TEAD

Pan-TEAD Inhibitor:

Treating Mesothelioma, and Solid Tumors

Current Stage: Phase I

Wholly-owned and Available for Licensing

Indication

Mesothelioma, epithelioid hemangioendothelioma (EHE), meningioma, glioblastoma, liposarcoma, and pancreatic cancers

• These cancers often have loss-of-function mutations in the NF2 gene, which encodes for Merlin, a protein that activates the Hippo pathway and inhibits YAP/TAZ-TEAD-mediated gene transcription. By blocking TEAD, inhibitors aim to restore the balance of the Hippo pathway and prevent the proliferation and survival of tumor cells. These cancers can benefit from Pan-TEAD inhibitors.

• ISM6631 is a potent pan-TEAD non-covalent inhibitor with a novel scaffold developed from Chemistry42, that has the potential to serve as a therapeutic approach for solid tumors in multiple cancer types resistant to current therapies.

• Broad Therapeutic Opportunities in Combination Therapy

• Combination with target therapy, chemotherapy and immunotherapy drugs for solid tumors treatment including EGFR and KRAS mutant Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Pancreatic cancer (PDAC) and other solid tumors.

About 6331

ISM6331 is a potent non-covalent small molecule inhibitor with a novel scaffold. The development of ISM6331 was significantly accelerated by Chemistry42, Insilico’s generative chemistry engine.

In preclinical studies, ISM6331 shows broad anti-tumor effect in multiple cell lines and potent efficacy at low doses in animal models, as well as a high safety margin and favorable ADMET profiles.

Assays Completed

Enzymatic

Toxicology studies

In vitro cell-based

Developability/CMC

In vitro ADME studies

In vivo PK studies

In vivo PK-PD

In vivo efficacy studies with single agent