MOMA Therapeutics Begins Phase 1 Trial for MOMA-313

MOMA Therapeutics, a clinical-stage biopharmaceutical company, has dosed its first patient in a Phase 1 clinical trial of MOMA-313, a new and highly selective oral polymerase theta helicase inhibitor. This trial aims to evaluate the safety and tolerability of MOMA-313, which is initially being developed in combination with a PARP inhibitor for solid tumors with specific DNA repair gene alterations. Such alterations are often found in subgroups of prostate, pancreatic, and breast cancers.

MOMA Therapeutics has also announced the selection of MOMA-341, a covalent Werner helicase inhibitor, as a development candidate for its second lead program. This oral inhibitor targets cancers with microsatellite instability, such as colorectal, gastric, and endometrial cancers. An IND application for MOMA-341 is expected to be filed with the FDA in the first quarter of 2025.

Dr. Asit Parikh, CEO of MOMA Therapeutics, expressed enthusiasm about the advancement of these two promising molecules. The progress from a conceptual idea to clinical development within a few years underscores the dedication and excellence of the MOMA team. Dr. Peter Hammerman, the company's chief scientific officer, highlighted the uniqueness of advancing two highly potent and selective drug candidates derived from MOMA's proprietary KNOMATIC platform, aiming to transform groundbreaking science into life-altering medicine.

MOMA-313 is a potent and selective oral polymerase theta (Polθ) helicase inhibitor. Polθ plays a crucial role in repairing DNA double-strand breaks that occur during DNA replication. The Phase 1 trial (NCT06545942) is a multi-center, open-label study designed to assess the safety and tolerability of MOMA-313 both as a monotherapy and in combination with the PARP inhibitor olaparib. PARP inhibitors are known to provide benefits, but their efficacy can be short-lived due to resistance. Pre-clinical studies have suggested that combining a PARP inhibitor with a Polθ inhibitor like MOMA-313 could enhance and prolong therapeutic responses.

MOMA-341 is being developed as an oral, potent, and selective covalent inhibitor of Werner helicase. It features a novel chemical scaffold and is intended for use both as monotherapy and in combination with chemotherapy and immunotherapy in tumors exhibiting microsatellite instability. This includes various types of cancers such as colorectal, gastric, and endometrial cancers.

The KNOMATIC platform, which facilitated the discovery and development of MOMA-313 and MOMA-341, integrates deep structural insights, advanced hit-finding technologies, and computational lead optimization. This platform accelerates the discovery of novel therapeutics targeting highly dynamic proteins like ATPases and GTPases.

MOMA Therapeutics is dedicated to targeting highly dynamic proteins that contribute to human diseases through a small-molecule approach, utilizing its proprietary KNOMATIC platform. The platform was designed to exploit the vulnerabilities of dynamic proteins, particularly their reliance on coordinated changes in protein conformation. By focusing on genetically validated targets with high translation potential, MOMA is rapidly advancing its pipeline towards clinical responses. In January 2024, MOMA announced a five-year discovery collaboration with Roche, focusing on critical cancer dependencies.