LOS ANGELES, Dec. 16, 2025 (GLOBE NEWSWIRE) — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company developing first-in-class therapies for cancer and autoimmune diseases, announced today the award of a new $2.7 million Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH). The award evaluates the combination of Trethera’s lead drug candidate, TRE-515, with KRAS inhibitor therapies to treat non-small cell lung cancer (NSCLC). Lung cancer is responsible for more deaths annually than breast, prostate, and colorectal cancer combined— with NSCLC causing 80% of lung cancer deaths. The grant will fund testing TRE-515 with standard of care KRAS inhibitors (KRASi) in NSCLC mouse models to inform future clinical trials.
“Securing this NIH lung cancer grant continues our multiple indication momentum, coming less than six months after receiving FDA Fast Track designation for prostate cancer. Such dual external validations are rare and substantiate the strength of our scientific rationale and clinical observations,” said Dr. Ken Schultz, Chairman and CEO of Trethera. “Combining TRE-515 with targeted KRAS therapies, is intended to exploit a metabolic vulnerability in NSCLC and address the significant unmet need for the 60% of patients who do not respond to KRASi monotherapy and those who experience relapse.”
TRE-515 inhibits deoxycytidine kinase (dCK), the key enzyme for the nucleoside salvage pathway that becomes activated and essential for abnormal cell growth in autoimmune diseases and cancer. Consistent with observations that dCK activity is relatively minimal in the regulated cell division of healthy cells, inhibiting dCK with TRE-515 has demonstrated favorable safety in addition to clinical benefit in ongoing first-in-human trials.
Estimates by the World Health Organization indicate that more than 2.5 million new cases and 1.8 million deaths from lung cancer occurred globally in 2024. While FDA approved KRAS inhibitors have transformed the NSCLC market, KRASi have a 40% response rate. Thus, 6 of 10 patients experience no clinical benefit from the treatment. Furthermore, those patients who do benefit from KRASi therapy find their results transient, with an average duration of 8-10 months before tumor growth resumes.
When treated with KRAS inhibitors alone, cancer cells can escape destruction by using the salvage pathway to gather additional nucleosides to repair the DNA damage. Combining TRE-515 with KRAS targeting drugs synergistically cripples the ability of cancer cells to grow or recover from DNA damage and enhances the therapeutic response.
“We are excited to receive this grant award, which underscores the strong mechanistic rationale for pairing a first-in-class dCK inhibitor with KRAS-targeted therapies,” said UCLA Assistant Professor Evan Abt and grant co-investigator. “KRAS inhibitor resistance remains a major challenge, and our data suggest that blocking the nucleoside salvage pathway directly disrupts a key metabolic escape route used by lung cancer cells.”
Dr. Steve Dubinett, Distinguished Professor at the UCLA School of Medicine and pulmonologist, added, “Lung cancer is the leading cause of cancer-related mortality worldwide, with limited effective therapies once the disease becomes resistant and metastatic. A novel, first-in-class drug such as TRE-515, paired with the KRAS inhibitor class, could redefine treatment for this devastating disease.”
In its written summary, the NIH peer review panel commented, “significance and market potential are high given the need for novel drug combinations for a deadly disease with limited treatment options… potential for commercialization in a short time if the research is successful… preclinical and early phase clinical data provide additional reassurance of safety… evaluation of biomarkers for the combinatorial approach so early in the drug development is a major strength… already shown clinical activity and demonstrates potential as a novel therapeutic agent… … a truly outstanding and accomplished group of investigators.”
Figure 1: Specialized [18F]CFA PET radiotracer showing persistent dCK activity following KRASi treatment in a mouse implanted with a tumor (left) then treated with TRE-515 to completely block dCK tumor activity (right).
Sources: Siegel, Cancer J Clin. 2024; 74(1); Bunimovich, PLoS One. 2014; 9(8); Hong, NEngl JMed. 2020; 383(13); Thandra, Cont Oncol 2021; 25(1); LumakrasTM and KrazatiTM FDA labels
Note: Statements taken from the official NIH peer review written summary reflect their personal scientific assessment and are not official NIH endorsements.
About Trethera
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. 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 might also respond to TRE-515 treatment. The FDA has designated TRE-515 a Fast Track drug for prostate cancer and an Orphan Drug for two autoimmune neurologic diseases. 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 [email protected]. You can also follow Trethera on Facebook and LinkedIn.
About KRAS Inhibitors
KRAS inhibitors represent a transformative advance in precision oncology, offering the first targeted therapies for patients whose tumors harbor the historically intractable KRAS G12C mutation. The two FDA approved agents, LumakrasTM and KrazatiTM, are orally administered small molecule inhibitors that directly target mutant KRAS signaling, a central driver of cancer cell proliferation and survival. Their continued development underscores the high potential of KRAS inhibitors to reshape treatment paradigms across multiple cancer types, both as monotherapies and as foundational components of rational drug combinations designed to overcome resistance and improve patient outcomes.
Note on Forward-Looking Statements
All statements other than statements of historical facts included in this press release that address activities, events or developments that Trethera believes or anticipates will or may occur in the future are “forward-looking statements,” which may often, but not always, be identified by the use of such words as “may,” “might,” “will,” “will likely result,” “would,” “should,” “estimate,” “plan,” “project,” “forecast,” “intend,” “expect,” “anticipate,” “believe,” “seek,” “continue,” “target” or the negative of such terms or other similar expressions. Although Trethera has a reasonable basis for the forward-looking statements contained herein, Trethera cautions that such statements are based on current expectations about future events and are subject to risks, uncertainties and factors relating to medical and scientific research, all of which are difficult to predict and many of which are beyond Trethera’s control, that may cause actual results to differ materially from those expressed or implied by the forward-looking statements in this press release. These potential risks and uncertainties include, without limitation: the extent to which development of any novel cancer therapies or therapies for autoimmune diseases succeeds; whether Trethera would obtain the necessary regulatory approvals to commence human trials or commercialize TRE-515 or any novel therapies resulting from such research; Trethera successfully implementing its growth strategy, including that relating to its disease therapies; the effects of the global Covid-19 pandemic; changes in economic conditions; competition; and risks and uncertainties applicable to the business of Trethera. The statements in this press release speak only as of the date hereof and Trethera does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.
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