Xanomeline Tartrate/Trospium Chloride

SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 17, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced that China’s National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) for KarXT for the treatment of schizophrenia in adults. “There are more than 8 million patients living with schizophrenia in China who face significant unmet needs due to the limited efficacy and undesirable side effects of current treatment options,” said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. “In clinical trials, KarXT demonstrated statistically significant reductions of schizophrenia symptoms along with a tolerable safety profile. If approved, KarXT has the potential to redefine the treatment landscape.” “KarXT is the first new class of treatment for patients with schizophrenia in several decades,” said Gang Wang, M.D., Dean of Beijing Anding Hospital, Capital Medical University and the leading principal investigator for the Phase 3 China study. “We are excited about this potentially transformative treatment option in clinical settings to benefit these patients as early as possible.” The NDA submission is supported by the results from a Phase 1 China Pharmacokinetics (PK) study, the Phase 3 China study (ZL-2701-001) and data from the global EMERGENT clinical programs. The China Phase 3 study met its primary endpoint, with KarXT demonstrating a statistically significant 9.2-point difference from placebo in the reduction in the Positive and Negative Syndrome Scale (PANSS) total score from baseline at Week 5 (-16.9 KarXT vs. -7.7 placebo, p=0.0014). The study also met all key secondary efficacy endpoints, demonstrating a significant improvement in PANSS positive symptom subscale score, PANSS negative symptom subscale score, PANSS negative Marder factor score, the Clinical Global Impression-Severity (CGI-S) scale at week five and percentage of PANSS responders at week five compared to placebo. There were no safety signals that were new or unexpected in comparison with prior KarXT trials in schizophrenia. Similar to the global program, the common treatment emergent adverse events in the treatment arm include vomiting, tachycardia, nausea, systemic hypertension, dizziness and diarrhea. In the global Phase 3 EMERGENT-2 and EMERGENT-3 trials, KarXT met its primary endpoint, demonstrating statistically significant reductions of schizophrenia symptoms compared to placebo. The safety and tolerability profile of KarXT has been established across acute and long-term trials. In September 2024, the U.S. Food and Drug Administration (FDA) approved COBENFY™ (xanomeline and trospium chloride) for the treatment of schizophrenia in adults. COBENFY does not have atypical antipsychotic class warnings and precautions and does not have a boxed warning. About KarXT KarXT (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, including schizophrenia and Alzheimer's-related psychosis. 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. Zai Lab has an exclusive license from Karuna Therapeutics, Inc., a company acquired by Bristol Myers Squibb, to develop, manufacture, and commercialize KarXT in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively). About Schizophrenia Schizophrenia is a persistent and often disabling mental illness affecting how a person thinks, feels, and behaves. It is characterized by positive symptoms (e.g., hallucinations and delusions), negative symptoms (e.g., difficulty enjoying life and withdrawal from others), and cognitive impairment (e.g., deficits in memory, concentration, and decision-making) – 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 the general 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 or problematic side effects while on current antipsychotic therapy, and approximately 75% of patients discontinue medication before 18 months. When schizophrenia treatment is discontinued, it can lead to impacts on health including relapse, hospitalization, and longer time to remission. More than 8 million people in China are living with schizophrenia, yet fewer than half are receiving treatment, and even fewer are obtaining adequate symptom improvement using the current treatment of antipsychotics. Like patients globally, there is a significant need for more effective therapies with improved safety to treat patients with schizophrenia in Greater China. About Zai Lab Zai Lab (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 worldwide. 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 KarXT, the potential benefits of KarXT, and the potential treatment of schizophrenia and other psychiatric and neurological conditions including Alzheimer’s-related psychosis. 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/20250117029564/en/ For more information, please contact: Investor Relations: Christine Chiou / Lina Zhang +1 (917) 886-6929 / +86 136 8257 6943 christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com Media: Shaun Maccoun / Xiaoyu Chen +1 (857) 270-8854 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited

The FDA approved five fewer novel medicines than in 2023 while the EMA improved its tally by seven. Image credit: Shutterstock / Tamakhin Mykhailo. The US Food and Drug Administration (FDA) has narrowly beaten the European Medicines Agency (EMA) to the most approved drugs with a new active substance in 2024. On 15 January, the two agencies released respective lists of medicines approved last year. The FDA approved 50 novel drugs that contained an active ingredient not previously approved by the agency, whilst the EMA authorised 46 new medicines. Whilst racking up 50 novel drug approvals, the FDA approved fewer than it did in 2023, when there were 55 greenlit to market . Conversely, the EMA’s 2024 figure of 46 was a step up from the 39 new active substance drugs approved in 2023. The highest proportion of new drugs approved by the EMA came in haematology/haemostaseology indications, with ten of the 12 approved medicines in this area containing a new active ingredient. Overall, however, oncology had the highest number of new drugs, matching trends seen in previous years. The FDA meanwhile highlighted the importance of rare diseases, reporting that over half its novel approvals came in orphan diseases that affect fewer than 200,000 people in the US. The FDA added that 68% of its novel drugs were approved in the US before any other country. Mirrored approvals Both the FDA and EMA approved Pfizer’s Hympavzi (marstacimab-hncq) for the treatment of adults and adolescents with severe haemophilia A or B without inhibitors. Hympavzi’s entry to market marked a significant advancement in treatment options available for patients with the rare disease, becoming the first approved anti-tissue factor pathway inhibitor. In the hepatological space, both the FDA and EMA have approved Ipsen’s Iqirvo (elafibranor) and Gilead’s Livdelzi (seladelpar), the latter being marketed at Seladelpar Gilead in Europe. The drugs were approved for the treatment of primary biliary cholangitis, a chronic disease that can eventually lead to liver failure. The agencies were also aligned on ARS Pharmaceuticals adrenaline-based nasal spray for anaphylaxis treatment. Marketed as neffy in the US and Eurneffy in Europe, the drug became the first needle-free adrenaline option for emergency treatment of allergic reactions. Its entry to market, despite a hiccup in 2023 when the FDA declined to approve it, is seen as a more convenient alternative to EpiPen. Neuro differences Perhaps the most significant contrasts came in neurological indications. First came the approval of the new Alzheimer’s treatment Kisunla (donanemab) by the FDA in July 2024. The drug, which is still being reviewed by the EMA, provides direct competition to Eisai and Biogen’s Leqembi (lecanemab), which the EMA approved in late 2024, more than a year later than the FDA. Both treatments are monoclonal antibodies that target beta plaques in the brain, though Kisunla is infused every four weeks rather than Leqembi’s two. In September 2024, the FDA approved the first new schizophrenia drug in more than 30 years, courtesy of Bristol Myers Squibb’s (BMS) Cobenfy (xanomeline and trospium chloride). The approval validated the company’s $14bn acquisition deal for Karuna Therapeutics in which it gained rights to the candidate. BMS has not yet submitted Cobenfy to the EMA for marketing authorisation, though there are plans to run a UK trial in Oxford in 2025. Cobenfy is forecast to reach blockbuster status by 2028, as per GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Medications that received EMA approval but not FDA approval last year include Egetis Therapeutics’ Emcitate (tiratricol) and Pfizer’s Emblaveo (aztreonam-avibactam). Emcitate is the first treatment approved for peripheral thyrotoxicosis in patients with the ultra-rare chronic disease Allan-Herndon-Dudley syndrome while Emblaveo is indicated for certain types of infections by aerobic Gram-negative bacteria resistant to antibiotics.