Maze Therapeutics Announces Positive Topline Data from Phase 2 HORIZON Trial of MZE829 Demonstrating the First Clinical Proof-of-Concept in Patients with Broad APOL1-Mediated Kidney Disease

Rhea-AI Summary

Maze Therapeutics (Nasdaq: MAZE) reported positive topline Phase 2 HORIZON data for oral APOL1 inhibitor MZE829 on March 25, 2026. At week 12, MZE829 produced a 35.6% mean uACR reduction in broad APOL1-mediated kidney disease (AMKD) patients; 50% achieved >30% uACR reduction.

Subgroups showed a 61.8% mean uACR reduction in FSGS patients and a 48.6% mean uACR reduction in non-diabetic AMKD. Fifteen patients were safety-evaluable and 12 were efficacy-evaluable. No serious adverse events were reported. Maze plans to continue enrollment and advance MZE829 to a pivotal program.

Positive

• Mean uACR -35.6% at week 12 across evaluated AMKD patients
• FSGS subgroup uACR -61.8% mean reduction
• Non-diabetic AMKD uACR -48.6% mean reduction
• Advancing to pivotal program planned by Maze

Negative

• Small efficacy set: only 12 patients evaluated per protocol for uACR
• Short follow-up: topline readout at 12 weeks limits long-term efficacy evidence
• Limited diabetic efficacy data: five evaluable diabetic patients with two meeting ≥30% uACR reduction

News Market Reaction – MAZE

-35.24% 7.1x vol

73 alerts

-35.24% News Effect

+13.2% Peak Tracked

-43.8% Trough Tracked

-$1.28B Valuation Impact

$2.36B Market Cap

7.1x Rel. Volume

On the day this news was published, MAZE declined 35.24%, reflecting a significant negative market reaction. Argus tracked a peak move of +13.2% during that session. Argus tracked a trough of -43.8% from its starting point during tracking. Our momentum scanner triggered 73 alerts that day, indicating high trading interest and price volatility. This price movement removed approximately $1.28B from the company's valuation, bringing the market cap to $2.36B at that time. Trading volume was exceptionally heavy at 7.1x the daily average, suggesting significant selling pressure.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

uACR reduction (broad AMKD): 35.6% mean reduction Patients ≥30% uACR drop: 50% of patients uACR reduction in FSGS: 61.8% mean reduction +5 more

8 metrics

uACR reduction (broad AMKD) 35.6% mean reduction Phase 2 HORIZON, week 12, broad AMKD population

Patients ≥30% uACR drop 50% of patients Phase 2 HORIZON, week 12 efficacy-evaluable patients

uACR reduction in FSGS 61.8% mean reduction Subgroup of AMKD patients with FSGS

uACR reduction non-diabetic 48.6% mean reduction Non-diabetic AMKD subgroup, Phase 2 HORIZON

HORIZON enrollment 15 patients Topline analysis safety population

Efficacy-evaluable patients 12 patients Met per-protocol compliance for uACR analysis

Non-diabetic AMKD 8 patients (5 FSGS) Baseline characteristics in HORIZON trial

uACR threshold impact 30% uACR → 10-year delay 30% uACR reduction linked to 10-year delay to ESKD

Market Reality Check

Price: $30.38 Vol: Volume 556,482 is 0.9x th...

normal vol

$30.38 Last Close

Volume Volume 556,482 is 0.9x the 20-day average of 615,289, showing typical pre-news activity. normal

Technical Shares at $49.00 are trading above the 200-day MA of $30.08 and about 8.67% below the 52-week high of $53.65.

Peers on Argus

Momentum data show 4 biotech peers split between gains and losses, with 2 up and...

2 Up 2 Down

Momentum data show 4 biotech peers split between gains and losses, with 2 up and 2 down; MAZE’s pre-news price was flat, so the impact of this trial update relative to sector flows cannot be inferred.

Previous Clinical trial Reports

2 past events · Latest: Sep 11 (Positive)

Same Type Pattern 2 events

Date	Event	Sentiment	Move	Catalyst
Sep 11	Phase 1 results	Positive	+54.8%	Positive Phase 1 MZE782 data with strong pharmacodynamic effects in volunteers.
Feb 07	Trial initiation	Positive	+2.9%	First patient dosed in Phase 2 HORIZON trial evaluating MZE829 in APOL1 disease.

Pattern Detected

Clinical trial announcements have historically triggered positive, aligned moves following favorable data disclosures.

Recent Company History

Over the past year, Maze reported key clinical milestones, notably two trial updates. A Feb 2025 release on first dosing in the Phase 2 HORIZON trial for MZE829 in APOL1 kidney disease led to a modestly positive reaction. In Sept 2025, positive Phase 1 data for MZE782 in PKU and CKD drove a strong gain of 54.81%. Today’s Phase 2 HORIZON topline results for MZE829 follow this pattern of advancing genetically targeted kidney programs.

Historical Comparison

+28.9% avg move · In prior clinical-trial updates, MAZE saw average moves of 28.87%, indicating that trial data has be...

clinical trial

+28.9%

Average Historical Move clinical trial

In prior clinical-trial updates, MAZE saw average moves of 28.87%, indicating that trial data has been a major stock driver for this name.

Maze’s clinical story progressed from dosing the first patient in the Phase 2 HORIZON trial for MZE829 in Feb 2025 to today’s positive Phase 2 topline data, alongside earlier Phase 1 proof-of-mechanism results for MZE782 in PKU and CKD.

Regulatory & Risk Context

Active S-3 Shelf · $200,000,000

Shelf Active

Active S-3 Shelf Registration 2026-02-04

$200,000,000 registered capacity

Maze has an effective S-3ASR automatic shelf with an at-the-market program authorizing up to $200,000,000 of common stock via Jefferies LLC, with no usage reported yet. This provides substantial flexibility to raise equity capital as clinical programs advance.

Market Pulse Summary

The stock dropped -35.2% in the session following this news. A negative reaction despite favorable P...

Analysis

The stock dropped -35.2% in the session following this news. A negative reaction despite favorable Phase 2 data could fit a pattern where markets reassess risk around small, early-stage datasets. HORIZON enrolled only 15 patients, and durability or hard renal outcomes were not yet addressed. The presence of an unused $200,000,000 ATM shelf also adds overhang concerns about future dilution as Maze advances MZE829 into a pivotal program and continues broader pipeline spending.

Key Terms

apol1, uacr, proteinuria, focal segmental glomerulosclerosis, +4 more

8 terms

apol1 medical

"an oral, small molecule, dual-mechanism APOL1 inhibitor, in patients with broad"

APOL1 is a human gene that makes a protein involved in blood particle handling; certain inherited changes (variants) in APOL1 substantially increase the risk of chronic kidney disease and kidney failure in affected people. Investors follow APOL1 because diagnostic tests, drugs, and transplant policies that target these variants can create new markets or change patient care decisions—similar to how discovering a common defect in a car part can reshape demand for repairs, warranties and replacement parts.

uacr medical

"clinically meaningful mean reduction in proteinuria, as measured by urinary albumin-to-creatinine ratio (uACR)"

UACR is a lab measure that compares the amount of albumin (a blood protein) found in urine to the amount of creatinine, and it indicates how much protein is leaking from the kidneys. Investors watch UACR because rising or falling values act like a car’s warning light for kidney damage — changes can show whether a therapy is working or a disease is progressing, which influences clinical trial outcomes, regulatory decisions and company value.

proteinuria medical

"clinically meaningful mean reduction in proteinuria, as measured by urinary"

Proteinuria is when abnormal amounts of protein are found in a person's urine. It can be a sign that the kidneys aren't working properly, since healthy kidneys usually prevent most proteins from passing into urine. Detecting proteinuria helps doctors identify and monitor kidney problems early.

focal segmental glomerulosclerosis medical

"non-diabetic patients with severe focal segmental glomerulosclerosis (FSGS)."

Focal segmental glomerulosclerosis is a chronic kidney disease in which some of the tiny filters in the kidneys (glomeruli) become scarred in parts, reducing the organ’s ability to remove waste and control fluid balance. For investors, it matters because the condition can drive sustained demand for specialized drugs, diagnostic tests, and treatment services, influence healthcare spending and reimbursement dynamics, and affect the commercial prospects of companies developing therapies or diagnostics for rare kidney disorders.

fsgs medical

"non-diabetic patients with severe focal segmental glomerulosclerosis (FSGS)."

Focal segmental glomerulosclerosis (FSGS) is a kidney disease in which small sections of the organ’s filtering units become scarred, lowering their ability to remove waste and manage fluids. Investors care because drug candidates, diagnostics, or clinical trial results addressing FSGS can meaningfully affect a biotech or pharmaceutical company’s revenue prospects and regulatory outlook—like fixing a specific engine fault that can restore performance and change a vehicle’s value.

chronic kidney disease medical

"background therapies for chronic kidney disease (CKD) for at least eight weeks"

Chronic kidney disease is a long-term, progressive loss of kidney function that reduces the organs’ ability to filter waste, control fluid levels and balance body salts. For investors, CKD matters because it creates sustained demand for tests, drugs, dialysis machines and transplants; advances in treatment or regulatory decisions can meaningfully change revenue prospects for companies—like a car that needs ongoing repairs, it creates predictable, long-term market needs.

sglt2 inhibitors medical

"Background therapies included SGLT2 inhibitors and GLP-1 receptor agonists."

SGLT2 inhibitors are a class of medicines that lower blood sugar by helping the kidneys remove excess glucose in the urine; think of them as a filter that lets extra sugar pass out of the body. They matter to investors because they are used to treat diabetes and related conditions, drive prescription sales, can gain new approvals for additional diseases, and influence healthcare costs, competition, and insurer reimbursement decisions.

rule 10b5-1 trading plan regulatory

"The sales were carried out under a pre-arranged Rule 10b5-1 trading plan"

A Rule 10b5-1 trading plan is a pre-arranged schedule that allows company insiders to buy or sell stock at specific times, even if they have inside information. It helps prevent accusations of unfair trading by making these transactions look planned and transparent, rather than sneaky or illegal.

AI-generated analysis. Not financial advice.

– At week 12, treatment with MZE829 resulted in a 35.6% mean uACR reduction in broad AMKD patients, 50% of the patients achieved a greater than 30% reduction in uACR, and treatment was well-tolerated –

– The subgroup of AMKD patients with FSGS that were treated with MZE829 showed a 61.8% mean reduction in uACR –

– Treatment of non-diabetic AMKD patients with MZE829 led to a clinically meaningful mean reduction in uACR from baseline of 48.6% –

– Results provide first clinical proof-of-concept in genetically defined, broad AMKD population, including patients with moderate proteinuria and diabetes –

– Maze plans to advance MZE829 to a pivotal program –

– Maze to host investor conference call and webcast today at 8:00 am EDT –

SOUTH SAN FRANCISCO, Calif., March 25, 2026 (GLOBE NEWSWIRE) -- Maze Therapeutics, Inc. (Nasdaq: MAZE), a clinical-stage biopharmaceutical company developing small molecule precision medicines for patients with kidney and metabolic diseases, today announced positive topline data from the Phase 2 HORIZON trial of MZE829, an oral, small molecule, dual-mechanism APOL1 inhibitor, in patients with broad APOL1-mediated kidney disease (AMKD). The results demonstrated that treatment with MZE829 led to a clinically meaningful mean reduction in proteinuria, as measured by urinary albumin-to-creatinine ratio (uACR), of 35.6% at week 12 in broad AMKD patients, with 50% of patients achieving a greater than 30% reduction in uACR. Maze expects to continue enrollment in the HORIZON trial and to advance MZE829 into a pivotal program in patients with AMKD.

“We are pleased to show initial promising proof-of-concept for MZE829, an oral precision medicine that was designed to treat the underlying cause of AMKD by uniquely inhibiting both pore formation and channel function in the podocyte,” said Harold Bernstein, M.D., Ph.D., president of R&D and chief medical officer of Maze. “Based on the data shown today, as well as genetics data derived through our Compass platform, we believe that MZE829’s dual mechanism approach has the potential to address the unmet need in AMKD patients. We look forward to meeting with regulators and key scientific leaders to align on a pivotal program in patients with AMKD, and anticipate presenting HORIZON data at a future medical conference.”

The HORIZON study is a Phase 2, open-label basket design trial that enrolled patients with broad AMKD carrying the APOL1 high risk genotype, including diabetic and non-diabetic patients and non-diabetic patients with severe focal segmental glomerulosclerosis (FSGS). The primary endpoints of the study are safety and tolerability, and the secondary endpoints are pharmacokinetics and reduction of proteinuria, as measured by urinary albumin-to-creatinine ratio. uACR is a sensitive measure of proteinuria across stages of glomerular kidney disease, particularly in hypertension and diabetes, and has been used to assess the risk of cardiovascular disease. Patients had to be on a stable background therapies for chronic kidney disease (CKD) for at least eight weeks prior to initiating MZE829 treatment. Background therapies included SGLT2 inhibitors and GLP-1 receptor agonists.

For this topline analysis, 15 patients were enrolled in the HORIZON study and all were included in a safety and tolerability analysis. Twelve patients were evaluated for efficacy, i.e., uACR reduction, based on meeting the per protocol compliance threshold. Patients were largely sub-nephrotic at baseline, with 10 patients having a baseline uACR of 300 to 1,000 mg/g. Across all enrolled patients, eight were diagnosed with AMKD without diabetes, of whom five patients had biopsy-confirmed FSGS, and seven were diagnosed with AMKD with diabetes.

Across all evaluated patients, a mean reduction in proteinuria from baseline of 35.6% was observed and 50% of patients achieved at least a 30% reduction in uACR. Reduction in proteinuria was seen throughout the course of the 12-week treatment period. In FSGS patients, treatment with MZE829 led to a mean reduction in uACR of 61.8%. In patients with AMKD without diabetes, treatment with MZE829 resulted in a clinically meaningful mean reduction in uACR of 48.6%. In patients with AMKD with diabetes, five patients were evaluable per protocol for efficacy, with two patients achieving at least a 30% reduction in uACR. MZE829 was well-tolerated across all doses evaluated. No serious adverse events (AEs) or severe treatment-related adverse events (TRAEs) were observed. Within the safety-evaluable population (n=15), the most common TRAEs were headache (n=2) and diarrhea (n=2). There was one early treatment discontinuation due to mild nausea that occurred just prior to the week 12 visit.

“AMKD is a subset of chronic kidney disease with a large unmet need, potentially affecting over one million patients in the United States alone and millions more globally,” said Kate Bramham, M.B.B.S., Ph.D., consultant nephrologist at King’s College Hospital, senior clinical lecturer at King’s College London, and HORIZON steering committee member. “APOL1 risk variants are linked to earlier disease onset and accelerated disease progression, with patients initiating dialysis an average of 10 years earlier than non-APOL1 CKD patients and progressing rapidly to end-stage kidney disease, despite treatment with available therapies. A 30% uACR reduction is strongly correlated with a 10-year delay in progression to end-stage kidney disease and is widely recognized as a clinically meaningful threshold. MZE829 has the potential to be a truly differentiated treatment option to deliver meaningful, much-needed benefit to patients who currently have no options for targeted therapies.”

Conference Call and Webcast

Maze will host a conference call and webcast with members of the executive team today at 8:00 am EDT to discuss the data and next steps.

To access the call, please dial 1-888-243-4451 (United States or Canada) or 1-412-542-4135 (international) and request to be joined into the Maze Therapeutics, Inc. call.

To access the live webcast and subsequent archived recording of this event and other company presentations, please visit the Investors section of Maze’s website. The archived webcast will remain available for replay and on Maze’s website for 90 days.

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 with kidney and metabolic diseases. Guided by its Compass™ platform, Maze pursues genetically validated targets by integrating variant discovery and functionalization to discover and advance small molecule programs with first- or best-in-class potential. Maze’s pipeline is led by MZE829, a dual-mechanism APOL1 inhibitor in Phase 2 development for APOL1-mediated kidney disease (AMKD), and MZE782, a SLC6A19 inhibitor advancing to Phase 2 with the potential to treat both phenylketonuria (PKU) and chronic kidney disease (CKD). Maze is headquartered in South San Francisco. For more information, please visit mazetx.com, or follow the company 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, MZE782 to treat AMKD or other indications, the planned timing of the company’s clinical trials, data results and further development of MZE829, MZE782 and other therapeutic candidates, the company’s expected cash runway, and the ability to drive financial results and stockholder value. 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 documents the company files from time to time with the U.S. Securities and Exchange Commission, including the company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. 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 the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

IR/Corporate Contact:
Amy Bachrodt, Maze Therapeutics
abachrodt@mazetx.com

Media Contact:
Amanda Lazaro, 1AB Media
Amanda@1ABMedia.com

FAQ

What were the key HORIZON Phase 2 results for MZE829 (MAZE) on March 25, 2026?

MZE829 showed a 35.6% mean reduction in uACR at week 12 in broad AMKD patients. According to the company, 50% of patients achieved more than a 30% uACR reduction, with stronger responses in FSGS and non-diabetic subgroups.

How did MZE829 perform in the FSGS subgroup in the HORIZON trial (MAZE)?

In FSGS patients, MZE829 produced a 61.8% mean uACR reduction at week 12. According to the company, this subgroup comprised biopsy-confirmed FSGS patients and showed the largest mean proteinuria decline in the study.

Were there safety concerns in the Phase 2 HORIZON trial of MZE829 (MAZE)?

No serious adverse events or severe treatment-related adverse events were reported in the safety-evaluable population. According to the company, most common TRAEs were headache and diarrhea, and one patient discontinued early for mild nausea.

How many patients were included in the efficacy analysis for MZE829 in HORIZON (MAZE)?

Twelve patients were evaluable for efficacy per protocol for the uACR endpoint at week 12. According to the company, 15 patients were safety-evaluable overall and 12 met compliance thresholds for efficacy analysis.

What are Maze's next steps for MZE829 after the HORIZON topline data (MAZE)?

Maze plans to continue HORIZON enrollment and advance MZE829 into a pivotal program in AMKD patients. According to the company, they will meet with regulators and scientific leaders to align on a pivotal development plan.