Litifilimab

Pictured: Biogen’s signage at its headquarters in Massachusetts iStock, JHVEPhoto With two late-stage programs set to read out in the next 48 months, Biogen is translating its wealth of experience in multiple sclerosis to lupus—developing a pipeline BMO Capital Markets analysts called “thoughtful.” With its storied multiple sclerosis franchise under increasing pressure from declining sales, Biogen’s other programs are stepping into the spotlight—including one where the biotech is leveraging that deep well of immunological experience. Last week, the Cambridge, Mass.–based company held an investor call highlighting its lupus portfolio, helmed by two late-stage assets representing a multi-faceted approach to the autoimmune disease. The first of these, dapirolizumab pegol, being developed in collaboration with UCB, is currently in a second Phase III study with confirmatory data expected in late 2027 or 2028. Meanwhile, litifilimab is involved in three ongoing Phase III studies, all reading out in the next couple of years. “We’re at this inflection point now,” Diana Gallagher, senior vice president of the Multiple Sclerosis and Immunology Disease Unit and Alzheimer’s and Dementia Disease Unit at Biogen, told BioSpace prior to the investor presentation. “We’ve been working in lupus for almost the whole decade that I’ve been here, but really are now at this really exciting point.” Diana Gallagher When asked if the lupus franchise is taking the place of MS in terms of clinical development, Gallagher said, “hopefully it’s a ‘yes, and’ kind of answer. “I still have this sort of really interesting MS portfolio,” she continued. “But yes, I do think that there is intention at Biogen to have this exciting neurology pipeline, an immunology pipeline and a rare disease pipeline. You’ll see the three really pillars of our strategy.” At least one analyst firm reacted positively to the peek under Biogen’s immunological hood. “Biogen lupus pipeline event highlights thoughtful approach to develop assets targeting a diease [sic] with high unmet need,” BMO Capital Markets wrote Sept. 3 in a note to investors. Zooming out on the company, the group added, “With commercial stories like Leqembi, Skyclarys, and Spinraza taking more priority, we are starting to get the feeling that Biogen’s pipeline may be underappreciated, a point emphasized by today’s presentation.” The Lupus Landscape A complex autoimmune disease affecting multiple organ systems and disproportionately afflicting women and people of color, lupus has long proven difficult to treat. In the past 50 years, there have only been two drugs approved for lupus, Gallagher said: GSK’s Belimumab, approved in 2011, and AstraZeneca’s Saphnelo , greenlit in 2021. “So it’s really been quite quiet.” In terms of barriers to therapeutic progress, Gallagher pointed to potential sociodemographic reasons and a complicated biology. “People felt like they couldn’t unravel it. They’re like, oh, there’s so much redundancy, we don’t know what targets to go after.” Adding to these challenges, she said, have been “a lot of failed trials, which makes people shy away, because they’re like, oh, nothing works.” However, she said, the space is “definitely making great strides.” Biogen’s Approach While tackling lupus is a tall order, Gallagher said Biogen “feel[s] like we understand the complexity of immunology and having to have a multi-faceted approach.” And while lupus and MS are certainly not the same, Gallagher pointed to several similarities. Both diseases are immunologically based, predominantly affect young women— approximately 90% of lupus diagnoses are in female patients—and have a relapsing/remitting course. Biogen was one of the first companies “to go into MS and uncouple all that and bring multiple drugs to market,” Gallagher said. “We see [lupus] as another sort of area that we can spend that time that it takes—and we’ve been at it for a couple decades now—to really unravel this and bring a multi-faceted approach for these patients who really have been waiting a long time to have adequate therapy.” As for this multi-faceted approach, dapirolizumab pegol (DZP), a humanized Fc-free polyethylene glycol (PEG)-conjugated antigen-binding fragment, is targeting SLE. DZP inhibits the signaling of CD40L, a key target to disrupt CD40 signaling and interrupt the immunological cascade in SLE, according to Biogen’s investor presentation on Wednesday. Biogen and UCB claimed a Phase III win for DZP last September in what Stifel analysts at the time called a “positive surprise.” This followed a Phase II failure for the drug in 2018 when it was unable to demonstrate a significant dose response at 24 weeks. Despite the missed endpoint, the partners pushed forward, betting on what they flagged as “consistent and potentially meaningful improvements” across “majority of clinical endpoints.” So far, this bet appears to have paid off. A second Phase III candidate, litifilimab, a humanized IgG1 monoclonal antibody targeting BDCA2, is in development for both SLE and cutaneous lupus erythematosus (CLE). The BDCA2 receptor is predominantly expressed on a subset of immune cells called plasmacytoid dendritic cells (pDCs). When binding to BDCA2, litifilimab has demonstrated the ability to reduce production of pro-inflammatory molecules by pDCs, including type-I interferon, cytokines and chemokines, pro-inflammatory mediators that are thought to play a significant role in both SLE and CLE, according to Biogen . The first Phase III data for litifilimab, from two trials in SLE, are expected by the end of 2026, Gallagher said, while Phase III CLE data should follow in 2027. Finally, Biogen’s 2024 acquisition of Human Immunology Biosciences (HI-Bio) brought into the fold felzartamab, an investigational antibody targeting CD38. Biogen is studying felzartamab in a range of disease areas, including lupus nephritis, where it’s currently in a Phase Ib trial. Gallagher hopes to see topline data from this trial next year. “So next year, for sure, a lot of cards flipping,” she said. “It’s exciting.”