CAMBRIDGE, Mass., Oct. 26, 2026 /PRNewswire/ -- Insilico Medicine ("Insilico", HKEX: 3696), a clinical-stage generative AI-driven drug discovery company, today announced promising first-in-human Phase 1 data for ISM6331, its investigational oral pan-TEAD inhibitor designed using Chemistry42 generative AI platform. Among response-evaluable participants with mesothelioma, the results showed a 40.0% objective response rate (ORR) at 130 mg once daily and an 18.2% ORR with a 68.2% disease control rate (DCR) across the dose cohorts. Findings were presented as a Rapid Oral at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid by Melina E. Marmarelis, MD of Abramson Cancer Center, University of Pennsylvania.
In the ongoing Phase 1 study (NCT06566079; data cutoff August 14, 2026; N=36 enrolled across 15-130 mg; median prior lines 2, range 1-12; dose escalation ongoing), ISM6331 showed antitumor activity in heavily pretreated mesothelioma.
At 130 mg once daily, ORR was 40.0% (two of five response-evaluable participants), with target-lesion reductions of 58% and 36%. Across 30-130 mg, mesothelioma ORR was 18.2% (four of 22 response-evaluable participants) and disease control rate (DCR) 68.2%, with responses at 30, 50, and 130 mg; three of four responders showed responses at the first Week-8 scan; partial responses were observed after five and six prior lines; three of four partial responses were ongoing at cutoff, including one lasting approximately one year.
Signal beyond mesothelioma included target-lesion shrinkage in heavily pretreated non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) (seven and eight prior lines) and stable disease beyond four months in epithelioid hemangioendothelioma and colorectal cancer.
No dose-limiting toxicity (DLT) was reported from 15 mg through 130 mg; no treatment-related adverse events (TRAEs) led to discontinuation; TRAEs were mostly low grades (Grade 1 or 2). Grade 3 TRAEs occurred in 8.3% of participants, including asymptomatic amylase and lipase increase, fatigue and drug dermatitis; treatment-related proteinuria (adverse event of special interest) in 11.1% was low-grade and reversible. Sustained reductions in circulating CCN2 support TEAD pathway engagement; terminal half-life of approximately 18-32 hours supports continuous once-daily dosing.
ISM6331 is an investigational oral, non-covalent, pan-TEAD1-4 inhibitor maximally multiparameter-optimized using Chemistry42 generative AI platform with continuous once-daily pharmacokinetics, patient CCN2 pharmacodynamic engagement, and dual U.S. FDA Orphan Drug Designation (June 2024) and Fast Track Designation (July 2026) for mesothelioma - Insilico's first Fast Track program.
The company plans to complete Phase 1 dose selection and, subject to emerging data, initiate a Phase 2a randomized dose-optimization study in mesothelioma.
"TEAD sat for years in the industry's 'too hard' category. Today we reported first-in-human data for our pan-TEAD inhibitor designed using generative AI with a 40% ORR at 130 mg in heavily pretreated mesothelioma, deep lesion reductions of 58% and 36%, disease control in more than two-thirds of evaluable participants, and responses by week eight - including after five and six prior lines. No dose-limiting toxicities so far, and falling blood CCN2 tells us we are hitting TEAD in patients. That is generative chemistry becoming a clinical signal. 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," said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine.
"The 40% ORR at 130 mg and manageable safety profile in previously treated mesothelioma support continued investigation. As we complete dose selection, we plan to advance to Phase 2a randomized dose optimization," said Halle Zhang, PhD (Med), Vice President, Clinical Development - Oncology at Insilico Medicine.
About ISM6331
ISM6331 is an investigational oral non-covalent pan-TEAD inhibitor designed to block TEAD-dependent transcription downstream of the Hippo pathway and is being evaluated in a global multicenter Phase 1 study in advanced solid tumors (NCT06566079). It holds U.S. FDA Orphan Drug and Fast Track designations for mesothelioma.
About Insilico Medicine
Insilico Medicine is a pioneering global biotechnology company dedicated to integrating artificial intelligence and automation technologies to accelerate drug discovery, drive innovation in the life sciences, and extend healthy longevity to people on the planet. The company was listed on the Main Board of the Hong Kong Stock Exchange on December 30, 2025, under the stock code 03696.HK.
By integrating AI and automation technologies and deep in-house drug discovery capabilities, Insilico is delivering innovative drug solutions for unmet needs including fibrosis, oncology, immunology, pain, and obesity and metabolic disorders. Additionally, Insilico extends the reach of Pharma. AI across diverse industries, such as advanced materials, agriculture, nutritional products and veterinary medicine.
For more information, please visit www.insilico.com
SOURCE Insilico Medicine
