Maze Therapeutics

advancing R&D in common disease

Utilizing Maze Compass™, Maze is harnessing the power of human genetics to transform the lives of patients. We are building a broad portfolio of wholly owned and partnered programs, with a focus on genetically informed therapies for common diseases such as chronic kidney disease.

Maze APOL1 Program

APOL1-Mediated Kidney Disease

APOL1-mediated kidney disease is a life threatening, genetically driven condition that is estimated to impact close to one million people of West African ancestry in the U.S. alone1.

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1. 2017-2020 NHANES; Grams et al. (2016) JASN 27:2842-50; Friedman et al. (2011) JASN 22:2098-105; Nadkarni et al. (2018) NEJM 379:2571-2

Maze Precision Renal Program

Chronic Kidney Disease

Chronic kidney disease impacts approximately 37 million, or 1 in 7 individuals in the U.S. alone2. Current treatments for chronic kidney disease do not address the underlying cause and instead focus on slowing the progression.

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2. Source: https://www.cdc.gov/kidneydisease/publications-resources/ckd-national-facts.html

Maze Pipeline

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MZE829 – a genetically-informed approach to APOL1-mediated kidney disease (AMKD)

APOL1-mediated kidney disease (AMKD) is a genetic kidney disease associated with 2 high risk variants of the APOL1 gene that lead to injury of the kidney and interfere with its ability to filter harmful substances from the blood. People who have two copies of these high risk gene variants have an increased risk of kidney disease. AMKD can have various clinical presentations, including focal segmental glomerulosclerosis, hypertension-associated kidney disease, HIV-associated nephropathy and lupus nephritis. Emerging information also suggests that AMKD may be responsible for increasing the likelihood of progressing to end-stage kidney disease in individuals with diabetes.

People of West African ancestry are most likely to carry the high risk variants of APOL1, which originally evolved to protect them from trypanosomiasis, which causes Sleeping Sickness. This includes many people who identify as Black, African American, Afro-Caribbean and Latina/Latino.  In the US alone, 13% of African Americans, or ~6 million people, carry 2 copies of the high risk APOL1 variant gene and are at risk for developing AKD.

While the association of APOL1 with kidney disease has been known for over a decade, we at Maze used our Maze Compass™ platform to uncover a fundamental mechanism by which the high risk APOL1 variants cause kidney disease. We used our access to anonymous genetic and clinical data from over 1.5 million individuals to identify a new APOL1 variant that protects against kidney disease, and designed a therapy, MZE829, that mimics this variant. We have shown in preclinical models of AMKD that MZE829 can stop or reverse important features of kidney disease, specifically breakdown of the kidney’s filtering system and loss of protein in urine.

MZE829 is currently being studied in healthy people, and our plans are to begin studies in patients with AMKD to determine who will benefit from Maze’s precision therapy for this disease.

MZE782 – a precision approach for chronic kidney disease

Maze’s MZE782 program is our second precision kidney disease program, and we plan to disclose the target later in 2024. Chronic kidney disease affects ~37 million people in the US alone, and while there have been some advances in treatment, patients are still waiting for better treatments that arrest or reverse their disease.

We used our Maze Compass™ platform to analyze a large set of genetic and clinical data to identify a previously unrecognized protein that has a big effect on kidney health. Genetic variants of this protein can either increase or protect against the risk of developing kidney disease in people. Maze has seen that mimicking the effects of these protective variants in preclinical models prevents the development of kidney disease. The way these variants behave also suggest that there are specific groups of people with chronic kidney disease that are most likely to benefit from a therapy directed at this specific protein. Based on these encouraging observations, scientists at Maze have designed a therapy, MZE782, that mimics the effects of protective variants.

We plan to start clinical trials with MZE782 in healthy people in the second half of 2024, followed by trials in patients with chronic kidney disease most likely to respond to MZE782.

MZE001 – an oral substrate reduction therapy for Pompe disease

People with Pompe disease have insufficient acid alpha-glucosidase (GAA) – the enzyme that breaks down extra glycogen in the body - because of mutations in the gene that encodes GAA. As a result, glycogen builds up in muscle tissues causing progressive problems with ambulation (walking and other movement), respiration (breathing) and heart function. The current standard of care, enzyme replacement therapy, attempts to add back GAA, but this doesn’t always get to the muscle tissues, and in some patients, loses effectiveness over time. In addition, current enzyme replacement therapies are delivered by intravenous infusion every 2 weeks, a time consuming and life-long treatment that places significant constraints on patient quality of life. Substrate reduction therapy slows down the production of glycogen to restore more normal levels of glycogen in muscle, and has the potential to remove the toxic effects of too much glycogen. While the idea for substrate reduction therapy is not new, and has been used to treat other diseases, Maze scientists have been able to solve 2 problems that have daunted the development of an oral medicine to treat Pompe disease by inhibiting Glycogen Synthase 1 (GYS1), the enzyme responsible for making glycogen in muscle. We used our CompassTM platform to analyze genetic and clinical data from large numbers of anonymous people to demonstrate that it would be safe to reduce glycogen production, and determined the molecular structure of GYS1 to allow the discovery of a potential therapy, MZE001, that would specifically slow down glycogen production in muscle but not other tissues that need glycogen for energy. We have already studied MZE001 in healthy people, and found that at safe doses, MZE001 slows down the production of glycogen specifically in muscle to a level that could restore normal muscle glycogen levels in patients with Pompe disease. The next step in bringing MZE001 closer to patients will be a Phase 2 study in patients with late-onset Pompe disease.