ISM3412 / Insilico Medicine - LARVOL DELTA

Insilico Medicine completes first-in-patient dosing of ISM3412, the novel MAT2A inhibitor for the treatment of locally advanced/metastatic solid tumors (Eurekalert) - "Insilico Medicine...announces that the first patient has been dosed in a global multicenter clinical trial (NCT06414460) to evaluate ISM3412, a potentially best-in-class, AI-empowered MAT2A inhibitor with novel structure, in patients with locally advanced and metastatic solid tumors....The Phase I study of ISM3412 is currently recruiting in multiple sites across the United States and China, aiming to evaluate the safety, tolerability, PK/PD profiles and preliminary efficacy in patients."

Trial status • Solid Tumor

Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: InSilico Medicine Hong Kong Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: InSilico Medicine Hong Kong Limited

Metastases • New P1 trial • Oncology • Solid Tumor

Insilico Medicine's AI-designed drug ISM3412 receives FDA IND approval (News-Medical) - "Clinical stage artificial intelligence (AI)-driven drug discovery company Insilico Medicine ('Insilico') announces that it has received approval from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for ISM3412...With the IND approval, Insilico is approved to launch a Phase I multicenter, open label study of ISM3412 as a single agent in adult subjects with locally advanced and metastatic solid tumors with primary endpoints to include safety, tolerability, recommended Phase II dose determination and preliminary efficacy. All subjects will receive oral daily dosing of ISM3412 as a monotherapy, and additional expansion arms are planned across multiple indications."

IND • Non Small Cell Lung Cancer • Solid Tumor

Discovery of novel MAT2A inhibitors by an allosteric site-compatible fragment growing approach. (PubMed, Bioorg Med Chem) - "X-ray co-crystal structure revealed that compound 7 fully occupies the allosteric pocket of MAT2A as a single molecule mimicking MAT2B. By introducing additional backbone interactions and rigidifying the requisite linker extensions, we generated compound 8, which exhibited single digit nanomolar enzymatic and sub-micromolar cellular inhibitory potency for MAT2A."

Journal • Oncology • MAT2A • MTAP

ISM3412, a novel and selective MAT2A inhibitor for the treatment of cancer (AACR 2023) - "Notably, ISM3412 showed improved efficacy when combined with docetaxel, compared to the individual monotherapy. Further, it was well tolerated with no significant hepatobiliary toxicity. In conclusion, ISM3412 is a novel and highly selective MAT2A inhibitor for MTAP-deficient cancers, and merits clinical evaluation."

Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Urothelial Cancer • MAT2A • MTAP