Researchers from Maze Therapeutics Inc. presented the discovery and preclinical characterization of MZ-101 as a potential candidate for the treatment of Pompe disease and other glycogen storage disorders.
Sanofi SA backed out of its $750 million effort to advance Maze Therapeutics Inc.’s oral Pompe disease candidate, MZE-001, after the U.S. FTC filed a federal lawsuit to block the deal, claiming the Paris-based firm was seeking to eliminate a nascent competitor.
It has been previously demonstrated that the two coding variants in the APOL1 gene (G1 and G2) are associated with a greater risk of progressive, proteinuric kidney disease; however, there currently are no therapies to address the causal genetic drivers of this disease. Researchers from Maze Therapeutics Inc. presented the discovery and preclinical characterization of a novel small-molecule inhibitor of APOL1, MZ-302, and they evaluated its efficacy in a new transgenic model of APOL1-mediated kidney disease (AKD).
African Americans are 10 times more likely to develop chronic kidney disease (CKD) than Americans of European descent in part due to inheritance of one of two high-risk (HR) APOL1 variants (G1/G2, not G0) that are only present in people of West African or Caribbean ancestry. By contrast, these two APOL1 HR variants confer a beneficial resistance to otherwise lethal trypanosomiasis, which is caused by a pathogen endemic to West Africa, but still this ultimately results in a 4-fold increased risk for end-stage kidney disease (ESKD).
Maze Therapeutics Inc. has identified apolipoprotein L1 (APOL1) inhibitors reported to be useful for the treatment of chronic kidney disease, focal segmental glomerulosclerosis, diabetic, hypertensive, HIV-associated nephropathy, lupus nephritis, pre-eclampsia and sepsis.
A mid-stage prospect for Pompe disease (PD) – this one from Maze Therapeutics Inc. – caught the eye of Sanofi SA, and the pair signed a potential $750 million deal to move along the oral glycogen synthase (GYS1) inhibitor MZE-001, a substrate reduction therapy.
Maze Therapeutics Inc. recently presented data from preclinical studies of a small-molecule APOL1 pore function inhibitor, MZ-301, describing the compound’s in vitro and in vivo activity. APOL1 G1 and G2 genetic variants are associated with an increased risk of progressive kidney diseases in African ancestry people. There are no APOL1-targeted therapies addressing the underlying driver of these diseases.
Maze Therapeutics has presented glycogen [starch] synthase, muscle (GYS1) inhibitors reported to be useful for the treatment of cancer and Pompe disease.
Maze Therapeutics has patented apolipoprotein L1 (APOL1) inhibitors reported to be useful for the treatment of chronic kidney disease, focal segmental glomerulosclerosis, HIV-associated nephropathy, lupus nephritis and sepsis.
