Alexion Pharmaceuticals, Inc.

Step back from the multitude of details that go into every big pharma pipeline, and you’ll see the influence that blockbusters have on the entire field. These days, making your mark in R&D at the level the top 15 spenders play requires not just one, two or three experimental drugs that can earn a billion dollars a year. It’s typically about a slate that includes candidates that can bring in $3 billion to $5 billion a year, preferably more. The numbers keep getting bigger. When Merck execs look at the $30 billion-plus hole they have to fill once Keytruda goes off-patent, they know that anything under a billion won’t count for much. And you can see the same math dominating discussions at J&J, Pfizer, Bristol Myers Squibb and more. On the plus side, the drive to move the dial on sales includes changing standards of care for large numbers of patients. That can open up some hard targets that have defied investigators for years. The hunt for first- and best-in-class drugs inspires truly innovative development work. But for patients — including me — who suffer from diseases that aren’t among the major league targets, it can be hard to find much interest among a set of companies that have to think big in order to survive. These days, with IPOs still out of favor, the blockbuster strategy of the big cap players is more influential than ever. Those R&D alliances that can sustain a biotech will be skewed to the companies that are breaking new ground where pharma sees the biggest upsides. And it will bend an entire global industry’s decision-making process. Success breeds success in this field. AstraZeneca, which once struggled to turn around the industry’s weakest pipeline, can now devote close to $14 billion a year for drug research in a variety of fields. And that has helped alter the landscape of the R&D 15, which once was long dominated by Roche. Other key themes emerge here. One of the most important is the emergence of China as a force in drug discovery. BD teams looking for R&D shortcuts have begun picking up drug candidates in bulk in China, presenting a thorny new reality for US and European biotechs that aren’t able to move as quickly. This year, I’m concentrating on public pharma companies, which have always dominated the list. But it excludes the privately-owned Boehringer Ingelheim, where it’s harder to find details on the pipeline. Takeda also drops off this year’s list, falling just short of the dollar mark needed. And Regeneron marks its arrival as the big biotech invests heavily in its pipeline. — John Carroll The big picture: During 2023, Merck bulked up on M&A deals that pumped up its R&D budget line to a whopping $30.5 billion. In 2024, the pharma giant continued shelling out the big bucks, but without a scale-tipping deal like the $10.8 billion Prometheus acquisition we saw included in the R&D line in 2023. Nevertheless, Merck easily held on to the top spot among the 15 biggest public company R&D spenders on the planet. By the end of last year, Merck had once again dwarfed the old R&D spending leaders like Basel-based Roche, where budget discipline remains a constant. Merck has been shoveling cash into the R&D engine because it’s three years away from a titanic collision with a key patent loss for Keytruda, the $30 billion — and counting — PD-1 behemoth that went a long way to changing the way cancer is treated. Merck continues to rack up big annual increases in Keytruda revenue, which has been essential as the company’s other big earner — Gardasil — fizzled in the face of some ambitious sales projections for the China market. There’s one ace in the hole, with analysts arguing over just how much Merck can make from their late-stage subcutaneous version of Keytruda, which will come with a whole new patent life to profit off of. But whether it’s $6 billion or $7 billion a year, that still leaves a Grand Canyon-sized gap in the budget that must be filled. And the rep of CEO Rob Davis and R&D chief Dean Li will be made or lost on their pipeline strategy for a Keytruda replacement. Or replacements. “The future is less monolithic Keytruda,” Davis said . “It’s going to be a lot of smaller, precision-based therapies aimed at specific tumors or indications.” It’s going to take a lot of smaller drugs to mend a rip that size. That means a long string of deals, including a move to elbow its way to the future of immunotherapy with a rival to Summit’s PD-1/VEGF combo. And that required a turn to China, following what is now a well-beaten path for new drugs that they’ve bet big on. Merck kept the focus on China when it inked a deal just days ago for an oral Lp(a) inhibitor from Hengrui . Novartis recently delayed the timeline for wrapping its Phase 3 study for an antisense candidate for Lp(a) (partnered with Ionis), pushing the results for data on 8,000 patients to the first half of 2026. Merck put up a $200 million down payment on a $2 billion deal for an oral treatment that will need to go through a global program. That’s a low-cost deal in front of a major trial expense, and it offers a chance to leap into a race where orals may well end up ruling the franchise. But it’s no Keytruda. Investors don’t care much for the overall picture. Merck’s shares have dwindled more than 21% over the past year, even as sales kept climbing. Wall Street wasn’t crazy about Merck’s decision to withdraw guidance on Gardasil, at all. And the Keytruda dilemma has created a narrative that has dominated the company for years now. Merck execs can project confidence, but R&D spending illustrates a high level of anxiety. The big picture: You can bet that Roche execs were paying particularly close attention to AstraZeneca’s recent release of a positive, preliminary slice of late-stage data for camizestrant, its oral SERD for hormone receptor-positive, HER2-negative breast cancer. The Basel-based pharma giant has been angling — alongside Eli Lilly — to beat a path to the market with a best-in-class oral SERD that can be expected to rack up billions a year, provided they get in early on a field that has been a primary concern for years. Roche CEO Thomas Schinecker has pegged giredestrant as one of its top late-stage drugs, putting it in the pole position of a chart of potential blockbusters as it waits for late-stage data from their persevERA and evERA trials. It’s in a group of seven pipeline therapies that Roche believes can pave the way to new franchises worth $3 billion or more. AstraZeneca has pegged its rival as a $5 billion-plus earner, offering some added insight here on where the market is focused. But the others include some high flyers that face daunting odds in the clinic, as well as a cluster of rivals that Roche has to race for best-in-class status. Take, for example, the amyloid buster trontinemab, which recently offered an early picture of its ability to target the plaque — cognition was not part of that study, though. And the road for Alzheimer’s drugs is long and frequently twisted, with a questionable marketing future if it fails to do more than slow progression. Prasinezumab has failed a couple of mid-stage studies for Parkinson’s, as investigators try to find a population where it works. Parkinson’s remains one of the toughest targets in the industry, with repeated setbacks for key players — including a rival with the mechanism as Roche’s drug. Trontinemab and prasinezumab are both up for Phase 3 enabling readouts this year. Astegolimab is a dark horse Phase 3 candidate in a group of drugs aimed at taking on Dupixent’s dominant role in COPD. That drug — which inhibits the IL-33 receptor ST2 — was flagged for pivotal readouts this year from the ALIENTO and ARNASA trials. A couple of years ago, Roche fronted $310 million to partner with Alnylam on the RNAi drug zilebesiran for hypertension, which has posted positive mid-stage data. That makes the cut as a major potential player. NXT007 offers a new shot at hemophilia A after Roche took a hit on its gene therapy out of the Spark buyout. Long term, Roche wants to keep building around the Hemlibra franchise, which brought in $5 billion in 2024. In the follow-up category of potential blockbusters, Roche counts four drugs with $2 billion to $3 billion in peak sales potential. That group includes their BTK inhibitor fenebrutinib, which has reportedly done well in Phase 2 for MS. That’s up for a pivotal readout this year, along with vamikibart, which is in two studies called SANDCAT and MEERKAT for uveitic macular edema. As one of the biggest R&D operators in the world, Roche can afford a big pipeline with a number of misses. It’s the one or two big successes in each group of contenders that sustain a company of this size, as it proved yet again with their Regeneron rival Vabysmo, which broke through the $4 billion barrier last year as Tecentriq flattened out and exhibited signs of erosion. Polivy also jumped into the blockbuster club, marking a key marketing success. The key thing for Roche R&D is putting up a slate of credible contenders, with a group of late-stage candidates tackling big diseases and at least one big prospect that looks competitive in the multibillion-dollar class. To that end, Roche continues to selectively snap up new candidates and forge new alliances around the globe. In recent months we’ve tracked an antibody pact with UK biotech Oxford BioTherapeutics, heavily weighted to biobucks as is common in discovery deals. And they went back to the China well for a new deal with Innovent on small cell lung cancer that cost $80 million in upfront cash. Paying $1 billion for the off-the-shelf CAR-T tech at Poseida amounted to a small bolt-on in this world. Roche paid $2.7 billion for Carmot, and had some positive early data to exhibit last year. A lot of this will sour or fizzle out. TIGIT was once a hot prospect, but it’s all been bad news on that front. You win some, you lose some in Big Pharma. Roche has been winning enough to stay on top, but the pressure is always on. The big picture: Pascal Soriot took plenty of painful shots during his early years as CEO of a woeful AstraZeneca — including more than a couple from me — with each setback cause for fresh concern. Slowly building a slate of giant franchises in oncology, and buying Alexion to beef up earnings, ended the fretting. By the end of 2024, AstraZeneca’s top execs could boast of full-year revenue growth of 21%. Industry buzz has Soriot spending big chunks of every year in China, where the company has been working to make a confrontation with the government into a commercial speed bump, hoping to continue to romp and stomp while using its international status and UK headquarters to steer clear of the showdown between the US and China. And it recently underscored the connection by unveiling plans for an expansion of its R&D work in China. Its growing commercial success with proven oncology drugs has spurred Soriot to invest heavily in the pipeline, stretching past cancer into other fields, like obesity. Five years ago, AstraZeneca shelled out $6 billion for R&D in 2019. In 2024, that tally had more than doubled as AstraZeneca surged from a cash-strapped player to an industry leader in research, trailing only Merck as the US outfit urgently tries to engineer a replacement set of drugs for an aging Keytruda franchise. Quite a few analysts are ready to offer their thumbs-up for AstraZeneca’s progress, but the question now is likely to center on whether AstraZeneca can keep its winning streak on track. Case in point: Camizestrant has been built into a $5 billion+ annual prospect. Some observers are ready to sign off on a blockbuster future for the oral SERD drug, especially after a recent Phase 3 win, but temper the enthusiasm with somewhat lower sales expectations. Baxdrostat also gets star billing, as Soriot touts “more than 90 late-stage trials underway with an average non-risk adjusted peak year revenue per trial of $1 billion.” The focus now is on performance in the clinic, but AstraZeneca’s financial results give it considerable range to consider more deals. Soriot picked up baxdrostat — exploring a new mechanism of action for hypertension that investigators have been exploring for close to 20 years — in a $1.8 billion deal for CinCor two years ago. And the pharma giant has helped blaze the BD path through China, leaving it in a position to scoop up fresh assets at discount prices. R&D risk is always huge, but investors have liked the odds. $AZN is up 16% over the past year. The big picture: With biosimilar competition ramping up this year for Stelara, one of J&J’s mainstay mega-franchises ($10.4 billion in 2024), the pharma giant needs to rack up some regulatory wins from the late-stage pipeline. The company’s R&D group breathed a sigh of relief when icotrokinra, its big program for IBD brought in from Protagonist, recently delivered — at least on the major points we could see in the company statement — in an important mid-stage trial of the oral IL-23 therapy. J&J execs, who have been slowly unfolding a pipeline-in-a-product strategy for this drug, believe icotrokinra can be a $5 billion-a-year earner, putting it at the tip of the big phalanx of R&D projects now in the pipeline. Another late-stage drug that gets a lot of attention at J&J is nipocalimab for generalized myasthenia gravis, which has nabbed breakthrough drug status at the FDA as it looks for an OK. And there’s a new fast-track designation for this drug in moderate-to-severe Sjögren’s disease. J&J is a behemoth with a long list of marketed drugs, a fact that comforts risk-averse investors. But the churn tends to deter anyone looking for some quick upside. Its medtech group spent $3.7 billion on R&D last year, helping maintain a stable of products that deliver on the bottom line. That helps keep the numbers steady. And it helps when one-time blockbusters-to-be — I’m talking about aticaprant here — flounders in its Phase 3. J&J had slated the anti-depressant in the $1 billion to $5 billion category, up until a few weeks ago when the drug giant wrote it off for insufficient efficacy. Anyone who’s been following depression R&D for the past 20 years wouldn’t have been too surprised to see yet another Phase 3 fail here. But neuro is still surging on increased confidence that scientists can deliver major drugs for unmet needs. For J&J, the belief helped inspire the Intra-Cellular Therapies buyout for $14.6 billion during JPM, finally breaking the year-plus drought of M&A deals that broke the $5 billion barrier. That deal, like the top drugs in its pipeline, underscores a well-known fact about J&J. The company is a global player in R&D — helping break the mold on China deals when it picked up the cancer drug Carvykti. But while the company can be a world-class drug picker, it’s not known for discovery work. J&J has also long been operating under a cloud brought on by its talc settlement talks, where the numbers people have set aside billions and appear to be close to finally completing a deal to shunt talc into a subsidiary and settle up with the bulk of the lawsuits. It’s manageable, but after 16 years and thousands of suits, J&J’s investors would like to move on. Following its spinout of the consumer division, J&J is on an R&D path — sticking with diseases its researchers understand well — it’s likely to follow for years. And that will keep BD busy. The big picture: AbbVie’s story in recent years has centered primarily around its fierce development and then commercialization of Rinvoq and Skyrizi to bridge its way past the revenue gorge created by Humira’s slow-motion loss of exclusivity. Once the biggest drug in the world, Humira is being steadily eclipsed by biosimilars, but the R&D group has kept the ball rolling with new studies to expand their pair of cash cows. The Botox buyout remains another key storyline as AbbVie proves yet again that it has an excellent set of marketing skills. Mission accomplished on the big moves, which isn’t to be underestimated. That may not add up to be the most exciting R&D story in biopharma in 2025, but it has certainly kept investors happy as AbbVie worked through a top-level executive transition and began to try kickstarting some fresh enthusiasm with a few ambitious deals. AbbVie took a major stab at neuroscience when it bought out Cerevel a couple of years ago for $8.7 billion , landing a lead asset in the field. But that strategy largely came a cropper recently with the failure of emraclidine, once intended to help change the standard for treating schizophrenia. Big Pharma has been making a few careful moves in neuro, but the unknowns are still legion, and the risks are extremely high. Roche’s setback on prasinezumab for Parkinson’s in late 2024 underscored that universal truth. AbbVie is still talking up the prospects of tavapadon as it racks up Phase 3 wins, but the upside isn’t as great, as far as the analysts are concerned. AbbVie was a late arrival to the obesity scene, talking up its potential for less frequent dosing and relatively competitive weight loss data with Gubra’s amylin drug. The BD team brought that in for $350 million upfront. There are some ADCs that the R&D group thinks highly of and a host of low-cost early-stage deals intended to raise its prospects for the future. For now, though, AbbVie is clearly relying on its marketing muscle and experienced research groups to keep building key franchises — which it is really, really good at. The jury’s out on whether AbbVie can add some major new franchises to grow the company faster. But they have time now. The big picture: Every time a CEO or biotech investor starts making the case for more M&A, often on background, they inevitably point to Bristol Myers as the poster child for Big Pharma pipeline demand. It faces huge looming patent losses — let’s start with Opdivo — and has a couple of years to wait for the kind of registrational data needed for its most promising late-stage drugs. The pharma giant has certainly been a player in the M&A club, snapping up Karuna ( $14 billion ), RayzeBio ( $4.1 billion for a radiopharmaceutical drug in a hotly contested arena) and Mirati ( $5.8 billion for KRAS) along the way. But recent moves aimed at cutting costs while boosting work in Phase 3 underscore just how tricky this can be. And all the buzz about its need for pricey buyouts hummed right along through a muted year of dealmaking in 2024. By all accounts, a few analysts on the Street seem satisfied that Cobenfy — out of Karuna — is on track to a blockbuster future, starting with schizophrenia and potentially expanding into Alzheimer’s. But its launch late last year didn’t come close to satisfying the skeptics rooting for more BD — which has been encouraged by a set of execs ready and willing to talk up their expectations on the acquisitions side of the business. Among the drugs in late-stage work, you’ll find new multiple myeloma therapies, which Samit Hirawat talked up in the last quarterly run-down. “ … It is very important to continue to develop small molecules, which are easy to deliver and can be combined with the standard of care therapies. And that’s exactly where iberdomide, mezigdomide sit,” he added, highlighting head-to-heads with pomalidomide (Pomalyst) — facing near-term generic competition — and Revlimid — already losing ground to copycats. Overall, costs have been headed up in R&D at Bristol Myers, and with all hands on deck for a Phase 3 revival of the portfolio, the pharma giant is poised to keep pouring money into drug development. The big picture: The CEO/R&D chief duo of David Ricks and Daniel Skovronsky took home the big prize with the successful launch of the drug juggernaut Zepbound/Mounjaro, which has emerged as the leading obesity/type 2 diabetes treatment in a world hungry for effective fat busters. They aced the main prize in the GLP-1+ field with their own particular take, and they are following up with additional studies to prove efficacy where it can gain reimbursements — while following up with an oral that is aimed at cementing this category in its favor for years to come. That storyline has proved enormously persuasive with investors, as Eli Lilly’s share price has grown 64% over the past two years and its biggest supporters among the analysts glow with enormous projections. But with that much money on the table, it’s no major surprise to see Novo Nordisk double down on its own obesity franchise — a story that’s had a few problems — while the competition aims at doing it better with fewer side effects and a more appealing form of administration has grown into a mob of biopharma companies. It does make you wonder where peak obesity lies. But Lilly is determined to hold onto the lead, no matter how rough this ride may get. And it promises to pay off in the tens of billions per year. To that end is a prospective 2026 launch of orforglipron, an oral GLP-1. Analysts have been on high alert for upcoming T2 data, which Lilly forecasts should look good in comparison to Novo’s semaglutide. That’s the key competitive number they’re looking for. There’s also the multi-targeted retatrutide in the pipeline to consider, where investigators tracked a 12% weight loss in a mid-stage study. Novo certainly has, inking a deal with China’s United Laboratories for an early-stage rival treatment as it looks to be competitive in a range of targets aside from GLP-1. That deal also underscores how Big Pharma can steal a march on a rival drug by scouting R&D programs in China. There’s also remternetug for Alzheimer’s, a quarterly injection to remove amyloid plaque, versus the monthly injection their approved drug donanemab (Kisunla) uses. Analysts once projected billions in upside for the new Alzheimer’s drugs making their way into the market, but skeptics wonder if their modest benefits for patients will win doctors and large numbers of patients over. Lilly’s late-stage cardio drug lepodisiran often earns a mention from leadership, along with their oral follow-up muvalaplin. Then there’s the KRAS contender olomorasib. Add in the occasional buyout — like Morphic — and you’ll get a picture of an ambitious pipeline funded with growing revenue from an effectively marketed drug with the kind of legs that can sustain a company like this for years to come. Given the company’s credibility in drug development, you’re likely to agree that Eli Lilly should never be underestimated. The big picture: By the end of 2022, Pfizer’s rep was pure gold. There was a king’s ransom in revenue for the multinational operation as it capitalized big time on its rapidly successful alliance with BioNTech for their mega-franchise mRNA vaccine to combat Covid. And CEO Albert Bourla basked in the glow of accolades for helping save the world — with the exception of some stray trolls. Then the world turned, vaccine demand plummeted far past most projections and Pfizer was left to pick up the pieces with a revised R&D game plan and revenue that only modestly improved in 2024 after bottoming out at $59.5 billion in ’23. Now, instead of continuing accolades for a truly historic vaccine rollout, analysts were reminded of Pfizer’s long track record for hit-and-miss performance in R&D and commercial ops. And it remains a big player in vaccines, where the long reach of the new Trump administration and its vaccine critics has extended to scrubbing out references to mRNA. Those persistent doubts led Pfizer to recruit Citi analyst — and longtime Pfizer doubter — Andrew Baum to help sell the company’s innovation plans. And he likely is more aware than most of just how hard that is as Pfizer looks to largely tread water on the numbers side this year. Buying Seagen set its course for a higher profile in oncology, which was on display as Bourla cheered their late-stage programs in his recent assessment of what’s ahead. Bourla earlier tapped oncology chief Chris Boshoff to take over R&D from Mikael Dolsten, signaling that it’s relying on a slate of cancer drugs to help replace Ibrance and Xtandi as those big blockbusters lose exclusivity in a couple of years — mere ticks of the clock in drug development cycles. So it’s no surprise to see company execs talking up prospects for the CDK4 inhibitor atirmociclib, now in a Phase 3 breast cancer study. But they took a nasty hit a few weeks ago when vepdegestrant, its protein degrader partnered with Arvinas, fell short in another breast cancer study. Baum also has his work cut out for him talking up Pfizer’s big plans for their oral obesity drug danuglipron, with analysts shaking their heads over a twice-daily dosing as rivals make progress on that front with drugs that may be much better positioned. Its cachexia drug ponsegromab, meanwhile, has had its late-stage development plan trimmed. Underscoring the doubts about Pfizer, analysts haven’t liked watching its sales of RSV vaccine Abrysvo plunge in a turbulent market for everyone involved. The pharma player has to perform consistently on sales if it expects to overcome the skeptics at this point. Add it all up and Pfizer looks like it will continue to operate under a cloud for some time to come, needing to establish a solid track record of significant new approvals and reliable marketing success. In the meantime, look for the company to keep shelling out big dividends to keep investors happy. The big picture: Under the watchful eye of chairman Joerg Reinhardt, Novartis CEO Vas Narasimhan has always proved ready to bring out the scalpel — or the axe — to trim away at its enormous global structure. So no analyst would have been surprised to see Novartis cutting away at its commercial ops in anticipation of a looming patent loss for its heavyweight therapy Entresto. A cliff like that would make many pharmas amp up R&D spending in a big way. Novartis actually cut back in 2024. The other Basel-based pharma giant is playing this one carefully for Wall Street, defending what’s left of patent exclusivity while signaling an LOE for Entresto in the middle of the year. It’s boosted revenue from Entresto in advance of the inevitable decline of its star drug — like pumping money from a dying well — and it’s pushing its other portfolio drugs hard, looking to make up for its blockbuster losses. That push includes building the franchises for Fabhalta, which just won its third approval, along with other drugs like Leqvio and Scemblix. Novartis has maintained a big focus in R&D on its radioligand portfolio, along with cell and gene therapies and RNA. Its late-stage pipeline includes OAV101 IT for spinal muscular atrophy, using a new delivery method aimed at widening the patient population for Zolgensma and now lining up for regulatory approvals. And there’s a big emphasis on votoplam (PTC518) for Huntington’s, in-licensed from PTC. Earlier this year Narasimhan and his execs spent a fair amount of time talking up the prospects of votoplam, which has to complete a mid-stage program successfully before Novartis takes over Phase 3. Huntington’s is wide open for anyone who can move the bar on this fatal neurodegenerative disease. But it’s also incredibly difficult to master, as Novartis knows from its own recent failure in the field with branaplam. Sage has also hit the wall here. But Novartis feels it’s learned a lot from its own setback — enough to believe that they can take the command here. Novartis, despite a busy pipeline overall, has a pretty thin set of late-stage drugs to tout, which led the Wall Street Journal to ask where Narasimhan expects to get its next round of drugs as Novartis sets out to perform with annual revenue increases in the mid-single digit range. Novartis spent a billion in cash on its Huntington’s alliance, underscoring just how careful they are with the R&D budget, which fell year-over-year in 2024. Not surprisingly, he centered on “smaller deals” while insisting he won’t make a move in obesity unless the BD team can line up something particularly distinctive. He also counts himself happy with their 2022/2023 reorganization. Happy, though, doesn’t mean content to leave things be. Novartis is always turning over stones to see where else it can cut. It adds up. And it’s shown zero interest in doing anything splashy. Its recent buyouts underscore that careful approach: MorphoSys was on the outer edge of the $1 billion to $3 billion range where Novartis prefers to play in M&A. At Novartis, financial discipline is a core value. And it’s part of the buttoned-down Swiss approach that isn’t expected to change. The big picture: There are a lot of moving parts at GSK, and not all are headed in the right direction. Its RSV vaccine sales have been on a roller coaster ride. The UK pharma’s big bet on Shingrix was dinged by slipping sales last quarter, all while the Trump administration helped cast a pall over vaccines in general that may well endure for four years. The vaccine market in China has also been wobbly, as Merck can attest to with Gardasil. On the other hand, GSK once again has high hopes for Blenrep, which was yanked from the market in 2022 after flunking a confirmatory study. The IL-5 therapy depemokimab has excited great expectations for £3 billion in annual sales, following up on the success of their asthma drug Nucala. All the while the BD group keeps turning up new deals that bolster their case without weighing heavily on the numbers side. And CEO Emma Walmsley, now an eight-year veteran in the top spot, is promising to move its top line to $50 billion, moving from £31.4 billion last year to 40 billion — a 27% increase in seven years. A lot of that increase will depend on how GSK’s commercial arm can capitalize on new therapeutics like their newly approved antibiotic gepotidacin. Commercial chief Luke Miels has cited analysts’ estimates for up to $1.25 billion for that program, but not everyone is nearly that enthusiastic about the near-term chances for a new antibiotic that could take years to gain a firm footing in the market. GSK has never been flashy. The stock is down about 10% over the past year. If you pull back over a three-year timeline, since GSK spun off its commercial group, the stock is down 19%, all of which has some analysts wondering if the large-cap company may once again become a target of the activist crowd. The big picture: I met Paul Hudson in Paris five years ago, when he stepped in as the new Sanofi CEO after a lengthy dry spell in R&D. Since then, he’s proven time and again that he’s ready and willing to invest in drug research, despite the inevitable ups and downs associated with bigger pipelines. A bit more than two years ago he was concentrating on what he called three major blockbuster candidates (€5 billion-plus): The OX40 drug amlitelimab, frexalimab and SAR441566, an oral TNFR1. And he was ready to sacrifice some profitability to move a pipeline where he counted another nine blockbuster candidates, mostly in immunology and inflammation. He kept that promise, with a boost in R&D spending of 14% in 2024 as Sanofi joined the industry migration out of consumer — staking its future on its ability to push new drugs to big futures. A few days ago Leerink noted that Sanofi was still juggling OX40 drugs to see whether amlitelimab, or its OX40L/TNF bispecific nanobody, would go into Phase 3 for hidradenitis suppurativa. That drug is in Phase 3 in atopic dermatitis and in Phase 2 in asthma and several other indications. Frexalimab failed a Phase 2 for Sjögren’s syndrome last year, narrowing its potential. That came with a Phase 3 failure of venglustat — another one of Hudson’s original top prospects — which nicked off part of its attraction as well. The next tier, where Hudson forecasts sales of €2 billion to €5 billion includes: Sanofi had one huge ace in the hole when Hudson took over the hand. It could rely on big sales of Dupixent ($13 billion in global sales last year) to keep it going in search of a new portfolio. And their marketing expertise in the field — built thanks to their alliance with Regeneron, which did the heavy lifting on the innovation side — would benefit any new drugs to warrant a regulatory approval while easing Aubagio out as generics took hold. The big picture: After hustling its way to the front of the GLP-1 line, Novo Nordisk is now all about the fierce rivalry it’s facing from Eli Lilly while positioning itself against any other entries that could sap its brilliant future in obesity. And that is no easy task, as execs have learned over the past year, while its stock plummeted 45% after peaking out as an obesity darling last summer. It turns out that superheating the stock price set up a supercooling series of events. After seeing explosive growth in revenue last year, Novo’s executive team is counseling analysts about a more modest growth path in 2025 as Eli Lilly brings the heat and pricing pressure grows. One of the big jobs they had to complete ASAP was being able to make enough semaglutide to satisfy the market and get off the drug shortage list — battling back against compounders who were carving up market share. While Novo Nordisk hasn’t been keeping up with average R&D spend among the top 15 — which generally comes in around the low 20s as a percentage of revenue — even 16.5% allowed for a 50% hike in R&D spending last year. In recent weeks Novo not only reorganized its growing R&D ops, it also struck back-to-back deals for new obesity drugs in an effort to stay ahead of the mob out to grab a share of the action. Now diabetes/obesity/MASH will be one R&D cluster focus, with cardio/chronic kidney disease and rare diseases making up the other two legs of its three-pronged research strategy. And like every other company in the R&D 15, it will rely on AI to make better bets on experimental drugs. Normally, that might make an intriguing proposition for investors, but analysts have been more focused on repeated setbacks in the clinic than the prospective benefits of a revised strategy. Novo Nordisk recently aired lackluster data for CagriSema, its follow-up drug that is a combination of the amylin analog cagrilintide and GLP-1. One of the big downsides to GLP-1 is the side effects of the drug, which the amylin analog is thought to limit while building weight loss. But it barely edged a high dose of Zepbound, leaving Lilly in the lead of the expectations game. And it earlier fell far short of the company’s stated expectation that it could trigger 25% weight loss. There’s lots more on the way, but Novo Nordisk has a lot riding on a head-to-head between CagriSema and Zepbound. Those data will come later this year, and failure is not an option. The big picture: Amgen has added a meaningful amount to its R&D budget, but it’s still hanging on in the second tier of the R&D 15. As always with CEO Bob Bradway, there’s a well-thought-out strategy that he’s pursuing — and selling to investors as the best path forward. And as always, the stakes are incredibly high. While looking to build on some existing drug franchises, Bradway once again used his Q4/2024 call with analysts to put the spotlight squarely on Amgen’s top prospect in the pipeline. This year it’s MariTide, an obesity drug that is looking to find a patch of marketing sun in the Big Kahuna of all drug rivalries. But it’s one tough sale. A few months ago, in a story covered by Max Bayer at Endpoints News , Amgen saw its stock take a dive on positive mid-stage data that illustrated a 20% weight loss for the drug. Once upon a time, you could have parlayed that into star status on Wall Street. But no more. It looked a little second-rate compared to the megablockbuster leaders in obesity, Novo Nordisk and a romping, stomping Eli Lilly, even if it can be effective at lower dosing. Amgen has a new take on the glucose-dependent insulinotropic polypeptide (GIP) receptor, blocking it instead of activating it. But it may just be the amped-up GLP-1 component that is delivering the benefit. Amgen has a huge Phase 3 for this one to answer all its questions, but you can see a few analysts are taking to the sidelines on this one, not quite won over by the dosing and design. On the upside: Any significant piece of obesity can be huge, even if in this case it’s relatively small compared to the leaders’ market share. On the downside: A big lead counts for a lot when you’re breaking new ground in therapeutic research, and Amgen definitely does not have the lead here. Amgen, though, will stick to its story. While it’s far from the top 10 in terms of R&D spending, the company has always punched above its weight when it comes to touting an experimental drug. So it was no surprise to see ex-Novartis vet Jay Bradner pick up his first Q4 call at Amgen by keeping his sights set on MariTide. But Bradner is also quick to highlight other late-stage prospects, topped by its Lp(a) drug olpasiran — now one of several drugs in the mix for this target — while waiting on the FDA decision for Uplizna. There’s also the Phase 3 program for rocatinlimab in atopic dermatitis, which has the potential to pursue other pathways, provided the data are strong. That could prove a major caveat, though, While Tim Anderson sees Amgen as 12 to 18 months ahead of Sanofi’s rival OX40 mab amlitelimab, he called one of the mid-stage data cuts “underwhelming” compared to Dupixent, hampered by some safety concerns. The big picture: Gilead has been anchored by HIV for years now, able to take multiple hits on the R&D side without triggering too much angst among investors. And Gilead CEO Daniel O’Day — who celebrated six years in the top post — has been winning over some mild converts to the cause recently, including Tim Anderson. Anderson, like the rank-and-file investor group, is comforted by Biktarvy’s big role in the HIV arena, where Gilead mints money. And he’s intrigued by the upside of a couple of late-stage plays, including anito-cel, which Gilead — partnered with Arcellx — believes can cut down Carvykti from J&J and Legend. That depends a lot on the safety profile that has been emerging in clinical trials. But at this stage, Gilead has seen a slate of oncology prospects go down in flames, which hasn’t done much to increase confidence in a cancer drug now. On the other hand, maybe they are due for a win. If they can cut into line with Carvykti, which is linked with Parkinson’s and other serious side effects, it has the potential to earn billions. And that would push them to their goal of getting 30% of revenue from oncology, rather than continue to rely so heavily on its longtime dominance in HIV. But there are some big ifs along the way, including the developers’ plans to look for an accelerated approval of the CAR-T. The big picture: Regeneron was close to making the R&D 15 in 2023, and it made it through last year with a surge of research spending in 2024 that slipped ahead of Takeda, based on their last four quarters. Regeneron arrives as the only company that still counters its two remarkable founders in the top posts: Science chief George Yancopoulos and CEO Len Schleifer. They got to this point by creating a company that is frequently held up as the gold standard of biotech startups, building two giant franchises in Dupixent (partnered with Sanofi) and Eylea. Now Eylea has biosimilar trouble, but Dupixent is still romping and stomping on the numbers side, giving Regeneron a nice runway to build new drugs. Tim Anderson at Bank of America counts two key drugs in the late-stage pipeline, and one to watch now in Phase 2. There’s fianlimab, a LAG3 treatment in frontline melanoma that hasn’t received a ton of attention. Anderson notes that Regeneron is several years behind Bristol Myers in LAG3, with 2030 sales set under the $900 million mark. LAG3 has had a number of problems in the clinic, though, and the jury is definitely out on what the potential is here. And there’s IL-33 mAB itepekimab, also partnered with Sanofi. Not the next-gen successor to Dupixent as once billed, Anderson still sees blockbuster potential. Then there’s trevogrumab — an anti-myostatin — and the anti-activin A garetosmab for obesity, in Phase 2 development with a host of rivals in the clinic. Of more immediate importance commercially, Regeneron has tagged linvoseltamab , its BCMAxCD3 drug delayed for manufacturing reasons, as a likely near-term entry for multiple myeloma. Sales projections are relatively muted, though. There’s also a CRISPR drug partnered with Intellia, NTLA-2001 for ATTR amyloidosis . Of everyone on the R&D 15, Regeneron is reinvesting a larger percentage of its revenue than any other player. Thirty-seven years after the biotech was created, the founders still see themselves on the cutting edge of drug research.

WILMETTE, Ill., March 31, 2025 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for patients with unmet medical needs, today announced fourth quarter and full-year 2024 financial results and summarized recent developments. “2024 was a productive year for Monopar, with the in-licensing of ALXN1840, the initiation of two first-in-human radiopharma Phase 1 clinical trials, and the strengthening of our balance sheet with net proceeds of over $55 million from financings,” said Chandler Robinson, MD, Chief Executive Officer of Monopar. “We are especially grateful to the Wilson disease patients. Their testimonies and support are what provided the opportunity for Monopar to progress ALXN1840 toward an NDA filing.” Recent Program Developments ALXN1840 – Plan to Submit NDA with FDA for Wilson Disease in Early 2026 Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised, leading to damage from toxic copper build-up in tissues and organs such as the liver and brain. ALXN1840 is a potent binder and mobilizer of copper, as demonstrated in a Phase 3 clinical trial that met its primary endpoint. In October 2024, Monopar announced the execution of a worldwide exclusive license to ALXN1840 with Alexion, AstraZeneca Rare Disease (“AZ”). As part of this transaction, AZ received a total cash payment of $4.0 million, was issued 9.9% ownership of Monopar’s outstanding common stock, and is entitled to receive regulatory approval and sales milestones along with a tiered royalty based on net sales. MNPR-101 – Currently Enrolling Phase 1 Imaging and Therapeutic Oncology Trials Imaging agent MNPR-101-Zr (MNPR-101 conjugated to zirconium-89) and therapeutic agent MNPR-101-Lu (MNPR-101 conjugated to lutetium-177) target the urokinase plasminogen activator receptor (“uPAR”), which is expressed in numerous aggressive cancers such as triple-negative breast, colorectal, and pancreatic cancers. Initiated Phase 1a clinical trial for novel therapeutic radiopharmaceutical MNPR-101-Lu in patients with advanced cancers Dosed first patient with MNPR-101-Lu in December 2024 Presented encouraging human clinical imaging and dosimetry data of MNPR-101-Zr at the European Association of Nuclear Medicine (“EANM”) 2024 Annual Congress uPAR expression, as detected by MNPR-101-Zr, has been seen to date in breast, colorectal, pancreatic, adrenocortical carcinoma, and ovarian cancer patients Filed a patent application covering new therapeutic radiopharmaceuticals based on a novel family of linkers used to connect radioisotopes with targeting agents, including Monopar’s uPAR targeting antibody MNPR-101 Recent Financings In Q4 2024, we raised net proceeds of over $55 million from the following financings: On October 30, 2024, pursuant to a placement agent agreement with Rodman & Renshaw LLC, we sold 1,181,540 shares of our common stock at $16.25 in a public offering, yielding net proceeds of approximately $17.8 million. On December 23, 2024, pursuant to an underwriting agreement with Piper Sandler & Co., we sold 798,655 shares of our common stock at $23.79 per share in a public offering. Concurrently with the public offering, we completed a private placement of 882,761 pre-funded warrants to purchase shares of common stock to an institutional investor at a purchase price of $23.789 per pre-funded warrant. The net proceeds of the December 23, 2024, public offering and private placement were approximately $37.4 million. Results for the Fourth Quarter and Year Ended December 31, 2024, Compared to the Fourth Quarter and Year Ended December 31, 2023 Cash and Net Loss Cash, cash equivalents and short-term investments as of December 31, 2024, were $60.2 million. Monopar expects that its current funds will be sufficient to continue operations at least through December 31, 2026, in order to: (1) assemble a regulatory package and file an NDA for ALXN1840; (2) continue to conduct and conclude its first-in-human imaging and dosimetry clinical trial with MNPR-101-Zr; (3) continue to conduct its first-in-human therapeutic clinical trial of MNPR-101-Lu; (4) advance its preclinical MNPR-101-Ac program into the clinic; and (5) invest in internal research and development projects to expand its radiopharma and rare disease pipeline. Net loss for the fourth quarter of 2024 was $10.9 million or $2.23 per share compared to $1.8 million or $0.60 per share for the fourth quarter of 2023. Net loss for the year ended December 31, 2024, was $15.6 million or $4.11 per share compared to $8.4 million or $3.04 per share for the year ended December 31, 2023. Research and Development (“R&D”) Expenses R&D expenses for the fourth quarter of 2024 were $9.9 million compared to $1.0 million for the fourth quarter of 2023. This increase of $8.9 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840 and (2) an increase of $0.4 million in R&D salaries, partially offset by a net decrease of $0.1 million in other R&D expenses. R&D expenses for the year ended December 31, 2024, were $13.0 million compared to $5.6 million for the year ended December 31, 2023. This increase of $7.4 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840; (2) an increase of $0.3 million in R&D personnel expenses; and (3) a net increase of $0.1 million in other R&D expenses, partially offset by a decrease of $1.6 million in trial closure related expenses. General and Administrative (“G&A”) Expenses G&A expenses for the fourth quarter of 2024 were $1.2 million, compared to $0.9 million for the fourth quarter of 2023. This increase of $0.3 million was primarily due to: (1) an increase of $0.1 million in G&A personnel salaries; (2) an increase of $0.1 million in G&A consulting fees; and (3) an increase of $0.1 million in Delaware franchise taxes. G&A expenses for the year ended December 31, 2024, were $3.2 million, compared to $3.2 million for the year ended December 31, 2023. About Monopar Therapeutics Inc. Monopar Therapeutics is a clinical-stage biotechnology company with late-stage ALXN1840 for Wilson disease, and radiopharma programs including Phase 1-stage MNPR-101-Zr for imaging advanced cancers, and Phase 1a-stage MNPR-101-Lu and late preclinical-stage MNPR-101-Ac225 for the treatment of advanced cancers. For more information, and links to SEC filings that contain detailed financial information, visit: https://ir.monopartx.com/annual-reports. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of these forward-looking statements include: that Monopar plans to submit an NDA for Wilson disease in early 2026; and that Monopar expects that its current funds will be sufficient to continue operations at least through December 31, 2026. The forward-looking statements involve risks and uncertainties including, but not limited to: uncertainties related to the regulatory discussions that Monopar intends to initiate related to ALXN1840 and the outcome thereof; that radiation dosimetry analytics in the future may not be consistent with the estimated data generated thus far; that Monopar may not find enough patients to successfully enroll its MNPR-101-Lu therapeutic study; that the Phase 1 imaging and dosimetry clinical trial in advanced cancer patients with MNPR-101-Zr may not yield consistently satisfactory results; that future preclinical, including MNPR-101-Ac, or clinical data may not be as promising as the data to date; that MNPR-101-Zr and/or MNPR-101-Lu may cause unexpected serious adverse effects or fail to be effective against the cancer tumors in humans; that the trials could result in a clinical hold should there be a serious adverse event; the rate of market acceptance and competitiveness in terms of pricing, efficacy and safety, of any products for which Monopar receives marketing approval, and Monopar’s ability to competitively market any such products as compared to larger pharmaceutical firms; Monopar’s ability to raise sufficient funds in order for the Company to support continued preclinical, clinical, regulatory, precommercial and commercial development of its programs and to make contractual milestone payments, as well as its ability to further raise additional funds in the future to support any existing or future product candidate programs through completion of clinical trials, the approval processes and, if applicable, commercialization; and the significant general risks and uncertainties surrounding the research, development, regulatory approval, and commercialization of imaging agents and therapeutics. Actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Monopar's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Monopar undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Any forward-looking statements contained in this press release represent Monopar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. CONTACT: Monopar Therapeutics Inc. Investor Relations Quan Vu Chief Financial Officer vu@monopartx.com Follow Monopar on social media for updates: X: @MonoparTx LinkedIn: Monopar Therapeutics Released March 31, 2025

点击蓝字关注我们本周，热点较多。首先看审评审批方面，国内外都有两个重磅药获批，国内来说，科睿药业抗流感1类新药玛舒拉沙韦获批上市，国外而言，first-in-class口服抗生素获FDA批准上市，成为近30年来首个获批治疗uUTI的新型口服抗生素。其次看研发方面，多个药物取得重要进展，值得一提的就是，中美瑞康公布小核酸癌症新药积极结果，完全缓解率超66%，但比较遗憾的是，Cassava Sciences阿尔茨海默病新药Ⅲ期研究失败；最后是交易及投融资方面，比较值得关注的就是，默沙东近20亿美元引进恒瑞Lp(a)抑制剂。本期盘点包括审评审批、研发以及交易及投融资三大板块，统计时间为2025.3.24-3.28，包含25条信息。 审评审批NMPA上市批准1、3月27日，NMPA官网显示，青峰医药下属子公司科睿药业1类新药玛舒拉沙韦片（GP681片）获批上市，用于既往健康的12岁及以上青少年和成人单纯性甲型和乙型流感患者的治疗，不包括存在流感相关并发症高风险的患者。玛舒拉沙韦片是青峰医药与银杏树药业联合开发的一种聚合酶酸性蛋白（PA）抑制剂，患者全病程只需服药一次。申请2、3月24日，CDE官网显示，Plethora Solutions和复星医药共同申报的5.1类新药利多卡因丙胺卡因气雾剂（研发代号：PSD502）申报上市，用于治疗早泄。这是一款利多卡因及丙胺卡因的专有配方，为一款定量透皮喷雾，最早于2013年11月在欧盟获批上市，2018年12月，复星医药控股子公司万邦生化医药获得该产品在中国商业化权益。3、3月25日，CDE官网显示，施维雅申报的5.1类新药艾伏尼布片新适应症申报上市，推测适应症为联合阿扎胞甘一线治疗携带易感IDH1突变的AML患者。艾伏尼布片是一种针对IDH1突变酶的口服靶向抑制剂，此前已作为“临床急需境外新药”在国内获批，用于治疗携带IDH1易感突变的复发或难治性急性髓系白血病（AML）成人患者。临床批准       4、3月24日，CDE官网显示，恩华药业1类新药NH140068片获批临床，拟开发治疗精神分裂症。NH140068是一款适于口服的多种神经递质受体激动剂，为新一代治疗精神分裂症的创新药。本次是该产品首次在中国获批临床。5、3月25日，CDE官网显示，科伦博泰1类新药SKB107注射液获批临床，拟开发用于晚期实体瘤骨转移。这是该公司与西南医科大学附属医院共同开发的靶向肿瘤骨转移的放射性核素偶联药物（RDC）药物。本次是该产品首次在中国获批IND。6、3月25日，CDE官网显示，映恩生物1类新药注射用DB-2304获批临床，拟开发治疗系统性红斑狼疮。DB-2304是映恩生物自主研发的靶向BDCA2这一浆细胞样树突状细胞（pDC）特异靶点的ADC产品，具有潜在“first-in-class”。7、3月25日，CDE官网显示，复宏汉霖的HLX79注射液获批Ⅱ期临床，联合利妥昔单抗（汉利康）治疗活动期肾小球肾炎。HLX79是复宏汉霖许可引进的一款潜在“first-in-class”人唾液酸酶融合蛋白，2024年12月，复宏汉霖与Palleon达成一项9530万美元的授权合作，获得HLX79在中国的独家许可。8、3月27日，CDE官网显示，华东医药1类新药HDM3019获批临床，拟开发治疗类风湿关节炎。HDM3019是靶向OX40L和TNFα的双特异性抗体。华东医药于2024年8月与IMBiologics达成独家许可协议，获得两款自身免疫性疾病新药在中国等37个亚洲国家的权益，其中就包括了这款IMB-101。该项合作的总金额超3亿美元。9、3月27日，CDE官网显示，阿斯利康旗下Alexion的1类新药Eneboparatide注射液获批临床，拟开发治疗慢性甲状旁腺功能减退症。这是一款治疗性多肽，2024年3月，阿斯利康宣布以10.5亿美元收购罕见内分泌疾病领域生物技术公司Amolyt Pharma，从而获得这款名为eneboparatide（AZP-3601）的Ⅲ期临床阶段研发项目。10、3月27日，CDE官网显示，礼来申报的1类新药注射用LY4052031获批临床，拟单药用于治疗晚期或转移性尿路上皮癌或其他实体瘤。这是一款在研的抗Nectin-4抗体偶联药物（ADC），正在国际范围内开展Ⅰ期临床研究。本次是该产品首次在中国获批IND。优先审评11、3月28日，CDE官网显示，默沙东的Clesrovimab注射液拟纳入优先审评，用于即将进入或出生在第一个呼吸道合胞病毒（RSV）流行季的新生儿和婴儿预防RSV所致的下呼吸道感染。Clesrovimab是一种在研的半衰期延长的单抗，可作为被动免疫手段，用于预防RSV疾病。2024年12月，该产品向FDA批准上市，用于保护婴儿在其首个RSV季节免受RSV疾病的侵害。FDA预定在2025年6月前完成审评。突破性疗法12、3月27日，CDE官网显示，恒瑞医药1类新药HRS-5965胶囊拟纳入突破性治疗品种，适应症为原发性IgA肾病。HRS-5965为一款补体因子B抑制剂。该产品针对原发性IgA肾病适应症目前正处于Ⅱ期临床阶段。HRS-5965的首个Ⅲ期临床正在进行中，旨在评估HRS-5965胶囊对比一款C5补体抑制剂治疗阵发性睡眠性血红蛋白尿（PNH）的有效性与安全性。FDA上市批准13、3月26日，FDA官网显示，GSK的Gepotidacin（商品名：Blujepa）获批上市，用于治疗单纯性尿路感染（uUTI）的成人及12岁以上青少年患者。Gepotidacin是一款具有独特作用机制的口服“first-in-class”抗生素。14、3月26日，FDA官网显示，Exelixis的卡博替尼新适应症获批，用于治疗既往接受过治疗、不可切除的、局部晚期或转移性的、分化良好的胰腺神经内分泌肿瘤（pNET）和胰腺外NET（epNET）儿童（≥12岁）和成人患者。这是第一个获FDA批准用于系统治疗无论原发肿瘤部位、分级、生长抑素受体表达和功能状态的经治NET的药物，于2012年11月在美国获批上市。临床批准15、3月24日，FDA官网显示，神济昌华的SNUG01获批Ⅰ/Ⅱa期国际多中心注册临床试验，用于治疗肌萎缩侧索硬化（ALS）。SNUG01是以重组腺相关病毒9型（rAAV9）为载体，通过鞘内注射（IT）的方式，将人源TRIM72基因靶向递送至神经元。16、3月24日，FDA官网显示，云顶新耀的EVM14注射液获批临床。EVM14是一款靶向多种肿瘤相关抗原（TAA）的通用型的现货肿瘤治疗性疫苗，拟用于非小细胞肺癌、头颈癌等多种癌症的治疗。该产品通过将编码多种肿瘤相关抗原的mRNA原液包封在脂质系统中配制而成。优先审评17、3月25日，FDA官网显示，赛诺菲的Tolebrutinib获优先审评，用于治疗非复发性继发进展型多发性硬化症（nrSPMS）并延缓成人患者独立于复发活动的残疾进展，PDUFA日期为2025年9月28日。欧盟也正在审评该药的上市申请。如果获得批准，Tolebrutinib将成为第一种也是唯一一款既能治疗nrSPMS又能减缓残疾累积而不受复发活动影响的脑穿透性BTK抑制剂。研发临床状态18、3月24日，索元生物宣布，其DB107治疗新诊断的高级别胶质瘤的临床Ⅰ/Ⅱ期试验首例受试者完成入组。这是一项评估DB107在切除时和术后静脉注射，联合DB107FC和放射治疗或DB107FC、替莫唑胺(TMZ)和放射治疗对新诊断的高级别胶质瘤患者进行治疗的研究，计划招募70名患者，证明DB107在生物标志物阳性脑瘤患者中无进展生存率的改善。临床数据19、3月24日，Opthea Limited公布了Sozinibercept治疗湿性年龄相关性黄斑变性（wAMD）的Ⅲ期COAST研究。结果显示，该研究未达到主要终点。在总体人群中，Sozinibercept（每4周1次）联合阿柏西普组、Sozinibercept（每8周1次）联合阿柏西普组和安慰剂联合阿柏西普组的BCVA评分分别增加了13.5个字母、12.8个字母和13.7个字母，组间p值分别为0.86和0.42。Sozinibercept是一款靶向血管内皮生长因子受体3（VEGFR3）的Fc融合蛋白，可阻断VEGF-C、VEGF-D与VEGFR2、VEGFR3的结合。20、3月24日，中美瑞康公布了RAG-01治疗非肌层浸润性膀胱癌（NMIBC）Ⅰ期临床试验的积极初步数据。数据显示，在接受卡介苗（BCG）治疗失败的患者中，最低两个剂量组的原位癌（CIS）患者完全缓解率（CR）达到66.7%，且安全性表现优异。RAG-01是一种创新性的saRNA（小激活RNA）疗法，旨在上调p21肿瘤抑制基因的表达。21、3月25日，Cassava Sciences公布了Simufilam治疗轻度至中度阿尔茨海默病（AD）的Ⅲ期REFOCUS-ALZ研究数据。数据显示，未达到主要终点。此前，该研究因Ⅲ期RETHINK-ALZ研究失败在2024年11月25日终止开展。Simufilam是一款靶向错构的细丝蛋白A（FLNA）的口服小分子药物。22、3月28日，劲方医药公布了氟泽雷塞联合西妥昔单抗一线治疗NSCLC的最新Ⅱ期（KROCUS）数据。数据显示，该药具有优秀的总体疗效、显著的脑转移患者肿瘤缓解、以及优于二线及以上氟泽雷塞单药疗法的安全性/耐受性；相较于包含免疫疗法的当前一线NSCLC标准治疗，KROCUS方案也提示了针对KRAS突变患者的更优治疗潜力。氟泽雷塞为一款KRAS G12C抑制剂，由信达生物和劲方医药合作开发，是中国批准上市的首个KRAS抑制剂药物。交易及投融资23、3月24日，联邦制药宣布，其全资附属公司联邦生物已与诺和诺德签订协议。诺和诺德将获得UBT251全球（不包括中国大陆、中国香港、中国澳门和中国台湾地区）的开发、生产和商业化权益。联邦生物保留中国权益。UBT251是一款长效GLP-1R/GIPR/GCGR三重激动剂，拟开发用于治疗肥胖症、2型糖尿病和其他疾病。根据协议，联邦生物将获得2亿美元首付款和最高18亿美元的潜在里程碑付款，以及分层销售提成。24、3月25日，恒瑞医药宣布，与默沙东就其脂蛋白(a)[Lp(a)]口服小分子项目（包括名为HRS-5346先导化合物）达成独家许可协议。根据协议，恒瑞医药将HRS-5346在大中华区以外的全球范围内开发、生产和商业化的独家权利有偿许可给默沙东。恒瑞医药将收取2亿美元的首付款，并有资格获得不超过17.7亿美元的与特定的开发、监管和商业化相关的里程碑付款，以及如果相关产品获批上市，基于HRS-5346的净销售额的销售提成。25、3月26日，浦合医药宣布，与拜耳就BAY 3713372（浦合原代号PH020）达成全球许可协议。根据协议，拜耳获得开发、制造和商业化该产品的全球独家许可。BAY 3713372是一种口服的强效选择性MTA协同PRMT5抑制剂，拜耳已招募首例患者参与Ⅰ期人体首次剂量爬坡临床试验，研究该产品用于治疗MTAP缺失型实体瘤。END2025金笔奖征文活动开启，来投稿吧！领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~