Amlitelimab

At this year’s American Academy of Dermatology annual meeting, companies like Amgen, Bristol Myers Squibb and Alumis took the stage to report the latest on their dermatology candidates. Here are the highlights: The partners’ anti-OX40 antibody, dubbed rocatinlimab, met the co-primary endpoints of the ROCKET-Ignite trial in moderate to severe atopic dermatitis, according to 24-week data presented Saturday. Just over 40% of patients in the higher dose cohort and around 36% of subjects in the lower dose group achieved a minimum 75% reduction from baseline in their Eczema Area and Severity Index score (EASI-75), with both results proving statistically significant compared with placebo. In the study’s other primary endpoint, around 24% of higher dose patients and 19% of lower dose participants attained a validated Investigator’s Global Assessment (IGA) for atopic dermatitis score of clear or almost clear with a minimum two-point reduction from baseline. Safety wise, pyrexia, chills and headache were the most common side effects. This means there’s still room for Sanofi to differentiate on safety with its OX40-targeting candidate amlitelimab, which seems to be associated with fewer fevers and chills, Jefferies analysts wrote Monday. ROCKET-Ignite is part of Amgen’s broader ROCKET registrational development program, which includes eight trials. Saturday’s results are “optically more compelling” than topline data from the ROCKET-Horizon study and “should help rebuild belief” in the drug class, the Jefferies analysts said. Topline data from the ROCKET-Horizon trial were unveiled in September but at the time, Leerink analysts described them as “underwhelming.” Bristol Myers’ Sotyktu hit the primary endpoint of ACR20 response (which is shorthand for a minimum 20% improvement in disease signs and symptoms) in the Phase 3 POETYK PsA-2 trial, according to late-breaking data presented Saturday. That study enrolled 730 patients with active psoriatic arthritis who had not previously received a biologic disease-modifying antirheumatic drug or had been treated with a TNFα inhibitor. In the primary endpoint, more than half of patients treated with Sotyktu achieved an ACR20 response versus 39% of placebo patients at 16 weeks. The treatment also met key secondary endpoints. Bristol Myers plans to discuss the data with regulatory authorities. Last year, Wall Street projected Sotyktu could reach $1.9 billion in sales in 2030. Johnson & Johnson and Protagonist Therapeutics’ IL-23 receptor blocker, dubbed icotrokinra, could be coming for Sotyktu’s market share, based on data presented Saturday. Icotrokinra met the co-primary endpoints and all key secondary endpoints in the Phase 3 ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 studies, including those measuring its efficacy against Sotyktu. These results were “fully expected based upon historical trial results,” Leerink analysts said in a Sunday note. But taken together with previously announced positive results from the Phase 3 ICONIC-LEAD study, the overall data “underscore the potential for icotrokinra to shift treatment expectations in moderate-to-severe plaque psoriasis,” Liza O’Dowd, J&J’s head of immunodermatology said in the release. The US drugmaker is now starting the Phase 3 ICONIC-ASCEND trial, which will set icotrokinra head-to-head against its own drug Stelara. The California biotech said its oral TYK2 inhibitor, dubbed ESK-001, showed “sustained or increasing clinical responses” in the open-label extension part of the Phase 2 STRIDE trial in moderate to severe plaque psoriasis. Almost 39% of the patients treated with the 40 mg dose experienced a complete resolution of their lesions at 52 weeks compared with almost 27% at 12 weeks, according to late-breaking data presented Saturday. The trial met its primary endpoint around a year ago. Alumis is already testing ESK-001 in the ongoing Phase 3 ONWARD program, which comprises two parallel studies enrolling 840 patients each. The 40 mg dose is being set against placebo and Amgen’s Otelza. Topline data from the program are expected in the first quarter of 2026. Sotyktu became the first oral TYK2 inhibitor to secure FDA approval for psoriasis back in September 2022. But last week, Leerink analysts said ESK-001 has best-in-class potential thanks to its “superior target inhibition.” The candidate is also being advanced for systemic lupus erythematosus.

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)