WEE1

编者按：本文来自药渡仿制，作者粽哥2025；赛柏蓝授权转载，编辑yuki在行政监管与市场竞争的双重压力下，医药行业面临战略抉择。中药企业正是期望通过转型实现“换挡提速”，其中不乏片仔癀、云南白药等龙头，积极研发创新药的天士力、众生药业、以岭药业等。01云南白药、片仔癀中药龙头“换挡提速”片仔癀、云南白药是A股总市值排名前二的中药龙头企业。其中，片仔癀以超1400亿元市值取得断层式第一。2023年度，片仔癀总营收首次超过100亿元，同比增长15.24%，归母净利润实现近28亿元，同比增长13%。2024年一季度，市场呈现出旺销态势，业绩延续增长，预计实现归母净利润同比增长不低于25%。片仔癀的主要业务板块包括医药制造业、医药流通业及化妆品业等。其中，医药制造业占据其收入的“半壁江山”，该业务板块以“片仔癀”为主，也包括安宫牛黄丸等系列产品，涵盖了肝病用药、感冒用药、皮肤科用药等多个领域。片仔癀业绩靓丽，得益于控股子公司业绩指标再度跃升。2023年上半年，控股子公司合并营业收入、利润总额均达两位数增长，特别是龙晖药业的安宫牛黄丸销售创历史新高。化妆品业务是片仔癀打造的第二增长曲线，拥有“片仔癀”及“皇后”等多个品牌，2017-2021年实现快速增长，不过近两年却出现业绩“失速”，2021年、2022年、2023年前三季度分别实现收入8.41亿元、6.34亿元、4.31亿元，占总收入比例为10.49%、7.30%、5.67%。对此，片仔癀计划一边通过专业团队、渠道优化、黄金单品、品牌建设、科研投入五大行动赋能化妆品渠道增长，一边将化妆品板块分拆上市，目前正在梳理IPO尽职调查问题，推进股份制改造流程。片仔癀化妆品公司营收及增速（单位：百万元）相较于片仔癀，云南白药的营收规模更大。凭借生产经营核心底座（药品、健康品、中药资源、省医药四大事业部），2022年、2023年前三季度分别实现总营收约365亿元、297亿元。目前，云南白药的业务布局涉及天然药物、中药材饮片、特色药、医疗器械、健康日化产品、保健食品等多个领域，从传统中药制造企业向现代化大健康企业转型。例如，药品事业部以云南白药主系列产品为主，同时涵盖伤风感冒、心脑血管等领域其他品牌中药；健康品事业部以牙膏品类为业务核心，开拓口腔护理、养元青防脱洗护新品类；中药资源事业部打造包括品牌药材等B端产品、保健食品族等C端产品。如今，云南白药还进军了百亿级核药赛道。2022年9月，云南白药以2000万元拿下北京大学第一医院、北京市肿瘤防治研究所合作研发的前列腺特异性膜抗原（PSMA）靶向核药相关专利。今年2月，其全资子公司云核医药靶向PSMA的诊断核药INR101注射液获NMPA批准开展临床试验。近年来，核药赛道投融资火热，并购和BD交易也频频发生，已经成为药企的兵家必争之地，其中不乏诺华、拜耳、礼来等MNC巨头、老牌核药龙头东诚药业、“后起之秀”先通医药，以及远大医药、恒瑞医药等进军的传统药企。02以岭、康缘、众生积极转型创新药除拓展化妆品业务、转型大健康公司外，更多中药企业选择研发创新药，包括中药创新药、化学药和生物药等。例如，以岭药业布局多条1.1类中药创新药管线，在研立项品种涵盖呼吸、消化、心血管系统等疾病，目前已有5款处于临床III期及申报上市阶段，针对糖尿病视网膜病变、过敏性鼻炎和类风湿性关节炎等适应症。以岭药业在研项目情况同时，以岭药业也积极布局化生药业务和健康产业。其中，化生药板块采取“转移加工切入—仿制药国际国内双注册—专利新药研发生产销售”齐步走的发展战略。截至2023年上半年，以岭药业已有4个1类创新药品种进入临床阶段，其中治疗术后疼痛的苯胺洛芬注射液已完成临床III期，即将申报NDA；另外3个管线针对的适应症，包括实体瘤、缺血性脑卒中和子宫肌瘤等。康缘药业也是国内中药创新药领域龙头之一，为实现研发创新转型、寻求新的增长点，其制定了“一体两翼”研发策略——以现代中药为主体，化药、生物药协同发展。据悉，康缘药业已有12个创新中药管线处于临床II期、III期及NDA阶段，主要以妇科中成药成熟度最高。在化生药方面，康缘药业杀入了多个市场潜力巨大的赛道，其中已有5款化药1类项目进入临床试验，包括治疗阿尔茨海默症的DC20、WXSH0493片（高尿酸血症）、DC042（前列腺增生）、KY0135片（胰腺癌）、KY1702胶囊（脑瘤）；在生物药领域主打的CD38单抗KYS202002A注射液已获批3个临床，针对多发性骨髓瘤、系统性红斑狼疮，并在中美两国开展临床试验。众生药业的主要收入来自中成药销售，2023年上半年占据54.53%的收入比例，其次为化学药销售，占比36.4%，中药材及中药饮片销售占比为7.14%。在创新药的布局上，众生药业主要聚焦代谢、呼吸和肿瘤等疾病领域，目前已有7个处于临床试验阶段，1个已获批上市（来瑞特韦片，研发代号：RAY1216），来瑞特韦片是中国首个3CL单药抗新冠病毒感染口服药。众生药业在研管线从进度上看，小分子RNA聚合酶抑制剂ZSP1273（昂拉地韦片）已完成治疗成人单纯性流感的III期临床试验顶线数据初步统计分析结果；治疗非酒精性脂肪性肝炎（NASH）/代谢功能障碍相关脂肪性肝炎（MASH）的一类创新药ZSP1601已完成Ib/IIa期临床研究，达到主要研究终点；长效GLP-1类创新结构多肽药物RAY1225注射液（RAY002），在临床前研究中，药代特性显著优于同靶点化合物，目前正在开展I期临床。此外，布局创新中药研发的中药企业，还有步长制药、方盛制药、健民集团等。03天士力聚焦容量大、发展快领域在众多中药企业中，积极投入研发、大刀阔斧向创新转型的，除康缘药业、以岭药业外，还有天士力、华润三九、济川药业等。以天士力为例，2021年、2022年、2023年前三季度的研发费用分别为5.8亿元、8.44亿元、5.58亿元。中药企业研发投入金额对比（单位：亿元）在研发策略上，天士力与康缘药业一样，都是利用现代中药、生物药、化学药协同发展优势进行创新药物的战略布局。不同之处在于，天士力的疾病领域更为聚焦，主要为中国市场容量最大、发展最快的心脑血管、消化代谢、肿瘤领域，而且创新药管线数量极为丰富，目前已拥有97款在研产品，其中包括41款1类创新药，并有39款已进入临床试验阶段，25款已处于临床II、III期研究阶段。从疾病领域看，心脑血管领域是天士力的主要收入来源，多年收入占比保持在60%左右，主要凭借核心产品复方丹参滴丸形成心脑血管品牌优势。目前，天士力已在这一领域布局18款产品，覆盖心衰、心梗、脑卒中和冠心病等适应症。在消化代谢领域，天士力主要聚焦糖尿病及并发症的治疗，共布局18款在研项目；在肿瘤领域，主要围绕肿瘤免疫治疗和肿瘤靶向治疗进行精准布局，拥有20个在研项目，涉及PARP抑制剂、新一代Wee1抑制剂、靶向EGFR单抗、PD-L1/VEGF双抗、靶向叶酸受体α的第三代ADC药物等。另外，在中枢神经领域及呼吸系统，天士力采取自主研发并行产品引进的研发策略，针对抑郁、失眠、帕金森等疾病领域。按药物类型看，天士力在生物药领域布局了12款产品，其中普佑克适应症从急性ST段抬高型心肌梗死（心梗）治疗拓展至急性缺血性脑卒中（脑梗）治疗，已处于III期验证性试验；在化学药领域布局了57款化学药产品，涵盖创仿结合研发管线。天士力生物药研发管线（部分）04结语总体来看，中药企业都在“求变”，创新药或许是个好的转变方向。然而，创新药研发之路道阻且长，不仅需要投入大量人力、物力和财力，更面临着技术难度高、市场风险大、政策环境复杂等多重挑战。中药企业能否在激烈的市场竞争中占据有利地位，需要更加关注市场需求变化，并灵活调整管线研发战略，尤其得实现研发成果的商业化变现。END内容沟通：13810174402医药代表交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联

Debiopharm announces poster presentations on data for their potentially best-in class compounds: Debio 0123, a brain-penetrant WEE1 inhibitor, and Debio 0432, a selective USP1 Inhibitor LAUSANNE, Switzerland--(BUSINESS WIRE)-- Debiopharm ( ), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard-of-care to cure cancer and infectious diseases, today announced preclinical data releases for two of their compounds inhibiting the DNA-damage response (DDR) of cancer cells, including Debio 0123 [selective WEE1 inhibitor] and Debio 0432 [Selective USP1 Inhibitor] at the 2024 Annual American Association for Cancer Research (AACR) summit in San Diego, California. “Since 2017, Debiopharm has been growing its expertise in the DDR inhibitor field, firstly through its WEE1-inhibitor Debio 0123 and through the recently in-licensed asset, targeting USP1. These posters are proof of our commitment to stay at the forefront of DDR-inhibitor development and outsmart hard-to-treat cancers through synthetic lethality or other groundbreaking combinations.” - Angela Zubel, Chief Development Officer at Debiopharm AACR 2024 Poster Presentations Debiopharm compound Title Presenter Mon, April 8th Poster display: 9:00-12:30pm Abstract #: CT064 Poster Section: 48 Poster Board #: 14 Debio 0123 Impact of food and high gastric pH on the bioavailability of the WEE1 inhibitor Debio 0123 assessed in a Phase 1 dose escalation study Anne Bellon, Clinical Pharmacology Lead Mon, April 8th Poster display: 1:30-5:00pm Abstract #: 3370 Poster Section: 29 Poster Board #: 27 Debio 0123 Anti-tumor activity of Debio 0123 in combination with sacituzumab govitecan in preclinical models of breast cancer Luke Piggott, Principal Scientist Tue, April 9th Poster display: 1:30-5:00pm Abstract #: 6507 Poster Section: 46 Poster Board #: 24 Debio 0123 Simulation driven identification of combination for the WEE1 inhibitor Debio 0123 results in synergistic effect with cabozantinib validated in vivo Luke Piggott, Principal Scientist & Turbine AI Wed, April 10th Poster display: 9:00-12:30pm Abstract #: 7145 Poster Section: 23 Poster Board #: 7 Debio 0432 Identification of Debio 0432 as a potent and selective USP1 inhibitor for cancer therapy Noemie Luong, Associate Principal Scientist About DNA-Damage Repair (DDR) When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells rely a lot on DDR as they divide and grow uncontrollably. Inhibition of DDR, particularly in combination with other anticancer agents, prevents cancer cells from repairing their DNA, which ultimately activates a self-destruction program in cancer cells. DDR inhibitors such as Debiopharm's WEE1 and USP1 inhibitors, are being tested in clinical and preclinical studies. Debiopharm’s commitment to cancer patients Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select large pharmaceutical commercialization partners to maximize patient access globally. Visit us Follow us @DebiopharmNews

~ The Company will showcase ATP-Max KinomeScreen, the latest evolution of its industry leading HotSpot™ kinase assays, alongside its broad end-to-end oncology platform ~ ~ Reaction Biology will also present 15 posters and exhibit at Booth #141 in the Exhibit Hall ~ MALVERN, Pa., April 3, 2024 /PRNewswire/ -- Reaction Biology ("Reaction" or the "Company"), an industry-leading provider of drug discovery and development services, today announced that it will feature its recently launched HotSpot™ ATP-Max KinomeScreen at the American Association for Cancer Research (AACR) Annual Meeting 2024, held April 7-10, 2024, in San Diego, California. "ATP-Max KinomeScreen represents our commitment to innovation in kinase testing and further cements Reaction Biology as the leader in kinase innovation for more than 20 years," said Haiching Ma, Ph.D., Chief Scientific Officer of Reaction Biology. "We are now delivering the highest level of sensitivity at 1mM ATP testing on the industry's largest portfolio of kinase targets using the gold standard filter binding radiometric assay. At AACR 2024, we are excited to showcase how this advancement will provide customers with even more physiologically relevant data to help identify more potent and specific kinase inhibitors as they advance their discovery programs." In addition, the Company will present fifteen abstracts highlighting data from its broad end-to-end oncology platform, with products and services ranging from protein production to in vivo services. For additional information on the data to be presented, please visit Reaction's website. "We provide biopharmaceutical companies with a comprehensive and robust end-to-end oncology platform," said John H. Johnson, Chief Executive Officer of Reaction Biology. "We maintain more than 2,000 targets across our portfolio of biochemical assays, a wide variety of cell-based assays, including target engagement and 2D/3D cell panel screening, and biophysical assays including SPR. Within our offering, we also have a unique portfolio of in vivo models, including one of the broadest collections of syngeneic tumor models used in conjunction with our in vitro and in vivo immuno-oncology applications, along with InVEST™, which is our in vitro safety screening service. Through the work of our highly qualified team of scientists within our state-of-the-art laboratories, we proudly deliver high integrity data with passionate service to help our customers more effectively discover and develop innovative medicines." New data will be presented on the Company's innovative assay technologies, preclinical profiling models and proprietary screening platforms. The full range of data to be presented at AACR include: Relevance of substrate selection for the results of biochemical WEE1 in-vitro kinase activity inhibition assays (Sunday, April 7, 2024, 1:30 – 5:30 PM; Poster Section 26, Poster Board Number: 25, Permanent Abstract Number: 648) Comprehensive 27-marker standard panel for immune monitoring of pre-clinical tumor mouse models using spectral analyzer technology (Sunday, April 7, 2024, 1:30 – 5:30 PM; Poster Section 3, Poster Board Number: 27, Permanent Abstract Number: 91) Screening the entire kinase-directed, FDA-approved pharmacopeia against the largest collection of wild-type and mutant kinases reveals many opportunities for drug repurposing and targeted therapy (Sunday, April 7, 2024, 1:30 – 5:30 PM; Poster Section 39, Poster Board Number: 6, Permanent Abstract Number: 938) The in vivo Hollow Fiber model is a valuable tool in drug development of selective Kras inhibitors (Monday, April 8, 2024, 1:30 – 5:00 PM; Poster Section 22, Poster Board Number: 12, Permanent Abstract Number: 3164) Comparison of MB-49_luc bladder carcinoma cell clones in the orthotopic superficial bladder tumor model in C57BL/6 female mice (Monday, April 8, 2024, 1:30 – 5:00 PM; Poster Section 10, Poster Board Number: 3, Permanent Abstract Number: 2816) Biochemical and cell-based assay platforms for development of RAF inhibitors against human cancers (Tuesday, April 9, 2024, 9:00 AM – 12:30 PM; Poster Section 28, Poster Board Number: 24, Permanent Abstract Number: 4704) Development and evaluation of a high-throughput method for rapid detection of surface antigen expression in fixed cells (Tuesday, April 9, 2024, 9:00 AM – 12:30 PM; Poster Section 44, Poster Board Number: 30, Permanent Abstract Number: 5157). These data are in collaboration with 4HF Biotec GmbH. Potency and selectivity of ERBB2-targeting antibody drug conjugates in vitro (Tuesday, April 9, 2024, 9:00 AM – 12:30 PM; Poster Section 29, Poster Board Number: 1, Permanent Abstract Number: 4708). These data are in collaboration with 4HF Biotec GmbH. Development of biochemical screening assays to facilitate drug discovery in RNA m6A modification regulators (Tuesday, April 9, 2024, 9:00 AM – 12:30 PM; Poster Section 17, Poster Board Number: 21, Permanent Abstract Number: 4417) Donor-dependent anti-tumoral efficacy of human CD19 CAR T cells in a leukemic xenograft mouse mode (Tuesday, April 9, 2024, 9:00 AM – 12:30 PM; Poster Section 2, Poster Board Number: 29, Permanent Abstract Number: 4020) Cell-based PROTAC screening for cancer drug discovery (Tuesday, April 9, 2024, 1:30 PM – 5:00 PM; Poster Section 30, Poster Board Number: 8, Permanent Abstract Number: 6049) In vitro cytotoxicity assays to support CAR T cell evaluation against solid tumors (Tuesday, April 9, 2024, 1:30 PM – 5:00 PM; Poster Section 1, Poster Board Number: 17, Permanent Abstract Number: 5242) Selectivity profiling of small molecule kinesin inhibitors using microplate-based ATPase activity assay (Tuesday, April 9, 2024, 1:30 PM – 5:00 PM; Poster Section 18, Poster Board Number: 23, Permanent Abstract Number: 5723) Paradoxical activation of kinases occurs directly with ATP-competitive kinase inhibitors and is observable biochemically at physiologically relevant drug concentrations (Tuesday, April 9, 2024, 1:30 PM – 5:00 PM; Poster Section 46, Poster Board Number: 6, Permanent Abstract Number: 6489) Modulation of human macrophage differentiation, phenotype and function in vitro as a strategy to characterize novel tumor microenvironment modulators (Tuesday, April 9, 2024, 1:30 PM – 5:00 PM; Poster Section 47, Poster Board Number: 23, Permanent Abstract Number: 6538) Copies of the poster presentations will be available at Reaction Biology's booth (#141) during Exhibit Hall hours from April 7-10, 2024. About Reaction Biology Founded in 2001, Reaction Biology is a global contract research organization (CRO) that provides drug discovery and development services to biopharmaceutical customers worldwide. Reaction specializes in supporting research goals with capabilities that include protein and peptide production, biochemical and biophysical assays, high throughput screening, exploratory toxicology, biomarker discovery tools, and an extensive array of cell-based and pharmacological assays modelling various diseases. Reaction also provides Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) analytical and functional bioassays for testing potency, efficacy, and safety of large biological molecules, enabling clinical and commercial manufacturing batch release. Reaction has helped to advance many of its customers' molecules through discovery and development pipeline stages into later clinical phases and commercialization. These molecules may ultimately benefit patients living with cancer and other serious diseases. Reaction maintains one of the largest panels of kinase assays in the world with over 800 unique targets and performs more than 5,000 client projects annually with its over 2,000 validated assays. Reaction has laboratory facilities in Malvern, PA, Hershey, PA, Freiburg, Germany, and Heidelberg, Germany. For more information, visit and follow us on Twitter / X @ReactionBiology and on LinkedIn. Contact: Elixir Health Public Relations Lindsay Rocco +1 862-596-1304 [email protected] SOURCE Reaction Biology