Maze Therapeutics, Inc.

Good day and welcome to the May Therapeutics Horizon MZE829 Top Line Data conference call. All participants will be in a listen-only mode. Should you need assistance, please signal conference specialists by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. And to withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Ms. Amy Backworld. Please go ahead.

Good morning, all, and thank you for joining us. Today, we will be discussing this morning's announcement of positive tap line data from the Phase II Horizon Trial of MZE829, an oral small molecule dual mechanism APOL1 inhibitor for the treatment of broad APOL1-mediated kidney disease, or AMKD. Please note this conference call is being recorded. Before we start, I would like to remind you that today's conference call will include forward-looking statements. Such statements represent management's judgment and intention as of today and involve assumptions, risks, and uncertainties. MAIS undertakes no obligation to update or revise any forward-looking statements. Please refer to MAIS's filings with the SEC, which are available from the SEC or on the MAIS website for information concerning the risk factors that could affect the company. Joining us on today's call are Jason Coloma, CEO of Maize, and Harold Bernstein, President of R&D and Chief Medical Officer at Maize. Today's presentation will begin with introductory remarks from Jason, followed by Harold, who will review the trial design and the data announced today. Jason will then provide closing remarks before we are joined by Misbah Tahir, Chief Financial Officer of Maize, and open up the call for Q&A. I will now turn the call over to Jason.

Thank you, Amy. Good morning, everyone, and thank you, Ann, for joining us. Before we start the call, I want to take a moment to give heartfelt thanks to the patients who are part of Horizon, as well as their families, caregivers, physicians, investigators, and MAIS employees who are all integral to today's announcement. Before we dive into our AMKD program and the data announced today, I'd like to provide an overview of our work at MAIS. We are a clinical stage biopharmaceutical company harnessing the power of human genetics to develop novel, small-molecule precision medicines to transform the lives of patients with kidney and metabolic diseases. As you can see from our pipeline, the Maize Compass platform has already delivered multiple clinical stage and preclinical programs in kidney and metabolic diseases. We are also well-capitalized to advance our pipeline and to deliver multiple catalysts over the coming months. but expected cash runway into 2028 based on our current business plan. On this next slide, we provide an overview of broad AMKD, our focus for today. Six million patients in the U.S. alone have the genetic variants that cause AMKD. Of those patients, one million have some form of kidney disease, and at least 250,000 individuals could benefit from a therapeutic approach based on the protein area cutoff of 300 milligrams per gram that was set for Horizon. At a major kidney medical conference late last year, we showed that about 40% of AMKD patients are diabetic, while about 60% are non-diabetic. These data were reinforced by multiple external studies. Despite the prevalence and the severity of the disease, there remains no approved therapy for AMKD. MZE829 stands out as a truly differentiated potential therapy for AMKD, due to its dual mechanism, which blocks the APOL1 pore and disrupts pore assembly in kidney cells. This is crucial for treatment as APOL1 pores rapidly turn over in kidney cells, so the ability to disrupt pore assembly has the potential to make MZE829 significantly more potent than other molecules for the treatment of AMKD. Proteinuria reduction is viewed across the field as a key clinical surrogate of disease outcome across a variety of CKD presentations. In terms of numerical measures, a 30% or greater reduction in UACR, or urine albumin creatinine ratio, relative to baseline is broadly accepted as clinically meaningful and would demonstrate clinical proof of concept in broad AMKD. In addition to its broad use in clinical development across other programs, In clinical guidelines, we have previously guided that seeing a UACR reduction of 30% or more from baseline in the Horizon study of MZE829 would meet the bar for demonstrating clinical proof of concept, and importantly, inform our plans for advancement into a pivotal program in AMKD. To frame the results based on analysis of published results, a different 801 inhibitor in FSGS patients demonstrated a mean reduction of about 43% in UACR and proceeded to a pivotal study. And now, I am thrilled to share our positive Phase II results. Today's data are the first to demonstrate results in broader, more moderate patients with AMKD, including those with diabetes. MZ829 demonstrated a favorable safety profile and was well tolerated across patients in the HORIZON study consistent with prior Phase I studies. I'm very pleased to share with you today that we have exceeded the 30% bar with MZE829 demonstrating 36% mean reduction in UACR in broad AMKD. In patients with FSGS, we showed a 61.8% mean reduction in UACR. The FSGS data we present from Horizon today reinforce MZE829's potentially best-in-class efficacy in AMKD and differentiation through its dual mechanism of action. In patients without diabetes, we saw a 48.6% mean reduction in UACR. 50% of patients achieved a reduction greater than 30%, demonstrating a meaningful reduction across these patients. Based on the highly promising results announced today, we intend to advance MZE829 into a pivotal program and look forward to providing updates on our regulatory progress and details on our clinical development plans over the course of the year. We are also reporting today some early promising data in patients with AMKD and diabetes. As Horizon continues to enroll, we will gather more data on these patients to inform next steps and plan to share an update in the future. And with that, I will turn the call over to Harold to discuss the positive data in further detail.