Systemic Lupus Erythematosus

“闷声发大财”的泽璟制药，开始被发现了。资深分析师：尧   今编审：苏   叶这是一家为数不多，大盘几乎涨了三年的未盈利创新药企。自2022年资本寒冬以来，整个行业面愁云密布。然而，泽璟制药涨幅却超400%，市净率显著高于行业平均，市值也翻了好几番，甚至已经超过了君实、荣昌、再鼎、诺诚健华等营收规模大了好几倍的药企。深挖各项数据后，这家药企似乎都在“闷声发展”。根据最新披露的2024财报，泽璟实现营业收入 5.33亿元，同比上年增长 37.91%；净利润-1.38亿，同比增长50.54%。2025年一季度延续这一趋势，实现营收1.68亿元，同比增长54.87%。但与亮眼股价和业绩涨幅形成鲜明反差的是，这家“小而美”的未盈利创新药企在大众印象中，却活得稍显透明。它成立于2009年，明明较不少创新药企成立时间更早，但却没什么名气，资本圈的相关讨论声也相对沉寂。外界对其最大认知，大多还停留在四五年前的“科创板首家适用第五套标准上市上市的未盈利企业”“国内首个氘代药研发者”两大标签。由此，外界不禁疑惑，泽璟用什么支撑起了高估值？迅速膨胀起来的估值背后，暗藏了投资者哪些预期？还有哪些潜在水面的风险点？CM10医药研究中心将从行业稀缺值、财务健康度、业务健康度等维度一一剖析。▲泽璟制药股价走势图，数据来源：百度股市通两大已上市产品的可预期验证它凭什么高估值？要回答这一问题，还得回归泽璟的核心竞争力——产品本身实力来论。一家年营收仅5亿左右的未盈利药企，之所以市值能超越众多营收规模数倍于己的同行，答案或藏于其“稀缺”的产品矩阵和可预期的商业化空间之中。一是已上市产品的稀缺性和可验证的商业化能力。目前，泽璟已上市两款药物，且均具有一定稀缺性和独特市场地位，分别为首个国产氘代药物甲苯磺酸多纳非尼片、国内唯一采用重组基因技术生产的人凝血酶产品重组人凝血酶。先看泽璟首个获批产品——甲苯磺酸多纳非尼片，这既是首个国产氘代药物，也是首个国产肝癌一线靶向药。作为泽璟的“现金牛”产品，多纳非尼已获批两大适应证。先是2021年6月获批一线治疗晚期肝癌适应证，成为继拜耳索拉非尼、卫材仑伐替尼后第三款被批准用于晚期肝细胞癌一线治疗的小分子靶向药物。后又于2022年8月再斩获一大适应证，用于治疗进展性、局部晚期或转移性放射性碘难治性分化型甲状腺癌。与索拉非尼、仑伐替尼相比，凭借安全性更优，且进入医保后价格优势显著，多纳非尼上市后销售额攀升明显。截至2024年底，多纳非尼已进入医院 1100 余家、覆盖医院 2000 余家、覆盖药房近1000家，销售持续放量。而2024年之所以营收涨幅超30%，便得益于多纳非尼片的销量增加。按照当前趋势，多纳非尼肝癌适应证应该仍有不少上升空间。再加上甲状腺癌适应证2022年获批后贡献增量，短时间业绩增长成为可预期。‌再看泽璟第二款上市产品——重组人凝血酶。这款产品的竞争格局就更为明了。凝血酶是一种重要的局部外用止血药物，由于血浆来源日益缺乏、血浆提取产品潜在残留病毒或免疫原性等安全性风险和血浆提取产品的生产成本日益升高等原因，中国市场上血源生化提取的多数凝血酶产品已经停产。根据卫健委《关于印发国家短缺药品清单的通知（国卫办药政发〔2020〕25 号）》，凝血酶属于《国家临床必需易短缺药品重点监测清单》中品种。而泽璟重组人凝血酶的稀缺性便得以体现，它是国内唯一采用重组基因技术生产的人凝血酶产品，于2024年1月获批上市，目前已进入医保目录，填补外科手术局部止血领域空白。全球同类产品仅有BMS的Recothrom，于2008年美国上市，不过该药物尚未进入国内市场。虽然凝血市场相较“小而美”，但是这款药的独特性，还是有望助泽璟在国内站稳一方脚跟。弗若斯特沙利文预测，外科手术局部止血市场将由2018年的73.0亿元增长至2030年的160.3亿元，年复合增长率为6.8%。对于这款药物，与自建团队进行多纳非尼片商业化不一样，泽璟这款商品未盲目选择自行商业化，而是选择了 “借力打力” 的商业化策略——与远大生命科学子公司远大辽宁达成独家合作，由后者负责大中华区的市场推广。目前，泽璟已累计收到合作方支付的独家市场推广权许可费人民币3.4亿元。此番考量背后不无道理。重组人凝血酶属于外科止血药品，泽璟制药的销售团队主要专注于肿瘤药物销售，与具备外科止血领域市场推广和销售实力的合作伙伴进行商业化合作，将更加有利于重组人凝血酶的市场推广和销售。泽璟看向远大生命科学，也是因为其在围术期和止血领域深耕多年，从而在止血药品入院和销售方面经验丰富。如以注射用矛头蝮蛇血凝酶为代表的止血产品，连续多年销量靠前。二是，泽璟的产品线并非孤立存在，可发挥更大协同效应。以首款上市的多纳非尼片为例，作为晚期肝癌一线治疗的核心药物，其主要覆盖肝胆外科领域；而 2024 年获批的重组人凝血酶，同样可应用于肝胆手术的止血环节。两者在临床场景上的高度契合，或有利于资源共享且提升市场推广效率。此外，临近上市的重组人促甲状腺激素，与多纳非尼新获批的甲状腺癌适应证形成 “诊断+辅助治疗” 搭档，未来或有望为核医学科提供一站式解决方案。这种产品间的聚焦与协同效应，或有助于其更好发挥自身优势。三是，泽璟在研基本无废管线，且具有稀缺价值拉升预期。纵观来看，无论是已临近上市产品，还是尚处临床阶段的在研管线，大多具备 “国产首创” 或 “全球前沿” 的竞争优势。高壁垒在研管线的预期与焦虑目前看来，与多数药企管线中存在 “哑弹” 不同，泽璟制药几乎无“废管线”。每款产品锚定市场空白，且研发都算是走在前列，算是一家梯度相对明晰的药企。细究到一众在研管线，最拉升泽璟当前预期，主要在于两款临近上市的产品——JAK抑制剂盐酸吉卡昔替尼片和注射用重组人促甲状腺激素。▲截图来自泽璟制药官网先看JAK抑制剂盐酸吉卡昔替尼片，这是一个拥有大适应证的大单品，目前共有11个适应证在研。其中进展最快的适应证为骨髓纤维化，已处于上市前审评审批阶段，这是首个提交治疗骨髓纤维化适应证NDA的国产JAK抑制剂类创新药物。目前，骨髓纤维化属于罕见病，治疗药物有限。全球范围内仅有芦可替尼、菲达替尼和帕瑞替尼三款靶向药物获批用于骨髓纤维化，但国内仅有诺华芦可替尼上市，是目前在我国唯一获批上市治疗骨髓纤维化的JAK抑制剂。也就是说，吉卡昔替尼片上市后将直接对标诺华这款产品。这一市场前景算是“小而美”。根据弗若斯特沙利文预测，目前国内骨髓纤维化患者规模或将超过6万人，2030年中国骨髓纤维化靶向药市场的临床可惠及人口渗透率将达到 30.7%，整体市场规模超过30亿元。更值得一提的是，借助这款药，泽璟大肆进军自免这一蓝海领域。不过其在斑秃、特应性皮炎等热门自免适应证中，几乎难抢到先发红利。其中，斑秃是吉卡昔替尼片布局自免领域进度最快的适应证，目前泽璟正推进重症斑秃适应证NDA资料准备工作。但是这一适应证在研情况还是颇为激烈的。泽璟斑秃适应证虽然研发进度靠前，但恐无法抢得国产首个名额了。斑秃这一市场空间较为可观。根据弗若斯特沙利文，2020年中国约有381.2万例斑秃患者，预计到2030年患者规模将达到464.9万人，患者规模大。相关指南和共识将 JAK 抑制剂作为斑秃系统疗法的首选治疗选择。迄今为止，国内已批准礼来巴瑞替尼及辉瑞利特昔替尼两款JAK抑制剂治疗斑秃，都是跨国药企。放眼国内企业，除泽璟外，还有恒瑞医药、石药集团等公司亦布局了JAK抑制剂。其中，针对重度斑秃这一适应证，恒瑞医药JAK抑制剂硫酸艾玛昔替尼片进度最为靠前，药物上市许可申请已于2024年下半年获国家药监局受理。这也意味着，在礼来、辉瑞产品相继在中国获批后，恒瑞很可能摘得“国产首个”。按照当前在研进度，待泽璟斑秃适应证上市后，市场或已较为激烈，不仅要从两大跨国巨头口中夺食，还需要从国内医药一哥恒瑞手中分羹，这对其商业化能力恐是一大较大考验。另一进度较为靠前的适应证是特应性皮炎，目前已处于III期阶段，竞争激烈程度同样不亚于此。此外，吉卡昔替尼片还被用于开展强直性脊柱炎（III期）、特发性肺纤维化（II 期）、移植物抗宿主病（II 期）、中重度斑块状银屑病（II 期）等自身免疫性疾病的临床试验，并于2022年获得了系统性红斑狼疮和重型新型冠状病毒肺炎适应证的临床试验批件。E药资本界认为，未来看点或在于，恒瑞若率先获批，将抢占斑秃市场；而对于泽璟而言，其选择骨髓纤维化这一“小而专”的适应证切入，有差异化定位，避开红海竞争，抢占国产JAK抑制剂在血液病领域的空白市场。若骨髓纤维化适应证先发优势确立，可反哺斑秃领域资源，但需追赶时间窗口。再则，还需考虑一大风险，大家都知道，FDA对JAK抑制剂的黑框警告（血栓、肿瘤风险）可能影响国内监管态度，安全性数据将成为核心审评因素。再看第二款临近上市产品——注射用重组人促甲状腺激素。这是中国首批取得用于甲状腺癌的辅助诊断和治疗临床试验批件的新药。从国内外竞争现状来看，目前国内尚无国产产品获批，全球仅默克的Thyrogen（重组人促甲状腺激素α）获批上市，国内已进口但未纳入医保，患者自费负担相对较重，为泽璟留了些生存口子。而其他国产药企进度大多落后于泽璟，如远大医药、智核生物等处于早期临床。海通证券最新预测，泽璟这款重组人促甲状腺素针对分化型甲状腺癌术后诊断的适应证有望于2025年获批上市，当年销售额达0.2亿元，次年收入达0.5亿元。除了这两款临近上市产品，泽璟生物还有8个处于临床I/II 期阶段的在研新药，投资者尤其对其双抗和多抗产品关注颇多。一款是ZG005（PD-1/TIGIT双抗）。Insight数据库显示，目前全球仅6款PD-1/TIGIT 双抗在研，尚无同类机制药物获批上市。其中阿斯利康Rilvegostomig进展最快，已进入入全球临床III期。泽璟PD-1/TIGIT双抗ZG005全球进度第二。另外国内还有信达IBI321在研，不过进度更靠后一些。另一款，ZG006是一款全球首创的DLL3三抗（CD3/DLL3/DLL3三抗），这款药物已于2024年8月获FDA颁发的孤儿药资格认定，主要针对小细胞肺癌适应证进行开发。横向对比ZG006和其他DLL3 CD3药物或DLL3 ADC，ZG006暂时展现出一定竞争力，ORR相比其他TCE药物接近翻倍。由于ZG005、ZG006等已获FDA临床试验批准，海外授权合作潜在可能性较高。再简单看下其它管线，VEGF/TGF-β双抗（ZGGS18）、LAG-3/TIGIT双抗（ZGGS15）等早期项目均进入Ⅰ/Ⅱ期，覆盖实体瘤及免疫微环境调控。不过，这些在研管线尚处研发早期，仍具有一定不确定风险。 推荐阅读 * 单日暴涨17%！创新药二哥提前盈利，引爆了什么？* 暴降90%，被集采重创的心血管“大玩家”，开始重生商业化与BD能力的大考在创新药企的估值逻辑中，已上市产品的商业化兑现程度，以及在研管线的BD潜力和潜在市场格局，都是重要的评估指标。市场普遍呈现 “赢家通吃” 特征，首款上市产品往往占据过半份额，后续产品市场空间逐级递减，尤其第四位及以后的产品往往难以获得更多市场预期。摆在泽璟面前的问题，同样如此。随着大产品即将上市，外界对其一大核心隐忧便在于，泽璟商业化能力能否匹配市场需求成为关键。其一，大产品上市后的商业化资源瓶颈。上市产品商业化打法，直接决定未来放量空间和机会。泽璟目前市净率显著高于行业平均，需警惕商业化不及预期带来的回调。要知道，对于目前已上市的两款产品，泽璟的商业化路径比较明晰了：一方面，自己搭建肿瘤销售团队，负责多纳非尼的商业化；另一方面，积极寻求外部合作，探索 CSO 等路径，选择与远大生命科学子公司合作推广重组人凝血酶。因同属肿瘤治疗领域，注射用重组人促甲状腺激素可借助现有商业化团队实现资源协同。相比之下，市场目光更聚焦于吉卡昔替尼片获批后的商业化策略。在最新披露的财报中，泽璟已透露，针对吉卡昔替尼片获批后的商业化工作，已提前积极布局，在现有商业化团队核心骨干架构的基础上，新增招聘擅长血液病领域的市场、医学和销售推广的优秀人才。尽管泽璟已着手血液病领域人才储备，但其“自建团队”的商业化模式成效存疑。随着自免适应证产品陆续获批，现有聚焦肿瘤领域的商业化团队将面临资源分散难题，团队扩建或成必然。这一挑战主要受两大因素制约：其一，现金流的可持续性，直接决定团队扩张与运营的资金保障；其二，市场竞争格局下，与头部企业的综合实力博弈，将考验其商业化资源整合与市场渗透能力。现金流压力。2025年一季度，泽璟营收增长但经营现金流净额骤降至-625.32万元（同比下滑107.02%），主因报告期内无大额市场推广授权款入账；同时销售费用同比大增56.49%，侵蚀利润空间。竞争格局严峻。骨髓纤维化适应证患者基数小，需直面诺华芦可替尼竞争；自免疾病市场虽大，但恒瑞、石药、礼来等已占据渠道与品牌优势。若吉卡昔替尼在斑秃等适应证安全性数据显著优于竞品，或存在突围机会。相较而言，泽璟商业化能力存在一些短板。比如销售团队经验不足，对比恒瑞、石药成熟的肿瘤/自免药销售网络，泽璟当前商业化团队规模较小，尚无太多重磅药物销售经验，可能影响市场渗透速度。还有一个老生常谈的问题——安全性数据仍需长期验证。JAK抑制剂类药物的黑框警告（血栓、肿瘤风险）是监管和医生处方的核心顾虑。尽管吉卡昔替尼片机制上有优势，但需大规模真实世界数据证明其风险低于同类产品，否则可能限制市场接受度。其二，纵观泽璟BD历史，在国际化合作方面，尚无经验可循。对于尚处早期研发阶段、已获FDA IND批准的ZG005、ZG006等管线，若参考康方生物AK112高达50亿美元的海外授权案例，考虑BD模式，可通过海外权益出让快速回笼资金。不过，这也将考验泽璟国际化能力，尤其体现在临床开发与BD经验。虽然在临床开发方面，泽璟凭借ZG005、ZG006成功获批FDA IND，已积累与美国监管机构的沟通经验，熟悉申报路径，能够有效降低合作伙伴的后期开发风险。然而在BD方面，泽璟经验明显不足。目前仅完成GS02 TIGIT单抗的国内授权交易，尚未开展与跨国药企的全球性合作。面对ZG006等复杂结构创新药，若把握不当，在国际授权谈判中议价能力不一定能充分体现。这并非不可解决。泽璟可通过多维度策略弥补国际化经验缺口：一方面，可引入具备跨国药企 BD 经验的高管及专业人才，快速提升团队国际化运作能力；另一方面，借助 CRO 机构或专业咨询公司的资源，加速积累行业经验。同样，在授权策略上，可采用分阶段推进模式，比如对早期非核心管线，参考荣昌生物与 Seagen 的合作模式，以技术授权形式快速积累交易经验并回笼资金；对晚期重磅产品如 ZG005，则优先将欧美市场权益授权给跨国药企，换取首付款与里程碑付款，同时保留中国市场自主开发权。E药资本界认为，泽璟若能在2025-2026年关键节点完成1-2笔全球授权交易，将有效验证其BD能力并再度打开市值空间。反之，若因经验不足导致交易条款不利或进度滞后，可能加剧 “重研发、轻变现” 的困境。因此，投资者需重点关注其 BD 团队组建进展，以及 2025 年关键临床数据披露后的合作动态，以此评估潜在风险与收益。总结作为一家小而美药企，泽璟已经逐渐走出了自己的节奏。对比君实生物、荣昌生物等同市值梯队药企，泽璟之所以能凭借5亿规模冲上去，与营收规模占优的它们一较高低，关键就在于差异化的产品定位与高效的协同布局：几乎没有“废管线”，具有差异性且进度领先，基本都能抢占一定市场。即便尚未商业化的产品，经 BD 合作潜力及潜在市场空间评估，前景同样总体向好。更具体来看，泽璟制药的当前市值逻辑源于两点，一是已验证的商业化能力（多纳非尼、重组凝血酶）；二是高壁垒管线预期（双/三抗、JAK抑制剂）的双重支撑。不过，未来需关注ZG005/ZG006的临床数据披露及吉卡昔替尼的上市放量节奏。另外，不要忽略，这家药企本质上“科学家底色”浓厚，或也回答了其为何频繁能再创新药竞争中占据先发优势。如董事长盛泽林拥有30余年新药研发经验，曾任职于BMS等跨国药企，并主导全球首个氘代抗肿瘤药物多纳非尼的研发及上市；首席科学官盛泽琪博士曾任安进药物研发高管，主导多款抗体药物的开发；首席医学官吴济生曾负责多个国际多中心临床试验设计……但挑战仍在。当前，泽璟正处于从“小而美”向 “专而强”的战略转型关键期。未来 2-3 年，吉卡昔替尼的商业化成效与双抗管线临床进展，将成为检验其估值合理性的试金石，也决定其能否突破质疑，成为本土创新药企的“新明星”。一审| 黄佳二审| 李芳晨三审| 李静芝精彩推荐CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化 ｜ 猎药人系列专题 | 出海启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖 ｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 |  荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药 ｜再鼎医药｜亚虹医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

调节性 T 细胞（Tregs）的 30 个标记物在其识别、功能、分化成熟、抑制活性以及在多种疾病中的作用等方面都具有重要意义。FoxP3作为 Treg 谱系最关键的标记，是一种转录因子，对 Tregs 的分化、成熟及获得抑制功能起着核心作用。其基因发生突变会引发 IPEX 综合征，导致多器官自身免疫疾病。FoxP3 有多种异构体，全长变体（FL）的 Tregs 表现出更高的抑制活性和增殖率。Helios属于 Ikaros 基因转录因子家族，多数人和小鼠的 Tregs 会表达。虽其在人类 Treg 稳定性和功能的确切作用尚未完全明确，但可作为 Tregs 稳定性和纯度的监测标记，还可能与细胞激活和增殖相关。CD25即 IL-2 受体的 α 链，高表达是常规 Tregs 的显著特征之一。在 T 细胞增殖、激活诱导的细胞死亡以及 Tregs 和效应（Teff）T 细胞的功能中发挥重要作用，FoxP3 + Tregs 中 CD25 水平最高的亚群具有最强的免疫抑制活性。CD127是 IL-7 受体的 α 链，在 T 细胞的动态调节、淋巴细胞分化和细胞免疫方面有重要影响。稳态时，Tregs 表达低水平的 CD127，激活时其表达显著上调，可辅助更精准地识别 Tregs。CD39作为一种外切酶，在调节嘌呤能信号传递给免疫细胞的持续时间、强度和化学性质方面发挥关键作用。其在 Tregs 上的表达存在个体差异，在炎症部位表达较高。CD39 + Tregs 被认为具有高活性、强抑制性，能分泌 IL-10，且高表达 CD39 可维持更高水平的 FoxP3 表达。CTLA-4属于 CD28 免疫球蛋白超家族的抑制性受体，对 Treg 细胞功能至关重要。它调节 T 细胞的共刺激，持续表达，在免疫抑制活动期间高度表达，可定义具有强抑制活性的 Tregs。CTLA-4 通过与树突状细胞表面的共刺激分子 CD80/86 结合，阻止其与效应 T 细胞上的 CD28 相互作用，从而抑制 T 细胞激活，还能诱导树突状细胞表达吲哚胺 2,3 - 双加氧酶（IDO），调节免疫反应。GITR是 TNF 受体超家族成员，通过提供共刺激信号来调节免疫反应，影响 T 细胞的激活、分化、存活和记忆形成以及巨噬细胞极化。然而，其在 Tregs 中的作用存在争议，既能导致 Tregs 不稳定、细胞耗竭和抑制功能下降，又能诱导 Tregs 在体外增殖和扩增。TIGIT是具有免疫球蛋白和 ITIM 结构域的 T 细胞免疫受体，为跨膜糖蛋白受体。在 Tregs 激活后高表达，TIGIT + Tregs 相比 TIGIT - Tregs 具有更强的抑制作用，能特异性抑制促炎的 Th1 和 Th17 细胞反应，但不影响 Th2 细胞反应。此外，TIGIT 表达与 Treg 效应分子表达增加相关，如颗粒酶 B、IL-10 和纤维蛋白原样蛋白 2（Fg12）。CD120b（TNFR2）具有抗炎活性，对少突胶质细胞、心肌细胞和角质形成细胞有保护作用，通过影响不同类型免疫细胞来实现免疫抑制功能。在激活的 Tregs 上高度且持续表达，TNF-α 与 TNFR2 的相互作用对 Tregs 的激活、扩增和表型稳定至关重要，还能维持 FoxP3 启动子的去甲基化，支持 Tregs 的分化和稳定。LAP即潜伏期相关肽，是转化生长因子 -β（TGF-β）前体的氨基末端结构域，与 TGF-β 形成潜伏复合物，调节单核细胞募集。LAP + Tregs 在 Treg 特异性去甲基化区域（TSDR）高度去甲基化，在体内外均具有抑制作用。CCR6属于 C-C 趋化因子受体蛋白，在协调免疫细胞向炎症部位迁移、维持免疫稳态和免疫系统完整性平衡方面具有关键作用。在多种炎症性疾病中，CCR6 + Tregs 的比例较高。CD223（LAG-3）是一种免疫检查点受体蛋白，可抑制细胞增殖、免疫功能、细胞因子分泌和维持免疫稳态。在 Tregs 上持续表达，通过抑制促进 Tregs 在炎症部位维持的信号通路来限制其增殖和功能，但也能刺激 Treg 介导的抑制作用，还可与 CTLA-4 和 PD-1 协同增强 Tregs 的抑制活性。GARP（LRRC32）作为潜伏 TGF-β 的膜受体，调节膜结合潜伏 TGF-β 的可用性并调节其在 Tregs 和血小板上的激活。在激活的 Tregs 表面表达，是具有高抑制活性的人类 Tregs 的特异性标记。然而，GARP 与 FoxP3 的表达关系存在争议，有研究表明二者相互依赖，也有研究显示它们并非相互调节。GPA33是一种细胞表面抗原，与免疫失调相关。高表达 GPA33 可定义 CD4 + CD25 + CD127 – FoxP3 + Helios + Tregs，这类 Tregs 无法产生常规 T（Tconv）细胞效应细胞因子。CD137CD137 是 TNFR 家族的共刺激受体，可促进自然杀伤（NK）细胞增殖和细胞因子分泌。CD137 + CD154 −是抗原激活的 FoxP3 + Tregs 的标记，具有高效抑制效应 T（Teff）细胞增殖的能力，具体作用取决于免疫反应类型。Nrp-1即神经毡蛋白 - 1，参与轴突导向和血管生成。在小鼠 Tregs 中富集，在人类中表达较低。在诱导 Tregs（iTregs）表面表达 Nrp-1 可识别和分离出在炎症条件下具有卓越抑制功能的 iTreg 亚群，且在周围淋巴器官中的表达高于胸腺 Tregs。FR4是叶酸结合蛋白的异构体，在小鼠中表达，与人类 FR-δ 高度同源。FR4 过表达可增强 Tregs 在体外的增殖能力，在天然和外周 Tregs 中均有表达。CD103属于整合素 αE，通过与 E-cadherin 相互作用介导细胞粘附、迁移和淋巴细胞归巢。CD103 + Tregs 在炎症部位积累的能力增强，参与皮肤局部 Treg 功能，与 FoxP3 的高表达相关，可能增强 TGF-β 依赖的 FoxP3 表达。CD44作为细胞表面的透明质酸受体，参与细胞的运动、存活和粘附等多种过程。其配体高分子量透明质酸（HMW-HA）可促进 Treg 介导的抑制作用，且与 HMW-HA 共刺激可促进 FoxP3 的表达。CD62L即白细胞粘附分子 L - 选择素，是一种跨膜凝集素受体，可调节幼稚和中枢记忆 T 细胞进入淋巴结以及激活的 CD8 + T 细胞向病毒感染部位的迁移，使 Tregs 归巢到次级淋巴器官。CCR7参与将树突状细胞和 T 细胞定位到淋巴结，在诱导外周免疫耐受方面有重要作用，可使 Tregs 归巢到次级淋巴器官。nTregs 高表达 CCR7，而中央记忆 Tregs（cmTregs）和效应记忆 Tregs（emTregs）下调其表达。CD31（PECAM-1）是高度糖基化的 Ig 样膜受体，在免疫和血管系统中均具有粘附和信号传导功能，是 Treg 分化的标记。ICOS属于 CD28 超家族的同源二聚体蛋白，参与 Tregs 的产生、增殖和存活。在癌症中，Tregs 高表达 ICOS，其与 ICOSL 的信号通路对 Treg 介导的自身耐受至关重要。此外，一小部分 ICOS + Tregs 在正常人和小鼠的外周血中可产生 IFN-γ 和 IL-17。Gal-1即半乳糖凝集素 - 1，参与细胞生长、迁移、炎症、血管生成等多种过程，在肿瘤进展、免疫逃逸和免疫耐受中发挥作用。其对 Treg 细胞的作用具有环境依赖性，阻断 Gal-1 会显著削弱 Tregs 的抑制作用。PD-1（CD279）属于 I 型跨膜蛋白，是免疫球蛋白超家族成员。PD-1 可调节 Treg 的生成及其免疫抑制特性，在癌症中，其阻断对 Tregs 的影响存在争议，既可能降低 Treg 介导的抑制作用，也可能增强 Treg 功能；在自身免疫疾病中，PD-1 在 Tregs 上的表达与疾病相关，如在系统性红斑狼疮中，PD-1 + 滤泡调节性 T 细胞功能受损。CCR7参与免疫细胞向淋巴结的定位和外周免疫耐受的诱导，对 Tregs 归巢到次级淋巴器官具有重要意义，其表达水平在 Tregs 的不同分化阶段有所变化。Granzyme B（GZMB）在结直肠癌中，表达升高，介导肿瘤免疫，参与 Tregs 对肿瘤细胞的抑制作用，是评估肿瘤免疫状态的重要指标之一。TIM-3在多种癌症（如结肠癌、黑色素瘤）中标记肿瘤内 Tregs，其表达与 Tregs 的抑制功能增强和肿瘤生长促进相关；在类风湿关节炎中，TIM-3 表达降低与 Tregs 功能活性下降有关；在移植物抗宿主病（GvHD）中，TIM-3 表达升高与 Tregs 功能活性增加相关。LAG-3 在结直肠癌中，LAG-3 + TIM-3 Tregs 表达更高水平的 TGF-β、IL-10 和 CTLA-4，具有更强的抑制功能，参与肿瘤免疫逃逸和疾病进展的调节。 CD45RA/RO属于受体蛋白酪氨酸磷酸酶，在 T 细胞受体信号起始中发挥作用，是 Tregs 分化状态的标记。初始 Tregs（nTregs）表达 CD45RA，记忆 Tregs 通常表达 CD45RO。参考资料Gootjes, C.; Zwaginga, J.J.; Roep, B.O.; Nikolic, T. Defining HumanRegulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function. Cells 2024, 13, 941. https://doi.org/10.3390/ cells1311094Santosh Nirmala S, Kayani K, Gliwin ´ski M, Hu Y, Iwaszkiewicz-Grzes ´ D, Piotrowska-Mieczkowska M, Sakowska J, Tomaszewicz M, Marı ´n Morales JM, Lakshmi K, Marek-Trzonkowska NM, Trzonkowski P, Oo YH and Fuchs A (2024) Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity. Front. Immunol. 14:1321228. doi: 10.3389/fimmu.2023.1321228Sayitoglu EC, Freeborn RA and Roncarolo MG (2021) The Yin and Yang of Type 1 Regulatory T Cells: From Discovery to Clinical Application. Front. Immunol. 12:693105. doi: 10.3389/fimmu.2021.693105

THOUSAND OAKS, Calif., May 1, 2025 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the first quarter of 2025. "Demand for our products was strong globally in the first quarter. Ongoing new product launches and successful Phase 3 trial results for several products make us feel confident in our long-term growth prospects," said Robert A. Bradway, chairman and chief executive officer. Key results include: For the first quarter, total revenues increased 9% to $8.1 billion in comparison to the first quarter of 2024. Product sales grew 11%, primarily driven by 14% volume growth, partially offset by 6% lower net selling price. U.S. sales grew 14%. Fourteen products delivered at least double-digit sales growth in the first quarter, including Repatha® (evolocumab), BLINCYTO® (blinatumomab), TEZSPIRE® (tezepelumab-ekko), EVENITY® (romosozumab-aqqg), TAVNEOS® (avacopan) and UPLIZNA® (inebilizumab-cdon). Our launch of IMDELLTRA ® (tarlatamab-dlle) generated $81 million of sales in the quarter and the Phase 3 confirmatory study demonstrated improved overall survival compared to chemotherapy. IMDELLTRA ® launched in Japan in April 2025. GAAP earnings per share (EPS) were $3.20 for the first quarter of 2025 compared with a GAAP loss per share of $0.21 for the first quarter of 2024, resulting from an unrealized gain on our BeiGene, Ltd. equity investment during the first quarter of 2025 compared to an unrealized loss during the prior year period, partially offset by an Otezla® intangible asset impairment charge of $800 million recorded during the first quarter of 2025. GAAP operating income increased from $1.0 billion to $1.2 billion, and GAAP operating margin increased 1.1 percentage points to 15.0%. Non-GAAP EPS increased 24% from $3.96 to $4.90, driven by higher revenues, partially offset by higher operating expenses. Non-GAAP operating income increased from $3.1 billion to $3.6 billion and non-GAAP operating margin increased 2.5 percentage points to 45.7%. The Company generated $1.0 billion of free cash flow in the first quarter of 2025 versus $0.5 billion in the first quarter of 2024. This increase reflects an $800 million tax deposit made in the first quarter of 2024 and current quarter business performance, partially offset by timing of working capital items and higher capital expenditures. References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis," and "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented in the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance General Medicine Repatha® (evolocumab) sales increased 27% year-over-year to $656 million in the first quarter, primarily driven by 41% volume growth, partially offset by 9% lower net selling price. EVENITY® (romosozumab-aqqg) sales increased 29% year-over-year to $442 million in the first quarter, driven by volume growth. Prolia® (denosumab) sales increased 10% year-over-year to $1.1 billion in the first quarter, primarily driven by 13% volume growth, partially offset by 5% lower net selling price. For 2025, we expect sales erosion driven by biosimilar competition, particularly in the second half of the year. Rare Disease TEPEZZA® (teprotumumab-trbw) sales decreased 10% year-over-year to $381 million in the first quarter, primarily driven by 9% lower volume and 8% from a decrease in inventory levels, partially offset by higher net selling price. KRYSTEXXA® (pegloticase) sales were flat year-over-year at $236 million in the first quarter, as 11% volume growth was offset by 10% from a decrease in inventory levels. UPLIZNA® (inebilizumab-cdon) sales increased 14% year-over-year to $91 million in the first quarter, primarily driven by volume growth. TAVNEOS® (avacopan) sales increased 76% year-over-year to $90 million in the first quarter, primarily driven by volume growth. Ultra-Rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), BUPHENYL® (sodium phenylbutyrate) and QUINSAIR® (levofloxacin), generated $179 million of sales in the first quarter. Sales increased 6% year-over-year for the first quarter, driven by volume growth. Inflammation TEZSPIRE® (tezepelumab-ekko) sales increased 65% year-over-year to $285 million in the first quarter, driven by volume growth. Otezla® (apremilast) sales increased 11% year-over-year to $437 million in the first quarter, driven by 12% favorable changes to estimated sales deductions, as volume growth of 4% was offset by 5% lower net selling price. Enbrel® (etanercept) sales decreased 10% year-over-year to $510 million in the first quarter, driven by 47% lower net selling price resulting from increased 340B Program mix and higher commercial discounts, partially offset by 19% favorable changes to estimated sales deductions, higher inventory levels and volume growth. The year-over-year impact on net selling price is expected to be less pronounced in future quarters. AMJEVITA® (adalimumab-atto)/AMGEVITA™ (adalimumab) sales decreased 19% year-over-year to $136 million in the first quarter, primarily driven by 33% lower net selling price, partially offset by 11% volume growth. WEZLANA™ (ustekinumab-auub)/WEZENLA™ (ustekinumab) generated $150 million of sales in the first quarter. WEZLANA launched in the U.S. in the first quarter of 2025 and is the first FDA-approved biosimilar for the treatment of adult and pediatric plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. PAVBLU® (aflibercept-ayyh) generated $99 million of sales in the first quarter. PAVBLU launched in the U.S. in the fourth quarter of 2024 and is the first available aflibercept biosimilar for the treatment of retinal conditions, including neovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy. Oncology BLINCYTO® (blinatumomab) sales increased 52% year-over-year to $370 million in the first quarter, primarily driven by volume growth. Vectibix® (panitumumab) sales increased 8% year-over-year to $267 million in the first quarter, driven by volume growth. KYPROLIS® (carfilzomib) sales decreased 14% year-over-year to $324 million in the first quarter, driven by lower volumes due to increased competition. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 4% year-over-year to $85 million in the first quarter, driven by volume growth, partially offset by lower net selling price. XGEVA® (denosumab) sales increased 1% year-over-year to $566 million in the first quarter. For 2025, we expect sales erosion driven by biosimilar competition, particularly in the second half of the year. Nplate® (romiplostim) sales decreased 1% year-over-year to $313 million in the first quarter as volume growth was more than offset by unfavorable changes to estimated sales deductions and foreign exchange impact. IMDELLTRA® (tarlatamab-dlle)/IMDYLLTRA™ (tarlatamab) generated $81 million of sales in the first quarter. Sales increased 21% quarter-over-quarter driven by volume growth. MVASI® (bevacizumab-awwb) sales decreased 11% year-over-year to $179 million in the first quarter, primarily driven by lower volume. Going forward, we expect continued sales erosion driven by competition. Established Products Our established products, which consist of Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), generated $557 million of sales in the first quarter. Sales decreased 3% year-over-year for the first quarter, driven by 10% lower net selling price and 3% unfavorable foreign exchange impact, partially offset by favorable changes to estimated sales deductions. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis: Total Operating Expenses increased 8% year-over-year for the first quarter. Cost of Sales as a percentage of product sales decreased 7.3 percentage points driven by lower amortization expense from the fair value step-up of inventory acquired from Horizon and lower manufacturing costs, partially offset by changes in our sales mix. Research & Development (R&D) expenses increased 11% driven by higher spend in later-stage clinical programs, partially offset by lower spend in marketed product support and research and early pipeline. Selling, General & Administrative (SG&A) expenses decreased 7% driven by lower commercial product-related expenses and lower Horizon acquisition-related expenses, partially offset by higher general and administrative expenses. Other operating expenses consisted primarily of the Otezla® intangible asset impairment charge of $800 million. Operating Margin as a percentage of product sales increased 1.1 percentage points in the first quarter to 15.0%. Tax Rate increased 78.5 percentage points in the first quarter due to the change in earnings mix as a result of the first quarter 2025 unrealized gains compared to the first quarter 2024 unrealized losses on our equity investments, primarily BeiGene. On a non-GAAP basis: Total Operating Expenses increased 4% year-over-year for the first quarter. Cost of Sales as a percentage of product sales decreased 0.8 percentage points driven by lower manufacturing costs, partially offset by changes in our sales mix. R&D expenses increased 12% driven by higher spend in later-stage clinical programs, partially offset by lower spend in marketed product support and research and early pipeline. SG&A expenses decreased 3% driven by lower commercial product-related expenses, partially offset by higher general and administrative expenses. Operating Margin as a percentage of product sales increased 2.5 percentage points in the first quarter to 45.7%. Tax Rate decreased 0.8 percentage points in the first quarter due to the change in earnings mix and net favorable items as compared to the prior year. Cash Flow and Balance Sheet The Company generated $1.0 billion of free cash flow in the first quarter of 2025 versus $0.5 billion in the first quarter of 2024. This increase reflects an $800 million tax deposit made in the first quarter of 2024 and current quarter business performance, partially offset by timing of working capital items and higher capital expenditures. The Company declared a first quarter 2025 dividend on December 10, 2024 of $2.38 that was paid on March 7, 2025 to all stockholders of record as of February 14, 2025, representing a 6% increase from the same period in 2024. During the first quarter of 2025, the Company reduced principal debt outstanding by $2.8 billion. During the first quarter, there were no repurchases of shares of common stock. Cash and cash equivalents totaled $8.8 billion and debt outstanding totaled $57.4 billion as of March 31, 2025. 2025 Guidance For the full year 2025, the Company expects: Total revenues in the range of $34.3 billion to $35.7 billion. On a GAAP basis, EPS in the range of $12.21 to $13.46, and a tax rate in the range of 11.0% to 12.5%. On a non-GAAP basis, EPS in the range of $20.00 to $21.20, and a tax rate in the range of 14.5% to 16.0%. Capital expenditures to be approximately $2.3 billion. Share repurchases not to exceed $500 million. This guidance includes the estimated impact of implemented tariffs, but does not account for any tariffs that could be implemented in the future, including potential sector-specific tariffs. First Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine MariTide (maridebart cafraglutide, AMG 133) MariTide is a differentiated peptide-antibody conjugate that activates the glucagon like peptide 1 (GLP-1) receptor and antagonizes the gastric inhibitory polypeptide receptor (GIPR). MARITIME-1, a Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of maridebart cafraglutide is enrolling adults living with overweight or obesity, without Type 2 diabetes mellitus. MARITIME-2, a Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of maridebart cafraglutide is enrolling adults living with overweight or obesity, with Type 2 diabetes mellitus. Planning for additional MARITIME Phase 3 studies across multiple indications remains on track, with additional studies expected to initiate throughout 2025. Part 2 of the Phase 2 chronic weight management study is ongoing in adults living with overweight or obesity, with or without Type 2 diabetes mellitus. Data readout is anticipated in H2 2025. A Phase 2 study investigating MariTide for the treatment of Type 2 diabetes mellitus has completed enrollment of adults living with and without obesity. Data readout is anticipated in H2 2025. AMG 513 A Phase 1 study of AMG 513 is enrolling people living with obesity following removal of the clinical hold by the U.S. Food and Drug Administration (FDA). Repatha VESALIUS-CV, a Phase 3 CV outcomes study of Repatha, is ongoing in patients at high CV risk without prior myocardial infarction or stroke. Data readout is event driven and anticipated in H2 2025. EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of CV events, is ongoing. Olpasiran (AMG 890) Olpasiran is a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver. The OCEAN(a)-outcomes trial, a Phase 3 secondary prevention cardiovascular (CV) outcomes study, is ongoing in patients with atherosclerotic CV disease and elevated Lp(a). A Phase 3 CV outcomes study in patients with elevated Lp(a) and at high risk for a first CV event is expected to be initiated in H2 2025/H1 2026. Rare Disease TAVNEOS A Phase 3, open-label study of TAVNEOS in combination with rituximab or a cyclophosphamide-containing regimen, is enrolling patients from 6 years to < 18 years of age with active ANCA-associated vasculitis (Granulomatosis with Polyangiitis (GPA)/Microscopic Polyangiitis (MPA)). TEPEZZA Regulatory review is underway in multiple additional geographies, including with the European Medicines Agency (EMA), where approval is anticipated in H2 2025. A Phase 3 study of TEPEZZA in Japan is enrolling patients with chronic/low clinical activity score thyroid eye disease (TED). A Phase 3 study evaluating the subcutaneous route of administration of teprotumumab is enrolling patients with TED. UPLIZNA In April, the FDA approved UPLIZNA for the treatment of Immunoglobulin G4-Related Disease (IgG4-RD) in adult patients. In April, data from the UPLIZNA Phase 3 MINT study in patients with generalized myasthenia gravis (gMG) were presented and simultaneously published in the New England Journal of Medicine. These data demonstrated durable and sustained efficacy of UPLIZNA treatment compared to placebo (adjusted difference, -1.8 at week 26; −2.8 at week 52) as measured by the change in baseline of Myasthenia Gravis Activities of Daily Living (MG-ADL) score in the acetylcholine receptor autoantibody-positive (AChR+) subpopulation through week 52. Among the AChR+ patients in the UPLIZNA group, 72% had a ≥3 point improvement in the MG-ADL score, compared to 45% in placebo at week 52. No new safety signals were identified. The FDA has accepted the regulatory submission of the MINT Phase 3 data with a PDUFA date of December 14, 2025. Dazodalibep Dazodalibep is a fusion protein that inhibits CD40L. Two Phase 3 studies of dazodalibep in Sjögren's disease are enrolling patients. The first study is in patients with moderate-to-severe systemic disease activity, and the second study is in patients with moderate-to-severe symptomatic burden and low systemic disease activity. Daxdilimab Daxdilimab is a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7). A Phase 2 study of daxdilimab is ongoing in patients with moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care. A Phase 2 study of daxdilimab is ongoing in patients with dermatomyositis and antisynthetase inflammatory myositis. Inflammation TEZSPIRE Two Phase 3 studies of TEZSPIRE were initiated and are enrolling adults with moderate to very severe chronic obstructive pulmonary disease (COPD) and a BEC ≥ 150 cells/µl. In March, data from the Phase 3 WAYPOINT study of TEZSPIRE in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) were presented and simultaneously published in the New England Journal of Medicine demonstrating that treatment with TEZSPIRE: significantly reduced Nasal Polyp Score (NPS) by -2.065 at week 52. significantly reduced nasal congestion (measured by participant-reported Nasal Congestion Score [NCS]) by -1.028 at week 52. Improvements in NPS were observed as early as week four, and NCS as early as week two, and were sustained through week 52. significantly reduced the need for nasal polyp surgery by 98%. significantly reduced the need for systemic corticosteroid treatment by 88%. had a safety profile consistent with its approved severe asthma indication. The FDA has accepted the regulatory submission of the WAYPOINT Phase 3 data with a PDUFA date of October 19, 2025. A Phase 3 study of TEZSPIRE is enrolling patients with eosinophilic esophagitis. Rocatinlimab (AMG 451/KHK4083) Rocatinlimab is a first-in-class T-cell rebalancing monoclonal antibody that inhibits and reduces OX40-positive pathogenic T-cells. The eight study ROCKET Phase 3 program evaluating rocatinlimab in patients with moderate-to-severe atopic dermatitis (AD) has enrolled over 3,300 patients. Enrollment is now complete in seven studies. In March, detailed data were presented from the ROCKET HORIZON Phase 3 study, which met its co-primary and all key secondary endpoints. In March, data were announced from three additional ROCKET program Phase 3 studies: The IGNITE study, which evaluated two dose strengths of rocatinlimab, met its co-primary endpoints and all key secondary endpoints at week 24: 42.3% of patients in the higher dose group achieved ≥75% reduction from baseline in Eczema Area and Severity Index score (EASI-75), a 29.5% difference vs. placebo. In the lower dose group, 36.3% of patients achieved EASI-75, a 23.4% difference vs. placebo. 23.6% of patients in the higher dose group achieved a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 0 (clear) or 1 (almost clear) with a ≥2-point reduction from baseline (vIGA-AD 0/1), a 14.9% difference vs. placebo. In the lower dose group, 19.1% of patients achieved this endpoint, a 10.3% difference vs. placebo. 22.7% of patients in the higher dose group achieved a revised Investigator's Global Assessment (rIGA™) score of 0/1 with a ≥2-point reduction from baseline (a more stringent measure of efficacy than vIGA-AD 0/1), a 14.4% difference vs. placebo. In the lower dose group, 16.3% of patients achieved this endpoint, an 8.0% difference vs. placebo. The SHUTTLE study, which evaluated two dose strengths of rocatinlimab in combination with topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), met its co-primary endpoints and all key secondary endpoints at week 24. The VOYAGER study, which successfully demonstrated that rocatinlimab does not interfere with responses to tetanus and meningococcal vaccinations. Across ROCKET program results to date, safety findings were generally consistent with the previously observed safety profile of rocatinlimab. The most frequent treatment-emergent adverse events (≥5%) with higher observed proportion in rocatinlimab groups were pyrexia, chills and headache. A higher number of patients receiving rocatinlimab vs. placebo experienced gastrointestinal ulceration events, with an overall incidence of less than 1%. Key upcoming milestones from the ROCKET Phase 3 program: ROCKET ASCEND is a study evaluating rocatinlimab maintenance therapy in adult and adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. ROCKET ASTRO is a 52-week study evaluating rocatinlimab in adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. A Phase 2 study of rocatinlimab is enrolling patients with moderate-to-severe asthma. A Phase 3 study of rocatinlimab is enrolling patients with prurigo nodularis (PN). Blinatumomab Blinatumomab is a bispecific T-cell engager (BiTE ®) molecule targeting CD19. A Phase 2 study of blinatumomab in autoimmune disease was initiated in adults with systemic lupus erythematosus (SLE). Inebilizumab Inebilizumab is a B-cell depleting monoclonal antibody targeting CD19. A Phase 2 study of inebilizumab in autoimmune disease was initiated in adults with SLE. AMG 104 (AZD8630) AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen-binding (Fab). A Phase 2 study is enrolling patients with asthma. Oncology BLINCYTO / blinatumomab In April, the FDA granted Breakthrough Therapy Designation for subcutaneous blinatumomab in the treatment of adults with relapsed/refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL). A Phase 1/2 study of subcutaneous blinatumomab is ongoing in the dose-expansion and optimization phase in adult patients with relapsed or refractory Philadelphia chromosome (Ph)-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025. Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy, is enrolling older adult patients with newly diagnosed Ph-negative B-ALL. IMDELLTRA / tarlatamab IMDELLTRA is the first and only FDA-approved delta-like ligand 3 (DLL3) targeting BiTE® molecule. In April, the Company announced that the global Phase 3 DeLLphi-304 study met its primary endpoint of improved overall survival at a planned interim analysis. This study evaluated IMDELLTRA compared to local standard-of-care chemotherapy as a treatment for patients with small cell lung cancer (SCLC) who progressed on or after a single line of platinum-based chemotherapy. The safety profile for IMDELLTRA was consistent with its known profile. Together these randomized data have the potential to establish IMDELLTRA as a new standard of care in second-line SCLC. Detailed data from DeLLphi-304 will be presented at the American Society of Clinical Oncology meeting (ASCO) in June. The Company is advancing a comprehensive, global clinical development program across extensive-stage and limited-stage SCLC: DeLLphi-303, a Phase 1b study of IMDELLTRA in combination with a programmed cell death protein ligand-1 (PD-L1) inhibitor, carboplatin and etoposide or separately in combination with PD-L1 alone, is ongoing in patients with first-line ES-SCLC. DeLLphi-305, a Phase 3 study of IMDELLTRA and durvalumab, is enrolling patients with first-line ES-SCLC in the maintenance setting. DeLLphi-306, a Phase 3 study of IMDELLTRA following concurrent chemoradiation therapy, is enrolling patients with limited-stage SCLC. DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab, is enrolling patients with second line or later ES-SCLC. DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens in second-line ES-SCLC, is enrolling patients. DeLLphi-310, a Phase 1b study, was initiated in patients with ES-SCLC evaluating IMDELLTRA in combination with YL201, a B7-H3 targeting antibody-drug conjugate, with or without anti-PD-L1. DeLLphi-312, a Phase 3 study of first-line IMDELLTRA with carboplatin, etoposide and durvalumab is planned to initiate in patients with ES-SCLC by mid-2025. Xaluritamig (AMG 509) Xaluritamig is a first-in-class BiTE® targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1). A Phase 3 study of xaluritamig is enrolling patients with metastatic castrate resistant prostate cancer (mCRPC) who have previously been treated with taxane-based chemotherapy. A Phase 1 study of xaluritamig monotherapy has completed enrollment of patients with mCRPC who have not yet received taxane-based chemotherapy and has also completed enrollment of patients with mCPRC who have previously received taxane-based chemotherapy in a fully outpatient treatment setting to further improve administration convenience. This study continues to enroll mCRPC patients into a combination treatment of xaluritamig and abiraterone. A Phase 1b study evaluating neoadjuvant xaluritamig therapy prior to radical prostatectomy is enrolling patients with newly diagnosed localized intermediate or high–risk prostate cancer. A Phase 1b study of xaluritamig is enrolling patients with high-risk biochemically recurrent prostate cancer after definitive therapy. AMG 193 AMG 193 is a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. A Phase 2 study evaluating the efficacy, safety, tolerability and pharmacokinetics of AMG 193 is enrolling patients with methylthioadenosine phosphorylase (MTAP)-null previously treated advanced non-small cell lung cancer (NSCLC). A Phase 1/1b/2 study of AMG 193 is enrolling patients with advanced MTAP-null solid tumors in the dose-expansion portion of the study. A Phase 1b study of AMG 193 alone or in combination with other therapies is enrolling patients with advanced MTAP-null thoracic malignancies. A Phase 1b study of AMG 193 in combination with other therapies is enrolling patients with advanced MTAP-null gastrointestinal, biliary tract and pancreatic cancers. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, will be discontinued following a wind-down period. Bemarituzumab Bemarituzumab is a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody. FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, is ongoing in patients with first-line gastric cancer. Data readout is anticipated in Q2 2025. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab, is ongoing in patients with first-line gastric cancer. Phase 3 data readout is anticipated in H2 2025. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab, is enrolling patients with first-line gastric cancer. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy, is ongoing in patients with solid tumors with FGFR2b overexpression. LUMAKRAS/LUMYKRAS CodeBreaK 301, a Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI, is enrolling patients with first-line KRAS G12C–mutated CRC. CodeBreaK 202 (CB202), a Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy, is enrolling patients with first-line KRAS G12C–mutated and PD-L1 negative advanced NSCLC. Nplate The final analysis of a Phase 3 study of Nplate as supportive care in chemotherapy-induced thrombocytopenia in gastrointestinal malignancies is complete. Data from this study will be presented at ASCO in June. Biosimilars A randomized, double-blind pharmacokinetic similarity study of ABP 206 compared with OPDIVO® (nivolumab) has completed enrollment of patients with resected stage III or stage IV melanoma in the adjuvant setting. Data readout is anticipated in H2 2025. A randomized, double-blind comparative clinical study of ABP 206 compared with OPDIVO is enrolling patients with treatment-naïve unresectable or metastatic melanoma. A randomized, double-blind pharmacokinetic similarity study of ABP 234 compared with KEYTRUDA® (pembrolizumab) is enrolling patients with early-stage non-squamous non-small cell lung cancer as adjuvant treatment. A randomized, double-blind combined pharmacokinetic/comparative clinical study of ABP 234 compared to KEYTRUDA is enrolling patients with advanced or metastatic non-squamous non-small cell lung cancer. A randomized, double-blind pharmacokinetic similarity/comparative clinical study of ABP 692 compared to OCREVUS® (ocrelizumab) was initiated and is currently enrolling patients with relapsing-remitting multiple sclerosis. TEZSPIRE is being developed in collaboration with AstraZeneca. AMG 104 is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. YL201 is an investigational B7-H3 targeting antibody-drug conjugate being developed by MediLink. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck & Co., Inc. OCREVUS is a registered trademark of Genentech, Inc. Non-GAAP Financial Measures In this news release, management has presented its operating results for the first quarters of 2025 and 2024, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2025 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the first quarters of 2025 and 2024. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, YouTube and Threads. Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast), our acquisitions of ChemoCentryx, Inc. or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions, including those resulting from geopolitical relations and government actions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our sustainability objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. The stated guidance also includes the estimated impact of implemented tariffs, but does not account for any tariffs that could be implemented in the future, including potential sector-specific tariffs. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED