Alumis crushed by midstage lupus flop but plots path to phase 3 for TYK2 inhibitor

Biotech Alumis crushed by midstage lupus flop but plots path to phase 3 for TYK2 inhibitor By Nick Paul Taylor Sep 1, 2026 9:27am Alumis lupus failed trials autoimmune disease A phase 2b lupus trial of Alumis’ envudeucitinib has missed its primary and secondary endpoints. But the biotech is still moving the TYK2 inhibitor into phase 3 in the autoimmune disease, pointing to evidence of efficacy in a prespecified subgroup of patients to support its decision. The failed Lumus trial randomized 408 adults with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) to receive one of three oral envudeucitinib doses or placebo for 48 weeks.

Envudeucitinib fared no better than placebo on a measure of overall disease activity, causing the trial to miss its primary endpoint. Alumis also reported the failure of secondary endpoints. Investors sent Alumis’ stock down 54% to below $10 in premarket trading.

Yet the biotech presented the data in a positive light, choosing to advance envudeucitinib toward a phase 3 trial based on responses in a subgroup of patients with high interferon gene signature (IFNGS‑high). “These results are consistent with the type I interferon target mechanism and confirm that envudeucitinib is working as designed,” Alumis CEO Martin Babler said on a conference call with investors to discuss the data. “The subgroup of the population is an established and readily identifiable patient group and represents a large opportunity of moderate-to-severe SLE patients.” On the primary endpoint, the company reported a 52.6% response rate on the top envudeucitinib dose in the IFNGS‑high subgroup, compared to a 24.4% result in IFNGS‑low patients.

Alumis reported a similar divergence between the IFNGS‑high and -low subgroups on other endpoints. The subgroup represented about 60% of patients in Lumus. The proportion of IFNGS‑high patients was lower than expected, Jörn Drappa, M.D., Ph.D., chief medical officer at Alumis, said on the call, with other phase 2 and 3 trials seeing an 80:20 split.

Drappa hypothesized that Lumus may have enrolled fewer IFNGS‑high patients because the availability of more SLE drugs has reduced the pool of patients with severe disease activity available for clinical trials. The Lumus patient population was skewed toward people with moderate—rather than severe—SLE. Alumis plans to discuss the data with the FDA and move into a phase 3 trial that either limits enrollment to IFNGS‑high patients or caps the proportion of participants with IFNGS‑low SLE, Drappa said.

While the phase 2b data necessitate some work to further characterize the responder population, Babler expects the timeline for further development in SLE to be largely unaffected by the midstage data. The biotech will advance envudeucitinib toward a phase 3 trial while preparing to submit the molecule for approval in psoriasis. Alumis reported a phase 3 win in psoriasis at the start of the year, establishing the drug candidate as a rival to Takeda’s TYK2 inhibitor zasocitinib, for which the Japanese pharma paid $4 billion to buy.

Alumis’ confidence in the potential of envudeucitinib beyond SLE and psoriasis was undiminished by the phase 2b data. The results have “strengthened our conviction that this is a rational target in type I interferon mediated diseases, at least those patients who have a bona fide interferon signature,” Drappa said. The results encouraged the executive that the TYK2 inhibitor should work in cutaneous lupus.

Alumis lupus failed trials autoimmune disease Biotech Clinical Data