STING agonist / 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

Inter-organelle cross-talk supports acetyl-coenzyme A homeostasis and lipogenesis under metabolic stress. (PubMed, Sci Adv) - "Knockout of both ACLY and ACSS2 (DKO) severely stunted but did not entirely block proliferation, suggesting that alternate pathways can support acetyl-CoA homeostasis. Metabolic tracing and PEX5 knockout studies link peroxisomal oxidation of exogenous lipids as a major source of acetyl-CoA for lipogenesis and histone acetylation in cells lacking ACLY, highlighting a role for inter-organelle cross-talk in supporting cell survival in response to nutrient fluctuations."

Journal • ACSS2