Owkin Achieves Milestone with First Patient Dosed in AI-Optimized Phase I Trial of OKN4395, a First-in-Class Triple Inhibitor for Solid Tumors
On January 22, 2025, Owkin, the pioneering end-to-end AI biotech company transforming drug discovery, development, and diagnostics through agent-based artificial intelligence, announced a significant milestone: the administration of the first dose to a patient in the Phase I clinical trial of OKN4395. This groundbreaking compound represents the first program developed entirely using Owkin’s proprietary AI-powered operating system, K1.0, from asset selection to clinical development optimization. The study, known as INVOKE (OKN-4395-121; NCT06789172), is sponsored by Epkin, an Owkin company, and marks a pivotal moment in the application of AI-driven technologies to advance precision medicine.
A Novel Approach to Cancer Treatment: OKN4395
OKN4395 is a highly selective triple inhibitor targeting the prostanoid receptors EP2, EP4, and DP1—a first-in-class therapeutic approach aimed at addressing unmet needs in patients with advanced solid tumors. These receptors are activated by prostaglandins E2 (PGE2) and D2 (PGD2), hormone-like molecules naturally produced in the body that play a critical role in suppressing the immune system.
The PGE2/EP2/EP4 and PGD2/DP1 signaling pathways have been extensively studied in oncology and are known to contribute to tumor progression, metastasis, and resistance to treatment by evading immune effector mechanisms. By selectively inhibiting these pathways, OKN4395 has the potential to restore immune function and offer transformative treatment options for patients with aggressive cancers.
This innovative mechanism builds on decades of research into prostaglandin biology and leverages Owkin’s cutting-edge AI capabilities to identify and optimize this novel therapeutic target. As Thomas Clozel, Managing Director, CEO, and co-founder of Owkin, stated, “OKN4395 not only reflects years of intensive research but also demonstrates the transformative power of Owkin’s K1.0 operating system. This milestone underscores our ability to rapidly translate promising assets into an AI-optimized clinical program.”
The Role of AI in Accelerating Drug Development
Owkin’s K1.0 operating system has been instrumental in advancing OKN4395 from its initial discovery to the design of its clinical development strategy. The platform integrates multiple layers of biological data and computational models to provide a comprehensive understanding of complex disease mechanisms. Key contributions of K1.0 to the OKN4395 program include:
- Target Identification and Validation: K1.0 analyzed vast datasets to uncover the intricate interplay between the EP2/EP4/DP1 pathways and their role in immune suppression, enabling the identification of this unique triple inhibition strategy.
- Indication Selection: Using AI-driven insights, Owkin identified specific patient populations likely to benefit most from OKN4395, ensuring a targeted approach to clinical trials.
- Clinical Trial Optimization: The platform employed digital twins—virtual representations of real-world patients—to simulate control arms and predict anti-tumor activity early in the trial process. This approach minimizes risks, reduces costs, and accelerates timelines.
- Biomarker Discovery: K1.0 facilitated the identification of biomarkers to stratify patients based on their likelihood of responding to treatment, enhancing the probability of clinical success.
By leveraging these capabilities, Owkin has streamlined the traditionally lengthy and resource-intensive drug development process, setting a new standard for innovation in oncology.
Addressing Unmet Needs in Oncology
The INVOKE study is designed to evaluate the safety, tolerability, and preliminary efficacy of OKN4395 in patients with advanced solid tumors. Phase Ia will focus on assessing the compound’s safety profile as both monotherapy and in combination with pembrolizumab, a widely used immunotherapy. Phase Ib will expand to include four additional cohorts, providing deeper insights into the drug’s antitumor activity and further exploring its safety profile.
With more than 100,000 patients per year in the U.S., EU4 (Germany, France, Italy, and Spain), and the UK eligible for Phase Ib indications, OKN4395 holds immense potential to address the urgent needs of patients who currently lack effective treatment options. Its novel mechanism of action offers hope for improved outcomes in difficult-to-treat cancers, particularly those resistant to existing therapies.
Scientific Foundations Supporting OKN4395
The rationale behind OKN4395 is rooted in extensive scientific research highlighting the immunosuppressive effects of the PGE2/EP2/EP4 and PGD2/DP1 pathways. Studies have shown that hyperactivity in these pathways allows tumors to evade immune detection, promoting growth and metastasis. For example:
- A 2023 study published in Frontiers in Oncology demonstrated the role of the cyclooxygenase-2 (COX-2)-prostaglandin E2 pathway in modulating tumor-associated immune cells, underscoring its importance in cancer progression.
- Another 2024 publication in Clinical Immunology explored how prostaglandins contribute to immunosuppression, reinforcing the need for therapies like OKN4395 to counteract these mechanisms.
By targeting all three receptors simultaneously, OKN4395 aims to disrupt these pathways comprehensively, potentially reactivating the immune system and halting tumor progression.
Transformative Potential of OKN4395
The initiation of the INVOKE study represents a significant step forward in Owkin’s mission to revolutionize oncology care through AI-driven innovation. If successful, OKN4395 could pave the way for a new class of therapies capable of overcoming immune evasion—a major hurdle in cancer treatment.
Moreover, this program exemplifies the broader impact of AI in drug development. By integrating advanced analytics, machine learning, and real-world data, Owkin is not only accelerating the discovery of novel therapeutics but also ensuring they reach the right patients at the right time.
As the global healthcare landscape continues to evolve, initiatives like OKN4395 highlight the critical role of technology in addressing complex medical challenges. With its groundbreaking approach and robust scientific foundation, OKN4395 has the potential to redefine the future of cancer treatment.
For more information about the INVOKE study or Owkin’s innovative AI-driven solutions, visit the official website or explore the original publications cited below.
References
- 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
- 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
Note: The source language version of the original text is the legally binding document. Translations are provided for convenience and should be cross-referenced with the original.
