Maze Therapeutics (NasdaqGM:MAZE) Conference Transcript

Summary of Maze Therapeutics Conference Call Company Overview - Company: Maze Therapeutics (NasdaqGM:MAZE) - Focus: Development of small molecule precision medicines, primarily targeting kidney diseases, particularly APOL1-mediated kidney disease [4][11] Key Highlights from the American Society of Nephrology (ASN) Conference - Abstracts: Maze Therapeutics had seven abstracts accepted at ASN, showcasing significant research contributions [4] - Genotyping Study: - Previous literature indicated that approximately 13% of the general population has pathogenic variants causing APOL1 kidney disease - Maze's study found about 18% prevalence in enriched kidney disease patients, indicating a higher incidence due to the specific population studied [5][6] - Approximately 1 million individuals in the U.S. have these variants, with at least 250,000 potentially benefiting from therapy [5] - Breakdown: 40% of affected individuals have diabetes, while 60% do not [6] - Disease Progression: - The progression of APOL1-mediated kidney disease occurs at similar rates in patients with and without diabetes [6][7] - A protective variant, N264K, was identified, showing protective effects regardless of diabetes status [7][19] Mechanistic Insights - Pathogenic Mechanism: APOL1 variants lead to nephrotoxicity through aberrant pore channel function in podocytes [9][10] - Therapeutic Approach: Maze's dual mechanism APOL1 inhibitor aims to block the pore and disrupt its assembly, showing significant potency advantages in preclinical models [11][12] Clinical Development Plans - Maze 829 Program: - Aiming for clinical proof of concept (POC) in broad APOL1-mediated kidney disease by Q1 2026, targeting a minimum 30% reduction in proteinuria [12][13] - The 30% threshold is based on historical data correlating with clinical significance and regulatory guidelines [21][23] - Patient Cohorts: Expecting data from both diabetes and non-diabetes cohorts, with a focus on demonstrating POC in a broader patient population [14][15] Market Potential - Patient Population: The broader AMKD landscape includes approximately 250,000 patients, significantly larger than the FSGS population [31][32] - Comparative Advantage: Maze aims to differentiate its therapy from existing treatments like inaxaplin by demonstrating superior efficacy and safety profiles [34][44] Additional Insights on SLC6A19 (782) Program - PKU Treatment: The therapy targets severe classical PKU, aiming to reduce plasma phenylalanine levels significantly, with a goal of improving patient outcomes [39][40] - CKD Insights: The program has shown promise in improving kidney health, with genetic associations and in vivo proof of concept supporting its efficacy [41][42] Conclusion - Maze Therapeutics is positioned to potentially lead in the treatment of APOL1-mediated kidney disease with its innovative therapeutic approaches and significant market opportunity, while also exploring promising avenues in PKU and CKD treatments [44][46]