FDA Clears TRE-515 Healthy Volunteer Study, Advancing Biomarker-Driven Oncology

The US FDA has granted clearance for a clinical trial of TRE-515, an investigational oral deoxycytidine (dC) kinase (K) inhibitor, in healthy volunteers.¹ The study is designed to provide critical pharmacokinetic and biomarker data that will inform the future development of the drug for both oncology and autoimmune disease indications. This clearance marks a strategic step for Trethera Corporation, reinforcing its commitment to a biomarker-driven approach to drug development and potentially accelerating the clinical path for this novel therapeutic.

The upcoming trial will enroll up to 72 healthy adults and will focus on evaluating the effects of food intake on the drug's plasma levels and the specific biomarker dC. Oral therapies, especially those that target metabolic pathways, can have their absorption and efficacy altered by a patient's dietary habits. By studying this interaction, Trethera aims to gain insights that could eliminate the need for mandatory fasting in future patient trials, thereby enhancing patient quality of life and improving the real-world utility of the drug. The study will also establish a comprehensive baseline for the dC biomarker in a nondiseased population, which will serve as a crucial benchmark for data collected in patients with solid tumors and other conditions.

“FDA clearance of our healthy volunteer protocol, combined with promising data from our ongoing oncology trial, underscores the strong safety profile of TRE-515 and positions Trethera to explore its full potential across a broad range of disease conditions,” said Ken Schultz, MD, chairman and CEO of Trethera, in a press release.

TRE-515 is a first-in-class small molecule inhibitor of dCK, a key enzyme in the deoxyribonucleoside salvage pathway. This pathway is a critical target in cancer because many rapidly proliferating cells, particularly those with compromised de novo synthesis, rely on it to acquire the building blocks for DNA replication. By inhibiting dCK, TRE-515 selectively targets these cancer cells. This mechanism of action is central to Trethera's strategy of developing a drug with a broad therapeutic window and applicability across multiple diseases.

The healthy volunteer trial complements an ongoing phase 1, open-label, first-in-human dose-escalation study (NCT05055609) of TRE-515 in patients with advanced solid tumors. TRE-515 has shown a favorable safety and tolerability profile in this trial, with zero dose-limiting toxicities observed up to a dose of 720 mg.² The company has already collected nearly 1000 biomarker samples from its oncology trial, and the new data from healthy volunteers will allow for a direct comparison, further solidifying the company's robust dC biomarker dataset.¹ This precision approach is foundational to the drug's development, as it not only supports dose optimization but may also enable the early identification of patients most likely to respond to therapy. This biomarker-driven strategy is known to significantly increase the likelihood of FDA approval for a drug.

Beyond its application in oncology, the mechanism of action of TRE-515 also positions it as a potential therapeutic for autoimmune and inflammatory diseases. Trethera is actively exploring its use in conditions such as Crohn's disease, amyotrophic lateral sclerosis (ALS), and lupus. The company has already received FDA designations for TRE-515 in indications including optic neuritis and acute disseminated encephalomyelitis. This multidimensional approach challenges the traditional "one drug, one disease" model and leverages a single mechanism to address a wide range of medical needs, both common and rare. The data generated from the healthy volunteer trial, being time-efficient and cost-effective, will provide a clear and advantageous path for the FDA drug approval processes across all of these potential indications.

REFERENCES:

1. FDA Provides Trethera Clearance to Initiate TRE-515 Clinical Trial in Healthy Volunteers to Study Food Effect and Biomarkers. News release. Trethera Corporation. July 30, 2025. Accessed August 1, 2025. https://tinyurl.com/js8c6wr

2. Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors. ClinicalTrials.gov. Updated May 22, 2025. Accessed August 1, 2025. https://clinicaltrials.gov/study/NCT05055609