Positive Phase 2 Results for ESK-001 TYK2 Inhibitor in Plaque Psoriasis

Alumis Inc., a biopharmaceutical firm focused on oral treatments for immune-mediated disorders, has reported positive results from a Phase 2 trial of ESK-001, a selective TYK2 inhibitor, for moderate-to-severe plaque psoriasis. The study involved 228 participants and aimed to measure the efficacy and safety of different ESK-001 dosages compared to a placebo. The primary goal was a 75% improvement in the Psoriasis Area and Severity Score (PASI 75) at 12 weeks, which was achieved, along with key secondary objectives across tested doses. The top dose of 40 mg twice daily showed the best results with a clear dose-dependent response and was well tolerated.

Preliminary data from an open label extension (OLE) study, where patients continued treatment with two ESK-001 dosages, showed increasing PASI responses over time. At 16 weeks, a significant majority of patients achieved PASI 75 with the 40 mg twice-daily dose, maintaining a favorable safety profile. These results are encouraging for the planned Phase 3 trials set to begin in late 2024.

Dr. Jörn Drappa, Alumis’ Chief Medical Officer, highlighted the importance of the trial's design to assess varying levels of target inhibition's impact on safety and efficacy. He expressed excitement over ESK-001's potential as a best-in-class treatment for psoriasis. Dr. Kim Papp, a clinical investigator in the trial, emphasized the need for well-tolerated and safe oral treatments with efficacy similar to biologics, which ESK-001 could provide.

Martin Babler, Alumis' CEO, noted that the Phase 2 study confirmed the necessity of full TYK2 target inhibition for high efficacy. He expressed confidence in initiating Phase 3 trials with the aim of developing an oral treatment superior to current options for psoriasis and other immune-mediated diseases.

The STRIDE trial's data showed a significant improvement in PASI scores with ESK-001 treatment, with the 40 mg twice-daily dose demonstrating the highest efficacy. The treatment was well tolerated, with no serious adverse events related to treatment and a low discontinuation rate due to adverse events. The most common side effects were headache, upper respiratory tract infection, and nasopharyngitis.

The ongoing OLE study's data as of December 8, 2023, indicated continued improvement in PASI responses and maintained good tolerance up to 28 weeks of treatment. At 16 weeks, 90% of evaluable patients achieved PASI 75 with the 40 mg twice-daily dose.

ESK-001 is also under evaluation in other clinical trials for systemic lupus erythematosus and non-infectious uveitis. Alumis is committed to leveraging its precision data analytics to explore ESK-001's potential in various autoimmune diseases and is developing a once-daily tablet formulation for ESK-001.

Psoriasis is a chronic condition affecting skin and sometimes other body parts, causing red, scaly plaques that can be itchy and painful. Moderate to severe psoriasis significantly impacts quality of life, affecting nearly a quarter of psoriasis patients.

ESK-001, Alumis' lead candidate, is a selective TYK2 inhibitor that has shown no Janus kinase-related safety events and was well-tolerated in Phase 1 studies.

Alumis is advancing a pipeline of oral therapies for immune dysfunction, with ESK-001 currently in trials for several conditions and A-005, a brain-penetrant TYK2 inhibitor, expected to enter Phase 1 trials in 2024. The company is also exploring new targets for immune-mediated diseases through its data analytics platform.