Hypertension, Renal

MZE829 Phase 2 HORIZON Trial Enrolling Patients with APOL1 Kidney Disease (AKD); Initial Data Expected in Q1 2026 MZE782 Phase 1 Healthy Volunteer Trial Ongoing; Initial Data Expected in H2 2025 Raised $140 Million in Gross Proceeds in Upsized IPO in February 2025, Providing Expected Cash Runway into H2 2027 SOUTH SAN FRANCISCO, Calif., March 31, 2025 (GLOBE NEWSWIRE) -- Maze Therapeutics, Inc. (Nasdaq: MAZE), a clinical-stage biopharmaceutical company developing small molecule precision medicines for patients with renal, cardiovascular and metabolic diseases, today reported financial results for the fourth quarter and year ended December 31, 2024, highlighted recent progress and reiterated upcoming milestones. “Maze has reached a pivotal moment in our journey. On the heels of a successful IPO and with two ongoing clinical-stage programs - MZE829 for AKD and MZE782 for both chronic kidney disease (CKD) and phenylketonuria (PKU) - we are making meaningful progress towards advancing genetic-based medicines with the potential to transform patient care,” said Jason Coloma, Ph.D., chief executive officer of Maze. “We look forward to reporting initial Phase 1 data for MZE782 in healthy volunteers in the second half of 2025, which will enable us to prepare to initiate Phase 2 trials in CKD and PKU. We also expect to report initial data from the Phase 2 HORIZON trial of MZE829 in patients with AKD in the first quarter of next year. With a strong financial foundation, highly accomplished team and clear mission, we are well-positioned to execute our milestones and deliver breakthrough medicines to patients.” Pipeline Accomplishments and Upcoming Milestones MZE829 for AKD MZE829 is an oral, small molecule APOL1 inhibitor that Maze is advancing as a potential treatment for patients with AKD, a subset of CKD estimated to affect over one million people in the United States alone. In February 2025, Maze dosed the first patient in the Phase 2 HORIZON Study of MZE829 in patients with AKD. The trial is enrolling a broad population of AKD patients, including those with more severe disease who have nephrotic range proteinuria, focal segmental glomerulosclerosis (FSGS), patients with lower levels of proteinuria and hypertensive nephropathy and patients with proteinuria and diabetic kidney disease. Maze expects to announce topline data from the Phase 2 trial in the first quarter of 2026. In October 2024, Maze reported positive Phase 1 results for MZE829 in healthy volunteers, which demonstrated that MZE829 was well tolerated at single doses up to 480 mg and multiple doses up to 350 mg daily over seven days, with dose-proportional pharmacokinetics and low variability. The observed half-life of approximately 15 hours supports once-daily dosing of MZE829. MZE782 in CKD and PKU MZE782 is an oral small molecule targeting the solute transporter SLC6A19, with potential to be a first-in-class treatment for approximately five million U.S. patients with CKD who have inadequate responses to currently available CKD therapies, as well as those with PKU, an inherited metabolic disorder. In September 2024, Maze initiated a Phase 1 clinical trial of MZE782 in healthy volunteers. Maze expects to report initial data, including proof-of-mechanism biomarkers, in the second half of 2025. Based on Phase 1 results, Maze plans to initiate two parallel Phase 2 clinical trials of MZE782 in CKD and PKU. Corporate Highlights In February 2025, Maze completed an upsized IPO, raising approximately $140 million in gross proceeds, before deducting underwriting discounts and commissions and other offering expenses, through the sale of 8,750,000 shares at $16.00 per share. In November 2024, Maze closed an oversubscribed $115 million Series D financing co-led by Frazier Life Sciences and Deep Track Capital, with participation from Janus Henderson Investors and Logos Capital. Approximately $40 million of the $115 million represented the conversion of previously issued convertible notes held by existing investors. Combined gross proceeds of approximately $255 million from the two financings are expected to provide runway into the second half of 2027, supporting completion of Phase 2 clinical trials for MZE829 in AKD and MZE782 in CKD and PKU, as well as continued advancement of additional preclinical programs. Fourth Quarter and Full Year 2024 Financial Results Cash Position: Cash and cash equivalents were $196.8 million as of December 31, 2024, compared to $29.2 million as of December 31, 2023. Maze expects its current cash and cash equivalents, which includes proceeds from its February 2025 IPO, will fund operations into the second half of 2027. License Revenue: License revenue was $167.5 million for the year ended December 31, 2024, compared to none for the year ended December 31, 2023. The increase was primarily due to the receipt of a one-time upfront payment of $150.0 million in May 2024 under the license agreement with Shionogi & Co., Ltd. (Shionogi) for the development of MZE001 in Pompe disease. No license revenue was recognized for the fourth quarter of 2024 and 2023. Research & Development (R&D) Expenses: R&D expenses were $22.2 million for the fourth quarter of 2024 and $83.5 million for the year ended December 31, 2024, compared to $16.0 million for the fourth quarter of 2023 and $73.9 million for the year ended December 31, 2023. This year-over-year increase primarily reflects higher clinical trial expenses for MZE829 and MZE782 as well as for preclinical studies for MZE782. General & Administrative (G&A) Expenses: G&A expenses were $7.5 million for the fourth quarter of 2024 and $26.4 million for the year ended December 31, 2024, compared to $7.0 million for the fourth quarter of 2023 and $24.6 million for the year ended December 31, 2023. This year-over-year increase primarily reflects higher personnel-related expenses, including non-cash stock-based compensation expense, partially offset by lower expenses for professional services. Net (Loss) Income: Net loss was $29.6 million for the fourth quarter of 2024 and net income was $52.2 million for the year ended December 31, 2024, compared to net loss of $26.6 million for the fourth quarter of 2023 and net loss of $100.4 million for the year ended December 31, 2023. Net income for the year ended December 31, 2024 includes $167.5 million in license revenue recognized under various license agreements, including the exclusive license agreement with Shionogi. 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. 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, MZE782 and other candidates under development, the ability of MZE829 to treat AKD or other indications, the ability of MZE782 to treat CKD, PKU or other indications, the planned timing of the company’s clinical trials, data results and further development of MZE829, MZE782 and other therapeutic candidates, and the sufficiency of the company’s cash and cash equivalents to fund its operating expenses and capital expenditure requirements. 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, tariffs, 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 Annual Report on Form 10-K for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission (SEC) on March 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. Corporate Contact:Jillian Connell, Maze Therapeuticsjconnell@mazetx.com(650) 850-5080 Media Contact:Dan Budwick, 1ABdan@1abmedia.com Maze Therapeutics, Inc. Select Condensed Financial Information (in thousands, except share and per share amounts) (unaudited) Condensed Statements of Operations Three months ended Year ended December 31, December 31, 2024 2023 2024 2023 License revenue$— $— $167,500 $— Operating expenses: Research and development 22,216 16,045 83,496 73,945 General and administrative 7,510 7,006 26,418 24,606 Total operating expenses 29,726 23,051 109,914 98,551 (Loss) income from operations (29,726) (23,051) 57,586 (98,551)Interest and other income, net 1,516 304 4,654 1,966 Change in fair value of convertible promissory notes (1,644) (3,830) (8,837) (3,830)(Loss) income before income tax expense$(29,854) $(26,577) $53,403 $(100,415)Income tax benefit (expense) 275 — (1,172) — Net (loss) income$(29,579) $(26,577) $52,231 $(100,415)Net (loss) income attributable to common stockholders, basic and diluted$(44,551) $(26,577) $3,405 $(100,415)Net (loss) income per share attributable to common stockholders: Basic$(18.32) $(11.46) $1.42 $(43.89)Diluted$(18.32) $(11.46) $1.25 $(43.89)Weighted-average shares used in computing net (loss) income per share attributable to common stockholders: Basic 2,431,764 2,318,137 2,396,094 2,287,980 Diluted 2,431,764 2,318,137 2,730,299 2,287,980 Condensed Balance Sheet Data December 31, December 31, 2024 2023 Cash and cash equivalents $196,812 $29,158 Total assets $240,542 $71,504 Total liabilities $43,638 $61,450 Total redeemable convertible preferred stock and stockholders’ deficit $196,904 $10,054

SOUTH SAN FRANCISCO, CA, USA I February 07, 2025 I 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 30% or greater reduction from baseline in urinary albumin-to-creatinine ratio (uACR) at week 12, a reduction threshold that is expected to offer clinically meaningful benefit, according to external, published literature. 1 uACR is a sensitive measure of proteinuria across stages of glomerular kidney disease, particularly in hypertension and diabetes, and has been used to assess risk of cardiovascular disease. Maze expects to have a potential proof of concept interim data readout in the first quarter of 2026. 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). 1 https://pubmed.ncbi.nlm.nih.gov/30635226/ SOURCE: Maze Therapeutics

Feb. 04, 2025 -- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease (CKD), obstructive sleep apnea (OSA) and other diseases driven by dysregulated aldosterone, today announced that it has completed enrollment in the Explore-CKD Phase 2 trial evaluating the efficacy and safety of lorundrostat for the treatment of hypertension in subjects with CKD and albuminuria, despite receiving stable treatment with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) and an SGLT2 inhibitor. “We are pleased to have completed enrollment in Explore-CKD and be on track to share topline data in the second quarter of 2025. This is our third trial to recently complete enrollment and we are grateful to all of the study participants, investigators, and our staff who made this possible,” stated David Rodman, MD, Chief Medical Officer of Mineralys Therapeutics. “In concert with our Target-HTN, Advance-HTN and recently announced Explore-OSA trials, Explore-CKD expands the spectrum of high-risk patients with poorly controlled hypertension who may benefit from this novel treatment modality. Poorly controlled hypertension, and hypertensive nephropathy, are a leading cause of renal failure in the United States and a strong predictor of major adverse cardiovascular events and premature death.” The Explore-CKD trial (NCT06150924) is a randomized, double-blind, placebo controlled, two-period, two-sequence (2x2) crossover trial. This proof-of-concept trial is designed to evaluate blood pressure reduction and safety of 25 mg once daily (QD) lorundrostat added to RAAS inhibition and an SGLT2 inhibitor for the treatment of hypertension in subjects with Stage 2 to 3b CKD and albuminuria. The primary efficacy endpoint of the trial is change from baseline in systolic blood pressure at week four in the active versus placebo treatment period. An exploratory endpoint will be to evaluate change from baseline in urine albumin-to-creatinine ratio at week four in the active versus placebo treatment period. CKD, which is characterized by the gradual loss of kidney function, is estimated to affect more than 10% of the global population and is one of the leading causes of mortality worldwide. According to the U.S. Centers for Disease Control and Prevention (CDC), an estimated 1-in-7 (15%) of U.S. adults have CKD. Diabetes and hypertension are responsible for approximately two-thirds of CKD cases. Early detection and treatment can often keep CKD from getting worse. When CKD progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life. Having sustained, elevated blood pressure (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the U.S. In 2020, more than 670,000 deaths in the U.S. included hypertension as a primary or contributing cause. Hypertension and related health issues resulted in an average annual economic burden of about $130 billion each year in the U.S., averaged over 12 years from 2003 to 2014. Less than 50 percent of hypertension patients achieve their blood pressure goal with currently available medications. Dysregulated aldosterone levels are a key factor in driving hypertension in approximately 25 percent of all hypertensive patients. Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension (uHTN) and resistant hypertension (rHTN), CKD and OSA. Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of 10-12 hours and demonstrated an approximately 70% reduction in plasma aldosterone concentration in hypertensive subjects. In a Phase 2, proof-of-concept trial (Target-HTN) in uncontrolled or resistant hypertensive subjects, once-daily lorundrostat demonstrated clinically meaningful blood pressure reduction in both automated office blood pressure measurement and 24-hour ambulatory blood pressure monitoring. Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia. Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, CKD, OSA and other diseases driven by dysregulated aldosterone. Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor that Mineralys Therapeutics is developing for the treatment of cardiorenal conditions affected by dysregulated aldosterone, including hypertension, CKD and OSA. Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific. For more information, please visit https://mineralystx.com. Follow Mineralys on LinkedIn and Twitter. The content above comes from the network. if any infringement, please contact us to modify.