NTX-452 / Nimbus Therap - LARVOL DELTA

NTX-452: a non-covalent, potent, selective and highly efficacious WRN inhibitor with best-in-class potential for the treatment of MSI-H tumors (AACR 2025) - "Washout studies using covalent inhibitors revealed that substantial target engagement was lost in MSI-H cells within 24- hours, suggesting rapid WRN resynthesis may limit sustained target inhibition...The preclinical profile of non-covalent NTX-452 was characterized and compared to clinical-stage WRN inhibitors, including those from Novartis (HRO761, non-covalent) and Roche/Vividion (RO7589831, covalent)...Moreover, NTX-452 promoted durable tumor regression and complete responses in MSI-H PDX models that were refractory to immunotherapy (anti-PD1) or chemotherapy. Lastly, resistance to clinical stage WRN inhibitors was explored and the potential for NTX-452 efficacy in WRN inhibitor resistant cell lines and tumors was evaluated.Taken together, our results highlight the broad, best-in-class potential of NTX-452 in MSI-H tumors and support its advancement to clinical evaluation."

MSI-H • Endometrial Cancer • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • WRN

Nimbus Therapeutics Presents First Preclinical Data on Novel WRN Inhibitor NTX-452 at 36th EORTC-NCI-AACR Symposium (Businesswire) - "Nimbus Therapeutics...announced that it is presenting preclinical data on its new development candidate, NTX-452, a novel Werner syndrome helicase (WRN) inhibitor, at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics....Treatment with NTX-452 at low doses in vivo exhibited a robust pharmacodynamic response, resulting in tumor regression across multiple MSI-H cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor models, including established models for colorectal, gastric and endometrial cancers. Significant tumor regression and complete responses were observed at low oral doses in MSI-H models refractory to immunotherapy and chemotherapy....Nimbus is advancing NTX-452 with plans to enter the clinic in the first half of 2025."

New trial • Preclinical • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability

Preclinical characterization of NTX-452, a potent, selective and highly efficacious WRN inhibitor for the treatment of MSI-H tumors (EORTC-NCI-AACR 2024) - "Furthermore, the preclinical profile and PK/PD relationship of NTX-452 and additional lead WRN inhibitors support the potential for a low efficacious dose in humans and will enable selection of a clinical candidate. ConclusionsOur WRN inhibitors, exemplified here by NTX-452, are potent and selective inhibitors of WRN with excellent drug properties that provide robust in vivo efficacy across multiple preclinical MSI-H CDX and PDX tumor models, and may offer a promising therapeutic option for MSI-H cancer patients."

Preclinical • Endometrial Cancer • Microsatellite Instability • Oncology • MSI • WRN

Nimbus Therapeutics to Present First Preclinical Data from Werner Syndrome Helicase Program at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (Businesswire) - "Nimbus Therapeutics...announced that it will present the first preclinical data on its novel Werner syndrome helicase (WRN) inhibitor in a poster presentation at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics....WRN is a helicase required for DNA replication and DNA repair and is a validated target for tumors with microsatellite instability (MSI). Nimbus will present preclinical data on NTX-452, a novel WRN inhibitor developed using the company's computational drug discovery platform."

Preclinical • Microsatellite Instability • Solid Tumor

Nimbus Therapeutics Announces Expansion of Its Immunology Drug Discovery Pipeline (Businesswire) - "Nimbus Therapeutics, LLC...announced the advancement and expansion of its pipeline with the addition of discovery programs targeting innate immunity pathways...'SIK and cGAS are critical targets in highly prevalent diseases that are well suited to Nimbus’ structure-based drug design approach. We look forward to advancing our discovery and development programs across oncology, immunology, and metabolism to deliver transformative medicines to patients.'...Nimbus is advancing its Phase 1/2 trial (NCT05128487) of NDI-101150...and has reported positive dose escalation data showing potential monotherapy clinical benefit for patients with solid tumors. Furthermore, the company expects to initiate IND-enabling activities this year for its oncology program targeting Werner syndrome helicase (WRN)....Jeb Keiper...will provide an overview of the company’s progress and pipeline and anticipated milestones for 2024 and beyond at the 42nd Annual J.P. Morgan Healthcare..."

Pipeline update • Trial status • Immunology • Metabolic Disorders • Oncology • Solid Tumor