Maze Therapeutics, Inc.

MZE829 Well-tolerated with Dose-proportional Pharmacokinetics Supporting Once Daily Dosing Data Support Advancement of MZE829 into Planned Phase 2 Clinical Trial in Patients with AKD Data Presented Today at the American Society of Nephrology Kidney Week 2024 SOUTH SAN FRANCISCO, CA, USA I October 25, 2024 I Maze Therapeutics, a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, today announced positive results from the Phase 1 clinical trial of MZE829 in healthy volunteers. MZE829 is an oral, small molecule inhibitor of APOL1 that Maze is advancing as a potential treatment for people living with APOL1 kidney disease (AKD), a subset of chronic kidney disease estimated to affect over one million patients in the United States alone. APOL1 is a protein encoded by the APOL1 gene in humans. Genetic variants of the gene (G1 and G2) are associated with increased risk for a spectrum of progressive kidney diseases in people of West African ancestry. MZE829 was identified through insights generated from Maze’s proprietary, purpose-built platform, Maze Compass™. The first-in-human Phase 1 randomized, placebo-controlled, single and multiple ascending dose trial was designed to evaluate the safety, pharmacokinetics (PK), food effect, and potential drug interactions of orally administered MZE829 in healthy volunteers and enrolled 111 participants. Results demonstrated that MZE829 was well tolerated at single doses up to 480 mg and multiple doses up to 350 mg, with all treatment-related adverse events reported as mild and no severe or serious adverse events reported. Dose-proportional PK was observed with low variability across doses. The observed half-life of approximately 15 hours supported that MZE829 can be dosed once daily. Evaluation of potential drug interactions demonstrated that MZE829 has the potential to be administered together with standard of care medicines used in patients with AKD, including cyclosporine and tacrolimus. “We are very pleased with the positive outcome of our Phase 1 trial of MZE829, demonstrating its tolerability and establishing the dosing regimen that we plan to take into our Phase 2 trial in patients with AKD,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “Based on its mechanism targeting APOL1, as well as genetics data derived through our Compass platform, we believe that MZE829 has the potential to address a large population of patients with AKD. As such, we intend to enroll patients with a wide array of characteristics into our Phase 2 trial to reflect the full spectrum of AKD patients and determine which patients may benefit from treatment with MZE829.” The company anticipates that the Phase 2 clinical trial will employ an open-label basket design to include a range of clinical phenotypes and moderate to severe forms of disease as determined by level of proteinuria. The Phase 2 trial will include AKD patients carrying two copies of the high-risk APOL1 alleles (G1 and G2) and evaluate efficacy using uACR reduction across a broad AKD population. The company expects to initiate the Phase 2 trial in the first quarter of 2025. About Maze Therapeutics Maze Therapeutics is a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, with a focus on renal, cardiovascular and related metabolic, including obesity. The company is advancing a pipeline using its Compass platform, which provides insights into the genetic variants in disease and links them with the biological pathways that drive disease in specific patient groups. The company’s pipeline is led by two wholly owned lead programs, MZE829 and MZE782, each of which represents a novel precision medicine-based approach for chronic kidney disease. For more information, please visit mazetx.com , or follow us on LinkedIn and X (formerly Twitter). SOURCE: Maze Therapeutics

First-in-Human Data from Phase 1 Trial of MZE829 Support Advancement to Phase 2; Phase 2 Trial Expected to Initiate Early 2025 Preclinical Data for MZE782 Support Recent Phase 1 Trial Initiation in Healthy Volunteers SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, today announced that upcoming presentations at the American Society of Nephrology’s (ASN) Kidney Week, being held October 23-27, 2024, in San Diego, and the American Society of Human Genetics Annual Meeting, being held November 5-9, 2024, in Denver, will highlight the company’s two lead clinical programs to treat kidney disease. Data from the company’s Phase 1 trial of MZE829 for the treatment of APOL1-mediated kidney disease will be presented at ASN Kidney Week 2024, and new preclinical data supporting the potential of its second lead program, MZE782, a potentially first-in-class, oral, small molecule targeting the solute transporter, SLC6A19, will be presented at ASN Kidney Week 2024 as well as at the American Society of Human Genetics Annual Meeting. “We look forward to presenting new, positive data for our two lead programs, MZE829 and MZE782, both of which have the potential to address severely underserved patients living with kidney disease,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “Importantly, the Phase 1 data from our study of MZE829 in healthy volunteers support this program’s advancement into our planned Phase 2 trial in patients, which we expect to initiate in the coming months. In addition, the preclinical data we’ll present from our MZE782 program formed the basis of our investigational new drug application and recently initiated Phase 1 trial in healthy volunteers. We are pleased by the progress we continue to make at Maze and excited to learn more about the potential of these programs, generated through novel insights from our Compass platform, as they progress through the clinic.” Details of the presentations are as follows: American Society of Nephrology Presentation Information Title: A Phase 1 Study in Healthy Adults of the Safety, Tolerability, and Pharmacokinetics of MZE829, an APOL1 Inhibitor for the Treatment of APOL1-Mediated Kidney Disease (AMKD) Date & Time: October 24, 2024, 10 a.m. – 12 p.m. PT Presenter: Susan Limb, M.D., Ph.D. Title: SLC6A19 (BOAT1) allelic series: loss of function is associated with improved kidney function Date & Time: October 24, 2024, 10 a.m. – 12 p.m. PT Presenter: Rob Graham, Ph.D. Title: Genetic ablation of SLC6A19 is protective against renal damage in mouse models of chronic kidney disease Date & Time: October 26, 2024, 10 a.m. – 12 p.m. PT Presenter: Laura Sanman, Ph.D. American Society of Human Genetics Presentation Information Title: Functional characterization of Hartnup’s disease missense variants in SLC6A19 shows loss of function by disparate mechanisms Date & Time: November 6, 2024, 2:30 – 4:30 p.m. MT Presenter: Nathan Sallee, Ph.D. Title: SLC6A19 loss of function is associated with improved kidney function and metabolic reprogramming of kidney cells Date & Time: November 9, 2024, 8:45 a.m. MT Presenter: Sahar Mozzafarri, Ph.D. About Maze Therapeutics Maze Therapeutics is a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, with a focus on renal, cardiovascular and related metabolic diseases, including obesity. The company is advancing a pipeline using its Compass platform, which provides insights into the genetic variants in disease and links them with the biological pathways that drive disease in specific patient groups. The company’s pipeline is led by two wholly owned lead programs, MZE829 and MZE782, each of which represents a novel precision medicine-based approach for chronic kidney disease. For more information, please visit mazetx.com , or follow us on LinkedIn and X (formerly Twitter). Contacts Jillian Connell, Maze Therapeutics jconnell@mazetx.com (650) 850-5080 Media: Dan Budwick, 1AB dan@1abmedia.com

Over the past decade, the medicine Enjaymo has been passed around no less than five times by developers large and small. Now its trading hands again, through a deal announced Friday.Sanofi is selling global rights to Enjaymo to the Italy-based drugmaker Recordati, in exchange for an upfront payment of $825 million. And if the medicine hits certain sales goals, Sanofi could take home up to $250 million more.For Recordati, which specializes in rare diseases, the deal adds a ninth marketed product to the companys portfolio. Enjaymo is approved in the U.S., Europe and Japan as a treatment for an uncommon type of anemia. In this condition, known as cold agglutinin disease or CAD, the bodys immune system mistakenly attacks and destroys some red blood cells. Enjaymo is designed to tamp down that immune response and spare the cells, thereby decreasing the need for red blood cell transfusions.Enjaymo won U.S. approval in early 2022 after a winding journey. In 2014, the medicine was in development at San Francisco-based iPerian. But that year, Bristol Myers Squibb bought the company for its work in neurodegenerative diseases. iPerians programs targeting the immune system were spun out into a new biotechnology firm, True North Therapeutics.True North wasnt around for very long, though. By 2017, it had been snapped up by Biogens hemophilia-focused spin off Bioverativ. John Cox, the then-CEO of Bioverativ, said at the time that Enjaymo was a central asset in the deal and filled an important gap in the companys research efforts.Enjaymo, however, would move to yet another owner in 2018, when Sanofi bought Bioverativ for $11 billion.Sanofi has turned to dealmaking several times since to further build out its rare disease business. Over the past year alone, the French pharmaceutical giant nabbed rights to an experimental drug for muscular dystrophy and spent $2.2 billion to acquire a biotech and its potential treatment for a rare lung disease.Sanofi also tried to license a drug for Pompe disease from the startup Maze Therapeutics, but gave up on that deal after facing a lawsuit from the Federal Trade Commission.From the Bioverativ acquisition, Sanofi got Enjaymo as well as another now-marketed hemophilia medicine, Altuviiio. According to Recordati, Enjaymo generated around 100 million euros, or roughly $108 million, over the 12-month period between September 2023 and August 2024. The company also expects revenue from the drug to exceed 150 million euros in the 2025 fiscal year, and reach peak annual sales of 250 million to 300 million euros.In a statement, Recordatis CEO Rob Koremans said the Enjaymo deal aligns with his companys broader strategy, complements its portfolio of cancer therapies, and expands its footprint in the U.S., Japan and Europe.Recordati says it will use its existing cash as well as new committed bank debt facilities to finance the deal, which is slated to close by the end of the year. '