Maze Therapeutics, Inc.

MZE829 Well-tolerated with Dose-proportional Pharmacokinetics Supporting Once Daily Dosing Data Support Advancement of MZE829 into Planned Phase 2 Clinical Trial in Patients with AKD Data Presented Today at the American Society of Nephrology Kidney Week 2024 SOUTH SAN FRANCISCO, CA, USA I October 25, 2024 I Maze Therapeutics, a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, today announced positive results from the Phase 1 clinical trial of MZE829 in healthy volunteers. MZE829 is an oral, small molecule inhibitor of APOL1 that Maze is advancing as a potential treatment for people living with APOL1 kidney disease (AKD), a subset of chronic kidney disease estimated to affect over one million patients in the United States alone. APOL1 is a protein encoded by the APOL1 gene in humans. Genetic variants of the gene (G1 and G2) are associated with increased risk for a spectrum of progressive kidney diseases in people of West African ancestry. MZE829 was identified through insights generated from Maze’s proprietary, purpose-built platform, Maze Compass™. The first-in-human Phase 1 randomized, placebo-controlled, single and multiple ascending dose trial was designed to evaluate the safety, pharmacokinetics (PK), food effect, and potential drug interactions of orally administered MZE829 in healthy volunteers and enrolled 111 participants. Results demonstrated that MZE829 was well tolerated at single doses up to 480 mg and multiple doses up to 350 mg, with all treatment-related adverse events reported as mild and no severe or serious adverse events reported. Dose-proportional PK was observed with low variability across doses. The observed half-life of approximately 15 hours supported that MZE829 can be dosed once daily. Evaluation of potential drug interactions demonstrated that MZE829 has the potential to be administered together with standard of care medicines used in patients with AKD, including cyclosporine and tacrolimus. “We are very pleased with the positive outcome of our Phase 1 trial of MZE829, demonstrating its tolerability and establishing the dosing regimen that we plan to take into our Phase 2 trial in patients with AKD,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “Based on its mechanism targeting APOL1, as well as genetics data derived through our Compass platform, we believe that MZE829 has the potential to address a large population of patients with AKD. As such, we intend to enroll patients with a wide array of characteristics into our Phase 2 trial to reflect the full spectrum of AKD patients and determine which patients may benefit from treatment with MZE829.” The company anticipates that the Phase 2 clinical trial will employ an open-label basket design to include a range of clinical phenotypes and moderate to severe forms of disease as determined by level of proteinuria. The Phase 2 trial will include AKD patients carrying two copies of the high-risk APOL1 alleles (G1 and G2) and evaluate efficacy using uACR reduction across a broad AKD population. The company expects to initiate the Phase 2 trial in the first quarter of 2025. About Maze Therapeutics Maze Therapeutics is a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, with a focus on renal, cardiovascular and related metabolic, including obesity. The company is advancing a pipeline using its Compass platform, which provides insights into the genetic variants in disease and links them with the biological pathways that drive disease in specific patient groups. The company’s pipeline is led by two wholly owned lead programs, MZE829 and MZE782, each of which represents a novel precision medicine-based approach for chronic kidney disease. For more information, please visit mazetx.com , or follow us on LinkedIn and X (formerly Twitter). SOURCE: Maze Therapeutics

First-in-Human Data from Phase 1 Trial of MZE829 Support Advancement to Phase 2; Phase 2 Trial Expected to Initiate Early 2025 Preclinical Data for MZE782 Support Recent Phase 1 Trial Initiation in Healthy Volunteers SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, today announced that upcoming presentations at the American Society of Nephrology’s (ASN) Kidney Week, being held October 23-27, 2024, in San Diego, and the American Society of Human Genetics Annual Meeting, being held November 5-9, 2024, in Denver, will highlight the company’s two lead clinical programs to treat kidney disease. Data from the company’s Phase 1 trial of MZE829 for the treatment of APOL1-mediated kidney disease will be presented at ASN Kidney Week 2024, and new preclinical data supporting the potential of its second lead program, MZE782, a potentially first-in-class, oral, small molecule targeting the solute transporter, SLC6A19, will be presented at ASN Kidney Week 2024 as well as at the American Society of Human Genetics Annual Meeting. “We look forward to presenting new, positive data for our two lead programs, MZE829 and MZE782, both of which have the potential to address severely underserved patients living with kidney disease,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “Importantly, the Phase 1 data from our study of MZE829 in healthy volunteers support this program’s advancement into our planned Phase 2 trial in patients, which we expect to initiate in the coming months. In addition, the preclinical data we’ll present from our MZE782 program formed the basis of our investigational new drug application and recently initiated Phase 1 trial in healthy volunteers. We are pleased by the progress we continue to make at Maze and excited to learn more about the potential of these programs, generated through novel insights from our Compass platform, as they progress through the clinic.” Details of the presentations are as follows: American Society of Nephrology Presentation Information Title: A Phase 1 Study in Healthy Adults of the Safety, Tolerability, and Pharmacokinetics of MZE829, an APOL1 Inhibitor for the Treatment of APOL1-Mediated Kidney Disease (AMKD) Date & Time: October 24, 2024, 10 a.m. – 12 p.m. PT Presenter: Susan Limb, M.D., Ph.D. Title: SLC6A19 (BOAT1) allelic series: loss of function is associated with improved kidney function Date & Time: October 24, 2024, 10 a.m. – 12 p.m. PT Presenter: Rob Graham, Ph.D. Title: Genetic ablation of SLC6A19 is protective against renal damage in mouse models of chronic kidney disease Date & Time: October 26, 2024, 10 a.m. – 12 p.m. PT Presenter: Laura Sanman, Ph.D. American Society of Human Genetics Presentation Information Title: Functional characterization of Hartnup’s disease missense variants in SLC6A19 shows loss of function by disparate mechanisms Date & Time: November 6, 2024, 2:30 – 4:30 p.m. MT Presenter: Nathan Sallee, Ph.D. Title: SLC6A19 loss of function is associated with improved kidney function and metabolic reprogramming of kidney cells Date & Time: November 9, 2024, 8:45 a.m. MT Presenter: Sahar Mozzafarri, Ph.D. About Maze Therapeutics Maze Therapeutics is a clinical-stage biopharmaceutical company harnessing the power of human genetics to develop novel, small molecule precision medicines for patients living with common diseases, with a focus on renal, cardiovascular and related metabolic diseases, including obesity. The company is advancing a pipeline using its Compass platform, which provides insights into the genetic variants in disease and links them with the biological pathways that drive disease in specific patient groups. The company’s pipeline is led by two wholly owned lead programs, MZE829 and MZE782, each of which represents a novel precision medicine-based approach for chronic kidney disease. For more information, please visit mazetx.com , or follow us on LinkedIn and X (formerly Twitter). Contacts Jillian Connell, Maze Therapeutics jconnell@mazetx.com (650) 850-5080 Media: Dan Budwick, 1AB dan@1abmedia.com

本届大会以“共建创新生态 共赢产业未来”为主题，聚焦生物医药出海与国际化创新、创新药投融资、医疗器械等产业发展风向标，打造“高端化、国际化、专业化、立体化”的年度盛会。 美东时间2024年10月4日，意大利公司Recordati宣布与赛诺菲达成一项协议，获得Enjaymo（sutimlimab）的全球销售权，这是目前唯一获准用于治疗冷凝集素病（CAD）的靶向生物制剂，冷凝集素病是一种罕见B细胞淋巴细胞增生性疾病。 根据协议条款，Recordati将支付给赛诺菲8.25亿美元的预付款，如果净销售额达到或超过高峰年预期销售额的上限，还将支付最高2.5亿美元的额外商业里程碑付款。 过去12个月（截至2024年8月），Enjaymo带来的收入约为1亿欧元，预计2025财年的收入将超过1.5亿欧元，销售峰值可能达到2.5-3亿欧元，是目前水平的两倍多。 Recordati预计，该交易对2024年的收入贡献很小，但将立即增加息税折旧摊销前利润（EBITDA），到2025年，其利润率将高于目前罕见病公司的平均水平。 1 Enjaymo背后的战略转变 Enjaymo（sutimlimab）是一种人源化单克隆抗体，用于治疗成人CAD溶血。2022年，它获得了FDA、欧盟委员会（EC）和日本厚生劳动省的批准。这种慢性静脉注射治疗药物满足了CAD患者尚未得到满足的医疗需求。 从疾病市场来看，CAD在美国、日本和欧洲大约仅有11000名患者。 这是一种罕见病，B细胞产生的自身抗体会攻击并破坏红细胞。该病理过程在寒冷条件下触发，通常在3°C至4°C之间，患者会出现严重的衰弱性疲劳、虚弱和其他典型的贫血症状。 针对CAD，Enjaymo选择性地靶向C1补体蛋白，阻止补体级联的激活。这种作用机制使它能够有效阻断补体介导的红细胞破坏，且不会抑制凝集素和替代补体途径。 Enjaymo一直被视作赛诺菲快速增长的资产，但其销售额一直处于中等水平。2023 年，该疗法产生了近8000万美元的收入，按固定汇率计算，比前一年增长了200%以上。2024年上半年，Enjaymo同比增长近73%，带来约6000万美元的收入。 对于赛诺菲来说，Enjaymo的出售似乎是更广泛战略转变的一部分，该公司放弃了之前到2025年达到32%营业利润率的目标后，首席执行官Paul Hudson正在努力恢复投资者的信心。 对于罕见病药物公司Recordati来说，这笔交易为该公司的产品组合增加了第九个上市产品，Enjaymo的交易符合其公司在全球广泛的战略布局，扩大了其在美国、日本和欧洲的市场。 2 在巨头之间辗转 Enjaymo曾经历过多次易主。 2014年，总部位于旧金山的iPerian公司还在研发Enjaymo这款药物。就在那一年，BMS因其在神经退行性疾病领域的工作而收购了iPerian公司。 iPerian针对免疫系统的项目被剥离出来，单独成立了一家新的生物技术公司True North Therapeutics。 不过，True North公司并没有独立存活太久。2017年，它被渤健分拆出来的专注于血友病的Bioverativ公司收购。当时的Bioverativ首席执行官John Cox说，Enjaymo是这笔交易中的核心资产，填补了公司研究工作中的一个重要空白。 然而，2018年赛诺菲以110亿美元收购Bioverativ后，Enjaymo又易主了。 赛诺菲多次转向交易，以进一步扩大其罕见病业务。在过去一年里，这家法国制药巨头就获得一种治疗肌肉萎缩症的实验性药物的权利，并斥资22亿美元收购了一家生物技术公司及其治疗罕见肺病的潜在治疗方法。 赛诺菲还试图从初创公司Maze Therapeutics那里获得治疗庞贝病的药物许可，但在面临联邦贸易委员会的诉讼后放弃了该交易。 通过收Bioverativ，赛诺菲获得了Enjaymo以及另一种现在上市的血友病药物Altuviiio。 参考资料： 1.RECORDATI ANNOUNCES AGREEMENT TO ACQUIRE THE GLOBAL RIGHTS TO ENJAYMO®, STRENGTHENING ITS RARE DISEASES FRANCHISE 2.Sanofi’s rare disease drug finds yet another home；BioPharma Dive 3.Sanofi Offloads Rare Autoimmune Drug to Recordati in Potential $1B Deal；Biospace 同写意媒体矩阵，欢迎关注↓↓↓