Trethera secured a $1.8 million NIH award to advance preclinical studies of TRE-515 in Crohn’s disease, following a prior $400,000 grant. The once-daily oral dCK inhibitor has shown comparative efficacy to biologic therapy in mouse models presented at the 2025 Crohn’s & Colitis Congress, where TRE-515 reportedly outperformed ustekinumab on disease activity readouts by limiting activated CD4 T-cell proliferation. The program is supported by an existing clinical safety footprint from oncology and ALS studies.
The core development is a push to reposition a metabolism-targeted agent into inflammatory bowel disease, backed by non-dilutive capital to expand pharmacology, toxicology, and translational packages before an IND in Crohn’s. TRE-515 is described as the only deoxycytidine kinase inhibitor in development, with ongoing Phase 1 studies in solid tumors and ALS, and prior FDA designations in other indications. Trethera’s grant-funded plan signals intent to build a first-in-class case in IBD with a small-molecule mechanism that diverges from cytokine blockade and JAK inhibition.
Strategically, this is an expansion play that leverages oncology-derived insights into nucleotide salvage pathway dependence to enter a crowded Crohn’s market dominated by IL-23s, anti-TNFs, and JAKs. An oral agent with selective effects on activated T cells could offer a safety and monitoring profile distinct from broad immunosuppression, and the small-molecule route simplifies logistics versus infusion and injection regimens. The head-to-head preclinical signal against ustekinumab is directional but not determinative; regulators will focus on endoscopic and histologic outcomes in humans, and sponsors will need to validate that metabolic targeting translates into mucosal healing without infection liabilities. The NIH funding cuts time and cost from the translational path while Trethera builds a differentiated story around mechanism, pharmacodynamic markers, and potential patient selection.
For sites and CROs, an oral, once-daily candidate reduces infusion chair demand and can facilitate decentralized visit schedules, but will intensify adherence monitoring and remote safety labs. Study designs will face the current bar in Crohn’s: endoscopic response/remission for induction, steroid-free clinical remission and maintenance durability, and performance in biologic-experienced populations. Trethera will need a clear biomarker strategy—potentially including dCK activity assays, blood-based PD, and exploratory imaging—to de-risk dose selection and enrich for responders. Regulators will expect robust nonclinical data addressing on-target effects on lymphocytes and hematopoiesis, plus chronic dosing safety relevant to IBD’s long treatment horizons. Vendors with strengths in central endoscopy reads, digital adherence tools, and translational immunology assays will be pivotal.
Next, watch for IND timing and the design of a first-in-patient Crohn’s trial, including whether Trethera moves directly into a randomized induction study or stages an adaptive Phase 1b/2 with endoscopic endpoints. Dose selection will likely bridge from oncology safety while optimizing GI exposure and PD effect. Competitive differentiation must be demonstrated against approved IL-23s and JAKs on depth and durability of remission, steroid sparing, and infection risk. Key risks include translational failure from mouse models, class-based immunosuppression signals that erode the safety thesis, and manufacturing readiness for chronic oral therapy at scale. Partnership appetite—from GI-focused CROs to co-development with larger immunology players—will be a signal of confidence as the program approaches clinical proof of concept.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
