SLC6A19

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

MZE782 is a potential first-in-class, oral, small molecule therapy targeting SLC6A19 Proof of mechanism data anticipated 2H 2025 SOUTH SAN FRANCISCO, CA, USA I October 01, 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 that the first participants have been dosed in the company’s Phase 1 clinical trial evaluating MZE782 in healthy volunteers. MZE782 is a potentially first-in-class, oral, small molecule targeting the solute transporter, SLC6A19. MZE782 has the potential to initially address approximately five million of the approximately 37 million chronic kidney disease (CKD) patients in the United States who have inadequate responses to currently available CKD therapies. “CKD is a serious and progressive disease that impacts millions of people in the United States, with standard therapies focusing on slowing disease progression, rather than targeting the underlying genetic drivers of disease,” said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. “Using our Compass platform, we identified the solute transporter SLC6A19 as a promising treatment target to address a subset of patients with CKD and have designed MZE782 to phenocopy the kidney protective effects of SLC6A19 protective variants. MZE782 has the potential to be a first-in-class therapy to treat approximately five million patients that do not respond to currently available treatments. This is our third clinical program, and the initiation of this first-in-human clinical trial is an important step forward in understanding the therapeutic potential of MZE782. The trial is designed to not only evaluate its safety and tolerability, but also to provide pharmacokinetic and pharmacodynamic insights using a non-invasive biomarker intended to optimize the design of future clinical trials in patients. We expect to provide initial results of this clinical trial, including potential proof of mechanism utilizing these biomarkers, in the second half of 2025.” The Phase 1 clinical trial is a randomized, double-blind, placebo-controlled single and multiple ascending dose study in healthy volunteers designed to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics as measured by urinary excretion of known SLC6A19 cargo, e.g., neutral amino acids. Beyond its use as a potential standalone therapy, MZE782 may also provide a significant benefit to patients in combination with standard of care, including as a complementary treatment to current approved regimens, or as an alternative option for those patients who do not adequately respond to the current standard of care. 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

Merck's surprise Gardasil decline in China, Leqembi's regulatory setback in Europe, and several U.S. lawmakers' plan to target certain Chinese clinical trial sites made our news this week. Merck is trying to determine the reasons behind the surprise decline of Gardasil in China. Eisai and Biogen's Leqembi was rejected by European authorities amid a continued slow sales ramp. Lawmakers behind the BIOSECURE Act are trying to block drugmakers from working with certain Chinese clinical trial sites. And more.1. Merck mystified by sudden 'step down' in Gardasil sales in ChinaMerck’s Gardasil suddenly slowed down in China. The HPV vaccine franchise has been a big growth driver for Merck’s overall business, having recently helped the company surpass AstraZeneca to become the biggest global pharma in China by sales. And the company’s 9% stock price declined after the news spoke to the vaccine’s importance. Merck is working with its local partner Zhifei Biological Products to understand the situation, and it already has a few theories.2. Eisai, Biogen's Alzheimer's med Leqembi turned down in Europe—but analyst says it's merely a 'delay'Biogen retains biosimilars as Eisai-partnered Leqembi plows ahead amid business pivotEisai, Biogen show Leqembi provides added benefits over time as Alzheimer's showdown with Lilly heats upEisai and Biogen’s Leqembi continued its slow ramp, with second-quarter sales reaching $40 million, including $30 million from the U.S. The drug’s expansion efforts hit a snag as regulators at the European Medicines Agency declined to recommend the anti-amyloid drug, citing a “small” benefit and ARIA as a safety concern. Meanwhile, an extended study showed Leqembi’s benefit in cutting average cognitive declines appeared to widen to 31% over three years, compared with 27% in the original 18-month study.3. Congress targeting trials at Chinese military hospitals and in Xinjiang Uyghur Autonomous Region (Biocentury)The House Select Committee on the Chinese Communist Party, the driving force behind the draft BIOSECURE Act, has set its eyes on the next target in its crackdown against China. Lawmakers are looking for ways to block drugs seeking U.S. approvals from being tested at facilities associated with the Chinese army, including those that serve civilian patients, Biocentury reports, citing people familiar with the matter.4. With BIOSECURE Act looming, WuXi AppTec shows declining revenueAs the draft BIOSECURE Act threatens to push WuXi AppTec out of the U.S. market, the CRO giant’s business has so far remained relatively stable. The company’s U.S. sales, which accounted for 62% of the firm’s total, only fell by 1% in the first half of 2024. As the bill moves forward, WuXi spent $360,000 on lobbying efforts in the second quarter, more than tripling the $100,000 it spent in the fourth quarter of 2023.5. Takeda's Entyvio holds onto IBD market share despite threat from AbbVie's SkyriziTakeda takes $140M charge on failed epilepsy drug, while touting continued FDA potentialLundbeck leaves Trintellix to partner Takeda in the US, opting for royalties as it focuses efforts on RexultiDespite the entry of newer inflammatory bowel disease therapies such as AbbVie’s Skyrizi, Takeda’s Entyvio still grew sales by 7.6% during the three months ended in June, reaching $1.5 billion. The company took an impairment charge of about $143 million tied to the Ovid Therapeutics-partnered epilepsy med soticlestat’s recent phase 3 flop. Meanwhile, the Japanese pharma will take full U.S. control of depression drug Trintellix as its long-time partner Lundbeck wants to reallocate resources. The drug will lose U.S. patent protection at the end of 2026.6. Otsuka pays $800M for Jnana Therapeutics and its clinical-stage PKU drugThe dealmaking streak among Japanese pharmas continues. Otsuka is acquiring Jnana Therapeutics for $800 million, plus up to $325 million in milestones, to obtain a clinical-stage oral phenylketonuria (PKU) drug coded JNT-517, an allosteric small-molecule inhibitor of SLC6A19. A registrational study for the med is planned for next year.7. Kyowa Kirin looks to cut small molecule research and manufacturing jobs, slims down in AsiaKyowa Kirin is making some major adjustments to its business. The Japanese pharma is planning “a significant reduction” in small molecule research activities as it focuses on biologics. It’s also looking to trim some manufacturing jobs. In two separate deals, Kyowa will divest its Chinese operations to WinHealth Pharma and transfer rights to seven established brands in certain Asian markets to DKSH Holding.8. Instil refills pipeline in $2B biobucks deal with China's ImmuneOnco for 2 cancer assetsAfter Akeso and Summit Therapeutics’ positive readout for their PD-1xVEGF bispecific ivonescimab against Merck’s Keytruda in a Chinese phase 3 trial, Instil Bio has agreed to pay Shanghai biotech ImmuneOnco Biopharmaceuticals $50 million in upfront and near-term payments, plus up to $2 billion in potential milestones, for two assets, including a PD-L1xVEGF bispecific.Other News of Note:9. After tense standoff, AstraZeneca and Daiichi's Enhertu turned away by NICE on pricing grounds10. Chasing Pfizer and Lilly, Sun Pharma wins FDA nod for alopecia areata med Leqselvi11. South Korea regulator hits GSK for problems with asthma, acne drugs: report12. Ideaya, eyeing drug combos, bags option on Biocytogen bispecific ADC in $400M deal13. In Eisai, Medidata finds its first big buyer for new clinical trial management platform