Maze Therapeutics, Inc. Common Stock Citigroup’s Biopharma Back to School Summit 2026

Eric, it's great to see you again, and I'm excited to represent Maze this afternoon. Just some background on Maze Therapeutics. We're a clinical stage biopharmaceutical company focused on developing precision medicines for kidney metabolic diseases. We have three programs in clinical development. Our lead program is MZE829. That's an APOL1 inhibitor for the treatment of patients who suffer from APOL1-mediated kidney disease, or AMKD. We're currently in a phase II trial, testing MZE829 in AMKD patients, and we've guided to data from this study, which we refer to as HORIZON, by the end of this year or early next year. We've also committed to initiating a pivotal program with MZE829 in the first half of 2027. Our second program is MZE782. That's an inhibitor of SLC6A19, a transporter of neutral amino acids.

We just announced last month that we initiated our phase II study of MZE782 for the treatment of patients with PKU, and we've guided to top-line data from that program in 2027. Our third program is also MZE782, the same drug. We're also testing that drug in patients who suffer from chronic kidney disease, or CKD. We've guided to initiating a phase II study in CKD in the first half of next year. All three of those programs, those drugs are small molecules. They're all wholly owned by Maze, and they're all built with the support of our Compass platform, our discovery platform, our discovery engine in which we harness the power of human genetics to develop precision medicines.

Yeah, I think the short answer to your question is there's a lot more work to be done here. Let's start with the genetics, as you were starting to do. If you have two copies of the APOL1 high-risk variants, you are at risk of developing a more aggressive, a more accelerated form of chronic kidney disease. You are potentially going to develop CKD at an earlier age, a younger age, potentially before you turn 50. You are likely, or you are at risk of reaching dialysis earlier, potentially as much as 10 years earlier. So it is a more aggressive, more accelerated form of CKD. The APOL1 high-risk variants were first described in literature in only just back in 2010, and there are no approved treatments today for AMKD. I also want to add that this is a disease that predominantly impacts people of West African descent.

We are starting from a very low base of awareness, and that is a key lever for testing, for enrollment in trials, et cetera. That is starting to change with sponsors like Maze in the field. There is certainly growing awareness of the disease. There is growing awareness of the need for testing, and with us and other sponsors, we are helping to drive that awareness. I suspect that over the next several years, the next several years of drug development and enrollment and testing will look very different than the last several years because the need is certainly there. I think the clinical data that we all collectively are generating in this field and the potential for new treatments to treat AMKD is only going to drive further testing.

Eric, I think this is an area of active exploration in the field. We estimate that there are roughly 6 million Americans who have two copies of the APOL1 high-risk variants. Roughly 15%-20% of that 6 million will actually develop CKD and eventually AMKD. It suggests that you need a second hit in order to develop or reach AMKD. There is a lot of work going on on what factors may represent that second hit, so to speak, whether it is genetic or more environmental. Some of the work we have seen or are doing suggests it might be more environmental, but there is a lot more work that needs to be done. We estimate currently, of the 6 million, roughly 1 million or so have CKD, and of that number roughly 250,000 patients in the U.S. could benefit from an APOL1 inhibitor drug such as MZE829.

That to us is the current addressable patient opportunity.

Sure. Let me start with some background on HORIZON. HORIZON is our Phase II open label basket study in which we are testing MZE829 in proteinuria CKD patients, adults who have two copies of the APOL1 high-risk variants. We are focusing on three segments within AMKD. The first is patients with FSGS, second, patients with diabetes, and then we have a third segment, patients without diabetes and without FSGS. We are testing across all three of those segments, a broad spectrum of AMKD patients. In March of this past year, March of 2026, we released some initial data from that HORIZON study, which is still ongoing. The results were really encouraging and positive to us at Maze. We had 12 evaluable patients. We saw responses defined as achieving a 30% or greater UACR reduction.

We saw responses in each of those three subtypes, and across all 12 evaluable patients, we saw a 36% average UACR reduction. Half of those patients achieved a response of 30% or more. Within FSGS patients specifically, we had four. We saw an average UACR reduction of 62%, with three out of those four patients achieving a response. These were highly encouraging results for us. Since we released that data in March, we have been focused on two priorities related to MZE829. The first is completing enrollment in HORIZON, and we have guided to releasing 10 to 15 patients' worth of data in each of those three segments by the end of this year, early next year. That 10 to 15 patient figure that I cited is inclusive of the patients we have already shown.

Sure. The second priority coming out of the data release is to get a pivotal trial with MZE829 up and running as quickly as possible, and we have guided to initiating a pivotal study in the first half of 2027.

The design and scope of that study is a topic of active discussion within the company. It is certainly going to be informed by our final HORIZON results, as well as our discussions with the FDA. A lot more to come on that.