Maze Therapeutics (NASDAQ:MAZE) is advancing a genetics-driven approach to drug development, using human genetic analyses to identify gene variants linked to disease and then applying those insights to small-molecule programs focused primarily on kidney and metabolic disorders, CEO Jason Coloma said at Guggenheim’s 2026 Emerging Biotech Summit.
Coloma highlighted two clinical-stage programs as near-term priorities: MZE829 for APOL1-mediated kidney disease (AMKD), with clinical data expected later in the quarter, and MZE782, an SLC6A19 inhibitor that Maze plans to move into two Phase 2 studies later this year—one in phenylketonuria (PKU) and another in chronic kidney disease (CKD).
MZE829: Focus on “broad AMKD” and an upcoming readout
On study size, Coloma said Maze has guided to a patient count “in the similar size” and order of magnitude to what Vertex reported in a New England Journal of Medicine paper. He added the company is blinded to the data and will provide more specific patient numbers and cohort splits at the time of the readout.
Coloma also addressed diagnostic heterogeneity. Because patients are not biopsy-confirmed, some individuals in the non-diabetic cohort could have focal segmental glomerulosclerosis (FSGS), he said. However, he suggested these patients would be less likely to resemble the “higher range” nephrotic, high-proteinuria FSGS patients described in some prior sponsor studies.
What Maze considers “clinically meaningful” efficacy
Coloma said Maze’s goal is to be the first company to show clinical proof of concept in what he called “broad AMKD,” including patients with or without diabetes. He described a 30% reduction in UACR (urine albumin-to-creatinine ratio) relative to baseline as the level Maze would view as clinically meaningful for proof of concept.
Maze is also collecting UPCR (urine protein-to-creatinine ratio) and intends to report it, Coloma said, but he emphasized that investigators have advised UACR as the preferred efficacy measurement in more moderate disease populations like those in the trial. He also noted a broader shift among sponsors toward using UACR as a proteinuria endpoint.
In terms of data presentation, Coloma said Maze expects to provide both average results and patient-level detail to assess how many individuals achieve at least a 30% UACR reduction—information he said could help guide the selection of patients for a potential registrational study.
Mechanism and dose selection: blocking the pore and disrupting assembly
Coloma discussed Maze’s view of APOL1 disease biology, describing APOL1 risk variants as causing a “toxic gain-of-function” through overexpression of a pore-forming process in podocytes. He said the pore inserts into the cell membrane and enables cation influx that contributes to cellular toxicity.
While he said “minimally” sponsors aim to block the pore to prevent cation flux, he argued Maze’s approach differs mechanistically. Coloma said Maze believes it is important not only to block pore function but also to disrupt assembly of the pore, citing APOL1’s high turnover in podocytes (with literature estimates on the order of less than an hour). Under that dynamic, he suggested that disrupting assembly could matter because new pores can continually form.
He also described Maze’s approach to dose selection. While other sponsors have used an in vitro thallium flux assay to guide dosing, Coloma said Maze combined in vitro work with an in vivo BAC transgenic mouse model aimed at predicting proteinuria reductions. He argued the in vitro assay primarily reflects pore blocking, while the in vivo model may better represent disruption of pore assembly in addition to blocking.
Recruitment and growing APOL1 awareness
Coloma said Maze has not changed its guidance on timing and still expects to deliver MZE829 data by the end of the quarter, implying recruitment has remained on track. He attributed an improved environment for identifying APOL1 patients to several factors, including increased awareness driven by advocacy groups and academia.
He also pointed to practical developments supporting diagnosis:
- Genotyping availability for APOL1 variants on standard panels at LabCorp and Quest, which physicians can request.
- An ICD-10 code established last year, which he said is important for billability and may help track diagnosis rates as usage becomes more prevalent.
MZE782: Phase 2 plans in PKU and CKD, with biomarkers in focus
Coloma said Maze plans to advance MZE782 into two Phase 2 trials later this year: one in PKU (starting around mid-year, with the company previously indicating initiation by the second quarter) and one in CKD (in the second half of the year). He said Maze expects to provide more specifics on dosing, study design, and patient populations after the MZE829 readout.
In PKU, Coloma emphasized precedent from another sponsor demonstrating proof of concept for SLC6A19 inhibition, including reductions in plasma phenylalanine (Phe)—which he described as an approvable endpoint—and use of a non-invasive biomarker, urinary Phe excretion, that “maps very well” to plasma Phe reduction.
Referring to Maze’s data presented in September, Coloma said the company observed what it believes are “best-in-class” properties, including maximal target inhibition reflected by a more than 40-fold increase in the urinary Phe biomarker versus a 10-fold increase observed by the other sponsor at a certain dose in healthy volunteers. He contrasted that with the other sponsor’s PKU patient data showing a 60% reduction in plasma Phe at the highest dose but only 3 of 19 patients reaching below 360 micromolar—a threshold he said influences whether clinicians believe patients can come off a restrictive medical diet.
For CKD, Coloma said Maze was the first to identify a genetic relationship between SLC6A19 and CKD and the first to show in vivo proof of concept in a preclinical model, including comparisons to SGLT2 inhibitors. He also pointed to a “proof of mechanism” signal in healthy volunteers based on an eGFR “dip” that he said has been observed with approved CKD agents and is considered indicative of long-term renal protection.
Coloma said Maze is exploring two potential contributors to SLC6A19-related kidney benefits: a hemodynamic effect similar to SGLT2 inhibitors and an “orthogonal” mechanism involving reduced accumulation of toxic metabolites in the proximal tubule. He said the company plans to further explore and publish additional biology in future conferences.
About Maze Therapeutics (NASDAQ:MAZE)
Maze Therapeutics, Inc (NASDAQ: MAZE) is a clinical‐stage biotechnology company focused on the discovery and development of novel therapeutics by leveraging insights from human genetics and genomics. The company applies advanced data analytics and proprietary platforms to identify targets with strong genetic validation, aiming to de‐risk early drug discovery and accelerate the development of medicines for patients with serious diseases. Maze’s approach centers on translating naturally occurring human mutations into a deeper understanding of disease biology, with an emphasis on validating therapeutic hypotheses before advancing into the clinic.
Since its inception, Maze has assembled a diversified pipeline of programs across metabolic, immunological and other therapeutic areas.
