Efruxifermin

iStock, z_wei Biopharma doubles down on immunology and inflammation as companies target new pathways and seek to improve on current options in inflammatory bowel disease, atopic dermatitis, myasthenia gravis and more. One of biopharma’s hottest therapeutic areas, immunology and inflammation has seen an uptick in M&A activity in recent years, with big names like Sanofi and Gilead dropping billions of dollars to expand their I&I pipelines. At the same time, the space is seeing an influx of new companies, including Bambusa Therapeutics , which launched Friday with $90 million in series A funds. Momentum in this space was sparked at the turn of the century by the arrival of therapeutic antibodies. After winning FDA approval in 2002, Abbvie’s Humira—the first tumor necrosis factor (TNF) inhibitor—became one of the best-selling drugs of all time, generating over $200 billion in lifetime sales to patients with rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn’s disease and more. Over 20 years later, with Humira and other key medicines having lost their exclusivity and research providing a better understanding of the biology underlying the field, it’s time for the next wave of I&I. Indeed, novel targets and modalities are attracting an influx of investment into the I&I space, said Thomas Smith, a senior research analyst covering immunology at Leerink Partners. “We’re seeing antibodies that are going after targets that have not been targeted before, small molecules that were previously thought to be undruggable,” he told BioSpace . “We’re seeing the emergence of cell therapies.” And there’s room for them all. The second largest therapeutic area by value in 2023, the immunology market is projected to be worth more than $257 billion by 2032. “[I&I] has large end markets of highly prevalent diseases that, despite having multiple treatment options, still have persistent, high medical need,” Smith said. M&A Expected to Continue in 2025 The I&I space has made headlines recently for a spate of high-pro In April 2024, Vertex struck the biggest deal in biopharma last year with its $ 4.9 billion buy of Alpine Immune Sciences. Then in June, Eli Lilly dropped $3.2 billion to acquire Morphic Holding. These deals followed Merck’s eyepopping $10.8 billion pick-up of Prometheus Biosciences a year earlier. While many big pharma companies already have their own immunology platforms, “innovation does not happen in isolation,” Shaju Backer, global head of immunology at Sanofi, told BioSpace in an email. This is why his company also complements its in-house R&D with a myriad of strategic partnerships and acquisitions. In 2021, Sanofi acquired Kymab for $1.4 billion to add an anti-OX40 ligand to its pipeline, hoping to address the underlying disease pathologies of inflammatory diseases like atopic dermatitis without depleting T cells. More recently, Gilead struck a deal last month with LEO Pharma worth up to $1.7 billion for its preclinical STAT6 program. Smith expects more of the same in the near future. “We have a lot of reason for thinking this is going to continue to be the case in 2025,” he said. Pursuit of Novel Targets TNF blockers like Humira cast a wide net, pulling in some ten indications. Yet patients and practitioners have seen the effects of Humira and other anti-TNF therapies wear off relatively quickly because ancillary pathways take over, according to Backer, making it necessary to target other pathways for disease management and, hopefully, remission. One of these, the TL1A pathway, plays a key role in driving inflammation and fibrosis in various autoimmune diseases, making its inhibition a promising strategy for multiple indications, including inflammatory bowel disease (IBD). Merck’s Prometheus buy brought in a potentially best-in-class TL1A inhibitor in late-stage studies for ulcerative colitis and Crohn’s disease. And Sanofi is co-developing a TL1A-targeting antibody, duvakitug, with Teva Pharmaceuticals. Another target generating a lot of interest is the signal transducer and activator of transcription 6 (STAT6) transcription factor, which is a key regulator of Th2-driven immune response. Indication potential is wide-ranging for STAT6-targeted oral drugs, which could offer an alternative to existing injectable biologics. Gilead’s recent deal with LEO Pharma is one example. While the specific indication has not yet been announced, Flavius Martin, executive vice president of research at Gilead, told BioSpace in an email that the program is “advancing rapidly” toward clinical testing. Elsewhere, Sanofi extended its collaboration with Nurix Therapeutics last year to include a targeted protein degrader of STAT6. These are but a few of the many targets now being explored in the I&I space. Others run the gamut from Sanofi’s T cell receptor–targeting amlitelimab for atopic dermatitis, with a 52-week data readout expected in March, to the microRNA-targeting obefazimod from Paris-based biotech Abivax, which is awaiting a Q3 2025 Phase III readout in ulcerative colitis. Finally, the “unbridled success” of cell therapies in hematological malignancies is now driving efforts to bring cell therapy to the I&I space, particularly for autoimmune disease , Smith said. Companies like Kyverna are developing CAR T cell therapies to deliver complete B cell depletion that could help reset a patient’s immune system to eliminate the need for chronic treatment. Kyverna is targeting a 2026 filing for its lead therapy KYV-101 in stiff person syndrome, with myasthenia gravis and lupus nephritis to follow. Meanwhile, Arcellx is taking its cell therapy pipeline from multiple myeloma into autoimmune disease. Last fall, the FDA cleared the company’s Investigational New Drug (IND) application to begin a Phase I trial of its CAR T anito-cell in generalized myasthenia gravis. If successful, Smith said the biggest challenges to cell therapies for autoimmune indications would be logistics, scalability, reimbursement and identifying the right patients for treatment. The beauty of the I&I space is that one molecule can have many different applications, Jorge Santos da Silva, CEO of Moonlake Therapeutics, which is developing treatments for inflammatory indications including hidradenitis suppurativa, told BioSpace . “In I&I, you can have these molecules that just walk across a whole lot of therapeutic areas,” a feature he said makes it ripe for investment by biopharma. Smith agreed. “The end markets for I&I relative to targeted oncology are much broader,” he told BioSpace . “There’s a lot of white space.” 5 I&I Diseases Poised for Disruption in 2025 Thomas Smith, a senior research analyst covering immunology at Leerink Partners, highlighted five indications within the I&I space that he believes could see substantive movement this year. Editor’s note: Lists of approved products and products in development are not comprehensive. Metabolic Dysfunction-Associated Steatohepatitis (MASH) The most severe form of nonalcoholic fatty liver disease, MASH affects 5% to 7% of the global population. Approved Products : Madrigal’s Rezdiffra In Development : Akero Therapeutics’ efruxifermin (Phase III) Boehringer Ingelheim’s survodutide (Phase III) Novo Nordisk’s semaglutide (Phase III) Eli Lilly’s tirzepatide (Phase II) Inflammatory Bowel Disease Inflammatory bowel disease (IBD)—including ulcerative colitis (UC) and Crohn’s disease (CD)—affects between 2.4 and 3.1 million people in the U.S. Approved Products : Eli Lilly’s Omvoh Johnson & Johnson’s Remicade AbbVie’s Humira In Development : Abivax’s obefazimod for UC (Phase III) Sanofi and Teva’s duvakitug for UC (Phase II) Equillium and Biocon’s Itolizumab for UC (Phase II) Myasthenia Gravis A chronic autoimmune disorder causing weakness in the voluntary muscles, myasthenia gravis afflicts up to 60,000 people in the U.S. Approved Products : Argenx’s Vyvgart AstraZeneca’s Ultomiris UCB’s Rystiggo In Development : Johnson & Johnson’s nipocalimab (under review) Cabaletta Bio and Kyverna Therapeutics’ CABA-201 (Phase I/II) COUR Pharmaceuticals’ CNP-106 (Phase II) Atopic Dermatitis Atopic dermatitis—a chronic skin condition that causes the skin to become red, itchy and inflamed—affects more than 7% of people in the U.S. Approved Products: Sanofi and Regeneron’s Dupixent Eli Lilly’s Ebglyss Galderma’s Nemluvio In Development : Sanofi’s amlitelimab (Phase III) Kymera Therapeutics and Sanofi’s IRAK4 (Phase II) Apogee Therapeutics’ APG777 (Phase II) Hidradenitis Suppurativa Another chronic, inflammatory skin condition, hidradenitis suppurativa afflicts 1% to 4% of the global population. Approved Products : AbbVie’s Humira Novartis’ Cosentyx UCB’s Bimzelx In Development : Moonlake Therapeutics’ sonelokimab (Phase III) Incyte’s povorcitinib (Phase III)

Welcome back to Endpoints Weekly, thanks for starting your weekend with us. This week’s news was dominated by Robert F. Kennedy Jr.’s confirmation hearings to be HHS Secretary, as Kennedy faced two rounds of questions from multiple Senate committees. It’s looking like a vote will either pass or fail by the slimmest of margins, so keep tuning in to our coverage — and live blogs! — of President Donald Trump’s new administration. Elsewhere in biopharma, earnings season started to get rolling in earnest, with some of the biggest companies like Roche, Novartis, AbbVie and more reporting full-year results from 2024. We’re expecting another big round of earnings next week from the likes of Merck, Pfizer, Eli Lilly and GSK, followed by much of the biotech world in the ensuing weeks. We also had big news this week from Leerink, which is making a comeback after the Silicon Valley Bank fiasco, more developments on the Inflation Reduction Act with regard to President Trump’s HHS communications freeze as it continues to affect agencies, and some long-term MASH data from Akero. Grab a coffee and take a load off as we get into the week’s biggest stories. — Max Gelman 🏛️ Kennedy faced two hearings this week as the Senate took up his nomination for HHS Secretary. The first, which took place Wednesday, was held by the Finance Committee that will ultimately decide whether he can advance to a full Senate vote to be confirmed. While he faced a grilling, Kennedy emerged relatively unscathed. He faced a second panel, held by the Health, Education, Labor and Pensions, or HELP, committee, in a courtesy hearing that will help inform the Finance Committee’s decision. Thursday’s hearing was much more contentious as Kennedy repeatedly declined to refute his past comments that vaccines cause autism, failed to explain the differences between Medicare Parts A, B and C and defended race-based conspiracy theories about how different “antigen levels” in a person’s immune system depend on their skin color and should impact vaccine schedules. And in written answers to follow-up questions from senators submitted Friday, Kennedy continued to avoid directly giving an answer on the debunked claim that vaccines cause autism. Kennedy can’t lose more than three Republican votes . The GOP currently has a 53-47 majority in the Senate, and all Democrats are expected to oppose him despite some early flirtations by Sens. Bernie Sanders (I-VT) and John Fetterman (D-PA) as potential crossover votes. ( Watch how Thursday’s hearing ended. ) Other senators who are likely, but not confirmed, to vote no are Susan Collins (R-ME), Lisa Murkowski (R-AK) and Mitch McConnell (R-KY), a polio survivor who voted against Trump’s pick for Secretary of Defense, Pete Hegseth. Senator Bill Cassidy (R-LA) has emerged as the key vote to confirm Kennedy. Not typically one to break ranks with his fellow Republicans, Cassidy is a longtime physician who sits on both committees that interviewed Kennedy and is chair of the HELP committee. Cassidy opened his remarks Thursday by lamenting how some of the Hepatitis patients he used to work with who died could have been saved if they’d received vaccines as infants. By the end, he said he was still “struggling” with his vote and told Kennedy he’d be reaching out to him over the weekend. Kennedy appeared to shore up support from other undecided Republicans, however. Senators James Lankford (R-OK) and Thom Tillis (R-NC) had earlier expressed reservations about voting for Kennedy. Lankford, who has called himself the “most pro-life senator,” said he was concerned over Kennedy’s past comments on abortion, while Tillis seemed hesitant over his anti-vaccine activism. But both asked friendly questions during their allotted times, and Tillis said afterward he’s leaning toward voting yes. 💵Earnings season is upon us. Several drugmakers gave fourth-quarter updates this week, including Roche , which laid out its M&A strategy during a media call. CEO Thomas Schinecker highlighted the company’s recent Carmot and Poseida acquisitions as blueprints for future deals. And he said Roche would look to China as a source of “potential innovations that we could take over.” Sanofi also hinted at M&A ambitions during a media call on Thursday morning. “We have always been very active in the M&A space. We may be a bit more in the near future due to the fact that we have a strong balance sheet,” CFO François Roger said. CEO Paul Hudson said on a separate call that Sanofi would likely target preclinical and Phase 1 assets. But Roger added that the company “doesn’t feel any pressure to go crazy on M&A” and would be “very disciplined.” Takeda’s longtime CEO Christophe Weber announced his retirement in the company’s third-quarter earnings update this week. Julie Kim, current president of Takeda’s US business unit, will take over in June 2026 as the company’s first female CEO. Until then, Weber will continue to steer Takeda through a multiyear restructuring he announced last May. Teva also revealed a handful of pipeline cuts this week, including a Phase 3 treatment for a form of epilepsy. AbbVie touted the success of Skyrizi and Rinvoq, raising its combined 2027 sales outlook for the two drugs by $4 billion. CEO Rob Michael said the strategy is expected to “drive a rapid return to growth for the company beyond Humira,” which faced its first biosimilar competition in 2023. And Teva told Endpoints News it expects sales growth to continue for Austedo, even after it becomes subject to prices negotiated under the Inflation Reduction Act. 📂Leerink Partners is on a hiring spree to build out its M&A practice. The investment bank has landed several veteran Wall Street dealmakers, and told Endpoints’ Andrew Dunn that it’s at a “distinct pivot point” in M&A. Leerink reemerged following the 2023 collapse of Silicon Valley Bank, which had acquired Leerink in 2019. Founder and CEO Jeff Leerink bought the firm back through bankruptcy proceedings. Now Leerink says it’s “at the strongest point in our history.” 💊The company’s stock price nearly doubled on new data looking at its efruxifermin program in the severe form of MASH, showing a 24% benefit on fibrosis reduction over placebo in a crucial mid-stage trial. Elizabeth Cairns notes there’s nuance to these data, however, as they come from the higher 50 mg dose in the so-called completer analysis. In the intention-to-treat analysis, the benefit over placebo shrank to 17%. That analysis counted the 47 patients who were dosed with efruxifermin but who had missing week 96 data as treatment failures. The drug could still get approved as there are still no treatments on the market for severe MASH, and this week’s data were nominally statistically significant. CMS announced that it will consider “opportunities to bring greater transparency” to the Medicare drug price negotiation process under the Inflation Reduction Act. It’s the first time the Trump administration has commented on how it plans to run the second cycle of negotiations, which begin in about a month. The administration said it is “committed to incorporating lessons learned to date from the program,” but also intends to give stakeholders the chance to “provide specific ideas to improve the negotiation program.” 🗓️Meanwhile, one February FDA advisory committee meeting has been canceled and another has been delayed as the presidential transition continues. A Feb. 24 meeting to discuss a label expansion for Novartis’ Fabhalta was canceled , while a Feb. 5 meeting on opioids was postponed. The cause for the meeting changes remains unclear. DON’T MISS: