Maze Therapeutics

discovery pipeline

Maze stands at the forefront of an emerging effort to harness the power inherent in the relationship between genes, the protein products encoded by those genes, and specific, observable human traits, and to translate these insights into innovative therapeutics.

Using our Compass platform, we are advancing the development of multiple new therapeutic candidates that have the potential to serve as precision medicines for rare diseases and mechanistically defined subsets of common diseases. We have rapidly established a robust pipeline of novel drug candidates, as summarized in the chart below.

GYS1: our therapeutic target for Pompe disease

Pompe disease is a rare, inherited autosomal recessive disorder that affects approximately 5,000 to 10,000 patients worldwide. It is caused by mutations in the gene coding for an enzyme responsible for breaking down lysosomal glycogen into glucose. Infantile-onset forms of the disease involve rapid progression of cardiac failure and death within one to two years without treatment. Late-onset forms of the disease involve the slow progressive weakness of skeletal muscle eventually leading to respiratory insufficiency, wheelchair dependency and a shortened lifespan.

We believe a novel approach to treating Pompe disease is halting skeletal and respiratory muscle glycogen synthesis and its subsequent accumulation by inhibiting the action of the gene GYS1 through substrate reduction therapy, or SRT.

High levels of accumulated glycogen are toxic to muscle and our GYS1 inhibitor has been shown to reverses that accumulation in preclinical models

While GYS1 has long been a therapeutic target of interest, its attractiveness as a therapeutic target has been limited due to its structural complexity and uncertainties related to the tolerability of a long-term reduction in muscle glycogen levels. Critical insights, in large part derived from Compass, have enabled us to overcome these challenges. We are rapidly progressing our lead series towards an IND.

key GYS1 publications


Restoration of muscle functionality by genetic suppression of glycogen synthesis in a murine model of Pompe disease
Human Molecular Genetics | Douillard-Guilloux et al.

APOL1: our therapeutic target for chronic kidney disease

Chronic kidney disease, or CKD, affects approximately 37 million people in the United States including more than 700,000 patients who suffer from end-stage renal disease (ESRD). It is estimated that 10-15% of African Americans carry two copies of the APOL1 risk variants translating to about 4 to 6 million individuals. These individuals are at significantly increased risk of developing CKD, and once diagnosed their rate of progression to ESRD is significantly increased. There are currently no approved therapies that address the underlying causes of APOL1-mediated kidney diseases and efficacious treatment options for high-risk APOL1 individuals with CKD represent a significant unmet medical need.

Despite a strong association between APOL1 renal-risk variants and kidney disease, the mechanism by which the APOL1 variants cause kidney damage is not well-understood. We are utilizing the Compass platform to determine the mechanism of action as well as identify and optimize small molecules that block the activity of APOL1.

key APOL1 publications


A brief history of APOL1: a gene evolving
Seminars in Nephrology | Friedman et al.


Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice
Nature Medicine | Beckermann et al.


APOL1 kidney disease risk variants – an evolving landscape
Seminars in Nephrology | Dummer et al.


APOL1 kidney risk alleles population genetics and disease associations
Advanced Chronic Kidney Disease | Limou et al.


APOL1 risk variants, race, and progression of chronic kidney disease
New England Journal of Medicine | Parsa et al.

ATXN2: our therapeutic target for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis, or ALS, is a progressive and fatal neurodegenerative disease that occurs in approximately 16,000 Americans each year. Gradual onset of muscle weakness is the most common initial symptom, leading to difficulties in speaking, swallowing, and breathing. Death, typically from neuromuscular respiratory failure, generally occurs within 2 to 5 years after the appearance of initial symptoms, however, a small number of ALS patients live well beyond the three to five-year life expectancy. Current available treatments for ALS are limited and are mainly focused on providing symptomatic management and have limited impact on disease progression.

One of Maze’s founders, Aaron Gitler, identified a potent genetic modifier whose inhibition has been shown to limit the toxicity of a certain protein, TDP-43, that is involved in pathologic aggregates seen in up to 97% of all ALS cases. We are currently translating these important insights by developing a microRNA gene therapy that targets ATXN2. We have used the proprietary application of our functional genomics tools to optimize its potency and have demonstrated that knockdown of ATXN2 prolongs survival in preclinical models of ALS.

key ATXN2 publications


Taking a risk: a therapeutic focus on ataxin-2 in amyotrophic lateral sclerosis
Trends in Molecular Medicine | Van den Heuvel et al.

other discovery initiatives

We are also developing a broad and deep research pipeline by applying the Compass platform to identify novel drug targets across multiple therapeutic areas and modalities. One approach we are taking is to identify genetic modifiers that can suppress the toxicity associated with certain drivers of disease. In addition, we are exploring applications of Compass in diseases of haploinsufficiency, where modifiers that increase the levels of a target protein may be developed into therapeutics.


To date we have two established joint ventures to advance precision medicine discovery efforts informed by Compass. Our Contour Therapeutics LLC joint venture is with BridgeBio Pharma LLC and addresses cardiovascular indications. Our Broadwing Bio LLC joint venture is with Alloy Therapeutics, Inc. and addresses ophthalmic diseases.

Bridge Bio Alloy Therapeutics

reach out

We believe that collaborating with exceptional people, academic institutions and industry leaders will be paramount to delivering on our mission of bringing precision medicines to patients.

Do you share our desire to fight disease by harnessing the power of genetics?

We’d love to hear from you: