Oral Therapy MZE001 Well-tolerated in Healthy Volunteers in Trial

Maze planning Phase 2 study of substrate reduction therapy in 2023

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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MZE001, an experimental oral substrate reduction treatment for Pompe disease, was well-tolerated in both single and multiple doses in a study conducted in healthy volunteers, according to Maze Therapeutics, the therapy’s developer.

Based on the trial’s findings, Maze is planning to launch a new study in 2023 to test MZE001 in people with Pompe disease.

“We look forward to carrying this program forward into a Phase 2 clinical trial in patients with Pompe disease who need improved treatment options for their disease,” Harold Bernstein, MD, PhD, president of research and development, and chief medical officer of Maze, said in a company press release.

Bernstein noted the treatment could prove to be a first oral therapy for Pompe disease patients.

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Pompe disease is caused by mutations that disrupt the function of the enzyme acid alpha-glucosidase, known as GAA, which is needed to break down a large sugar molecule called glycogen.

As a consequence of GAA dysfunction, glycogen builds up to toxic levels inside cells, with muscle cells — which normally store glycogen as an energy source — most heavily affected.

MZE001 is designed to function as a substrate reduction therapy, decreasing levels of glycogen inside muscle cells by blocking the activity of glycogen synthase (GYS1), the enzyme chiefly responsible for producing glycogen in muscle cells.

The therapy, which this year was granted orphan drug designation by the U.S. Food and Drug Administration (FDA), had shown promising GYS1-inhibiting effects in preclinical studies.

“We’ve designed MZE001 to inhibit GYS1 and reduce skeletal and respiratory muscle glycogen synthesis and its subsequent accumulation in patients with Pompe disease,” Bernstein said, adding, “Accumulation in these important muscle groups has proven particularly resistant to treatment with intravenous enzyme replacement therapy, the current standard of care.”

The Phase 1 trial (NCT05249621) enrolled 112 healthy adults, who were administered single or multiple doses of MZE001, or a placebo, and assessed for safety and pharmacological outcomes.

Safety results showed that the therapy was generally well-tolerated, and pharmacological data support twice-daily dosing, according to Maze.

The company did not provide further details on these endpoints, noting that full results will be presented at the annual WORLD Symposium meeting in February 2023.

“These topline results give us confidence that GYS1 may be safely inhibited, supporting MZE001’s advancement as the potential first oral therapy, alone or in combination with enzyme replacement, to treat Pompe disease and possibly other glycogen storage disorders,” Bernstein said.