MOMA-341 / MOMA Therapeutics - LARVOL DELTA

DNA repair and synthetic lethality (AACR-NCI-EORTC 2025) - "Here, I will review DNA Polymerase Theta (PolQ) as a potential therapeutic for the treatment of HRD associated tumors and present new data regarding MOMA-313, a highly potent and selective inhibitor of PolQ currently in Phase I clinical development. I will also discuss inhibition of the Werner (WRN) helicase, a synthetic lethal target in tumors with microsatellite instability (MSI), in which the WRN protein is required to resolve TA dinucleotide repeats and present new preclinical data regarding MOMA-341, a novel WRN inhibitor. These two opportunities represent dual approaches to expand the repertoire of agents targeting tumors with specific defects in genomic maintenance."

Synthetic lethality • Microsatellite Instability • Oncology • BRCA • HRD • MSI • POLQ • WRN

Orally administered MOMA-341 as monotherapy or combination therapy in participants with advanced or metastatic solid tumors: Phase 1 study design (AACR-NCI-EORTC 2025) - P1 | "DNA damage and anti-tumor activity are enhanced when MOMA-341 is combined with standard chemotherapies (eg, irinotecan). TA repeat expansions will be measured to further refine patient stratification biomarkers. Study sites are currently open and recruiting."

Combination therapy • IO biomarker • Metastases • Monotherapy • P1 data • Microsatellite Instability • Oncology • Solid Tumor • MSI • RECQL • WRN

Orally Administered MOMA-341 as Monotherapy or Combination Therapy in Participants With Advanced or Metastatic Solid Tumors: Phase 1 Study Design (MOMA Press Release) - "This is a phase 1, first-in-human, multi-center, open-label dose escalation and dose optimization study designed to assess the safety, tolerability, PK, PDx, and preliminary clinical activity of MOMA-341 (NCT06974110). MOMA-341 will be administered orally as monotherapy or in combination with either chemotherapy or immunotherapy in participants with advanced or metastatic solid tumors harboring MSI-H/dMMR alterations."

Clinical protocol • dMMR • MSI-H • Solid Tumor

Discovery of MOMA-341, a chemically distinct, potent and selective covalent inhibitor of Werner Syndrome Helicase (WRN) (ACS-Fall 2025) - "Optimization of potency and ADME properties in this rigidified background, guided by in silico prediction methods to maximize modeled in vivo target occupancy, led to the discovery of clinical candidate MOMA-341. MOMA-341 demonstrates tumor regression at low doses when dosed orally in several sensitive MSI-H CDX and PDX mouse xenograft models and is in Phase I clinical development."

Metabolic Disorders • Microsatellite Instability • MSI • WRN

Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: MOMA Therapeutics | Not yet recruiting ➔ Recruiting

dMMR • Enrollment open • Monotherapy • MSI-H • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor

MOMA Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial for MOMA-341, a Highly Potent and Selective Werner Helicase Inhibitor (MOMA Press Release) - "MOMA Therapeutics...announced that the first patient has been dosed in its Phase 1 clinical trial to assess the safety and tolerability of MOMA-341, a potent and selective Werner helicase inhibitor with a novel chemical scaffold. MOMA-341 is being developed as a monotherapy and in combination with chemotherapy or immunotherapy for the treatment of advanced or metastatic solid tumors that exhibit high microsatellite instability (MSI-H) and/or DNA mismatch repair deficiency (dMMR), including colorectal, gastric and endometrial cancers....MOMA anticipates an initial readout of monotherapy data in mid-2026."

dMMR • MSI-H • P1 data • Trial status • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability

TA repeat expansion outperforms MSI-H as a predictor of sensitivity to the novel WRN inhibitor MOMA-341 (MOMA Press Release) - "In contrast to dMMR or MSI-H status, direct measurement of genome-wide TA repeat expansions by long read sequencing produces a near-perfect prediction of sensitivity to WRN inhibition across a large cohort of preclinical tumor models. While MSI-H tumors with highly expanded TA repeat regions were very sensitive to MOMA-341, incomplete single agent antitumor activity was observed in MSI-H tumors with lower levels of TA repeat expansion."

Biomarker • dMMR • MSI-H • Preclinical • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability

Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=132 | Not yet recruiting | Sponsor: MOMA Therapeutics

dMMR • Monotherapy • MSI-H • New P1 trial • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor

Direct measurement of TA repeat expansions significantly outperforms MSI-H status as a predictor of sensitivity to the novel WRN inhibitor MOMA-341 (AACR 2025) - "However, these tumor responses could be converted to regressions when MOMA-341 was combined with chemotherapies such as irinotecan. This work demonstrates clearly that direct and specific measurement of the TA repeats that serve as a WRN helicase substrate is feasible, quantifiable and results in near perfect prediction of MOMA-341 anti-tumor activity in preclinical models, thereby successfully matching the relevant biology with pharmacologic response. Guided by this work, TA repeat expansions will be assessed in patient tumors within the upcoming Phase 1 clinical trial of MOMA-341 in dMMR/MSI-H tumors to better inform patient selection and the choice of single agent or combination dosing regimens."

MSI-H • Microsatellite Instability • Oncology • MSI • RECQL • WRN

MOMA Therapeutics to Present Multiple Posters at the American Association for Cancer Research Annual Meeting 2025 (Businesswire) - "MOMA Therapeutics...today announced three poster presentations at the 2025 American Association for Cancer Research (AACR) Annual Meeting, being held April 25 – 30, 2025 in Chicago, IL."

Clinical data • Solid Tumor

MOMA Therapeutics Provides Corporate Update… (Businesswire) - "MOMA-313 is currently in a Phase 1a dose escalation study designed to evaluate its potential as monotherapy and in combination with olaparib, an approved, non-selective PARP inhibitor (NCT06545942). An initial readout of olaparib combination efficacy data is anticipated in mid-2026, with development of the proprietary combination with MOMA-989 to initiate in late 2026. The company remains on track to file an IND for MOMA-341 during the first quarter of 2025....The company plans to assess the potential of MOMA-341 as a treatment for patients with cancers demonstrating microsatellite instability (MSI-H). Following successful IND clearance, MOMA anticipates an initial readout of early single agent efficacy data in mid-2026."

IND • P1 data • Breast Cancer • Microsatellite Instability • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer