Alumis (NASDAQ:ALMS) used a conference call to highlight positive top-line Phase III results for envudeucitinib, its next-generation oral TYK2 inhibitor, in adults with moderate to severe plaque psoriasis. Management said the program met all primary and secondary endpoints with “high statistical significance,” showed rapid onset of effect, and delivered deepening skin clearance through 24 weeks while maintaining a safety and tolerability profile consistent with earlier studies.
Phase III ONWARD program: design and endpoints
Chief Medical Officer Dr. Jörn Drappa outlined the Phase III ONWARD program, which includes two global, randomized, double-blind, placebo-controlled trials (ONWARD1 and ONWARD2) evaluating envudeucitinib in adult patients with moderate to severe plaque psoriasis.
The trials’ co-primary endpoints were measured at week 16 versus placebo:
- The proportion of patients achieving PASI 75 (≥75% reduction in Psoriasis Area and Severity Index)
- The proportion of patients achieving sPGA 0/1 (static Physician Global Assessment indicating clear or almost clear skin)
Efficacy highlights: rapid onset and deepening responses
Drappa reported that both Phase III trials met all primary and secondary endpoints with p-values of less than 0.0001 for the co-primary endpoints. Averaged across the two studies, envudeucitinib-treated patients achieved 74% PASI 75 and 59% sPGA 0/1 at week 16.
He also described rapid clinical separation from placebo, with PASI 90 responses emerging as early as week 4. By week 24, the company reported “leading skin clearance rates” at higher thresholds, with approximately 65% of patients achieving PASI 90 and more than 40% achieving PASI 100 on average across both trials.
In Q&A, the company said PASI 75 tended to plateau earlier, while PASI 90 and PASI 100 “were still pointing upwards” at week 24, with additional longer-term data expected at 48 weeks. Drappa also said results were broadly similar between ONWARD1 and ONWARD2; one trial had a slightly higher placebo PASI 75 response at week 16, but placebo-adjusted responses were described as the same between trials, and higher-hurdle endpoints (PASI 90/100) were “highly consistent.”
Patient-reported outcomes and itch
Management emphasized improvements in patient-reported outcomes, including quality of life and itch. In response to an analyst question, Drappa confirmed that itch results were statistically significant and of a magnitude that, in his view, has traditionally supported inclusion of itch reduction in FDA labeling.
CEO Martin Babler also framed itch as a key symptom influencing patients’ perception of how quickly a therapy is working, suggesting that rapid relief could contribute to perceived onset of action alongside improvements in skin clearance metrics.
Safety and tolerability
Drappa said envudeucitinib was generally well tolerated through week 24, with a safety profile consistent with Phase II and open-label extension data. Treatment-emergent adverse events were described as similar across studies, mostly mild to moderate and transient, and responsive to standard therapy when needed. The most commonly reported adverse events included headache, nasopharyngitis, upper respiratory tract infection, and acne. He said no new safety signals were observed.
In Q&A, the company said discontinuation due to adverse events was “very low,” in the low single digits, and described as lower than many comparable trials.
Regulatory timing, additional data, and pipeline plans
Babler said Alumis plans to file a New Drug Application in the second half of 2026. In response to a question about what is “gating” the filing, management pointed to the need to complete the randomized withdrawal portion of the Phase III program to generate durability and maintenance data before filing.
The company said additional Phase III results will be presented at an upcoming medical meeting, including further secondary endpoints (skin clearance at weeks 16 and 24, patient-reported outcomes, and exploratory assessments of scalp, palmoplantar disease, and nail psoriasis) as well as planned biomarker and pharmacodynamic analyses.
Beyond psoriasis, management highlighted two additional development efforts:
- A potentially pivotal Phase IIb trial of envudeucitinib in systemic lupus erythematosus (SLE), with top-line data expected in Q3 2026.
- A-005, described as a CNS-penetrant TYK2 inhibitor with positive Phase I data, expected to enter a Phase II multiple sclerosis trial in the first half of the year.
Babler also referenced lonigutamab, which the company obtained through its merger with ACELYRIN, and said a fourth program is planned to enter the clinic this year.
On commercialization strategy, Babler said Alumis has a “small but mighty” commercial team and has medical science liaisons in the field, but indicated that launching globally across multiple indications would be unlikely and that the company is evaluating the timing and structure of potential partnering for envudeucitinib.
Management also discussed efforts to develop a once-daily formulation. Babler said the company identified a once-daily formulation that achieved a once-daily pharmacokinetic profile but did not meet all target product profile parameters, and work is ongoing. He added that market research suggested two-thirds of patients would prefer a twice-daily oral therapy with no food restriction over a once-daily option with a fasting requirement.
About Alumis (NASDAQ:ALMS)
Our mission is to significantly improve the lives of patients by replacing broad immunosuppression with targeted therapies. Our name, Alumis, captures our mission to enlighten immunology, and is inspired by the words “allumer”-French for illuminate-and “immunis”-Latin for the immune system. We are a clinical stage biopharmaceutical company with an initial focus on developing our two Tyrosine Kinase 2 (TYK2) inhibitors: ESK-001, a second-generation inhibitor that we are developing to maximize target inhibition and optimize tolerability, and A-005, a central nervous system (CNS) penetrant molecule.
