AI-Based Pan-TEAD Inhibitor Wins FDA Fast Track Designation in Mesothelioma

The FDA has granted fast track designation to ISM6331, an AI-designed pan-TEAD inhibitor, for the treatment of adult patients with unresectable malignant pleural mesothelioma whose disease has progressed on or after prior anti–PD-1 antibody therapy, with or without anti–CTLA-4 antibody therapy, and platinum-based chemotherapy, according to a news release from the developer, Insilico Medicine.¹

The designation marks the first fast track designation for the company’s AI-driven pipeline. Separately, data for the agent in a first-in-human phase 1 trial (NCT06566079) have been accepted for an oral presentation at the 2026 European Society for Medical Oncology (ESMO) Congress.²

What is ISM6331 and how does it work?

ISM6331 is a novel, potential best-in-class, small-molecule pan-TEAD inhibitor discovered and designed using Insilico Medicine’s proprietary generative AI platform, Chemistry42. The agent targets TEAD transcription factors, the principal downstream effectors of the Hippo signaling pathway, which is a regulator of cell proliferation, survival, tissue homeostasis, and therapeutic resistance across a range of solid tumors. Through pan-TEAD inhibition, ISM6331 is designed to restore balance to the Hippo pathway and prevent the proliferation and survival of tumor cells. In preclinical studies, the agent showed broad antitumor efficacy, potent activity at low doses, and a favorable safety profile, as well as synergistic antitumor effects and the potential to overcome drug resistance in combination with other agents.

What does fast track designation mean for ISM6331?

Fast track designation is intended to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. With the designation, ISM6331 gains access to enhanced FDA engagement, including more frequent meetings and written feedback on clinical trial design, biomarker strategies, and overall development plans. The program may also qualify for accelerated approval, priority review, and rolling review, subject to meeting the relevant criteria; under rolling review, completed sections of a biologic license application or new drug application may be submitted to the FDA as they become available.

“Receiving fast track designation validates the strong clinical potential of ISM6331,” said Halle Zhang, PhD, vice president of clinical development–oncology at Insilico Medicine, in the press release.¹ “Moreover, ISM6331 boasts synergistic antitumor effects and potential to overcome drug resistance as combination therapy. We hope to work even more closely with the FDA as we accelerate clinical evaluation of ISM6331 for future development.”

What is the ISM6331 phase 1 trial studying?

ISM6331 is being evaluated in a global, multicenter phase 1 clinical trial in patients with malignant mesothelioma and other advanced solid tumors. The study is assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the agent to inform its continued clinical development. First-in-human data from the trial have been accepted for a rapid oral presentation in the Developmental Therapeutics session at the 2026 ESMO Congress, to be held October 23 to 27 in Madrid, Spain.

The trial’s primary end points include the incidence of dose-limiting toxicities, adverse effects, clinically significant laboratory value abnormalities, and the recommended phase 2 dose.³ Secondary end points include objective response rate, best objective response, and duration of response.

What is ISM6331’s regulatory and development history?

Developers nominated ISM6331 as a development candidate in June 2023, and the agent was featured at the 2024 American Association for Cancer Research Annual Meeting (AACR).⁴ In June 2024, the FDA granted orphan drug designation to ISM6331 for the treatment of mesothelioma. Additionally, the first patient was dosed in the global multicenter phase 1 trial in January 2025.

References

1. Insilico Medicine receives FDA fast track designation for ISM6331, the AI-driven pan-TEAD inhibitor, in advanced mesothelioma. News release. Insilico Medicine. July 29, 2026. Accessed July 29, 2026. https://tinyurl.com/yk8vedcx
2. Insilico Medicine announces oral presentation at ESMO 2026 for phase 1 clinical study of ISM6331 in mesothelioma and advanced solid tumors. News release. Insilico Medicine. July 27, 2026. Accessed July 29, 2026. https://tinyurl.com/4akkcj73
3. Study of ISM6331 in participants with advanced/​metastatic malignant mesothelioma or other solid tumors ClinicalTrials.gov. Updated February 17, 2026. Accessed July 29, 2026. https://tinyurl.com/5z2tzabh
4. Li Q, Wan J, Liu J, et al. Abstract 1656: ISM6331, a novel and potent pan-TEAD inhibitor, exhibits strong anti-tumor activity in preclinical models of Hippo pathway-dysregulated cancers. Cancer Res. 2024;84(suppl 6):1656. doi:10.1158/1538-7445.AM2024-1656