MOMA Therapeutics Initiates First-in-Human Trial of Werner Helicase Inhibitor MOMA-341 for MSI-H Solid Tumors

Key Insights

• MOMA Therapeutics has dosed the first patient in a Phase 1 clinical trial of MOMA-341, a novel oral Werner helicase inhibitor targeting advanced or metastatic solid tumors with high microsatellite instability.
• The drug represents a potentially best-in-class therapeutic with a novel chemical scaffold discovered through MOMA's proprietary KNOMATIC platform, designed to exploit Werner helicase dependency in MSI-H/dMMR tumor cells.
• The global multi-center trial will evaluate MOMA-341 as monotherapy and in combination with chemotherapy or immunotherapy, with initial monotherapy data expected in mid-2026.

MOMA Therapeutics has achieved a significant milestone in precision oncology by dosing the first patient in a Phase 1 clinical trial of MOMA-341, a highly potent and selective Werner helicase inhibitor. The Cambridge-based clinical-stage biopharmaceutical company is targeting advanced or metastatic solid tumors characterized by high microsatellite instability (MSI-H) and DNA mismatch repair deficiency (dMMR), including colorectal, gastric, and endometrial cancers.

Novel Mechanism Targets Critical Tumor Dependency

MOMA-341 represents a breakthrough in targeting Werner helicase, an enzyme essential for the survival of MSI-H/dMMR tumor cells. This dependency makes Werner helicase a promising emerging drug target in precision oncology. The compound features a novel chemical scaffold identified through MOMA's proprietary KNOMATIC platform, which integrates deep structural insights, advanced hit-finding technologies, and computation-enabled lead optimization.

"We are proud to enter the clinic for the second time in less than a year, with initial readouts for both MOMA-341 and MOMA-313, our novel Pol θ helicase inhibitor, expected in early-to-mid 2026," said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA. "Given that MOMA-341's novel chemical scaffold confers excellent target coverage, we are eager to evaluate its best-in-class potential for patients through this Phase 1 study."

Comprehensive Trial Design for Combination Strategies

The Phase 1 clinical trial (NCT06974110) is designed as a global multi-center, open-label dose escalation and dose optimization study. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of MOMA-341 administered orally as a single agent or in combination therapy with either the chemotherapy agent irinotecan or immunotherapy.

Adult participants enrolled in the study must have unresectable advanced or metastatic microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR) solid tumors. MOMA anticipates an initial readout of monotherapy data in mid-2026.

Platform-Driven Drug Discovery Approach

The development of MOMA-341 showcases the capabilities of the KNOMATIC platform, which was specifically designed to target families of highly dynamic proteins such as ATPases and GTPases. This platform exploits key vulnerabilities inherent to all dynamic proteins, particularly their dependence on well-coordinated, stepwise changes in protein conformation.

Both MOMA-341 and MOMA-313 were discovered and developed through the application of this proprietary platform, demonstrating MOMA's systematic approach to accelerating discovery of novel therapeutics targeting genetically validated targets with high translation potential.