Maze Therapeutics Doses First Patient in Phase 2 HORIZON Clinical Trial Evaluating MZE829 as a Potential Treatment for APOL1 Kidney Disease
Maze Therapeutics (NASDAQ: MAZE) has initiated patient dosing in its Phase 2 HORIZON clinical trial, evaluating MZE829, an oral APOL1 inhibitor for APOL1 kidney disease (AKD). The trial targets a condition affecting over one million patients in the United States.
The HORIZON Study employs an open-label basket design, enrolling AKD patients with two high-risk APOL1 alleles (G1, G2), stratified by clinical phenotype and proteinuria levels. The study includes patients with severe disease, nephrotic range proteinuria, FSGS, hypertensive nephropathy, and diabetic kidney disease, marking the first trial of a small molecule APOL1 inhibitor in diabetic AKD patients.
The primary endpoint focuses on reducing proteinuria, measured by a 30% or greater reduction in urinary albumin-to-creatinine ratio (uACR) at week 12. Maze anticipates an interim data readout in Q1 2026.
Maze Therapeutics (NASDAQ: MAZE) ha avviato la somministrazione ai pazienti nel suo studio clinico di Fase 2 HORIZON, che valuta MZE829, un inibitore orale di APOL1 per la malattia renale APOL1 (AKD). Lo studio si rivolge a una condizione che colpisce oltre un milione di pazienti negli Stati Uniti.
Lo Studio HORIZON adotta un design a coorti aperte, arruolando pazienti con AKD che presentano due alleli APOL1 ad alto rischio (G1, G2), stratificati per fenotipo clinico e livelli di proteinuria. Lo studio include pazienti con malattia severa, proteinuria nell'intervallo nefrosico, FSGS, nefropatia ipertensiva e malattia renale diabetica, segnando il primo trial di un inibitore APOL1 a piccole molecole in pazienti diabetici con AKD.
Il principale obiettivo finale si concentra sulla riduzione della proteinuria, misurata da una riduzione del 30% o più del rapporto albumina-creatinina urinaria (uACR) alla settimana 12. Maze prevede una lettura intermedia dei dati nel primo trimestre del 2026.
Maze Therapeutics (NASDAQ: MAZE) ha iniciado la dosificación de pacientes en su ensayo clínico de Fase 2 HORIZON, que evalúa MZE829, un inhibidor oral de APOL1 para la enfermedad renal APOL1 (AKD). El ensayo tiene como objetivo una condición que afecta a más de un millón de pacientes en los Estados Unidos.
El Estudio HORIZON emplea un diseño de canasta abierto, inscribiendo a pacientes con AKD que presentan dos alelos APOL1 de alto riesgo (G1, G2), estratificados por fenotipo clínico y niveles de proteinuria. El estudio incluye pacientes con enfermedad severa, proteinuria en rango nefrótico, FSGS, nefropatía hipertensiva y enfermedad renal diabética, marcando el primer ensayo de un inhibidor de APOL1 de pequeñas moléculas en pacientes diabéticos con AKD.
El objetivo principal se centra en la reducción de la proteinuria, medida por una reducción del 30% o más en la relación de albúmina a creatinina urinaria (uACR) a las 12 semanas. Maze anticipa una lectura de datos intermedios en el primer trimestre de 2026.
메이즈 테라퓨틱스 (NASDAQ: MAZE)는 MZE829의 경구용 APOL1 억제제를 평가하는 2상 HORIZON 임상 시험에서 환자 투약을 시작했습니다. 이 시험은 미국에서 100만 명 이상의 환자에게 영향을 미치는 상태를 목표로 하고 있습니다.
HORIZON 연구는 개방형 바스켓 디자인을 채택하여 두 개의 고위험 APOL1 대립유전자(G1, G2)를 가진 AKD 환자를 모집하며, 이는 임상 표현형과 단백뇨 수준에 따라 층화됩니다. 이 연구는 심각한 질병, 신증후군 단백뇨, FSGS, 고혈압성 신병증 및 당뇨병성 신장 질환을 가진 환자를 포함하여 당뇨병 AKD 환자에서 소분자 APOL1 억제제를 임상 평가하는 첫 번째 시험입니다.
주요 목표는 단백뇨의 감소에 중점을 두며, 이는 12주 차에 소변에서의 알부민-크레아티닌 비율(uACR)이 30% 이상 감소하는 것으로 측정됩니다. 메이즈는 2026년 1분기에 중간 데이터를 발표할 계획입니다.
Maze Therapeutics (NASDAQ: MAZE) a lancé l'administration de patients dans son essai clinique de Phase 2 HORIZON, évaluant MZE829, un inhibiteur oral d'APOL1 pour la maladie rénale APOL1 (AKD). L'essai cible une condition touchant plus d'un million de patients aux États-Unis.
La plus récente étude HORIZON utilise un design en panier ouvert, recrutant des patients AKD présentant deux allèles APOL1 à haut risque (G1, G2), stratifiés par phénotype clinique et niveaux de protéinurie. L'étude comprend des patients présentant une maladie sévère, des protéinuries dans la plage néphrotique, une FSGS, une néphropathie hypertensive et une maladie rénale diabétique, marquant le premier essai d'un inhibiteur de petites molécules d'APOL1 chez des patients diabétiques avec AKD.
Le principal objectif de l'étude est de réduire la protéinurie, mesurée par une réduction de 30% ou plus du ratio albumine/créatinine urinaire (uACR) à la semaine 12. Maze prévoit une première lecture des données au premier trimestre 2026.
Maze Therapeutics (NASDAQ: MAZE) hat die Patientendosierung in seiner Phase-2-HORIZON-Studie initiiert, die MZE829, einen oralen APOL1-Inhibitor für APOL1- Nierenerkrankung (AKD), bewertet. Die Studie richtet sich an eine Erkrankung, die über eine Million Patienten in den Vereinigten Staaten betrifft.
Die HORIZON-Studie verwendet ein offenes Basket-Design und rekrutiert AKD-Patienten mit zwei hochriskanten APOL1-Allel (G1, G2), die nach klinischem Phänotyp und Proteinurie-Niveaus stratifiziert sind. Die Studie umfasst Patienten mit schwerer Erkrankung, nephrotischer Proteinurie, FSGS, hypertoner Nephropathie und diabetischer Nierenerkrankung und markiert die erste Studie eines kleinen Molekül-APOL1-Inhibitors bei diabetischen AKD-Patienten.
Der primäre Endpunkt konzentriert sich auf die Reduzierung von Proteinurie, gemessen an einer Reduktion von 30 % oder mehr im Verhältnis von Urinalbumin zu Kreatinin (uACR) nach 12 Wochen. Maze erwartet eine Zwischenanalyse im ersten Quartal 2026.
- First-in-class small molecule APOL1 inhibitor targeting large market of 1M+ US patients
- Broad patient inclusion criteria, potentially expanding the addressable market
- First trial to include diabetic AKD patients, opening new market opportunities
- Clear timeline with interim data expected in Q1 2026
- Initial proof of concept data not available until Q1 2026
- Open-label trial design may limit data interpretation
- Success depends on meeting 30% uACR reduction threshold
Insights
The initiation of the HORIZON Phase 2 trial for MZE829 represents a significant milestone in the development of targeted therapies for APOL1 kidney disease. The study's innovative design incorporates several strategically important elements that enhance its potential impact:
The trial's basket design, encompassing multiple patient phenotypes, is particularly noteworthy as it could accelerate the path to market by simultaneously evaluating efficacy across different AKD manifestations. This approach is especially valuable for identifying the most responsive patient subgroups, potentially leading to a more focused and efficient Phase 3 program.
Being the first to study diabetic AKD patients with a small molecule APOL1 inhibitor creates a important competitive advantage in a market segment with substantial unmet needs. The inclusion of patients with diabetic kidney disease is particularly strategic, as diabetes is a leading cause of kidney failure, potentially expanding the drug's commercial opportunity significantly.
The selection of proteinuria reduction as the primary endpoint, with a 30% reduction threshold in uACR at 12 weeks, is well-aligned with regulatory precedent and clinically meaningful outcomes. This endpoint could support an accelerated approval pathway if the data is compelling.
The market opportunity is substantial, with over 1 million patients in the US alone affected by AKD. The ongoing observational study to identify patients with APOL1 mutations demonstrates a comprehensive approach to patient identification and market development, critical for commercial success.
The Q1 2026 timeline for interim data positions MAZE competitively in the race to address this significant unmet medical need, potentially capturing first-mover advantage in certain patient populations. The broad patient inclusion criteria could facilitate faster enrollment and generate more representative real-world evidence, potentially supporting broader adoption post-approval.
From a clinical perspective, the HORIZON trial's design reflects sophisticated understanding of AKD pathophysiology and treatment challenges. The focus on APOL1 inhibition through an oral, small molecule approach offers several potential advantages over existing treatments:
The stratification by clinical phenotype and proteinuria levels enables precise evaluation of treatment response across different disease manifestations. This is important as AKD presents heterogeneously and understanding response patterns in different subgroups will be vital for optimal patient selection.
The inclusion of patients with nephrotic range proteinuria, FSGS and hypertensive nephropathy alongside diabetic kidney disease patients creates a comprehensive efficacy profile. This broad approach could reveal important insights about disease modification potential across the spectrum of AKD severity.
The selection of uACR reduction as the primary endpoint is particularly astute. A 30% reduction threshold at 12 weeks represents a clinically meaningful improvement that correlates with better long-term outcomes. This endpoint's sensitivity across different stages of glomerular kidney disease makes it an excellent surrogate marker for treatment efficacy.
SOUTH SAN FRANCISCO, Calif., Feb. 07, 2025 (GLOBE NEWSWIRE) -- Maze Therapeutics, Inc. (Nasdaq: MAZE), a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with renal, cardiovascular, and metabolic diseases, today announced the first patient has been dosed in the company’s Phase 2 clinical trial, the HORIZON Study, of MZE829 in patients with APOL1 kidney disease (AKD). MZE829 is an oral, small molecule APOL1 inhibitor that Maze is advancing as a potential treatment for people living with AKD, a subset of chronic kidney disease estimated to affect over one million patients in the United States alone.
“We are excited to announce the initiation of our HORIZON Study for MZE829, a Phase 2 clinical trial with a novel, potential new medicine that could disrupt current treatment for AKD,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “We have designed HORIZON to include a broad spectrum of patients, reflecting the diverse characteristics of AKD, beyond the narrow criteria of existing studies. By evaluating MZE829 across a wider population and organized by cohorts, we aim to demonstrate proof of concept and refine patient selection for future pivotal trials. With its potential to be a truly disease-modifying therapy, MZE829 represents hope for the many patients living with AKD, addressing a critical unmet need in kidney disease treatment.”
The HORIZON Study is a Phase 2, open-label basket design trial that will enroll AKD patients carrying the two high-risk APOL1 alleles (G1, G2), stratified by clinical phenotype and level of proteinuria, as well as patients who have type 2 diabetes. The trial will enroll patients with a wide array of characteristics of AKD, including patients with more severe disease who have nephrotic range proteinuria, such as those with focal segmental glomerulosclerosis (FSGS), patients with lower levels of proteinuria and hypertensive nephropathy, and patients with proteinuria and diabetic kidney disease. The HORIZON study is the first clinical trial with a small molecule APOL1 inhibitor to study diabetic AKD patients. Maze initiated a multicenter, clinical observational study in August 2024 to identify black and African American individuals who carry the APOL1 G1 and G2 mutations, and to explore kidney disease biomarkers in patients with proteinuric kidney disease.
The primary endpoint of the HORIZON Study is reduction of proteinuria, or elevated protein in the urine, as measured by the percentage of subjects with a
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 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 patients. For more information, please visit mazetx.com, or follow us on LinkedIn and X (formerly Twitter).
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect the current beliefs and expectations of management. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including, without limitation, statements concerning the company’s future plans and prospects, any expectations regarding the safety or efficacy of MZE829 and other candidates under development, the ability of MZE829 to treat APOL1 kidney disease or other indications, and the planned timing of the company’s clinical trials, data results and further development of MZE829 and other therapeutic candidates. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to the company may identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Although the company believes the expectations reflected in such forward-looking statements are reasonable, the company can give no assurance that such expectations will prove to be correct. Readers are cautioned that actual results, levels of activity, safety, performance or events and circumstances could differ materially from those expressed or implied in the company’s forward-looking statements due to a variety of factors, including risks and uncertainties related to the company’s ability to advance MZE829, MZE782 and its other therapeutic candidates, obtain regulatory approval of and ultimately commercialize the company’s therapeutic candidates, the timing and results of preclinical studies and clinical trials, the company’s ability to fund development activities and achieve development goals, its ability to protect its intellectual property, general business and economic conditions, and risks related to the impact on its business of macroeconomic conditions, including inflation, volatile interest rates, instability in the global banking sector, and public health crises. Further information on potential risk factors that could affect the company’s business and its financial results are detailed under the heading “Risk factors” included in the company’s prospectus dated January 30, 2025, filed with the U.S. Securities and Exchange Commission (SEC) on January 31, 2025, and the company’s annual and quarterly reports and other filings filed from time to time with the SEC. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date of this press release and Maze undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.
Contacts:
Jillian Connell, Maze Therapeutics
jconnell@mazetx.com
(650) 850-5080
Media:
Dan Budwick, 1AB
dan@1abmedia.com
1 https://pubmed.ncbi.nlm.nih.gov/30635226/
FAQ
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