Owkin Announces First Patient Dosed in Phase I AI-optimized Clinical Trial of OKN4395, a First-in-Class EP2/EP4/DP1 Triple Inhibitor for Patients with Solid Tumors

• OKN4395 is the first Owkin development program to leverage K1.0, Owkin’s AI-powered Operating System, from asset selection to clinical development optimization
• This asset is a highly selective triple inhibitor of EP2/EP4 and DP1, with a first-in-class profile targeting select solid tumors in patients with high unmet need
• >100,000 patients per year in the US, EU4 and UK initially addressable through Phase Ib indications
• The INVOKE study (OKN-4395-121; NCT06789172) is sponsored by Epkin (an Owkin company)

PARIS--(BUSINESS WIRE)--Owkin, the first end-to-end AI-biotech that uses agentic AI to revolutionize drug discovery, development, and diagnostics, today announced that the first patient has been dosed in its Phase I clinical trial of OKN4395 on January 22, 2025. OKN4395 builds upon well-characterized EP2/EP4 inhibition, through a newly identified and equipotent inhibition of DP1. The clinical significance of this first-in-class triple inhibition is being evaluated in this trial.

AI-optimized study design

Owkin’s proprietary K1.0 Operating System was instrumental in advancing OKN4395 from asset selection through to clinical development. By building a detailed biological understanding of the EP2/EP4/DP1 targets and their complex mechanisms of action, Owkin’s AI operating system was used to optimize the clinical development strategy. The program integrates Owkin’s expertise in AI-driven indication selection, external control arms (digital twins) for early anti-tumor activity insights in Phase I, and biomarker-led patient subtyping to enhance the probability of clinical success.

Thomas Clozel, MD, CEO & Co-founder of Owkin, said: "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."

A first-in-class asset: OKN4395

Prostaglandins E₂ and D₂ (or PGE₂, PGD₂) are hormone-like molecules produced naturally in the body, and are the natural ligands for prostanoid receptors EP2, EP4, and DP1, respectively. The PGE₂/EP2/EP4 and PGD₂/DP1 pathways are both known to be immunosuppressive^1,2. Well-described in oncology, hyperactivity of the PGE₂/EP2/EP4 pathway in certain cancers allows them to avoid the immune system’s effector mechanisms, leading to progression and resistance through tumor growth or metastasis¹.

OKN4395 is the first compound in the clinic to selectively inhibit EP2, EP4, and DP1 receptors. This novel mechanism offers the potential to restore immune function, providing transformative treatment options for patients with advanced solid tumors.

The INVOKE Study (OKN-4395-121)

INVOKE is a global, multicenter, Phase Ia/1b, first-in-human, open-label trial evaluating OKN4395 in patients with advanced solid tumors. Phase Ia primarily assesses safety and tolerability through dose escalation of OKN4395 as both a monotherapy and in combination with pembrolizumab. Phase Ib will expand into a further four cohorts, and assess preliminary anti-tumor activity, as well as safety and extensive exploratory analyses.

References

1. Jin, K., Qian, C., Lin, J., & Liu, B. (2023). Cyclooxygenase-2-Prostaglandin E2 pathway: A key player in tumor-associated immune cells. Frontiers in Oncology, 13, 1099811. https://doi.org/10.3389/fonc.2023.1099811
2. Luo, M., He, N., Xu, Q., Wen, Z., Wang, Z., Zhao, J., & Liu, Y. (2024). Roles of prostaglandins in immunosuppression. Clinical Immunology, 265, 110298. https://doi.org/10.1016/j.clim.2024.110298