Alumis Announces Expansion of Allosteric TYK2 Inhibitor, ESK-001, Phase 2 Program into Systemic Lupus Erythematosus (SLE) and Uveitis
- Category: Small Molecules
- Published on Friday, 30 June 2023 10:11
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– Patient dosing initiated in LUMUS, a 388 patient Phase 2b clinical trial of ESK-001 for the treatment of SLE –
– Patient dosing initiated in OPTYK-1, a proof-of-concept clinical trial of ESK-001 for the treatment of uveitis –
SOUTH SAN FRANCISCO, CA, USA I June 29, 2023 I Alumis Inc., a clinical stage biopharmaceutical company developing oral therapies using a precision approach to transform the lives of patients with immune-mediated diseases, today announced that patient dosing has commenced in LUMUS, a Phase 2b clinical trial of ESK-001 for the treatment of patients with systemic lupus erythematosus (SLE) and in OPTYK-1, a proof-of-concept Phase 2 clinical trial in uveitis. SLE is a chronic immune-mediated disease involving multiple organs. ESK-001 is Alumis’ proprietary lead clinical candidate and is a highly selective and potentially best-in-class allosteric tyrosine kinase 2 (TYK2) inhibitor.
“TYK2 mediated cytokines have been shown to be critical drivers of disease in lupus, and there is a large unmet need for oral treatments with improved efficacy and side effect profiles,” said Martin Babler, chief executive officer of Alumis. “ESK-001 is a highly selective allosteric inhibitor of TYK2 that demonstrated full, sustained target inhibition and was well tolerated in Phase 1 studies of healthy volunteers. The promising data to date for ESK-001 enables us to explore optimal dosing to drive efficacy, with the ultimate goal of achieving a best-in-class profile tailored to each disease indication. We are very excited to have started this rigorously designed Phase 2b program for ESK-001, and evaluate its potential benefit for people living with SLE.”
LUMUS is a global, multicenter, randomized, double-blind, placebo-controlled trial that is designed to evaluate the efficacy, safety and pharmacokinetics of multiple doses of ESK-001 in adult patients with moderately to severely active, autoantibody-positive SLE. The trial is powered, and will be executed, with the rigor of a potentially pivotal trial and will enroll approximately 388 patients across multiple doses of ESK-001 or placebo for 48 weeks. Following the trial, eligible patients may enroll in an open-label extension study or participate in a four-week safety follow-up period. The primary endpoint of the trial will compare the proportion of patients with improvement in BICLA at Week 48 relative to baseline across doses of ESK-001 and placebo. British-Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) is an accepted composite measure of overall SLE disease activity. Secondary endpoints include safety and tolerability, as well as various measures of disease activity.
Alumis also announced that patient dosing has commenced in OPTYK-1, a Phase 2 clinical trial of ESK-001 for the treatment of patients with active noninfectious uveitis. Uveitis is a form of eye inflammation that causes swelling of the uvea, the middle layer of the wall of the eye. Uveitis is commonly associated with systemic immune mediated diseases such as psoriasis, rheumatoid arthritis, Crohn’s disease and sarcoidosis, in which dysregulation of TYK2 mediated pathways may also play an important role. The Phase 2 uveitis clinical trial is proof-of-concept, multi-center, randomized, double-masked, trial that is designed to evaluate the efficacy, safety and pharmacokinetics and pharmacodynamics of two doses of ESK-001 in adult patients with active noninfectious intermediate, posterior or panuveitis (uveitis). The primary endpoint is the proportion of patients failing treatment for active non-infectious uveitis (NIU) by Week 24 and will be compared between the two ESK-001 treatment groups.
Dr. Jörn Drappa, Alumis’ chief medical officer, added, “Leveraging our proprietary precision data analytics and multi-platform approach, we determined that uveitis would be a compelling indication for several reasons. We see an opportunity to reach patients in need of more effective, oral therapeutics, in a disease with well-defined outcome measures in which TYK2 is likely to be an important driver. Data generated in this study may also inform how we can best advance ESK-001 into larger, more complex indications that may also be addressed by TYK2 inhibition. Furthermore, our precision approach includes evaluation of genomic and proteomic data to guide our TYK2 development for other indications such as inflammatory bowel disease and psoriatic arthritis.”
Alumis now has three ongoing Phase 2 clinical trials evaluating ESK-001 including the STRIDE clinical trial (NCT05600036) in patients with moderate to severe plaque psoriasis, from which data are anticipated in the third quarter of 2023. Alumis continues to leverage its precision data analytics and a multi-platform approach to explore ESK-001’s potential application in other autoimmune indications.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and is the most common type of lupus. Lupus occurs when the immune system attacks its own tissues, causing inflammation, and in some cases permanent tissue damage, which can be widespread and affect many parts of the body like the skin, joints, heart, lung, kidneys, circulating blood cells and brain. Currently approved treatments aim to alleviate symptoms of lupus or reduce inflammation to minimize organ damage; there is no cure for lupus.
Uveitis is a form of eye inflammation that causes swelling of the uvea, the middle layer of the wall of the eye. Symptoms include eye redness, pain, sensitivity to light and blurred vision. The condition can affect one or both eyes, and it can affect people of all ages, even children. Causes of uveitis include infection, eye injury, or a systemic inflammatory or autoimmune disease such as inflammatory bowel disease (IBD), rheumatoid arthritis or lupus. Uveitis can damage vital eye tissue, leading to permanent vision loss.
Alumis’s lead clinical candidate, ESK-001 is an allosteric tyrosine kinase 2 (TYK2) inhibitor that reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-a. ESK-001 is a highly selective and potentially best-in-class allosteric TYK2 inhibitor. In Alumis’ Phase 1 studies, ESK-001 demonstrated complete inhibition of the pharmacodynamic assay over the dosing schedule of 24 hours, with no observed JAK-related safety events to date. ESK-001 was well-tolerated in these studies, with no serious adverse events observed.
Alumis is a clinical-stage biopharmaceutical company developing oral therapies using a precision approach to optimize outcomes and transform the lives of patients with immune-mediated diseases. Leveraging its precision data analytics and a multi-platform approach, Alumis is advancing a pipeline of oral therapies designed to address immune dysfunction. Alumis’ lead candidate ESK-001 is a highly selective and potentially best-in-class allosteric tyrosine kinase 2 (TYK2) inhibitor, and is currently being evaluated for the treatment of patients with moderate to severe plaque psoriasis, systemic lupus erythematosus (SLE), and uveitis. Alumis also has discovery efforts in undisclosed immune-mediated diseases and targets identified by our data analytics platform. Incubated by Foresite Labs and led by a team of experts with deep experience and proven track records in drug discovery, development and immunology, Alumis is developing transformative therapies that aim to reimagine the lives of people with immune-mediated diseases. For more information, please visit alumis.com.