South San Francisco-based Alumis Inc. (Nasdaq: ALMS) reported new Phase III data from its ONWARD program showing that envudeucitinib (ESK-001), an investigational oral TYK2 inhibitor, produced durable scalp clearance, itch resolution, and quality-of-life improvements in adults with moderate-to-severe plaque psoriasis, with the company saying it remains on track to submit an NDA in Q4 2026.
Envudeucitinib binds the regulatory JH2 pseudokinase domain of TYK2, blocking ATP binding at the catalytic JH1 domain and suppressing downstream IL-23, IL-12, and type I interferon signaling central to plaque psoriasis pathogenesis.
In the new ONWARD3 analysis, more than 80% of patients maintained clear or almost clear scalp skin at Week 48, nearly 80% sustained clinically meaningful itch reduction, and more than 70% maintained a Dermatology Life Quality Index (DLQI) score of 0/1, indicating no effect of psoriasis on their quality of life. Alumis reported no new safety signals with longer-term treatment.
Previously reported ONWARD1 and ONWARD2 results showed Week 24 PASI 90 response rates—at least a 90% improvement in skin disease severity—of 68.0% and 62.1%, respectively. Complete skin clearance, or PASI 100, was achieved by 41.0% and 39.5%, respectively. Previously disclosed ONWARD3 results showed a PASI 100 response rate of 54% at Week 48 of continuous treatment.
The randomized, double-blind Phase III trials ONWARD1 and ONWARD2 enrolled 1,771 adults with moderate-to-severe plaque psoriasis. Patients were assigned 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or apremilast for 24 weeks.