Kainova Therapeutics Reports Phase I Data for Oral EP4 Receptor Antagonist DT-9081 in Advanced Solid Tumors
Montreal-based Kainova Therapeutics announced topline results from its Phase I EPRAD study of DT-9081, an oral EP4 receptor antagonist, in patients with advanced, recurrent, and metastatic solid tumors. The data, which showed no dose-limiting toxicities and early signs of anti-tumor activity, mark the first clinical validation of selective EP4 antagonism in oncology patients and position Kainova to advance DT-9081 into combination studies with immune checkpoint inhibitors.
Trial specifics
The Phase I EPRAD study was an open-label, dose-escalation trial conducted across four sites in France and Belgium. It enrolled adults with advanced, recurrent, or metastatic solid tumors. The study evaluated DT-9081 at multiple oral dose levels, though specific doses and patient numbers were not disclosed in the topline readout. Primary objectives centered on safety, tolerability, pharmacokinetics, and pharmacodynamics. The company reported that all primary objectives were met: no dose-limiting toxicities occurred at any dose level, exposure was dose-proportional, and sustained EP4 receptor engagement was observed across all cohorts. Early signs of anti-tumor activity were noted, though no quantitative efficacy data were provided. The study has been completed, and no extension phase was described.
Kainova's Chief Medical Officer Jean-Marie Cuillerot said the study "generated a clear and coherent dataset that precisely characterizes DT-9081's clinical profile." CEO Sean MacDonald stated the findings "reinforce the relevance of GPCR-modulating strategies in addressing complex immune pathways." The company has not disclosed specific regulatory timelines for advancing DT-9081 into later-stage trials, though the press release positions the molecule as a candidate for combination with immune checkpoint inhibitors. DT-9081 has no prior regulatory approvals in any indication.
Research context
DT-9081 blocks the EP4 receptor, one of four receptors for prostaglandin E2 (PGE2). In the tumor microenvironment, COX-2-positive cancer cells produce PGE2, which signals through EP4 to suppress CD8+ T cell function, expand regulatory T cells, and promote immunosuppressive myeloid cell populations. By selectively antagonizing EP4, DT-9081 aims to reverse this PGE2-driven immune evasion and restore anti-tumor immunity. The approach differs from broad COX inhibition — which carries gastrointestinal and cardiovascular risks — by targeting a single downstream receptor. Principal investigator Jean-Pascal Machiels noted that because chemotherapy itself can trigger PGE2 production, EP4 inhibition offers "a rational and versatile strategy to overcome resistance."