Alumis, a late-stage biopharmaceutical company focused on next-generation targeted therapies for immune-mediated diseases, has announced positive topline results from its Phase 3 ONWARD1 and ONWARD2 trials of envudeucitinib, a highly selective oral TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis.

Envudeucitinib met all primary and secondary endpoints with high statistical significance, delivering superior skin clearance compared with placebo on the co-primary endpoints of Psoriasis Area and Severity Index (PASI) 75 and static Physician’s Global Assessment (sPGA) 0/1 at Week 16. Across both trials, 74% of patients achieved PASI 75, and 59% achieved sPGA 0/1, with responses deepening over time. Placebo-adjusted response rates were consistent between the two studies.

At Week 24, envudeucitinib continued to impress on higher hurdles: ~65% of patients achieved PASI 90, and over 40% reached complete skin clearance (PASI 100). Rapid responses were evident, with PASI 90 separation from placebo as early as Week 4. Patients also reported clinically meaningful improvements in itch and quality of life. Envudeucitinib outperformed apremilast on all PASI endpoints at Week 24.

“We believe envudeucitinib demonstrates the full promise of TYK2 inhibition,” said Dr. Jörn Drappa, Chief Medical Officer of Alumis.

“By maximally inhibiting TYK2, envudeucitinib blocks both IL‑23 and IL‑17 to deliver comprehensive disease control. In Phase 3, this translated into rapid onset of action, high rates of skin clearance, and meaningful symptom improvements that rank among the strongest reported for an oral therapy. We are deeply grateful to the patients, families, and investigators whose commitment made this milestone possible.”

The therapy was well tolerated through Week 24, with a safety profile consistent with Alumis’ Phase 2 data. Most treatment-emergent adverse events (TEAEs) were mild to moderate, transient, and manageable with standard therapy. The most common TEAEs were headaches, nasopharyngitis, upper respiratory infections, and acne. No new safety signals emerged.

“Patients with moderate-to-severe psoriasis have to choose between oral and biologic therapies,” said Dr. Andrew Blauvelt, leading dermatologist and psoriasis expert.

“And for individuals seeking the best chance for clearance, biologics have long been superior to oral therapies. But now, with these new data on envudeucitinib, we’re seeing an exciting possibility of a new oral drug for psoriasis that can deliver high levels of efficacy in a safe manner.”

“These pivotal data strengthen our conviction in envudeucitinib’s potential to transform the treatment landscape for IL‑23/IL‑17–driven diseases as well as those driven by Type I interferon,” said Martin Babler, Chief Executive Officer of Alumis.

“These results reinforce our enthusiasm that envudeucitinib’s highly differentiated clinical profile positions it at the forefront of next-generation TYK2 inhibitors in psoriasis, with potential in systemic lupus erythematosus and beyond as a true pipeline-in-a-pill.”