Summary of Maze Therapeutics Conference Call Company Overview - **Company**: Maze Therapeutics (NasdaqGM: MAZE) - **Focus**: Development of precision medicines for kidney and metabolic diseases, leveraging human genetics Key Points from the Call Clinical Development Updates - **MZE-782**: Phase I study completed in healthy volunteers, with Phase II trials expected to start in 2026 for both PKU (Phenylketonuria) and CKD (Chronic Kidney Disease) [2][21] - **MZE-829**: Ongoing Phase II trial for APOL1-mediated kidney disease, with initial top-line data expected in Q1 2026 [2] - **Licensing Agreement**: MZE-001 for Pompe disease licensed to Shionogi & Co. in May 2024 for $150 million upfront, with potential milestone payments and royalties [3] Clinical Data Highlights - **Safety Profile**: MZE-782 demonstrated an excellent safety profile with no serious adverse events reported [10][21] - **Pharmacokinetics (PK)**: Linear and consistent exposure observed across single and multiple ascending dose cohorts, with a half-life of approximately 11 hours [12][20] - **Pharmacodynamics (PD)**: Significant increases in urinary phenylalanine (up to 42-fold) and glutamine (up to 68-fold) excretion observed, indicating effective target engagement [9][15][20] Mechanism of Action - **SLC6A19 Inhibition**: MZE-782 inhibits SLC6A19, a transporter involved in amino acid absorption, which is validated by human genetics and previous clinical data [4][16] - **Kidney Function**: Initial eGFR dip observed, consistent with hemodynamic effects seen with SGLT2 inhibitors, suggesting potential long-term kidney benefits [19][23] Future Plans - **Phase II Trials**: - **PKU**: Focus on plasma phenylalanine reduction as the primary endpoint [22] - **CKD**: Targeting proteinuria reduction as the primary endpoint [22] - **Regulatory Engagement**: Plans to finalize trial designs and seek regulatory input before initiating Phase II studies [22][23] Market Opportunity - **PKU**: Over 60% of patients remain inadequately controlled despite newborn screening, indicating a significant unmet need [5] - **CKD**: Targeting patients who do not adequately respond to current therapies, including SGLT2 inhibitors [6][22] Additional Insights - **Combination Therapy Potential**: Exploration of MZE-782 in combination with existing therapies for enhanced efficacy in PKU patients [80] - **Patient Stratification**: Consideration of demographic needs and dosing flexibility in future development efforts [53] Conclusion Maze Therapeutics is positioned to advance MZE-782 into Phase II trials for both PKU and CKD, with promising early clinical data supporting its safety and efficacy. The company aims to address significant unmet needs in these patient populations, leveraging its genetic insights and innovative drug development approach [87][88]