MORF-057

根据Evaluate的数据显示，生物制药行业在第三季度完成了22起并购交易，总价值达到82亿美元。在2023Q4季度和2024Q1这两个繁忙且花费高昂的季度之后，生物制药领域的并购活动在今年第三季度急剧下降，这是连续第二个季度出现下滑。交易数量和总交易价值均环比下滑，而该季度最大的交易规模也明显小于第二季度记录的最大交易。 值得注意的是，这一疲软的交易总额也是自2022年第一季度记录的约46亿美元以来，一个完整季度内最低的生物制药并购支出。同时，第三季度单笔交易价值亦有所下降。第一季度有7笔交易的前期估值达到或超过10亿美元，第二季度增至8笔，但第三季度仅有3笔交易突破了10亿美元的门槛。这反映了近期小型并购的趋势，自2023年第一季度辉瑞以430亿美元收购Seagen以来，生物制药行业再未出现过价值300亿美元或以上的大型合并案。 以下为今年第三季度生物制药领域最大的5笔并购交易。 1、礼来收购MorphicTherapeutic 7月8日，礼来宣布已与MorphicTherapeutic达成协议，将以每股57澳元/股的价格现金收购后者的所有流通股，总交易金额约为32亿美元。礼来旨在通过该笔交易增强其在胃肠道疾病领域的产品组合。 Morphic是一家专注于开发整合素靶向药物以满足严重慢性疾病需求的生物制药公司。目前，Morphic管线中仅有一款临床在研产品——用于治疗炎症性肠病（IBD）的口服小分子α4β7抑制剂MORF-057。Morphic正在开展MORF-057治疗溃疡性结肠炎（UC）的一项II期研究和治疗克罗恩病（CD）的一项II期研究。 2、勃林格殷格翰收购NerioTherapeutics 7月29日，勃林格殷格翰（BoehringerIngelheim）宣布以高达13亿美元的总额收购了Nerio Therapeutics公司，并囊获其创新蛋白酪氨酸磷酸酶N1和N2（PTPN1和PTPN2）小分子抑制剂临床前项目。勃林格殷格翰预计将该项目发展为其免疫肿瘤学产品组合的潜在核心组成，以实现改善癌症患者治疗效果的目标。 Nerio Therapeutics是一家专注于靶向磷酸酶的药物研发公司。Nerio所开发的新型、强效、潜在“first-in-class"小分子可以高选择性抑制PTPN1/2，这两个蛋白具有免疫检查点作用。通过抑制PTPN1/2，可使肿瘤对促炎信号敏感，并可增强患者免疫功能，激活免疫系统对抗癌细胞。Nerio的小分子抑制剂将成为勃林格殷格翰产品组合的重要补充，既可以作为单药疗法使用，也具潜力与该公司内部正在开发的多种癌症疗法联合使用。 3、欧加农收购Dermavant Sciences 9月18日，欧加农（Organon）宣布将收购Roivant子公司Dermavant Sciences。根据协议条款，收购总交易额约为12亿美元，包括1.75亿美元的首付款、7500万美元的监管里程碑付款以及9.5亿美元的某些商业里程碑付款。此外，欧加农将向Dermavant Sciences股东支付净销售额的分层特许权使用费。交易完成后，作为收购价格对价的一部分，欧加农将承担Dermavant Sciences的负债（截至2024年6月30日，负债约为2.86亿美元）。 据悉，欧加农此次收购的主要目标是本维莫德乳膏（商品名：VTAMA），Dermavant Sciences拥有该产品在中国以外的全球权益。该交易预计将于2024年Q4完成。欧加农预计该交易不会导致其资本配置的优先级发生变化。 4、Crown Laboratories收购Revance Therapeutics 8月12日，Crown Laboratories宣布将以9.24亿美元现金收购医美小巨头Revance Therapeutics（NASDAQ: RVNC），收购价为每股6.66美元。该交易预计将于年底前完成。合并完成后，Revance将由Crown全资拥有，Revance的股票将不再在纳斯达克公开交易。 Revance是一家新兴的生物科技公司，核心资产包括一款创新的长效肉毒素注射剂DAXXIFY®（DaxibotulinumtoxinA-lanm），该产品一经上市便引发了业界的广泛关注。此次交易是医美领域的一次强强整合，通过此次合并，Revance与Crown将共同构建起护肤品领域内最为广泛和强大的分销网络之一，进一步巩固并扩大其市场版图。 5、大冢制药收购Jnana Therapeutics 8月1日，大冢制药（Otsuka）和Jnana Therapeutics共同宣布，双方已达成最终协议，大冢制药将收购Jnana公司，使其成为大冢制药子公司Otsuka America的全资子公司。根据协议条款，大冢制药将在收购完成后向Jnana公司的股东支付8亿美元，以及高达3.25亿美元的开发和监管里程碑。此次收购预计将在2024财年第三季度完成。 基于此次收购，大冢制药将获得潜在“first-in-class”小分子抑制剂JNT-517，并扩展其自身免疫产品组合以及药物发现技术。JNT-517是一款在研的治疗苯丙酮尿症（PKU）的口服药物。2024年1月，Jnana公司宣布JNT-517在治疗PKU患者的1期临床试验中获得具有统计学意义的积极中期结果，该结果支持JNT-517在2025年上半年开始关键性3期临床试验。 参考资料： [1]Q3 Round up:Two out of Three Ain't Bad OCTOBER-2024-Evaluate. [2]32亿美元！礼来收购Morphic，持续进军炎症性肠病领域.医药魔方.2024年07月09日. [3]勃林格殷格翰13亿美元囊获潜在“first-in-class"抗癌小分子.药明康德.2024年07月30日. [4]欧加农12亿美元收购Dermavant，获得本维莫德乳膏权益.医药魔方.2024年09月19日. [5]9.24亿美元！这家医美企业被溢价111%收购.动脉新医药.2024年08月13日. [6]超11亿美元！大冢制药收购一家自身免疫创新药公司.医药观澜.2024年08月01日. 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。 点赞本文！

At three years, over 80% of patients with moderately to severely active UC who were in remission with mirikizumab sustained long-term remission and relief from disruptive symptoms, including bowel urgency Mirikizumab also helped over 50% of patients with moderately to severely active Crohn’s disease sustain long-term endoscopic remission for up to five years INDIANAPOLIS, IN, USA I October 28, 2024 I Eli Lilly and Company (NYSE: LLY ) announced results from two, multi-year, Phase 3 studies that showed patients treated with mirikizumab sustained stable, long-term remission across two types of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease. Data from the two trials – LUCENT-3 in moderately to severely active UC and VIVID-2 in moderately to severely active Crohn’s disease – will be presented at the American College of Gastroenterology (ACG) Annual Meeting from October 25-30, 2024 in Philadelphia. Mirikizumab is an interleukin-23p19 (IL23p19) antagonist that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Inflammation due to the overactivation of the IL-23 pathway plays a critical role in pathogenesis of UC and Crohn’s disease. Inflammation from UC and Crohn’s disease can lead to disruptive symptoms, including bowel urgency, that can result in decreased health-related quality of life and potentially irreversible complications for patients if left untreated. Mirikizumab is approved in the United States (U.S.) for the treatment of moderately to severely active UC in adults and is under review with the U.S. Food and Drug Administration (FDA) for moderately to severely active Crohn’s disease. “Mirikizumab is the first and only IL23p19 antagonist to report multi-year, long-term sustained efficacy data in both ulcerative colitis and Crohn’s disease,” said Mark Genovese, M.D., senior vice president of Lilly Immunology development. “This achievement reflects our commitment to help people with immune system conditions sustain long-standing remission and relieve disease burden.” Long-Term Data in Adults with UC In LUCENT-3, mirikizumab helped patients with moderately to severely active UC achieve long-term outcomes, including histologic-endoscopic mucosal remission, defined as mucosal healing. Mirikizumab also provided sustained benefit across symptomatic, clinical, endoscopic and histologic endpoints for up to three years, regardless of previous failure to TNF inhibitors, tofacitinib or other biologics. Among those who achieved clinical remission with mirikizumab at one year in the LUCENT-2 study, the following results were achieved based upon observed case analysis after an additional two years of treatment (up to three years total): These results were also evaluated using a modified non-responder imputation and are presented in the About the Mirikizumab Ulcerative Colitis Program section below. Among patients receiving mirikizumab in the LUCENT-3 study, 7.4% of patients reported a serious adverse event (AE), while 5.3% discontinued treatment due to an AE. The long-term safety profile in patients with moderately to severely active UC was consistent with the already known safety profile of mirikizumab. These data were recently published in Inflammatory Bowel Diseases . Long-Term Data in Adults with Crohn’s Disease New data from patients in the Phase 2 program who enrolled into the VIVID-2 long-term extension study showed that patients with moderately to severely active Crohn’s disease treated with mirikizumab maintained high rates of clinical and endoscopic remission over time. The following results were achieved based upon observed case analysis after an additional three years of treatment (up to five years total): These results were also evaluated using a modified non-responder imputation and are presented in the About the Mirikizumab Crohn’s Disease Program section below. “Despite continued advances, people living with ulcerative colitis and Crohn’s disease are still seeking treatments that can address difficult-to-manage symptoms such as bowel urgency, and provide lasting results over time,” said Bruce Sands, M.D., M.S., Dr. Burrill B. Crohn Professor of Medicine and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai. “These multi-year data show mirikizumab is a targeted therapy that can provide intestinal healing over time and improvement in key symptoms that matter most to patients.” Among these patients who enrolled into the VIVID-2 long-term extension study, 8.5% reported a serious AE and 1.9% discontinued treatment due to an AE. The long-term safety profile in patients with moderately to severely active Crohn’s disease was consistent with the already known safety profile of mirikizumab. Omvoh ® (mirikizumab-mrkz) was approved by the FDA in October 2023 as the first IL23p19 antagonist for the treatment of moderately to severely active UC in adults and is also approved in 44 countries around the world. Lilly submitted marketing applications for mirikizumab in Crohn’s disease around the globe, including in the U.S., Canada, Europe, Japan and China. Additional global regulatory submissions are planned. Additionally, Lilly has a combination study in UC with mirikizumab and eltrekibart, a humanized monoclonal antibody that binds to the seven ligands that signal through the CXCR1 and CXCR2 chemokine receptors involved in neutrophil movement to sites of inflammation ( NCT06598943 ). There are also ongoing studies in both UC ( NCT05611671 ) and Crohn’s disease ( NCT06226883 ) with MORF-057, a selective oral small molecule alpha-4/beta-7 integrin inhibitor that may improve outcomes and expand treatment options for people with IBD. Disclosure: Dr. Sands is a paid consultant for Lilly. He has not been compensated for any media work. About the Mirikizumab Ulcerative Colitis Program Mirikizumab was studied in two, Phase 3 clinical trials which evaluated the efficacy and safety of mirikizumab in adults with moderately to severely active ulcerative colitis (UC) and included patients who had never tried a biologic (biologic-naïve) and harder-to-treat patients who had previously taken a biologic that failed. The induction LUCENT-1 and maintenance LUCENT-2 studies were randomized, double-blind, and placebo-controlled and included those who had inadequate response, loss of response, or failed to tolerate any of the following: corticosteroids, immunomodulators (6-mercaptopurine and azathioprine), biologic therapy (TNF blocker, vedolizumab) or Janus kinase inhibitors (JAKi, tofacitinib). Additionally, 41% of patients in LUCENT-1 had failed at least one biologic, 3% had failed a JAKi and 57% were biologic and JAKi-naïve. LUCENT-3, the ongoing long-term Phase 3 extension of LUCENT-1 and LUCENT-2 evaluated the efficacy and safety of mirikizumab in patients with UC for up to three years. Using a modified non-responder imputation analysis to handle discontinuation and missing data, among Week 52 mirikizumab remitters, 70% maintained long-term clinical remission at Week 152, and response rates for major efficacy endpoints (including endoscopic remission, histologic-endoscopic mucosal remission, corticosteroid-free remission and clinical response) ranged from 63% to 85%. About the Mirikizumab Crohn’s Disease Program VIVID-1 was a Phase 3, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo and an active control (ustekinumab) in adults with moderately to severely active Crohn’s disease. Patients randomized to mirikizumab were administered 900 mg of mirikizumab intravenously every four weeks from Week 0-12, then 300 mg subcutaneously every four weeks from Weeks 12-52. In this study, 49% of patients taking mirikizumab or placebo had experienced a prior biologic failure. SERENITY, the Phase 2, multi-center, randomized, parallel-arm, double-blind, placebo-controlled trial was designed to assess the safety and efficacy of mirikizumab in patients with moderately to severely active Crohn’s disease. At baseline, participants were randomized with a 2:1:1:2 allocation across four treatment arms (placebo, mirikizumab 200 mg, mirikizumab 600 mg and mirikizumab 1000 mg). The primary endpoint was endoscopic response as determined by the proportion of participants achieving at least 50% reduction from baseline on the Simple Endoscopic Score for Crohn’s Disease (SES-CD) at Week 12. In May 2019, Lilly reported Phase 2 results showing more patients with moderate to severe Crohn’s disease receiving mirikizumab compared with placebo achieved clinical response and remission at 12 weeks. Overall, the safety profile at 12 weeks was consistent with that of mirikizumab in studies of ulcerative colitis and with the IL23p19 class. VIVID-2, the ongoing long-term Phase 3 extension of SERENITY and the VIVID-1 study, evaluated the efficacy and safety of mirikizumab in patients with Crohn’s disease for up to five years. Using a modified non-responder imputation analysis to handle discontinuation and missing data, 61% and 44% achieved endoscopic response and endoscopic remission, respectively, at Week 156. In addition, 79% and 72% achieved clinical response and clinical remission, respectively, at Week 156. Indications and Usage for Omvoh ® (mirikizumab-mrkz) (in the United States) Omvoh ® is indicated for the treatment of moderately to severely active ulcerative colitis in adults. Please click for Prescribing Information and Medication Guide for Omvoh. Please click for Instructions for Use included with the device. About Omvoh ® Omvoh ® (mirikizumab-mrkz) is an interleukin-23p19 antagonist indicated for the treatment of moderately to severely active ulcerative colitis in adults. Omvoh selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of ulcerative colitis. Treatment of ulcerative colitis with Omvoh starts with 300-mg IV infusions, once every four weeks for a total of three infusions, and transitions to two, 100-mg subcutaneous injections every four weeks during maintenance treatment. Omvoh and its delivery device base are trademarks owned by Eli Lilly and Company. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news , or follow us on Facebook , Instagram and LinkedIn . P-LLY SOURCE: Eli Lilly