Cambridge, Massachusetts, U.S., October 25, 2026
Insilico Medicine has reported encouraging preliminary clinical findings for ISM6331, an investigational cancer drug designed using generative artificial intelligence (AI), with a 40% objective response rate (ORR) at a 130 mg once-daily dose in patients with mesothelioma. The results were presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, marking an important milestone for the company’s AI-driven drug discovery strategy. ISM6331 is an oral, non-covalent pan-TEAD inhibitor developed using Insilico’s Chemistry42 generative chemistry platform. It is designed to block TEAD transcription factors involved in the Hippo signaling pathway, which regulates cell growth and survival and can contribute to cancer development when dysregulated. The ongoing Phase 1 study is evaluating the candidate’s safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with advanced solid tumors, including mesothelioma. The findings provide an early clinical signal for an AI-designed oncology candidate targeting a challenging cancer-related pathway, although larger studies are needed to establish its efficacy and safety.
ISM6331 Shows Preliminary Antitumor Activity in Mesothelioma
In the Phase 1 study, two of five response-evaluable patients receiving 130 mg of ISM6331 once daily achieved an objective response, corresponding to an ORR of 40%. The company reported target-lesion reductions of 58% and 36% in these patients. Across dose cohorts from 30 mg to 130 mg, four of 22 response-evaluable patients with mesothelioma achieved objective responses, resulting in an ORR of 18.2%. The disease control rate (DCR) across these dose cohorts was 68.2%, indicating that some patients experienced a partial response or disease stabilization. Three of the four reported responders had responses at their first assessment around Week 8, and responses were observed in patients who had previously received five or six lines of treatment. Three of the four partial responses remained ongoing at the August 14, 2026, data cutoff, including one lasting approximately one year. The Phase 1 trial enrolled 36 participants across dose levels ranging from 15 mg to 130 mg, and dose escalation was ongoing at the time of analysis. These results are preliminary and based on small patient groups, particularly at the 130 mg dose, so the response rate should not be interpreted as a confirmed estimate of treatment benefit for a broader population.
Safety Findings and TEAD Pathway Engagement
Insilico Medicine also reported an encouraging early safety profile. No dose-limiting toxicities were reported from 15 mg through 130 mg, and no treatment-related adverse events led to treatment discontinuation at the data cutoff. Most treatment-related adverse events were Grade 1 or Grade 2. Grade 3 treatment-related events occurred in 8.3% of participants and included increases in amylase and lipase, fatigue, and drug-related dermatitis. Treatment-related proteinuria was reported in 11.1% of participants and was described as low-grade and reversible. The company also observed sustained reductions in circulating CCN2, a biomarker associated with TEAD pathway activity, supporting biological target engagement in patients. The reported terminal half-life of approximately 18–32 hours may support the candidate’s once-daily dosing schedule. These findings will require confirmation as more patients receive treatment and longer-term safety information becomes available. An acceptable early safety profile does not establish that ISM6331 is safe or effective for routine clinical use.
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Generative AI Advances Oncology Drug Development
ISM6331 illustrates how generative AI can support the design and optimization of investigational medicines. Insilico used its Chemistry42 platform to help design a molecule intended to inhibit TEAD1–4, transcription factors downstream of the Hippo pathway. The company is investigating ISM6331 in a global, multicenter Phase 1 trial involving patients with mesothelioma and other advanced solid tumors. The candidate has received U.S. FDA Orphan Drug Designation and Fast Track Designation for mesothelioma. Insilico plans to complete dose selection and, subject to the emerging clinical evidence, advance the program into a randomized Phase 2a dose-optimization study. These regulatory designations support development but do not constitute marketing approval. The next stages of research will be important in determining the appropriate dose, durability of response, and potential role of ISM6331 in cancer treatment.
Source: Insilico Medicine press release
