Drug Candidate for Treatment of Autoimmune Diseases

Etrasimod (APD334), is an oral, next generation, selective S1P receptor modulator, discovered by Arena, designed to provide systemic and local cell modulation by selectively targeting S1P receptor subtypes 1,4 and 5. Etrasimod has therapeutic potential in autoimmune diseases such as ulcerative colitis. S1P receptors have been demonstrated to be involved in the modulation of several biological responses, including lymphocyte trafficking from lymph nodes to the peripheral blood. By isolating subpopulations of lymphocytes in lymph nodes, fewer immune cells are available in the circulating blood to effect tissue damage.

About Autoimmune Diseases

Autoimmune diseases are characterized by an inappropriate immune response against substances and tissues that are normally present in the body. In an autoimmune reaction, a person’s antibodies and immune cells target healthy tissues, triggering an inflammatory response. Reducing the immune and/or inflammatory response is an important goal in the treatment of autoimmune disease.

About Ulcerative Colitis

Ulcerative colitis, or UC, is a chronic disease that affects the large intestine. The innermost lining of the large intestine becomes inflamed and ulcers may form on the surface, which can cause symptoms such as frequent bowel movements, diarrhea and bloody stools. The inflammation is usually found in the rectum and can include all or a portion of the colon. Currently available treatment options have limitations in terms of side effects, patient response, efficacy and administration. We believe that an effective, oral, selective S1P receptor modulator that provides clinical benefits without current limitations has the potential to improve treatment for patients with ulcerative colitis.

About Dermatological Conditions of IBD

Extraintestinal manifestations, or EIMs, of Inflammatory Bowel Disease are common in both UC and CD. Inflammatory manifestations of the skin, eyes, liver, and joints are considered the primary types of EIMs associated with IBD. Cutaneous disorders associated with IBD occur in up to 15% of patients. Erythema nodosum, pyoderma gangrenosum, and psoriasis are the most common skin manifestations of IBD, in total affecting up to 11% of the IBD population.

IBD and these major skin EIMs in IBD share some common pathogenic mechanisms including T lymphocyte infiltration. We believe S1P receptor modulation’s ability to sequester lymphocytes should result in fewer immune cells available to affect these inflammatory processes. In addition to the potential anti-inflammatory benefits resulting from reducing systemic lymphocyte circulation, activity on S1P1 and SIP4 are known to exert anti-proliferative effects in human keratinocytes, the predominant type of cell found in the outer-most layer of the skin, and inhibit skin dendritic cell migration. Therefore, the potential role of S1P receptor modulation in skin EIMs of IBD might involve both systemic and local dermal mechanisms.

There are no therapies currently approved specifically for treatment of IBD-mediated dermatologic manifestations. Therefore, a significant unmet need remains and we believe that etrasimod may represent a significant opportunity to provide an effective treatment for patients with IBD experiencing dermatologic EIM.

About Pyoderma Gangrenosum

Pyoderma gangrenosum, or PG, is a rare inflammatory skin disease characterized by painful recurrent ulcerations. Lesions may occur either in the absence of any apparent underlying disorder or in association with other diseases, such as UC, CD, and other conditions. Diagnosis of PG is based on the history of the underlying disease, typical clinical presentation, histopathology, and exclusion of other diseases that would lead to a similar clinical picture. The clinical course can be mild or malignant, and chronic or relapsing.

Treatment is challenging and the prognosis of PG remains unpredictable. Current treatments involve wound care and the use of anti-inflammatory agents, including antibiotics, corticosteroids, immune-suppressants and biologics, and attempts to target a broad spectrum of immunologic mediators and inflammatory cells, including T-lymphocytes shown to be involved in PG. Reduction of lymphocytes by S1P receptor modulators such as etrasimod may represent a novel therapeutic approach in PG.

About Primary Biliary Cholangitis

Primary biliary cholangitis, or PBC (previously referred to as primary biliary cirrhosis), is a chronic cholestatic liver disease which is classified as a rare disease.

Progressive bile-duct injury from portal and periportal inflammation could result in progressive fibrosis, cholangitis and eventually cirrhosis. Evidence to date suggests that immunological and genetic factors might cause the disease. The treatment goal is to slow the progression rate of the disease and to alleviate the symptoms. Liver transplantation appears to be the only life-saving procedure for PBC patients.

Inflammation, the underlying cause of PBC, is believed to be T lymphocyte mediated. In research models with etrasimod, we have demonstrated modulation of the specific subtypes of T lymphocytes implicated in PBC.


Ulcerative Colitis

We are conducting a dose finding randomized, double-blind, placebo-controlled multinational Phase 2 clinical trial of etrasimod in moderate to severe UC. The aim of the trial includes investigating a clear dose response and establishing a clinically meaningful signal for the active arm(s) from placebo. The trial is expected to evaluate the effects of etrasimod, 1mg and 2mg, versus placebo on multiple efficacy measures including total Mayo Score (TMS), clinical remission and clinical response in up to 160 patients. Subjects from this study have the possibility to continue after 12 weeks in an open label extension study for up to 46 weeks with the focus on safety and maintenance of therapeutic effect.

Dermatologic Extraintestinal Manifestations of IBD

We are evaluating the efficacy and safety of etrasimod in IBD patients with active dermatologic extraintestinal manifestations in an open-label study in the context of the UC study. The objective is to determine the treatment effect of etrasimod in IBD patients on the clinical improvement of active dermatologic extraintestinal manifestations and to determine the safety profile and tolerability of etrasimod over a 12-week treatment period. The study includes patients with IBD experiencing active dermatologic extraintestinal manifestations including psoriasis, erythema nodosum, and PG.

Pyoderma Gangrenosum

We are conducting a Phase 2a, proof of concept, open-label study to determine the efficacy and safety of etrasimod in patients with PG. The objective is to evaluate the efficacy, safety and tolerability of etrasimod in patients with PG over a 12-week treatment period. The study includes patients with diagnosed PG independent of IBD as a background disease.

Primary Biliary Cholangitis

We are conducting a Phase 2a, proof of concept, open-label study to determine the safety and tolerability of etrasimod in patients with primary biliary cholangitis over a 24-week treatment period.

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Drug Candidate Disease Area Target Status
Etrasimod (APD334) Ulcerative Colitis (UC) S1P Receptor Phase 2 Trial Ongoing
Pyoderma Gangrenosum S1P Receptor Phase 2 Trial Ongoing
Primary Biliary Cholangitis S1P Receptor Phase 2 Trial Ongoing
Retained Rights
Worldwide, excluding rights granted to Everest Medicines for Greater China & certain other Asian territories

Etrasimod has not been approved by the US Food and Drug Administration or any other regulatory agency.


Drug Candidate Disease Area Status
Etrasimod (APD334) Ulcerative Colitis (UC) Ph2b
S1P Receptor Pyoderma Gangrenosum Ph2a
Primary Biliary Cholangitis Ph2a
Retained Rights
Worldwide, excluding rights granted to Everest Medicines for Greater China & certain other Asian territories