Los Angeles, January 24, 2023 — 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 8th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). 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, that suggests a functional role for deoxyribonucleoside salvage and dCK in multiple sclerosis (MS) mouse models.
Figure 1: PET scans showing mouse brain before (left) and after (right) MS induction (brain encircled in a dashed white line). The enzyme dCK becomes upregulated during MS disease.
Targeting dCK with first-in-class inhibitor TRE-515 is shown to block symptoms across multiple MS mouse models by specifically limiting activated B and CD4 T cell proliferation. The ACTRIMS meeting is a specialized gathering of translational science experts highlighting notable, novel and rigorous scientific discoveries made in MS that advance understanding of the clinical care of MS patients. 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: Clinical Stage Deoxycytidine Kinase Inhibitor TRE-515 Blocks Lymphocyte Proliferation and Disease in Three Mouse Models of Multiple Sclerosis
- Authors: Peter M. Clark, PhD; Kenneth A. Schultz, MD; Bao Ying Chen, PhD; Jessica R. Salas, PhD; H. Michael Shepard, PhD; Lawrence Steinman, MD
- Abstract: 422
- Poster Number: P138
- Poster Session: 1
- Date: Thursday, February 23, 2023; 6:30PM – 7:30PM
- Location: The Marriott Marquis; San Diego, California
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 ameliorating MS progression and blocking MS symptoms. Likewise, cancer cells have the capability to upregulate dCK to increase the intracellular nucleotide pool providing the basic DNA precursors for rapid growth and cancer cell division. TRE-515 is twice designated an Orphan Drug by the FDA in demyelinating diseases, in both optic neuritis and acute disseminated encephalomyelitis (ADEM) and is currently being studied in a Phase 1 oncology trial. This ACTRIMS 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 administered 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.
For more information, please visit us at trethera.com or e-mail Investor Relations at firstname.lastname@example.org.
About Multiple Sclerosis
MS is an autoimmune neurologic disease that affects almost 1 million Americans. The National Multiple Sclerosis Society estimates that the total cost of care for MS patients in the US during 2020 was $28 billion, including both direct and indirect healthcare expenses. Patients are typically diagnosed between the ages of 20 and 40 when changes of sensation, coordination, or motor strength occur. Relapsing remitting multiple sclerosis (RRMS) is the most common form of MS and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. The majority of patients who are diagnosed with RRMS will eventually transition to secondary progressive multiple sclerosis (SPMS), in which they experience steadily worsening disability over time.
Note on Forward-Looking Statements
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