Maze Therapeutics

our programs

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.

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's pipeline

MZE829 Program for APOL1 Kidney Disease: A common disease with a disproportionate impact on the Black Community

APOL1 Kidney Disease

APOL1 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. alone. All people have two copies of the APOL1 (apolipoprotein L1) gene.

Some individuals of Western or Central African ancestry have genetic mutations in one or both copies of their APOL1 genes (known as the G1 and G2 risk variants) that help protect against trypanosomiasis, a parasitic infection endemic in sub-Saharan Africa also known as African sleeping sickness. Without treatment, African sleeping sickness is frequently fatal.

While this genetic variant protects against a fatal parasitic infection, the long term consequences are that it creates an elevated risk of developing kidney disease and progressing to end stage kidney disease later in life.

Addressing APOL1 Kidney Disease with MZE829

We are developing a potential oral medicine to help protect the kidneys from APOL1 kidney disease by blocking the function of the alternate APOL1 proteins produced from the variant APOL1 genes. While the genetic link between APOL1 and kidney disease has been known for over a decade, the mechanism by which it causes kidney disease was not known.

Maze scientists analyzed a new APOL1 genetic variant, now known as N264K, that protects people with the G1 and G2 risk variants, and revealed the details of how APOL1 may cause kidney disease through a series of genetic and biological experiments. Through our research, we have established a better understanding APOL1’s role in kidney disease and how we might intervene with a new product candidate, MZE829, specifically designed to copy the effects of the N264K protective variant.

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translating data to therapeutics

Our inherited genetic makeup shapes who we are, and it also contributes to the risk of disease throughout our lifetimes. Some genetic variants can increase the risk of certain diseases, while others may provide protection from disease.

The availability of longitudinal genetic and clinical data across millions of individuals around the globe, as well as new technology, cellular engineering and computational tools, have made it practical to identify variations in genes associated with disease, and study how those variations may alter the course of a disease. If we can understand how specific genetic variants protect against a disease, we may be able to mimic those effects and address the specific drivers of that disease, thereby changing outcomes for patients.

Compass™, our end-to-end platform, was purpose-built to capitalize on these advancements in an expedited fashion and is intended to produce a steady stream of targeted medicines for patients. Variant functionalization—looking not just at genetic variation but at the way that genetic variants impact proteins and disease course—is a critical piece of our process that in our view has not yet been fully harnessed in the fields of drug discovery and development. We believe that identifying the right variant in a sea of genetic information, mimicking its beneficial effects, and using these insights to identify those patients most likely to benefit, will translate into life-changing therapies for patients.

publications

published data and literature for Maze’s platform technology

maze programs

OCTOBER 2023 | MAZE THERAPEUTICS Million Veteran Program and Vanderbilt University Medical Center

Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease
Journal of the American Society of Nephrology | Hung et al.

MARCH 2023 | MAZE THERAPEUTICS

Muscle glycogen reduction in healthy adults treated with MZE001, an oral inhibitor of GYS1 and potential substrate reduction therapy for Pompe Disease
Muscular Dystrophy Association (MDA) Clinical and Scientific Conference | Ullman, et al.

FEBRUARY 2023 | MAZE THERAPEUTICS

Results from a first in human study of MZE001, an orally bioavailable inhibitor of glycogen synthase 1 and potential substrate reduction therapy for Pompe Disease
WORLDSymposium 2023 | Ullman.

FEBRUARY 2023 | MAZE THERAPEUTICS

Small molecule inhibition of glycogen synthase I restores autophagolysosomal and metabolic pathway dysfunction in a mouse model of Pompe Disease
WORLDSymposium 2023 | Xi.

FEBRUARY 2023 | MAZE THERAPEUTICS

Results from a first in human study of MZE001, an orally bioavailable inhibitor of glycogen synthase 1 and potential substrate reduction therapy for Pompe Disease
WORLDSymposium 2023 | Ullman et al.

FEBRUARY 2023 | MAZE THERAPEUTICS

Quantification of peripheral blood mononuclear cell (PBMC) glycogen as a novel biomarker for therapeutic intervention in Pompe Disease
WORLDSymposium 2023 | Satterfield et al.

FEBRUARY 2023 | MAZE THERAPEUTICS

Small molecule inhibition of glycogen synthase I restores autophagolysosomal and metabolic pathway dysfunction in a mouse model of Pompe disease
WORLDSymposium 2023 | Xi et al.

NOVEMBER 2022 | MAZE THERAPEUTICS

Genetic Inhibition of APOL1 Pore Forming Function Prevents APOL1 Kidney Disease
American Society of Nephrology’s 2022 Kidney Week | Hung et al.

NOVEMBER 2022 | MAZE THERAPEUTICS

MZ-301 Is a Small Molecule Inhibitor of APOL1 Pore Function That Attenuates Albuminuria in a Mouse Model of APOL1-Mediated Kidney Disease
American Society of Nephrology’s 2022 Kidney Week | Assimon et al.

FEB 2022 | MAZE THERAPEUTICS

Genetic reduction of muscle glycogen is well tolerated in UK biobank participants
WORLDSymposium 2022 | Homburger et al.

FEB 2022 | MAZE THERAPEUTICS

Pharmacology of small molecule inhibitors of GYS1 in canines and mouse model of Pompe Disease
WORLDSymposium 2022 | Xi et al.

JUNE 2021 | EXTERNAL EXPERTS

APOL1 at 10 years: progress and next steps
Kidney international | Freedman, Barry I., et al.

DECEMBER 2013 | EXTERNAL EXPERTS

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

human genetics

APR 2021 | INTERNAL EXPERT

Identifying therapeutic drug targets using bidirectional effect genes
Nature Communications | Estrada et al.

JAN 2020| MAZE FOUNDER

A brief history of human disease genetics
PLOS Genetics | Claussnitzer et al

DEC 2019 | EXTERNAL EXPERTS

Are drug targets with genetic support twice as likely to be approved
PLOS Genetics | King et al.

JUL 2019 | EXTERNAL EXPERTS

Priority index for human genetics and drug discovery
Nature Genetics | Plenge et al.

AUG 2016 | MAZE FOUNDER

Leveraging human genetics to guide drug target discovery
Trends in Cardiovascular Medicine | Stitziel et al.

functional genomics

FEB 2022 | NATURE

TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A
nature | Ma, X.R., Prudencio, M., Koike, Y. et al.

SEPT 2021 | EXTERNAL EXPERTS

From variant to function in human disease genetics
Science | Lappalainen, Tuuli, and Daniel G. MacArthur

OCT 2020 | MAZE THERAPEUTICS

A framework to integrate genome-wide CRISPR functional genomics screens with human
genetics to nominate novel therapeutic targets in ALS

American Society of Human Genetics 2020 Virtual Meeting | Cummings et al.

AUG 2018 | MAZE FOUNDER

Mapping the genetic landscape of human cells
Cell Press | Horlbeck et al.

JULY 2013 | EXTERNAL EXPERTS

Validating therapeutic targets through human genetics
Nature | Robert M. Plenge, Edward M. Scolnick, David Altshuler

want to know more?

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

Do you share our desire to transform the lives of patients by harnessing the power of genetics?

We’d love to hear from you: info@mazetx.com.