MOMA Therapeutics Initiates Phase 1 Trial for Novel DNA Repair Inhibitor MOMA-313
核心洞察
MOMA Therapeutics has dosed the first patient in a Phase 1 clinical trial evaluating MOMA-313, a highly potent and selective oral polymerase theta helicase inhibitor with best-in-class potential.
The trial will assess MOMA-313 as monotherapy and in combination with PARP (搜索) inhibitor olaparib for patients with solid tumors harboring DNA repair gene alterations, including prostate, pancreatic, and breast cancers.
The company simultaneously selected MOMA-341, a Werner helicase inhibitor, as its second development candidate for microsatellite instability cancers, with IND filing anticipated in Q1 2025.
MOMA Therapeutics has achieved a significant milestone by dosing the first patient in a Phase 1 clinical trial for MOMA-313, a novel polymerase theta helicase inhibitor designed to target cancers with DNA repair gene mutations. The Cambridge-based clinical-stage biopharmaceutical company announced this development on August 19, 2024, marking the transition of their lead compound from preclinical research to human testing.
Novel Mechanism Targets DNA Repair Vulnerabilities
MOMA-313 represents a highly potent and selective oral inhibitor of polymerase theta (Polθ) helicase, a protein involved in repairing DNA double-strand breaks that occur during DNA replication. The compound is initially being developed in combination with PARP (搜索) inhibitors for patients with solid tumors harboring alterations in specific DNA repair genes, including subgroups of prostate cancer, pancreatic cancer, and breast cancer.
The Phase 1 trial (NCT06545942) is designed as a multi-center, open-label study to evaluate the safety and tolerability of MOMA-313 both as monotherapy and in combination with the PARP (搜索) inhibitor olaparib. This combination approach addresses a critical clinical challenge, as response to PARP inhibitors can be short-lived due to primary and acquired resistance mechanisms.
According to preclinical studies referenced by the company, combining a PARP (搜索) inhibitor with a Polθ inhibitor could provide unique mechanistic potential to deepen and prolong therapeutic responses in patients where PARP inhibitors would be expected to provide benefit.
Dual Pipeline Advancement
In parallel with the MOMA-313 clinical initiation, MOMA Therapeutics announced the selection of MOMA-341 as the development candidate for its second lead program. MOMA-341 is described as an oral, potent and selective covalent inhibitor of Werner helicase featuring a novel chemical scaffold. The compound is being developed for treatment of cancers with microsatellite instability, including colorectal, gastric, and endometrial cancers, both as monotherapy and in combination with chemotherapy and immunotherapy. An IND application filing with the FDA is anticipated in the first quarter of 2025.
"We are excited to be progressing two molecules with best-in-class potential toward the benefit of cancer patients in need in such close proximity," said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA. "The advance into clinical development for a company founded as an idea on paper a few years back is humbling. This progress serves as a testament to the excellence and unwavering commitment of the entire MOMA team."
KNOMATIC Platform Drives Discovery
Both MOMA-313 and MOMA-341 were discovered and developed through the application of MOMA's proprietary KNOMATIC platform. This platform integrates deep structural insights, advanced hit-finding technologies, and computation-enabled lead optimization to accelerate discovery of novel therapeutics targeting families of highly dynamic proteins, such as ATPases and GTPases.
Peter Hammerman, M.D., Ph.D., chief scientific officer of MOMA, emphasized the platform's significance: "Advancing two highly potent and selective drug candidates derived from our proprietary KNOMATIC platform toward the clinic is a unique privilege. The goal with each candidate is to translate groundbreaking science into life-altering medicine."
Strategic Partnerships and Company Background
MOMA Therapeutics positions itself as a clinical-stage, next-generation precision medicine company dedicated to targeting highly dynamic proteins that underlie human disease through a small molecule approach. The KNOMATIC platform was specifically designed to exploit key vulnerabilities inherent to all dynamic proteins, namely their dependence on well-coordinated, stepwise changes in protein conformation.
The company's focus on genetically validated targets with high translation potential supports its strategy of rapidly advancing pipeline candidates toward clinical responses. In January 2024, MOMA announced a five-year discovery collaboration with Roche focused on critical cancer dependencies, demonstrating industry recognition of their platform's potential.