Emerging biotech

Soon after starting a new biotechnology company, David Li realized he needed to rethink his strategy. 

Li had been conducting the competitive research biotech entrepreneurs typically undertake before soliciting investment. He drew up a list of drug targets that his startup, Meliora Therapeutics, could pursue and checked them against the potential competition. 

Li quickly found that biotechs in China were already working on many of the targets he had on his list. Curious, he visited Shanghai and Suzhou and witnessed a buzzing scene of startups set frenetically to task. 

“They're not really thinking about the U.S. at all. They're just trying to create more value and stay alive to differentiate themselves from the next guy in China,” he said. “They're moving quick. There are a lot of them and they're just quite competitive.”

Li’s experience is illustrative of a trend that could pressure biotech companies in the U.S. and alter their drug development strategies. More and more, large pharmaceutical companies are licensing experimental drugs from China. Venture companies are testing similar tactics by launching new U.S. startups around compounds sourced from China’s laboratories. This shift has been sudden, with licensing deals ramping rapidly over the past two years. And it is occurring even as the shadow of U.S.-China competition within biotech grows longer. 

Executives and investors interviewed by BioPharma Dive share Li’s outlook. They expect such deals will accelerate and, in the process, force U.S. biotechs to work harder to stand out. 

“We’ve been warning people for a while, we're losing our edge,” said Paul Hastings, CEO of cell therapy maker Nkarta and former chair of the U.S. lobbying group the Biotechnology Innovation Organization. “Innovation is now showing up on our doorstep.”

There’s perhaps no clearer example of this than ivonescimab, a drug developed by China-based Akeso Therapeutics and licensed by U.S.-based Summit Therapeutics. Recent results from a lung cancer study run in China showed ivonescimab outperformed Keytruda, Merck’s dominant immunotherapy and currently the pharmaceutical industry’s most lucrative single product. 

The finding “put a huge focus on what’s happening in China,” said Boris Zaïtra, head of business development at Roche, which sells a rival to Keytruda. 

Fast-moving research

The deal boom has roots in efforts by the Chinese government to upgrade the country’s biotech capabilities by upping investment in technological innovation. In the life sciences, the initiative provided funding, discounted or even free laboratory space and grants to support what Li described as a “robust ecosystem” of biotechs. 

The results are clear. Places like Shanghai and Suzhou are home to a skilled workforce of scientists and hundreds of homegrown companies that employ them. Science parks akin to the U.S. biotech hubs of Cambridge, Massachusetts and San Francisco have sprouted up. 

Chinese companies generally can move faster, and at a lower cost, than their U.S. counterparts. Startups can go from launch to clinical trials in 18 months or less, compared to a few years in the U.S., Li estimated. Clinical trial enrollment is speedy, while staffing and supply chain costs are lower, helping companies move drugs along more cost effectively. 

“If you're a national company within China running a trial, just by virtue of the networks that you work within, you pay a fraction of what we pay, and the access to patients is enough that you can go really fast,” said Andy Plump, head of research at Takeda Pharmaceutical. “All of those are enablers.” 

And what they’ve enabled is a large and growing stockpile of drug prospects, many of which are designed as “me too better” versions of existing medicines, analysts at the investment bank Jefferies wrote in a December report. Initially focused in oncology, China-based companies are now churning out high-quality compounds across multiple therapeutic areas, including autoimmune conditions and obesity. 

“There was a huge boom of investment in China, cost of capital was very low, and all these companies blew out huge pipelines,” said Alexis Borisy, a biotech investor and founder of venture capital firm Curie.Bio. ”Anything that anybody was doing in the biotech and pharmaceutical industry, you could probably find 10 to 50 versions of it across the China ecosystem.”

Me-toos become me-betters

For years now, Western biopharma executives have scouted the pipelines of China’s biotech laboratories — exploration that yielded a smattering of licensing deals and research collaborations. Borisy was among them, starting in 2020 a company called EQRx that sought to bring Chinese versions of already-approved drugs to the U.S. and sell them for less. EQRx’s plan backfired amid scrutiny by the U.S. Food and Drug Administration of medicines tested only in people from a single country.

Now, however, the pace of deals has accelerated rapidly. There are a few reasons for this. According to Plump, one is the improving quality of the drug compounds being developed. The “me toos” are becoming “me betters” that could surpass available therapies and earn significant revenue for companies — like BeiGene’s blood cancer drug Brukinsa, which, in new prescriptions for the treatment of leukemia, overtook two established medicines of the same type in 2024. 

Another reason, Plump said, is that China-based companies are becoming more innovative, studying drug targets that might not have yet yielded marketed medicines, or for which the most advanced competition is in early testing. Li notes how Chinese companies are going after harder “engineering problems,” like making complex, multifunctional antibody drugs, or antibody-drug conjugates. 

“There are so many [companies] that the new assets are going to keep coming,” Li said. 

Much as in the U.S., China-based biotechs are also fighting for funding, pushing them to consider licensing deals with multinational pharma companies. At the same time, these pharmas are hunting for cheap medicines they can plug into their pipelines ahead of looming patent cliffs. The two trends are “colliding,” said Kristina Burow, a managing director with Arch Venture Partners. “I don’t see an end to that.”

The statistics bear Burow’s view out. According to Jefferies, the number and average value of deals for China-developed drugs reached record levels in 2024. Another report, from Stifel’s Tim Opler, showed that pharma companies now source about one-third of their in-licensed molecules from China, up from around 10% to 12% between 2020 and 2022. 

“I see huge opportunities for us to partner and work together with Chinese companies,” said Plump, of Takeda. 

Several venture-backed startups have been built around China-originated drugs, too, among them Kailera Therapeutics, Verdiva Bio, Candid Therapeutics and Ouro Medicines, all of which launched with nine-figure funding rounds. 

“There's been a lot of really good, high quality molecules and data that have emerged from China over the last couple of years,” said Robert Plenge, the head of research at Bristol Myers Squibb. “It's also no longer just simply repeating what's been done with the exact same type of molecule.”

Geopolitical risks

These deals are happening against an uncertain backdrop. The U.S. Congress has kicked around iterations of the Biosecure Act, a bill that would restrict U.S. biotechs from working with certain China-based drug contractors. A committee in the House of Representatives is calling for new limits on clinical trials that involve Chinese military hospitals. And the Trump administration has threatened tariffs that could ripple across industrial sectors. 

“We don’t know what this new administration is going to do,” said Jon Norris, a managing director at HSBC Innovation Banking.

The Biosecure Act “keeps going sideways,” added Hastings, who believes that any impact from the legislation, if passed, would be minimal. Instead, Hastings wonders if future tariffs may be more problematic. “There will be tariffs on other goods coming from China. Does that include raw materials and innovation? It’s hard to imagine that it won’t,” he said. 

But executives and investors expect deals to continue, meaning U.S. biotechs will have to do more to compete. 

“U.S. companies will need to figure out what it is they’re able to bring to the table that others can’t,” said Burow, of Arch. 

Borisy said startups working on first-of-their-kind drugs need to be more secretive than ever. “Do not publish. Do not present at a scientific meeting. Do not put out a poster. Try to make your initial patent filing as obtuse as possible,” he cautioned. 

“The second that paper comes out, or poster at any scientific meeting, or talk or patent, assume it has launched a thousand ships.”

Those that are further along should assume companies in China will be quick on their heels with potentially superior drugs. “The day when you could come out with a bad molecule and open up a field is over,” he said. 

Greater competition isn’t necessarily a bad thing, according to Neil Kumar, CEO of BridgeBio Pharma. Drug development could become more efficient as pharmas acquire medicines from a “cheaper” starting point and advance them more quickly. 

Venture dollars could be directed towards newer ideas, rather than standing up a host of similar companies.“If all of a sudden this makes us less ‘lemming-like,’” Kumar said, “I have no problem with that.”

Li similarly argues that, going forward, U.S. companies need to focus on “novelty and innovation.” At his own company, Li is now working on things “we felt others were not able to access.”

“The game has always been the same. Bring something super differentiated to market,” he said. But “the bar has risen.” 

Gwendolyn Wu and Jacob Bell contributed reporting. 

The makeup of the world’s pharmaceutical pipeline is changing. China’s fast-growing biotechnology industry is a big reason why. 

Over the past decade, China’s government has sought to upgrade the country’s drugmaking capabilities. Its efforts birthed a burgeoning ecosystem of homegrown companies and science parks that mirror — and even rival —  U.S. hubs in Boston and San Francisco. Lower costs and regulatory flexibility have helped China’s biotech startups move faster than their U.S. counterparts, producing a sprawling inventory of drug prospects. While many are designed to be superior versions of medicines either on the market or in development elsewhere, more and more are innovative, challenging the U.S.’s long-held biotech advantage. 

Large pharma companies and venture capital investors have taken note. Many are licensing experimental drugs from China, either to add to their drug portfolios or build new biotechs around. The shift has been rapid, with dealmaking spiking in recent years. According to analysts, licensing agreements are on a record pace in 2025. Fully one-third of the industry’s licensing spending this year has involved drugs sourced from China, per the investment bank Jefferies.

These deals reveal important insights about the types of medicines drugmakers and investors want in their portfolios. With this database, we’re tracking 2025 deals in which China-based drugmakers licensed to U.S. and European companies rights to human therapeutics. We show the companies involved, the financial terms of their alliances and details about the medicines and drug targets. 

If we’ve missed a deal, or there’s any additional information you’d like to see, please reach out and let us know.

Jump to database

Jump to methodology

Ned Pagliarulo contributed reporting.

Biotechnology industry watchers were hopeful at the start of 2025. Venture funding appeared to be rebounding after a lengthy slump, and a smattering of new stock offerings and company acquisitions brewed optimism that the public markets might be similarly warming up to young drugmakers.

But the positivity quickly dissipated. Trump administration policies gutted scientific research funding and raised questions about U.S. drug prices. Large layoffs and upheaval at public health agencies created regulatory turmoil that added risk to what’s already, by its nature, a risky sector to invest in. 

The results were laid out in a June report from David Windley and Tucker Remmers, two analysts at the investment bank Jefferies. According to that report, funding in public biotech companies — be it from initial public offerings, follow-on stock offerings, or “PIPE” deals — plummeted in May. The “political and economic uncertainties” have "cast a cloud over biotech investment,” they wrote. 

“Since product development cycles can range 12-15 years in this industry, biotechs (and their boards and investors) want clarity on FDA regulation, drug pricing, and funding before committing to large, [long-term] investments,” Windley and Remmers wrote.

Investors and industry insiders interviewed by BioPharma Dive say that the public slowdown is trickling down to startups that have already been under intense pressure during a prolonged pullback. Companies and investors are struggling to align on valuations, making funding rounds more difficult to close than in prior years. The uphill battle in the public markets is further delaying IPO plans, too. 

"People are waiting to see what happens, and it's extended that winter," said Tim Scott, the president of Biocom California, an industry trade group.

To date, nine biotech companies have priced IPOs in 2025, and only one large offering has occurred since mid-February. One of the last to publicly disclose IPO ambitions, Odyssey Therapeutics, pulled its offering in May and later raised more private funding. In a letter to the Securities and Exchange Commission, CEO Gary Glick wrote that it was “not in the best interests of the company” to go public at that time.

One reason IPOs have ground to a halt, experts say, is that the public markets aren’t rewarding drug startups as predictably as they once were. Typically, drug companies can expect their value to climb after delivering positive clinical results. But “even companies with good data aren’t seeing a lot of movement in the public markets,” said Jonathan Norris, a managing director at HSBC Innovation Banking.

As a result, Norris said, companies are looking at the time and expense it takes in the monthslong process to go public and wondering: “What’s the benefit?”

“If you have any readouts that are even eye squinting, you’re going to get crushed,” he said. “It’s a tough, tough endeavor.”

The shuttered IPO window is exacerbating problems for young biotechs. "If you don't have a public market opportunity, then the companies that are private have to think about ways to raise capital and stay private for longer," said Maina Bhaman, a partner at Sofinnova Partners.

Feeling that burden, venture investors are becoming more conservative. While private funding hasn’t plummeted as much as its public counterpart, investors are more selective and slower-moving. Funding has become increasingly consolidated into fewer and larger “megarounds,” to the extent that more firms are compiling similar portfolios. And they’re hard to finalize, even when most of a funding syndicate is already onboard, according to Norris.

"People are struggling to figure out where the bottom of the market is and what's the appropriate valuation and expectation for that investment,” he said. 

"A lot of VCs are pencils down right now on deals they would otherwise be moving forward on,” Scott added.

Pullbacks are nothing new in biotech. But what has been unusual, some say, is how long the sector has spent in the doldrums after peaking in early 2021. One reason is the most recent boom flooded the market with more companies than it could support. But another is that the ensuing correction has intensified amid regulatory and political upheaval. 

A report in June from Roel van den Akker, PwC’s U.S. pharma and life science deals leader, predicted that companies will be “preparing contingency plans” to account for delays in “trial oversight” and drug applications.

Drug companies are used to dealing with a high level of risk, as most experimental medicines never make it to market. But “now you've got a lot more macro uncertainty that is being layered on top," Bhaman said.

On the public side, that uncertainty has resulted in less patient investors, some of whom are pressing company boards to shut down after setbacks rather than change course. But some startups are taking drastic steps, too, such as cutting programs and staff to, some experts believe, depress their value so they can still attract investment. 

The "lack of surety" is pressuring biotechs to be as efficient as possible with their cash, Scott said, perhaps working on one program instead of a few. 
 
There have been multiple high-profile examples of late. Eikon Therapeutics and Insitro, two well-funded startups, both cited a need for “prudence” in laying off staff.

Norris expects more companies to proactively cut staff, or even close, as the longer-than-expected winter drags on. 

“Most of those companies are not going to find the investors that they're hoping for,” he said. “And I think that's just the unfortunate truth.” 

Otello Stampacchia has watched the biotechnology industry survive many dark days in the two decades he’s led one of its premier investment firms.

Stampacchia formed Omega Funds in 2004, just a few years before the Great Recession caused a lengthy pullback in biotech investment. An exuberant period, during which a record number of drug companies went public, followed, only to later give way to another downturn that again tested the fortitude of biotech investors.

Companies and their backers have a new set of challenges in 2025. Layoffs and leadership changes at public health agencies, competitive pressure from China and cuts to U.S. science funding have left biotech startups with a state of disquietude. Initial public offerings are harder than ever to price. Many public companies are worth less than their cash holdings, and face growing pressure from investors to shut down. And politics have seeped into science, eroding confidence in proven medical interventions like vaccines.

Still, Stampacchia, whose firm raised a $647 million fund in July, is optimistic that better days lie ahead for biotech. The industry needs a reset that will “lead to the greater good,” he told BioPharma Dive.

“This is medicine, and medicine sometimes tastes bitter,” Stampacchia said.

BioPharma Dive spoke with Stampacchia about biotech investing. The following conversation has been lightly edited and condensed for clarity.

BIOPHARMA DIVE: How has the slowdown in biotech IPOs affected your decision-making as an investor?

OTELLO STAMPACCHIA: We like to tell our companies to stay private for longer, if possible. It's been more than five years now that we've been operating under the assumption that the IPO market should not be our road to a potential exit, which is usually via some acquisition.

With M&A, you’re selling to sophisticated buyers who know what they want. In the IPO market in our space, you're selling to relatively sophisticated public investors. But there's a lot of other variables that come into play — interest rates, the environment and so on. Generalists have basically deserted the space for quite a bit now, because there's a more attractive, in their opinion, risk-reward profile somewhere else.

Has anything changed this year, when IPO activity appears especially slow?

STAMPACCHIA: What we are seeing — and this could lead to some changes, actually — is the repercussions of some of these public investors being somewhat distressed. These were investors people traditionally used to go to syndicate the later-stage rounds. That's going to become a lot harder, which is going to make valuations more attractive for those later-stage rounds. So we are doing a bit of a tactical reallocation toward that later-stage opportunity set, because it's quite an interesting sweet spot.

What do you make of investors pressuring struggling, publicly traded biotechs to close and return cash to shareholders?

STAMPACCHIA: Necessity is the mother of all invention, as they say. There is a trend about not willing to give management the benefit of the doubt anymore. What you are seeing is a return to discipline, which has been quite a bit loose in the years where everybody could go public. Capital was abundant, interest rates were lower, all that.

It all stems from the fact these public investors are suffering themselves. As a result, they need more liquidity, and some of these stocks are illiquid. It's more efficient to return that cash to shareholders. Each situation is a little bit different, but the reality is these companies all burn cash. If the cash is not going towards clinical programs that could potentially deliver either stock price appreciation or, even better, an M&A exit, it's a logical and rational decision to try to get some of the cash back.

Overall, the market is trying to be more rational than it has been in the past. In the long term, it's not pretty when you're the employee of a company that is having to wind down. But on the macro level, it’s kind of healthy.

What can be done earlier to make sure fewer companies end up in this spot?

STAMPACCHIA: The issue is the step where the company goes from a stricter governance model, which is what we try to implement as venture investors. A stricter governance model implies a very close collaboration between those investors, the board members and management. And that collaboration should — not always, but should — result in a tighter screw on what programs get funded and go forward, and the bar for those programs to move forward.

When that collaboration and governance starts to become looser, some of these problems emerge. Companies spend money on unproductive projects, raise more money than they should, or don't raise enough. If I were to think, what should we do differently, it would be to ensure that control, governance and collaboration between those two important constituencies — the providers and users of capital — remains very tight for longer.

A dirty little secret in the industry is that the reason companies love to go public are twofold: One is to get access to other sources of capital, because there's only so much money on the private side. The other, in my opinion, is that they can eventually get rid of their venture investors on the board. We have certain practices, which are not always correct, but they're usually fairly accurate, as they've been repeated hundreds of times across thousands of companies. Access to different sources of capital is great, but then you start losing some of the discipline, collaboration and governance.

Does the politicization of mRNA vaccines and pullback in federal funding make you more hesitant to invest in vaccines?

STAMPACCHIA: To be fully transparent, it's not like we have backed hundreds of vaccine companies. But the short answer is yes.

The public health implications are more profound — obviously, measles and all that. The issue is vaccine hesitancy, which is potentially quite dangerous to society and public health. But from the very narrow investor mindset, it makes investing in that whole field much trickier. Across the spectrum in the community, there will be more hesitancy to invest in these companies. And that's not great.

How have leadership changes at the FDA affected the sector, from your vantage point?

STAMPACCHIA: We probably need a bit more distance and time to figure out how impactful these changes are. It is fair to say that there's a perception of instability, and perhaps even more importantly, a lack of consistency from the agency.

All the statistics that I can find, as well as interactions our companies have with the agency, [show] the reviewers are doing their job. The issue is how is this going to play out in not just the short term, but the medium term, and how it will affect this perception of instability. Because perception of instability is instability in its own way.

How has the inflow of biotech assets from China influenced your decision-making?

STAMPACCHIA: This is relatively new, at least in terms of the percentage of these assets that have been licensed or acquired over the last two or three years. So there's quite an impact. And there's not a lot of visibility on companies in the country, versus we have a lot of visibility on companies in Europe. We need to do our job of competitive landscaping and positioning better.

Fundamentally, and particularly for biologics, if there is a very validated target that could be improved by half-life or some heavy-duty iteration on the biological structure, and if it is a large enough market, somebody in China is probably doing it. And they have an advantage with the early stage trials.

I don't think U.S. or European regulators understand that this is a massive advantage in enrolling patients early. That advantage is perhaps even more important than the advantages they have on [manufacturing] and iterating on biologics. The real speed is in the clinic to prove stuff. That has profound political implications for countries that want to maintain a healthy pharma/biotech industry.

Four years ago, a record number of biotechnology companies flooded public markets, capitalizing on investor interest in drugmakers amid the COVID-19 pandemic.

Since then, though, many of those once high-flying biotechs have failed to meet expectations, leaving scores of them worth less than the cash in their bank accounts.

Historically, struggling biotechs would attempt to pivot, staking their future on a different strategy, a sale, or even a merger with a privately held firm. But recently, frustrated investors are pressing these “zombie” biotechs to shut down and return cash to shareholders instead.

This pressure has created an investment opportunity for an unlikely beneficiary. Over the last year or so, Xoma Royalty, a company known for betting on others’ future drug revenues, has started winding down distressed biotechs. Through those deals, Xoma returns cash to shareholders waiting for a payout, and profits by selling the rest of a shuttering biotech's intellectual property.

“We’re creating a small brand for ourselves as someone that wants to do the right thing for A, our partners, and B, the biotech ecosystem,” said Owen Hughes, Xoma’s CEO.

Xoma was once a traditional biotech company that developed and licensed out drugs. But in 2017, it changed course to become an aggregator of drug royalties. Since adopting that strategy, Xoma has acquired royalty rights to six drugs now on the market, among them Roche’s fast-selling eye drug Vabysmo. Others it has a stake in are advancing through clinical testing.

Recently, Xoma noticed the many firms that went public several years ago, but have since fallen on hard times, said Brad Sitko, the firm’s chief investment officer. “Those companies are now maturing to the point where they have negative data and are deciding not to exist,” he said. “They’re trying to figure out how to get capital back to shareholders.”

Xoma decided to step in, viewing the glut of biotechs worth less than their cash reserves — one firm in April estimated there to be nearly 300 — as a way to diversify and boost its own balance sheet. In 2024, it cut deals to acquire and liquidate Kinnate Biopharma and Pulmokine. Then between June and August, it scooped up Turnstone Biologics, Mural Oncology, HilleVax and Lava Therapeutics. Xoma also backed a deal that XenoTherapeutics, a nonprofit, struck for Essa Pharma.

These deals reflect both biotech’s difficult fundraising climate and public investors’ willingness to challenge the boards of struggling drugmakers. Several biotech companies, such as Acelyrin, Essa, Keros Therapeutics and Pliant Therapeutics, have faced shareholder pressure or outright calls to liquidate instead of pursuing mergers. Some, like iTeos Therapeutics and Third Harmonic Bio, have done so.

In the past, biotech boards rarely discussed liquidations as a "bona fide path forward,” but that's changing now, according to Eason Hahm, a director at investment bank William Blair.

“Boards and investors [are] saying, ‘Look, I think I can make the decision better on where that capital would be best used, perhaps better than just rolling it into another company,” she said.

Xoma isn’t alone. Some investment firms, like KKR and OrbiMed, are providing creative ways to finance companies that might have a tougher time raising cash through public stock sales. Others, like hedge fund Tang Capital Partners and investment fund Alis Biosciences, are joining Xoma in pursuing buy-and-liquidate deals. Tang, through its acquisition vehicle Concentra Biosciences, has been particularly active, buying out Cargo Therapeutics, Elevation Oncology and Kronos Bio, among others.

An analysis by William Blair of the six buy-and-liquidate deals in the second quarter of 2025 found $1.5 billion in combined net cash on the sellers’ balance sheets.

“We’ve seen the rate of these types of deals accelerate in 2025 primarily because we came to a crossroads in biotech where it continued to be a difficult fundraising market, and there was a stronger call from investors to return that capital,” Hahm said.

Some of the pressure can be attributed to the limited partners that back venture firms. "They get very frustrated when the VCs don't send any money back,” said Chris Garabedian, chairman and CEO of biotech company creator Xontogeny and portfolio manager of the Perceptive Xontogeny Venture Fund.

“‘We committed $30 million to your fund, and we haven't even gotten one check back after five years?’” Garabedian said. “And so that’s where every VC is focused on: how do we exit?”

When firms like Xoma or Tang show they’re willing to make a liquidation offer, biotechs are pushed to be "more accountable" for their R&D spending, Cantor Fitzgerald analysts wrote in a February note. Should they succeed, investors can redirect their freed cash to other biotechs, they said.

"Most would say that would be a good thing," Garabedian said. “The problem is the board of directors, the management teams, are usually [concerned] about survival. They're the last ones that want to see something shut down [because] they lose their jobs."

Xoma sees the deals it’s striking as a short-term, but critical service that should help the biotech sector regain its footing. Returns on many IPOs have been poor, and illustrate how biotechs need to be more efficient with their cash, Hughes said.

“We will rebound. We always have,” Hughes said. “But we, as an industry, need to do certain things in order to actually invite the capital back.”

“Acquiring these companies,” he added, “is just one of many things that need to be done.”

In the notoriously expensive business of drug development, SiteOne Therapeutics made do with little. The biotechnology startup formed in 2010, aiming to create new, non-addictive pain relievers at a time when overdoses involving opioids were killing more than 20,000 people in the U.S. each year.

Yet the dire need for safer medications didn’t resonate with most investors. To them, pain was too risky. Scientists knew the general outline of how it worked: a cut, scald, break, pinch, slam or zap would alert special proteins and chemicals, which, like sentries, relay pain signals through the body. But the finer details of this process were — and, in many cases, still are — fuzzy, like how people who suffer the same injuries can report very different pain experiences.

This uncertainty meant SiteOne had to, for most of its life, rely on small grants to stay afloat. “There was certainly a difficult period,” CEO John Mulcahy said late last year. “Pain was out of favor, so it was difficult to raise capital around these assets.”

That period now appears over. Since late 2024, SiteOne not only closed a $100 million fundraising round led by Novo Holdings, the controlling stakeholder of Ozempic-maker Novo Nordisk, but also agreed to sell to Eli Lilly in a deal that could be worth up to $1 billion.

The newfound interest and investment can be attributed, in good part, to Vertex Pharmaceuticals, which has led the charge investigating a group of tube-shaped, pain-regulating proteins called sodium ion channels. After a quarter century of meticulous, onerous work, Vertex’s labs finally crafted a channel-blocking molecule the company viewed as safe, effective and precise enough to help address the opioid epidemic.

In January, the Food and Drug Administration approved this molecule, known commercially as Journavx, as a treatment for the sharp, short-lived “acute” pain felt after an accident or surgery. Ken Harrison, a senior partner at Novo Holdings, said a core reason his firm decided to back SiteOne was that Vertex had established these drugs can be successfully studied and brought to market.

While Journavx has so far proven remarkably safe and absent of addictive properties, doctors remain torn about how useful it will ultimately be for patients. At its best, the drug looks to be only as potent as a weak opioid. 

Still, TD Cowen analysts recently described the drug’s approval as a “watershed moment that could pave the way for a new era of non-opioid pain treatments.” Indeed, SiteOne and at least 10 other developers want to follow in Vertex’s footsteps with their own medicines that stopper either the “NaV1.8” sodium ion channel, as Journavx does, or a close cousin, “NaV1.7.”

What are sodium channel inhibitors, and how do they work?

Found in the outermost layers of many cells, these proteins function like faucets for charged sodium particles. They open in response to various stimuli — a bright light switching on, a bite of a salty food, a handful of ice from the freezer — at which point ions flood into the cell. This rush creates an electrical pulse that travels through the nervous system and to the brain, where it's used as information to determine how the body should feel and react.

Of the nine known types of sodium ion channels, three are primarily found in the peripheral nervous system, where they play key roles in pain signaling. The signaling process resembles a line of dominoes. At the start is the root of the pain, at the end the brain. By blocking these channels, scientists are effectively removing a couple of the earliest tiles so they can’t continue the cascade.

“You’re stopping the pain as close as you can to the source,” and leaving “other modalities of sensory signaling intact,” explained Stephen Waxman, a neurology professor at the Yale School of Medicine who’s made significant discoveries about the role ion channels play in pain, on a 2023 podcast run by The New England Journal of Medicine.

For drugmakers, NaV1.7 and NaV1.8 have emerged as the two most popular pain targets. One reason is their location. Being on the outer edge of the nervous system, rather than thoroughly embedded in organs like the heart or brain, reduces the risk that channel-blocking drugs will disrupt other vital body functions.

These proteins also work in different ways, offering researchers a shot at treating a variety of pain types. NaV1.7 acts like a light switch, abruptly turning the pain signal on and off, while NaV1.8 is more akin to a dimmer. SiteOne’s Mulcahy has said NaV1.8 could therefore be a more desirable target for chronic pain management, since the goal there usually is not to shut pain off, but to dial it back down to “normal.”

Designing medicines that bind to a specific sodium channel remains exceptionally challenging, as the subtypes all share very similar structures. Additionally, the proteins move extremely fast — opening and closing in milliseconds — and are exposed to relatively large electrical fields. Only in the last 15 or so years, with the creation of new tools, have drugmakers been able to adequately study and precisely drug ion channels.

What are the advantages over other drugs for pain?

Scientists believe that, by avoiding the central nervous system, sodium channel blockers can alleviate pain without eliciting the side effects or addictive risks posed by opioids. The late-stage studies that led to Journavx’s approval support this theory.

Together, the two trials recruited more than 2,000 people who had just undergone either a “tummy tuck” surgery or a bunion removal. Participants received either Vertex’s drug, a placebo, or a combination of Tylenol and a commonly prescribed opioid that served as an “active comparator.” Investigators found lower rates of nausea, dizziness and headache among those given Journavx than in the other groups.

Journavx was generally safe and well-tolerated, according to Vertex, and nearly all of the adverse events seen in these studies were mild to moderate in severity. Drug-treated patients did, however, show higher rates of itchiness, rash and muscle spasms compared to their placebo-treated counterparts.

As for its effectiveness, Journavx proved significantly better than the placebo at alleviating acute pain. Both trials measured this with a 0-to-10 scale wherein patients rate their pain intensity at a series of time intervals over two days.

Notably, the drug was not more effective than the active comparator regimen. That’s raised debate about its utility in a setting like acute pain, where both patients and healthcare providers are typically looking for a powerful, quick-acting medication. While Vertex leadership has maintained this finding won’t deter doctors from prescribing Journavx, some pain experts have described the pill’s effects as modest. Richard Vaglienti, medical director of the Center for Integrative Pain Management at West Virginia University, even classified the results as “glaring.”

That could leave the door open for other developers to compete — even those working outside the field of sodium ion channels. In May, Pittsburgh-based Viatris reported positive results from late-stage studies evaluating a reformulated version of an old medication, an “NSAID” called meloxicam, in people who had bunion removal or hernia repair surgeries. Viatris said its drug didn’t just beat a placebo at providing acute pain relief, an after-the-fact analysis found it also offered “significantly superior pain control” to tramadol, an opioid less potent than the one used in Vertex’s studies.

Following this release, Brian Skorney, an analyst at the investment firm Baird, noted how Viatris’ data “highlight a number of concerns we have with Journavx’s profile, in particular, onset of action, a critical factor for post-operative pain.”

The results, Skorney argued, make Journavx “look like an inferior option” compared to a “pretty old” drug. “If NSAID’s don’t have the highest efficacy, as Vertex is fond of saying, what does that say about Journavx?” he wrote.

Which companies are developing NaV1.7 and NaV1.8 inhibitors?

The majority of developers researching sodium ion channels for pain are small biotechs.

One, Dogwood Therapeutics, formed in late 2024 through the reverse merger of Wex Pharmaceuticals and Virios Therapeutics. It had 12 full-time employees at the end of December. Another, Channel Therapeutics, had four, and is now in the process of combining with a subsidiary of drug commercialization specialist Ligand Pharmaceuticals.

Such deals could suggest that, while this area is receiving more attention, building a company around it remains challenging and may require less conventional methods for raising money at a time when investors are viewing biotech more skeptically.

Other players include Praxis Precision Medicines, Newron Pharmaceuticals, RaQualia Pharma and Xenon Pharmaceuticals. Two more, Sangamo Therapeutics and privately held Navega Therapeutics, are taking a genetic approach, with therapies built to suppress the gene that encodes for NaV1.7 proteins.

Latigo Biotherapeutics is further ahead, and like SiteOne touts a drug aimed at NaV1.8 in mid-stage testing. That drug, LTG001, is being evaluated in acute pain following a tummy tuck, bunionectomy or wisdom teeth removal.

Latigo is backed by prominent life sciences investors such as Westlake Village BioPartners, 5AM Ventures and Alexandria Venture Investments, and in March announced the closing of a $150 million funding round that CEO Nima Farzan said should keep the company going at least until it has late-stage data for LTG001.

Vertex and Eli Lilly, with its pending purchase of SiteOne, currently appear to be the sole big pharmaceutical firms in this space, though others have shown interest. AbbVie had “ABBV-318,” an oral molecule designed to inhibit both NaV1.7 and NaV1.8, but no longer lists the drug in its pipeline. Scientific American reported in 2024 how Merck & Co.’s patent activity also suggests it may be stealthily exploring ion channels for pain.

A Merck spokesperson said the company is “committed to neuroscience research,” including chronic and acute pain. “At this time, it’s too early to share information related to sodium ion channel inhibitors, but we will continue to collaborate with scientists and investigators worldwide to advance innovation and find solutions that may address complex and debilitating neurological diseases.”

At Vertex, company leaders are trying to expand Journavx’s approval beyond acute pain and into chronic, though testing has thus far delivered mixed results. Vertex is working on a series of other, small molecule pain drugs, too, including a “next-generation” NaV1.8 inhibitor named VX-993.

The investment bank Stifel models Journavx sales reaching $1.1 billion in 2030 and $3.6 billion in 2038. The average analyst estimate on Wall Street, according to Stifel, is that sales of the drug will hit nearly $2 billion by the end of this decade.

What is the status of these companies’ research?

Vertex is now enrolling a Phase 3 study to evaluate Journavx as a treatment for the chronic nerve pain experienced by some patients with diabetes. Simultaneously, it’s running a smaller study of VX-993 in the same setting.

The assets from Latigo, Newron and Dogwood have either entered or gone through mid-stage trials. A roughly 250-participant study is exploring Latigo’s LTG001 for wisdom teeth removal pain, with results set to arrive sometime in 2025. The active ingredient in Dogwood’s Halneuron is actually the neurotoxin found in pufferfish. Investigators are now hoping to enroll about 200 patients in an experiment that will assess the drug as a treatment of chemotherapy-induced neuropathic pain.

Meanwhile, a federal database of clinical trials shows the most recent listings for Newron’s ralfinamide were last updated in 2009 and 2017. The Italy-based company didn’t respond to requests for more recent information about the program.

SiteOne hopes to “rapidly advance” into Phase 2 testing the medicine that caught Lilly’s eye and encouraged it to pursue an acquisition. Like Journavx, this “STC-004” therapy is designed to obstruct NaV1.8.

Mark Mintun, group vice president of Lilly’s neuroscience research and development, in May said that the company is “eager to continue” advancing STC-004. “Innovation in pain management is critical to address the unmet needs of millions of patients around the world.”

A new biotechnology company debuted in July with a hefty bankroll and an immunotherapy approach it claims has the potential to treat an array of tough-to-reach solid tumors.

Called Dispatch Bio, the startup was formed in 2022 through a collaboration between Arch Venture Partners and the Parker Institute for Cancer Immunotherapy and built around technologies from scientific labs in Pennsylvania and California. It has since raised $216 million and developed a lead program that’s expected to enter clinical testing in 2026.

Dispatch aims to deliver to cancer cells a sequence for a unique type of protein flag, known as an antigen, that it says can draw in specially engineered immune cells it plans to administer afterwards. The company believes its approach could yield a “universal” solid tumor treatment.

Immunotherapy became a mainstay of cancer care over the past decade. Drugs like Merck & Co.’s Keytruda, known as checkpoint inhibitors, can spur the immune system to fight cancer. They’re used to treat dozens of tumor types and, when they work, extend survival in ways previously thought impossible.

Treatments made from a patient’s own cells and engineered in a lab to attack cancer have come of age, too. Seven of these CAR-T therapies are available in the U.S., where they’re used to treat several kinds of blood cancers.

A good portion of people, though, don’t respond to checkpoint blockers, especially those whose tumors don’t have a particular protein that’s associated with immunotherapy response. Many “cold” tumors that don’t elicit a strong immune reaction also remain frustratingly beyond the drugs’ reach.

Cell therapies, meanwhile, haven’t proven as beneficial against cancers beyond the blood. One reason is that solid tumors co-opt a protective barrier of immune-suppressing cells and other molecules to exhaust CAR-T cells and shield themselves from immune defenders. Additionally, these tumors often have cells expressing different antigens, making them harder to target with a treatment aimed at just one.

The pharmaceutical industry has spent billions of dollars in a yearslong and mostly unsuccessful hunt for better immunotherapies, often by pairing checkpoint inhibitors with medicines that might boost responses. Cell therapy companies, too, have experimented with various ways to get to solid tumors, with limited success.

Dispatch believes it may have better luck with an approach that marries elements of immunotherapy and cell therapy with gene therapy.

According to Dispatch, its therapies use an engineered virus — a common gene therapy delivery tool — to seek out cancerous cells and tag them with what it refers to as a “flare.” This flare is an antigen that a CAR-T therapy Dispatch subsequently administers is designed to seek out. Once its target is found, the tagged cell is destroyed, releasing viral particles carrying the flare into nearby tumor tissue that’s then also flagged.

The engineered virus also delivers inflammatory cytokines and chemokines to help take down a tumor’s surrounding environmental defenses.

In a statement, Arch managing director and Dispatch board member Steve Gillis referred to the process as a “tumor-agnostic approach to immunotherapy” that could treat “a majority of solid tumors.” It may also be a way to combat resistance mechanisms that tumors sometimes develop to other medicines, Dispatch said.

Dispatch’s work is based on research from University of Pennsylvania cell therapy pioneer Carl June; Stanford University professor Chris Garcia; University of California, San Francisco professor Kole Roybal; and Memorial Sloan Kettering Cancer Center new chair of immuno-oncology Andy Minn.

The seed for Dispatch came at a Parker Institute retreat where the four scientists, now company co-founders, and institute head Sean Parker debated how best to solve the problems solid tumors pose in immunotherapy.

Merck & Co.’s cancer immunotherapy Keytruda is one of the pharmaceutical industry’s biggest successes. The drug's arrival in 2014 introduced a new way of treating cancer and, over time, it became standard therapy for a panoply of different tumors. Clinical achievements brought about commercial performance, making Keytruda the world's best-selling medicine.

After the repeated failure of past attempts to improve on Keytruda, a new class of drugs might finally offer a better backbone for immunotherapy's next decade.

In September 2024, biotechnology companies Summit Therapeutics and Akeso revealed clinical trial results showing one of these drugs significantly outperformed Keytruda. Called ivonescimab, it cut the risk of lung cancer progression in half compared to Keytruda in a Phase 3 study — a result so striking it sparked a wave of investment in oncology research practically overnight.

“This really was a ‘black swan’ event,” said Allen Yang, Summit’s chief medical officer. “It’s clearly what everybody’s been looking for.”

In the wake of Summit’s results, drugs like ivonescimab, which block cell signaling via proteins called PD-1 and VEGF, have become the “new shiny object” in cancer research, according to analysts with the investment bank William Blair. More than a dozen companies, from pharmaceutical giants to newly formed biotech startups, are now developing them.

Proponents see these “PD-1/VEGF inhibitors” as building upon Keytruda and drugs like it, such as Bristol Myers Squibb’s Opdivo. The hope, some say, is they’ll improve response rates, shrink tumors their predecessors can’t and become cornerstone cancer treatments of the future.

“These drugs are going to work,” said David Epstein, the former CEO of Seagen and head of Ottimo Pharma, a startup developing a PD-1/VEGF inhibitor. “The question is, how big is the order of magnitude going to be, and across how many different tumor types?”

Many aren’t as convinced as Epstein. Ivonescimab hasn’t shown it can extend overall survival by more than Keytruda. It wasn’t tested against the Keytruda-chemotherapy combination that’s standard of care in most lung cancers. And the trial demonstrating ivonescimab’s superiority to Keytruda took place only in China, leaving it unclear whether a similar benefit will be observed in broader testing. Those questions hang over not only Summit, but others working on PD-1/VEGF inhibitors, too.

“The jury is out,” said Samit Hirawat, the chief medical officer of Bristol Myers Squibb.

What are PD-1/VEGF inhibitors and how do they work?

Cancer cells are survivalists. They’re adept at siphoning the body’s resources to fuel their rampant growth, and skilled at slipping past immune defenses evolved to stop them. Even when beat back by drug therapies, malignant cells can acquire new abilities to thwart treatment.

Drugmakers and researchers have spent enormous effort studying cancer’s weaponry, uncovering along the way many tools that have improved care. Two breakthroughs from the 1990s helped researchers design protein drugs that can pinch off a tumor’s supply chains and, years later, unleash the immune system against cancerous growth.

In the former case, antibodies that block VEGF, such as Avastin, can stop tumors from forming new blood vessels. The latter kind of antibodies, which are called PD-1 or PD-L1 inhibitors for the proteins that they block, prevent cancer cells from shutting down powerful defenders known as T cells. Keytruda is the most famous example.

Both classes of medicines are now used to treat dozens of tumor types. PD-1 and PD-L1 immunotherapies, also called “checkpoint” inhibitors, are sometimes a patient’s first line of defense after a tumor is surgically removed — or even before.

Developers like Akeso and Summit aim to combine the power of both types of drugs into a single, multi-pronged antibody, typically termed “bispecific” or “bifunctional.” These medicines can interfere with PD-1 and VEGF signaling in ways their makers contend will maximize the benefits and minimize the flaws of their predecessors.

Akeso designed ivonescimab to have a “tetravalent” structure, in theory giving it better binding to PD-1 and to VEGF. Yang, Summit’s CMO, says the simultaneous targeting of both proteins helps increase the affinity the drug has for each.

“We believe that those two features make ivonescimab, and the whole class of PD-1/VEGFs, unique,” he added. “Now people seem to believe us.”

Others have different twists on the concept. BNT327, a drug acquired by German biotech BioNTech, binds to the ligand PD-L1 instead of the PD-1 receptor. A drug licensed by Merck consists of an anti-VEGF antibody fused to two PD-1-targeting antibodies, while Ottimo’s lead program, jankistomig, specifically targets a related protein called VEGF receptor 2.

Crescent Biopharma has a drug its CEO, Jonathan Violin, said on a conference call October was “purpose-built” to mimic the pharmacology of ivonescimab while enhancing its “stability and manufacturability.”

They’re joined by other companies pursuing more variations, such as drugs that block three proteins or use different strategies to block VEGF.

The glut of similar drugs means “many or most of the resulting companies seem unlikely to succeed,” wrote Paul Rennert, the head of consulting firm Sugarcone Biotech, in a report. Still, Epstein, Ottimo’s CEO, said the sheer size of the commercial opportunity leaves ample room for many to prosper.

“How many PD-1s and PD-L1s are there? How big is the market currently? And how big is it going to be if people live twice as long, or at least twice as long before their cancer progresses?” Epstein said.

What are the advantages over drugs like Keytruda?

Keytruda and other checkpoint inhibitors like it are the standard choice for many tumor types because trial data has shown they can extend lives to degrees that weren’t possible with other cancer medicines.

There’s no better example than in lung cancer. Some studies have shown that, in the years before cancer immunotherapy, the average five-year survival rate for people with metastatic non-small cell lung cancer was around 5%. That rate has climbed since the arrival of Keytruda and its cousins. In Phase 3 testing, around 20% of people given a Keytruda-chemotherapy combination survived at least five years.

Yet that statistic also shows checkpoint inhibitors aren’t panaceas. In lung cancer and other malignancies, they still don’t work well for a good portion of people — particularly those whose tumors express little of the PD-L1 protein that’s linked to an immunotherapy response. They also struggle against so-called cold tumors that don’t tend to provoke as strong immune reactions.

In response, drugmakers have searched for more than a decade to find new immunotherapies that work better, but the hunt has yielded far more failures than successes.

“It’s been one disappointment, honestly, after another,” said Srini Akkaraju, a founder and managing general partner of Samsara BioCapital, and an investor in Ottimo.

Among the approaches tested, with mixed results, were combinations of PD-1 inhibitors together with anti-VEGF drugs. Roche found that pairing Avastin with its immunotherapy Tecentriq improved survival in liver cancer and won an approval in that tumor type as well as lung cancer. Further testing showed a limited survival benefit as well as significant side effects, however. And the combination hasn’t been as broadly successful as hoped.

Merck has had a similarly uneven experience. It has gained clearances of regimens involving Keytruda and the VEGF-inhibiting drugs Lenvima and Inlyta in a few tumors, but these combinations have fallen short in others.

“You see, in many cases, clear evidence of [delaying tumor progression]. But then as we go longer out, we're not able to hit [on survival] as often as we wish to,” said Merck research chief Dean Li, during a conference presentation in January.

At least so far, ivonescimab seems to work more effectively than delivering two separate drugs together. The initial evidence “raises the possibility that there may be some true synergy when the two are combined with a single molecule,” John Heymach, chair of thoracic, head and neck oncology at the MD Anderson Cancer Center, said in an interview.

Supporters say that will play out with further testing. If they’re right, the “emerging blue sky story” is that these drugs might make immunotherapy useful to more people and against more tumors, wrote Stifel analyst Bradley Canino in a research note.

More data could burst those expectations, too, though. Bristol Myers’ CMO Hirawat noted how ivonescimab hasn’t yet been proven to extend survival. Moreover, its advantage over Keytruda on tumor progression appeared to shrink after six months. And for earlier-stage drugs also targeting the PD-1 and VEGF pathways, promise in single-arm studies will need to be replicated in more rigorous tests.

“There is some level of additional data that is required,” Hirawat said. “We'll keep an eye on it and continue to look for what the right opportunities are from a scientific perspective, and what we need to continue to learn.”

In their report, William Blair analysts had a similarly skeptical take. Citing the multiple “disappointing datasets” with checkpoint inhibitor and Avastin combinations, they wrote that developers need more results from global studies and a clear survival advantage to prove these drugs can become “a new standard of care.”

Safety is also a concern. VEGF-blocking drugs are associated with sometimes severe side effects like high blood pressure, bleeding or protein in the urine. In clinical practice, doctors can stop treatment when these instances occur. With a combined therapy, though, “if we see [concerning] proteinuria, then we have to hold the whole drug,” Jyoti Malhotra, director of thoracic medical oncology at City of Hope Orange County, said in an interview.

Which companies are developing PD-1/VEGF inhibitors?

More than a dozen companies are developing dual-targeting antibodies that block PD-1 or PD-L1 and VEGF in one way or another.

Akeso, a Guangdong, China-based cancer drug developer, originally discovered ivonescimab. Summit got involved in 2022 when it paid Akeso $500 million upfront. And in February, Pfizer and Summit agreed to test ivonescimab alongside some of Pfizer’s targeted cancer medicines in the hopes of finding yet more powerful drug combinations.

BioNTech is best known for successfully developing a COVID vaccine with Pfizer. But the company’s initial focus was in cancer. It bought into PD-L1/VEGF drug development first by partnering with and then in 2024 acquiring Biotheus, a cancer biotech based in Zhuhai, China.

Instil Bio went public in 2021 to fund work on cancer cell therapy. But manufacturing issues led the company to restructure and, last August, it licensed partial rights to a PD-L1/VEGF drug from Shanghai’s ImmuneOnco Biopharmaceuticals.

Ottimo Pharma was formed in 2020 by U.K. venture firm Medicxi and prolific biotech founder and former Pfizer researcher Jonny Finlay. The company emerged from stealth in October with Epstein, a former Seagen and Novartis executive, as its CEO and raised $140 million in Series A funding two months later. Ottimo’s lead prospect is a bifunctional antibody, meaning its “arms” can interact with both of its targets.

Crescent Biopharma spun out of Paragon Therapeutics in 2024 armed with a PD-1/VEGF prospect and two other medicines. In October, it merged with struggling drug developer GlycoMimetics, giving the company enough cash to fund operations into 2027.

Merck in November paid $588 million for worldwide rights to a PD-1/VEGF drug discovered by Shanghai-based LaNova Medicines.

Joining them are at least 12 more companies, many of which of are based in China, reflecting a fast-advancing biotech sector there that’s created a broad pipeline of drug candidates in competitive areas of pharmaceutical research.

“They all have little variations. They all have a reason to be best in class,” said Yang, Summit’s CMO, of the medicines following ivonescimab. “But we think ours has all the features that are important, and that have been proven to be important.”

What is the status of their research?

The study result that set many of these investments in motion was signaled last May, when Summit trumpeted that ivonescimab had “decisively” beaten Keytruda in a Phase 3 trial. Details revealed at a medical meeting six months later backed up that claim, as ivonescimab kept tumors from progressing for a median of almost half a year longer than Merck’s medicine without an accompanying uptick in side effects.

The data “are really quite striking,” said Heymach, of MD Anderson, at the time.

Overall survival results from that study could be revealed in 2025. Also coming are data from a global, Phase 3 study in a subset of non-small cell lung cancer patients with so-called EGFR mutations that could prove ivonescimab is “equally safe/effective” in people outside of China, Stifel’s Canino wrote in a note to clients. An additional Phase 3 trial headed by Akeso could point to the type of benefit treatment offers on top of chemotherapy.

“We are watching carefully,” Merck’s Li told analysts in 2024.

BioNTech has reported promising early results for BNT327 in several tumor types, among them an aggressive and tough-to-treat form of breast cancer. Going forward, it intends to combine BNT327 with a variety of different medicines and has registrational trials either ongoing or planned in lung and breast cancer. Several Phase 2 readouts are expected in 2025.

The drug could be a “foundational component in the treatment regiments for multiple cancer types,” CEO Ugur Sahin told analysts in 2024.

Several others chasing Summit and BioNTech are either just starting human testing or soon will be.

Instil Bio should report results from an early-stage trial in lung cancer in China, and start a similar type of trial in the U.S., in 2025. Merck’s prospect was in a Phase 1 trial in China when licensed from LaNova. Merck aims to explore its use in multiple tumor types, but hasn’t been specific.

Crescent could start testing in 2025 and report early data in 2026. Ottimo, too, has said it should begin a trial in late 2025 or early 2026.

By then, the study that could establish how much of an advance PD-1/VEGF inhibitors really are will be well underway. Dubbed Harmoni-3, that trial has already begun enrolling what’s expected to be more than 1,000 lung cancer patients, who will receive chemotherapy and either ivonescimab or Keytruda. Initial results are due in 2027, according to a federal database. If positive, they could unlock a market opportunity Stifel’s Canino estimated to be worth around $20 billion.

“Keytruda is the biggest oncology drug in the world,” said Akkaraju, of Samsara. “Is this finally the thing that unseats it? It’s quite possible.”

Gwendolyn Wu, Jonathan Gardner and Ned Pagliarulo contributed reporting.