LIB Therapeutics LLC

None   Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week.  Madrigal snags Sanofi's Bill Sibold as CEO Madrigal Pharmaceuticals Sanofi’s Bill Sibold has left after a 12-year run, departing for Madrigal Pharmaceuticals, where he is taking the top spot.   Sibold most recently served as Sanofi’s executive vice president of specialty care and president of North American operations. In those roles, he oversaw 10,000 staffers and grew his operations into the pharma’s largest global business unit. The Big Pharma’s current head of specialty care in North America, Brian Foard, has assumed Sibold’s post while the company searches for a permanent successor.  At Madrigal, Sibold takes the reins from Paul Friedman, M.D., who has helmed the organization for seven years. The CEO change-up comes as the organization gears up for a potential FDA green light for lead candidate resmetirom, which would be the first nonalcoholic steatohepatitis treatment to make it to market if approved. The FDA has given resmetirom priority review and expects to make a decision by March 14, 2024. Fierce Biotech  Jazz changes octaves with COO swap Jazz Pharmaceuticals Jazz Pharmaceuticals is singing a new executive tune, after President and Chief Operating Officer Dan Swisher decided to move on from the company. Taking his place is Chief Financial Officer Renée Galá, who’s being fully promoted after joining the company in 2020. She’s previously worked at Theravance, Grail and Lilly.  The changing of the guards comes as Jazz’s pipeline is in the midst of its own transition. Sales of narcolepsy drug Xyrem are being crunched as generics enter the fold, but low-sodium alternative Xywav raked in $327 million in sales in the second quarter. Additional marketed meds Epidiolex and Rylaze each had double-digit growth in the second quarter compared to the same period in 2022.  Beyond just betting on its existing portfolio, Jazz is hunting for additional deals, according to CEO Bruce Cozadd. He told Fierce Biotech in June that the company was on the hunt for deals involving neurology and oncology treatments. Fierce Pharma  Amanda Kay to oversee business development at Flagship Flagship Pioneering Some four months ago, Amanda Kay was hired as president of new Flagship spinout Metaphore Biotechnologies. Now, she’s taking on a significantly larger role, leading business development for the whole firm as chief business development partner. She’s also being promoted from operating partner to senior partner. A spokesperson confirmed that she’s relinquished her role at Metaphore as part of move. Before joining the Flagship ecosystem, Kay was the chief business officer and head of finance at Deep Genomics. She was also the head of corporate development at Synlogic and was the chief operating officer for Pfizer’s inflammation and immunology research units. The CEO of Metaphore, Lovisa Afzelius, Ph.D., overlapped with Kay at Pfizer.  Needless to say, business development is a crucial staple of drug development across the industry but especially at Flagship. Companies like Generate Biomedicines, Moderna and Foghorn, to name a few, all have made considerable licensing and/or research pacts since launching. Release  > Sling Therapeutics has tapped Raymond Douglas, M.D., Ph.D., to serve as chief scientific officer. Douglas' research contributed to the development of Horizon Therapeutics' Tepezza, the first and only FDA-approved treatment for thyroid eye disease. Release > Mitchell Jones, M.D., Ph.D., is joining Palisade Bio as chief medical officer. He previously was the VP of corporate development and strategy at Chemomab Therapeutics. Release > LIB Therapeutics co-founder and CEO Evan Stein, M.D., Ph.D., is transitioning out of the top leadership role but taking on CSO and COO duties. Replacing him as CEO is David Cory, former CEO of Eiger BioPharmaceuticals. Release > SpringWorks Therapeutics hopes a new scientific chief can help propel forward the company’s research ambitions, naming Tai-An Lin, Ph.D., for the role. Lin previously oversaw translational research and discovery biology at Black Diamond Therapeutics. Release > Philip Vickers, Ph.D., has been tapped as the new CEO and president of Solu Therapeutics. He most recently was the CEO of Faze Medicines and also sits on the board of AVROBIO. Release > Pliant Therapeutics is welcoming on Minnie Kuo as chief development officer. Before Pliant, Kuo held roles of increasing responsibilities at Vir Biotechnology, most recently serving as SVP of translational and clinical development operations. Release > German biotech Repairon has chosen executive chair and co-founder Lothar Germeroth, Ph.D., to helm the company. Germeroth, also a major shareholder of Repairon, is a biochemist and serial biotech entrepreneur. Release > Confo Therapeutics has chosen Stephen Dowd, Ph.D., as its chief business officer. Dowd joins the GPCR company from Rallybio, where he served as head of business development for European operations, and also has past experience at Kymab (acquired by Sanofi), SNIPR Biome and GSK. Release > Jacob Jacobsen, Ph.D., is succeeding Joseph Patti, Ph.D., as Evecxia Therapeutics’ president and CEO. Patti has stepped down to pursue other interests, while Jacobsen joins from Duke University and Duke-National University Singapore, where he conducted research. Release > Innate Pharma is bringing on Sonia Quaratino, M.D., Ph.D., as EVP and chief medical officer starting in October. Quaratino succeeds Joyson Karakunnel, M.D., and has previously held positions at Georgiamune, Kymab (acquired by Sanofi), Novartis and Merck Serono (Merck KGaA). Release > Belgium biotech Augustine Therapeutics is growing its team with three new additions: Marie Trad, M.D., as chief medical officer; Jonathan van Eyll, Ph.D., as head of pharmacology; and Cédric Szyndralewiez as head of nonclinical and early development. Trad is a neurologist and founder of Neuraltra, while von Eyll helped establish UCB Pharma’s translational bioinformatics unit and Szyndralewiez has more than 25 years of drug research and development, most recently from Pherecydes Pharma. Release > Myricx Bio has tapped Dr. Robert McLeod as VP of clinical development. McLeod joins the U.K. biotech having previously served as Daiichi Sankyo’s senior director and global clinical lead, a research physician at Cancer Research UK's Center for Drug Development and various roles at Emergent BioSolutions, Novartis and Chiron. Release > Biostax’s Immune Therapeutics CEO Kelly Wilson and President and Director Robert Wilson both resigned July 25, departures that were not due to any dispute or disagreement relating to the company, according to Securities and Exchange Commission documents. The board immediately appointed Immune Therapeutics’ VP Noreen Griffin to serve as CEO. Release > Spine and orthopedics company Orthofix has ousted its President and CEO Keith Valentine, Chief Financial Officer John Bostjancic and Chief Legal Officer Patrick Keran after the board of directors “determined that each of these executives engaged in repeated inappropriate and offensive conduct that violated multiple code of conduct requirements and was inconsistent with the company’s values and culture.” Effective immediately, Orthofix’s board chair Catherine Burzik is taking on the CEO spot. Fierce Medtech > 4D Molecular Therapeutics has appointed Uneek Mehra as chief financial and business officer, succeeding August Moretti in his retirement. Mehra joins from Myovant Sciences (acquired by Sumitovant Biopharma), where he also served as CFO and CBO, and also held a senior leadership role at Novartis among other companies. Release > Oculis is welcoming Rebecca Weil, Ph.D., to serve as the eye care company’s chief commercial officer. Before Oculis, Weil was Idorsia’s VP and head of global marketing. Release

国内药企引进长效降脂针，每月一次，降脂幅度高于他汀类药物；国内有十余家药企的在研药物有望成为非他汀类调血脂药新宠。 01突破他汀类降脂上限每月一次，副作用更小 9月12日，海森生物与LIB Therapeutics就第三代长效PCSK9抑制剂Lerodalcibep的开发与商业化达成许可协议。 LIB Therapeutics是一家成立于2015年自筹资金私人公司，资产来自百时美施贵宝。Lerodalcibep是其最主要的在研产品，这款第三代长效PCSK9抑制剂将主要被用于解决当前临床降脂治疗中未被满足的需求，每月一针皮下注射，目前正处于3期临床阶段。 按照协议，LIB Therapeutics将获得2000万美元的预付款，并有可能额外获得最高达3.05亿美元（按当前汇率折合人民币约22.2亿元）的临床、注册和销售里程碑付款。LIB Therapeutics也将根据Lerodalcibep在大中华区的年净销售额获得特许权使用费。 与目前最主流的降脂产品HMG-CoA还原酶抑制剂，即他汀类药物相比，PCSK9抑制剂的优势主要体现在降脂效果以及用药频次等方面。 常用的他汀类药物可以把低密度胆固醇（LDL-C）水平降低40%~50%，同时，每种他汀类药物都有较为固定的降脂幅度，即使剂量加倍其降幅只能再增加6%左右，但不良反应却会显著增加。 接受大剂量他汀治疗者主要面临肝功能异常，肌痛、肌炎和横纹肌溶解，新发糖尿病（发生率约10%~12%）等不良反应风险，相比之下，PCSK9抑制剂不良反应小，其中最常见的注射部位反应，主要表现是红斑，疼痛或瘀青，其他严重的不良反应很少见。 因此，对于使用他汀类药物LDL-C水平仍不能达标、对他汀类药物不耐受等患者，例如家族性遗传性高胆固醇血症患者，特别是纯合子患者而言，他汀类药物作用有限，选择其它药物或联用其它药物是更合适的选择。 今年8月末，LIB Therapeutics在欧洲心脏病学会（ESC）年会上公布了Lerodalcibep的全球3期试验积极结果。该试验共纳入478例杂合子家族性高胆固醇血症患者，校正安慰剂效应后，每月一针皮下注射Lerodalcibep的治疗组患者在第24周时LDL-C平均下降58.6%，在第22周/24周平均下降65.0%。 在用药频次方面，他汀类药物一般为每日服用，PCSK9抑制剂的注射周期一般在两周以上。 与最早上市的两款PCSK9单抗药物——安进/安斯泰来的依洛尤单抗（瑞百安）、赛诺菲/再生元的阿利西尤单抗（波立达）相比，此次海森生物引进的Lerodalcibep将用药频次从普遍的两周一次延长至每月一次，接近信达的托莱西单抗（2~6周一次）。 02纳入医保目录后销售额同比增长700%+ 目前，全球共有4款PCSK9靶点药物获批上市，包括三款单抗药物——安进/安斯泰来的依洛尤单抗、赛诺菲/再生元的阿利西尤单抗、信达的托莱西单抗，以及一款小分子干扰核糖核酸（siRNA）药物——诺华的英克司兰钠。 在国内，依洛尤单抗于2018年7月获批上市，成为首个在中国上市的PCSK9抑制剂；2019年底，阿利西尤单抗获批上市。 今年8月16日，信达的托莱西单抗注射液获批上市，成为首个上市的国产PCSK9抑制剂，打破该赛道进口药物垄断的格局。 8月22日，诺华的英克司兰钠正式在华获批上市，此前该药在博鳌乐城先进医疗示范区的相关政策下已被海南省多家医院提前使用。 临床使用方面，PCSK9抑制剂虽具有更强的降低LDL-C作用机制，但其价格也比他汀类药物高得多。 以依洛尤单抗为例，此前其在中国定价为1298元/140mg/支，按照两周一针的用药频次计算，年费用约为33748元；阿利西尤单抗的定价更高，为1888元/75mg/支；相比之下，集采中标的阿托伐他汀（20mg）年费用不超过200元。 价格高昂也在一定程度上影响了PCSK9抑制剂的市场开拓。米内网数据显示，依洛尤单抗和阿利西尤单抗上市后销售额虽保持上涨态势，但均未过亿，直至2021年被纳入医保目录后迎来转机。 数据显示，纳入2021版国家医保目录（乙类）后，阿利西尤单抗2022年在公立医疗机构的销售额一举突破2亿元，同比增长779.34%；依洛尤单抗2022年销售额也突破了4亿元，同比增长263.91%。 可以看到，对仍未上市的同类药品而言，除了要争取在疗效、不良反应方面优于现有产品，上市后的定价策略以及医保政策更是不小的挑战。 03多家国内企业布局 今年3月25日，由国家心血管病专家委员会联合中华医学会心血管病学分会、内分泌学分会等组成的中国血脂管理指南修订联合专家委员会修订的《中国血脂管理指南（2023）》正式发布，指南明确，高脂血症正呈逐年上升趋势，儿童青少年脂质异常血症发生率已高达20.3%～28.5%，我国现有心血管病患人数或将增长至3.3亿人。 现阶段，我国成年人血脂异常知晓率、治疗率和控制率均处于较低水平，ASCVD高危/极高危人群的降脂治疗率和达标率较低，降脂治疗仍存在未被满足的临床需求。 在这一治疗领域，他汀类药物和PCSK9抑制剂是用量大和增速快的品类。 经历多轮集采降价后，多款他汀类药物销售额出现萎缩，一些“药王”级的品种销售额降幅超过60%。尽管他汀类药物仍占据八成的降脂市场，但仍有不少企业开始提前布局不同靶点、不同类型的降脂新药。 国内有十余家药企的在研药物有望成为非他汀类调血脂药新宠。 其中，君实的重组人源化抗PCSK9单抗昂戈瑞西单抗、恒瑞的抗PCSK9单抗SHR-1209、康方生物与东瑞制药共同开发的PCSK9单抗Ebronucimab均已提交上市申请，另外，还有更多药物正处于临床阶段，涉及重组融合蛋白、siRNA疗法等。 以PCSK9抑制剂为例，随着后续更多产品获批上市以及药物市场渗透率逐步提升，其在中国的市场规模预计到2030年可达90亿元。 国内部分在研PCSK9药物图源：一度医药END作者 | 陈芋来源 | 赛柏蓝医药代表转型之一一患者招募扫描下方二维码，进入赛柏蓝患者招募群

「  本文共：15条资讯，阅读时长约：3分钟 」今‍日‍头条海思科镇痛药报带疱神经痛NDA。海思科1类化药HSK16149胶囊（crisugabalin）的新适应症上市申请获CDE受理，用于带状疱疹后遗神经痛。HSK16149是一种电压门控钙离子通道类新型镇痛药，属于普瑞巴林的me-better药物，具备高靶点选择性、强效镇痛、长效镇痛、中枢副作用小等特点。去年10月，该新药用于糖尿病周围神经痛治疗的首个上市申请已获得CDE受理。‍‍‍国‍‍‍‍‍‍‍‍‍内‍‍‍‍药‍‍讯‍‍‍‍1.清华PLpro抑制剂获批新冠临床。清华大学与复旦大学合作的木瓜蛋白酶样蛋白酶（PLpro）小分子抑制剂HL-21获国家药监局临床许可。冠状病毒通过其主水解酶（Main Protease，简称Mpro或者3CLpro），RNA依赖的RNA聚合酶（RdRp）和PLpro等关键蛋白协同工作实现病毒复制。HL-21旨在通过PLpro BL2结构域以阻断PLpro对于底物的切割，有望为多种新冠病毒株细胞感染提供新的治疗选择。2.诺诚健华BTK抑制剂见刊AJH。诺诚健华布鲁顿酪氨酸激酶（BTK）抑制剂奥布替尼在《美国血液学杂志》（American Journal Of Hematology）上发表用于治疗复发/难治性边缘区淋巴瘤（MZL）患者的临床研究结果。中位随访24.3个月时，独立审查委员会（IRC）评估的总缓解率（ORR）为58.9%，92.2%的患者观察到肿瘤缩小。12个月的PFS率和总生存（OS）率分别为82.8%和91.0%。药物的安全性良好。3.宜明昂科CD24单抗临床前研究积极。宜明昂科CD24单抗IMM47临床前研究成果发表于《Antibody Therapeutics》上。IMM47能够阻断从CD24/Siglec-10通路传递至巨噬细胞、自然杀伤细胞(NK)和T细胞的免疫抑制信号。在临床前动物体内药效研究中，IMM47能够显著提高肿瘤组织中M1巨噬细胞的数量以及下调肿瘤细胞CD24表达，单药或者与PD-1/PD-L1免疫检查点抑制剂联用显示出强大的抗肿瘤疗效。4.海森生物引进长效PCSK9抑制剂。海森生物与LIB Therapeutics就后者一款临床后期、拟开发用于高胆固醇血症的长效PCSK9抑制剂Lerodalcibep达成合作许可协议，获得该新药在大中华区（包括中国大陆和港澳台地区）开发及商业化独家专有权。根据协议，LIB Therapeutics将获得2000万美元的预付款，最高达3.05亿美元的临床、注册和销售里程碑后期付款，以及产品的销售分成。5.英矽智能USPI抑制剂授权Exelixis。Exelixis公司与英矽智能达成独家授权协议，获得后者基于其人工智能生成平台Chemistry42开发的一款USP1抑制剂ISM3091，及其他USP1靶向化合物的全球独家开发和商业化权益。根据协议，英矽智能将获得8000万美元的预付款，开发、商业和销售的里程碑潜在付款，以及净销售额的分级版税。今年以来，ISM3091已先后在中美两国获批临床，拟开发治疗晚期实体瘤。‍‍‍‍国‍‍‍‍‍‍‍‍‍‍际‍‍‍‍药‍讯‍‍1.PDE3/4抑制剂吸入剂报慢阻肺NDA。FDA受理Verona公司吸入式磷酸二酯酶3/4（PDE3/4）抑制剂ensifentrine（恩塞芬汀）的新药申请（NDA），用于维持治疗慢性阻塞性肺病（COPD），PDUFA日期为明年6月26日。在两项国际III期临床（ENHANCE-1和ENHANCE-2）中，ensifentrine维持治疗使患者的平均1秒平均用力呼气量（FEV1）分别增加87mL和94mL，COPD恶化率分别降低36%和42%。优锐医药拥有ensifentrine的大中华区独家权利。2.阿斯利康IL-5Rα单抗EGPA临床积极。阿斯利康IL-5Rα单抗benralizumab（本瑞利珠单抗）用于嗜酸性肉芽肿性多血管炎（EGPA）附加维持治疗的III期MANDARA研究达到主要终点。在接受伴或不伴免疫抑制剂的口服糖皮质激素（OCS）治疗基础上，benralizumab附加维持治疗在第36周和第48周达到缓解状态的患者比例的统计非劣效于美泊利珠单抗。详细结果将在医学会议上公布。3.艾伯维IL-23抗体克罗恩病Ⅲ期临床成功。艾伯维IL-23抑制剂Skyrizi（risankizumab）治疗中重度活动性克罗恩病（CD）的Ⅲ期临床（SEQUENCE）达到双主要终点和所有次要终点。与活性对照组相比，Skyrizi治疗组第24周时临床缓解率的统计达到非劣效性（59%vs40%）；第48周达到内窥镜评分[SES-CD]≤4和至少降低2分，且任何单个组分的分项评分均不超过1分的患者比例为32%（vs16%，p<0.0001）。临床中未观察到新的安全性风险。4.CRF1拮抗剂治疗CAH的Ⅲ期临床积极。Neurocrine公司选择性促肾上腺皮质激素释放因子1型受体（CRF1）拮抗剂crinecerfont，在治疗经典先天性肾上腺皮质增生症（CAH）的Ⅲ期临床CAHtalyst达到主要终点和关键次要终点。在第24周，与安慰剂相比，该新药在维持雄激素控制的同时，还显著降低患者每日所需糖皮质激素剂量百分比；该组约63%的患者所使用的糖皮质激素降低至生理剂量，而安慰剂组这一数值约为18%（p<0.0001）。Crinecerfont总体耐受性良好。5.慢性鼻窦炎创新疗法Ⅱ期临床积极。Lyra Therapeutics鼻基质创新药物LYR-220治疗慢性鼻窦炎（CRS）的Ⅱ期临床结果积极。LYR-220旨在向鼻窦通道连续递送六个月的抗炎药物糠酸莫米松以达到治疗目的。结果显示，与假性治疗组相比，LYR-220治疗组患者第24周时鼻塞、流鼻涕和面部疼痛/压力的综合改善具统计学意义（-1.50；p=0.02）；鼻腔鼻窦结局测试22（SNOT-22）评分也显著改善（-16.8；p=0.007）。联拓生物拥有在大中华区开发和商业化LYR-220的优先权利。6.百时美施贵宝LPA1拮抗剂Ⅱ期临床积极。百时美施贵宝口服溶血磷脂酸受体1（LPA1）拮抗剂BMS-986278治疗进行性肺纤维化（PPF）的Ⅱ期临床结果积极。与安慰剂组相比，BMS-986278（60mg）治疗组预测用力肺活量百分比（ppFVC）的变化率降低69%（治疗组与安慰剂组的差异为2.9%；95% CI：0.4，5.5），治疗组ppFVC的变化率相对于安慰剂组降低74%（3.2%；95% CI：0.7，5.6）。药物不良事件（AEs）发生率与安慰剂相似。‍‍‍‍‍‍‍‍‍医‍‍‍‍‍‍药‍‍‍‍‍‍‍‍‍‍‍‍‍热‍‍‍‍‍‍‍点‍‍‍。1.重庆九价HPV疫苗接种已纳入补贴。9月8日，重庆沙坪坝区适龄女生HPV疫苗接种在歌乐山社区卫生服务中心正式启动，沙坪坝区本次疫苗接种面向全区无免疫史的初二在校女生。目前，重庆多个城区多个街道的社区卫生服务中心已启动适龄女生HPV疫苗接种，接种女孩和家长可自主选择接种二价、四价或九价疫苗，均按照最高每人600元的标准，以不超过疫苗总费用为限实施定额补助。2.北京出台药品创新服务提质增效行动方案。近日，北京市药监局印发《药品创新服务提质增效行动方案（2023-2025年）》。《方案》明确，到2023年底，全面落实项目制管理工作机制，本市在研品种纳入项目制管理品种数量不少于100项；启动在线咨询、重点项目跟踪服务管理模块等信息化建设；到2024年底，累计纳入项目制管理品种数量不少于200项；完成在线咨询、重点项目跟踪服务管理模块等信息化建设并上线运行；到2025年底，累计纳入项目制管理品种数量不少于300项；三年内获批药物临床试验创新药项目不少于200项。3.王大军任首都医科大学附属复兴医院党委书记。9月12日，首都医科大学附属复兴医院召开干部大会，宣布复兴医院领导干部任免决定：王大军同志任首都医科大学附属复兴医院党委书记，刘云军同志不再担任首都医科大学附属复兴医院党委书记职务。首都医科大学附属复兴医院始建于1950年，前身为公安部直属医院，1958年归属地方管理，并与国家计委三里河门诊部合并后更名为北京市复兴医院，1998年被首都医科大学认定为附属医院。‍‍‍‍‍‍‍评‍‍‍‍‍审‍‍‍‍动‍‍态‍‍‍‍‍‍‍  1. CDE新药受理情况（09月13日) 2. FDA新药获批情况（北美09月11日）股市资讯上个交易日 A 股医药板块 -0.91%涨幅前三     跌幅前三通化金马+9.98%  福安药业-9.15%艾 力 斯 +5.79%   仟源医药-6.78%*ST 太安+4.91%   金凯生科-6.57%【亚虹医药】APL-1202口服联合替雷利珠单抗作为肌层浸润性膀胱癌(MIBC)新辅助治疗的I/II期临床试验完成I期临床试验期中分析并取得积极结果。【海思科】公司收到关于创新药HSK16149胶囊新适应症的上市申请受理通知书。【凯普生物】公司及子公司收到关于一种猴痘病毒假病毒颗粒及其制备方法的授予发明专利权通知书。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。