Itepekimab

Talking over pharma pipelines with a major drugmaker’s development chief, he noted that if you looked at the biggest 50 drugs by revenue, the final one on the list brought in about $4 billion last year. Number one, of course, was Keytruda, at $32 billion. To understand what goes into pivotal trials at the R&D 15 — our in-depth review of the biggest pharma research spenders — you have to recognize that the industry’s bar for success has been steadily rising for years. To get a callout by the CEO in their end-of-year reviews, you need to be in blockbuster territory. Real success takes peak sales projections of $4 billion to $5 billion. Pipelines-in-a-product remain the holy grail of R&D, with the prospect of expanding indications and rising revenue. In this club, you play with big stakes for even larger pots. As a result, you’re seeing a continued shift toward big population drugs, where remarkable efficacy and reliable safety are essential. That competition for winners that can match the success of the obesity drug franchises has driven a growing demand for deals in China, the US and Europe. Together, J&J, Merck and Novartis committed close to $100 billion to M&A deals from the start of 2024 through the end of this year’s first quarter. And the tab is growing as a group of biopharmas look to replace their aging franchise therapies that are losing patent protection. The upside to that dealmaking will be better therapies to control some debilitating and very lethal diseases. The downside is that there’s less and less interest in marginal products. Right now, small markets are the kiss of death. 1. Merck: When being No. 1 means you have to try even harder The scoop: Over the past 12 years, Merck has become the Keytruda company — with a few other blockbusters. And in the next few years it will try to become the Big Pharma that kept investors happy after moving on from its record-setting franchise. A lot of people in the business don’t remember that back in 2014, when Keytruda was approved, Merck was barely a player in oncology. Now it’s fleshed out a plan to transition to an injectable version of Keytruda that can keep a chunk of that megablockbuster revenue flowing, while looking to M&A to fill the rest of the gap when the original version loses exclusivity. And analysts have been fretting about Merck’s wobbly sales pace for its Gardasil vaccine, which adds only more pressure. Just weeks ago it worked out a hefty $6.7 billion deal for Terns Pharmaceuticals to see if it could steal a march on Novartis’s Scemblix and earn billions more in chronic myeloid leukemia — which will have a lot to do with its ability to win an initial OK and then migrate to frontline therapy. It’s all part of a $15 billion M&A commitment that Merck has made to oncology since the start of 2019, and there may well be billions more added to that tally by the end of this year. Even at a significantly reduced budget of close to $16 billion, Merck remains the top spender in drug R&D among the big 15. And while oncology has been dominant, CEO Rob Davis and research chief Dean Li have been casting a wide net. Merck has been focused on drugs with a clear clinical timeline to market, which helps explain why it came out on top of a bidding war to gain Cidara Therapeutics’ antiviral drug for a bit more than $9 billion last year. And it plunked down $10 billion for Verona Pharma and its newly approved COPD drug. Merck can never expect to have another Keytruda and is building around a steady development of several major market drugs. On that list are the oral PCSK9 enlicitide decanoate, which posted positive results for slashing bad cholesterol in Phase 3 a few months ago. Merck has been racing AstraZeneca on that front, looking to score big after the original injectables failed to catch on. The FDA is reportedly fast-tracking the review along with sacituzumab tirumotecan (sac-TMT), a TROP2 ADC from a multibillion-dollar deal with Kelun. That’s performed well in Phase 3 when paired with Keytruda — so well that the investor Blackstone will provide $700 million to back Merck’s 15 Phase 3s in 2026. Another Phase 3 combo program is underway for calderasib (MK-1084) with an eye on developing a new KRAS G12C drug. Then there’s the IBD drug tulisokibart (MK-7240), which has been moving into a slate of Phase 3 trials. In the meantime, Merck has been working on a patent strategy that could extend its market protection for Keytruda well into 2029 while positioning its new injectable version of Keytruda to maintain a large chunk of the market after biosimilar manufacturers try to position their new IV knockoffs. 2. Roche: Setting its sights on new franchises and spending big on R&D The scoop: For a player like Roche, with two R&D organizations straddling the globe, late-stage development requires plenty of forward thinking about the franchises its losing, and the franchises it needs to add to keep the Swiss francs adding up. On the way out: Its top-selling drug Ocrevus, which earned $9 billion and change last year and faces a patent cliff starting in 2029. On its way in: High hopes are being polished up among the analysts with positive Phase 3 data for fenebrutinib, an oral BTK inhibitor Roche badly needs to look better than its top blockbuster. The drug achieved non-inferiority to Ocrevus in the first big Phase 3 readout for primary progressive multiple sclerosis, with a 12% reduction in the risk of disease progression. Researchers also boasted about a particularly positive readout for upper limb function. A Phase 3 for relapsing MS is looming, and will make up the key data being presented for an approval on both types of MS. A lot is riding on that one. If they can make a case for marginally better efficacy in an easier-to-take pill (and overcome worry about higher numbers of elevated liver enzymes), they can make a case for a blockbuster replacement. If not, the generic rivals will bust up the franchise, leaving a large gap to fill elsewhere. That could have come from giredestrant — until a Phase 3 failure in estrogen receptor-positive, HER2-negative breast cancer. The setback left analysts to ponder whether Roche’s dreams of a multibillion-dollar treatment had been destroyed. Roche has put in an application with the FDA, expecting that the positive late-stage data in advanced breast cancer will be enough. But the trial flop could limit its market potential. Roche has a lengthy Phase 3 path to travel on trontinemab, the latest amyloid buster to rouse excitement in Alzheimer’s. Evidence shows it can remove amyloid , a chief suspect in disease progression, along with reduced brain bleeds that afflict the two marketed rivals from Eli Lilly and Eisai/Biogen. But it will take quite some time to see how the drug works on disease progression — particularly when they cross over to prospective patients who have yet to suffer from memory loss. If it can get over the finish line, there’s significant potential. Roche is also attempting a late entry in another key category that has gripped many in the R&D 15: obesity. And it’s following the same route Eli Lilly took with Zepbound, pursuing a GLP-1/GIP combo approach with CT-388 that produced weight loss numbers that were quite similar to the drug that now dominates new prescriptions. There’s excitement about data showing the drug could avoid plateauing on weight loss. But Roche has a long way to go in Phase 3 before it can prove it. It grabbed CT-388 with its $2.7 billion deal for Carmot Therapeutics, which also came with the drug CT-996. Roche has high hopes for a triple approach with petrelintide, an amylin analog from Zealand Pharma. Traditionally, once a drug seizes a best-in-class rep, it’s incredibly difficult to leapfrog it in the market. But the obesity market may be so substantial that those rules may not hold. Back in early 2023, Roivant CEO Matt Gline was beaming when he talked about the Phase 2b data that they were seeing for RVT-3101, freshly picked up in a deal with Pfizer. Roche R&D execs were also pretty impressed, and nabbed it for $7.1 billion. Roche put it right on a Phase 3 fast track for ulcerative colitis and Crohn’s disease. The anti-TL1A antibody approach has become a hot target at several big players. Merck made it a top priority with its $10.8 billion deal to buy Prometheus Biosciences and tulisokibart (MK-7240). Sanofi and partner Teva have their own advanced program for duvakitug. CEO Thomas Schinecker includes pegozafermin, a MASH drug obtained in the 89bio buyout, and zilebesiran, a hypertension therapy partnered with Alnylam, among other top prospects in Phase 3. Zilebesiran was steered into Phase 3 despite a mid-stage flop, but the partners believe they found the right dose to take to regulators, once they have the data to back it up. Dealmaking got Roche to this point with its late-stage pipeline, and dealmaking will continue to be a big part of its planning. Schinecker also hasn’t ignored the pacts being signed in China, so don’t be surprised if you hear of something new on that score in the coming months. 3. AstraZeneca: With more than 100 Phase III studies underway, analysts expect some big readouts in 2026 The scoop: When I started working on this piece in late March, AstraZeneca’s R&D group scored two significant wins on the same day. Its in vivo CAR-T, acquired in a $1 billion deal for EsoBiotech, provided a batch of promising data on a tiny group of multiple myeloma patients. And its COPD drug tozorakimab, an IL-33-targeting antibody , came up with positive results in a pair of Phase 3 studies — after it flunked Phase 2. Significantly, tozorakimab was developed internally by the R&D team and has a peak sales estimate of $3 billion to $5 billion. For CEO Pascal Soriot, the announcements offered a payback for AstraZeneca’s growing bet on R&D, which jumped to $14.2 billion in 2025 from $13.6 billion in 2024. And listening to Soriot discuss the strategy to grow revenue to $80 billion in 2030, there was no mistaking the company’s intention of staying laser-focused on drugs with multibillion-dollar potential. Soriot got into the top five based on a slate of new cancer drugs that reversed years of failure in the clinic. But with Novo Nordisk offering the latest lesson on how a reliance on a couple of big drugs can blow up in your face, he’s built a development machine that entered this year with more than 100 Phase 3 studies underway. “Think about that,” he told his audience of investors and analysts. “One hundred Phase 3 trials. It’s an enormous momentum going through the pipeline. This year, we should have 20 Phase 3 readouts. Those readouts, fingers crossed of course, if they are positive, they will collectively drive another more than $10 billion of peak revenue.” In vivo was called out in that session. Along with the oral PCSK9 drug AZD0780 , an oral GLP-1 called elecoglipron that scored in Phase 2, eight homegrown ADCs, radioligands, next-generation I/O bispecifics, “in particular, rilvegostomig” (despite all the problems we’ve seen with TIGIT), the BCMA/CD19 targeted AZD0120 , gene therapies and a new T cell-engager platform, you could say that AstraZeneca has a lot on its plate. Soriot is a relentless builder. That’s led to one of the most ambitious plays in China, where he has devoted a considerable amount of his own time sharpening both commercialization and R&D activities in a country that has made biopharma a top economic priority. 4. Eli Lilly: The most stubborn drug developer in biopharma goes big on R&D as obesity delivers The scoop: Now that Eli Lilly has sealed its rep in obesity, trouncing a sometimes hapless Novo Nordisk, it’s no wonder that Eli Lilly juiced its R&D budget in 2025, betting on a new round of obesity drugs while broadening its research horizons. The FDA wasted no time in approving Lilly’s oral obesity pill orforglipron, perhaps a reward for all the US investments the pharma giant has laid out before the Trump administration. It’s a few months behind Novo, but Lilly has already shown that its marketing team can compete and catch up. And then there’s retatrutide, its next-gen triple-G agonist , where Lilly has been balancing solid results on weight loss against side effects. Staying out front of the global obesity market won’t be easy, as other giants like Merck and Pfizer make a play. But Lilly earned its kudos and has a lot of momentum in its favor. Lilly had similarly high hopes for its Alzheimer’s drug, but weak efficacy data has been holding down sales. Can it do better with remternetug , its N3pG beta amyloid treatment? The late-stage candidate hopes to do what the current marketed drugs do in clearing amyloid, but with a self-injectable that will be far easier for patients to use than the current infusion. That could go a long way to building a market of patients who are at risk of developing Alzheimer’s years in the future. There’s a lot here to suggest that Lilly faces another uphill battle in Alzheimer’s, but it’s been plugging away for decades and shows no signs of conceding defeat or calling a truce. To the contrary. Last fall CEO David Ricks wooed Carole Ho away from her chief medical officer post at Denali Therapeutics — which is celebrating its first new drug approval — and made her president of Lilly Neuroscience. Ho led the $6.3 billion deal to buy Centessa Pharmaceuticals and its sleep disorder drug cleminorexton (ORX750), which is in Phase 2 studies for narcolepsy and hypersomnia. That’s a chunk of change for a relatively small market, which has analysts thinking that Eli Lilly may be targeting a much bigger opportunity in fatigue and focus — which would put it much more squarely in a familiar realm of population drugs. Alongside Ho, Adrienne Brown was put in charge of immunology while R&D chief Daniel Skovronsky was given a range of impressive titles. So look for more deals in the hot immunology arena as well. Lilly is not known for big buys. It’s been more comfortable going after biotechs like Scorpion Therapeutics, where it beefed up its oncology franchise with the PI3Kα inhibitor program STX-478 , targeting a large segment of the breast cancer market. Now in Phase 3, it now faces a major rival in Novartis, which recently picked up its own contender for a less-toxic treatment in a $2 billion deal for Synnovation Therapeutics. Lilly upped the ante with its purchase of Kelonia Therapeutics, putting up $3.25 billion in cash on a $7 billion M&A deal that will make Lilly a player in in vivo CAR-T. That’s become one of the hottest areas in biotech, with companies looking to leapfrog allogeneic versions of CAR-T that have moved slowly in the clinic. The original autologous CAR-Ts delivered jaw-dropping data, but in the US have proven too complex for most community cancer centers, where the bulk of treatment occurs. Lilly has built a powerhouse rep, and it’s also splashing some big bucks to go after a new supercomputer with Nvidia. It remains one of the top pharmas to watch in R&D after going a long way to shed its historical profile as the slowest player in the big leagues. 5. Johnson & Johnson: The healthcare giant breaks out of the pack with a big buyout The scoop: CEO Joaquin Duato likes to talk up the big numbers of marketed and experimental drugs under J&J’s broad umbrella. But when it comes to near-term growth drivers, the discussion always boils down to a few big players. On the marketed side, that means products like Carvykti — the star CAR-T out of China — and Tecvayli, which sparked recent headlines with data for treatment-refractory patients with multiple myeloma. The Tecvayli/Darzalex combo was approved as a second-line treatment for multiple myeloma after FDA Commissioner Marty Makary blessed it with a special rapid review. Its IL-23 Tremfya has broken above $5 billion in sales, leaving the ever optimistic Duato predicting a crest above $10 billion. The psoriasis drug icotrokinra Icotyde just got approved, the payoff of a longtime partnership with Protagonist and another example of how J&J’s business development team has scored key deals for the pharma giant. J&J has reportedly been in talks to buy its partner Protagonist , but so far, no deal. And with Protagonist’s stock up 140% over the last year, that would be pricey. And now that Caplyta has an FDA nod to be marketed for major depressive disorder — the big bet that came with the Intra-Cellular buyout for $14.6 billion — J&J can be more confident about generating more than $5 billion a year for that franchise. That has all gone a long way to putting the loss-of-exclusivity for Stelara in the rearview mirror, as Duato delighted in telling analysts during its Q4 results call. It’s not all been clear sailing. The Phase 3 for another depression therapy, aticaprant, was axed after it flopped (as did a key rival). And its other big depression program for seltorexant stumbled badly last fall when it failed to beat out quetiapine extended release in a head-to-head study. J&J had vowed to stand by both after the Caplyta buyout. And there’s been plenty of trouble for milvexian, partnered with Bristol Myers Squibb, which I cover in more depth below. One of its next big bets was on Halda, which J&J made a deal to acquire for $3.05 billion at the end of 2025. Using tech derived inside the biotech — which was founded by Yale’s Craig Crews — researchers targeted BRD4 “in the presence of androgen receptors” common in prostate cancer, as explained by Endpoints’ science writer Ryan Cross . In an early study, the biotech found it had a big impact on PSA, a common biomarker for prostate cancer. And the same approach on RIPTACs — regulated induced proximity targeting chimeras — could work in a variety of cancers, potentially overcoming resistance to currently marketed drugs with more targeted therapies that protect most healthy cells. Another closely watched drug in J&J’s pipeline is JNJ-4804, which targets both IL-23 and TNF. Now in Phase 2, the drug is going after ulcerative colitis, psoriatic arthritis and Crohn’s disease. And Royalty Pharma recently bet $500 million on its future in autoimmunity, co-funding its research work on the therapy for the next two years. That’s quite a vote of confidence. Whatever happens with Protagonist, J&J has been effective in nailing down blockbuster deals over the years. And those deals have included some very bold plays, which include reaching into China for a game-changer when that was still considered suspicious. Given its track record on M&A, you can expect more ahead in 2026. 6. Novartis: Key patent losses keeps R&D scrambling to build late-stage pipeline The scoop: Novartis has been engaged in a delicate balancing act with its late-stage portfolio and rising generic competition. In its 2025 wrap-up, CEO Vas Narasimhan championed sales growth for mainstays like Kisqali, Kesimpta and Pluvicto. All of which are expected to help fill up most of the $4 billion hole this year from the loss of exclusivity on Entresto, Promacta and Tasigna. And with Cosentyx facing knock-offs by the end of the decade, there’s lots more pipeline work being done. Some analysts have been keen to trumpet the blockbuster potential for ianalumab, which has been racking up positive data for Sjögren’s disease and primary immune thrombocytopenia (ITP), a blood disorder. It’s targeted at B-cell driven autoimmune disorders. Novartis bagged that drug in its buyout of MorphoSys in 2024, which was primarily about pelabresib — an oncology program that quickly disappointed Novartis with evidence of emergent malignancies. It’s going to take more than one added blockbuster to satisfy Wall Street. So it was at least slightly concerning that Narasimhan had to push back readouts for its late-stage pipeline by a bit. Now zigakibart is expected to deliver Phase 3 data for kidney disease in early 2027, while pelacarsen should make its Phase 3 data debut for lipoprotein(a) now in the second half of this year. Zigakibart is part of a trio of drugs in the pharma giant’s IgA nephropathy (IgAN) portfolio — including Vanrafia and Fabhalta. A couple of months ago Vanrafia flunked a Phase 3 for kidney function decline. That was close enough for Novartis, though, as it plans to push ahead on an OK for a full IgAN approval. Travere had a near miss on the same endpoint, before its approval, so don’t count Novartis out yet. Novartis likely had Cosentyx in mind when it agreed to pay $12 billion for Avidity last fall. That’s significantly higher than the single-digit billion-dollar deals Narasimhan is noted for — which includes Tourmaline Bio, Regulus Therapeutics and recently Excellergy. There are two key late-stage drugs that inspired the neuromuscular deal, along with multibillion-dollar expectations for both: delpacibart etedesiran (del-desiran) for myotonic dystrophy type 1 and delpacibart braxlosiran (del-brax) for facioscapulohumeral muscular dystrophy (FSHD). The deal also delivered delpacibart zotadirsen (del-zota) in Duchenne muscular dystrophy, and with it peak sales projections that tend to drag well below the blockbuster mark. That should be first up for an accelerated approval. Like everyone else in the R&D 15, R&D disappointment is no stranger to Novartis. There were blockbuster expectations for the PI3K drug Piqray in breast cancer at one point, but Roche has crimped any future in that direction with the approval of Itovebi, a better drug that’s now used in frontline therapy. Novartis, though, doesn’t take disappointment lying down and handed over $2 billion upfront to get a new drug that could do Piqray and Itovebi one better. The drug is dubbed SNV4818, and Novartis threw in a billion dollars in milestones to purchase the PI3Kα a few weeks ago. The big idea here is that SNV4818 is designed to spare healthy wild-type PI3Kα and zero in on the mutated version in cancer cells. That may well eliminate much of the toxicity that has scuttled its combination approaches. And it gives Novartis a new inside track on a market that covers 40% of HR+/HER2- breast cancer, plus a shot at other solid tumors as well. The pipeline isn’t solely devoted to blockbusters. Novartis developed Coartem for malaria decades ago and sold it cheap in Africa, priced for the poor. Now that new drug-resistant strains are coming along, Novartis has a new combo approach — GanLum — that looks just as effective . There are major players that wouldn’t spend a dime on a program like that. So some added credit is due here. Don’t be surprised if Novartis picks up its pace on China deals. Argo Biopharma (a siRNA deal focused on cardio) and SciNeuro (in Alzheimer’s) have been brought into the fold recently. And R&D was a big focus with its announced $480 million plan to beef up research and manufacturing in China. 7. Pfizer: Repeated setbacks taint expectations, setting the stage for more dealmaking The scoop: Pfizer has a long tradition of disappointing investors in late-stage development, and 2025 was no exception. Its sickle cell drug inclacumab went down in the summer , following the withdrawal of Oxbryta. That led to some quick math about the billions wasted on the Global Blood Therapeutics buyout — though the GBT drug osivelotor remains in the pipeline. Danuglipron for obesity was a bust . Not surprisingly, a raft of experimental programs at Seagen were slashed, but that’s standard after a big buyout. Pfizer’s once magnificent hopes for gene therapy came to an end — along with much of the rest of the AAV field — early last year with the discontinuation of sales of the $3.5 million hemophilia B treatment Beqvez. And weeks ago trouble recruiting for the Phase 3 study of its Lyme disease vaccine left a cloud over that program. It failed the trial, but will still go to the FDA. The Lyme disease setback was quickly followed by an even more troublesome issue with its newly acquired obesity drug that came with the $10 billion Metsera acquisition. It didn’t fail. But it also didn’t impress many analysts with its rather bland weight-loss numbers. Pfizer is going for an easier monthly dose, but it’s also arrayed against two well-established leaders in the field, both of which are doubling down on their own second-gen therapies. And they aren’t alone. The bar for carving out a blockbuster entry in obesity will be very high. And based on their Q4 review of the pipeline you can expect a relentless focus there. Every time Pfizer experiences a flop, it goes right back at it, inking new deals and pushing R&D to come up with a few new winners. And there’s always plenty to talk about in Phase 3 to excite the discussion anew. Pfizer trumpeted an early cut of Phase 2 progression free data for atirmociclib, which it hopes can succeed its blockbuster CDK 4/6 Ibrance in breast cancer. Ibrance earned more than $4 billion last year despite less competitive overall survival data compared to its rivals. Atirmociclib, though, still has a few years of late-stage trials before it can reach the finish line on first-line metastatic breast cancer. Cancer clearly remains a major focus in Phase 3. The company has accelerated its work on mevrometostat for castration-resistant prostate cancer, looking to build on the positive data researchers gathered in a Phase 1 combo with Xtandi and released at an ASCO session early last year. Metastatic treatment-resistant patients saw a 49% decline in the risk of disease progression or death. Pfizer has big hopes for this drug with a rapid-fire plan to win a quick FDA OK, but some analysts have been less than impressed with the data they’ve seen on other EZH2 inhibitors, which they believe might be typical of the class. Now that Pfizer has had a chance to absorb the Seagen pipeline and come up with its own strategy, several of its oncology plays are centered around the assets it acquired. There’s the anti-HER2 ADC disitamab vedotin, multi-tumor prospect sigvotatug vedotin, which should offer up Phase 3 data soon, and PDL1V, another Seagen ADC that targets PD-L1 expressing cells with a microtubule-disrupting agent payload. Pfizer is pushing PDL1V — which could theoretically work in a variety of tumors — into pivotal trials, but it’s been flying largely under the radar. Henlius, though, has flagged its own rival in the pipeline, touting its prospects of coming out ahead. Finally, prifetrastat (PF-07248144) is one of several KAT6 inhibitors angling for the spotlight. Padcev remains Pfizer’s top prospect for expansion studies, with a slate of new Phase 3 data on bladder cancer. Their Padcev/Keytruda combo beat out chemo in pre-surgery muscle invasive bladder cancer cases, promising a larger market for their drug out of Seagen. It’s unlikely, though, that Pfizer can recapture the glory it saw during the pandemic, when its mRNA vaccine out of BioNTech scored huge — only to fade away faster than once thought possible. 8. Bristol Myers Squibb: A high wire act in Phase 3 leaves analysts fretting over their future The scoop: Bristol Myers has had its sights set on a successor franchise to Revlimid and Pomalyst for years. And 2026 is shaping up as a key turning point for a pair of programs that it hopes will fill at least part of the big gap left by generic competition. Iberdomide and mezigdomide are a pair of molecular glues in late-stage development. Mezigdomide looked promising in a Phase 2 study back in 2023 and was hailed earlier this year for a win in Phase 3 . We have yet to see the numbers, and some analysts want to see how the head-to-head with Pomalyst looks. Iberdomide, meanwhile, is up for a decision by the FDA this summer in multiple myeloma, and could break past into blockbuster territory once on the market. They’re both part of a class of drugs dubbed cereblon E3 ligase modulators (or CELMoD), the tip of the spear in protein degradation. A third CELMoD, golcadomide, is in Phase 3 for large B-cell lymphoma. Meanwhile, dark clouds have been gathering around another late-stage effort for milvexian, an oral factor XI inhibitor that was seen as a potentially safer successor to the blockbuster blood thinner Eliquis. Two big studies have been scrapped on disappointing data and the field is still reckoning with the failure of Bayer’s oral program. Regeneron and Novartis are pursuing injectables, which could eclipse the orals on efficacy. Admilparant, an LPA1 antagonist which showed promise in Phase 2 for IPF, is up on the frontlines of the pipeline, along with pumitamig (PD-L1 x VEGF-A bispecific antibody with BioNTech) and the radiopharmaceutical RYZ101, which it picked up in its $4.1 billion buyout of RayzeBio. Like most of the rest of the top 15, Bristol Myers has been busily scooping up biotechs to fill out late-stage development work. Cobenfy, approved for schizophrenia in 2024, came out of Karuna and is now triggering worries for its late-stage program for Alzheimer’s-related psychosis following some “irregularities” that delayed an interim analysis. Bristol Myers doesn’t have a whole lot of wiggle room when it comes to the late-stage pipeline. It’s being hammered by the loss of exclusivity on legacy blockbusters, with Opdivo — its current reigning champ — and Eliquis looking at a patent cliff event over the next two years. Revlimid is in significant decline. Even with some new approvals contributing to the bottom line, revenue slipped slightly in ’25 and will slide even more this year. So its recently approved franchise therapies and Phase 3 drugs are all meant to be major contributors. Which is why this is one big pharma that frequently signals to the biopharma research community that it has no appetite for small-market drugs. Its late-stage pipeline today was shaped by a reorganization two years ago that dropped a slate of early and mid-stage drugs from the pipeline that were seen as runners-up in the blockbuster race. That included a CTLA-4 drug that was seen as a cut below Yervoy. To compete at the level Bristol Myers needs, it all has to be seen as a contender for first-in-class or best-in-class. 9. GSK: The new CEO brings some added enthusiasm to play in bolstering late-stage expectations The scoop: Historically, GSK has avoided anything flashy. It buys biotechs, but tends to go for deals on the lower end of the bolt-on spectrum. Its pipeline work has drawn mixed reviews over the years, sometimes spurring the activist set. The new, new thing in biopharma R&D often fails to pan out, as they know from experience: One of the reasons why the company saw a spike in R&D spending last year was due to its write-off on belrestotug, its TIGIT program partnered up while Hal Barron was running research. The original deal with iTeos cost $625 million in upfront cash. GSK execs aren’t diving into obesity, either — or at least they’re avoiding the commercial slugfest developing around GLP-1. It’s too frothy. So after its ADC Mo-Rez (mocertatug rezetecan) delivered strong Phase 1b data recently, it caught our attention. GSK heralded the results in platinum-resistant ovarian or endometrial cancer as “extremely exciting.” They were so excited, GSK said it would pivot directly into an ambitious Phase 3 program with five trials set to begin soon. The ADC was picked up in a modestly priced licensing deal with China’s Hansoh Pharma, targeting the B7-H4 antigen. And if the data hold up, it will help make GSK a force to be reckoned with in oncology, a goal that ex-CEO Emma Walmsley set out when she took over a decade ago, picking up the pieces left from its big asset swap with Novartis in 2015. It’s not the only ADC GSK is excited about. The other one — also from Hansoh — is dubbed Ris-Rez and targets small cell lung cancer. And GSK talked it up in its Q4 review earlier this year. GSK expects Mo-Rez can earn more than £2 billion a year, making it a key drug in its quest for £40 billion a year in revenue by 2031, up from 2025’s £32.7 billion. Ris-Rez, meanwhile, has picked up a breakthrough drug designation at the FDA and earned equally ambitious peak sales projections. You could call all that part of GSK’s tactical acceleration to achieve some longtime strategic goals. Rounding out its newfound prospects for oncology, GSK is following up its IDRx buyout — just $1 billion upfront — from a little more than a year ago with pivotal plans for velzatinib/IDRX-42. If successful, new CEO Luke Miels will be headed back to an arena where he found success at AstraZeneca. And he clearly relishes that prospect. Miels, a marketing specialist, offered a similar projection for bepirovirsen, its hep B “functional cure,” projecting equivalent peak sales as its top cancer drug. Some of the analysts, though, aren’t ready to go that high, but breaking the billion-dollar mark seems plausible. Then there’s the pivotal campaign for camlipixant, a P2X3 antagonist for chronic cough that’s also earned some blockbuster love, along with fresh prospects for Jemperli. In some respects, a brighter horizon for GSK reflects Miels’ cheerleading style for R&D. Where Walmsley would be somewhat more guarded, he’s encouraged high expectations. But it’s also based on hard data, where he’s been reaping the rewards of Walmsley’s dogged ambitions for GSK. GSK has had its successes, particularly with Shingrix, which has helped the company manage the market volatility for RSV. And the global pharma continues to talk up vaccines and respiratory, two traditional mainstays. It’s also been a longtime runner-up to Gilead Sciences in the HIV market, whereto majority-owned ViiV continues to carve out significant sales. 10. AbbVie: Researchers set out to prove they’re more than just Skyrizi and Rinvoq The scoop: Skyrizi and Rinvoq kept AbbVie in the big leagues as Humira gradually faded, and AbbVie execs have shown real zeal about adding to those franchises with new indications. Moving beyond its two cash cows, there’s a slate of late-stage bets — along with an aspirational play for in vivo CAR-T. AbbVie had high hopes for their neuroscience division when it paid $8.7 billion to get Cerevel Therapeutics back in 2024. The readouts aren’t over, but it had to write off a good chunk of that when emraclidine foundered in a slate of schizophrenia studies. It did better with another drug picked up in the buyout when tavapadon hit in Parkinson’s. But execs can’t be happy with a group of modest peak sales projections. Maybe AbbVie can do better with bretisilocin, a 5-HT2A receptor agonist and 5-HT releaser which had a positive slice of Phase 2a data for major depressive disorder when AbbVie bought it. It didn’t pay a lot for it , failing to disclose the upfront and leaving it at $1.2 billion all in for the psychedelic mimic. But it’s a near-term shot in a high-risk segment of the business that’s been seeing growth with Vraylar and Ubrelvy. ABBV-932 rounds out its top neuroscience prospects. Then there’s oncology. Etentamig (ABBV-383) was dosed in Phase 3 for the first time in 2024, highlighting AbbVie’s shot at a BCMAxCD3 bispecific T-cell engager for multiple myeloma. By silencing the Fc tail, researchers hope to extend the half-life of the drug so they can stretch dosing to every four weeks. The downside is it’s late to the game, with Tecvayli from J&J out on the market and following up with a recent accelerated approval for a combo with Darzalex. Pivekimab sunirine (PVEK), its CD123 ADC, was filed with the FDA last fall. AbbVie submitted early Phase 1/2 data for blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive cancer, hoping to gain a quick entry on a drug that earned a breakthrough drug designation from the FDA. Temab-A (ABBV-400), which targets cancers with high c-Met expression, got started in Phase 3 with a shot at colorectal cancer, where it’s being studied as a monotherapy and in combo with bevacizumab. AbbVie is looking for data from a slate of mid- to late-stage studies to gauge its potential for solid tumors. ABBV-706, an SEZ6 targeted ADC, is in trials for solid tumors. You don’t hear a lot about BoNT/E, the fast-acting botulinum neurotoxin that works for shorter spans. AbbVie picked it up in mid-stage development way back in 2018, bringing a potential rival to Botox in-house. That treatment was filed with the FDA a year ago and could bolster its big business in aesthetics. AbbVie will go the distance when it feels there’s sufficient upside, and that’s what it committed to do when the company bought Capstan Therapeutics, one of the leading early-stage biotechs working in the sizzling in vivo CAR-T space. There’a a very long row to hoe on that one, but a win here could put AbbVie out front with a next-gen cancer drug. Also, the $2.1 billion deal didn’t cost the moon, giving it a relatively low-cost method for generating some added enthusiasm for the pipeline. 11. Sanofi: Another new CEO looks for a better path in Phase 3 The scoop: Big pharma players with a solid record of success in Phase 3 don’t fire their CEOs, so Paul Hudson’s exit a couple of months ago set the stage for a recital of all his setbacks in R&D. Hudson bet big on immunology at Sanofi, where board members have repeatedly demonstrated their readiness to make a change when they feel a course correction is needed. So when the strategy failed to set the company squarely on a new path that could carry it past Dupixent, the enormous cash cow (out of Regeneron) that pays the freight at Sanofi, the rest was Greek theater. New CEO Belén Garijo will need to make some tough decisions, and that typically starts with the pipeline. About two years ago, and Hudson was cheering mid-stage data for its anti-inflammatory OX40L drug amlitelimab, once billed as a product that could excel over Dupixent. These days execs spend their time defending mixed data from the Phase 3 program that followed. Analysts highlighted lower efficacy than Dupixent for atopic dermatitis and Sanofi has been dropping indications instead of building the pipeline-in-a-product it badly needs. It’s not a bust, but it is far from megablockbuster heaven. The same “meh” reaction followed last summer’s approval of rilzabrutinib (Wayrilz) for immune thrombocytopenia (ITP). That followed a major setback on atopic dermatitis. It edged ahead after the key drug in the Principia Biopharma buyout, tolebrutinib, hit a series of setbacks in clinical trials. And the oral TNF inhibitor balinatunfib has gone down on data twice in mid-stage studies, failing an effort to prove it could work as a monotherapy. That only leaves the anti-CD40L frexalimab from one of Hudson’s old lists of experimental drugs capable of generating more than $5 billion a year in revenue. That’s in Phase 3 for multiple sclerosis, after a failure for Sjögren’s disease. Its bispecific lunsekimig, meanwhile, hit in mid-stage studies of asthma and an inflammatory sinus condition, but flopped in atopic dermatitis. Sanofi stayed at the blockbuster feast because of its partnership with Regeneron on Dupixent. But it’s only managed to disappoint analysts with its COPD data for next-gen drug itepekimab. That leaves R&D working away to keep building Dupixent as it gets close to a reckoning on its patents in the early 2030s. Sanofi also isn’t catching much of a break with analysts on its latest CEO pick. Garijo never established Merck KGaA’s reputation in R&D and there are plenty of doubters that she can do it at Sanofi. Nevertheless, she’s holding the reins now. 12. Novo Nordisk: After fumbling the lead in obesity, R&D hunts for a new way forward The scoop: Novo Nordisk has been channeling more cash into its R&D division in recent years, emboldened by its mega-blockbuster semaglutide and vowing to beat back competition from fierce rival Eli Lilly. Some of that money went into a critical head-to-head study of its GLP-1/amylin analog against Lilly’s tirzepatide, and Novo lost — big time. With that went its market cap, which has shriveled back to levels from five years ago. Novo had a big head start on Eli Lilly, and its steady backward drift — as a tide of new GLP-1s courses through the industry — has escaped no one. The early arrival of its pill has done nothing to change perceptions. Novo Nordisk isn’t done with CagriSema. With weight loss averaging more than 20%, why should it be? But a lot of attention has now shifted to zenagamtide (amycretin), a GLP-1/amylin dual agonist that was slated to begin Phase 3 this year with both oral and injected versions. Adding insult to injury, Novo also had to concede late last year that its Phase 3 attempt to see if semaglutide could help Alzheimer’s patients came up as a loser. Practically no one expected it to succeed, and Novo clearly flagged the lottery-ticket strategy, but the stock took a hit anyway. But don’t expect Novo to take a back seat on obesity just because of a few key setbacks. That was apparent with its failed bid for Metsera, which fell — inevitably — to Pfizer. But it also has UBT251, a triple agonist that it hopes can put it out front again. Long a leader in the diabetes field, Novo is also using its deep scientific knowledge in the field with its late-stage program for ziltivekimab to see if it can make an impact in cardiovascular disease with a disease-modifying approach. That’s another huge field, with enormous potential — if Novo can catch a break. 13. Amgen: The new R&D chief is determined to score big with protein degradation The scoop: The star of Amgen’s late-stage pipeline remains MariTide, its obesity drug that’s meant to rival the two frontrunners. There’s a twist, built around GIPR antagonism, as opposed to the agonism that has succeeded so far. Over the years, Amgen CEO Bob Bradway has managed to foster star coverage for its leading experimental drugs. Lumakras, its breakthrough offering on KRAS, was an example of that. But there are too many questions about the obesity market now to get a free pass among the analysts. For Amgen to succeed with obesity, it’d have to clear a very high bar on efficacy (that hasn’t looked good), hold the line on safety and offer a better dosing regimen to compete against the leaders. That’s not so easy, particularly as more and more rivals elbow their way into the obesity pipeline looking for any kind of edge. And Amgen still has a ways to go before it can hunt up an approval. In reviewing 2025 for investors, R&D chief Jay Bradner offered its Phase 3 drug desodoliveb for Sjögren’s disease. And there’s daxdilimab. But there were also a couple of duds. Bradner axed an anti-OX40 rocatinlimab collaboration with Kyowa Kirin — a precursor to the Japanese company’s decision to scrap the whole thing — as well as the program for bemarituzumab, which produced positive data for gastric cancer. Where Amgen execs see their most likely near-term growth coming from is franchise expansion. But it has also had to stare down the FDA, which wanted their rare disease drug Tavneos to be pulled after the agency spotlighted a reassessment of the benefit/risk profile the drug presented. Given the less-than-stellar prospects of its late-stage pipeline, it’s no wonder that Bradner turned to Dark Blue, buying out the UK biotech for $840 million earlier in the year. The move puts Bradner back in the driver’s seat of protein degradation, an early and long-lasting love of his. 14. Regeneron: Cash cows carry it through a challenging fight in R&D The scoop: Regeneron execs Len Schleifer and George Yancopoulos have been working hard to get investors excited about the near-term prospects for their late-stage pipeline, beginning with their LAG-3 fianlimab. But it can be an uphill climb with the analysts who haven’t been that impressed with late arrivals in questionable markets. Where Yancopoulos boasts about a drug with “best-in-class” potential, some analysts wonder how well they can do with a follow-up to Bristol Myers Squibb’s pioneering LAG-3. Bristol Myers has had plenty of trouble with the drug since it was approved. It isn’t effective enough to work as a monotherapy, so it has to be rolled out as a combo. Follow-up studies have failed, and rivals like Immutep have seen their candidates go down in flames, blighting a field that once looked like it would be a successor to CTLA-4 and PD-L1. Libtayo (the PD-1 cemiplimab) itself is a follow-up to Keytruda and Opdivo. It hit the $1.4 billion revenue mark last year, leaving it well behind the two market leaders as Regeneron’s research group pushes for expanded approvals. Building that market with combo drugs like fianlimab is important for Regeneron, which is run by two of the most persistent self-made billionaires in biotech. Another oncology prospect in mid-stage development is marlotamig (REGN7075), an EGFRxCD28 bispecific. Cancer overall, though, has proven to be a complex challenge for Regeneron. Odronextamab — its CD20xCD3 candidate — has run into repeated issues at the FDA as rivals crowd around. And when linvoseltamab was approved last summer (as Lynozyfic) for multiple myeloma, more delays had forced it further behind rivals at Pfizer and J&J. In addition, Regeneron has had trouble following up on its own market leader Dupixent. Last year its next-gen replacement partnered with Sanofi, itepekimab, fizzled in late-stage testing. But during Regeneron’s Q4 call Schleifer shifted the spotlight to “long-acting IL-13, IL-4, and IL-4/13 bispecifics as well as… a new soupy doopy molecule that is a new version of Dupixent that was naturally selected that might have even more improved properties.” In the meantime, Sanofi’s been working on legal strategies to extend the patents on Dupixent to 2040. Where R&D fails, patent thickets can often fill the gap. Regeneron has a much broader focus these days than when it achieved early successes with Dupixent and Eylea, including a foray into obesity and diabetes. Last summer it forked over a modest $80 million in cash to China’s Hansoh Pharma for olatorepatide, a GLP-1/GIP drug following elimination Lilly’s dominant play with tirzepatide. Even Regeneron says the drug looks similar to Eli Lilly’s, but it sees it as a pathway to developing a better drug that can maintain the muscle lost to GLP-1s. China’s late-stage trial passed muster in Phase 3 a few weeks ago, with Regeneron laying the groundwork for pivotal development ex-China. Trevogrumab (REGN1033) may help with the muscle loss issues, where researchers have been posting evidence of significantly reduced loss of lean mass. And there’s a triplet with garetosmab for obesity, though safety issues have clouded expectations. Once again, though, Regeneron finds itself competing in a hot, crowded field dominated by market leaders. Coming out on top will prove a tremendous challenge. Regeneron has had success with its C5 siRNA drug cemdisiran, reporting positive Phase 3 data for generalized myasthenia gravis as it steered toward an FDA filing. Jefferies, for one, has estimated sales of a billion dollars. But it’s been flying under the radar until recently at Regeneron, which rarely happens at a biotech led by such bullish players. 15. Gilead: Time to bury the dead and move ahead The scoop: Gilead’s MO on the R&D side has remained largely unchanged during Daniel O’Day’s seven-year tenure as CEO. It buys up intriguing new drugs from cutting-edge biotechs and watches as the experiments gradually fail in the clinic. But each year it’s saved by a growing, dominant HIV business. Biktarvy, its 3-in-1 daily tablet for HIV, provides about half of Gilead’s revenue. The R&D group has a deep understanding of HIV and the maintenance therapies needed to keep it in check, developing regimens that are easier on patients while keeping the big bucks rolling in. Yes, there have been failures in HIV — notably in GS-1720 and and GS-4182 recently — but its dominance in HIV shows no signs of deterioration. You don’t have to look long at the deals Gilead has done to see the missteps in cancer. Immunomedics is a prime example. The recent Q4 and 2025 review contains no reference to TIGIT, once a hot field in immunotherapy that “seems doomed,” in the words of analyst Tim Anderson. And does anyone remember magrolimab, the anti-CD47 “don’t eat me” antibody? O’Day, though, isn’t throwing in the towel. On the contrary. Gilead recently decided to go all in on anito-cel, buying out its partner Arcellx in a deal worth $7.8 billion. It believes the CAR-T can outperform Carvykti, the reigning champ in CAR-T, and help revive its commercial work in a field that has been flagging with its aging Kite originals. This is no long-term wager. The company is looking for a green light from the FDA just before Christmas. Then there was the $3.15 billion upfront pact to buy out an ADC from Tubulis. Gilead spent $1.68 billion in cash to bag Ouro, gaining the T cell engager gamgertamig, a BCMAxCD3 candidate now in Phase 1/2. In biotech, sometimes you have to bury the dead (programs) and move ahead. O’Day’s clearly decided that the time has come for Gilead. Its durable success in HIV gives him the means to do just that.

4月20日，阿斯利康宣布其抗IL-33单抗Tozorakimab在COPD的Ⅲ期MIRANDA试验中达到主要终点[1]。这是继3月OBERON和TITANIA两项Ⅲ期临床告捷后，Tozorakimab取得的第三项关键胜利，标志着IL-33通路靶向治疗迎来重大突破。 然而，这条赛道也曾充满坎坷 IL-33抗体：再生元/赛诺菲的Itepekimab在COPD中仅在前吸烟者或高加重风险亚组显示获益，关键Ⅲ期研究未达主要终点；AnaptysBio的Etokimab因疗效不足终止开发。 ST2抗体：罗氏的Astegolimab虽在Ⅱb期显著降低加重率（15.4%），但Ⅲ期ARNASA试验未能取得统计学显著性；GSK的Melrilimab同样因疗效不佳提前终止。 值得注意的是，Tozorakimab本身在Ⅱ期FRONTIER-4（慢性支气管炎）和FRONTIER-3（哮喘）试验中也曾折戟，仅在高加重风险亚组观察到改善趋势。此次连续三项Ⅲ期成功，不仅夯实了其作为IL-33通路首个COPD生物制剂的地位，更为整个领域重新注入信心。 图1 Tozorakimab又一项Ⅲ期研究成功[1] COPD：亟待破局的全球健康挑战 慢性阻塞性肺疾病（COPD）是全球第三大死因，影响近4亿人。即使患者接受了双联或三联吸入剂的标准维持治疗，仍有超50%会经历中重度急性加重。首次重度加重后，仅半数患者存活时间超过3.5年［2-5］。因此，开发能够从根本上抑制炎症通路、减少急性加重的新型靶向疗法，已成为该领域的迫切需求。 图2 全球COPD疾病负担统计[2] 机制解析：IL-33/ST2/IL1RAP ——炎症级联的"上游开关" IL-33作为IL-1家族成员，扮演着独特的“警报素”（Alarmin）角色。在组织机械损伤、病毒感染或过敏原刺激下，IL-33会迅速从屏障组织的细胞核释放至胞外。其生物学功能的发挥高度依赖由ST2（IL1RL1）和IL1RAP组成的异源二聚体受体复合物。IL-33作为IL-1家族成员，扮演着独特的“警报素”（Alarmin）角色。在组织机械损伤、病毒感染或过敏原刺激下，IL-33会迅速从屏障组织的细胞核释放至胞外。其生物学功能的发挥高度依赖由ST2（IL1RL1）和IL1RAP组成的异源二聚体受体复合物。 图3 IL-33信号通路在多种病理状态下的关键作用[13] 当IL-33结合主受体ST2后，招募共受体IL1RAP形成三元复合体，激活MyD88-NF-κB及MAPK通路，诱发大量2型细胞因子释放，成为桥接先天免疫与适应性炎症的关键上游开关［6-7］。 图4 IL-33/ST2/IL1RAP复合物结构及下游信号传导[7] 研发格局：从单一阻断到多重协同 鉴于IL-33/ST2/IL1RAP在2型免疫与炎症中的枢纽地位，该轴已成为呼吸、自身免疫及肿瘤领域的战略高地。全球药企正加速从单一配体/受体中和单抗，向双特异性抗体（如IL-33×TSLP、IL-33×IL-4Rα）及多通路协同抑制剂演进。 图5 IL-33/ST2主要在研管线布局 以Tozorakimab为例，其独特优势在于能够同时抑制IL-33的还原型与氧化型信号传导：一方面阻断IL-33与ST2结合，抑制ST2依赖的炎症信号；另一方面阻断氧化型IL-33通过RAGE/EGFR通路引发的上皮功能障碍。这种双重机制更全面地干预COPD病理循环，为高加重风险患者带来显著获益［8］。 图6 Tozorakimab的双重抑制机制[8] IL33/ST2：多疾病领域的广阔应用潜力 1、自身免疫性疾病：在类风湿关节炎、重度哮喘、特应性皮炎及溃疡性结肠炎中，IL-33/ST2轴显著上调。阻断该通路已在临床试验中展现出控制急性加重的高潜力[9-10]。 2、肿瘤免疫：该通路在肿瘤微环境中呈双重作用：在软组织肉瘤中与良好预后相关，而在急性髓系白血病（AML）中促进T细胞耗竭[11-13]。 3、代谢与心血管疾病：可溶性ST2（sST2）已获FDA批准用于心力衰竭风险分层，血清阈值>35 ng/mL提示不良心血管事件风险显著增加[14]。在肥胖及2型糖尿病患者脂肪组织中，IL-33/ST2信号可改善胰岛素敏感性，但循环sST2升高与代谢综合征严重程度独立相关[15]。 IL1RAP：多通路阻断的核心枢纽 作为IL-1、IL-33和IL-36三条炎症通路的共享共受体，IL1RAP（IL1R3）不仅是IL-33信号传导的必需组分，更是极具潜力的广谱靶点。其与主受体（IL1R1、ST2、IL-36R）及配体形成三元复合体后，经TIR招募MyD88/IRAK/TRAF6，激活NF-κB/MAPK通路，驱动炎症级联与肿瘤微环境重塑。 肿瘤免疫双效协同：IL1RAP在AML及多种实体瘤（胰腺癌、非小细胞肺癌）中显著过表达。靶向IL1RAP的ADCC增强型抗体（如Nadunolimab）展现"阻断炎症微环境+靶向清除肿瘤细胞"双重机制，在实体瘤和血液瘤中前景广阔［16-19］。 自身免疫广谱抑制：靶向IL1RAP的Fc静默拮抗单抗（如SAR445399、CAN10）在斑块状银屑病、化脓性汗腺炎等疾病中，验证了对多条炎症通路的广谱抑制潜力及良好安全性［20-21］。 图7 IL1RAP作为IL-1、IL-33、IL-36三条通路的共享共受体[16] 相较于单一通路靶向策略，IL1RAP在适应症拓展方面展现出更广阔的应用潜力，其靶向疗法在临床前研究及临床试验阶段已覆盖广泛的疾病谱：在自身免疫与炎症性疾病领域，包括斑块状银屑病（PsO）、化脓性汗腺炎（HS）、系统性硬皮病（SSc）以及急性痛风性关节炎（GA）；在肿瘤领域，则涵盖胰腺癌（PC）、三阴性乳腺癌（TNBC）、结直肠癌（CRC）以及急性髓系白血病（AML）等多种实体瘤与血液系统恶性肿瘤。 图8 重要IL1RAP靶向抗体药物管线 赛业生物IL-33/ST2/IL1RAP人源化 小鼠模型：赋能下一代免疫疗法研发 尽管IL-33/ST2/IL1RAP靶向药物研发火热，但人鼠核心蛋白在序列与构象上存在显著差异。目前多种高度特异性的人源化抗体（如Tozorakimab和Itepekimab均不与小鼠IL-33结合）难以在常规野生型小鼠中准确评估亲和力、药代动力学及体内药效。为全面赋能IL-33/ST2/IL1RAP通路疗法的临床前验证，赛业生物重磅推出涵盖三个核心靶点的人源化小鼠模型。 IL33人源化小鼠模型（产品编号：C001722）验证数据 图9 IL33人源化小鼠体内中人源/鼠源IL33基因及蛋白表达检测 IL1RL1 (IL33R/ST2）人源化小鼠模型（产品编号：C001632）验证数据 图10 IL1RL1 (IL33R/ST2）人源化小鼠体内中人源/鼠源IL1RL1基因及蛋白表达检测 IL1RAP人源化小鼠模型（产品编号：C001631）验证数据 图11 IL1RAP小鼠体内各组织中人源/鼠源IL1RAP基因及蛋白表达检测 模型总结 从主导COPD炎症循环的IL-33，到介导微环境重塑的ST2与IL1RAP复合物，这一关键信号轴正深刻重塑呼吸系统疾病、自身免疫及抗肿瘤创新药的研发格局。在阿斯利康等跨国药企的持续突破为IL-33通路临床成药性注入强心剂的背景下，赛业生物紧跟前沿临床需求，推出的IL33、ST2及IL1RAP人源化模型凭借人源基因与蛋白的高保真稳定表达，实现了与临床高度契合的转化价值，不仅能全面覆盖COPD、哮喘等呼吸系统疾病拮抗型单抗的药效学评价，还可深度支持AML、PDAC等肿瘤免疫治疗的机制探索，从而有效扫清早期靶标验证向临床转化跨越的关键技术障碍。 本文作者：Layne 编辑：西米 审核：西米、🍑momo 参考文献： [1]AstraZeneca. (2026) Tozorakimab met primary endpoint in Phase III MIRANDA trial in patients with COPD. AstraZeneca Press Release. [2]Montes de Oca M et al. (2025) The global burden of COPD: epidemiology and effect of prevention strategies. Global Epidemiol Chronic Respir Dis. 13(18):709-724. [3]WHO. (2024) The top 10 causes of death. WHO Fact Sheet. [4][Chen S et al. (2018) Symptomatic burden of COPD for patients receiving dual or triple therapy. Int J Chron Obstruct Pulmon Dis. 13:1365-1376. [5]Singh D et al. (2024) Implications of cardiopulmonary risk for the management of COPD: a narrative review. Adv Ther. 41:2151-2167. [6]Sheng F et al. (2025) IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential. Front Immunol. 16:1533335. [7]Riera-Martínez L et al. (2023) The role of IL-33/ST2 in COPD and its future as an antibody therapy. Int J Mol Sci. 24(10):8702. [8]England E et al. (2023) Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep. 13(1):9825. [9]Griesenauer B et al. (2017) The ST2/IL-33 axis in immune cells during inflammatory diseases. Front Immunol. 8:475. [10]Mok MY et al. (2010) Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology. 49(3):520-527. [11]Kang BH et al. (2025) Unlocking IL-33: new insights into tumor immunity. Immune Netw. 25(5):e36. [12]Che K et al. (2025) IL-33 in cancer immunotherapy: pleiotropic functions and biological strategies. Cytokine Growth Factor Rev. 85:81-92. [13]Chen H et al. (2018) Integrated expression profiles analysis reveals correlations between the IL-33/ST2 axis and CD8+ T cells, regulatory T cells, and myeloid-derived suppressor cells in soft tissue sarcoma. Front Immunol. 9:1179. [14]Chen J et al. (2022) Growth stimulation expressed gene 2 (ST2): clinical research and application in cardiovascular related diseases. Front Cardiovasc Med. 9:1007450. [15]Missous G et al. (2024) Circulating interleukin-33 levels in obesity and type 2 diabetes: a systematic review and meta-analysis. Am J Physiol Endocrinol Metab. 327(6):E686-E699. [16]Garlanda C et al. (2025) IL-1 family cytokines in inflammation and immunity. Cell Mol Immunol. 22(11):1345-1362. [17]Frenay J et al. (2022) IL-1RAP, a key therapeutic target in cancer. Int J Mol Sci. 23(23):14918. [18]Zarezadeh Mehrabadi A et al. (2024) Interleukin-1 receptor accessory protein (IL-1RAP): a magic bullet candidate for immunotherapy of human malignancies. Crit Rev Oncol Hematol. 193:104200. [19]Rydberg Millrud C et al. (2023) Blockade of IL-1α and IL-1β signaling by the anti-IL1RAP antibody nadunolimab (CAN04) mediates synergistic anti-tumor efficacy with chemotherapy. Cancer Immunol Immunother. 72(3):667-678. [20]Fields JK et al. (2024) Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling. Cell Rep. 43(5):114099. [21]Meijs A et al. (2025) The novel, first-in-class IL-1R3 antagonist SAR445399 reduces skin inflammation in an innovative proof-of-mechanism study with dual immune challenge models and comparator drugs. Sanofi Medical Congress. 相关推荐 从“快乐假象”到疾病真相：Ube3a KO小鼠揭秘天使综合征的“微笑”之殇 诺华31亿重金回购FXI靶向疗法，F11“人源化”小鼠助力终结【抗凝出血】难题 小身躯，大使命：挑战人体最大基因DMD的人源化小鼠 靶向成纤维细胞的Col1a2-iCre小鼠（附赠工具鼠取材验证重组效率的解决方案） 工具鼠系列：MerCreMer与CreERT2的诱导方式有何异同？ 寻找更好的动脉粥样硬化模型——B6J-Apoe KO小鼠 HFD+CCl4诱导的代谢功能障碍相关性脂肪肝炎MASH（NASH）小鼠 结直肠癌（CRC）&家族性腺瘤性息肉病（FAP）研究模型——Apc KO小鼠 SKG小鼠——类风湿性关节炎（RA）和强直性脊柱炎（AS）研究好帮手 点击“阅读原文” 立即咨询