San Francisco Pharma Co.'s HORIZON Phase 2 Data Validates APOL1 Path to Pivotal Trial
Research Report

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Disclosures for H.C. Wainwright & Co., Maze Therapeutics Inc., April 7, 2026

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H.C. Wainwright & Co, LLC (the “Firm”) is a member of FINRA and SIPC and a registered U.S. Broker-Dealer. I, Ananda Ghosh, PhD and Andrew S. Fein , certify that 1) all of the views expressed in this report accurately reflect my personal views about any and all subject securities or issuers discussed; and 2) no part of my compensation was, is, or will be directly or indirectly related to the specific recommendation or views expressed in this research report; and 3) neither myself nor any members of my household is an officer, director or advisory board member of these companies. None of the research analysts or the research analyst’s household has a financial interest in the securities of Maze Therapeutics, Inc. (including, without limitation, any option, right, warrant, future, long or short position). As of March 31, 2026 neither the Firm nor its affiliates beneficially own 1% or more of any class of common equity securities of Maze Therapeutics, Inc.. Neither the research analyst nor the Firm knows or has reason to know of any other material conflict of interest at the time of publication of this research report. A research analyst of the firm and/or the research analyst’s household has a financial interest in and own the securities of Vertex Pharmaceuticals Inc. (including, without limitation, any option, right, warrant, future, long or short position). As of March 31, 2026 neither the Firm nor its affiliates beneficially own 1% or more of any class of common equity securities of Vertex Pharmaceuticals Inc.. Neither the research analyst nor the Firm knows or has reason to know of any other material conflict of interest at the time of publication of this research report. The research analyst principally responsible for preparation of the report does not receive compensation that is based upon any specific investment banking services or transaction but is compensated based on factors including total revenue and profitability of the Firm, a substantial portion of which is derived from investment banking services. The Firm or its affiliates did not receive compensation from Maze Therapeutics, Inc. and Vertex Pharmaceuticals Inc. for investment banking services within twelve months before, but will seek compensation from the companies mentioned in this report for investment banking services within three months following publication of the research report. The Firm does not make a market in Maze Therapeutics, Inc. and Vertex Pharmaceuticals Inc. as of the date of this research report. The securities of the company discussed in this report may be unsuitable for investors depending on their specific investment objectives and financial position. Past performance is no guarantee of future results. This report is offered for informational purposes only, and does not constitute an offer or solicitation to buy or sell any securities discussed herein in any jurisdiction where such would be prohibited. This research report is not intended to provide tax advice or to be used to provide tax advice to any person. Electronic versions of H.C. Wainwright & Co., LLC research reports are made available to all clients simultaneously. No part of this report may be reproduced in any form without the expressed permission of H.C. Wainwright & Co., LLC. Additional information available upon request. H.C. Wainwright & Co., LLC does not provide individually tailored investment advice in research reports. This research report is not intended to provide personal investment advice and it does not take into account the specific investment objectives, financial situation and the particular needs of any specific person. Investors should seek financial advice regarding the appropriateness of investing in financial instruments and implementing investment strategies discussed or recommended in this research report. H.C. Wainwright & Co., LLC’s and its affiliates’ salespeople, traders, and other professionals may provide oral or written market commentary or trading strategies that reflect opinions that are contrary to the opinions expressed in this research report.

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Published April 7, 2026, analysts Ananda Ghosh, PhD, and Andrew S. Fein of H.C. Wainwright & Co. reiterate their Buy rating on Maze Therapeutics Inc. (MAZE:NASDAQ), with a price target of US$110.00, implying approximately 279% upside from the current share price of US$29.00.

The rating follows the company's HORIZON Phase 2 topline readout and subsequent key opinion leader (KOL) consultations, which reinforced the analysts' conviction in the APOL1 inhibition mechanism and the path to a pivotal trial.

HORIZON Phase 2 Results and KOL Perspectives

Following the HORIZON readout, H.C. Wainwright convened two KOL calls with leading academic nephrologists — one a pediatric nephrologist and glomerular disease trial expert, the other an APOL1 biology expert at Duke University. Both KOLs independently characterized the HORIZON dataset as biologically coherent and internally consistent, framing the three trial cohorts as a predictable signal-to-noise gradient. The FSGS cohort, which is biopsy-confirmed and APOL1-dominant, delivered the cleanest signal at 61.8% UACR reduction, followed by non-diabetic AMKD at 48.6%, and diabetic AMKD showing the most modest but still notable response given the complexity of the patient population and maximally optimized background therapy including SGLT2 inhibitors and GLP-1 agents.

The KOLs described APOL1 as a "disease amplifier" rather than a primary disease cause — an important distinction for both the non-diabetic and diabetic cohorts. The analysts note that the KOLs positioned APOL1 inhibitors on the spectrum of disease-modifying therapies rather than curative interventions, drawing an analogy to PCSK9 inhibitors layered on top of statins as precision add-ons to standard of care.

Diabetic Cohort Signal Viewed as Proof of Concept

Despite the modest response in the diabetic cohort, both KOLs were explicit that the UACR improvement observed in the two diabetic responders is not random noise. The analysts highlight that the KOLs noted the normal UACR trajectory in diabetic kidney disease over a 12-week period without additional intervention is "either flat, slowly worsening, or at best stable" on the established standard of care.

A spontaneous improvement, as one of the two diabetic responders achieved, does not fit that expected distribution, leading the KOLs to characterize the signal as drug-attributable rather than artifactual. Both KOLs described the diabetic cohort data as "genuinely encouraging" and representing the first clinical proof-of-concept that APOL1 inhibition is active in diabetic kidney disease.

Pivotal Trial Design Framework

The KOLs recommended separating the non-diabetic and diabetic arms in the pivotal program, with distinct endpoints for each. For the non-diabetic cohort, which demonstrated a clean and clinically meaningful UACR reduction, the KOLs recommended advancement to a registration-intent Phase 3 trial powered on a 30% UACR reduction endpoint, with the regulatory path being actively pursued through the PARASOL framework.

For the diabetic cohort, the KOLs recommended continuing the current HORIZON cohort to generate eGFR trajectory and biomarker data before designing a subsequent pivotal trial, where eGFR slope — rather than proteinuria — may serve as the primary endpoint. The analysts note that the challenge remains the prospective identification of APOL1-primary patients within the broader diabetic CKD population, a biomarker challenge the field is actively working to address through enrichment criteria.

MZE829 Potential Long-Term Advantage

The analysts highlight a mechanistic argument for MZE829's potential long-term advantage over Vertex Pharmaceuticals' (NASDAQ: VRTX) inaxaplin. While inaxaplin blocks existing APOL1 pores but does not address new pore formation, MZE829 addresses both.

In the analysts' view, over a longer duration, MZE829's assembly-disruption component may progressively reduce the total burden of APOL1 protein embedded in the podocyte membrane, effectively reverting the cell toward a healthier phenotype as pore synthesis slows. The analysts conclude that the current 12-week comparison understates the differential that may emerge in a longer-duration pivotal study.

AMPLIFIED Readout as External Catalyst

Both KOLs independently concluded that the HORIZON dataset provides external validation of the APOL1 inhibition mechanism and that Vertex Pharmaceuticals' (NASDAQ: VRTX; Buy; PT US$641.00; Market Cap US$110.3B) upcoming AMPLIFIED Phase 2 readout, expected mid-2026, could reinforce rather than undermine confidence in MAZE.

The analysts note that two mechanistically distinct compounds from different companies with different chemical scaffolds showing consistent proteinuria reductions across APOL1 high-risk populations constitute strong and reproducible target validation. A positive AMPLIFIED result could simultaneously confirm MZE829's mechanism, expand physician awareness, build out genetic testing infrastructure, and broaden payer engagement for the entire APOL1 inhibitor class.

Near-Term Catalysts and Open Questions

The analysts identify the formal HORIZON data presentation at a medical conference as the most important near-term MAZE-specific catalyst, expected to include cohort-specific confidence intervals, the full waterfall plot, eGFR directional trends, and pharmacokinetic substudy results. Open questions include what biomarker or enrichment strategy Maze can embed in the diabetic pivotal design to prospectively identify APOL1-primary patients, and what the eGFR trajectory looks like in the HORIZON diabetic patients. The firm also intends to convene an investor-focused KOL call to further explore the implications of HORIZON for the AMPLIFIED and AMPLITUDE trial readouts.

Valuation and Risks

H.C. Wainwright's US$110.00 price target is based on an equally weighted composite of a PE-based valuation of US$88 per share (25x multiple on taxed and diluted 2034 EPS of US$9.00 discounted to December 2026 at 12%) and a DCF-based valuation of US$132 per share (12% discount rate, 2% terminal growth rate).

MAZE currently trades at US$29.00, with a 52-week range of US$6.71 to US$53.65, a market cap of approximately US$1.4B, and cash on hand of US$360M with no debt. Key risks include clinical failure of MZE782 or MZE829, failure to obtain regulatory approval in the US or EU, and failure to achieve peak commercial revenue estimates due to market size, penetration rates, or pricing dynamics.