TRE-515 inhibits deoxycytidine kinase (dCK), the key enzyme for the nucleoside salvage pathway that becomes activated and essential for the growth of abnormal cells in autoimmune diseases and cancer. Blocking this pathway deprives diseased cells of the DNA building blocks needed for uncontrolled proliferation. Because dCK is relatively conserved in the regulated cell division of healthy cells, inhibiting it with TRE-515 has demonstrated a superb safety profile and early signs of clinical benefit in an ongoing first-in-human oncology trial. Based on these observations, the NIH award will expand development into preclinical lupus models.
"Our ongoing research shows TRE-515's unique mechanism of inhibiting nucleotide metabolism has the potential to address multiple autoimmune and oncology indications," said Dr. Ken Schultz, principal investigator and Trethera CEO. "This Phase II grant builds on the momentum from our successful Phase I grant, which demonstrated increased dCK activity is associated with lupus in mouse models and blocking dCK with TRE-515 stops disease progression."
"Lupus remains a chronic, debilitating disease with limited therapeutic choices, many of which are associated with heightened infection risk," said Dr. Larry Steinman, Trethera Scientific Advisory Board member and distinguished immunologist at Stanford University. "A novel, first-in-class agent such as TRE-515 offers a differentiated mechanism of action, potentially improving patient outcomes while reducing treatment burden."
