CH41 / CellarisBio - LARVOL DELTA

First-in-class stabilizing inhibitor of CHD4 that traps and disassembles the NuRD complex (AACR 2026) - "Functionally, CH41 disables CHD4-dependent DNA repair and transcriptional control, re-sensitizing temozolomide-resistant glioblastoma cells. The data establishes CH41 as the first selective CHD4 inhibitor and illustrates how advances in cellular biophysics and cellular target engagement profiling are transforming the discovery of small molecule modulators of challenging transcription factor targets, such as chromatin remodelers."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CHD4 • HRD • RAD51 • RBBP4 • TP53BP1 • ZMYND8

Targeting the NuRD component, CHD4, impairs Foxp3+ Treg cell production and function and promotes anti-tumor immunity (AACR 2025) - "Thereafter, a DEL screen involving cell target engagement led to discovery of a compound CH41, binding to the CHD4 chromodomain...Importantly, neither WT tumor bearing mice nor their immunodeficient partners developed evidence of autoimmunity under CHD4i therapy, consistent with our previous data that tumor-associated Tregs have distinctive properties rendering them especially susceptible to immunotherapy versus their peripheral counterparts. We conclude that CHD4 targeting has interesting immunologic effects that include preferentially inhibiting Treg vs. conventional T cell responses, leading to significantly increased anti-tumor immunity."

IO biomarker • Liver Cancer • Oncology • Solid Tumor • CD4 • CD8 • CHD4 • FOXP3 • IFNG • IL2