The novel AI-designed pan-TEAD inhibitor ISM6331 has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with unresectable malignant pleural mesothelioma whose disease has progressed on or after prior treatment with an anti–PD-1 antibody, with or without an anti–CTLA-4 antibody, and platinum-based chemotherapy.  

ISM6331 was designed using Insilico’s proprietary generative drug design platform, Chemistry42, to inhibit TEAD and block the tumor growth signaling that occurs when the Hippo pathway is inactivated. 

The agent’s structure was selected using a generative AI model and demonstrated strong inhibition of TEAD1/2/3/4. In preclinical models, the inhibitor showed dose-dependent antitumor activity as a monotherapy and was well tolerated in toxicity studies. It also demonstrated synergy with EGFR and KRAS G12C inhibitors, helping to overcome drug resistance and inhibit tumor growth.  

The novel agent is currently being evaluated in a global, multicenter phase I trial, in which the first patient was dosed in January 2025. Findings from the first-in-human study are expected to be presented at the European Society for Medical Oncology (ESMO) Congress 2026 in October.  

With the Fast Track designation, ISM6331 will be eligible for regulatory benefits intended to accelerate its clinical development.  

ISM6331 also received Orphan Drug designation from the FDA in June 2024 for the treatment of patients with mesothelioma.  

“Through pan-TEAD inhibition, ISM6331 holds best-in-class potential by aiming to restore balance to the Hippo pathway and prevent the proliferation and survival of tumor cells, and we’re proud to see the Chemistry42-driven candidate have its value recognized by regulatory authorities through both [Orphan Drug designation] and [Fast Track designation],” stated Feng Ren, PhD, co-CEO and Chief Scientific Officer of Insilico Medicine.

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