Early results from a Phase 1 clinical trial of ISM6331, an investigational AI-designed cancer drug developed by Insilico Medicine, were presented at the European Society of Medical Oncology (ESMO) Congress in Madrid. The first set of clinical findings, in a small group of patients, are showing promising anti-tumor activity against mesothelioma.
Notably, this first set of results reported a 40% objective response rate in its Phase 1 trial for patients with the deadly and highly treatment-resistant cancer mesothelioma, giving Insilico a strong platform to proceed onward with its research and a planned Phase 2a randomized dose operation.
“That is generative chemistry becoming a clinical signal,” said Alex Zhavoronkov, founder and CEO of Insilico Medicine, in a press release. “For Insilico, Hippo–TEAD sits at the intersection of cancer and aging biology, a multi-indication opportunity spanning Hippo-driven cancers and, potentially, age-related disease and aging itself, consistent with our dual-purpose discovery strategy. We will finish dose selection rigorously and push this molecule as hard as the data deserve.”
More on Insilico’s Pan-TEAD Inhibitor for Mesothelioma
Insilico’s announcement in July that they would be presenting data for their pan-TEAD inhibitor for mesothelioma at ESMO 2026 was met with significant anticipation. The U.S. Food and Drug Administration (FDA) followed this news by granting ISM6331 a “fast-track” designation, which is meant to facilitate an expedited development and review and could lead to a much quicker approval and availability of the drug once it is ready for market.
In a small sample, at least, the results have been intriguing. The 40% objective response rate figure was achieved from two of five response-evaluable participants with mesothelioma at a dose of 130 mg once daily, and Insilico reported target-lesion reduction of 58 and 36%. Across 22 participants at a lower dose – 30-130 mg – the objective response rate was 18.2%, and about two-thirds of this cohort achieved disease control.
Notably, Insilico reported no dose-limiting toxicity and no significant treatment-related adverse effects among the study’s participants. And perhaps most promisingly, these results were achieved among patients that had all been through multiple other forms of treatment, with some patients previously undergoing upwards of five or six lines of treatment.
ISM6331 also displayed promising results in other forms of cancer, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), epithelioid hemangioendothelioma and colorectal cancer.
According to Halle Zhang, Insilico’s Vice President, Clinical Development – Oncology, the particular success of the 130 mg cohort has emboldened Insilico to undergo preparations for its next stage, a Phase 2a randomized dope optimization
What is a Pan-TEAD Inhibitor?
Developed with Insilico’s generative AI-powered Chemistry42 drug discovery platform, the drug known as ISM6331 is part of a class of medications known as a pan-TEAD inhibitor. It works within the Hippo signaling pathway, which is one of the biological processes through which cells in the human body interact with one another.
TEAD (transcriptional enhanced associate domain) proteins are one of the primary mechanisms through which the Hippo pathway performs its duties in regulating cell development within tumors. As such, the “Hippo-TEAD axis” has been long considered a promising target for novel cancer therapies, although the unique structure of TEAD proteins made it a rather difficult nut to crack.
However, progress is being made. Aside from these recent results from Insilico, Vivace Therapeutics also presented proof-of-concept at last year’s ESMO Congress that their own TEAD inhibitor could successfully targeted the Hippo-TEAD axis in mesothelioma, while Orion Pharma is also proceeding with a Phase 1/2 trial targeting the Hippo pathway in mesothelioma.
These studies could be an indicator that a long-anticipated avenue of cancer treatment may finally be opening, one that could have implications for many more types of cancer beyond just mesothelioma. Many more steps remain from a Phase 1 trial to ultimate approval for wide usage, but these results should be considered a promising first step.
Sources & Author
- Insilico Medicine’s AI Drug Posts 40% Response Rate in Treatment-Resistant Mesothelioma. Tech Times. Retrieved from https://www.techtimes.com/articles/329538/20261027/insilico-medicines-ai-drug-posts-40-response-rate-treatment-resistant-mesothelioma.htm. Accessed on 10/28/2026.
- Insilico Medicine Reports 40% ORR at 130 mg for Pan-TEAD Inhibitor ISM6331 Designed Using Generative AI in Heavily Pretreated Mesothelioma at ESMO 2026. Insilico press release. Retrieved from https://www.prnewswire.com/news-releases/insilico-medicine-reports-40-orr-at-130-mg-for-pan-tead-inhibitor-ism6331-designed-using-generative-ai-in-heavily-pretreated-mesothelioma-at-esmo-2026-302919241.html. Accessed on 10/28/2026.
