Maze Therapeutics, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Good morning, Ananda. It's great to be here. Thanks for having us. Thank you.

Let me give a little bit of background on Maze for folks who might be newer to the story. We are a clinical-stage biopharmaceutical company focused on the development of precision medicines for the treatment of kidney and metabolic diseases. We have three programs in clinical development. The first is MZE829. That's an APOL1 inhibitor for the treatment of APOL1-mediated kidney disease, or AMKD. We're currently testing that drug in a phase II study that we call HORIZON, and we've guided to data from that trial end of this year, early next year. Our second program is MZE782. That's an inhibitor of SLC6A19, a neutral amino acid transporter, and we're developing that for the treatment of PKU. We just announced last month the initiation of our phase II- Right study in PKU.

That's a trial we refer to as CIPheR. The third clinical program is also MZE782. It's the same drug, but we're developing it for the treatment of chronic kidney disease, or CKD, and we've guided to initiating a phase II study in CKD in the first half of next year. All three of the programs I just mentioned are small molecule drugs, and Maze owns all the rights to those drugs. They're all built with the support of our Compass platform, in which we harness the power of human genetics to develop precision medicines. That's a little bit of the background on Maze.

These are exciting times for the company and for the field. I referred to a couple of our programs and our upcoming catalysts. For MZE829, our APOL1 inhibitor drug in AMKD, we've guided to data from our phase II HORIZON study end of this year, early next year. For our phase II MZE782 program in PKU, we just initiated the phase II clinical trial, CIPheR, and we've guided to top-line data in 2027. We're going to learn a lot about the company, our programs over the next 12 to 18 months, but there's certainly significant work to do from there.

That's great. Let me give a little bit of background on the program, maybe let's start with the genetics. If you have two copies of the APOL1 high-risk variants, you're at risk for developing a more severe, more aggressive, more accelerated form of CKD. You're likely to develop it at an earlier age, perhaps before you turn 50, and you're likely to progress to dialysis faster, maybe as fast as 10 years earlier than you normally would with CKD. We started this trial, this phase II trial, HORIZON, to test MZE829 in proteinuric CKD adults across all the different patient groups within AMKD. We're testing it and focusing on AMKD patients with FSGS, AMKD patients with diabetes, and AMKD patients without diabetes, hypertensive non-diabetics.

In March of this past year, we released initial data from that HORIZON study, and it was highly encouraging and positive to us and supported advancing the drug and continuing to dose patients in HORIZON. What we saw was, we saw responses in each of those three patient groups that I just mentioned, FSGS patients, diabetic patients, hypertensive non-diabetic patients. Across all the patients, we achieved an average UACR reduction of 36% with a response rate of 50%, response rate being defined as patients who achieve a 30% or greater reduction in UACR. Within FSGS patients, that particular subgroup, we had four of those patients. We saw an average UACR reduction of 62%, with three out of the four patients achieving response. Across the board, MZE829 appeared to be well-tolerated.

Those results certainly were encouraging and promising to us and supported continuing to dose patients and accelerating the program as quickly as we could. We're continuing to dose patients now. Again, we've guided to releasing the final data from HORIZON end of this year, early next year.

Well, to your point, there's significant unmet need. We estimate that there are 6 million patients in the U.S. who have two copies of the APOL1 high-risk variants. Roughly 1 million of those individuals have CKD, and we think roughly 250,000 patients in the U.S. could benefit from an APOL1 inhibitor. To your point, there are no approved treatments today, so there's significant unmet need. At this time, we're just focused on executing HORIZON and generating that data to support moving forward. I should mention, we'd also have guided to initiating a pivotal program with MZE829 in the first half of next year. The HORIZON data that we're generating now will be incredibly informative to the design of that study along with some other initiatives that are going on.

There's a public-private initiative called PARSOL® Shield, which is focused on accelerating drug development and clinical development in kidney diseases, and they seem to be focusing on surrogate endpoints. They may release some recommendations in the coming months. HORIZON learnings from the PARSOL® Shield initiative certainly will help inform how we develop MZE829 going forward. It comes back to there's significant unmet need.