LOS ANGELES — October 1, 2026
Trethera Corporation announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to TRE-515 in combination with KRAS inhibitors for patients with KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) previously treated with an anti-PD-(L)1 antibody and platinum-based chemotherapy. The designation expands the clinical development opportunity for TRE-515 in oncology and represents the company’s second FDA Fast Track designation for the program, following its earlier designation in metastatic castration-resistant prostate cancer. Trethera is developing TRE-515 as an orally administered inhibitor of deoxycytidine kinase (dCK), with the company seeking to evaluate whether targeting nucleotide metabolism can complement existing targeted cancer therapies. The FDA Fast Track designation is intended to facilitate development and regulatory interaction for therapies addressing serious conditions with unmet medical needs.
TRE-515 Targets a Metabolic Vulnerability in Cancer
TRE-515 inhibits dCK, the rate-limiting enzyme in the nucleoside salvage pathway, which Trethera is targeting as a potential metabolic vulnerability in cancer cells. The company’s development strategy is based on the observation that tumors exposed to KRAS inhibitors may increase their reliance on nucleotide salvage mechanisms to support continued growth and survival under therapeutic pressure. Trethera is therefore evaluating TRE-515 as a combination approach with KRAS G12C inhibitors, rather than targeting the KRAS pathway directly. The company said preclinical work using specialized PET imaging demonstrated continued dCK activity following KRAS inhibitor treatment and subsequent blockade of tumor dCK activity after administration of TRE-515. TRE-515 is also being evaluated in an ongoing first-in-human clinical trial, supporting the company’s broader strategy of developing the candidate across cancer and autoimmune disease indications.
FDA Fast Track Expands TRE-515 Oncology Development
The new Fast Track designation strengthens Trethera’s regulatory development pathway for TRE-515 in KRAS G12C-positive NSCLC, an indication where treatment resistance and disease progression remain important clinical challenges. Fast Track status can provide opportunities for more frequent interactions with the FDA during development and may facilitate eligibility for programs such as Accelerated Approval and Priority Review when applicable regulatory criteria are met. Trethera’s lung cancer program also builds on a $2.7 million NIH grant awarded in 2025 to investigate TRE-515 in combination with KRAS inhibitor therapies. The company is positioning the program around the potential to address metabolic adaptation that may occur during KRAS-targeted treatment. While the current evidence includes preclinical findings and early clinical development, additional clinical data will be required to determine whether the approach can improve outcomes in patients with KRAS G12C-mutated NSCLC.
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Trethera Advances TRE-515 Across Oncology
TRE-515 is emerging as the lead clinical-stage program in Trethera’s strategy to target nucleotide metabolism across cancer and autoimmune diseases. The company describes TRE-515 as a first-in-class oral dCK inhibitor designed for development both as a monotherapy and in combination with other therapies. In oncology, Trethera is pursuing opportunities in KRAS G12C-positive NSCLC and metastatic castration-resistant prostate cancer, with FDA Fast Track designations supporting both development programs. The company’s broader approach is based on targeting the nucleoside salvage pathway, which it believes can represent an important source of metabolic support for certain disease states. The second FDA Fast Track designation gives Trethera an additional regulatory pathway for advancing TRE-515 in lung cancer and provides a new development focus for the company as it evaluates the candidate in combination with KRAS-targeted therapies.
Source:Trethera, press release
