ESK-001 for the Treatment of Psoriasis

In psoriasis, there is a significant need to have a safe and highly effective oral therapy. ESK-001 has the potential to offer an oral therapy with superior efficacy compared to other available or investigational treatments for plaque psoriasis.

About Psoriasis
Psoriasis is an autoimmune skin condition that causes itchiness and discomfort. It is a common, chronic disease with no cure. Plaque psoriasis, the most common type of psoriasis, causes dry, itchy, raised skin patches (plaques) covered with scales. Disease severity can vary depending on intensity of symptoms. Moderate to severe disease has a greater negative impact on quality of life, with nearly one-quarter of psoriasis patients considered to have moderate to severe disease. 

About the ONWARD Phase 3 Clinical Program
The ONWARD Phase 3 clinical program consists of two identical global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis. Comparators will include placebo, through Week 16, and apremilast, a widely used oral drug for the treatment of psoriasis, through Week 24. Each trial will enroll approximately 840 patients 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 with moderate-to-severe plaque psoriasis achieving greater than or equal to 75% reduction in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment (sPGA) score 0/1 of ESK-001 compared to placebo at Week 16. Patients completing Week 24 will have the opportunity to participate in a long-term extension (LTE) trial, ONWARD3, that will evaluate durability and maintenance of response and long-term safety. In parallel with the Phase 3 clinical program, Alumis is developing a once-daily modified release (MR) oral formulation of ESK-001 that can replace the current immediate release (IR) oral formulation that is dosed twice daily.

About the STRIDE Clinical Trial
The STRIDE clinical trial is a randomized, double-blind, placebo-controlled Phase 2 dose ranging clinical trial that evaluates the efficacy, safety, pharmacokinetics and pharmacodynamics of ESK-001 in patients with moderate to severe plaque psoriasis. The trial has enrolled more than 200 patients across multiple doses of ESK-001 for 12 weeks. The primary endpoint of the trial is the proportion of patients with moderate to severe plaque psoriasis achieving greater than or equal to 75% reduction in PASI score (PASI 75) across doses of ESK-001 and placebo. PASI, or Psoriasis Area and Severity Index, is an instrument used to score, assess and grade the severity of psoriatic lesions and the patient's response to treatment. Enrollment of this trial has been completed. Upon completion of the STRIDE clinical trial, patients were eligible to be enrolled in an OLE study evaluating two ESK-001 doses (40 mg once daily and 40 mg twice daily). The OLE study is currently ongoing.

ESK-001 for the Treatment of SLE (Lupus)

ESK-001 is a TYK2 inhibitor that reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-a. ESK-001 has the potential to reduce SLE disease activity by interfering with pro-inflammatory pathways known to be involved in the pathogenesis of SLE.

About SLE (Lupus)
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 – affecting many parts of the body like the skin, joints, heart, lung, kidneys, circulating blood cells, and brain. Current treatments aim to alleviate symptoms of lupus or reduce inflammation to minimize organ damage; there is no cure for lupus.

About the LUMUS Clinical Trial
LUMUS is a global, multicenter, randomized, double-blind, placebo-controlled Phase 2 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 expected to enroll  388 patients across multiple doses of ESK-001 or placebo for a treatment period of 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 effect on disease activity. Link to clinicaltrials.gov.