Maze Therapeutics, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Sadia, thanks for having us at the conference. It's great and exciting to represent Maze this morning.

Well, let me start with a little bit of background on Maze for folks who might be newer to the story. Maze is a clinical-stage biopharmaceutical company focusing on the development of precision medicines for patients who suffer from kidney and metabolic diseases. We have three programs in clinical development. The first is MZE829. It's an APOL1 inhibitor for the treatment of patients who suffer from APOL1-mediated kidney disease or AMKD. We're currently testing 829 in a phase II study called HORIZON. During the course of the fireside chat, we'll be talking a lot about the HORIZON study. Our second asset is MZE782. That's an inhibitor of SLC6A19. That's a transporter of neutral amino acids, and we're testing that. We just announced that we initiated a phase II study to test that in patients who suffer from PKU.

Our third program is also MZE782, but we're also testing that drug in patients who suffer from chronic kidney disease or CKD, and we've guided to initiating that study in the first half, that phase II study, in the first half of next year. All of those drugs are small molecules. They're wholly owned by the company, and they're driven by the support of our Compass platform, which is our drug discovery engine in which we harness the power of human genetics to develop precision medicines.

Maybe a little bit of background on HORIZON and APOL1. If you suffer from AMKD, it starts with the genetics. If you have two copies of the APOL1 high-risk variants, you're at risk for developing a more aggressive, more accelerated form of chronic kidney disease. You may develop CKD at an earlier age, likely perhaps before you turn 50, and you may progress much faster and potentially even get to dialysis 10 years earlier. We're testing 829 in a phase II open label basket study of proteinuria CKD adults who have two copies of the APOL1 high-risk variants. We're testing across a spectrum of AMKD patients, so AMKD patients who have FSGS, as well as AMKD patients with diabetes and AMKD patients without diabetes. Certainly, we're testing for safety and tolerability, but we're also looking to see what level of proteinuria reduction we can achieve with MZE829.

Back in March of 2026, we released some initial data from the HORIZON study. We had 12 evaluable patients, and the results were positive. Not only was 829 well-tolerated, but we saw an average UACR reduction of 36% across the 12 evaluable patients. Half of those patients achieved a response, and we're defining response as a 30% or greater UACR reduction, and that's a threshold that's been established by KOLs based on research. There's linkages between that threshold and improved kidney outcomes, long-term benefits, so we set that as the bar that we would look at going forward. We saw a 36% average UACR reduction in half the patients were achieving a response. In FSGS patients specifically, there were four of them in that initial data set, we saw an average UACR reduction of 62% with three out of the four patients achieving a response.

But perhaps most importantly, we saw responses across each of the three patient segments: AMKD patients with FSGS, AMKD patients with diabetes, and AMKD hypertensive patients without diabetes. We saw responses across each of those three segments, and so we believe the potential is still very much there for MZE829 to work across the broad spectrum of AMKD patients.

I think it's too early to make conclusions based on that initial HORIZON data set, but we certainly liked what we saw in that data set across the range of patients. From a biology perspective, we know that if you have AMKD, you're more likely to develop a more aggressive form of CKD and to progress faster and reach dialysis faster, irrespective of where you are on that spectrum. So we see that faster progression in patients with diabetes, without diabetes, with FSGS, without FSGS. So APOL1 impacts all those different patient segments. We also know that there's a protective variant called N264K that confers protection for these patients irrespective of their diabetes status or FSGS status, and we've used that variant to inform the design of MZE829.

So in theory, and based on what we saw in the initial data set from HORIZON, we think 829 could still very much work across those segments of patients.

Yeah. We talked about the three different segments that we're testing in HORIZON, AMKD patients with FSGS, with diabetes, hypertensive without diabetes. We estimate that there are 250,000 of such patients in the United States. AMKD predominantly impacts people, starting with the genetics, going back to the genetics, impacts people of West African descent, 250,000 potential patients in the United States. There are no approved treatments today. FSGS, we've estimated to be roughly 10,000 patients or so, but it's possible that folks have underestimated that patient population. Recall that it is a biopsy-driven diagnosis, so it's relatively clean in that respect. As we're finding, as more and more patients get biopsied, as awareness around FSGS with newly approved treatments and awareness around AMKD grows, it certainly wouldn't be surprising if we see that estimate of FSGS patients grow over time.