Pegfilgrastim (Amgen)

CHS-114 shown to have an acceptable safety pro no dose-limiting toxicities (DLTs) in heavily pretreated patients with solid tumors Selective depletion of peripheral CCR8+ regulatory T cells (Tregs) was observed and depletion was maintained over the dosing interval, establishing proof of mechanism Preclinical data and preliminary clinical results support further evaluation of CHS-114 in combination with the anti-programmed cell death protein 1 (PD-1) antibody, toripalimab-tpzi, and other immuno-oncology (IO) agents REDWOOD CITY, Calif., May 23, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced clinical data from the CHS-114, single agent dose escalation stage of its Phase 1 study at the ASCO Annual Meeting, taking place May 31 to June 4, 2024, at McCormick Place in Chicago. CHS-114 is a novel afucosylated human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that selectively and potently targets human CCR8 with no off-target binding. CCR8 is a G protein-coupled receptor (GPCR) that shows preferential expression on tumor resident Treg cells and has promise as a drug target for selectively targeting immune suppression in the tumor microenvironment (TME) without broadly depleting Treg cells, which has the known unwanted side effect of autoimmune activation. “The Phase 1 preliminary dose escalation results are an important milestone as we progress our innovative I-O pipeline. We are very pleased with the safety profile, the predictable dose proportional pharmacokinetic profile, and the selective depletion of peripheral CCR8+ Tregs that were observed,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “By targeting CCR8, we believe CHS-114 has the potential to overcome Treg immune suppression in the TME and allows T cell recruitment, which turns cold tumors hot and enhances anti-tumor activity when combined with I-O agents. The data support further evaluation of CHS-114 in combination treatment with our anti-PD-1 antibody, toripalimab, and other I-O agents.” CCR8 is a chemokine receptor predominantly expressed by tumor infiltrating Tregs that suppress the body’s natural anti-cancer immune response. Targeting CCR8 is a promising potential therapeutic strategy designed to selectively deplete intratumoral CCR8+ Tregs, reshape the tumor microenvironment by alleviating local immunosuppression, and enhance anti-tumor immune response when combined with I-O agents. Data presented at ASCO demonstrate proof of mechanism for selective depletion of CCR8+ Tregs and an acceptable safety pro date. Poster presentation: Abstract # 2664: Preliminary Results of a Phase 1, First-in-human, Dose Escalation Study of the Anti-CCR8 Cytolytic Antibody, CHS-114 (formerly SRF114) in Patients with Advanced Solid Tumors. Poster Session: Developmental Therapeutics - Immunotherapy Date and Time: Saturday, June 1, 2024, 9:00 a.m. – 12:00 p.m. Central Daylight Time Poster presentation data are summarized as follows: CHS-114 has demonstrated an acceptable safety pro 20 evaluable, heavily pre-treated patients with advanced solid tumors, with no DLTs reported to date. Treatment emergent adverse events (TEAEs) were generally low grade. One patient experienced a treatment-related serious adverse event (SAE) of Grade 2 colitis. There were no treatment related adverse events (AEs) leading to discontinuation or death. CHS-114 PK exposure was approximately dose proportional, and the elimination appeared linear with a half-life of about 10 days (range 9-17 days). Depletion of peripheral CCR8+ Treg cells was observed and depletion was maintained over the dosing interval, establishing proof of mechanism. Preliminary results and acceptable safety pro further evaluation of CHS-114 in combination treatment with toripalimab and other I-O agents. In 19 patients evaluable for response, no objective responses were yet noted, while the stable disease rate was 47%. About the Phase 1 trial (NCT05635643): SRF114-101 is a Phase 1, First-In-Human, open-label, dose escalation study, evaluating CHS-114 as a single agent and in combination with toripalimab. The study enrolled patients with advanced solid tumors who received more than one line of prior treatment (75% had more than three prior lines). Stage 1a of the study included CHS-114 administered intravenously (IV) on day one of each Q3W cycle as part of single-agent dose escalation and employed the Bayesian optimal interval (BOIN) design, including accelerated titration and 3+3 run-in. Stage 1b will enroll an additional five patients with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) at each of two dose levels. Primary endpoints: rate of DLTs and TEAEs, with the overarching objective of determining two recommended doses for expansion (RDE). Key secondary endpoints: objective response rate (ORR) based on Investigator review per RECIST v1.1, pharmacokinetics, pharmacodynamic assessments (changes in FOXP3 expression within tumor tissue –Stage 1b). Exploratory pharmacodynamic endpoint: Changes in frequency of CCR8-expressing immune cell subsets in the periphery. About CHS-114 CHS-114, a human, afucosylated anti-CCR8 monoclonal antibody, is designed to selectively target human CCR8 and preferentially deplete CCR8+ Tregs within the tumor microenvironment, while preserving effector T (Teff) cells in tumors or Tregs in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In addition, treatment with CHS-114 alone reduced tumor growth in murine models, and enhanced antitumor activity was observed in combination with anti-PD-1 treatment. CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643) as a monotherapy and in combination with toripalimab in advanced solid tumors, including head and neck cancer. As reported in June 2023, early evidence of biological effect has been seen with CCR8+ Tregs depletion in blood following treatment with CHS-114, with no effect observed on non-CCR8+ Tregs. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on researching, developing, and commercializing innovative therapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline expected to synergize with its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4, with a response from the FDA on Coherus’ IND filing expected in the second quarter of 2024. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, and YUSIMRY® (adalimumab-aqvh), a biosimilar of Humira®. Neulasta® is a registered trademark of Amgen, Inc. Humira® is a registered trademark of AbbVie Inc. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to identify synergies between its I-O pipeline and its commercial capabilities; Coherus’ expectation for the timing of the FDA’s response for its IND for CHS-1000; Coherus’ expectation that CHS-114 has the potential to overcome Treg immune suppression in the TME; and Coherus’ expectations that its immunotherapy candidates will enhance outcomes for patients with cancer. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance, or achievements to differ significantly from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the preclinical and clinical drug development process; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ competitive position; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; the risks of competition; the risk that Coherus is unable to complete commercial transactions; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2024 filed with the Securities and Exchange Commission on May 9, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission. UDENYCA®, YUSIMRY® and LOQTORZI®, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Coherus Contact Information: For Investors: Jami Taylor Head of Investor Relations IR@coherus.com For Media: Jodi Sievers VP, Corporate Communications media@coherus.com

与其抓风口，不如攥拳头。撰文| 石若萧编辑| 顿河试想，有这样一家国内药企。它创立于世纪之初，从原料药和仿制药起家，为了追赶时代，收购了多家创新药公司。但它并没有把本来的业务落下，不光在一些原料药类别上有一定议价权，还在国谈、集采上取得了不少成果。此外，它还有中药板块，拥有高达100多个中药品种，其中还有不少是全国独家品种。并且它的创新药业务也绝非业内常见的“干打雷不下雨”，正儿八经有产品获得了美国FDA上市批准。出海它也没闲着，是中国目前为数不多的在国内、欧洲及亚太区域同时拥有药品研发、生产和营销网络的企业。而就在最近，它还赶上了最近大热的合成生物学热点，受到了二级市场不少关注。这样一家全方位开花的企业，市值应该多少比较合理？以下是一些参考：华东医药近600亿，济川药业近400亿，恒瑞医药近3000亿，和黄医药超300亿（港元），中国生物制药近600亿（港元），石药集团超800亿（港元）。可本文的主角——亿帆医药，市值竟然只有“可怜巴巴”的170亿，几乎只是一个中游Biotech的水平。梳理亿帆医药旗下的板块，该有的都有了，布局不可谓不庞大，但市值看上去却一点都不匹配。这是为什么？是个人的不努力？还是历史的不给力？浙商与徽商的结合追溯历史，亿帆医药最初共有两个前身。首先是成立于2000年，以精细化工产品、食品和饲料添加剂，泛酸钙等原料药为主营业务的鑫富药业，创始人名叫过鑫富，看经营作风，是个典型的浙商。浙商历来以生猛著称，创业往往不是慢慢生根发芽，而是只要看准方向，就什么都敢做，版图越打越大，便成了集团。比如新和成集团创始人胡柏藩，横店集团创始人徐文荣，复星集团创始人郭广昌，都是江浙企业家的典型代表。过鑫富也不例外，他本是一名国企员工，80年代辞职下海，创建了一家电缆厂，觅得了第一桶金，算是个敢想敢干的“狠人”了。然而好景不长，90年代，光缆取代了电缆，逼得他只好另选赛道。这一次他选定了饲料添加剂维生素B5，创办了临安生物化学有限公司，即后来鑫富药业的前身。这一次过鑫富赌对了。2004年，深交所中小板正式开板，同年鑫富药业在深交所挂牌上市，2005年，鑫富药业成功收购国内第二大维生素B生产商，并成为了世界上最大的B5生产商。本可以好好当个大老板的过鑫富，或许是性格使然，始终没法安定下来。接下来几年，他在资本市场上大展身手，涉足行业众多，却接连卷入了行贿案、财务造假等风波中。加上原料药价格的周期性波动，搞得公司一度处于ST退市风险警示状态。直到2014年公司被亿帆生物借壳上市后，过鑫富本人才逐渐淡出了公司的经营。而第二个前身，正是成立于2003年的“合肥亿帆医药经营”有限公司，这家公司原本也没什么创新药基因，而是专注于药品流通环节，主要从事药品的配送、代理和销售。同浙商过鑫富相比，徽商程先锋的打法显得稳重得多，十多年来一直在医药行业深耕，在亿帆内部不断增资扩股，扩大经营范围，并推动了公司上市，此外还在多家医药公司担任董事长、执行董事等职位。2014年，经过重大资产重组，程先锋将亿帆生物和亿帆药业分别作价14.8亿和2.7亿注入鑫富药业构成借壳上市，过鑫富等股东及原管理层陆续减持并退出。但和许多借壳上市的案例不同的是，亿帆医药没有把鑫富药业本来的业务“甩掉”，许多业务至今仍在运行。据亿帆医药年报披露，公司原料药维生素B5及原B5产品全球市场占有率40%-45%，居龙头地位。或许正是当年这段复杂的历史，奠定了亿帆医药如今业务“四面分叉”的基础格局。早期“BD狂人”借壳上市成功后，恰逢泛酸钙进入上行周期，公司业绩不错，账上有了钱，亿帆医药便顺势开启了它的一连串收购战事。先是在2015年，与国药一心签订协议，以2.35亿元自有资金受让国药一心制药的7个血液肿瘤药品种和1个皮肤科肿瘤药品种。除了化药，还有中药。同年，又以自有资金2.4亿元收购安徽天康药业100%股权（现名天长亿帆）。彼时后者拥有治疗白血病、妇科病及品牌OTC等药品批准文号62个，其中独家品种、独家剂型与规格产品10个，中药三类新药产品7个。最具亮点的独家品种为复方黄黛片，主要用于治疗白血病。同年年底，又以自有资金3.03亿受让四川天联药业有限公司100%的股权；以自有资金7142万元受让沈阳澳华制药有限公司100%的股权。前者拥有除湿止痒软膏、银杏叶丸等产品；后者的独家产品皮敏消胶囊较为知名。总体来看，2015年的一系列收购占用的资金虽不算大，却有点乱，肿瘤药、皮肤病药、降血脂中成药都有涉及，找不出一个重点方向。引发资本市场更大关注的，还是自2016年起的一系列收购。比如当年以10亿人民币控股创新药公司健能隆（后更名为“亿一生物”），相当于正式宣告了进军创新药。同年，公司中文证券简称由“亿帆鑫富”变更为“亿帆医药”，证券代码不变，宣示其终于成功去“过鑫富”化。拿下健能隆后，亿帆医药的国际化野心进一步显露，2017年以1.36亿元收购了进口药品代理商业公司NovoTek的100%股权，后者拥有面向全球的医药行业商业谈判、技术引进及进口产品在中国境内成功准入的完备的国际化团队。2018年，亿帆医药的关注重心基本就移到了胰岛素上，先是以2.5亿人民币从Summit Bioteck收购了胰岛素类似物产品（Insulin Analogues）平台技术；然后要约收购了赛臻公司（SciGenLtd），后者的业务同样也是胰岛素；与佰通公司（Bioton S.A.）签订了《全球产品代理协议》，成为其重组人胰岛素国际销售的唯一代理商。次年，亿帆医药又拿下了佰通公司31.65%股权，成为其第一大股东。而佰通此前正是赛臻的母公司。此外值得一提的是，2018年底，亿帆医药以3000万美元收购了注册于意大利的非索医药和特克医药，从而拥有了具有美国FDA与欧盟GMP等审计认证的小分子注射剂药品的生产能力和质控水平，以及意大利、德国、加拿大、克罗地亚、荷兰、英国、以色列等10余个国家或地区的药品销售与市场资源。粗略总结一下，2016年亿帆医药改掉名字后，渐渐明确了自身的发展方向：即在原料药、化药和中药的基础上，猛烈发力生物药——主要是胰岛素和健能隆的艾贝格司亭α注射液。同时还立下了出海的大志向，一出手，就是横跨欧美的全球布局。这套打法颇受业界青睐。彼时，健能隆的独立上市一度还成为了资本市场关注的焦点。如今回顾这段历史，不得不感叹亿帆医药管理层的眼光足够超前，动作也是真的快。其收购健能隆，入局创新药的时间点，几乎和中国药审改革的节奏是一致的。做个对比，如今的华东医药常被业界称为“BD狂人”，然而华东虽早有转型意愿，但直到2020年初拳头产品阿卡波糖集采失标后，才开始了大手笔的连续BD。反观亿帆医药的一系列动作，比华东医药提前了足足三四年。可惜时也运也，接下来的发展，并没按照管理层设想的剧本走下去。梦想接连“破灭”就在亿帆医药成为佰通公司大股东后的第二年，新冠疫情汹汹来袭。疫情影响了出行。亿帆医药收购控股的许多胰岛素公司都在海外，交流不顺，一定程度上阻碍了第三代胰岛素产品的研发进度。但这还不算什么，更伤元气的是随后执行的国家第六批集中带量采购，导致胰岛素市场大幅“缩水”，行业龙头甘李药业、通化东宝都出现了业绩承压，亿帆医药代理的波兰佰通第二代胰岛素A类虽然中标，销量增长了42.83%，但销售收入却下降了18.63%。胰岛素战略受挫，一条支柱摇摇欲坠；另一边，创新药也没能给公司续上一口气。2023年5月，艾贝格司亭α注射液（亿立舒）在国内获批上市，同年11月，亿立舒的在美上市申请（商品名Ryzneuta）获FDA通过。亿帆医药便成为了国内首家以药品上市持有人（MAH）身份在美国FDA获得批准的创新生物药企业。虽然如今肿瘤新疗法此起彼伏，但许多患者依然需要接受化疗，并承受其副作用，对升白药的需求一直在增长。据弗若斯特沙利文预测，中国长效GCSF类药物在2025年预计达到102.70亿元的销售规模，在2030年将达到135.37亿元。作为与安进的原研Neulasta头对头达到非劣效成果的自主研发创新型1类生物药，全球首个双分子G-CSF Fc融合蛋白，亿帆医药对亿立舒无疑寄予了厚望。然而现实残酷，升白药领域实在太卷了。海外有安进的原研药，在国内，竞争者有百克生物的津优力、齐鲁的新瑞白、恒瑞的艾多、鲁南的申力达，甚至还有一些中药，比如梦阳药业的生白口服液。亿立舒想从中切下一块蛋糕，还欠许多市场教育工作要做。重磅原研药的市场推广不及预期，只能在财报中进行大额减值。今年4月20日，亿帆医药发布公告称，本次计提资产减值准备合计约9.52亿元，其中对亿立舒的无形资产计提就高达8.48亿元。直接导致的结果是，2023年，亿帆医药的利润为负值，亏掉5.5个亿，同比下降388%。至此，亿帆医药的生物药转型战略不说一败涂地，离最初的目标也是相去甚远。现在回到文章开头的那些对标企业，不难发现，其中不少都有“大单品”以及相匹配的强悍销售团队。比如济川药业有蒲地兰口服液；和黄医药拿出了在美超高定价的呋喹替尼；华东医药在仿制药时代有阿卡波糖，现今又处在国产GLP-1研发进度第一梯队中。两条腿走路，无论当下的业绩支撑还是未来预期，都有故事可讲。反观亿帆医药，庞大版图下，竟连一个拳头产品都找不出来。并且在多年的生物药转型战略执行之下，2023年生物药营收占总销售比例仅4%出头。更尴尬的是，公司自2016年股价就在15元上下来回波动，现在8年过去，几乎没怎么变。真是起了个大早，赶了个晚集的典型。究其原因，宏观战略眼光到位了，但具体的赛道选择和战术执行上却出现了偏差，外加运气实在太差，导致理想与现实相去甚远。不过，至少一口气将减值风险出清，宣告“认栽”后，亿帆医药的业绩终于开始了回升。2024年第一季度，公司实现营业收入13.26亿，增长41.28%；归母净利润1.46亿，同比增长125.55%。公司表示，业绩大幅增长主要系公司新增及原有医药自有产品（含进口）完成市场初步布局，销售毛利增长幅度大于费用增长幅度，以及取得与收益相关政府补助同比增加所致。如此看来，有厚实的资产包托底，亿帆医药其实还是能打的，输个一回两回，也不是输不起。既然过去选择的方向都未达预期，那么当务之急，就是选定下一个重点发展方向。这个方向会是什么？合成生物类产品或是答案。前些天，亿帆医药宣布，合成生物类产品是公司未来发展的重要方向之一，首个合成生物研发项目预计将于2024年年底建设完成。目前还无法判断这一决策是否能见效，但就过去的经验来看，当下的亿帆医药，比起急于抓住风口，更重要的恐怕是好好梳理一下自己旗下庞大的资产，明确自己的优势，削减不必要的开支，把张开的手掌攥成一个拳头。然后，再轻装上阵，开启下一趟征程。回复“CM10”，获取医药资本市场E周动态，欢迎订阅~