Owkin, a pioneering AI-biotech company dedicated to transforming drug discovery, development, and diagnostics through agentic AI, has announced the dosing of the first patient in its Phase I clinical trial of OKN4395. The trial commenced on January 22, 2025, and marks a significant milestone in leveraging AI to optimize clinical research.
OKN4395 is a novel compound that builds on well-characterized EP2/EP4 inhibition while incorporating a newly identified and equipotent inhibition of DP1. This triple inhibition mechanism is first-in-class and is being evaluated for its potential clinical significance in treating patients with advanced solid tumors.
AI-Optimized Study Design
Owkin’s proprietary K1.0 Operating System played a crucial role in advancing OKN4395 from asset selection to clinical development. By developing a comprehensive biological understanding of the EP2/EP4/DP1 targets and their complex interactions, Owkin utilized AI to optimize the trial’s design. The program integrates AI-driven indication selection, the use of external control arms (digital twins) to gain early insights into anti-tumor activity, and biomarker-based patient subtyping to enhance the probability of clinical success.
Thomas Clozel, MD, CEO & Co-founder of Owkin, emphasized the importance of this achievement, stating, “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. This milestone underscores our ability to rapidly translate a promising asset into an AI-optimized clinical program.”
OKN4395: A First-in-Class Triple Inhibitor
Prostaglandins E2 (PGE2) and D2 (PGD2) are hormone-like molecules that interact with prostanoid receptors EP2, EP4, and DP1, respectively. Both the PGE2/EP2/EP4 and PGD2/DP1 pathways are known to be immunosuppressive. In oncology, excessive activation of the PGE2/EP2/EP4 pathway in certain cancers enables tumors to evade immune system attacks, leading to disease progression and resistance to treatment.
OKN4395 is the first clinical-stage compound designed to selectively inhibit EP2, EP4, and DP1 receptors. By targeting these pathways, it offers the potential to restore immune function, providing a transformative therapeutic option for patients with advanced solid tumors. This unique mechanism of action differentiates OKN4395 from existing immunotherapies and underscores the potential impact of AI-driven drug discovery.
The INVOKE Study (OKN-4395-121)
The INVOKE study is a global, multicenter, Phase Ia/1b, first-in-human, open-label clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of OKN4395 in patients with advanced solid tumors.
- Phase Ia: This phase focuses on dose escalation to determine the safety and tolerability of OKN4395 as both a monotherapy and in combination with pembrolizumab, a widely used immune checkpoint inhibitor.
- Phase Ib: Upon establishing a safe dose, this phase will expand into four cohorts to assess preliminary anti-tumor activity, safety, and extensive exploratory biomarker analyses.
The trial aims to leverage AI-driven methodologies to enhance patient stratification and treatment response prediction, ensuring that OKN4395 is positioned for maximum clinical impact. By integrating digital twins and biomarker-led patient subtyping, Owkin seeks to increase the probability of success in later-stage trials.
AI in Clinical Research: A New Paradigm
Owkin’s AI-first approach to drug development represents a paradigm shift in clinical research. Traditional drug development is often hindered by inefficiencies, long timelines, and high failure rates. Owkin’s K1.0 Operating System addresses these challenges by:
- Enhancing Target Identification: AI algorithms analyze vast biological datasets to identify the most promising drug targets.
- Optimizing Trial Design: AI-driven simulations enable the selection of optimal trial parameters, reducing costs and increasing the likelihood of success.
- Predicting Patient Responses: Machine learning models help stratify patients based on biomarker profiles, ensuring that therapies reach the most responsive populations.
- Accelerating Drug Development Timelines: By streamlining data analysis and decision-making, AI shortens the time required to bring new therapies to patients.
With OKN4395, Owkin is demonstrating how AI can revolutionize every stage of the drug development process, from discovery to clinical trials.
The Future of AI-Optimized Drug Development
The successful initiation of the INVOKE study marks a crucial step toward establishing AI-optimized drug development as a standard in oncology. Owkin’s approach has the potential to reshape how novel therapies are developed, reducing trial-and-error inefficiencies and improving patient outcomes.
If OKN4395 proves effective in clinical trials, it could represent a new class of immunotherapy that targets previously untapped pathways. The triple inhibition of EP2, EP4, and DP1 offers a novel strategy to enhance immune response and counteract tumor resistance mechanisms.
Owkin’s long-term vision extends beyond OKN4395. The company aims to leverage its AI-driven platform to develop additional novel therapeutics, refine patient stratification techniques, and contribute to a more personalized approach to cancer treatment.
