Owkin Initiates Phase I Trial of AI-Optimized Triple Inhibitor OKN4395 for Solid Tumors
Owkin has commenced dosing in its Phase I clinical trial of OKN4395, marking a significant milestone in the development of an innovative triple inhibitor for advanced solid tumors. The first patient received treatment on January 22, 2025, initiating the evaluation of this first-in-class compound that simultaneously targets EP2, EP4, and DP1 receptors.
The drug candidate represents a novel approach to cancer treatment by targeting the immunosuppressive prostaglandin pathways. OKN4395 builds upon established EP2/EP4 inhibition mechanisms while introducing a newly identified and equipotent inhibition of DP1, creating a unique therapeutic profile in oncology.
AI-Powered Drug Development
The development of OKN4395 showcases the integration of artificial intelligence in modern drug development. Owkin's proprietary K1.0 Operating System has been instrumental throughout the process, from initial asset selection to clinical strategy optimization. The platform's capabilities include AI-driven indication selection, implementation of external control arms through digital twins for early efficacy assessment, and sophisticated biomarker-led patient subtyping.
"OKN4395 reflects not only a decade of discovery efforts by Idorsia and its collaborators but also exemplifies the transformative power of Owkin's K1.0 Operating System," stated Thomas Clozel, MD, CEO & Co-founder of Owkin. "This milestone underscores our ability to rapidly translate a promising asset into an AI-optimized clinical program."
Novel Mechanism of Action
The drug's mechanism targets key immunological pathways involving prostaglandins E2 and D2 (PGE2, PGD2). These naturally occurring hormone-like molecules interact with prostanoid receptors EP2, EP4, and DP1. In certain cancers, hyperactivity of the PGE2/EP2/EP4 pathway enables tumors to evade immune system detection, leading to disease progression and treatment resistance.
By simultaneously inhibiting EP2, EP4, and DP1 receptors, OKN4395 aims to restore immune function in patients with advanced solid tumors, potentially offering a new treatment paradigm for those with limited therapeutic options.
The INVOKE Clinical Trial
The INVOKE study (OKN-4395-121; NCT06789172) is designed as a global, multicenter, Phase Ia/1b first-in-human trial. The study comprises two main parts:
- Phase Ia focuses on safety and tolerability evaluation through dose escalation, testing OKN4395 both as a monotherapy and in combination with pembrolizumab
- Phase Ib will expand into four additional cohorts, assessing preliminary anti-tumor activity alongside safety and conducting extensive exploratory analyses
The trial aims to address an initial market of over 100,000 patients annually across the United States, EU4, and United Kingdom through its Phase Ib indications.