Zhitong Finance App News, Insili Intelligence (03696) issued an announcement. The company recently announced preliminary positive data from the first human phase I clinical trial of ISM6331. ISM6331 is an oral pan-TEAD inhibitor under research designed with the help of the Chemistry42 generative AI platform. As of the data cutoff date of August 14, 2026, among mesothelioma subjects whose efficacy can be assessed, the objective response rate (ORR) reached 40% in the 130 mg dose group once a day, and the disease control rate (DCR) at the time of initial tumor evaluation reached 68.2% within the 30-130 mg dose range. The findings were presented as a quick oral report at the 2026 European Society of Medical Oncology (ESMO) Annual Meeting in Madrid, Spain.
In this phase I clinical study (NCT06566079, data end date: August 14, 2026, where 36 subjects were included in the 15-130 mg dose range, the median number of previous treatment lines was 2 lines, ranging from 1 to 12, and the dose escalation phase is currently underway), the ORR of mesothelioma subjects was 18.2% in the 30-130 mg dose range (relief in 4 subjects with 22 patients whose efficacy can be assessed) was observed in the 30 mg, 50 mg, and 130 mg cohorts. Of the 4 subjects who achieved remission, 3 achieved remission when the tumor was first assessed at week 8. As of the data cutoff date, 3 out of 4 cases of partial remission were still in continuous remission, and 1 of these cases had been in remission for close to 1 year.
In addition to mesothelioma, initial anti-tumor signals also include target lesion reduction observed in non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) subjects (line 7 and 8, respectively), and disease stability (SD) for more than 4 months in subjects with epithelioid hemangioendothelioma (EHE) and colorectal cancer (CRC).
None of the studies reported dose-limiting toxicity (DLT) and no treatment-related adverse events (TRAEs) leading to permanent discontinuation of the drug in the 15-130 mg dose group. Most TRAEs were low grade (grade 1 or 2); only 8.3% of subjects developed grade 3 TRAE, including asymptomatic amylase and lipase elevation, fatigue, and drug-induced dermatitis; treatment-related proteinuria (adverse events of particular concern in this study) occurred in 11.1% of subjects, all grade 1 or 2 and were reversible. Cyclic CCN2 levels continued to decrease, verifying the drug's effective targeted inhibition of the TEAD pathway; the final half-life is about 18-32 hours, supporting continuous administration once a day.
ISM6331 is an investigational oral non-covalent pan-TEAD inhibitor aimed at blocking TEAD-dependent gene transcription downstream of the Hippo pathway. The drug candidate is currently being evaluated in a global multicenter phase I clinical study (NCT06566079) for advanced solid tumors. ISM6331's innovative non-covalent structure is guided by Chemistry42's structure-based drug design strategy.
In preclinical studies, ISM6331 showed a wide range of anti-tumor efficacy, strong activity at low doses, ideal safety, and good ADMET characteristics. In 2024, ISM6331 was granted orphan drug qualification by the FDA for the treatment of mesothelioma; in January 2025, its global multi-center phase I clinical trial completed administration for the first patient; in July 2026, ISM6331 obtained FDA fast-track qualification.