Alumis Announces Topline Results from Envudeucitinib Phase 2b Trial in Systemic Lupus Erythematosus (SLE)

Alumis Inc., a late-stage biopharmaceutical company, announced today the results of its Phase 2b LUMUS trial for envudeucitinib, a next-generation, highly selective, oral allosteric inhibitor of tyrosine kinase 2 (TYK2), in the treatment of moderate-to-severe systemic lupus erythematosus (SLE). The trial did not meet its primary and secondary endpoints in the overall trial population. However, robust responses were observed in a prespecified subgroup of patients with a high interferon gene signature (IFNGS-high), supporting the potential for further Phase 3 development.

In the overall trial, envudeucitinib failed to achieve the primary endpoint, which was measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 48. Key secondary efficacy endpoints, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), SLE Responder Index 4 (SRI-4), and Lupus Low Disease Activity State (LLDAS), also did not meet their targets. Notably, the trial enrolled 408 patients, who were classified as IFNGS-high or IFNGS-low based on a commercially available interferon gene signature assay. IFNGS-high patients, representing the majority of moderate-to-severe SLE cases, typically respond more favorably to interferon pathway-targeted therapies and show lower placebo response rates. In the LUMUS trial, the IFNGS-high subgroup unexpectedly showed a higher placebo response rate, reducing the overall trial's response rates.

Dr. Jörn Drappa, Chief Medical Officer of Alumis, expressed gratitude to the patients, families, and investigators who participated in the trial. He stated, "Although envudeucitinib did not meet its primary objective in the overall trial population, the magnitude of effect observed in the prespecified IFNGS-high subgroup is highly compelling in a disease with no targeted oral therapies currently available. We plan to engage regulators to discuss Phase 3 development for envudeucitinib."

Pharmacodynamic data from the trial confirmed robust dose-dependent suppression of the interferon pathway, with maximal suppression observed at the highest dose of 40mg twice daily. This further supports the potential of envudeucitinib in interferon-driven immune-mediated diseases. The drug was generally well tolerated, with no new safety signals observed.

Martin Babler, Chief Executive Officer of Alumis, commented, "The mechanism validated by these data underscores a multi-indication opportunity for envudeucitinib across Type I interferon-driven diseases, including cutaneous lupus erythematosus and Sjögren’s disease. We are actively evaluating opportunities to maximize the value of our oral TYK2 portfolio and remain on track to file an NDA for envudeucitinib in moderate-to-severe plaque psoriasis in the fourth quarter of this year."

Alumis will host a webcast on September 1, 2026, at 8:30 am EDT, to review the Phase 2 LUMUS trial results. The live webcast can be accessed via the company's website or on the Events tab in the Investors section. A replay of the webcast will be available after the call.

Envudeucitinib is currently in the process of regulatory submission for moderate-to-severe plaque psoriasis, with plans to file an NDA in the fourth quarter of 2026. The company remains committed to advancing its pipeline of targeted therapies for immune-mediated diseases.