INSILICO (03696) Announces Preliminary Positive First-in-Human Clinical Trial Data for Generative AI-Designed ISM6331 in the Treatment of Mesothelioma and Other Solid Tumors at ESMO 2026

INSILICO (03696) Announces Preliminary Positive First-in-Human Clinical Trial Data for Generative AI-Designed ISM6331 in the Treatment of Mesothelioma and Other Solid Tumors at ESMO 2026 INSILICO (03696) issued an announcement that the Company recently presented preliminary positive first-in-human Phase I clinical trial data for ISM6331. ISM6331 is an investigational oral pan-TEAD inhibitor designed with the empowerment of the Chemistry42 generative AI platform. As of the data cutoff date of August 14, 2026, among efficacy-evaluable mesothelioma subjects, the objective response rate (ORR) in the 130 mg once-daily dose group reached 40%, and across the 30-130 mg dose range, the disease control rate (DCR) at the first tumor assessment reached 68.2%. These research findings were presented in a rapid oral presentation at the 2026 European Society for Medical Oncology (ESMO) Annual Congress held in Madrid, Spain. In this Phase I clinical study (NCT06566079, data cutoff date: August 14, 2026, 36 subjects enrolled across the 15-130 mg dose range, median prior lines of therapy of 2, ranging from 1 to 12 lines, currently in the dose-escalation stage), across the 30-130 mg dose range, the ORR for mesothelioma subjects was 18.2% (4 responses among 22 efficacy-evaluable subjects), with responses observed in the 30 mg, 50 mg, and 130 mg cohorts. Among the 4 subjects who achieved response, 3 achieved response at the first tumor assessment at week 8. As of the data cutoff date, 3 of the 4 partial responses remain ongoing, with 1 response having a duration approaching 1 year. In addition to mesothelioma, preliminary antitumor signals also included target lesion shrinkage observed in heavily pretreated non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) subjects (7 and 8 prior lines, respectively), as well as stable disease (SD) lasting more than 4 months observed in epithelioid hemangioendothelioma (EHE) and colorectal cancer (CRC) subjects. The study reported no dose-limiting toxicities (DLTs) across the 15-130 mg dose groups, and no treatment-related adverse events (TRAEs) leading to permanent discontinuation occurred. Most TRAEs were low grade (Grade 1 or 2); only 8.3% of subjects experienced Grade 3 TRAEs, including asymptomatic amylase and lipase elevation, fatigue, and drug-induced dermatitis; treatment-related proteinuria (an adverse event of special interest in this study) occurred in 11.1% of subjects, all Grade 1 or 2 and reversible. Circulating CCN2 levels were persistently downregulated, validating effective targeted inhibition of the TEAD pathway by the drug; the terminal half-life is approximately 18-32 hours, supporting once-daily continuous dosing. ISM6331 is an investigational oral non-covalent pan-TEAD inhibitor designed to block TEAD-dependent gene transcription downstream of the Hippo pathway. The candidate is currently being evaluated in a global multicenter Phase I clinical study (NCT06566079) in advanced solid tumors. The innovative non-covalent structure of ISM6331 was guided by the structure-based drug design strategy of Chemistry42. In preclinical studies, ISM6331 demonstrated broad antitumor efficacy, potent activity at low doses, a favorable safety profile, and good ADMET properties. In 2024, ISM6331 was granted orphan drug designation by the FDA for the treatment of mesothelioma; in January 2025, the first patient was dosed in its global multicenter Phase I clinical trial; in July 2026, ISM6331 received Fast Track designation from the FDA.