Core Insights - Maze Therapeutics, Inc. has shared promising clinical results for MZE782, an oral small molecule targeting the solute transporter SLC6A19, which may serve as a best-in-class therapy for phenylketonuria (PKU) and a first-in-class therapy for chronic kidney disease (CKD) [1] Pharmacokinetics (PK) - MZE782 exhibited a favorable plasma pharmacokinetic profile with consistent absorption, a tmax of six hours, and a half-life of 11 hours [2] - Exposure to MZE782 increased proportionally with dose, achieving steady-state by Day 3, indicating potential for once- or twice-daily dosing in Phase 2 trials [2] Neutral Amino Acid Excretion - MZE782 resulted in dose-dependent increases in 24-hour urinary excretion of neutral amino acids Phe and Gln, confirming target engagement and SLC6A19 inhibition [3] Urinary Excretion Results - A 39-fold increase in urinary Phe excretion was observed with a single 960 mg dose, and a 42-fold increase was noted on Day 7 in the 240 mg twice-daily cohort [4] - A 55-fold increase in urinary Gln excretion was recorded with a single 960 mg dose, and a 68-fold increase was observed on Day 7 in the 240 mg twice-daily cohort [4] Estimated Glomerular Filtration Rate (eGFR) - MZE782 demonstrated a dose-dependent initial dip in eGFR over seven days of dosing, comparable to effects seen in patients starting SGLT2 and RAAS inhibitors [5] Next Steps - Maze plans to initiate two Phase 2 proof-of-concept trials for MZE782 in 2026, focusing on plasma Phe reduction in PKU and proteinuria reduction in CKD [6] - MZE782 was well tolerated across all doses, with no serious or treatment-related adverse events leading to discontinuation [6] Financial Update - Maze Therapeutics announced an oversubscribed private placement of approximately $150 million, consisting of 4 million shares at $16.25 per share [7] - Following the announcement, Maze Therapeutics shares rose by 52.15% to $24.37, reaching a new 52-week high [7]

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]

MZE782 Phase 1 Trial Results - MZE782 demonstrated an excellent safety profile with no serious adverse events observed[18] - MZE782 exhibited linear pharmacokinetics (PK) across single doses ranging from 30 mg to 960 mg, with a half-life of approximately 11 hours[18, 32] - The trial showed up to a 42-fold increase in urinary phenylalanine (Phe) excretion and a 68-fold increase in urinary glutamine (Gln) excretion at Day 7[18] - MZE782 induced a dose-dependent initial estimated glomerular filtration rate (eGFR) dip, similar to SGLT2 inhibitors[18] Planned Phase 2 Trials in 2026 - The company plans to initiate Phase 2 trials for both Phenylketonuria (PKU) and Chronic Kidney Disease (CKD) in 2026[18] - The PKU Phase 2 trial aims to demonstrate proof-of-concept (PoC) with plasma Phe reduction as the endpoint[56] - The CKD Phase 2 trial will focus on demonstrating PoC with proteinuria reduction as the primary endpoint[56] MZE782 Therapeutic Potential - MZE782 aims to deliver potential best-in-class plasma phenylalanine (Phe) reduction with a good safety profile for PKU patients[17] - MZE782 could be a new mechanism of action (MoA) to address CKD patients with inadequate response to current therapies, including SGLT2 inhibitors[56] Company Financial Position - The company has a strong cash position with an expected runway into 2028[12]

Core Viewpoint - Maze Therapeutics has successfully entered into an oversubscribed private placement agreement, raising approximately $150 million to advance its clinical programs and research initiatives [1][4]. Group 1: Private Placement Details - The private placement consists of 4,000,002 shares of common stock priced at $16.25 per share, along with 5,231,090 pre-funded warrants priced at $16.249 each [3]. - The transaction is expected to close on September 12, 2025, pending customary closing conditions [4]. - The placement has attracted both new and existing investors, including notable firms such as Frazier Life Sciences and Janus Henderson Investors [2]. Group 2: Use of Proceeds - Proceeds from the private placement will be utilized to further the development of MZE829 for APOL1-mediated kidney disease, initiate Phase 2 trials for MZE782 targeting phenylketonuria and chronic kidney disease, and support ongoing research and development efforts [4]. - Additional funds will be allocated for working capital and general corporate purposes [4]. Group 3: Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for kidney and metabolic diseases [8]. - The company's lead candidates include MZE829, an APOL1 inhibitor in Phase 2 development, and MZE782, a SLC6A19 inhibitor also advancing to Phase 2 [8].

Core Insights - Maze Therapeutics announced positive Phase 1 clinical results for MZE782, indicating its potential as a best-in-class therapy for phenylketonuria (PKU) and a first-in-class therapy for chronic kidney disease (CKD) [1][2] Study Design - The Phase 1 trial was a randomized, double-blind, placebo-controlled study involving 112 healthy adult volunteers, assessing single ascending doses (SAD) and multiple ascending doses (MAD) of MZE782 [3][4] - SAD doses ranged from 30 to 960 mg, while MAD doses ranged from 120 to 240 mg twice daily and 120 to 720 mg once daily [3] Safety and Tolerability Profile - MZE782 was well tolerated across all doses, with no serious adverse events reported [5][6] - Mild treatment-related adverse events included headache (4%) and diarrhea (2%) in the SAD cohort, with no adverse events in the MAD cohort [6] Pharmacokinetics - MZE782 demonstrated a favorable plasma pharmacokinetic profile, with consistent absorption and a half-life of 11 hours [7] - Steady-state was achieved by Day 3, supporting a once- or twice-daily dosing regimen for Phase 2 trials [7] Pharmacodynamics - MZE782 produced dose-dependent increases in urinary excretion of phenylalanine (Phe) and glutamine (Gln), confirming target engagement [8][9] - A 42-fold increase in urinary Phe excretion was observed in the 240 mg twice-daily dose cohort after seven days [9] Estimated Glomerular Filtration Rate (eGFR) - MZE782 showed a dose-dependent initial eGFR dip similar to SGLT2 inhibitors, suggesting a potential beneficial effect on kidney physiology [9] - The combined 240 mg BID cohorts demonstrated a change of -11.5 mL/min/1.73m² after seven days, compared to -2.5 mL/min/1.73m² in the placebo cohort [9] Next Steps - The company plans to initiate two Phase 2 proof-of-concept trials for MZE782 in 2026, focusing on plasma Phe reduction in PKU and proteinuria reduction in CKD [10] Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for kidney and metabolic diseases, utilizing its Compass platform [15]

Core Insights - Maze Therapeutics has appointed Misbah Tahir as Chief Financial Officer, effective immediately, during a critical phase for the company [1][2] - The company is preparing for significant milestones, including data releases for MZE782 and MZE829 in 2025 and 2026 [2] - Mr. Tahir brings over 20 years of experience in the biopharmaceutical industry, having previously served as CFO at IGM Biosciences and held senior finance roles at other notable companies [2][3] Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for kidney and metabolic diseases [4] - The company utilizes its Compass platform to pursue genetically validated targets, integrating variant discovery and functionalization [4] - Maze's pipeline includes MZE829, an oral APOL1 inhibitor in Phase 2 development, and MZE782, an oral SLC6A19 inhibitor in Phase 1, targeting chronic kidney disease and phenylketonuria [4] Financial Position - Maze Therapeutics has a strong balance sheet with an expected cash runway extending into the second half of 2027 [3] - The company aims to create significant value for patients and shareholders through its differentiated precision genetics platform and disciplined development approach [3]

Financial Performance - The company incurred net losses of $33.7 million and $66.5 million for the three and six months ended June 30, 2025, respectively, compared to net income of $139.1 million and $106.6 million for the same periods in 2024[93]. - The company has not generated any revenue from product sales and does not expect to do so in the foreseeable future[92]. - License revenue for the three and six months ended June 30, 2025, was $0, compared to $165.0 million for the same periods in 2024, primarily from agreements with Shionogi and Trace Neuroscience[116]. - The company anticipates continued net losses for the foreseeable future and will require additional capital to fund operations and develop therapeutic candidates[129]. - Income tax expense was zero for the three and six months ended June 30, 2025, compared to $1.7 million for the same periods in 2024, due to a net loss in 2025[124]. Cash Flow and Liquidity - As of June 30, 2025, the company had an accumulated deficit of $424.9 million and does not expect positive cash flows from operations in the foreseeable future[93]. - The company had cash and cash equivalents of $264.5 million as of June 30, 2025[94]. - Net cash used in operating activities was $59.6 million for the six months ended June 30, 2025, compared to net cash provided of $121.6 million for the same period in 2024, reflecting a change of $181.2 million[138]. - The company reported a net loss of $66.5 million for the six months ended June 30, 2025, which contributed to the negative cash flow from operating activities[138]. - Net cash provided by financing activities increased significantly to $128.0 million for the six months ended June 30, 2025, up from $24.7 million in the same period of 2024, marking a change of $103.3 million[140]. - The net increase in cash, cash equivalents, and restricted cash was $67.7 million for the six months ended June 30, 2025, compared to a decrease of $78.2 million from the previous year[136]. Expenses - Research and development expenses are expected to significantly increase due to planned clinical trials for lead programs MZE829 and MZE782[93]. - Research and development expenses increased to $28.1 million for the three months ended June 30, 2025, from $19.5 million in 2024, reflecting a rise of $8.6 million due to clinical trial and personnel-related costs[117]. - General and administrative expenses rose to $8.4 million for the three months ended June 30, 2025, compared to $5.9 million in 2024, an increase of $2.5 million driven by higher personnel-related costs[120]. - Total operating expenses for the six months ended June 30, 2025, were $71.9 million, an increase of $18.4 million from $53.5 million in 2024[115]. Initial Public Offering - The company completed its initial public offering in February 2025, issuing 8,750,000 shares at $16.00 per share, resulting in gross proceeds of $140.0 million[94]. - The company completed its initial public offering in February 2025, raising net proceeds of approximately $127.8 million from the sale of 8,750,000 shares at $16.00 per share[127]. - The company expects interest income to increase due to net proceeds from the initial public offering, estimated at approximately $127.8 million[109]. Agreements and Obligations - The exclusive license agreement with Shionogi, entered in March 2024, provided an upfront payment of $150 million and potential milestone payments of up to $605 million[97]. - The company is obligated to pay $4.9 million under consortium agreements with the University of Helsinki and Queen Mary University through December 31, 2027[134]. Other Financial Information - Interest and other income, net was $2.8 million for the three months ended June 30, 2025, up from $1.0 million in 2024, reflecting increased interest income from higher cash balances[122]. - Non-cash charges for the six months ended June 30, 2025, included $9.4 million related to depreciation, stock-based compensation, and lease expense[138]. - The company experienced a net change in operating assets and liabilities of $2.5 million for the six months ended June 30, 2025, compared to $2.7 million in 2024[138]. - The company has not reported any significant changes in critical accounting policies and estimates during the six months ended June 30, 2025[141]. Regulatory Status - The company intends to rely on exemptions and reduced reporting requirements provided by the JOBS Act, which may affect the comparability of its financial statements with other public companies[145]. - The company remains classified as an emerging growth company (EGC) under the JOBS Act until certain revenue or filing thresholds are met[146].

Financial Position - Maze Therapeutics reported a cash position of $264.5 million as of June 30, 2025, up from $196.8 million as of December 31, 2024, providing a cash runway into H2 2027[6]. - Total liabilities as of June 30, 2025, were $41.3 million, down from $43.6 million as of December 31, 2024[18]. Revenue and Expenses - The company recognized no license revenue for the three and six months ended June 30, 2025, compared to $165.0 million for the same periods in 2024, primarily due to an upfront payment from Shionogi[7][10]. - Research and Development (R&D) expenses increased to $28.1 million for Q2 2025, compared to $19.5 million in Q2 2024, reflecting higher clinical trial and manufacturing costs[8]. - General and Administrative (G&A) expenses rose to $8.4 million for Q2 2025, compared to $5.9 million in Q2 2024, driven by higher personnel-related expenses[9]. - The net loss for the three months ended June 30, 2025, was $33.7 million, compared to a net income of $139.1 million for the same period in 2024, largely due to the absence of license revenue[10]. Clinical Trials and Pipeline - MZE782 is currently in a Phase 1 trial, with initial data expected in Q3 2025, aimed at treating chronic kidney disease (CKD) and phenylketonuria (PKU)[12]. - The Phase 2 HORIZON trial for MZE829 is actively enrolling patients, with initial proof-of-concept data anticipated in Q1 2026[5][2]. - MZE829 targets APOL1-mediated kidney disease, which affects over one million people in the U.S.[3]. - Maze's pipeline includes MZE782, which targets SLC6A19, potentially benefiting approximately five million U.S. patients with CKD[4].

Core Insights - Maze Therapeutics is advancing two clinical-stage programs, MZE782 and MZE829, targeting chronic kidney disease (CKD) and phenylketonuria (PKU) [2][4] - The company reported a strong cash position of $264.5 million, expected to fund operations into the second half of 2027 [5][16] - Significant milestones are anticipated, including initial data from the Phase 1 trial of MZE782 in Q3 2025 and proof-of-concept data from the Phase 2 HORIZON trial of MZE829 in Q1 2026 [1][7][8] Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for kidney and metabolic diseases [13] - The company utilizes its Compass platform to pursue genetically validated targets, aiming for first- or best-in-class therapies [13] Clinical Programs - MZE829 is an oral APOL1 inhibitor for APOL1-mediated kidney disease, which affects over one million people in the U.S. [3] - MZE782 targets the solute transporter SLC6A19 and has potential as a first-in-class treatment for approximately five million U.S. patients with CKD who do not adequately respond to existing therapies [4] Financial Performance - For Q2 2025, Maze reported no license revenue, contrasting with $165 million in license revenue for the same period in 2024, primarily due to an upfront payment from Shionogi [6][12] - Research and development expenses increased to $28.1 million for Q2 2025, up from $19.5 million in Q2 2024, reflecting higher clinical trial and manufacturing costs [10] - General and administrative expenses also rose to $8.4 million in Q2 2025, compared to $5.9 million in Q2 2024 [11] Balance Sheet Highlights - As of June 30, 2025, total assets were $303.5 million, with total liabilities at $41.3 million, indicating a strong financial position [16] - The company’s total stockholders' equity improved to $262.2 million from a deficit of $311.2 million as of December 31, 2024 [16]

Group 1 - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for patients with renal, metabolic, and cardiovascular diseases [2] - The company will participate in two upcoming investor conferences in July, with live webcasts available on their website [1] - Maze Therapeutics utilizes its Compass platform to link genetic variants with biological pathways in disease, advancing a pipeline that includes two wholly owned programs, MZE829 and MZE782 [2] Group 2 - The H.C. Wainwright 4th Annual Kidney Virtual Conference is scheduled for July 14, 2025, at 2:30 p.m. ET [3] - The BTIG Virtual Biotech Conference will take place on July 30, 2025, at 9:20 a.m. ET [3]