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Category: Research and Discovery

  • BMS’ Phase 3 win for lung drug clouded by high-dose miss

    BMS’ Phase 3 win for lung drug clouded by high-dose miss

    Bristol Myers Squibb’s late-stage lung disease asset has scored in a low-dose cohort while failing to improve exhalation capacity at a higher dose, leaving analysts wanting more.

    The Big Pharma’s LPA1 antagonist, dubbed admilparant, ultimately met the primary endpoint of an idiopathic pulmonary fibrosis (IPF) study at the 60-mg dose, demonstrating a statistically significant improvement over placebo in patients’ absolute change in forced vital capacity (FVC) from baseline at week 52. But the 120-mg dose failed to reach statistical significance on the same measure. The company didn’t provide the data behind the results.

    Leerink called the findings “mixed,” writing in a Monday note that the ALOFT-IPF Phase 3 results “could be sufficient to support admilparant regulatory approval, but the lack of dose response raises questions about its profile.

    “We await detailed results to better understand the drug’s efficacy,” the analyst added.

    William Blair was more bullish, estimating $1.3 billion in admilparant sales for IPF in 2032.

    “While there will be some lingering questions on dose response and the magnitude of benefit for admilparant from the ALOFT-IPF study, we believe the success of the 60 mg dose is likely to open a blockbuster opportunity given we view the novel mechanism and non-overlapping toxicities with current therapies in IPF as positive for combination approaches,” William Blair wrote Monday.

    BMS is still evaluating the data and plans on meeting with heath authorities to “support planned regulatory submissions,” according to its news release. Detailed results from the trial are expected for presentation at an unnamed future medical meeting.

    The pharma’s stock fell 3% within the first hour of trading on Monday, from $60.11 per share at open to $57.14.

    Bristol Myers Squibb will soon release Phase 3 data for admilparant that could make or break Contineum Therapeutics’ rival product. But reports of a death due to liver injury in the pharma’s program have caused some unease about the drug class.

    October 1, 2026

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    As for safety, BMS said the drug was well-tolerated across both doses in ALOFT-IPF and noted that discontinuations due to adverse events were comparable to placebo. The Big Pharma did not provide details on safety events, such as hypotension or liver toxicity risk. Earlier this month, BMS reported a death due to multi-organ failure after acute liver injury in its ALOFT program, which includes another Phase 3 trial for progressive pulmonary fibrosis that is expected to read out early next year.

    BMS management told William Blair that the deceased patient was in the 120-mg admilparant arm, and an adjudication committee determined the death was unlikely related to study treatment, according to a Monday note from the analysts.

    A limited number of liver events were observed in the ALOFT program, BMS told BioSpace earlier this month. Most were mild, transient and linked to other medical conditions or in patients taking other medications that have known liver risk factors.

    “A key concern recently has been around liver safety and we think the data reported showing admilaparant [sic] was well tolerated across both doses with AE associated discontinuations low and similar to [placebo] on both active arms addressed this overhang,” Truist wrote Monday morning.

    BMO Capital Markets is more impressed by Merck’s plans to replace lost Keytruda revenue than on Bristol Myers Squibb’s efforts to fill the expected void that will come from loss of exclusivity for both Opdivo and Eliquis.

    October 2, 2026

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    “All in, today’s update points to a derisked regulatory submission path for Bristol pending full data release,” BMO Capital Markets’ Evan Seigerman and colleagues wrote in a Monday investor note.

    “Importantly, the result validates the LPA1 mechanism in a large registrational study; however, the data are unlikely to be viewed as entirely clean given the 120mg arm slowed FVC decline but failed to achieve statistical significance,” BMO said.

    Pulmonary fibrosis is a chronic, life-threatening disease that occurs when lung tissue becomes irreversibly damaged, impacting the organ’s function. William Blair noted that BMS’ trial win is likely a positive for Contineum Therapeutics, which is also developing an LPA1 for pulmonary fibrosis and chronic pain.

    As for BMS’ admilparant, the next step will be about “understanding the magnitude of benefit, consistency across subgroups and the explanation for the unexpected dose-response relationship,” the BMO group wrote Monday.

    “Taken together, we view ALOFT-IPF as an incremental positive as we set up for a catalyst rich period,” the analysts added.

    The Big Pharma is expecting a Cobenfy readout in Alzheimer’s disease psychosis in early 2027, plus topline results next year for milvexian, a Johnson & Johnson–partnered investigational oral factor XIa inhibitor, in atrial fibrillation.

    Last month, Seigerman told BioSpace that he was bearish on BMS’ plans to restock its pipeline as exclusivity loss looms for best-selling drugs Opdivo and Eliquis.

    “We remain on the sidelines as we continue to be wary of the binary risk setup for one of our major pharma names,” he wrote Monday.

    The centerpiece of Bristol Myers Squibb’s 2024 RayzeBio buy has read out, hitting the primary endpoint in a late-stage tumor trial.

    October 12, 2026

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    BMS shared the IPF data on the same day it announced a Phase 3 win for RYZ101, the centerpiece of its $4.1 billion RayzeBio acquisition. The investigational radiopharmaceutical significantly improved progression-free survival for patients with gastroenteropancreatic neuroendocrine tumors.

  • RevMed’s Rasonque gets a subtype data asterisk, but analysts remain bullish

    RevMed’s Rasonque gets a subtype data asterisk, but analysts remain bullish

    A little over a month after Revolution Medicines received an early FDA approval for its RAS inhibitor Rasonque in pancreatic adenocarcinoma, review documents released by the agency showed that a subtype of patients had a lower objective response rate than others. While the biotech’s stock dropped more than 6% last Thursday on the news, analysts largely saw the investor reaction as overblown.

    Rasonque reached a 33% objective response rate (ORR) across all KRAS mutations in the Phase 3 RASolute 302 trial, but digging deeper into that figure showed that certain subgroups fared better, as others performed worse. While patients with a G12V mutation, representing 36% of study participants, achieved an ORR of 50%, the drug’s performance in those with G12D mutations, which represented 43% of the trial’s population, led to an ORR of just 24%.

    A smaller cohort with G12R mutations was the weakest subgroup with a 7% ORR, lower even than the control group that received chemotherapy. Patients with G12R mutations represent a small portion of the pancreatic cancer population, RevMed said.

    Still, analysts expect a record launch for Rasonque. Prior to the newest FDA document release, analysts at Leerink Partners said that “we think this may earn a place as one of the top oncology launches of all time.”

    A future expansion of Rasonque into first-line pancreatic ductal adenocarcinoma could set Revolution Medicines up to hit $2.3 billion in sales by 2028, according to Truist Securities.

    August 27, 2026

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    Rasonque’s approval, which arrived months ahead of schedule, was based on overall survival of 13.2 months compared to 6.7 months for patients receiving chemotherapy. At the time, the FDA’s Oncology Center of Excellence director Angelo de Claro said the early approval was the result of “unprecedented results in an area of high unmet need,” in a disease with a five-year survival rate of just 13%. The data received widespread acclaim and greased the wheels for a quick regulatory push, which included a Commissioner’s National Priority Voucher.

    Upon release of the subtype data, Leerink analysts were still bullish on RevMed’s ability to hold strong in the KRAS market, calling it “premature to assume” that Rasonque would lose its position in G12D mutation subtypes. They cited robust progression-free survival (PFS) and overall survival (OS) data, as well as RevMed’s ongoing development program with multiple approaches to KRAS mutations across subtypes.

    Similarly, Truist Securities analysts called the release “a small crack in the data” that would be unlikely to change RevMed’s market trajectory in the long run.

    “While the divergence warrants attention, we see more nuance, than a fundamental challenge to our RevMed PDAC thesis,” Truist analysts wrote to investors on Oct. 8. “We note that in these new data, G12D efficacy remains clinically meaningful across ORR, PFS and OS, and these exploratory analyses were not powered for cross-mutation comparisons.”

    The analysts added that Rasonque is already positioned as the new second-line pancreatic adenocarcinoma standard of care with no nearby competitors in the RAS/KRAS space.

    Still, even the small gap in RevMed’s data could provide an opening for others developing KRAS-based treatments in pancreatic cancer. In particular, Astellas’ setidegrasib, currently in Phase 3 studies, is designed to specifically target the G12D mutation. Analysts from Jefferies wrote in a Monday note that Rasonque’s weakness there could be a competitive opportunity for Astellas.

  • BMS’ $4.1B RayzeBio bet delivers Phase 3 radiopharma win

    BMS’ $4.1B RayzeBio bet delivers Phase 3 radiopharma win

    Bristol Myers Squibb’s experimental radiopharmaceutical therapy significantly improved progression-free survival in a late-stage trial for gastroenteropancreatic neuroendocrine tumors, a rare type of cancer that typically forms in the gastrointestinal tract.

    BMS picked up the radiopharma candidate, known as RYZ101, in its $4.1 billion RayzeBio acquisition announced at the end of 2023 and closed in early 2024.

    Now, the Big Pharma said that an interim analysis of the Phase 3 portion of the study has met its main goal, with a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as measured by blinded independent central review. BMS did not provide data behind the win in its Monday news release.

    The ACTION-1 study included patients with advanced somatostatin receptor–expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that progressed after treatment with Novartis’ Lutathera, a targeted radiopharmaceutical therapy that serves as the condition’s current standard of care. The primary endpoint was to be measured after 143 PFS events occurred, according to ClinicalTrials.gov.

    RYZ101 is made with actinium-225, a radioisotope that is teed up to be the next big thing in radiopharma—to the point of straining supply of the isotope. The high demand even prompted a pause in the enrollment of ACTION-1 back in 2024, shortly after BMS’ acquisition of RayzeBio was completed.

    Suppliers are investing in production to support deals with AstraZeneca, Bayer and other drugmakers that are advancing radioisotope-based cancer therapies.

    February 17, 2026

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    RYZ101 secured orphan drug status from the FDA in August based on significant unmet need, BMS said. The designation paired with the interim results support further development efforts and “plans to engage with the FDA to discuss next steps toward a regulatory submission,” according to the pharma.

    Safety results were consistent with the known RYZ101 profile, BMS said. In a previous Phase 1b test in 17 patients, RYZ101 was well tolerated, with no treatment-related serious adverse events or dose discontinuations due to adverse events reported.

    More detailed findings from ACTION-1 are slated for presentation at an upcoming medical meeting, the New Jersey company said.

    Telix is Regeneron’s entry ticket into the radiopharma game, helping to better round out the company’s cancer portfolio, according to Truist Securities.

    April 13, 2026

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    “These are the first results from a Phase 3 trial of an alpha-isotope based targeted RPT (225Ac) in any indication, and we are moving with urgency to bring these data to the FDA and, ultimately, provide a novel option for patients,” RayzeBio Chief Medical Officer Amreen Husain said in the release.

    GEP-NETs have a global prevalence of fewer than 200,000 patients. While current lutetium-177–based radiopharmaceutical therapies such as Lutathera have shown significant clinical benefit for GEP-NETs, most patients progress following treatment, according to BMS.

    RYZ101 is also being evaluated in earlier-stage trials for hormone receptor–positive metastatic breast cancer.

  • Successful CDMO partnerships hinge on honest—and sometimes critical—support

    Successful CDMO partnerships hinge on honest—and sometimes critical—support

    As CDMO and sponsor relationships have evolved, the definition of what constitutes a good partner has changed, along with how value is defined. A decade ago, clients viewed service providers through a transactional lens. Now, it has become increasingly important to have a CDMO as a strategic partner that has a significant amount of expertise to ensure client success, thus changing the value propositions of the CDMO.

    In an interview with BioSpace, Jeff Mocny, vice president for Scientific Leadership at Rose BioSolutions, discussed why the CDMO-client connection has transitioned and what steps CDMOs should take to ensure they are true collaborators rather than just suppliers. He discussed how Rose BioSolutions anticipates potential manufacturing hurdles before they arise and the importance of a CDMO to challenge customer assumptions rather than simply execute against a scope of work.

    Mocny also considered the key areas that sponsors underestimate in terms of potential roadblocks and how they should be addressed.

    Evolving CDMO-sponsor relationships

    The deeper collaboration and partnership among participants along the product development value chain, as well as commercial supply chain, is driven by value recognition, Mocny said. And those values need to align. As industry experience with cell and gene therapy has grown, sponsors have recognized the expertise in CDMOs for successful deliverables, but also how those values reflect relationships.

    “As programs mature, the shared needs change, but the values must remain consistent. Like any relationship, with time, we look for different things from our partners, but ultimately, the goal of CDMOs is to protect our clients from unacceptable risk and serve their needs to achieve the objective,” said Mocny. “Our success is directly related to the success of the partner.”

    In addition, the enhanced partnership has been fostered by a greater drive towards efficiency, BioSpace reported in its CDMOs At a Crossroads white paper.

    Jeff Mocny, Vice President for Scientific Leadership, Rose BioSolutions

    Jeff Mocny, Vice President for Scientific Leadership, Rose BioSolutions

    This can mean cost efficiency: rising costs, driven by increased prices for raw materials and transportation, lead to the compression of margins, especially as pharmaceutical companies face limits on their ability to pass costs on to customers. However, efficiency is not just about capital spending. In this new environment, CDMOs must act adeptly as innovation collaborators, allowing pharma companies to stay nimble and attuned to political and regulatory headwinds.

    Recently, these headwinds have meant a move toward increasing U.S. manufacturing capacity. This may include nearshoring, or shifting manufacturing, IT or operational processes to nearby or bordering countries rather than distant ones, and retaining diverse manufacturing sites to account for political instability while also considering global scope. On the regulatory front, FDA inspections rose sharply in 2025, with 694 more than in 2024. Untitled letters jumped to 58 from five, and Form 483 observations exceeded 600.

    In this environment, outsourcing partners are being asked to support a sharpened focus that delivers rapid data, specialized expertise and landscape knowledge to ensure product and manufacturing success.

    Strategic partnership success

    For the CDMO partnership to be truly collaborative, it is key for the service provider to understand how the product is defined so that the CDMO and sponsor align on the correct regulatory stipulations, Mocny said. “Strategy and execution are not the same, but they complement one another.,” he added. “The strategy points in one direction and the execution enables identification of landmarks along the way necessary to achieve to reach the goal laid out by the strategy.”

    The correct product definition enables the CDMO to predict where problem areas may lie and to anticipate potential challenges before they occur. Leveraging the experience of a CDMO partner, coupled with a clear understanding of the path forward, allows companies to foresee challenges that can be more readily solved together, Mocny said.

    Consequently, it’s key that regulatory understanding is baked into the program at the outset, he said. The introspective questions that collectively should be asked are simple and a little bit philosophical: “What is it you think you need to do, how do you execute it effectively, do you need to do that to stay aligned with the plan and why do you need to do it?”

    This approach can provide clarity, direction and communicate intent with the team for alignment. Communication builds trust, Mocny emphasized. “It is crucial that trust is established with the client to address these matters, to share information and move forward collectively to satisfy mutual business goals,” he said.

    In collaboration with a sponsor, a partner CDMO should contest customer assumptions if warranted, Mocny said. “A true partner will be politely critical, inquisitive and thoughtful with their support,” he noted. In customer proposals, Rose BioSolutions sets out a development/CMC strategy that encompasses the manufacturing approach and expected output at specific points in the therapeutic development life cycle.

    Attention is given to program-specific risks as understood by Rose based on what a sponsor presents, as well as to recommendations to address them.

    Developers consistently underestimate compliance when selecting and working with a CDMO partner. That said, a good partner employs the product definition and regulatory strategy to resolve potential issues, Mocny said.

    For example, with complicated product types that don’t fall neatly into any one category, there are multiple elements that need to be considered in the final composition during product development. In turn, the CDMO and sponsor need to consider each element individually and collectively to apply across these product types. This is why product definition is key at the outset.

    “Sometimes sponsors struggle with understanding how to interpret the compliance landscape,” Mocny noted. This is where the real value proposition of a CDMO can be seen, contextualizing and bridging the gap between compliance/scientific justification and regulated body guidance. An ideal CDMO partner will have an in-depth understanding of the regulatory frameworks and guide clients to success.

  • Bowel cancer “melted away” after immunotherapy, then stayed away

    Bowel cancer “melted away” after immunotherapy, then stayed away

    Patients with a particular form of bowel cancer remained free of recurrence for almost three years after receiving a short course of immunotherapy before surgery, according to new findings from the NEOPRISM-CRC clinical trial led by researchers at UCL and UCLH.

    The results, which are due to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in April, extend earlier findings from the trial. Those initial results showed that nine weeks of treatment with the immunotherapy drug pembrolizumab before surgery caused major tumor shrinkage in people with stage two or three bowel cancer.

    Earlier data showed that 59% of patients had no detectable signs of disease after pembrolizumab treatment and their planned bowel cancer surgery.

    Zero Recurrences After 33 Months

    After 33 months of follow-up, none of the patients treated in the trial had experienced a return of their cancer. That was true both for patients who had no signs of cancer after treatment and for those who still had small amounts of disease remaining. In the latter group, the remaining cancer did not grow or spread during follow-up.

    By comparison, around 25% of patients treated with the standard approach of surgery followed by chemotherapy are expected to relapse within three years. The findings suggest that giving a short course of immunotherapy before surgery may provide more durable cancer control for this specific type of bowel cancer than the usual combination of surgery and post-operative chemotherapy.

    Researchers also studied blood samples to investigate why the treatment worked so well and to find ways of identifying which patients were most likely to benefit. They developed personalized blood tests designed to show early whether treatment had worked and whether traces of cancer were still circulating in the bloodstream.

    Dr. Kai-Keen Shiu, Chief Investigator of the trial from UCL Cancer Institute and a Consultant Medical Oncologist at UCLH, said: “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.

    “What is particularly exciting is that we now may be able to predict who will respond to the treatment using personalized blood tests and immune profiling. These tools could help us tailor our approach, identifying patients who are doing well and may need less therapy before and after surgery versus patients at higher risk of disease progression or relapse who need additional treatment.”

    Bowel Cancer Survival Varies by Stage

    Bowel cancer is the fourth most common cancer in the UK, with roughly 44,000 new cases diagnosed each year. It continues to affect older adults most often, although rates among people younger than 50 have been rising in recent decades.

    As with many cancers, outcomes are much better when bowel cancer is detected early. Around nine in ten people treated for stage one bowel cancer survive for at least five years. However, some tumor sub-types respond less effectively to treatment and are more likely to return. Five-year survival drops to 65% for stage three bowel cancer and 10% for stage four disease.

    The NEOPRISM-CRC trial enrolled 32 patients with stage two or three bowel cancer and a particular genetic profile (MMR deficient/MSI-high bowel cancer) at five hospitals across the UK. Around 10-15% of people with stage two or three bowel cancer have this genetic make-up, equivalent to roughly 2,000-3,000 cases each year in the UK.

    Instead of undergoing surgery followed by three to six months of chemotherapy, participants received up to nine weeks of pembrolizumab before their bowel surgery. Researchers then continued monitoring them over time.

    Personalized Blood Tests Could Guide Treatment

    The latest phase of the ongoing trial, presented this month at AACR in San Diego, California, was led by UCL and UCLH. University Hospital Southampton, St. James’s University Hospital in Leeds and the Christie NHS Foundation Trust in Manchester also helped recruit patients and supplied valuable translational samples. All translational work was carried out by UCL and biotechnology company Personalis.

    Professor Marnix Jansen, a clinician scientist and consultant histopathologist who is leading the translational research on the trial from UCL Cancer Institute and UCLH, said: “These results not only confirm the durability of responses we saw almost three years ago, but also provide crucial biological insights into why immunotherapy is so effective in this setting.”

    Researchers found that changes in tumor DNA in the bloodstream closely reflected how well patients were responding. Disappearance of tumor DNA from the blood was strongly associated with having no cancer remaining.

    Yanrong Jiang, first author of the latest abstract and clinical PhD student at the UCL Cancer Institute, said: “As a research team, we were thrilled to be able to follow patients very closely using the personalized blood tests. When tumor DNA disappeared from the blood, patients were much more likely to have no cancer remaining, and this matched the long-term results we’re now seeing.

    “In addition, we also saw that immune profiling from tumor tissue, before patients start their first cycle of treatment, can help to predict response. We hope these tests may be used to guide treatment decisions in a more practical and timely way.”

    Patient’s Story

    UCLH patient Christopher Burston was diagnosed with bowel cancer in February 2023 after taking part in routine screening. He had completed bowel screening kits sent through the post for several years before one test came back positive.

    Christopher, 73, of Portland, Dorset, said: “One came back with indications of blood in my stool. I went through further tests, and it was at the colonoscopy that they identified a cancer in my bowel.”

    A few weeks after his diagnosis, Christopher’s oncologist told him he might qualify for the NEOPRISM clinical trial, which was testing immunotherapy before surgery. Although taking part meant traveling to London for treatment, he chose to enroll and was referred to UCLH.

    He received three doses of immunotherapy across nine weeks before undergoing surgery in May 2023. Christopher experienced few side effects and recovered well after spending one week in the hospital.

    He said: “The outcome of the surgery was essentially that the cancer had melted away, these were the doctor’s words. The immunotherapy had had an almost immediate effect. I saw the images when I had the first colonoscopy and could see it was really quite a substantial lump. So as I say, it wasn’t a minor thing, I was diagnosed with stage 3 cancer.”

    More than three years later, Christopher remains cancer-free. He has returned to his normal activities while continuing to attend regular follow-up appointments.

    Christopher said: “The recovery went fine. I didn’t have any problems. And since then, I’ve been feeling pretty much back to normal. I feel very lucky that I’ve reached the stage where my main problem is age rather than cancer or any illness.”

  • TRexBio, Retension raise $161.7M in IPOs; City, Iambic set proposed offering terms

    TRexBio, Retension raise $161.7M in IPOs; City, Iambic set proposed offering terms

    The biotech IPO frenzy is very much alive this October spooky season, with TRexBio and Retension Pharmaceuticals set to begin trading Friday with offerings totaling $161.7 million. City Therapeutics and Iambic Therapeutics are lined up behind them, outlining expected prices for their own offerings.

    First up is TRexBio, hitting the Nasdaq with a $116.7 million offering. The immunoregulatory medicine developer sold 8.3 million common stock shares at $14 per share, coming in at the low end of its expected $14 to $16 range. Underwriters also have a 30-day option to buy 1.25 million more shares at the same price.

    Big Pharma Eli Lilly reported direct holdings of 5.4 million TRex shares, according to a Thursday SEC filing. The biotech’s CEO is Johnston Erwin, who spent nearly 20 years at Lilly before leading TRex. In 2023, TRex and Lilly linked up in a deal worth more than $1.1 billion in biobucks to develop treatments for immune-mediated diseases.

    Now, TRex will use the new funds to advance its investigational fusion protein TRB-061, currently in early-stage development for atopic dermatitis. A topline Phase 1b readout is expected in mid-2027. TRex will also put some of the money into the preclinical CD30 agonist TRB-071.

    Twenty-five biotechs have used the IPO route to go public this year—with five of those debuts occurring this month alone. It’s the most IPOs since 2021, when the industry recorded 78 during the height of the COVID-19 pandemic.

    August 25, 2026

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    Joining TRex on the markets Friday is Retension Pharmaceuticals, which will debut with $45 million. The cardiovascular-focused company sold 3.75 million shares at $12 a piece—the midpoint of its expected price range. Underwriters also have the option to purchase up to 562,500 more shares at the IPO price over the next 30 days.

    The Virginia biotech will use the proceeds to back its sole clinical candidate: RTN-001, a daily oral small-molecule PDE-5 blocker being developed for hypertension. The money will support ongoing Phase 2b development and the advancement to Phase 3, according to Retension.

    Including the two newest additions, 29 biotechs have gone public in 2026, an incredible leap from 2025’s total of eight public biotech debuts. Already this year, the industry has had its most IPOs since 2021, when biopharma recorded 78 at the height of the COVID-19 pandemic.

    Up next to potentially go public is RNAi biotech City Therapeutics, which filed IPO plans at the end of September and just revealed that it expects to raise around $158.3 million, according to a Friday SEC filing. That estimate is based on an expected pricing at $18 per share.

    Founded in 2023 by former Alnylam leader John Maraganore, the biotech plans on divvying up the cash, with $30 million expected to bankroll the development of CITY-FXI, which is currently being evaluated in a Phase 1 trial for thrombosis, while also launching a Phase 2 trial to assess the asset’s efficacy in preventing blood clotting in knee replacement surgery.

    Another $20 million will fuel clinical development of RNAi therapy CITY-RBP4 in Stargardt disease and geographic atrophy, while $40 million is intended to fund the clinical tests of CITY-TFR2 in anemia associated with myelofibrosis. The biotech has also earmarked $70 million for platform development and preclinical activities.

    Two RNA biotechs, ADARx Pharmaceuticals and City Therapeutics, are taking advantage of the IPO frenzy, which has led to a total of 27 newly public biotechs so far this year.

    September 25, 2026

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    Lastly, AI-fueled Iambic Therapeutics has targeted a $15 to $17 per share range for an expected $135 million IPO. The Nvidia-backed cancer company has allotted $75 million of that money for its lead candidate IAM1363, an oral HER2 inhibitor designed to penetrate the brain and target several known disease-causing mutations of the protein. IAM1363 is currently being studied in a Phase 1/1b trial for HER2-altered solid tumors, with registrational studies planned for 2027.

    Some of the money will also go toward moving the KIF18A blocker IAM217 for triple-negative breast cancer and the dual CDK2/4 inhibitor IAM-C1 into clinical testing.

  • How Abogen went from COVID hype to a $7.8B Novartis deal

    How Abogen went from COVID hype to a $7.8B Novartis deal

    Novartis’ agreement with Abogen Biosciences stands out even in today’s increasingly busy biotech licensing market.

    The agreement gives Novartis an exclusive worldwide license to ABO2203, Abogen’s mRNA-encoded CD19×CD3 T cell engager being developed for B-cell malignancies and autoimmune diseases, plus exclusive options to license additional programs from Abogen’s RNA platform. Abogen will get $575 million upfront and could receive up to roughly $7.2 billion more if all options are exercised and development, regulatory and commercial milestones are met, plus potential royalties.

    From my vantage point working on healthcare investment banking transactions across U.S. and Asian markets, the $575 million upfront makes the deal notable. The buyer makes it more so.

    Novartis has made RNA therapeutics—which it broadly calls xRNA—one of its three advanced technology platforms and has committed substantial capital to the field. Recent transactions include partnerships with Argo Biopharma and Arrowhead Pharmaceuticals and the $12 billion acquisition of Avidity Biosciences, announced last October.

    ABO2203 also fits another Novartis priority: deeper B cell depletion in autoimmune disease. Novartis has explicitly highlighted immune reset as a goal in its immunology pipeline and has been pursuing this approach through CAR T therapies, although several trials were recently paused following patient deaths. ABO2203 offers a different way to pursue that goal using an RNA-encoded T cell engager.

    A $575 million upfront commitment from a buyer with that level of RNA experience is therefore meaningful—not only for ABO2203 as an asset, but for Abogen’s broader move beyond infectious disease prevention. That matters because Abogen was built up during the COVID boom, when much of the attention was tied to a vaccine opportunity that ultimately faded.

    Novartis is licensing an mRNA-based therapy designed to produce a CD3xCD19 T cell engager inside the body. Abogen Biosciences says the in vivo approach could reduce the likelihood of dangerous cytokine release.

    October 2, 2026

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    Built during the COVID boom

    Abogen was founded in 2019 by Bo Ying, who had previously worked on oligonucleotide and mRNA programs at Moderna and Dicerna Pharmaceuticals. From the start, the company aimed to build an mRNA and delivery platform across infectious disease, oncology and other therapeutic areas.

    Then COVID arrived and transformed the company.

    As Moderna became one of the defining biotech stories of the pandemic, China had yet to develop a domestic mRNA vaccine. That put Abogen in a favorable position as capital and attention flooded into the field.

    Its COVID vaccine received clearance to start clinical trials in China in June 2020 and reached Phase 3 in 2021. Financing followed rapidly. Abogen raised more than $700 million in August 2021 and another $300 million that November.

    The COVID vaccine remained the program attracting the most external attention. While the vaccine did not fail in the conventional sense—it completed a large global Phase 3 program and received emergency-use authorization in Indonesia in September 2022—it did not catch the commercial wave. By the time Abogen’s vaccine rolled out, billions of vaccine doses had already been administered, Omicron had altered the trajectory of the pandemic and mass vaccination campaigns were winding down.

    The product reached regulatory authorization, but the commercial opportunity that had attracted so much capital largely disappeared. By 2024, development partner Walvax terminated further clinical development of Abogen’s original COVID vaccine.

    Abogen’s COVID-19 mRNA vaccine on display at China’s Military Museum in Beijing

    Abogen’s COVID-19 mRNA vaccine on display at China’s Military Museum in Beijing

    / Courtesy of Lewis Zhang

    By then, the question was no longer whether Abogen could develop a good COVID vaccine but whether it could build a meaningful pipeline beyond the COVID program that had driven its financing boom.

    How ABO2203 brought the transition into view

    The company continued building out programs across vaccines and therapeutics, but few attracted the same level of external attention as its pandemic-era work. ABO2203 changed that.

    Rather than using mRNA to encode a viral antigen, ABO2203 uses the modality to instruct cells to produce a CD19×CD3 T cell engager (TCE) in vivo.

    At the annual meeting of the American Association for Cancer Research in April 2026, Abogen reported updated data from nine patients with relapsed or refractory B cell non-Hodgkin lymphoma in the dose-escalation stage. The patients had received a median of four prior lines of therapy, and all had experienced disease advance after CD20-targeted treatment.

    ABO2203’s early safety profile was notable. No dose-limiting toxicities, cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported across the dose levels tested. The pharmacokinetics help explain why the approach may behave differently from conventional protein TCEs. Abogen reported a flatter and more sustained exposure of the encoded TCE than was seen with an identical TCE delivered as a protein. The biotech has suggested that the lower peak exposure could help mitigate cytokine release.

    There was also an early efficacy signal. Response rates to ABO2203 increased depending on the dose, with overall response rates of 33%, 67% and 100% across the low-, medium- and high-dose cohorts, respectively. The highest-dose cohort also reached a 100% complete response rate in the updated presentation.

    Beyond cancer, Abogen has also begun testing ABO2203 for autoimmune indications, and these data may be even more relevant to Novartis’ strategic rationale. A Cell study published in September described three patients with refractory secondary immune thrombocytopenia who after taking ABO2203 achieved rapid, complete peripheral B cell depletion, sustained depletion in bone marrow and durable platelet recovery through six months of follow-up. Only mild adverse events were reported, with no CRS.

    Three patients are far too few to establish efficacy or safety. What they do show is that the same mRNA-encoded TCE architecture can produce a biological and clinical signal outside of oncology. That extension into B cell–mediated autoimmune disease makes the program particularly relevant to Novartis’ existing interest in immune reset.

    Big Pharma needs more—not fewer—bold bets on rare and difficult diseases after Novartis’ efforts to invest in muscular dystrophy and ALS hit major roadblocks this month.

    September 17, 2026

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    What Novartis is actually underwriting

    The deal structure reflects both sides of the opportunity: Novartis is paying $575 million upfront for ABO2203 while securing options on follow-on programs from Abogen’s RNA platform. Similar to its earlier multi-asset partnerships with Argo Biopharma, this arrangement allows Novartis to back a lead asset while retaining access to additional programs as they emerge.

    For Abogen, the more important inflection is that the company is no longer being judged primarily on the promise of its RNA platform; it now has a Big Pharma–backed asset in the clinic, with early results supporting its potential use in cancer and autoimmune disease. Five years ago, more than $1 billion of private capital backed the company during the COVID vaccine boom; today, Novartis is committing $575 million upfront to a therapeutic asset generated from those capabilities.

    ABO2203 remains early, and larger oncology and autoimmune cohorts will be the next test. Beyond that, additional programs will show whether the same RNA capabilities can support a broader therapeutic pipeline. For Novartis, its investment buys a front-row seat to that evolution.

  • Reusing data could cut R&D costs and greatly increase gene editing’s reach: ARM

    Reusing data could cut R&D costs and greatly increase gene editing’s reach: ARM

    The gene-editing space has a new playbook aimed at radically reducing the work needed to bring these therapies to the clinic.

    Building on the FDA’s draft guidance published this summer, the advocacy organization Alliance for Regenerative Medicine (ARM) has set out how developers can reuse data to eliminate redundant studies and drive down costs. ARM argues that by reusing data, developing genetic medicines for ultrarare diseases can be viable even though these indications affect too few patients to generate a return on typical R&D budgets.

    “If we can leverage the platform and make the cost of the incremental effort to treat a mutation very minimal, rare disease patients suddenly get this kind of therapy where they wouldn’t have otherwise,” John Evans, CEO of Beam Therapeutics, which was involved in creating the playbook, told BioSpace.

    While both Beam Therapeutics and Wave Life Sciences touted notable biomarker benefits for their respective alpha-1 antitrypsin deficiency assets, analysts said that Beam might have the efficacy advantage as Wave’s drug hits an efficacy “ceiling.”

    May 20, 2026

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    Implementing the platform approach

    ARM’s playbook, published late last month, provides a guide for developers seeking to reuse data to streamline drug development. Josephine Lembong, ARM’s associate director for scientific affairs, outlined the first steps for developers that want to implement the proposed plan.

    “First, developers should decide on their main objective,” Lembong told BioSpace via email. “Especially for rare diseases, that goal may be rapid clinical proof of concept, full licensure or long-term commercial viability, and the choice should factor in population size, unmet need and the availability of alternative treatments.”

    Whatever the objective, Lembong recommended preparing for a regulatory filing from the outset, designing and building programs for a potential submission. That approach aligns with how Beam operates under Evans, who said that the biotech designs Phase 1 trials to be registrational. In doing so, Beam aims to go from first-in-human trials to FDA approval in four to five years, compared to eight to 10 years in the traditional clinical pathway.

    In parallel with discussions of their main objectives, Lembong said developers should shape their regulatory strategy by mapping their programs to existing FDA frameworks and guidance. At the same time, she added, companies should “define the platform’s scientific boundaries, distinguishing its fixed components from its variable ones.”

    Fixed and variable components “depend on the target disease and its known mutations,” Lembong explained. The delivery vehicle, route and formulation may be fixed, allowing developers to reuse data. In contrast, guide-specific biology cannot be assumed from the first product and should be evaluated directly.

    Reusing data

    Acute toxicity studies offer the biggest opportunity to reuse data under the platform model, Evans said. A lipid nanoparticle will trigger “the exact same acute toxicity outcome” when the payload is adapted to a new target mutation, he continued, making repeat studies redundant.

    Chemistry, manufacturing and controls tasks provide further opportunities to reuse data. Such tasks are “a huge amount of the overhead in genetic medicine,” Evans said, reflecting the complexity of the drugs. Under the platform approach, he said, Beam can “use the same assays every time and we know exactly what we’re going to get.”

    Those opportunities apply to a range of genetic medicines, but Evans sees further streamlining opportunities that are “somewhat more unique” to Beam’s base-editing method. Companies could use the plausible mechanism pathway, which the FDA unveiled last year, to stop generating animal data in each genetic driver of a disease that may have many such drivers, Evans said. He highlighted phenylketonuria (PKU), for which Beam is actively pursuing a treatment, as being caused by hundreds of variants.

    The plausible mechanism pathway “could accelerate gene therapy/editing development,” analysts at William Blair said Thursday, while adding that additional clarity is needed.

    November 13, 2025

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    3 min read

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    After reusing safety, efficacy and manufacturing data, developers will have short lists of product-specific tasks that they need to perform every time. Beam will need to show every new editor is potent enough, which can often be done in cells, Evans said. Beyond that, companies will continue to run on- and off-target editing studies.

    “That might be 10% of the work of a full package. Everything else is cross-referenced to studies we’ve already run,” Evans said. Investigational new drug (IND) applications “are now effectively platform INDs where multiple edits can live together, all trying to deliver the same functional outcome on the gene and on the patient. That’s the really novel part of this.”

    Further enhancements

    The platform model alone “may not be sufficient to fully address the cost and access challenges facing the field,” ARM said in its playbook. This concern led ARM to conclude its report with a call for “a broader discussion of whether certain traditional development expectations should be modified, abbreviated or, in carefully justified cases, removed altogether”—when risks are low and potential benefits are high.

    ARM argued that existing accelerated clinical development pathways are “untenable” for many sponsors in the rare and ultrarare disease space. Developing drugs for diseases that affect very small numbers of patients or are especially severe or urgent will “require a higher appetite for risk,” ARM said.

    The group proposed a bifurcated regulatory framework allowing higher-risk, streamlined development of treatments for severe rare diseases that have no standard of care. ARM’s push to further streamline development is part of a broader focus on maximizing genetic medicine’s impact.

    “We don’t want to look up in five or 10 years and see that we’ve done this once or twice. We want to have done this 10, 20, 100 times,” Evans said. “There’s a direct line from the efficiency with which we can move these products through the regulatory process . . . and how many diseases we can tackle.”

  • Argenx shutters Sjogren’s study, losing blockbuster expansion opportunity for Vyvgart

    Argenx shutters Sjogren’s study, losing blockbuster expansion opportunity for Vyvgart

    Argenx is discontinuing a late-stage study of Vyvgart Hytrulo in Sjogren’s disease due to futility, a surprise setback that removes “the next potential blockbuster expansion opportunity” for the drug, William Blair analysts wrote on Thursday.

    The biopharma is ending its Phase 3 UNITY trial after an independent data committee determined that the study would not meet its primary endpoint of improving systemic disease activity, according to a Thursday release.

    As of market open, argenx’s stock had tumbled nearly 14%, or about $130 per share, resting at around $797 as of 11 a.m. ET.

    UNITY had been evaluating argenx’s Vyvgart Hytrulo injection for Sjogren’s, an autoimmune disorder that most often affects moisture glands, with the most common symptoms of dry eyes and dry mouth. Vyvgart Hytrulo is currently approved to treat generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy and recently scored a late-stage win in autoimmune myositis, a group of rare diseases that cause the immune system to attack the muscles.

    Today’s futility announcement is surprising given that the trial results weren’t expected until the second half of 2027, William Blair wrote in a Thursday note.

    Argenx told the firm that the futility analysis included data from more than 500 patients—as compared to the 630 enrolled—indicating that the review may have been conducted earlier than the primary endpoint assessment expected at week 48.

    “Sjogren’s disease drug development has been bogged down by high placebo response rates, making it difficult to achieve robust separation versus placebo,” according to William Blair.

    In argenx’s Phase 2 RHO study, the asset appeared differentiated in Sjogren’s compared to placebo at week 24. However, the study was underpowered and there was no difference compared to placebo in percentage of patients achieving at least a three-point improvement on an industry scale measuring disease activity, William Blair wrote.

    The analysts had previously estimated peak sales of $1.4 billion in Sjogren’s but noted competition in the space, specifically from Novartis’ investigational monoclonal antibody ianalumab and Amgen’s CD40L antagonist fusion protein dazodalibep, both of which have recorded Phase 3 wins.

    The star of the takeover is Forte Biosciences’ investigational antibody therapy, FB102, which has shown early potential in vitiligo and celiac disease.

    July 27, 2026

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    2 min read

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    Meanwhile, argenx announced a mid-stage celiac disease win in a separate release. The Phase 2 trial evaluated the biotech’s investigational CD122 inhibitor FB102, which it picked up from Forte Biosciences in a $2.2 billion acquisition this summer.

    Patients receiving FB102 demonstrated a statistically significant change from baseline in a health measure of the small intestine, meeting the study’s primary endpoint. Given the findings, which argenx heralded as the “first Phase 2 evidence that blocking CD122 can prevent gluten-induced intestinal damage in people living with celiac disease,” the biopharma plans to move the asset into late-stage development.

    The celiac disease plans expand argenx’s late-stage pipeline ahead of the closely-watched Phase 3 findings expected soon for monoclonal antibody empasiprubart in multifocal motor neuropathy.

  • FDA-approved epilepsy drug may help reverse osteoarthritis damage

    FDA-approved epilepsy drug may help reverse osteoarthritis damage

    For millions of people with osteoarthritis, pain and stiffness can make everyday activities increasingly difficult. Common treatments, including over-the-counter medications and steroid injections, may reduce symptoms for a time, but they do not prevent the underlying joint damage from progressing.

    New research from Yale suggests a different approach. In a study published in Bioactive Materials, scientists found that the medication lacosamide can serve two purposes in osteoarthritis, reducing joint pain while also reversing cartilage damage. The effects were particularly strong when the drug was delivered directly into the joint using a specialized hydrogel.

    Why osteoarthritis damages cartilage

    Osteoarthritis is often called a condition caused by wear and tear, but that description leaves out much of the biology involved.

    Within a healthy joint, cells known as chondrocytes help maintain cartilage by continuously balancing the creation of new tissue with the removal of old material. Osteoarthritis disrupts that balance. Cartilage begins to break down faster than it can be replaced, eventually allowing bones to rub against one another. As the disease advances, some patients may ultimately require joint reconstruction procedures such as a total knee replacement.

    “There is a major unmet need in osteoarthritis,” says the study’s principal investigator and Charles W. Ohse Professor of Orthopaedics & Rehabilitation, Chuan-Ju Liu, PhD. “We need therapies that don’t just mask pain but actually change how the disease progresses.”

    At present, no medicine approved by the U.S. Food and Drug Administration can both stop osteoarthritis pain and prevent the structural breakdown of cartilage. The work led by Liu suggests that it may be possible to address both problems with a single therapeutic strategy.

    The researchers repurposed an existing medication and paired it with an advanced gel designed to keep the drug inside the joint. The approach could potentially preserve joint tissue while delivering sustained pain relief without relying on addictive opioids.

    A protein linked to pain and cartilage loss

    The research focuses on Nav1.7, a protein that functions as a sodium channel. These channels act as microscopic gates in cell membranes and play an important role in electrical signaling.

    Nav1.7 was long thought to operate primarily in specialized nerve cells that transmit pain signals to the brain. More recent work from Liu and his team, however, revealed that the protein is also highly active in chondrocytes, the cells responsible for maintaining cartilage.

    Nav1.7 is relatively quiet in healthy joints. In osteoarthritis, however, its activity increases substantially. The researchers found that this heightened activity can intensify pain signaling while also pushing chondrocytes toward breaking down the cartilage they would normally help preserve.

    That makes Nav1.7 an unusual therapeutic target because it appears to influence both the sensation of pain and the physical deterioration of joint tissue.

    “When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain,” Liu says. “Our findings suggest that Nav1.7 is a dual-acting target. By blocking this single protein, we can potentially quiet the pain nerves and tell the cartilage cells to not only stop breaking down but start repairing as well.”

    Epilepsy drug shows potential for cartilage repair

    Instead of creating an entirely new medication, Liu’s team tested drugs that already inhibit sodium channels. Among them, lacosamide produced strong biological effects at considerably lower concentrations and offered a better safety profile than older drugs in the same class.

    Lacosamide is already used as a treatment for epilepsy, but the researchers found that its effects on cartilage depended heavily on the dose.

    More was not necessarily better. At an ideal low concentration, lacosamide encouraged cells to produce proteins involved in building cartilage while also suppressing processes that break tissue down. When the concentration was either too high or too low, those benefits began to fade.

    “This tells us the system is finely tuned,” Liu notes. “There is an optimal range where the drug helps restore balance without overcorrecting. What stood out was not just its effectiveness, but how little of a dose was needed.”

    Further investigation revealed that lacosamide also changes the way cells communicate. The drug stimulated the release of two beneficial signaling proteins, HSP70 and midkine.

    HSP70 helps cells respond to stress and supports tissue repair, while midkine helps regulate inflammation and protect joint tissue from degeneration. Together, the proteins appear to create conditions that are more favorable for maintaining cartilage.

    “These proteins create a supportive environment for cartilage maintenance,” Liu explains. “They allow the effects of the drug to extend beyond individual cells and influence the entire tissue.”

    Smart hydrogel keeps the drug inside the joint

    Oral treatment with lacosamide was effective in preclinical testing, but drugs taken by mouth circulate throughout the body, increasing the potential for unwanted effects elsewhere.

    The researchers therefore investigated intra-articular injection, which allows the medication to be placed directly inside the affected joint.

    There was still a significant problem to overcome. “The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket,” Liu says. “The body’s drainage system can clear out liquids injected into the knee within hours.”

    To keep the medication in place longer, the team created a specialized hydrogel made from Collagen II. The material responds to temperature. It remains liquid while inside a cool syringe, then becomes a firm, jelly-like material after reaching body temperature.

    Once inside the joint, the gel acts as a storage site for lacosamide, keeping the medication concentrated in the affected area while gradually releasing it over several weeks.

    “The hydrogel acts as a local reservoir,” Liu says. “It holds the drug in place in the location it is needed most and releases it slowly over time. It transforms a daily pill into a long-lasting, local treatment that stays active for a month or longer.”

    In the same preclinical studies, one injection of the lacosamide-containing gel every four weeks prevented cartilage loss more effectively than taking an oral dose every day.

    Existing drug could speed clinical testing

    One important advantage of lacosamide is that the medication is already approved for use in people. That could make it possible to move toward clinical studies in osteoarthritis patients more quickly than would be possible with a completely new drug.

    Lacosamide has also been tested in humans with certain nerve-related pain conditions caused by Nav1.7 mutations. Those results give the researchers greater confidence that the effects seen in laboratory studies could eventually translate into meaningful pain relief for patients.

    The work also reflects a broader direction in medicine that combines drugs with advanced biomaterials to control exactly where and how treatments are delivered. If the approach proves successful in people, it could eventually reduce the number of procedures patients need, limit unwanted side effects, and provide longer-lasting protection against structural joint damage.

    “We are not just developing a treatment,” Liu concludes. “We are developing a system that allows the medicine to work more effectively where it matters most. Our goal is to move beyond symptom control and towards true disease modification. This effort brings us closer to that reality.”