OKN4395 / Owkin, Idorsia - LARVOL DELTA

INVOKE: A PHASE 1 STUDY OF OKN4395, A FIRST-IN-CLASS EP2/EP4/DP1 TRIPLE PROSTANOID RECEPTOR ANTAGONIST, IN PATIENTS WITH ADVANCED SOLID TUMORS, INCLUDING SARCOMAS (CTOS 2025) - P1 | "OKN4395 is hypothesized to modulate the tumor microenvironment to allow an effective immune response, and to potentiate the effect of other immunotherapies, both evaluated in INVOKE. INVOKE (OKN-4395-121; NCT06789172) is a Ph1a/1b, first-in-human study of OKN4395 (oral, BID) as monotherapy (mono) or in combination with pembrolizumab 200mg IV 3-weekly (combo), in patients with COX-associated immunosuppressed advanced tumors. N/A"

Clinical • IO biomarker • Metastases • P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

OKN4395: A first-in-class highly potent and selective EP2, EP4, and DP1 triple inhibitor for solid cancer treatment alone or in combination with anti-PD1 (SITC 2025) - P1 | "Finally, pharmacokinetic and tolerability profiles from non-clinical studies supported further clinical development.Conclusions Our studies demonstrate that triple inhibition of EP2, EP4, and DP1 with OKN4395 is more effective than dual EP2/EP4 inhibition in restoring anti-tumor immune responses in presence of both PGE2 and PGD2. These compelling results strongly endorse the clinical development of OKN4395, currently in a Phase 1 trial (NCT06789172), as a novel immunotherapy for solid tumors, both as a standalone treatment and in combination with anti-PD1.Ethics Approval All human derived material used in the study were obtained under ethics and regulatory approvals."

Combination therapy • Oncology • Solid Tumor • CD8 • IFNG

Context-based drug positioning and multimodal characterization for OKN4395 (ESMO 2025) - P1 | "The "Unfavorable" group was immune-cold with very low PGE2, produced either by malignant or immune cells. Conclusions We present a unique pipeline for drug positioning and translational research using biological contexts and multimodal data, supporting early clinical development."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

INVOKE: A phase 1 study of OKN4395, a first-in-class EP2/EP4/DP1 triple prostanoid receptor antagonist, in patients with advanced solid tumors. (ASCO 2025) - P1 | "COX2 inhibitors, aspirin and nonsteroidal anti-inflammatories (NSAIDS) have shown some survival benefit in patients with colon, lung, prostate, and endometrial cancer (Cao et al., 2016; Lim et al., 2012; Huang et al., 2014; Takiuchi et al., 2018), however results are inconsistent, likely due to toxicity limiting complete blockade of the pathway, highlighting the need for more potent but selective COX pathway inhibitors... INVOKE (OKN-4395-121; NCT06789172) is a Ph1a/1b, first-in-human study of OKN4395 (oral, BID) as monotherapy (mono) or in combination with pembrolizumab 200mg IV 3-weekly (combo), in patients with advanced solid tumors that have evidence of COX-associated immunosuppression...Trial data, paired pre- and on-treatment biopsies, and exploratory biomarkers will be used to enhance development using advanced agentic AI systems, including a synthetic digital twin control arm. Ph1a of the study is currently recruiting in the US, UK, and Australia."

Clinical • IO biomarker • Metastases • P1 data • Colorectal Cancer • Endometrial Cancer • Head and Neck Cancer • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8

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 (Businesswire) - "Owkin...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....INVOKE is a global, multicenter, Phase Ia/1b, first-in-human, open-label trial evaluating OKN4395 in patients with advanced solid tumors."

Trial status • Solid Tumor

INVOKE: A Phase 1, First-in-human Study of OKN4395 and Pembrolizumab in Patients with Solid Tumors (clinicaltrials.gov) - P1 | N=166 | Recruiting | Sponsor: Epkin

Monotherapy • New P1 trial • Head and Neck Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Owkin Unveils AI-Driven Oncology and Immunology Pipeline, In-Licenses Best-in-Class Asset OKN4395 (Businesswire) - "Owkin...has unveiled an innovative drug pipeline in oncology and immunology following an exclusive global licensing agreement with Idorsia...to develop and commercialize OKN4395, a clinic-ready best-in-class dual inhibitor of prostanoid receptors EP2 and EP4...To de-risk OKN4395’s clinical trial, Owkin will apply AI to build an external control arm in phase 1B and use multimodal patient data to select optimal inclusion/exclusion criteria and prognostic covariates to strengthen the treatment signal in a data-driven way."

Licensing / partnership • New molecule • Oncology