Maze Therapeutics Announces New Clinical Data Supporting MZE001 as a Potential Treatment for Pompe Disease

Maze Therapeutics, a company translating genetic insights into new precision medicines, today announced new data from an exploratory muscle biopsy cohort of its Phase 1 clinical trial of MZE001 in healthy volunteers to evaluate the effects of MZE001 on glycogen synthesis in Pompe Disease patients. The data are being presented today, March 22, 2023, from 3:00-3:15 p.m. CT, during a late-breaking clinical session at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Dallas.

The buildup of glycogen in skeletal, respiratory and cardiac muscle tissues is the primary driver of disease progression in patients with Pompe disease. Enzyme replacement therapy has been partially effective at clearing toxic glycogen accumulation in these tissues. MZE001, a selective inhibitor of glycogen synthase 1 in muscle, is being developed to address this therapeutic gap. Maze has developed a novel biomarker, peripheral blood mononuclear cell (PBMC) glycogen, as a surrogate for glycogen in skeletal muscle.

In the exploratory muscle biopsy cohort, Maze evaluated glycogen synthesis and total glycogen levels in four healthy volunteers following oral administration of twice-daily MZE001 480mg compared to placebo (n=4). Administration of MZE001 led to an approximately 60% reduction in muscle glycogen synthesis and an approximately 50% reduction in total muscle glycogen following ten days of treatment. These data correlated to an approximately 50% reduction in PBMC glycogen at the same dose. Further, there was no impact on blood glucose or insulin levels following twice-daily administration of MZE001 480mg in this cohort, consistent with previously reported Phase 1 data supporting the tolerability of MZE001 with respect to glucose homeostasis.

“We are very excited to see the results from this biopsy evaluation of MZE001 in healthy volunteers, which showed that reduction in muscle glycogen in healthy adults was similar to PBMC glycogen. These findings are a further proof of mechanism for MZE001 and suggest PBMC could be a useful biomarker for response to substrate reduction therapy in patients with Pompe disease, providing further confidence in MZE001’s potential as the first oral treatment for this life-threatening disease,” said Harold Bernstein, president, research and development and chief medical officer of Maze Therapeutics. “These data build on the positive results from our Phase 1 study presented earlier this year, demonstrating good tolerability and MZE001’s ability to inhibit GYS1, the enzyme that controls glycogen production. We look forward to advancing this program and beginning our Phase 2 trial later this year.”