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]

Company Overview - Maze Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for patients with renal, metabolic, and cardiovascular diseases [3] - The company utilizes its Compass platform to gain insights into genetic variants associated with diseases and their biological pathways [3] Pipeline Development - Maze Therapeutics is advancing a pipeline that includes two wholly owned programs, MZE829 and MZE782, which represent novel precision medicine approaches [3] - The company aims to address conditions such as obesity and other related metabolic diseases through its innovative therapies [3] Upcoming Presentation - Jason Coloma, Ph.D., the CEO of Maze Therapeutics, will present a company overview at the Jefferies 2025 Global Healthcare Conference on June 5, 2025, at 2 p.m. ET [1] - A live webcast of the presentation will be available on the company's website and archived for 60 days [2]

[PART I FINANCIAL INFORMATION](index=6&type=section&id=PART%20I%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The unaudited statements reflect a significantly improved cash position and stockholders' equity following the February 2025 IPO [Condensed Balance Sheets](index=6&type=section&id=Condensed%20Balance%20Sheets) The balance sheet reflects a substantial increase in assets and a shift from a stockholders' deficit to equity, driven by the IPO Condensed Balance Sheet Comparison (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $294,374 | $196,812 | | Total current assets | $299,707 | $201,671 | | Total assets | $332,840 | $240,542 | | **Liabilities and Stockholders' Equity (Deficit)** | | | | Total liabilities | $40,772 | $43,638 | | Redeemable convertible preferred stock | $— | $508,087 | | Total stockholders' equity (deficit) | $292,068 | $(311,183) | [Condensed Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The net loss remained stable year-over-year as increased operating expenses were offset by higher interest income Statement of Operations Summary (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $27,580 | $21,877 | | General and administrative | $7,821 | $6,137 | | **Loss from operations** | **$(35,401)** | **$(28,014)** | | Interest and other income, net | $2,615 | $281 | | Change in fair value of convertible promissory notes | $— | $(4,761) | | **Net loss and comprehensive loss** | **$(32,786)** | **$(32,494)** | | Net loss per share, basic and diluted | $(1.15) | $(13.91) | [Condensed Statements of Cash Flows](index=9&type=section&id=Condensed%20Statements%20of%20Cash%20Flows) A significant cash inflow from the IPO offset increased cash used in operations, resulting in a net cash increase of $97.6 million Cash Flow Summary (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(29,516) | $(23,437) | | Net cash used in investing activities | $(299) | $(279) | | Net cash provided by financing activities | $127,378 | $24,581 | [Notes to Condensed Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Financial%20Statements) Notes detail the $127.8M IPO, confirm one-year operational funding, and clarify 2024 revenue from license agreements - In February 2025, the company completed its IPO, selling 8,750,000 shares of common stock for net proceeds of approximately **$127.8 million**[30](index=30&type=chunk) - As of March 31, 2025, the company had **$294.4 million in cash and cash equivalents** and believes this is sufficient to fund operations for at least one year[33](index=33&type=chunk) - The company entered into significant license agreements in 2024 with Shionogi ($150.0M upfront), Trace ($15.0M upfront), and Neurocrine ($2.5M upfront), with revenue recognized in 2024[75](index=75&type=chunk)[78](index=78&type=chunk)[80](index=80&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=21&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management analyzes rising R&D expenses for its clinical programs and the strengthened financial condition post-IPO [Results of Operations](index=24&type=section&id=Results%20of%20operations) Operating expenses increased by $7.4 million year-over-year, driven primarily by higher clinical trial and personnel costs Comparison of Operating Results (in thousands) | | Three Months Ended March 31, | Change | | :--- | :--- | :--- | | | **2025** | **2024** | | | Research and development | $27,580 | $21,877 | $5,703 | | General and administrative | $7,821 | $6,137 | $1,684 | | **Total operating expenses** | **$35,401** | **$28,014** | **$7,387** | | **Loss from operations** | **$(35,401)** | **$(28,014)** | **$(7,387)** | - The **$5.7 million increase in R&D expenses** was primarily driven by a $3.1 million rise in clinical trial expenses for the Phase 2 trial of MZE829 and the Phase 1 trial of MZE782[110](index=110&type=chunk) [Liquidity and Capital Resources](index=26&type=section&id=Liquidity%20and%20capital%20resources) The company's liquidity was significantly boosted by its February 2025 IPO, providing sufficient capital for at least the next year - As of March 31, 2025, the company had cash and cash equivalents of **$294.4 million** and an accumulated deficit of $391.2 million[116](index=116&type=chunk) - The company believes its existing cash and cash equivalents are **sufficient to fund operations for at least one year** from the date of the report[118](index=118&type=chunk) - Future funding requirements are substantial and depend on the progress of clinical trials for MZE829 and MZE782 and other pipeline candidates[120](index=120&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=30&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company indicates it does not have material exposure to market risks requiring disclosure - The report states **"Not applicable"** for this item[138](index=138&type=chunk) [Controls and Procedures](index=30&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective, with no material changes to internal controls - Based on an evaluation as of March 31, 2025, the Chief Executive Officer concluded that the company's **disclosure controls and procedures were effective**[140](index=140&type=chunk) - **No changes in internal control** over financial reporting occurred during the quarter that materially affected or are likely to materially affect internal controls[141](index=141&type=chunk) [PART II OTHER INFORMATION](index=31&type=section&id=PART%20II%20OTHER%20INFORMATION) [Legal Proceedings](index=31&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently party to any material legal proceedings - The company is not currently a party to any legal proceedings that management believes would have a **material adverse effect** on the business[144](index=144&type=chunk) [Risk Factors](index=31&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks related to its history of losses, dependence on early-stage programs, and reliance on third parties - The company is a clinical-stage biopharmaceutical company with a limited operating history, a history of **significant operating losses**, and expects to incur continued losses[146](index=146&type=chunk)[147](index=147&type=chunk) - The business is **highly dependent on the success of its lead programs**, MZE829 and MZE782, which are in early stages of development[165](index=165&type=chunk) - The company **relies on third parties** for critical functions, including genetic data, manufacturing, and conducting clinical trials[204](index=204&type=chunk)[218](index=218&type=chunk)[226](index=226&type=chunk) - The company faces **significant competition** from major pharmaceutical and biotechnology companies with greater financial resources and expertise[291](index=291&type=chunk)[296](index=296&type=chunk) [Unregistered Sales of Equity Securities, Use of Proceeds, and Issuer Purchases of Equity Securities](index=82&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%2C%20Use%20of%20Proceeds%2C%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company details its IPO proceeds and confirms no material change in their planned use - The company's IPO closed on February 3, 2025, resulting in **net proceeds of approximately $127.8 million** from the sale of 8,750,000 shares[418](index=418&type=chunk) - There has been **no material change** in the planned use of proceeds from the IPO as described in the final prospectus[419](index=419&type=chunk) [Defaults Upon Senior Securities](index=83&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon its senior securities - The report states **"Not applicable"** for this item[420](index=420&type=chunk) [Mine Safety Disclosures](index=83&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable as the company is not engaged in mining operations - The report states **"Not applicable"** for this item[421](index=421&type=chunk) [Other Information](index=83&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted, modified, or terminated a Rule 10b5-1 trading plan during the quarter - During the three months ended March 31, 2025, **no directors or officers adopted, modified, or terminated a Rule 10b5-1 trading arrangement**[422](index=422&type=chunk) [Exhibits](index=84&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including required certifications and XBRL data [Signatures](index=85&type=section&id=SIGNATURES) The report is duly signed by the company's Chief Executive Officer on May 14, 2025

Financial Position - Maze Therapeutics reported a cash position of $294.4 million as of March 31, 2025, up from $196.8 million as of December 31, 2024, providing a cash runway into H2 2027[6]. - Total stockholders' equity improved to $292.1 million as of March 31, 2025, from a deficit of $311.2 million as of December 31, 2024[17]. Expenses - Research and Development (R&D) expenses increased to $27.6 million in Q1 2025 from $21.9 million in Q1 2024, primarily due to higher clinical trial expenses for MZE829 and MZE782[7]. - General and Administrative (G&A) expenses rose to $7.8 million in Q1 2025 compared to $6.1 million in Q1 2024, reflecting higher personnel-related expenses and professional services fees[8]. - Total operating expenses for Q1 2025 were $35.4 million, compared to $28.0 million in Q1 2024[15]. Net Loss - The net loss for Q1 2025 was $32.8 million, slightly higher than the net loss of $32.5 million in Q1 2024[8]. Clinical Trials - Maze is actively enrolling patients in the Phase 2 HORIZON trial of MZE829, with initial proof-of-concept data expected in Q1 2026[5]. - MZE782 is currently in a Phase 1 clinical trial, with initial data, including biomarker results, expected in Q3 2025[11]. - The company plans to initiate two separate Phase 2 clinical trials of MZE782 in CKD and PKU based on Phase 1 results[11]. Target Diseases - MZE829 targets APOL1 Kidney Disease, which affects over one million people in the U.S., while MZE782 targets approximately five million U.S. patients with CKD[3][4].

Core Insights - Maze Therapeutics is advancing two clinical programs, MZE829 and MZE782, which are expected to drive growth and innovation in the treatment of chronic kidney disease (CKD) and phenylketonuria (PKU) [2][10] Clinical Programs - MZE829 is an oral small molecule APOL1 inhibitor targeting APOL1 kidney disease (AKD), a subset of CKD affecting over one million people in the U.S. The Phase 2 HORIZON trial is actively enrolling patients and initial data is expected in Q1 2026 [3][7] - MZE782 is an oral small molecule targeting the solute transporter SLC6A19, with potential as a first-in-class treatment for approximately five million U.S. patients with CKD who do not adequately respond to existing therapies, and as a best-in-class therapy for PKU. Initial data from the Phase 1 trial is expected in Q3 2025 [4][8] Financial Performance - As of March 31, 2025, Maze Therapeutics reported cash and cash equivalents of $294.4 million, an increase from $196.8 million as of December 31, 2024. This cash position is expected to fund operations into the second half of 2027 [5][14] - Research and development expenses for Q1 2025 were $27.6 million, up from $21.9 million in Q1 2024, primarily due to increased clinical trial costs for MZE829 and MZE782 [6] - General and administrative expenses rose to $7.8 million in Q1 2025 from $6.1 million in Q1 2024, reflecting higher personnel-related costs [9] Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for renal, cardiovascular, and metabolic diseases. The company utilizes its Compass platform to link genetic variants with disease pathways [10]