Xanomeline Tartrate/Trospium Chloride

COBENFY is the first major advance in schizophrenia treatment in decades, offering a novel mechanism of action distinct from other therapies COBENFY has already been included in China’s national-level schizophrenia treatment guidelines, underscoring the urgent need for new therapeutic options in China SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 23, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced that China’s National Medical Products Administration (NMPA) approved the New Drug Application (NDA) for COBENFY® (xanomeline and trospium chloride) for the treatment of schizophrenia in adults. COBENFY is the first schizophrenia therapy with a novel mechanism of action approved in over 70 years [1], offering a fundamentally new approach to treating schizophrenia. By selectively activating M1 and M4 receptors in the brain, COBENFY addresses core disease pathways beyond traditional dopamine-blocking antipsychotics. Schizophrenia is a chronic and often disabling mental health disorder affecting how a person thinks, feels, and behaves. It is characterized by three core symptom domains including positive symptoms (e.g., hallucinations and delusions), negative symptoms (e.g., deficits in motivation, pleasure and social withdrawal), and cognitive impairment (e.g., deficits in memory, concentration, and decision-making). In China, despite the availability of antipsychotic therapies, many patients experience inadequate improvement across symptom domains and intolerable side effects. “We are pleased to receive NMPA approval for COBENFY, marking a groundbreaking milestone for schizophrenia care in China,” said Rafael G. Amado, M.D., President, Head of Global Research and Development at Zai Lab. “Approximately 8 million [2] adults in China are living with schizophrenia, many of whom continue to struggle with persistent symptoms or challenging side effects from existing therapies. With its broad symptom improvement and unique safety profile, COBENFY has the potential to redefine how schizophrenia can be managed, and we look forward to bringing this transformative therapy to patients as soon as possible.” “COBENFY represents the first truly new therapeutic approach for schizophrenia in decades,” said Prof. Gang Wang, M.D., Dean of Beijing Anding Hospital, Capital Medical University and the leading principal investigator for the Phase 3 China study. “COBENFY has demonstrated comprehensive improvement across positive, negative and cognitive symptoms, while avoiding many of the adverse effects commonly associated with traditional antipsychotics, including weight gain, hyperprolactinemia, and a problematic movement disorder called extrapyramidal symptoms, offering a meaningful new option for patients.” The NMPA’s approval of COBENFY is supported by the results from a Phase 1 pharmacokinetics (PK) study conducted in China, the Phase 3 China study (ZL-2701-001), and data from three global EMERGENT clinical studies. In September, the Chinese Medical Association released the “China Schizophrenia Prevention and Treatment Guidelines (2025 Edition)” which included COBENFY as a novel treatment. This is the first national-level guideline to include COBENFY. [1] Kingwell, K. (2024). Muscarinic drugs breathe new life into schizophrenia pipeline. Nature Reviews Drug Discovery, 23(9), 647–649. https://doi-org.libproxy1.nus.edu.sg/10.1038/d41573-024-00129-w [2] Huang, Y., Wang, Y., Wang, H., Liu, Z., Yu, X., Yan, J., Yu, Y., Kou, C., Xu, X., Lu, J., Wang, Z., He, S., Xu, Y., He, Y., Li, T., Guo, W., Tian, H., Xu, G., Xu, X., … Wu, Y. (2019). Prevalence of mental disorders in China: A cross-sectional epidemiological study. The Lancet Psychiatry, 6(3), 211–224. https://doi-org.libproxy1.nus.edu.sg/10.1016/S2215-0366(18)30511-X About COBENFY COBENFY (xanomeline and trospium chloride) is a combination of an oral M1/M4-preferring muscarinic acetylcholine receptor agonist and a muscarinic acetylcholine receptor antagonist. This combination is in development for the treatment of psychiatric conditions. Xanomeline stimulates muscarinic receptors in the central nervous system implicated in these conditions, as compared to current antipsychotic medicines, which mostly target dopamine or serotonin receptors. Trospium does not appreciably cross the blood-brain barrier and acts peripherally to mitigate xanomeline-induced peripheral cholinergic adverse events. Zai Lab has an exclusive license from Karuna Therapeutics, Inc., a company acquired by Bristol Myers Squibb, to develop, manufacture, and commercialize COBENFY in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively). About Schizophrenia Schizophrenia is a chronic and often disabling mental health disorder affecting how a person thinks, feels, and behaves. It is characterized by three core symptoms including positive symptoms, negative symptoms and cognitive impairment – all of which can severely impact functioning, with only 10% of patients gainfully employed and many struggling to meet adult milestones, such as living independently. The life expectancy of people living with schizophrenia is reduced by 10-20 years compared to a healthy population. Schizophrenia affects nearly 24 million people worldwide and is most commonly treated with antipsychotics. Unfortunately, many people with schizophrenia continue to experience limited efficacy in negative symptoms as well as cognitive symptoms or problematic side effects including weight gain, hyperprolactinemia, and a problematic movement disorder called extrapyramidal symptoms while on current antipsychotic therapy. Due to these problems, approximately 75% of patients discontinue medication before 18 months. When schizophrenia treatment is discontinued, it can adversely impact patient health including relapse, hospitalization, and longer time to remission. Approximately 8 million adults in mainland China are living with schizophrenia, yet few are obtaining adequate symptom improvement with the current treatment using antipsychotics. Like patients globally, there is a significant need for more comprehensive effective therapies with improved safety to treat patients with schizophrenia in Greater China. About Zai Lab Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global. Zai Lab Forward-Looking Statements This press release contains forward-looking statements relating to our future expectations, plans, and prospects, including, without limitation, statements regarding the prospects of and plans for developing and commercializing COBENFY, the potential benefits of COBENFY, and the potential treatment of schizophrenia and other psychiatric and neurological conditions. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business decisions, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission. We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Our SEC filings can be found on our website at www.zailaboratory.com and the SEC’s website at www.sec.gov. View source version on businesswire.com: https://www.businesswire.com/news/home/20251223179134/en/ For more information, please contact: Zai Lab Investor Relations: Christine Chiou / Cyan Liu +1 (917) 886-6929 / +86 195 3130 8895 christine.chiou1@zailaboratory.com / cyan.liu@zailaboratory.com Zai Lab Media: Shaun Maccoun / Xiaoyu Chen +1 (415) 317-7255 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited

Steve Paul is back with a fresh take on schizophrenia drugs, co-founding a new biotech called Syremis Therapeutics that’s already landed $165 million in a Series A, Endpoints News has learned. The serial founder and force behind the $14 billion sale of Karuna Therapeutics is making his next bet on the M1/M4 muscarinic agonist approach that helped spark a resurgence in psychiatric drug development and pharma dealmaking. The Series A funding came together earlier this month, Syremis told Endpoints. For Paul, one goal is to beat Cobenfy, which he helped shepherd through clinical development in a rotation of executive positions over the years. While Cobenfy (formerly known as KarXT) is already being prescribed to patients — and companies such as MapLight Therapeutics are also making inroads — the target at Syremis is less about speed and more about pursuing a best-in-class approach. “It’s often not the first-in-class that become the most important medicines in a given space, if you look at statins or almost any drugs, SSRIs, SNRIs,” Paul, who was Karuna’s chair and CEO at one point, said in an interview. It’s the second or third drug that “becomes the most important medically and commercially.” The $165 million will get Syremis’ investigational M1/M4 muscarinic agonist and NMDA antagonist through Phase 2 proof-of-concept studies, set to begin around 2027, co-founder and CEO Elisabeth Kogan said in a joint interview with Paul. The Series A was led by Third Rock Ventures and Dexcel Pharma, which is known for being the founding investor in Roivant Sciences. Other backers include Bain Capital Life Sciences, Google Ventures, QVT and Pictet. Syremis’ origins trace to Israeli startup Clexio Biosciences, which has brought multiple experimental neuro medicines into the clinic since its 2018 founding. Clexio spun out Syremis in this year’s second quarter with many of its team members moving to the new entity, which now has about 30 employees. Other Syremis co-founders include chief development officer Elena Kagan and technology chief Menashe Levy. Kogan declined to comment on the future of the Clexio pipeline programs that didn’t make the move. Paul said his Karuna team never came across Clexio and its M1/M4 program while developing Cobenfy, describing the Israeli company as having been mainly in stealth mode. Kogan reached out to him after Bristol Myers Squibb bought Karuna. Now, Syremis’ ST-905 is in a healthy volunteer study in Europe, with plans to expand that Phase 1 into the US next year, Kogan said. The M1/M4 muscarinic agonist is being tested as a once-daily oral drug, versus Cobenfy’s twice-daily profile. Paul and Kogan said they haven’t seen any liver toxicities with ST-905. Paul said ST-905 has “much higher oral bioavailability, so less variability patient to patient” than Cobenfy. Eventually, Syremis plans to test a once-monthly injectable version as well, in hopes of helping with compliance of the drug, the CEO said. Adding an injectable would also likely extend the drug’s life on the market. Lyndra Therapeutics, another biotech working on a long-acting version of a different type of schizophrenia drug, shut down earlier this year. Syremis will look to repeat Karuna and Bristol Myers’ strategy of bringing ST-905 into other indications, such as Alzheimer’s disease psychosis and agitation, Kogan said. Beyond schizophrenia, Syremis is also in the major depression space with an NMDA antagonist called ST-901 that will enter Phase 1 around the middle of next year, Kogan said. Johnson & Johnson broke open this field with its blockbuster nasal spray, the esketamine product known as Spravato. Axsome Therapeutics has an oral NMDA-directed drug called Auvelity; Syremis is working on an oral medicine as well. The biotech’s board includes Paul, Kogan, Dexcel co-CEOs Ilan Oren and Uri Oren, Third Rock’s Reid Huber, and Bain Capital’s Ray Sanchez. Sanchez was previously chief medical officer of Cerevel. Shortly after AbbVie bought Cerevel, its schizophrenia drug failed a key clinical trial, dooming AbbVie’s hopes of quickly following Cobenfy.