Milestones, grant awards, and peer-reviewed publications tracing more than a decade of TRE-515’s development, from the lab to the clinic.
Deoxycytidine kinase (dCK) is the rate-limiting enzyme of the deoxyribonucleoside salvage pathway, phosphorylating deoxyadenosine, deoxycytidine, and deoxyguanosine to sustain intracellular deoxyribonucleoside triphosphate (dNTP) pools.
This study in EAE mouse models of MS shows that TRE‑515, a dCK inhibitor, reduces disease severity by limiting lymphocyte proliferation and CNS infiltration—without impacting innate or naive immune cells. Indicates dCK’s key role in disease progression.
This study demonstrates that 18F-FAC PET crosses the blood–brain barrier and accumulates in brain-infiltrating leukocytes in EAE mice, and that it can monitor therapeutic effects—like fingolimod treatment—on immune cell infiltration in the CNS.
Using crystal structures of dCK bound to lead compounds, researchers enhanced inhibitor design to isolate an R‑isomer with >60-fold greater affinity and improved metabolic stability—creating a promising candidate for leukemia and broader cancer treatment.
This study elucidates how ATM-mediated phosphorylation of deoxycytidine kinase (dCK) enhances DNA repair by increasing dCTP pools post-radiation. Loss of dCK increases radiosensitivity, suggesting its inhibition could serve as a radiosensitization strategy.
In a mouse model, deoxycytidine kinase (dCK) deficiency caused dCTP depletion, replication stress, and hematopoietic defects that were nearly reversed in dCK/TK1 double knockouts. This uncovers mechanisms of nucleotide regulation and therapeutic potential.
This study reports the synthesis and evaluation of novel PET probes—L‑18F‑FAC and L‑18F‑FMAC—that offer improved stability and selective affinity for deoxycytidine kinase. In vitro and in vivo testing showed successful imaging of dCK in leukemia and autoimmune mouse models.
In mice, genetic inactivation of deoxycytidine kinase caused a 90-fold decrease in thymic cellularity and a 5–13-fold reduction in lymphocyte numbers, revealing that dCK—and the nucleoside salvage pathway—is vital for normal T and B cell development.
The study describes [18F]FAC, a new PET probe that images lymphoid organs and detects immune activation in anti‑tumor and autoimmune mouse models, offering potential for monitoring immune function in disease and therapy.
Trethera will present at the 16th Annual Biocom Global Partnering & Investor Conference following completion of its Phase 1 solid tumor dose escalation trial. The company will highlight TRE-515’s clinical momentum, Fast Track status, and upcoming indication expansion plans.
Trethera receives a $2.7M NIH grant to study TRE-515 in combination with KRAS inhibitors for lung cancer. The funding supports preclinical studies aimed at overcoming resistance in NSCLC by targeting the nucleoside salvage pathway, with strong rationale and favorable early safety data.
Trethera announced completion of the Phase 1 dose-escalation trial for TRE-515 in solid tumors. The drug was well tolerated with no dose-limiting toxicities. Results showed strong safety, confirmed target engagement, and durable tumor control, supporting advancement to Phase 2.
Trethera received a $1.8M NIH grant to accelerate TRE-515 development for Crohn’s disease. The oral dCK inhibitor showed promising results outperforming Stelara in mice. NIH reviewers called the drug “highly innovative” with “exciting potential” and a “favorable safety profile.”
Trethera has completed enrollment of its Phase 1 dose escalation trial for TRE-515 in solid tumors. Doses increased 36-fold without dose-limiting toxicities, and early clinical benefit was observed. Data will be presented at an upcoming scientific conference.
Trethera has been awarded a $2.3M NIH SBIR grant to evaluate TRE‑515 in combination with radiation therapy against mCRPC in preclinical models—building on its recent FDA Fast Track designation and reinforcing its drug candidate’s therapeutic rationale.
Trethera has been awarded a $3M NIH SBIR grant to advance TRE‑515 for the treatment of systemic lupus erythematosus (lupus). The funding supports toxicology, pharmacology, and efficacy studies in preclinical models, paving the way toward future clinical trials.