NP1867 / NeoPhore - LARVOL DELTA

Pharmacological inhibition of PMS2 induces MMR deficiency and response to immune checkpoint blockade. (PubMed, Cancer Discov) - "Inoculation of syngeneic immunocompetent mice with cancer cells pretreated with NP1867 leads to CPI sensitivity, tumour growth delay, and complete responses. For the first time, we demonstrate pharmacological targeting of MMR to proactively rewire the tumour-host relationship for therapeutic purposes."

Checkpoint inhibition • IO biomarker • Journal • Tumor mutational burden • Microsatellite Instability • Oncology • MSI • PMS2 • TMB

Pharmacological inhibition of PMS2 increases tumor mutational burden, induces microsatellite instability and elicits immune mediated rejection in vivo (AACR 2024) - "In conclusion, small molecule NP1867 functionally inhibits DNA MMR by targeting PMS2, enriches gained mutations with MMR-d COSMIC signatures, elicits MSI-H status, and enhances immune surveillance in preclinical models. These findings pave the way for the development of orally bioavailable compounds suitable for long-term dosing in animal models."

IO biomarker • Preclinical • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • PMS2 • TMB

A Cell-Based MSI Reporter Platform Identifies QHT025: A First-in-Class MMRd-Inducing Compound Sensitizing MMRp Tumors to Immunotherapy (SITC 2025) - "QHT025 showed superior potency in driving MSI-H and converting MMRp→MMRd versus reference compounds (NP1867, TMZ).Conclusions This platform establishes an innovative cell-based assay for assessing MSI activity...Acting as an immune-priming agent, it remodels the TME to convert 'cold' tumors to 'hot' lesions. The platform and compound pioneer a novel therapeutic approach to sensitize MMRp tumors to immunotherapy."

dMMR • IO biomarker • Tumor mutational burden • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • TMB