Envudeucitinib Phase 3 data show durable gains in psoriasis scalp, itch and quality of life

Alumis Inc. (Nasdaq: ALMS), a late-stage biopharmaceutical company developing next-generation targeted therapies for patients with immune-mediated diseases, today announced new envudeucitinib data from the ONWARD Phase 3 clinical program—ONWARD1, ONWARD2, and the long-term extension ONWARD3.

The results, presented at the 26th Annual Fall Clinical Dermatology Conference, reinforce the potential of envudeucitinib to become a leading oral therapy for patients with moderate-to-severe plaque psoriasis. Envudeucitinib is an investigational, next-generation oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition.

New data across key measures of disease burden build on envudeucitinib’s high-threshold skin clearance across the ONWARD program, including a 54% Psoriasis Area and Severity Index (PASI) 100 response rate at Week 48—the highest publicly reported among existing and investigational oral psoriasis therapies. The data demonstrated early and durable improvements across scalp disease severity (a high-impact, difficult-to-treat area), itch resolution, and quality of life measures.

“For people living with psoriasis, achieving early and sustained relief in difficult-to-treat areas like the scalp and reduction of burdensome symptoms like itch are outcomes that can meaningfully improve quality-of-life,” said Mark Lebwohl, MD, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai. “The consistency of these findings across the ONWARD3 program—alongside high-threshold skin clearance and a favorable tolerability profile—is highly encouraging and underscores the clinical relevance of targeted TYK2 inhibition designed for maximal 24-hour target coverage.”

Fall Clinical Data* Highlights:

• High-rate of scalp clearance: Over 80% of patients in ONWARD3 maintained clear or almost clear scalp skin (scalp-specific Physician Global Assessment [ss-PGA] 0/1) at 48 weeks.
• Rapid, robust and sustained itch relief: In ONWARD 1/2, approximately one-third of patients—including those with moderate-to-severe scalp disease (ss-PGA ≥3)—achieved clinically meaningful itch reduction (≥4-point NRS improvement) as early as Week 2. By Week 16, about 40% reached complete itch resolution (NRS 0) and approximately 60% reported minimal or no itch (NRS 0/1). In ONWARD3, nearly 80% of patients sustained clinically meaningful itch reduction through Week 48.
• Early, durable quality-of-life improvements: Approximately 50% of patients in ONWARD 1/2 achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1 by Week 12, reflecting minimal to no impact of psoriasis on daily activities. In ONWARD3, more than 70% of patients maintained DLQI 0/1 at 48 weeks.
• Rapid crossover convergence: Patients switching from placebo or apremilast achieved rapid improvements across primary and key secondary endpoints, comparable to those continuously treated at Week 48

*ONWARD3: N=1,509, data reported from non-responder imputation analysis in 773 patients from envudeucitinib arms who received up to 48 weeks of continuous treatment (24 weeks in ONWARD1/2 and up to 24 weeks in ONWARD3). ONWARD1/2: N=1771 (envudeucitinib n=459, 433; placebo n=230, 211, apremilast n=223, 215, respectively).

Treatment with envudeucitinib was generally well tolerated in the ONWARD program. No new safety signals were observed with long-term exposure in ONWARD3.

“The dataset presented at Fall Clinical further demonstrates envudeucitinib’s highly competitive clinical profile, reinforcing the strength of our precision engineering approach and its potential to become a leading therapy in the oral psoriasis market,” said Martin Babler, Chief Executive Officer of Alumis. “With our fourth-quarter 2026 NDA submission firmly on track, our organization is focused on regulatory execution and building the foundation designed to bring this next-generation therapy to patients.”

About the Phase 3 ONWARD Clinical Program
The Phase 3 ONWARD clinical program includes two parallel global, multicenter, randomized, double-blind, placebo- and active-comparator-controlled 24-week trials—ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738)—evaluating the efficacy and safety of envudeucitinib in adults with moderate-to-severe plaque psoriasis. More than 1,700 patients were enrolled and randomized 2:1:1 to receive envudeucitinib 40 mg twice daily, placebo, or apremilast.

Patients completing Week 24 of ONWARD1 or ONWARD2 were eligible to enter the ONWARD3 (NCT06846541) study, an ongoing long-term extension study assessing durability, maintenance of response, and long-term safety. In ONWARD3, all patients received open-label envudeucitinib treatment for the first 24 weeks, regardless of their treatment assignment in ONWARD1 and 2. To assess durability and maintenance of response, the first 200 patients achieving PASI 75 at Week 24 in ONWARD3 could enter a 24-week randomized withdrawal period (RWP), in which they were randomized to receive either blinded envudeucitinib or placebo, and reassigned to open-label envudeucitinib upon loss of response or completion of the RWP, whichever occurred first. Patients not entering the randomized withdrawal period continued to receive open-label envudeucitinib treatment. ONWARD3 is designed to provide up to 96 weeks of long-term safety and efficacy data.

About Envudeucitinib
Envudeucitinib is a next-generation, highly selective, oral allosteric inhibitor of tyrosine kinase 2 (TYK2) precision-engineered for maximal 24-hour TYK2 inhibition to correct immune dysregulation across a range of diseases driven by IL-23, IL-17, and Type I interferon. It is the only TYK2 inhibitor shown to deliver maximal target inhibition over 24 hours in humans, with clinical data demonstrating sustained TYK2 blockade in patients with psoriasis while minimizing off-target binding and effects. Envudeucitinib has been administered with or without food, with no fasting requirement. Alumis has reported positive results from its Phase 3 ONWARD program of envudeucitinib in moderate-to-severe plaque psoriasis and plans to file an NDA in moderate-to-severe plaque psoriasis in the fourth quarter of 2026.