The first-in-human trial is open-label and follows patients with mesothelioma or another advanced solid tumor across multiple sites. Its stated objectives are to assess dose-limiting toxicities, determine a recommended dose for a subsequent Phase 2 study and evaluate the compound’s preliminary antitumor activity. The ESMO abstract has been published, while detailed and updated study data have been submitted for presentation. Insilico said the program’s clinical development team would discuss the study at the meeting and that further information would be announced afterward.

ISM6331 inhibits TEAD transcription factors downstream of the Hippo signaling pathway, which the company describes as helping regulate cell growth and tissue maintenance. Dysregulation of this network can contribute to cancer biology, providing the rationale for investigating TEAD inhibition in selected tumors. Mesothelioma is the program’s principal disease focus, although the study also includes patients with other advanced solid tumors. Insilico nominated ISM6331 as a preclinical candidate in June 2023, and the global multicenter Phase 1 study entered clinical testing in January 2025.

The candidate was designed and optimized with Chemistry42, Insilico’s generative chemistry platform. The company said the program combined computational molecular design with laboratory evaluation and clinical development, illustrating how an AI-designed candidate can progress into human testing without establishing that it provides a clinical benefit. Insilico has also announced U.S. Food and Drug Administration Orphan Drug Designation for mesothelioma and Fast Track Designation for adult patients with previously treated, unresectable malignant pleural mesothelioma. These designations support continued development but do not establish efficacy or constitute marketing approval.

Melina E. Marmarelis, MD, of the Abramson Cancer Center at the University of Pennsylvania, will deliver the presentation in the Developmental Therapeutics rapid oral session. The scheduled title is “First-in-human Multicenter Phase 1 Study of ISM6331, an AI-Designed Pan-TEAD Inhibitor, in Patients with Mesothelioma or Other Advanced Solid Tumors,” under abstract number 997. The rapid oral session runs from 08:30 to 10:00 Central European Time on October 25, with the presentation itself scheduled for 08:57–09:02 in Madrid’s Cordoba Auditorium, Hall 4. The ongoing study is registered as NCT06566079. Because this is an initial Phase 1 safety, dose-finding and preliminary activity evaluation in a selected cancer population, the presentation will not by itself resolve questions about therapeutic benefit or the agent’s role in future treatment.

Subject of Research: Phase 1 evaluation of AI-designed pan-TEAD inhibitor ISM6331 in mesothelioma and other advanced solid tumors

Article Title: Insilico Medicine to present first human data for AI-designed cancer drug ISM6331 at ESMO 2026

Article References: Insilico Medicine to present first human data for AI-designed cancer drug ISM6331 at ESMO 2026. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: ISM6331, artificial intelligence, drug discovery, pan-TEAD inhibitor, mesothelioma, advanced solid tumors, Phase 1 trial, ESMO 2026, Hippo pathway, Insilico Medicine, Insilico, Medicine