Etrasimod

Drug Candidate for Treatment of Immune and Inflammatory-Mediated Diseases

Etrasimod (APD334), is a next generation, oral, selective sphingosine 1 phosphate (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 immune and inflammatory-mediated diseases such as ulcerative colitis, Crohn’s disease, primary biliary cholangitis (PBC) and atopic dermatitis. 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.

Etrasimod is an investigational compound that is not approved for any use in any country.

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 (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 Crohn’s Disease

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Crohn’s most commonly affects the end of the small bowel (the ileum) and the beginning of the colon, but it may affect any part of the gastrointestinal (GI) tract. Crohn’s disease can also affect the entire thickness of the bowel wall. Symptoms vary from patient to patient, but typically include persistent diarrhea, rectal bleeding, urgent need to move bowels, abdominal cramps and pain, constipation (can lead to bowel obstruction), fever, loss of appetite, weight loss, fatigue and night sweats. In more severe cases, Crohn’s can lead to tears (fissures) in the lining of the anus, which may cause severe pain and bleeding. Inflammation may also cause a fistula to develop which can be very serious and require immediate medical attention. A large number of patients suffering from Crohn’s disease are given opioids to help manage their pain. Opioids can cause further irritation to the GI tract and are becoming strictly regulated due to high rates of addiction.

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.

About Atopic Dermatitis

Atopic dermatitis (AD), also known as eczema, is a condition in which symptoms vary from patient to patient, but include dry skin, severe itching, patches, swollen skin and raised bumps which may leak fluid. It’s common in children but can occur at any age. AD is long lasting (chronic) and tends to flare periodically. It may be accompanied by asthma or hay fever. No cure has been found for AD, but treatments and self-care measures can relieve itching and may prevent new outbreaks.

Status

Ulcerative Colitis

We have received positive Phase 2 results for etrasimod and have initiated planning for Phase 3.  In March 2018, we completed 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, 1 mg and 2 mg, versus placebo on multiple efficacy measures including a 3-component Mayo Score, 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.

Crohn’s Disease

In light of the overwhelmingly positive Phase 2 data in UC, we have initiated a program in Crohn’s disease. Phase 2/3 planning is ongoing.

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.

Atopic Dermatitis

Phase 2 planning is ongoing.

Visit https://clinicaltrials.gov/ for more information.

Drug Candidate Disease Area Target Status
Etrasimod (APD334) Ulcerative Colitis (UC) Study 1 S1P Receptor Phase 3 Planning
Ulcerative Colitis (UC) Study 2 S1P Receptor Phase 3 Planning
Crohn’s Disease (CD) S1P Receptor Phase 2/3 Planning
Primary Biliary Cholangitis S1P Receptor Phase 2 Trial Ongoing
Atopic Dermatitis (AD) S1P Receptor Phase 2 Planning
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) Study 1 Ph 3 Planning
Ulcerative Colitis (UC) Study 2 Ph 3 Planning
Crohn’s Disease (CD) Ph 2/3 Planning
Primary Biliary Cholangitis Ph 2
Atopic Dermatitis (AD) Ph 2 Planning
Retained Rights
Worldwide, excluding rights granted to Everest Medicines for Greater China & certain other Asian territories