HLX-301

好日子谁都想过，但复宏汉霖偏不。2022年，仅汉利康、汉曲优和汉达远3款产品，就为复宏汉霖带来23.58亿元收入（含授权许可收入），然而为了长久的“幸福”，复宏汉霖将钱砸向研发，毅然选择继续勒紧裤腰带“吃苦”，终于在2023年迎来了曙光。近日，复宏汉霖发布了2023年正面盈利预告，全年利润不低于5亿元，值得一提的是，这是复宏汉霖首次实现年度盈利。从亏损到盈利，复宏汉霖靠什么华丽转身？01做仿制，实现Biopharma的早期出彩复宏汉霖的5款上市产品，分别为利妥昔单抗（汉利康）、曲妥珠单抗（汉曲优）、阿达木单抗（汉达远）、贝伐珠单抗（汉贝泰）和斯鲁利单抗（汉斯状），前4款均为生物类似药。精准定位，仿制同样也能差异化。复宏汉霖的汉利康是其首款获批上市的产品，也是国内首个获批的利妥昔单抗生物类似药，率先打破了进口药垄断格局。然而，仅打破进口垄断还不仅仅是复宏汉霖的目标，因原研药在国内未获批类风湿关节炎适应症，复宏汉霖瞄准适应症差异化“缺口”，在2022年3月获批了该适应症，让汉利康在适应症覆盖面上赶超原研药，大大增加了撕开被垄断市场的成功几率，据药智数据显示，汉利康自上市以来，年度销售额持续增长，2022年为17.13亿元，同比增长18.04%。适应症的差异化布局，让汉利康在海外同样“受宠”，2023年4月，Boston Oncology与复宏汉霖达成合作协议，获得在沙特阿拉伯、埃及、巴林等中东和北非地区商业化汉利康的权利，但这不并不是复宏汉霖的生物类似药首次“走出”国门。瞅准市场，与原研药PK国际市场。汉曲优是复宏汉霖获批上市的第2款产品，为曲妥珠单抗（赫赛汀）生物类似药，由于赫赛汀在全球范围均属昂贵药物，2018年时，单瓶（440毫克）在美国的价格为4500-5100美元，在欧盟，则以单剂量（150毫克）销售，价格为500-700美元，此外，尽管赫赛汀已被纳入国家医保目录大幅降价，但单瓶（440毫克）价格仍高达7270元，据弗若斯特沙利文报告显示，当时中国仅有约25%患者能负担治疗费用。复宏汉霖抓住市场机遇，及时布局，让汉曲优成为首款在中国开发且同时在全球多个地区进行3期临床试验的赫赛汀生物类似药。2020年7月，汉曲优在欧盟获批上市，成为首个在欧盟获批的国产单抗生物类似药，2020年8月，汉曲优又在国内获批，又一次打破进口药的垄断。时至今日，汉曲优已成为国产生物类似药“出海”代表，据复宏汉霖2023半年报显示，已在约40个国家和地区获批上市，上半年实现销售收入12.39亿元，同比增长54.8%。还有多款重磅仿制药在手。据复宏汉霖2023半年报显示，产品管线中已处于IND及以上阶段的单抗类似药还有6款，分别为HLX11（帕妥珠单抗）、HLX14（地舒单抗）、HLX05（西妥昔单抗）、HLX15（达雷妥尤单抗）、HLX13（伊匹木单抗）和HLX17（帕博利珠单抗），其中，HLX11和HLX14已处于3期临床阶段。图1 复宏汉霖进入临床阶段产品管线图片来源：复宏汉霖2023半年报值得一提的是，HLX11和HLX14如汉曲优一样也采取国际化战略开发，进行了国际多中心临床研究，其中，HLX11已获中国和欧盟临床许可，HLX14已获中国、欧盟和澳大利亚临床许可。02为创新，不惜再苦熬几年4款生物类似药的陆续获批上市，为复宏汉霖带来了营收的持续剧增，到2022年，仅汉利康、汉曲优和汉达远3款产品就为其带来23.58亿元的收入（含授权许可收入），然而，复宏汉霖仍无法实现盈利，原因在于研发上的巨额支出，2022年研发开支为13.95亿元，同比增长36.19%，这也解释了复宏汉霖赚的钱都去哪了。一切为了创新。梳理复宏汉霖历年研发开支可以发现，其也算的上是研发上的“烧钱王”，产品一路获批的越多，反而研发开支却越来越大，在第4款产品汉贝泰获批（2021年12月）后的2022年，研发开支反而是首款产品获批（2019年2月）前一年度的近4倍，5年时间研发开支总额超43亿元。图2 复宏汉霖2018年-2022年研发开支情况数据来源：复宏汉霖历年年报复宏汉霖本可凭借4款产品迎接利润“黎明”，却“为难”自己在亏损的“黑暗”中继续前行数年。据其招股书显示，在2019年时，管线中就包含多款创新药，其中，HLX06、HLX07、HLX10、HLX20和HLX22已经进入临床阶段。先苦后甜，终于迎来“天”亮。2022年，复宏汉霖首款自研创新药斯鲁利单抗（汉斯状）获国家药监局批准上市，虽然汉斯状为PD-1单抗，但却是全球首个获批用于一线治疗广泛期小细胞肺癌（ES-SCLC）的PD-1药物，再一次的差异化布局，让这款PD-1的“后来者”在PD-1/L1极度内卷的市场中站稳脚跟。据复宏汉霖2023半年报显示，汉斯状上半年实现销售收入5.56亿元，值得一提的是，2022年12月，复星医药获得汉斯状在美国商业化权利，复宏汉霖将获得10亿元首付款和不超7亿元里程碑付款，截至2023年6月，已收到9亿元许可费用。此外，汉斯状也得到国外药企青睐，2023年8月，KGbio进一步扩大与复宏汉霖在2019年关于汉斯状的合作，进而获得沙特阿拉伯、埃及等12个国家包括ES-SCLC在內的2项适应症独家权利；2023年10月，Intas Pharmaceuticals与复宏汉霖达成合作，获得欧洲地区和印度现有适应症独家权利。笔者分析，复宏汉霖2023年的首次年度盈利，除了汉斯状销售收入持续增长的获益外，很大程度上得利于下半年几笔汉斯状海外授权的首款款及里程碑付款收入。值得一提的是，2023年12月，KGbio成功将汉斯状在印度尼西亚获批用于治疗ES-SCLC，实现了汉斯状海外市场进军的第一步。截至2023年底，汉斯状用于ES-SCLC的欧盟上市申请已获受理，同样适应症的美国桥接试验也正在进行中，此外，用于局限期小细胞肺癌的国际多中心试验在美国、澳大利亚、欧盟已处于3期阶段，汉斯状海外进军路已越走越宽。03“天”亮后，全面创新期开启如今的复宏汉霖，临床管线项目早已不再是生物类似药的天下，除了临床前产品均为创新药外，IND及以上阶段的项目也以创新药为主，且异常丰富，包括单抗创新药HLX04-O、HLX07、HLX22、HLX60和HLX51；双抗创新药HLX301；融合蛋白创新HLX53；ADC药物HLX42和HLX43；小分子创新药HLX208，以及围绕汉斯状开发的多个临床项目。图3 复宏汉霖非生物类似药管线图片来源：复宏汉霖2023半年报HLX04-O是复宏汉霖在上市产品贝伐珠单抗（汉贝泰）基础上进行优化，自主研发的重组抗VEGF人源化单克隆抗体眼科产品，截至2023年7月，用于湿性年龄相关性黄斑变性（wAMD）患者的国际多中心3期临床研究，已在欧盟国家拉脱维亚、澳大利亚及美国完成首例患者给药，据1/2期临床研究结果显示，HLX04-O在wAMD患者中安全性和耐受性良好，且展现出初步疗效。HLX07是复宏汉霖自主研发的靶向EGFR创新生物药，截至2023年底，已在中国、美国、欧盟、澳大利亚、日本等多个国家地区获得专利，且在中美获得临床试验许可，值得一提的是，复宏汉霖还围绕食管鳞癌、鳞状非小细胞肺癌、皮肤鳞癌等多个实体瘤适应症，开展HLX07单药或联合的2期临床探索。据一项HLX07联合汉斯状与化疗联用一线治疗晚期/复发性鳞状非小细胞肺癌患者2期研究数据显示，A组（6例）和B组（6例）根据RECIST 1.1评估未确认的ORR分别为83.3%和66.7%，两组的疾病控制率均为100.0%，该研究结果在2023年欧洲肿瘤学会亚洲分会（ESMO Asia）年会上得以展示，一同展示的还有小分子创新药HLX208。2023年4月，HLX208被正式纳入突破性治疗品种名单，用于治疗BRAF V600E突变的成人朗格汉斯细胞组织细胞增生症（LCH）和Erdheim-Chester病（ECD），ECD与LCH均为《第一批罕见病目录》中的疾病。随着上述产品临床试验进展的加持，复宏汉霖创新药研发实力将全面崛起。04结语好日子谁都想过，尤其是凭借已获批产品实现营收暴涨的复宏汉霖，过几天好日子更是理所当然，但为了长久“幸福”，毅然选择继续“吃苦”，终于在2023年迎来了光明，这段坚守初心静待花开的历程值得同行参考学习。参考来源：复宏汉霖官网、公告、招股书及半年报、年报声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 蓝色转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信） 阅读原文，是受欢迎的文章哦

DUBLIN--( BUSINESS WIRE )--The "Non-Small-Cell Lung cancer (NSCLC) - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 100+ companies and 120+ pipeline drugs in Non-Small-Cell Lung cancer (NSCLC) pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The reportoutlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Non-Small-Cell Lung cancer (NSCLC) pipeline landscape is provided which includes the disease overview and Non-Small-Cell Lung cancer (NSCLC) treatment guidelines. The assessment part of the report embraces, in depth Non-Small-Cell Lung cancer (NSCLC) commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Non-Small-Cell Lung cancer (NSCLC) collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Non-Small-Cell Lung cancer (NSCLC) R&D. The therapies under development are focused on novel approaches to treat/improve Non-Small-Cell Lung cancer (NSCLC) . Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs Chapters This segment of the Non-Small-Cell Lung cancer (NSCLC) report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs V940: Merck Sharp & Dohme LLC V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient's tumor. It is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. The drug is in Phase III stage for the treatment of NSCLC. QL1706: Qilu Pharmaceutical Co., Ltd. QL1706 is an investigational bifunctional antibody with additional anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody could increase the anti-tumor effect of anti-programmed cell death 1 (PD-1) antibody. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. The drug is in Phase III stage for the treatment of NSCLC. Zenocutuzumab (MCLA-128): Merus N.V. Zenocutuzumab (MCLA-128; Zeno) is a Biclonics antibody that overcomes HER3 mediated NRG1 (or NRG1 fusion) signaling in tumor cells. Zeno docks on HER2, then binds to and blocks the NRG1 fusion-HER3 interaction and HER3 heterodimerization with HER2. It has a dual mechanism against cancer, as it prevents NRG1 fusions from binding to the protein HER3 and it blocks the interaction of HER3 with HER2, which the cancer cells depend on to survive and multiply. Currently, the drug is in Phase II stage for the treatment of NSCLC. ZW49: Zymeworks BC Inc. ZW49 (zanidatamab zovodotin) is a bispecific anti-HER2 ADC that is based on the same antibody framework as ZW25 but armed with a cytotoxic payload. A biparatopic (targeting two different non-overlapping epitopes on ERBB2, on extracellular domains 2 (ECD2) and 4 (ECD4). ZW25 is an anti-HER2 biparatopic antibody which binds to the same domains as trastuzumab and pertuzumab. ZW25 simultaneously binds two distinct sites on HER2, a protein expressed on many types of cancer cells. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased antibody binding, receptor clustering, and removal of HER2 from the cell surface, and potent e?ector function. ZW49 is in Phase I of clinical trials for the treatment of non-small cell lung cancer. Non-Small-Cell Lung cancer (NSCLC): Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Non-Small-Cell Lung cancer (NSCLC) therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Non-Small-Cell Lung cancer (NSCLC) drugs. Non-Small-Cell Lung cancer (NSCLC) : Therapeutic Assessment Major Players in Non-Small-Cell Lung cancer (NSCLC) There are approx. 100+ key companies which are developing the therapies for Non-Small-Cell Lung cancer (NSCLC). The companies which have their Non-Small-Cell Lung cancer (NSCLC) drug candidates in the most advanced stage, i.e. Phase III include, Merck Sharp & Dohme LLC. Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Non-Small-Cell Lung cancer (NSCLC) Report Insights Non-Small-Cell Lung cancer (NSCLC) Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Non-Small-Cell Lung cancer (NSCLC) Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Merck Sharp & Dohme LLC Suzhou Puhe Pharmaceutical Technology Co., LTD Merus N.V. Zymeworks BC Inc. Cytos Biotechnology Exelixis ProfoundBio US Co. Beijing Pearl Biotechnology Limited Liability Company Pfizer OncoResponse, Inc. Next Point Therapeutics, Inc. Light Chain Bioscience - Novimmune SA Medolution Ltd. Immunitas Therapeutics Shanghai Henlius Biotech Key Products V940 YK-029A Zenocutuzumab (MCLA-128) ZW49 CMP 001 XL092 PRO1184 PLB1001 PF-07257876 OR2805 NPX267 NI-1801 Keynatinib IMT-009 HLX301 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/w14gce About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.