

China’s 2026 drug pricing reform is more than a pricing policy. It is an attempt to close the structural gap that has prevented China’s innovative biopharma sector from becoming fully self-sustaining, while simultaneously creating the conditions for China to emerge as a tier-1 global drug market. The science and the talent are already there. If the commercial foundation now being laid holds, the industry’s center of gravity shifts — gradually, but meaningfully.

Cofounder of ISWT Community

PD-1xVEGF vs. TROP2: An ASCO preview

As AACR was underway, ASCO released the abstract titles for its annual meeting.

Attention is being drawn to the overall survival result from Akeso/Summit’s HARMONi-6 trial (LBA4), which shares a plenary spot with Revolution Medicines’ groundbreaking RASolute 302 study (LBA5), along with three other late-breaking abstracts. (No plenary from AstraZeneca this year, ending its record seven-year streak.)

Placement on the plenary session elevated enthusiasm over the data. For background, HARMONi-6 is a Chinese study of the PD-1xVEGF bispecific ivonescimab, used in combination with chemotherapy, in first-line squamous non-small cell lung cancer. Results presented during a presidential symposium at ESMO 2025 linked the combo to a significant 40% progression-free survival benefit compared with BeOne’s PD-1 Tevimbra and chemo. At that time, the median follow-up for PFS was 10.3 months, and no information on OS was offered.

In an April 21 note, Leerink Partners analysts led by Dr. Daina Graybosch believed that a strong OS benefit with a hazard ratio below 0.72 was met at the first interim analysis, while a Jefferies team put their estimate at below or close to 0.75. The Leerink team argued that although the data could theoretically be from an ad hoc OS analysis requested by the Chinese authorities—and therefore likely lack statistical significance—the plenary status suggests this scenario may be unlikely.

That said, Leerink found that past ASCO plenary presentations showed a mix with sometimes ambiguous OS or debatable clinical relevance. For example, AZ’s Serena-6 study for the company’s oral SERD camizestrant in a novel first-line switch setting of HR-positive, HER2-negative breast cancer was a plenary at ASCO 2025. However, the FDA is set to scrutinize this study’s results at an advisory committee meeting next week. AZ will have an update of Serena-6 at ASCO 2026.

Recall, Summit recently updated its plan for the global HARMONi-3 trial with an interim PFS look at the squamous population in the second quarter, which might coincide with H-6’s ASCO presentation. Based on the H-6 data, Jefferies deemed a roughly 35% PFS improvement in H-3 as being consistent China vs. ex-China. A final PFS and interim OS look of that population in H-3 is expected in the second half of the year.

Compared with PFS, a statistically significant OS has always been more difficult to attain for VEGF antagonist. Therefore, an OS win here could prove that the bispecific construct is meaningfully improving on standalone VEGF—beyond the fact that VEGF is prohibited in squamous NSCLC specifically because of bleeding problems.

A positive OS readout from H-3 could boost confidence across the PD-(L)1xVEGF class, as it did briefly for the stock prices of Akeso, Summit and BioNTech. Nevertheless, the Leerink team argued that novel combinations are the key to value inflection. Before that, Summit “cannot become too expensive to acquire/engage in partnerships,” Leerink said, citing multiple PD-(L)1xVEGF competitors and a long development timeline across multiple indications, as well as lack of movement from several major oncology players, including Merck & Co., AZ, Roche, J&J, Eli Lilly and Novartis.

Merck represents an interesting case here. At AACR 2026, Merck gave a much-anticipated first look at its PD-1xVEGF data from its deal with LaNova Medicines (now part of Sino Biopharm). The data were simply too early to draw any conclusions, so I won’t elaborate too much on them.

In a Chinese phase 1/2 trial, the Merck drug, MK-2010, triggered an unconfirmed overall response rate (ORR) of 55% among 11 first-line PD-L1-positive NSCLC patients in one of two randomized backfill cohorts that got a 20mg/kg Q3W dose. The number looks similar to the 50% ORR reported by ivonescimab in the HARMONi-2 China phase 3 trial. But small patient populations, differences in PD-L1 expression levels and histology compositions prevent any reliable cross-trial comparison.

MK-2010 appears to preliminarily show a better safety profile. Again, data are very premature here. In a bigger group that also included previously treated patients, the rate of grade 3 or above treatment-related adverse events was 17% for MK-2010 in the 20 mg/kg cohort. By comparison, ivonescimab, also dosed at 20 mg/kg, recorded 29% in H-2 in a pure first-line setting.

But when asked about their phase 3 development plan, Merck only said: “While it is too early to disclose clinical development plans, we will leverage insights gleaned from our robust oncology development programs to inform where MK-2010, as a monotherapy and in various combination settings, may have the greatest benefit for patients.”

As we’ve mentioned before in our newsletter, Merck’s slow update here (the LaNova deal closed at the end of 2024) comes in stark contrast to the expansive phase 3 programs BioNTech/BMS have devised for pumitamig (11 late-stage/pivotal trials as of BioNTech Q4 update in March) and Pfizer/3SBio have for PF-08634404 (two investor webinars dedicated to the drug).

Merck instead has made major investments in its Kelun-Biotech-partnered TROP2 ADC, sac-TMT.

At ASCO 2026, we’ll have a showdown between PD-1xVEGF and TROP2, as Kelun will present results from its Chinese phase 3, OptiTROP-Lung05 in first-line PD-L1-positive NSCLC. Back in November, Kelun said the trial showed that sac-TMT beat Keytruda on PFS, with a positive trend in OS. We’ll be able to make a cross-trial comparison (with all the caveats considered) with ivonescimab’s H-2.

Just a few years ago, it would have been unimaginable for China-only clinical trials to command such significant attention at a major conference like ASCO.

At ASCO 2026, Gilead and AZ/Daiichi will present additional data from their TROP2 ADCs in first-line triple-negative breast cancer. Data unveiled at ESMO 2025 gave AZ/Daiichi’s Datroway an edge. We also eagerly await Datroway’s first-line NSCLC readout from the Avanzar trial, which has been pushed back to the second half of the year.

Either way, PD-1xVEGF and TROP2 may not be mutually exclusive. As Pfizer Chief Oncology Officer Dr. Jeff Legos recently said: “I’m not sure it’s an either-or, because they’re doing two very different things.” The goal of the PD-1xVEGFs is to replace Keytruda, while ADCs are considered as targeted chemo. Whether these two can be combined, “those experiments would have to be done,” Legos said.

, Deputy Editor of Fierce Pharma and ISWT Community volunteer

Three Near-Deaths, One $7-Billion Win: How Kelonia Defied Odds to Secure a 70-time Return

Eli Lilly has cemented its position in the competitive in vivo CAR-T space with the $7 billion acquisition of Kelonia Therapeutics. This deal, comprising a $3.25 billion upfront payment and $3.75 billion in milestones, is the largest of the six acquisitions in the in vivo CAR-T sector and follows Lilly’s $2.4 billion acquisition of Orna Therapeutics two months prior.

The high valuation is primarily driven by Kelonia’s compelling 4-patient clinical data for KLN-1010, initially presented at ASH 2025.

The data showed a 100% response rate—one complete response and three partial responses. Crucially, KLN-1010 also demonstrated a superior safety profile compared to rival therapies. Unlike EsoBiotec’s ESO-T01, which caused severe Grade 3/4 Cytokine Release Syndrome (CRS) in all five treated patients, including one fatality, Kelonia’s KLN-1010 resulted only in Grade 1 or 2 CRS and no neurotoxicity. This favorable safety margin establishes KLN-1010 as a potentially best-in-class candidate in the in vivo CAR-T for oncology.

Best-in-Class Clinical Data Trumps First-Mover Advantage

While some expected the high volume of 5 acquisitions and numerous partnerships prior to this deal to cool the market, Lilly’s move proves that superior clinical data is the dominant driver of M&A activity.

The acquisition makes strategic sense for Lilly, using strong cash flow from its obesity franchise to fund diversification. The deal provides Lilly with both RNA-based (from Orna) and lentiviral-based (from Kelonia) in vivo CAR-T platforms, enabling competition across various immunological indications where lentiviral therapies may not be ideal.

The Chinese in vivo CAR-T space is also rapidly expanding, with an estimated 200 companies developing in vivo CAR-T assets. While most are “fast followers,” innovative companies like METiS are gaining traction. METiS, which is developing an LNP-mRNA based in vivo CAR-T therapy showing impressive efficacy and low toxicity, is a key appeal for its incoming HKEX IPO.

Horizon Watch: Key Trends in In Vivo CAR-T

According to a popular post by Yu Cao, a member of ISWT Community, presentations at AACR highlighted three major areas of innovation in the in vivo CAR-T space:

1. Novel Platforms: Development of new delivery vehicles based on lentiviral vectors, lipid nanoparticles (LNPs), and virus-like particles.

2. Focus on Autoimmune Diseases: The belief that clinical validation for immune reset in autoimmune conditions may be faster to achieve.

3. Next-Gen Design: Emphasis on improving specificity, persistence, and safety profiles.

The Kelonia Story: A Reward for Betting on First-in-Class

Kelonia, founded in 2020 on technology from Michael Birnbaum of MIT, faced near-financial collapse three times during its almost seven-year journey according to its lead investor Bryan Roberts.

At some point, Bryan Roberts concluded with CEO Kevin Friedman, “We need to figure out a way to get ourselves to clinical data and that will fundamentally change the availability of capital for us.”

And sure they did! After presenting the pivotal 4-patient data at ASH 2025, the company quickly entered months-long due diligence and a six-week, serious price negotiation process that culminated in the Lilly acquisition.

Kelonia’s major investor venRock stands to receive a potential 70-fold return on its initial investment if all milestones are paid, demonstrating the massive reward for taking a risk on first-in-class, transformative technology.

, Founder of ISWT BioAdvisory

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Summary

In this week’s issue,

• recaps RevMed’s unprecedented pancreatic cancer data. A near doubling of overall survival from RevMed’s pan-RAS inhibitor sheds light on its previous rejection of Merck & Co.’s reported ~$30 billion buyout offer.

• , following Kailera’s successful IPO, examines the rising "Buy and Build" model for China Newcos, analyzing recent high-value exit of China newco deals and opine the future direction of this model.

BioVerse #30 will be our third AACR conference recap. We will hear the insights and discussion from Anu Connor from Ipsen, Zhen Su from Marengo Therapeutics, Elizabeth McKenna from Cancer Discovery, and Dennis Chang from Lumanity.

Book your calendar on April 29th, register for the webinar here, and network with other attendees here.

Almost 200 ISWT Community members attending AACR have joined our WeChat networking group. Scan the QR code to mingle with fellow members. Please add Leon Tang (WeChat ID LeonTangBiotech) for assistance if QR code doesn’t work.

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

RAS is On

Revolution Medicines’ pancreatic cancer readout this week was greeted with much enthusiasm across the industry. The company said its daraxonrasib, a RAS(ON) inhibitor, nearly doubled overall survival versus chemotherapy in previously treated patients in the phase 3 RASolute 302 trial.

Descriptions of the topline data were filled with such acclamations as “impressive,” “transformative,” a “game changer” and a “revolution.”

We heard the same praise when Amgen’s Lumakras became the first KRAS inhibitor to reach the market, successfully cracking what was once considered an undruggable target. However, after a messed-up phase 3 and an FDA snub in non-small cell lung cancer, Lumakras only brought in $363 million sales in 2025.

This time, with daraxon, things could be different.

According to RevMed, median OS for the daily pill reached 13.2 months, compared to 6.7 months for those in the chemotherapy group, translating into a 60% reduction in the risk of death in second-line metastatic pancreatic ductal adenocarcinoma (PDAC). The pan-RAS inhibitor was also said to be “generally well tolerated, with a manageable safety profile and with no new safety signals.”

Daraxon’s 13.2-month median OS in 2L mPDAC matched the median OS demonstrated by this 1L regimen of nab-paclitaxel plus gemcitabine, followed by mFOLFOX, as described in this randomized phase 2 trial in early 2024.

Before the readout, Evercore ISI analysts noted after interviewing 16 KOLs that many set the median OS bar at around 10-11 months, with one saying a 20% OS improvement would be enough.

“[T]he unmet need is so severe that even a modest gain vs chemo is practice changing,” Evercore summarized the responses.

RevMed has an FDA Commissioner’s Priority Review Voucher for this, and the KOLs interviewed by Evercore “see a significant 1st-mover advantage in PDAC for daraxon and believe RVMD can easily entrench it across the treatment paradigm through various regimens.”

PDAC is notoriously difficult to treat, with a five-year survival rate of just 8%. This cancer type affects more than 50,000 people in the U.S. every year. Evaluate Pharma recently named daraxon the most valuable orphan drug with projected $4 billion sales in 2032 based on “the considerable unmet need in pancreatic cancer, due in part to the ineffectiveness of immunotherapy in this setting.”

It’s quite the feat for RevMed after the company faced significant questions and market volatility after Merck & Co. reportedly walked away from acquisition talks at the beginning of the year. RevMed management apparently stood its ground and rejected the Keytruda maker’s offer at around $30 billion, according to The Wall Street Journal.

Following the positive RASolute 302 readout, RevMed’s market cap now sits at nearly $31 billion.

On a side note. RevMed, formed with funding from Third Rock Ventures in 2014, absorbed EQRx in an all-stock transaction in 2023. Before its high-profile exit, EQRx was Alex Borisy’s (who still sits on RevMed’s board) enterprise designed to in-license fast-follower Chinese drugs for potential quick market entry in the U.S. at a lower price. That model collapsed after the FDA rejected China-only data in its denial of Innovent Biologics’ PD-1 inhibitor.

It’s interesting to see how the biotech industry’s China strategy has shifted—or not—over the years. Today, the “NewCo” model seems to reign supreme. Rather than relying solely on China data to gain FDA approval, these U.S. NewCo startups license Chinese drugs and leverage Chinese data to accelerate their U.S. development path.

The RevMed data report this week coincided with the $625 million IPO of Kailera Therapeutics, which only emerged in 2024 with a $400 million series A and a portfolio of GLP-1 drugs licensed from Hengrui. Kailera’s shares surged more than 60% in their Nasdaq debut.

Rather than a fast-follower, RevMed is breaking new ground.

Unlike Lumakras, which targets KRAS G12C at its inactive, GDP-bound KRAS (OFF) state, daraxon goes after RAS(ON), the active, GTP-bound form of RAS variants which directly fuel cancer progression by sending growth signals. Cancer cells could adapt to RAS(OFF) inhibition by increasing the proportion of active RAS, leading to treatment resistance.

Developed with RevMed’s Tri-Complex platform, daraxon binds to the chaperone protein cyclophilin A to form a new complex with high affinity for RAS(ON) proteins, thereby blocking other cancer-promoting bindings.

A potential competitor to daraxon is Erasca’s ERAS-0015. The Nasdaq-listed firm licensed the pan-RAS molecular glue from China’s Joyo Pharmatech for $12.5 million upfront in 2024. The candidate is way further behind daraxon in development, currently in phase 1 dose escalation with initial monotherapy data expected in H1 2026.

In January, just a few days before WSJ’s report that Merck and RevMed couldn’t reach a deal, Erasca rode the hype of a potential deal in the space to a $225 million raise.

Following its readout, RevMed closed an upsized public offering, gaining about $2.2 billion in additional funding.

, Deputy Editor at Fierce Pharma and ISWTC volunteer

After Kailera IPO Success, What’s Next for China Newco?

Kailera completed a successful IPO, raising $625 million, one of the largest biotech IPOs in recent years. It closed its first trading day with a 62.5% increase, valuing the company at approximately $3 billion. HengRui Pharma, the originator of Kailera’s four pipeline assets, holds about 10% of Kailera’s shares, now worth ~$300 million—a threefold increase from their initial value two years ago (see Issue 046 published on 2024-05-19).

The “Buy and Build” Model with “Chinese Characteristics”

Kailera’s founder, Don Renaud, is a highly successful serial biotech entrepreneur. His previous company, Cerevel—a “buy and build” biotech based on Pfizer assets—was acquired by AbbVie for $8.7 billion. As of today, Renaud’s biotech ventures have led to ~$16 billion in acquisitions.

The “newco” model, exemplified by Kailera, is a well-established “Buy and Build” strategy, used in successful acquisitions like Cerevel, Akero, Intracellular, and Rapt Therapeutics. This model typically requires a clinical pipeline, an experienced management team, substantial capital, and focus on M&A-active fields. The new wave of Chinese newcos, largely in the “buy and build” category, only differs by sourcing assets from Chinese biotech and biopharma instead of Western counterparts.

Scorecard for the “Class of 2024” China Newcos

The 2024 cohort of China Newcos has performed well. In addition to Kailera’s ~$3 billion IPO, Ouro Medicines was acquired by Gilead for up to $2.2 billion last month, and Candid Therapeutics closed a pre-IPO financing of $505 million at a ~$1.3 billion valuation.

Ouro Medicines is currently the most successful. Its single asset, a BCMA TCE from KeyMed, provided the originator with $250 million cash and up to $70 million in milestones. KeyMed’s equity in the newco was initially valued at $10 million, resulting in an astounding return of up to 32 times. Notably, all five successful newcos are focused on autoimmune diseases and obesity, two hot fields for deal-making.

Newco vs. Direct Licensing to MNC

Many Chinese companies prefer direct licensing to pharma companies due to higher upfront payments and seemingly generous total deal values. However, less than 10% of “biobucks” are realized over time, making the Probability of Success (PoS)-adjusted Net Present Value (NPV) of these deals much less attractive than their headline value suggests.

Successful newcos like Candid, Kailera, and Ouro offer Chinese companies what they often lack: access to top-tier KOLs, well-connected investors, and exclusive insights into pharma companies’ acquisition priorities (”shopping list”). This access has been a critical factor in the impressive acquisitions of Aiolos Bio, Rapt Therapeutics, and Ouro Medicines.

What’s next for China Newco?

At a recent BioCentury show, Forbion founder Sander Slootweg noted that China has “commoditized” best-in-class drug development. Forbion, a pioneer in the China newco space, has invested in Aiolos Bio, Verdiva, Braveheart, and Solstice Oncology. Slootweg acknowledged that arbitrage opportunities for clinical-stage assets are shrinking due to increased competition from large pharma.

He suggests that Western VCs are now targeting earlier-stage Chinese innovations. He believes Western VC capital, executive experience, and KOL networks complement China biotech’s fast, cost-effective execution in early-stage R&D.

There is also growing interest in the “reverse newco” model, where Western biotechs partner with Chinese biotechs to accelerate the development of their first-in-class assets. Success stories include EsoBiotec, as well as the recent Rapport/Tenacia and Crescent/Kelun deals.

The future of the China newco trend may point to “Going Early” and “Going Reverse”.

, Founder of ISWT BioAdvisory

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Summary

In this issue

• discusses the FDA’s legislative request to create an expedited IND pathway, noting how it differs from China’s IIT track which has recently become the talk of the biotech town.

• contemplate on “The Biotech Three-Body Problem” regarding how to navigate the US, Europe, and China innovation triangle based on a few publications and events last week.

• captured a rare closed-door conversation in which executive search partner Cissy Young speaks candidly with East Asian biopharma veterans — sharing what boards really look for in C-suite candidates, and what you can do about it. (Exclusive: paid subscribers)

ISTC Community, in collaboration with BioPlus Partners, will host a China IIT panel discussion during AACR in San Diego where will share their first-hand experiences. Space is limited, review the agenda and sign up for the event here.

Scan the QR code below to join our AACR2026 In-Person networking WeChat group

, , and have been the proud writers and editors of this newsletter since 2023.

Email us at contact@iswtc.org to learn how to support or contribute to our newsletter.

Pressured by China’s IIT, FDA proposes IND reform

Recognizing China’s efficient regulatory framework for early clinical trial initiation, FDA Commissioner Dr. Marty Makary is petitioning the U.S. Congress to allow the agency to open a new pathway for clearing phase 1 clinical trials.

Among his legislative proposals within the FDA’s fiscal year 2027 budget, Makary described this new pathway as an “optional, risk-based” alternative to the “burdensome existing investigational new drug pathway.” It will be open to cases “where there is existing preclinical data that can potentially satisfy the regulatory standard with validated [New Approach Methods].” NAMs are non-animal testing tools in drug development.

“This policy would be particularly important for smaller biotechnology firms that face greater barriers to entry under the current paradigm, which has fueled the increase in early stage preclinical, and Phase 1 activity in China and Australia,” Dr. Makary wrote.

During his one-year anniversary speech to FDA staffers on April 1, Dr. Makary called China “the biggest threat that we have in the drug space.” He noted that China surpassed the U.S. around 2021 with the number of clinical trials. China counted four times the initiation of phase 1 trials than the U.S. in 2024, he said.

“We have to be efficient,” he said in his speech. “We should not be requiring things that are not central to safety or efficacy. So we are changing the requirements on the IND itself.”

As we discussed in our newsletter Issue 132 on March 22, China’s fast clinical development pace, especially in the cell & gene therapy space, owes mainly to its Investigator-Initiated Trial (IIT) pathway. Our readers are likely already familiar with this pathway, but as a brief intro for those who are relatively new to this concept: IITs are sponsored by qualified Chinese investigators at major medical institutions and are regulated not by China’s drug regulators but by the National Health Commission (NHC), which oversees hospitals. Requiring approvals only by local science and ethics committee, plus registration with the government, IITs can start very fast.

Through an updated rule titled “Regulation on the Administration of Clinical Research and Clinical Translational Application of New Biomedical Technologies” (Chinese) which will go into effect in May, drugmakers can also launch IIT-like studies in collaboration with major healthcare institutions.

As Strand Therapeutics CEO Dr. Jacob Becraft noted during a recent Congressional hearing, China’s ability to yield early clinical evidence faster and cheaper than the U.S. created a “flywheel effect” that has put the U.S. biotech industry on notice.

“When a therapy produces early human results, that program becomes de-risked. Investors step in, partnerships form, companies grow, and manufacturing capacity expands. Clinical centers gain experience running more clinical trials. And the cycle repeats,” he said.

But what Makary is proposing is apparently not a U.S. version of IIT.

• First, the FDA chief is only looking to “reduce duplicative and time-consuming requirements” rather than removing federal review and approval. In contrast, with IIT, according to China’s new rule, go-ahead decisions are made by local institutional review boards (IRBs), while the government is focused on post-initiation regulation.

• Second, while Makary’s proposed “Expedited IND” pathway serves as an alternative to a traditional IND, China’s IIT does not. IITs cannot lead to drug approvals. Instead, IITs offer early insight into e.g. safety and dose exploration and therefore potentially enable a smoother, more robust IND development, or help drugmakers eliminate bad candidates or technologies before committing too many resources to a full IND.

• Third, China’s IIT is commonly used on certain novel technologies that mostly fit the cell & gene therapy category, although, as with most rules in China, authorities have left an opening for “other methods” deemed appropriate by the NHC. Details of Makary’s proposed pathway remain unclear, but it seems more broadly applicable. So far, the only stated bar is for “drugs with adequate preclinical data.”

In summary, China’s IIT pathway may still be faster, cheaper and easier to set up, but the FDA’s proposed expedited IND might cover more areas.

Cumbersome FDA requirements are not the only problem slowing U.S. phase 1s down. During his April 1 address, Makary also criticized delays at IRBs, recalling one case where it took him a year and a half to get a study through the IRB at Johns Hopkins.

“The entire U.S. research infrastructure is dependent on this rate-limiting step that is log jamming researchers and making us non-competitive with IRBs overseas,” he said.

“I don’t know what the right solution is, but we are smart people in the United States. We can fix this log jam. We are losing business. We are seeing trials go overseas.”

That means, even if the U.S. copies China’s IIT, it won’t be able to match China’s speed in launching the studies because of slow-moving IRBs.

In another potential way to ultimately accelerate the entire clinical development process in the U.S., Makary during his speech teased the launch of a “real-time continuous” trial framework. By streamlining the entire path from phase 1 to phase 3, the FDA could potentially make starting phase 1 in the U.S. more attractive.

“This would be a pilot program, but we are very close to announcing a real-time, continuous trial whereby sponsors can allow regulators to see the data as it is happening in real time,” Makary said.

Details remain scarce, but the idea is to forgo the traditional step-wise approach. From what Makary has shared, he envisions that FDA regulators would get clinical trial data directly from the electronic health record as an ongoing trial unfolds, so the agency can stop a trial when it sees clear efficacy or a safety signal. The goal is to reduce the stop-and-start intervals between trial phases.

Trials with combined phases are pretty common these days. Some phase 1/2 or phase 2/3 have supported FDA approvals. But I don’t recall any past FDA approvals based on a single trial that runs all the way from phase 1 to phase 3.

Friends of Cancer Research explored seamless trial designs in rare cancers in a recent White Paper (PDF). The white paper mentioned Gavreto’s (pralsetinib’s) phase 1/2 Arrow trial that led to FDA accelerated approvals in RET fusion-positive non-small cell lung cancer and thyroid cancer.

There could be some challenges with this seamless design, considering how fast treatment landscapes evolve, which dictates how much a sponsor can determine when launching what would become essentially a series of trials. We await full details to see how FDA’s pilot design could work in real life.

Angus Liu, Deputy Editor of Fierce Pharma, ISWTC Volunteer

The Biotech Three-Body Problem: Navigating the US, Europe, and China Innovation Triangle

Recent articles in The Wall Street Journal, STAT News, CNBC, and The Wire China highlight how the rise of China’s biotech sector is transforming the global pharmaceutical industry. This includes major pharmaceutical companies pivoting to China for drug ideas, US biotech VCs adopting new business models, and European biotechs facing challenges from China and aggressive US policies.

For drug companies with global goals, engaging with China biotech is now essential.

The US Perspective: China Biotech Forces New Models

As I pointed out at the Cancer Progress conference last week, China biotech’s speed and cost advantages are rapidly narrowing the gap between first-in-class and best-in-class assets. For example, in the pan-RAS space, US frontrunner Revolution Medicines is followed by US biotech Erasca, which licensed a similar molecule from China, and China-domicile GenFleet, with a molecule based on a different structure.

The gold rush of T-cell engagers (TCEs) for autoimmune diseases is probably the best example of how China biotech has rewritten the R&D playbook, and Candid Therapeutics is probably the best case study. Candid Therapeutics is well-positioned by not only licensing five assets from China, including two clinical-stage “first-in-class” and three “best-in-class” molecules, but also running early clinical trials there. This led to Candid Therapeutics’ impressive nearly $900 million fundraising and an upcoming IPO at a generous valuation.

Inspired by successes like this, US investors are adapting; the standard formula of “$20-25 million and 3 years for target-to-IND” is no longer acceptable. VCs like Vivo Capital, RA Capital, OrbiMed, and RTW are setting up incubators or partnering locally to access early Chinese innovation, according to the STAT News article.

The European Perspective: China Biotech Offers an Escape from the Productivity Trap

Europe is losing R&D market share to the US and China. In 2025, Europe accounted for only 26% of global R&D, down from 49% in 1990, while the US rose to 55%. Europe lacks the scale, speed, cost advantages, and large, high-risk-tolerance investors of the US.

However, European investors remain active. The recent ~$2.2 billion acquisition of Ouro Medicines, whose single asset originates from China, received investment from Europe-based Monograph Capital and GSK corporate ventures. European biotech talent is also a key asset; the $411 million Series A for Verdiva, with Chinese-asset backing, was led by Forbion and features experienced largely European management.

EsoBiotec demonstrates successful collaboration, leveraging European leadership and “first-in-class” technology with China’s rapid preclinical and early-stage clinical capabilities, leading to acquisition by AstraZeneca.

The China Biotech Perspective: Selling Innovation is a Necessity

Data presented at BioVerse last week clearly shows that China-to-West dealmaking is surging. Q1 2026 saw 47 deals with $4.1 billion in upfront payments and $60.2 billion total value, already exceeding the 2024 annual total. Projections for 2026 suggest ~$16 billion in upfront payments and ~$240 billion total value, far exceeding the total of $7.1 billion upfront and ~$136 billion total value in 2025.

(Link to download the the presentation is accessible to paid subscribers in this newsletter)

To avoid direct competition with China’s focus on “best-in-class” drugs, many Korean and US biotech firms, such as Orum Therapeutics and Candid Therapeutics, are shifting their strategies. They are pursuing either “first-in-class” drug development or “best-in-class” approach that fully leverages China’s R&D infrastructure.

Despite some positive deal announcements, the HKEX China biotech index remains at half its 2021 peak. This modest performance is largely because Chinese drug companies have only a negligible share of revenue in high-margin markets like the US and Europe. This situation disproportionately channels the value of China-originated innovation to its Western partners.

As I concluded in the Wire China article: “It doesn’t matter how strong [China’s] biotech is. In the end, big pharma is the [primary] customer of [China] biotech companies.”

, Founder of ISWT BioAdvisory & BD Head of Mianus Accelerator

Breaking In, Moving Up

What East Asian Biopharma Executives Need to Know

A conversation with Cissy Young, executive search partner, and Chinese biopharma veterans — condensed for the ISWT Community

What does it actually take for an East Asian professional to reach the C-suite in biotech? At a recent closed-door session, executive search partner Cissy Young, Ph.D., sat down with a group of Chinese biopharma veterans to speak candidly about bias, selection dynamics, and the personal career direction frameworks that can make or break a career trajectory. Below is an edited summary of that conversation.

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