Pharma Focus America

Alumis to Extend Phase 2 Program of Allosteric TYK2 Inhibitor, ESK-001, to Address Systemic Lupus Erythematosus (SLE) and Uveitis

Friday, June 30, 2023

Alumis Inc., a clinical stage biopharmaceutical company, has recently announced the initiation of patient dosing in two Phase 2 clinical trials for their lead clinical candidate, ESK-001. The trials are aimed at evaluating the efficacy and safety of ESK-001 in treating patients with systemic lupus erythematosus (SLE) and active noninfectious uveitis.

SLE is a chronic immune-mediated disease that affects multiple organs. Alumis' proprietary lead clinical candidate, ESK-001, is a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor. TYK2 mediated cytokines have been identified as critical drivers of disease in lupus, and there is a significant need for oral treatments with improved efficacy and side effect profiles.

The first trial, LUMUS, is a global, multicenter, randomized, double-blind, placebo-controlled trial that aims to enroll approximately 388 adult patients with moderately to severely active, autoantibody-positive SLE. The trial will assess the efficacy, safety, and pharmacokinetics of multiple doses of ESK-001 over a 48-week period. The primary endpoint of the trial is the comparison of the proportion of patients with improvement in overall SLE disease activity at Week 48 relative to baseline using the British-Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Secondary endpoints include safety, tolerability, and various measures of disease activity.

The second trial, OPTYK-1, is a proof-of-concept Phase 2 trial in adult patients with active noninfectious intermediate, posterior, or panuveitis. Uveitis is a form of eye inflammation associated with systemic immune-mediated diseases, and TYK2 dysregulation may play a role in its pathogenesis. The trial is designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of two doses of ESK-001. The primary endpoint is the proportion of patients failing treatment for active noninfectious uveitis by Week 24, which will be compared between the two ESK-001 treatment groups.

Dr. Martin Babler, CEO of Alumis, expressed excitement about the Phase 2b program for ESK-001 in SLE, highlighting the potential benefit it may offer to people living with the disease. Dr. Jörn Drappa, Alumis' chief medical officer, mentioned the company's precision approach and its evaluation of genomic and proteomic data to guide the development of ESK-001 for other indications, such as inflammatory bowel disease and psoriatic arthritis.

In addition to the two Phase 2 trials mentioned, Alumis also has an ongoing Phase 2 trial, called STRIDE, evaluating ESK-001 in patients with moderate to severe plaque psoriasis. The company plans to leverage its precision data analytics and multi-platform approach to explore the potential applications of ESK-001 in other autoimmune indications.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the immune system attacking the body's own tissues, resulting in inflammation and potential damage to various organs. It can affect multiple parts of the body, including the skin, joints, heart, lungs, kidneys, blood cells, and brain. While there is no cure for lupus, current treatments aim to alleviate symptoms and reduce inflammation to minimize organ damage.

Uveitis is a form of eye inflammation that affects the uvea, the middle layer of the eye's wall. Common symptoms include eye redness, pain, sensitivity to light, and blurred vision. Uveitis can occur in one or both eyes and can affect individuals of all age groups, including children. Causes of uveitis can include infections, eye injuries, or systemic inflammatory or autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, or lupus. If left untreated, uveitis can lead to permanent vision loss due to damage to essential eye tissues.

ESK-001, developed by Alumis, is an allosteric tyrosine kinase 2 (TYK2) inhibitor. It selectively reduces signaling through various cytokine receptors, including those for interleukin (IL)-12, IL-23, and interferon (IFN)-a. ESK-001 has shown promising results in Phase 1 studies, demonstrating complete inhibition of the pharmacodynamic assay over a 24-hour dosing schedule. The drug has been well-tolerated, with no serious adverse events or safety concerns related to TYK2 inhibition reported so far.

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