Alumis Begins Phase 3 Trial of ESK-001 for Moderate-to-Severe Plaque Psoriasis

Alumis Inc., a clinical-stage biopharmaceutical company focusing on precision oral therapies to enhance clinical outcomes for patients with immune-mediated diseases, has commenced patient dosing in the ONWARD Phase 3 clinical program. This program includes two identical 24-week global Phase 3 clinical trials (ONWARD1 and ONWARD2) aimed at assessing the efficacy and safety of ESK-001 in adults with moderate-to-severe plaque psoriasis, along with a long-term extension (LTE) trial, ONWARD3, to evaluate response durability and long-term safety.

Dr. Jörn Drappa, Chief Medical Officer at Alumis, emphasized the ongoing need for an effective oral treatment for moderate-to-severe plaque psoriasis that does not compromise safety. ESK-001, with its potential to maximally inhibit the TYK2 target, offers a promising option to meet this need. The Phase 3 program mirrors the successful Phase 2 results, which showed ESK-001 to be well tolerated and efficacious, especially in the open-label extension (OLE) study that demonstrated increasing and durable responses over extended treatment periods.

Alumis' President and CEO, Martin Babler, highlighted the significance of the ONWARD Phase 3 program as a pivotal step towards improving clinical outcomes for patients with immune-mediated diseases. He believes this program will solidify the profile of ESK-001 as potentially the first and only oral allosteric TYK2 inhibitor that is well tolerated at doses that achieve maximal target inhibition for treating moderate-to-severe plaque psoriasis.

Additionally, ESK-001 is under evaluation in the LUMUS Phase 2b clinical trial for systemic lupus erythematosus. Alumis employs its precision data analytics platform to explore ESK-001’s potential for other autoimmune indications.

The ONWARD Phase 3 Clinical Program comprises two global, multi-center, randomized, double-blind, placebo-controlled 24-week clinical trials (ONWARD1 and ONWARD2). These trials aim to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis, with comparators including placebo (through Week 16) and apremilast (through Week 24). Approximately 840 patients will be enrolled in each trial, randomized 2:1:1 to receive either ESK-001 40 mg twice daily, placebo, or apremilast.

The co-primary efficacy endpoints will be the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) and a static Physician’s Global Assessment (sPGA) score of 0/1 at Week 16 compared to placebo. Key secondary endpoints will include PASI 90, PASI 100, and sPGA 0 at Weeks 16 and 24, along with safety and tolerability measures. Patient-reported outcomes, including quality of life and pruritus, will also be recorded.

Participants completing Week 24 will be eligible for the long-term extension (LTE) trial, ONWARD3, to assess the durability and maintenance of response and long-term safety. Alumis is also developing a once-daily modified release (MR) oral formulation of ESK-001 to potentially replace the current twice-daily immediate release (IR) formulation.

Plaque psoriasis is a chronic autoimmune inflammatory skin condition characterized by red, scaly plaques that can be itchy and painful. It significantly affects patients' quality of life, particularly in moderate-to-severe cases. Alumis’ lead candidate, ESK-001, is a selective allosteric TYK2 inhibitor that reduces signaling through several cytokine receptors. The ongoing Phase 3 program is backed by positive Phase 2 STRIDE trial data, showing dose-dependent efficacy and safety.

Alumis, leveraging its precision data analytics platform, continues to develop a broad pipeline of therapies targeting immune-mediated diseases. The company's mission is to optimize clinical outcomes and significantly improve patients' lives through innovative treatments.