NOVARTIS

Leqvio (inclisiran) monotherapy demonstrated superiority in LDL-C reduction vs placebo and ezetimibe in the Phase III V-MONO study, part of the 60,000-patient VictORION program for ASCVD prevention.

NST-628 is an oral, brain-penetrant pan-RAF–MEK non-degrading molecular glue that prevents paradoxical pathway activation, differentiating it from other RAS/RAF/MAPK pathway inhibitors.

July's Molecules of the Month feature Novartis' molecular glue degrader for sickle cell disease, Pfizer's tinlorafenib for melanoma with brain metastasis, AstraZeneca's AZ-PRMT5i-1 for MTAP-deficient cancers, MTX-531 for dual EGFR/PI3K inhibition, and LifeMine Therapeutics' XC219 discovered via top-down approach. Paxalisib shows promising data in glioblastoma, and Takeda's OX2R-selective agonist offers potential in Alzheimer's disease.

Novartis receives FDA accelerated approval for Fabhalta (iptacopan) to reduce proteinuria in primary IgA nephropathy (IgAN), targeting the alternative complement pathway. Approval based on Phase III APPLAUSE-IgAN study interim analysis showing 44% reduction in proteinuria at 9 months vs. 9% with placebo. Continued approval contingent on eGFR data expected in 2025.

Novartis' HRO761, an oral allosteric WRN helicase inhibitor for MSI-high and dMMR tumors, was discovered through specific HTS assays and optimized for LipE, TPSA, chameleonicity, and non-classical zwitterions. Its X-ray structure and preclinical activity are detailed, differentiating it from Vividion's VVD-214.