Los Angeles, October 4, 2022 — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announces an upcoming poster presentation at the 147th Annual Meeting of the American Neurological Association (ANA). Dr. Peter M. Clark, of the University of California Los Angeles, will present preclinical research highlighting the use of Trethera’s deoxycytidine kinase (dCK) inhibitor, TRE-515, to selectively inhibit symptoms in experimental autoimmune encephalomyelitis (EAE) mouse models of multiple sclerosis (MS). The ANA meeting is one of the largest annual gatherings of MS researchers and a key venue for presenting noteworthy neurology discoveries. The work presented by Dr. Clark also has application for optic neuritis, a rare neurologic disease which affects the optic nerve causing visual impairment. TRE-515 is currently being evaluated in a Phase 1 dose escalation solid tumors study.
- Poster Title: Inhibiting Deoxycytidine Kinase Significantly Improves Multiple Sclerosis Symptoms in Experimental Autoimmune Encephalomyelitis Mouse Models
- Authors: Peter M. Clark, PhD; Kenneth A. Schultz, MD; Bao Ying Chen, PhD; H. Michael Shepard, PhD; Lawrence Steinman, MD
- Abstract: S215
- Date: Sunday, October 23, 2022; 5:30PM – 7:00PM
- Location: Riverside East Center; Chicago, Illinois
TRE-515 is an orally delivered first-in-class therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway. A common characteristic of MS is the aberrant proliferation of peripheral T and B cells that mistakenly recognize and attack the myelin sheaths surrounding nerves in the central nervous system. The abnormal clonal expansion of T and B cells during autoimmunity requires elevated levels of nucleotides – including those provided by nucleoside salvage and dCK – to support rapid cellular DNA replication necessary for accelerated division. In contrast, dCK activity is highly restricted in healthy adult human cells. By targeting dCK, scientists hope to selectively and effectively deprive abnormally activated immune cells of this needed nucleotide source, thereby blocking MS symptoms. TRE-515 is twice designated an Orphan Drug by the FDA in demyelinating diseases, in both optic neuritis and acute disseminated encephalomyelitis (ADEM). This ANA presentation builds on the research work described earlier in the journal Immunology: Chen et al. (2022), Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis. Immunology. https://doi.org/10.1111/imm.13569.
Trethera is a clinical stage privately held biopharmaceutical company dedicated to pioneering the development of novel treatments for autoimmune diseases and cancers. Founded by prominent UCLA scientists, Trethera is led by experienced management and board members. Trethera’s innovative approach to targeting nucleotide metabolism led to the development of TRE-515, an orally taken capsule twice designated by the FDA as an Orphan Drug. TRE-515 is a first-in-class clinical stage drug that inhibits deoxycytidine kinase (dCK), the rate-limiting enzyme in the nucleoside salvage pathway, one of two biosynthetic pathways that generate DNA precursors. It is believed that some forms of cancer may be preferentially dependent on the salvage pathway to support tumor growth, and certain autoimmune diseases, such as multiple sclerosis, might also respond to TRE-515 treatment. Trethera is developing TRE-515 for use as a monotherapy or in combination, to precisely target a metabolic vulnerability of cancer or autoimmune diseases that will transform outcomes for patients.
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