Alumis Inc.’s investigational oral tyrosine kinase 2 (TYK2) inhibitor, ESK-001, demonstrated a positive clinical response and safety profile after 52 weeks in patients with plaque psoriasis, according to late-breaking Phase 2 data presented at the 2025 American Academy of Dermatology Association (AAD) Annual Meeting in Orlando, FL.
In the open-label extension (OLE) STRIDE Trial, patients receiving 40mg twice daily (BID) dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week 52 compared to Week 12 as measured by Psoriasis Area and Severity Index (PASI), Static Physician’s Global Assessment (sPGA), Numeric Rating Scale (NRS) for Itch, and quality-of-life via Dermatology Life Quality Index (DLQI)I0/1. At Week 52, patients maintained robust clinical improvements in control of itch (NRS≤4, 81.3%) and quality-of-life (DLQI0/1, 61.3%). Moreover, Treatment with ESK-001 continued to be generally well tolerated at week 52, with safety and tolerability consistent with previously reported Week 16 and Week 28 data and no new safety findings.
ESK-001 is currently being evaluated in the Phase 3 ONWARD clinical program, which consists of two parallel global Phase 3, multicenter, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2. Each trial will enroll approximately 840 patients randomized 2:1:1 to receive either ESK-001 40mg twice daily, placebo, or apremilast (Otezla, Amgen). The co-primary efficacy endpoints will be the proportion of patients with moderate-to-severe plaque psoriasis achieving a PASI 75, and sPGA score 0/1 of ESK-001 compared to placebo at Week 16. Patients completing Week 24 will have the opportunity to participate in a long-term extension (LTE) trial, ONWARD3, that will evaluate the durability and maintenance of response and long-term safety. (Alumis will soon merge with Acelyrin.)
Study author Andrew Blauvelt, MD, MBA, Chair of the Medical Board of the National Psoriasis Foundation, sat down with TDD to go over the results of the late breaker and the role that oral therapies may play in psoriasis in the future.
TDD: Tell us how ESK-001 fits in with the TYK2 class of medications.
Dr. Blauvelt: “We know about this class of drugs because of the drug deucravacitinib (Sotyktu, Bristol Myers Squibb), which has been approved for moderate-to-severe psoriasis for the last several years. Following the approval of deucravacitinib, we’ve seen several new TYK2 inhibitors come from other companies into the space and are being developed for plaque psoriasis. The second generation of TYK2s has been focused on improving upon the deucravacitinib results. And for this molecule in particular [ESK-001], Alumis has done lots of in vitro work to increase the selectivity to TYK2, to make sure the dosing is correct, and to make sure it has a complete inhibition of its target with in vivo dosing. With this drug, there’s an inhibitory concentration of greater than 90%, with 40mg twice daily (BID) dosing, which was selected for the Phase 2 study.”
TDD: How did ESK-001 perform in the of the OLE Phase 2 STRIDE trial?
Dr. Blauvelt: “The main reporting was about the Week 52 data in people who are now on 40mg BID. Some of the patients had been on 40mg twice a day for the entire 52 weeks, and some had been switched over at various times to that optimal dose. We reported the PASI 75, 90, and 100 results in that long-term extension. We found that over the course of one year, 38.8% of patients achieved PASI 100, 61.3% of the patients achieved PASI 90, and 77.5% of patients achieved PASI 75. These results are higher than what we’ve seen from previous TYK2 inhibitors. That’s the exciting part or one of the exciting parts of this study.”
TDD: What other oral molecules look promising in psoriasis?
Dr. Blauvelt: “There’s a Johnson & Johnson targeted oral peptide that selectively blocks interleukin (IL)-23 called Icotrokinra, and then ESK-001. These raise the bar…for oral therapies, and if you look at the efficacy of these two newer agents, you actually see them very similar. It’s a good thing for patients because we need more oral therapies. Both of these drugs actually [appear] very safe as well.”
