Bortezomib

Sarclisa recommended for EU approval by the CHMP to treat transplant-ineligible newly diagnosed multiple myeloma Recommendation based on IMROZ phase 3 study demonstrating Sarclisa in combination with VRd significantly improved progression-free survival, compared to standard-of-care VRd aloneIf approved, Sarclisa would be the first anti-CD38 therapy in the EU available for use in combination with VRd for adult patients with transplant-ineligible NDMM Paris, November 14, 2024. The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT). A final decision is expected in the coming months. Dietmar Berger, M.D., Ph.D.Chief Medical Officer, Global Head of Development at Sanofi“The positive CHMP opinion is an important step forward for people with transplant-ineligible newly diagnosed multiple myeloma for whom effective front-line therapy may improve long-term outcomes. If approved, this Sarclisa-based combination could establish a new standard-of-care treatment approach for patients in the EU, helping to address a critical care gap in multiple myeloma treatment, and reinforcing Sarclisa’s potential as the anti-CD38 therapy of choice.” In September 2024, the US Food and Drug Administration (FDA) approved Sarclisa in combination with VRd for the treatment of adult patients with NDMM who are not eligible for ASCT, representing the first global approval for Sarclisa in the first line setting. In addition, the FDA granted orphan drug exclusivity for Sarclisa in the approved indication. Sarclisa is currently approved in two indications for the treatment of certain adult patients with relapsed or refractory MM in more than 50 countries, including the US and EU. First positive global phase 3 study combining anti-CD38 therapy with VRd to significantly improve PFS versus VRd alone in transplant-ineligible NDMM supports CHMP decisionThe positive CHMP opinion is based on data from the IMROZ phase 3 study, which was presented at the American Society of Clinical Oncology 2024 annual meeting, European Hematology Association 2024 meeting, and published in The New England Journal of Medicine. IMROZ is the first global phase 3 study of a CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve progression-free survival (PFS) versus VRd alone. The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals. About SarclisaSarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA. Currently Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. In Europe, based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is also approved in combination with VRd as a first line treatment option for adult patients with NDMM who are not eligible for ASCT, based on the IMROZ phase 3 study. Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. In addition, the company is evaluating a subcutaneous administration method for Sarclisa in clinical studies. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery. In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers. For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov. About SanofiWe are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | + 33 6 25 09 14 25 | sandrine.guendoul@sanofi.comEvan Berland | +1 215 432 0234 | evan.berland@sanofi.comNicolas Obrist | + 33 6 77 21 27 55 | nicolas.obrist@sanofi.comVictor Rouault | + 33 6 70 93 71 40 | victor.rouault@sanofi.comTimothy Gilbert | + 1 516 521 2929 | timothy.gilbert@sanofi.com Investor RelationsThomas Kudsk Larsen |+ 44 7545 513 693 | thomas.larsen@sanofi.comAlizé Kaisserian | + 33 6 47 04 12 11 | alize.kaisserian@sanofi.comArnaud Delépine | + 33 6 73 69 36 93 | arnaud.delepine@sanofi.comFelix Lauscher | + 1 908 612 7239 | felix.lauscher@sanofi.comKeita Browne | + 1 781 249 1766 | keita.browne@sanofi.comNathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@sanofi.comTarik Elgoutni | + 1 617 710 3587 | tarik.elgoutni@sanofi.comThibaud Châtelet | + 33 6 80 80 89 90 | thibaud.chatelet@sanofi.com Sanofi Forward-Looking StatementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the fact that product may not be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related future litigation and the ultimate outcome of such litigation, and volatile economic and market conditions, and the impact that pandemics or other global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2023. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group. Attachment Press Release

瞪羚社/粽哥 又一超高潜力赛道横空出世。 强生CD38单抗Darzalex，凭借在多发性骨髓瘤领域大放异彩，以惊人的年销售额逼近百亿美元大关，强势印证了CD38靶点的非凡实力。然而，这只是CD38靶点广阔蓝图中的一抹亮色。 继血液瘤之后，CD38靶点正在跨界自免领域，开辟新的蓝海战场。其中，武田制药、渤健/天境生物和康诺亚是迈向新风口的“先行者”。 01 “一超多强”格局 CD38靶点的市场潜力不容小觑，由于其在多发性骨髓瘤细胞上高度表达，成为多发性骨髓瘤抗体治疗的理想靶点。 多发性骨髓瘤（MM）是一种克隆浆细胞异常增殖的恶性疾病，全球每年有超过13万例新确诊患者，在许多国家的血液系统恶性肿瘤中排名第二，5年总生存率大约为55%。 如今，针对CD38靶点的药物研发正在如火如荼地进行中，涵盖了多种类型，包括单抗、双抗、ADC、CAR-T疗法等。其中，已有2款用于治疗多发性骨髓瘤的CD38单抗获批上市，分别为强生/Genmab的全球首款CD38单抗Darzalex（达雷妥尤单抗）、赛诺菲/ImmunoGen（已被艾伯维收购）的Sarclisa（Isatuximab，艾沙妥昔单抗）。 具备先发优势的Darzalex，取得了优异的市场表现：2023年全球销售额高达97.4亿美元，占强生全年总收入的11.4%，2024年上半年销售额继续同比增长18.6%至55.7亿美元。这得益于其在MM领域获批用于多个治疗阶段，覆盖了一线、二线和多线治疗。 根据Evaluate预测，Darzalex有望在今年取得近120亿美元的营收，跻身百亿美元俱乐部，并预计2028年销售额达170.22亿美元。VisibleAlpha也预测Darzalex最终销售峰值将达到166亿美元。 不过，Darzalex面临着专利悬崖的危机，其在美国、欧洲和日本的组合物专利将于2026年3月到期，目前已有生物类似药在研发当中，例如复宏汉霖HLX15已完成I期临床试验。 另一边，赛诺菲/ImmunoGen的Sarclisa正在挑战Darzalex的霸主地位，目前已在50多个国家获批用于治疗多发性骨髓瘤，使得销售额从2020年的1.76亿欧元增长至2023年的3.81亿欧元，今年上半年继续同比增长32%至2.27亿欧元。 此外，Sarclisa还在持续拓展适应症，开发计划涵盖MM治疗连续体的六个潜在适应症，以及评估开发皮下给药方法。今年9月，Sarclisa获FDA批准了第3项适应症：联合硼替佐米、来那度胺和地塞米松（VRd）一线治疗不符合自体干细胞移植（ASCT）条件的新诊断多发性骨髓瘤（NDMM），后续有望带来新的增量。 CD38单抗赛道的“后来者”还有不少，渤健/天境生物的Felzartamab（菲泽妥单抗）、武田制药的Mezagitamab等也在加速追赶，形成“一超多强”的市场竞争格局。 值得一提的是，CD38单抗的战场不只在多发性骨髓瘤，还有自免领域。 02 自免新蓝海崛起 正如本文开头所言，CD38单抗正在拓展至自免领域。这是由于，CD38的表达还与自免疾病有关。 CD38是B细胞尤其是浆细胞表面重要的生物标志物，而异常活化的B细胞及浆细胞是自免疾病的重要致病机制之一，利用靶向CD38抗体清除过度活化的B细胞/浆细胞，可用于治疗自免疾病。 目前，武田制药的Mezagitamab（TAK-079）和康诺亚的CM313，均已在免疫性血小板减少症（ITP）的临床研究中展现出积极疗效。而且，Mezagitamab还被开发用于IgA肾病。 根据治疗ITP的2b期研究结果显示：在所有三个剂量水平上，Mezagitamab治疗均显著改善了血小板应答，并且在最后一剂治疗后持续 8周直至第16周，展示了Mezagitamab对血小板应答的快速和持久疗效。此前，武田宣布计划在2024财年下半年启动Mezagitamab在ITP患者中的全球性3期临床试验。 在肾病治疗领域，最受关注的莫过于渤健重金收购的Felzartamab（菲泽妥单抗）。 为了扩大免疫学研发管线，渤健在今年5月宣布以总交易额18亿美元（11.5亿美元预付款+6.5亿美元里程碑付款）收购HI-Bio公司，后者拥有核心资产CD38单抗Felzartamab。 Felzartamab最初由MorphoSys开发，天境生物在2017年引进了该药在大中华区所有适应症的开发和商业化权益，HI-Bio在2022年引进了该药在大中华区以外的全球其他地区所有适应症的权益。渤健通过收购HI-Bio，将Felzartamab纳入囊中。 目前，Felzartamab正在开展多项临床研究，适应症包括原发性膜性肾病（PMN）、肾移植术后抗体介导的排斥反应（AMR）、IgA肾病等，其中前2个适应症已完成Ⅱ期研究，IgA肾病的Ⅱ期研究正在进行中。渤健计划在2025年启动针对这3个适应症的Ⅲ期试验。 渤健开发主管Priya Singhal医学博士表示，“Felzartamab已经证明了对三种严重未满足需求的肾脏疾病的关键生物标志物和临床终点的影响，是渤健投资组合的战略补充”。 正是基于Felzartamab在PMN和AMR适应症上显示出积极疗效，FDA均授予了突破性疗法认定（BTD）和孤儿药资格认定（ODD）。目前，晚期AMR尚无获批疗法，Felzartamab有望成为首个治疗晚期AMR的有效疗法。 由此可见，赛诺菲/ImmunoGen（已被艾伯维收购）的Sarclisa同样有治疗自身免疫性肾科领域的潜力，适应症范围还能进一步扩展。如果Sarclisa能斩获肾病适应症，无疑将有更多的筹码挑战强生Darzalex的霸主地位。 03 康诺亚“破局” 视线回到国内市场。 如前文所述，天境生物在2017年从MorphoSys公司引进了Felzartamab（菲泽妥单抗）在大中华区的开发和商业化权益。 目前，天境生物正在开展菲泽妥单抗联合来那度胺和地塞米松二线治疗多发性骨髓的III期注册性临床研究，此前还在2021年获得国家药监局批准开展治疗系统性红斑狼疮（SLE）的1b期研究。 除了天境生物，还有一些国内药企也布局了CD38靶向药物，包括康诺亚、石药集团/友芝友生物、康缘药业、艾森药业，药物类型涵盖了单抗、双抗、ADC和CAR-T疗法。 康诺亚自研的CM313，是中国首款获国家药监局临床试验申请批准的国产CD38抗体，目前已开展了多项临床试验，适应症包括多发性骨髓瘤、免疫性血小板减少症（ITP）、系统性红斑狼疮、淋巴瘤。 不仅仅是武田制药Mezagitamab，康诺亚CM313也在治疗成人原发免疫性血小板减少症的1/2期临床研究中展现出了积极疗效：CM313在95.5%的既往接受过多种治疗的原发免疫性血小板减少症患者中表现出快速且持续的疗效反应，且安全性良好。 这一研究结果发表在了医学顶级期刊《新英格兰医学杂志（NEJM）》上，该研究共入组22例患者，除1例患者首次给药后脱落，其余21例患者均完成了8次给药和16周的随访。21例患者在整个研究期间达到总体缓解（完全或部分缓解），其中20例患者达到完全缓解。大多数患者因CM313治疗后血小板计数恢复正常或安全水平而停用伴随治疗药物。 （经CM313治疗，患者的中位血小板计数变化） 系统性红斑狼疮与异常活化的B细胞有关，而CD38是这些细胞表面的关键标志物。目前CM313针对系统性红斑狼疮已处于Ib/IIa期临床，有望成为治疗这类疾病的创新型治疗选择。据公开资料显示，系统性红斑狼疮是我国最常见的系统性自身免疫性疾病之一，中国的患者人数超100万，患病率高居世界第二。 另外，友芝友生物布局了一款靶向CD3和CD38的双抗药物Y150，目前正在开展针对多发性骨髓瘤的I期临床研究；艾森药业布局了靶向CD38的ADC药物STI-6129，在研适应症包括多发性骨髓瘤、淀粉样变性。 除此以外，国内还有一些药企正在探索研发靶向CD38的CAR-T疗法，大多处于临床早期阶段。 结语：从血液瘤到自免赛道的差异化探索，CD38靶向药物正展现出新的市场机遇。而且，肾病治疗领域仍是一片未被充分挖掘的蓝海，CD38抗体有望带来更大的想象空间。 往 期 推 荐 1 “懂王”之后，接下来看药王的悬念 2 华东医药自免大跃进 _ 3 下一个现象级大药蓄势 _ *声明：本稿件为转载，仅用于分享，不代表本公众号立场，如涉及版权等问题，请尽快联系我们，我们将第一时间更正或删除，谢谢！ 投稿请添加小助手：bioclub666