Maze Therapeutics Presents New Preclinical Data Supporting Advancement of MZE001 as a Potential Treatment for Pompe Disease
Tags:
Preclinical
Phase 1
Findings Highlight Potential of Oral Substrate Reduction Therapy to Lower Disease-Causing Glycogen Build-up as a Treatment for Pompe Disease
Data Support Advancement of MZE001 into Phase 1 Clinical Trial Expected to Start in First Half of 2022
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a company translating genetic insights into new precision medicines, today announced new preclinical data supporting the advancement of MZE001, which aims to address Pompe disease by reducing pathologic glycogen accumulation through the inhibition of muscle glycogen synthase (GYS1). Data are being presented during two oral presentations and two poster sessions at the 18th Annual WORLD Symposium being held February 7-11, 2022.
Pompe disease is a rare, inherited disorder caused by mutations in the gene coding for acid alpha-glucosidase (GAA), an enzyme responsible for degrading lysosomal glycogen into glucose monomers. These mutations lead to the buildup of lysosomal glycogen, primarily in skeletal muscle, respiratory muscle and cardiac muscle tissues, leading to progressive weakness and respiratory compromise.
In several in vitro and in vivo analyses with GYS1 inhibitors presented and highlighted below, data demonstrated potent inhibition of GYS1, leading to reduced accumulation of glycogen through a substrate reduction approach. Importantly, GYS1 inhibition was generally well tolerated with no on-target or off-target toxicity observed.
“Pompe disease affects both people who are living with the disease, as well as their caregivers. Whilst enzyme replacement therapy has been lifesaving, disease progression, including skeletal muscle and respiratory muscle weakness still occurs in some patients,” said Priya Sunil Kishnani, M.D., Duke Department of Pediatrics, Duke University Medical School. “I am encouraged by the preclinical data from Maze’s program targeting glycogen synthesis, which could potentially offer a new and complementary treatment option for these patients.”
“These data are the first to be presented from a program that has emerged from our proprietary Compass platform, providing validation for our approach focused on translating genetic insights from disease-associated pathways to design and develop novel therapeutics,” said Sarah Noonberg, M.D., Ph.D., chief medical officer of Maze. “This work demonstrates the potential value of our substrate reduction approach across the Pompe disease spectrum both as combination therapy and as monotherapy. We are excited to continue our efforts with this program as we advance MZE001 toward the clinic.”
Taken together, the preclinical data support the potential for a GYS1 inhibitor, such as MZE001, as a treatment for Pompe disease. Based on these findings, Maze is advancing MZE001 toward clinical development, with plans to initiate a Phase 1 clinical trial in healthy volunteers in the first half of 2022.
Detailed findings from each of the presentations are as follows:
Title: In vitro characterization of MZE001, an orally active GYS1 inhibitor to treat Pompe disease
Data Summary: In in vitro assays, treatment with MZE001 demonstrated:
Title: Substrate reduction therapy for Pompe disease: small molecule inhibition of glycogen synthase 1 in preclinical models
Data Summary: In in vivo models, treatment with GYS1 inhibitors demonstrated:
Title: #327. Pharmacology of small molecule inhibitors of GYS1 in canines and a mouse model of Pompe disease
Data Summary: In in vivo mouse and canine models, inhibition of GYS1 demonstrated:
Title: #122. Genetic reduction of muscle glycogen is well tolerated in UK Biobank participants
Data Summary: Analyses of individuals in the UK Biobank with reduced muscle glycogen levels due to variants in PPP1R3A, a regulator of glycogen metabolism, showed:
About Maze Therapeutics
Maze Therapeutics is a biopharmaceutical company applying advanced data science methods in tandem with a robust suite of research and development capabilities to advance a pipeline of novel precision medicines for patients with genetically defined diseases. Maze has developed the Maze CompassTM platform, a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. Using Compass, Maze is building a broad portfolio of wholly owned and partnered programs. Maze is based in South San Francisco. For more information, please visit mazetx.com, or follow us on LinkedIn and Twitter.
Contacts
Jillian Connell, Maze Therapeutics jconnell@mazetx.com 650.850.5080
Media: Katie Engleman, 1AB katie@1abmedia.com
Jillian Connell, Maze Therapeutics jconnell@mazetx.com 650.850.5080
Media: Katie Engleman, 1AB katie@1abmedia.com
