Trethera Corporation, a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announced today that it was awarded a Small Business Technology Transfer (STTR) grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) division of the National Institute of Health (NIH)

Crohn’s disease is a chronic, relapsing, inflammatory gastrointestinal disorder that can present with diarrhea, fatigue, severe abdominal pain, and weight loss. Almost 1 million Americans suffer from the disease today, with complications including intestinal fistulas, strictures, and colorectal cancer. Up to a third of patients fail to respond to first line therapy drugs and nearly half lose their drug response within 5 years. Steroids can induce remissions but are less effective at maintaining durability and have significant side effects. The disease is primarily driven by autoreactive CD4 T cells of the patient’s own immune system that target antigens in the gut.  

“A high unmet medical need exists for safe, oral therapies that can be used with first-in-line treatments to help patients maintain disease remission, thereby reducing the need for aggressive broadly immunosuppressive agents.   TRE-515 potentially offers a benefit-risk profile that will be ideally suited for patients with moderate to severe Crohn’s disease seeking a well-tolerated agent to diminish relapses,” said Dr. Ken Schultz, principal investigator and Trethera CEO.

“We are very pleased to receive this grant that recognizes the strong therapeutic potential that could be provided for the treatment of Crohn’s disease through a first-in-class drug targeting deoxycytidine kinase (dCK),” said UCLA’s Dr. Peter Clark, member of the Trethera Scientific Advisory Board and grant co-investigator. “The STTR program at NIH plays a vital role in helping companies develop new technologies that serve important U.S. health care needs.”

TRE-515 is an orally delivered, once daily, therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway. A common characteristic of pathological immune cells in autoimmune diseases is the requirement for elevated nucleotide levels to support abnormal and accelerated cell division. In contrast, dCK activity is not required in most healthy adult human cells. Mediated by the rate-limiting enzyme, dCK, the nucleoside salvage pathway may play a pivotal role in enabling the aberrant activated lymphocytes found in Crohn’s disease to divide, suggesting dCK as a potential therapeutic target with expected enhanced safety.