Phase 2 Study Shows ESK-001 Oral TYK2 Inhibitor Effective for Psoriasis Over 28 Weeks

Alumis Inc., a clinical-stage biopharmaceutical company specializing in precision approaches to enhance clinical outcomes for immune-mediated diseases, has shared positive 28-week data from the open-label extension (OLE) phase of its Phase 2 STRIDE clinical trial of ESK-001. These findings were presented at the 2024 European Academy of Dermatology & Venereology (EADV) Congress in Amsterdam.

ESK-001, a highly selective allosteric oral tyrosine kinase 2 (TYK2) inhibitor, is under evaluation in the Phase 3 ONWARD clinical program for moderate-to-severe plaque psoriasis. The data revealed that the 40 mg twice daily dosage was well-tolerated, with most patients attaining significant improvements. Specifically, 93% of patients, based on observed data, and 82.7%, using modified non-responder imputation, reached PASI 75 – the primary endpoint. This indicates a substantial and sustained improvement over time.

Dr. Jörn Drappa, Chief Medical Officer of Alumis, remarked that the OLE results bolster confidence in ESK-001’s potential as a leading oral treatment for moderate-to-severe plaque psoriasis. The upcoming full 52-week OLE data, expected in the first half of 2025, will provide further insights.

Aside from PASI 75, other efficacy measures such as PASI 90, PASI 100, and static Physician’s Global Assessment (sPGA) scores showed strong positive outcomes, reinforcing the drug’s efficacy. The safety profile remained favorable, with most treatment-emergent adverse events being mild or moderate, such as upper respiratory tract infections, nasopharyngitis, and headaches.

In addition to the primary data, three more data presentations at EADV supported ESK-001's promising profile. An oral presentation detailed biomarker data from the Phase 2 STRIDE trial, and an e-poster summarized exploratory exposure-response analyses from the ESK-001 trials. Both underscored the efficacy of the 40 mg twice daily dosage. Another e-poster correlated positive clinical outcomes with significant improvements in patient-reported quality of life and psoriasis-associated pruritus.

Alumis’ lead candidate, ESK-001, is presently involved in two identical global Phase 3 trials – ONWARD1 and ONWARD2. Each involves around 840 patients, assessing ESK-001’s efficacy and safety over 24 weeks. The primary endpoints focus on achieving PASI 75 and sPGA scores. Successful patients will have the option to participate in the ONWARD3 long-term extension trial to evaluate the durability and long-term safety of the treatment.

Supported by promising Phase 2 STRIDE trial results, ESK-001 demonstrated clear dose-dependent responses, achieving maximum efficacy at the 40 mg twice daily dose. Alumis is also working on a once-daily modified release formulation to enhance patient convenience.

Moreover, a Phase 2b trial named LUMUS is evaluating ESK-001 for systemic lupus erythematosus, broadening its potential applications. Alumis’ precision data analytics platform continues to explore additional autoimmune indications for ESK-001.

Alumis, leveraging its proprietary precision data analytics platform, aims to develop a range of molecules targeting various immune-mediated diseases. With a pipeline that includes ESK-001 for both plaque psoriasis and systemic lupus erythematosus, and A-005 for neuroinflammatory and neurodegenerative diseases, Alumis is poised to revolutionize treatments for immune dysfunctions.