FW-UC

通过并购来扩充管线，几乎成为所有MNC都在做的事情。MNC需要找到新的增长引擎，来缓解专利断崖危机。2023上半年，随着全球市场的放开，并购交易也呈回暖趋势。那么MNC都把宝押在哪里了呢？根据BioPharma Dive网站的盘点以及公开数据，2023上半年药企并购案交易情况整理如下：2023上半年MNC并购交易事件来源：BioPharma Dive，公司网站几项值得关注的重磅交易01辉瑞430亿美元天价收购Seagen，扩充肿瘤管线今年3月，辉瑞宣布将斥资约430亿美元收购Seagen公司，扩充其肿瘤学管线。据悉，Seagen是一家总部位于美国西雅图的生物技术公司，1997年由前BMS高管创办，2001年在纳斯达克上市。作为ADC领域的先锋，Seagen雄厚的ADC管线布局和研发能力为行业熟知。目前，Seagen共有四款产品上市，分别是：Adcetris、Padcev、Tivdak和Polivy。2022年，这四款产品共计收入17亿美元，同比增长23%。来源：Seagen官网此外，公司的研发管线中还有15款处于I/II期临床试验阶段的在研疗法。其中，与荣昌生物联合开发的disitamab vedotin是一款靶向HER2的ADC药物，已在中国获批治疗特定胃癌和尿路上皮癌患者。Seagen作为ADC行业龙头，凭借专利技术储备建立了竞争优势和专利护城河，这也是吸引辉瑞的原因。辉瑞2022年实现营业收入1003亿美元，净利润为314亿美元，但如果去掉新冠疫苗Comirnaty和口服药物Paxlovid的市场销售收入，辉瑞2022年的营业收入不到500亿美元。产品方面，仅阿哌沙班（64.80亿美元）、肺炎球菌疫苗（63.37亿美元）和哌柏西利（51.20亿美元）3款产品销售额突破50亿美元，但均不再是能打之将。同时，辉瑞还面临着兑现2030年实现非新冠新业务收入250亿美元的承诺。因此，辉瑞丰富研发管线和转型的需求迫在眉睫。过去一年，ADC市场的火爆大家有目共睹，MNC纷纷重金入局，可见对这一赛道未来前景的看好。有数据预测，全球ADC药物市场规模于2026年将达到164亿美元，市场潜力巨大。辉瑞表示，Seagen预计将以28%的年复合增长率在2028年实现77亿美元的业绩收入，而Padcev也将取代Adcetris成为主要业绩驱动。Padcev是全球首个获批上市的Nectin-4 ADC产品，目前其适应症仍在不断拓展，与同类布局企业相比，在速度上具有绝对优势。因此，辉瑞收购Seagen选择了商业确定性。不过430亿美元的投资回报率究竟如何，还需要时间给出答案。  02默沙东108亿美元押注IBD赛道今年4月，默沙东宣布将以108亿美元收购生物技术公司Prometheus Biosciences（简称Prometheus），获得其溃疡性结肠炎（UC）、克罗恩病（CD）等炎症性肠病（IBD）和其他自免候选药物，以增强免疫领域的产品管线。来源：默沙东官网Prometheus成立于2016年，是一家处于临床阶段的生物技术公司，采用精准医学方法发现、开发和商业化用于治疗免疫介导疾病的新型治疗和辅助诊断产品。Prometheus公司的拳头产品是PRA023，拟开发用于UC、CD和其他自身免疫性疾病的治疗。PRA023是一款针对肿瘤坏死因子（TNF）类配体1A（TL1A）的人源化单克隆抗体药物，目前已经完成了两项II期临床试验。TL1A是一种2型跨膜蛋白，主要由内皮细胞表达，通过介导炎症和纤维化，TL1A在T细胞介导的炎症性自免疾病中发挥重要作用。去年3月，Prometheus披露了PRA023治疗UC、CD的两项II期临床试验数据。结果显示：在治疗中重度UC的随机双盲II期临床试验中，在用药12周治疗后，PRA023组中26.5%的患者达到临床缓解的主要终点，对照组仅为1.5%；36.8%的患者达到内镜改善的次要终点，对照组仅为6.0%。这一临床缓解率高于目前市面上治疗UC的常用药物，具有best-in-class潜力。在治疗CD患者的IIa期临床试验中，PRA023组中有26.0%的患者获得内镜缓解，对照组仅为12%。IBD是一组不明原因的慢性肠道炎症性疾病，分为UC和CD，常见症状是严重腹泻、疲劳等，严重影响患者生活质量。据估计，全世界约有1260万人患有 IBD。目前还没有治愈IBD的方法，治疗目的主要是减少引发病症的炎症，从而提供短期或长期的缓解，降低并发症的风险。用于治疗IBD的药物包括氨基水杨酸、皮质类固醇激素、免疫抑制剂、生物制剂和抗生素等。生物制剂是当下IBD药物市场主流产品，不过大约有三分之一的患者对生物制剂疗法没反应，另有一半的初始治疗有效患者会发生继发性反应丧失现象，因此，亟需新的治疗方法。根据2022年中金创新药前沿系列报道，目前全球IBD市场约为180亿美元，预计到2030年将增长至约490亿美元。在IBD巨大的商业化市场面前，众多大药企如强生、礼来、辉瑞、艾伯维等纷纷入局。国内药企如科兴、恒瑞、正大天晴、华东医药等也在布局IBD领域。此次收购，意味着默沙东将重心放在拓展自身免疫病领域的布局。TL1A抗体在IBD适应症上表现亮眼，或将成为自免领域又一款重磅炸弹产品。辉瑞2022年实现营业收入1003亿美元，净利润为314亿美元，但如果去掉新冠疫苗Comirnaty和口服药物Paxlovid的市场销售收入，辉瑞2022年的营业收入不到500亿美元。产品方面，仅阿哌沙班（64.80亿美元）、肺炎球菌疫苗（63.37亿美元）和哌柏西利（51.20亿美元）3款产品销售额突破50亿美元，但均不再是能打之将。同时，辉瑞还面临着兑现2030年实现非新冠新业务收入250亿美元的承诺。因此，辉瑞丰富研发管线和转型的需求迫在眉睫。过去一年，ADC市场的火爆大家有目共睹，MNC纷纷重金入局，可见对这一赛道未来前景的看好。有数据预测，全球ADC药物市场规模于2026年将达到164亿美元，市场潜力巨大。辉瑞表示，Seagen预计将以28%的年复合增长率在2028年实现77亿美元的业绩收入，而Padcev也将取代Adcetris成为主要业绩驱动。Padcev是全球首个获批上市的Nectin-4 ADC产品，目前其适应症仍在不断拓展，与同类布局企业相比，在速度上具有绝对优势。因此，辉瑞收购Seagen选择了商业确定性。不过430亿美元的投资回报率究竟如何，还需要时间给出答案。  03诺华收购Chinook，巩固肾脏领域布局2023年6月，诺华宣布与加拿大公司Chinook Therapeutics（简称Chinook）达成协议，以35亿美元的总金额收购Chinook。Chinook是一家临床阶段生物制药公司，致力于发现、开发和商业化罕见的、严重的慢性肾脏疾病精准疗法。其核心资产Atrasentan是一款强效高选择性内皮素A（ETA）受体拮抗剂，目前正在开展免疫球蛋白A（IgA）肾病III期临床研究。Zigakibart是一款抗增殖诱导配体(APRIL)的新型人源化单克隆抗体，目前正在开展IgA肾病的I/II期临床研究。Chinook产品管线来源：Chinook官网IgAN肾病是一种罕见的自身免疫性和进行性肾病，由于肾脏中免疫复合物的积累，导致器官炎症和损伤，进而表现为血尿、蛋白尿甚至肾衰竭。据弗若斯特沙利文报告，全球IgAN患者人数由2016年的887.64万人增加至2020年的926.69万人（包括中国的220万人），预计2030年将达到1016.52万人（包括中国237万人）。虽然IgA市场潜力巨大，但是关于IgA肾病的创新获批疗法并不多。首个IgA肾病靶向治疗药物，是来自Calliditas Therapeutics的Nefecon（布地奈德迟释胶囊），于2021年获FDA批准。不过布地奈德是一种糖皮质激素，副作用较大。因此，临床仍存在巨大的未满足治疗需求。Atrasentan作为一种ETA受体拮抗剂，通过阻断ETA受体，进而阻断肾小球系膜细胞活化，直接抗炎和抗纤维化，降低球囊内压力和肾小球滤过屏障大分子通透性，来减少IgAN患者的尿蛋白。在II期AFFINITY中期研究中，结果显示在第24周时蛋白尿平均减少54.7%。另外，Atrasentan 在其他罕见肾脏疾病的开发也处于早期阶段。Zigakibart通过阻断APRIL与其受体的作用，耗竭降低致病性半乳糖缺陷型IgA1(Gd-IgA1)的产生，并阻断致病性免疫复合物的生成，潜在改变IgA肾病的治疗进程。在已完成的临床研究中，Zigakibart表现出了潜在的疗效和良好的安全性。目前，诺华肾病管线中有一款口服补体因子B抑制剂Iptacopan（LNP023），其在非典型溶血性尿毒综合征、lgAN，C3肾小球病、成人阵发性睡眠性血红蛋白尿症（PNH）等多个适应症中进展到了III期临床研究。此次收购，将进一步巩固诺华在肾病领域的地位。另外，在免疫领域，礼来于6月20日，以24亿美元的金额收购了DICE Therapeutics（简称DICE），获得DICE的口服IL-17抑制剂DC-806等项目。目前，礼来的糖尿病业务作为现金流支柱已有较好表现，肿瘤板块阿贝西利销售额也在迅猛增长。此次礼来收购DICE，主要是为了补强其免疫管线。从收购方来看，今年MNC们似乎更偏向于并购有后期管线，中短期内能够实现药物获批，或是已有上市药物的公司。与去年纷纷并购罕见病领域的公司不同，今年上半年的并购方向更加多元化：不仅有罕见疾病领域，还有免疫调节/治疗、慢病治疗、胃肠疾病、呼吸健康、皮肤疾病等，以前比较冷门的肾病领域也在逐渐成为投资热点。总之，在行业寒冬下，并购为现金流紧张的Biotech提供了一条出路，使得更多有临床价值的产品得以继续研发下去。MNC们在对旗下管线进行削减的同时，也在通过并购扩张新的领域，为自己打造新的增长曲线，希望各自都能找到属于自己的制胜法典。参考来源1.https://www.biopharmadive.com/news/biotech-pharma-deals-merger-acquisitions-tracker/604262/.2.Pfizer in talks to acquire Seagen in deal likely valued at more than $30 Billion.3.Immunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics，National Library of Medicine.END👇关注药渡数据媒体矩阵

BRISBANE, Australia I June 27, 2023 I Microba Life Sciences Limited (ASX: MAP) (“Microba” or the “Company”) today announces that the first participants have been successfully dosed in the Phase I Clinical Trial of MAP 315, in Microba’s Therapeutic Program in Inflammatory Bowel Disease (IBD). This milestone brings Microba’s drug candidate MAP 315 into clinical development as a potential new treatment option for the millions of people suffering from ulcerative colitis. Professor Trent Munro, SVP of Therapeutics at Microba said: “Microba has now matured into a clinical stage drug development company. I am proud of our team and what we have built to bring novel microbiome drugs all the way from human-data guided discovery, through to an orally delivered drug product now dosed in a first in human clinical trial. We are uniquely positioned at the forefront of drug development from the microbiome and excited about the future potential impact of MAP 315 as a new treatment for Inflammatory Bowel Disease sufferers.” The Phase I clinical trial is a randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of MAP 315 in 32 healthy adults. The trial is being conducted by Nucleus Network in Melbourne, Australia, under the Company’s Human Research Ethics Committee (HREC) approval and in alignment with formal feedback received from an FDA pre-IND engagement. MAP 315 Phase 1 Clinical Trial Details The clinical trial is titled “A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MAP 315 in Healthy Adults”. The study will enroll 2 cohorts of 16 participants each, who will be randomised 3:1 to receive MAP 315 or its matching placebo for 14 consecutive days (2 weeks). Results from the trial are expected to be available in December 2023. Full study details can also be found in the Australian New Zealand Clinical Trials Registry (ANZCTR) under study ID: ACTRN12623000291684. Microba’s Novel Drug Candidate MAP 315 MAP 315 was identified using Microba’s unique analysis of its large proprietary human databank , demonstrating that this previously uncharacterised and novel bacterial species is commonly observed in healthy individuals but consistently deficient in individuals with IBD. Subsequent pre-clinical investigation of MAP 315 through both in vitro and in vivo models demonstrated that MAP 315 promotes epithelial restitution and mucosal healing - biological activities that are critical for sustained disease remission but not adequately addressed through existing therapy. MAP 315 is a live biotherapeutic product (LBP) consisting of lyophilised bacteria in an enteric coated capsule which is orally administered and being developed as an investigational product for the treatment of ulcerative colitis (UC). Microba worked in partnership with leading microbiome contract drug manufacturer Bacthera to produce GMP compliant MAP 315 at large-scale in their state-of-the-art facilities in Europe to supply material for the MAP 315 clinical trial. Inflammatory Bowel Disease – Large unmet need & commercial opportunity IBD causes prolonged inflammation of the digestive tract and now affects more than 7 million people globally, with this number increasing each year 1 . Ulcerative colitis (UC) is one of the two major forms of IBD, which results in inflammation and ulcers (sores) in the digestive tract, causing a debilitating chronic condition. Patients are currently treated with anti-inflammatory and immunomodulatory medication to dampen the disease and control symptoms, often with significant side effects. These available treatment options commonly fail, with more than 50% of patients unable to achieve sustained remission 2 , which sees them experiencing regular episodes of inflammation, diarrhoea, bleeding and abdominal pain 3 , with as many as 25% of patients requiring hospitalisation 4 . The market for UC treatment was valued at US$7.5 billion in 2020 and is forecast to grow to US$10.8 billion by 2030 5 . Microba’s novel drug candidate MAP315 presents an opportunity to improve the current standard of care and treatment for millions of people suffering from the debilitating effects of UC. Therapeutic Platform & Programs There is a growing body of evidence that the gut microbiome plays a central role in the maintenance of health and the development of chronic disease. With microbiome-based therapeutics now in clinical development and the first FDA approvals, these novel drugs represent an exciting new opportunity for the treatment of chronic diseases that are underserved by current pharmaceuticals. Microba is at the forefront of this field using its advanced proprietary metagenomics technology developed by leading Australian researchers in the top 1% of cited researchers globally. Using this technology, Microba has established a data-driven platform for drug discovery and development from the human gut microbiome. This platform leverages a large, growing, proprietary databank collected through the Company’s Microbiome Testing Services, and is generating multiple potent therapeutic candidates to address chronic diseases. Microba has established three therapeutic programs spanning IBD, Immuno-Oncology and Autoimmune Diseases, with lead candidate MAP 315 under the Company’s IBD program the first program to enter human clinical trials. About Microba Life Sciences Limited Microba Life Sciences is a precision microbiome company driven to improve human health. With world-leading technology for measuring the human gut microbiome, Microba is driving the discovery and development of novel therapeutics for major chronic diseases and delivering gut microbiome testing services globally to researchers, clinicians, and consumers. Through partnerships with leading organisations, Microba is powering the discovery of new relationships between the microbiome, health and disease for the development of new health solutions. 1 https://www.thelancet.com/journals/langas/article/PIIS2468-1253(19)30333-4/fulltext 2 https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf 3 Scribano, M.L. Adverse events of IBD therapies. Inflamm Bowel Dis. (2008). https://doi.org/10.1002/ibd.20702 . 4 Pola, S. et al. Strategies for the care of adults hospitalized for active ulcerative colitis. Clin Gastroenterol Hepatol. (2012). https://doi.org/10.1016/j.cgh.2012.07.006 . 5 https://www.nature.com/articles/d41573-021-00194-5 , https://www.alliedmarketresearch.com/ulcerative-colitis-market SOURCE: Microba Lie Sciences