IMM-2510

Merck recently announced that it has signed a global exclusive licensing agreement with Lixin Pharmaceuticals for an innovative PD-1/VEGF bispecific antibody named LM-299. According to the agreement, Merck will pay $588 million upfront, and Lixin Pharmaceuticals may receive up to $2.7 billion in additional payments upon achieving specific milestones related to the transfer, development, approval, and commercialization of LM-299 for multiple indications. In 2024, the deal between Merck and Lixin Pharmaceuticals, due to its massive value, has entered the top ten global biopharmaceutical deals by transaction amount, highlighting the significance of oncology drug transactions in the global pharmaceutical R&D market. Although the total transaction amount in 2023 exceeded $53 billion, that year included a $22 billion agreement between Daiichi Sankyo and Merck, making a direct comparison between the two years' totals unfair. However, 2024 has still seen numerous significant transactions, with the top ten expected to exceed $31 billion in total. Among the Top 10 global biopharmaceutical transactions in 2024, each deal has a potential value exceeding $2 billion, with some reaching or surpassing $4 billion. While cardiovascular and neurological diseases are reflected in these deals, oncology treatments remain the most prominent theme, accounting for six of the top ten deals. Novartis has demonstrated a particularly aggressive strategy in oncology, dominating the TOP 10 deals with more than half related to oncology, including partnerships with Dren Bio, PeptiDream, ImmuneOnco, and MOMA Therapeutics. This trend underscores the central role of oncology in biopharmaceuticals, especially in emerging fields such as bispecific antibodies and radioligand therapies. In July 2024, Novartis entered a strategic collaboration agreement with California-based Dren Bio, focusing on developing innovative bispecific antibodies, particularly in the field of tumor immunotherapy. According to the agreement, Novartis will pay up to $3 billion to develop novel antibody drugs targeting myeloid cells. Dren Bio's bispecific antibody platform can activate myeloid cells, potentially offering superior safety and efficacy compared to traditional T-cell activators and antibody-drug conjugates (ADCs). Currently, Dren Bio’s bispecific antibody DR-0201, the first bispecific antibody targeting CD8-positive T cells, is undergoing Phase 1 clinical trials in patients with B-cell non-Hodgkin lymphoma (B-NHL). Through this collaboration, Novartis will acquire Dren Bio’s technology and take responsibility for late-stage clinical development and commercialization, further solidifying its leadership in cancer immunotherapy. Bispecific antibodies, as an emerging immunotherapy strategy, can bind to two different targets simultaneously, potentially inducing a stronger immune response and offering higher efficacy than traditional therapies. Particularly in the field of tumor immunotherapy, bispecific antibodies are becoming a critical component of next-generation cancer treatments. In addition to the collaboration with Dren Bio, Novartis has executed a series of transactions in the oncology space, including the €2.7 billion acquisition of antibody company MorphoSys in February and obtaining the rights to develop Arvinas' androgen receptor protein degrader for prostate cancer in April, a deal valued at $1.16 billion. Other pharmaceutical companies are also making significant strides in the oncology field. Instil Bio signed a licensing agreement with ImmuneOnco, gaining development rights for two Phase 1 clinical candidates targeting solid tumors. ImmuneOnco's IMM2510, a novel PD-L1xVEGF bispecific antibody, can simultaneously target PD-L1 and vascular endothelial growth factor (VEGF), showing significant advantages in enhancing antibody-dependent cellular cytotoxicity (ADCC) and tumor penetration. Additionally, IMM27M, as a next-generation anti-CTLA4 antibody, exhibits stronger ADC activity with relatively low toxicity. These two drugs are currently undergoing combination therapy clinical trials, aiming to bring new hope to the field of tumor immunotherapy soon. In the field of precision medicine, Roche’s collaboration with MOMA Therapeutics has garnered widespread industry attention. In January 2024, Roche and MOMA signed a $2 billion cooperation agreement, leveraging MOMA's KNOMATIC platform to develop precision oncology drugs. The KNOMATIC platform focuses on studying the motion and structural patterns of ATPases and other hard-to-target enzymes, offering new targets for cancer and other disease treatments. This collaboration represents a crucial strategy for Roche in precision medicine, with MOMA providing early-stage drug discovery and target validation support, while Roche takes responsibility for late-stage clinical development and commercialization. The goal of precision oncology is to develop more personalized and effective therapeutic drugs by understanding the dynamic characteristics of cancer cells. Among the Top 10 transactions of 2024, Prime Medicine and Bristol Myers Squibb’s (BMS) subsidiary Juno Therapeutics reached a collaboration worth $3.595 billion, marking a significant milestone for CRISPR Prime Editing technology in its commercialization journey. This deal not only represents a landmark in the CRISPR field but also reflects the rising importance of gene-editing technology as a core driver in the biopharmaceutical industry. Juno Therapeutics gained Prime Medicine's Prime Editing technology license to develop ex vivo T-cell therapies, aiming to provide more precise solutions for complex diseases like cancer. Novartis continues to strengthen its presence in the protein-based drug space in 2024, highlighted by its expanded collaboration agreement with PeptiDream. PeptiDream, a Japanese biotechnology company, uses its core Peptide Discovery Platform System (PDPS) to generate highly diverse cyclic peptide libraries for screening against various biological targets. These targets are further optimized into peptide drugs, small molecules, or peptide-drug conjugates (PDCs). Under the expanded agreement, Novartis will pay $180 million upfront, with potential milestone payments up to $2.71 billion, alongside royalties from product sales. PeptiDream's PDPS platform holds a vital position in current peptide drug research. Compared to traditional linear peptides, cyclic peptides exhibit greater stability and bioactivity, with broad application potential in treating cancer, diabetes, and autoimmune diseases. Through its partnership with PeptiDream, Novartis not only strengthens its research advantage in radiopharmaceuticals but also makes breakthroughs in peptide drug development. Expanding the agreement with PeptiDream aligns with Novartis' trend of advancing radiopharmaceutical development, as evidenced by collaborations with Bicycle Therapeutics and 3B Pharmaceuticals in March and April 2023. In addition, 2024 has seen rapid development in the protein degradation field, driven by capital markets. Multiple biotechnology companies with protein degradation technologies or pipelines have secured funding globally. In April, Novartis entered an exclusive licensing agreement with Arvinas, paying over $1 billion for worldwide rights to Arvinas' second-generation androgen receptor (AR) targeted PROTAC drug ARV-766 and another preclinical AR-targeted PROTAC degrader AR-V7. While global pharmaceutical companies focus on popular drugs like GPL-1, Novartis is blazing new trails by withdrawing from less advantageous areas to expand its presence in emerging technology platforms, including targeted protein degradation, cell therapy, gene therapy, radioligand therapy, and RNA therapy. The protein drug sector is expected to bring more clinical breakthroughs in the coming years. In a globalized environment, cross-border transactions in the pharmaceutical industry are becoming increasingly frequent, driving industry development. In the first half of 2024, there were 2,674 transactions in the global pharmaceutical industry. Facing a new market landscape, companies worldwide are actively seeking opportunities through collaborations. In recent years, Chinese biopharmaceutical companies have performed exceptionally in international collaborations, particularly in technology exports and candidate drug transfers. By 2024, there have been over 50 domestic innovative drug out-licensing deals, dominated by biopharmaceuticals and supplemented by chemical drugs. From E-link/Roche’s c-MET single-target ADC deal at the start of the year to YingEn/GSK’s ADC agreement, China’s impressive partnerships span ADC drugs, monoclonal antibodies, TCE bispecific/trispecific antibodies, fusion proteins, and vaccines. More Chinese companies are expected to make their mark on global pharmaceutical markets.

来源：医药观澜 12月16日，宜明昂科生物医药技术(上海)股份有限公司（简称“宜明昂科”，香港交易所股票代码：01541.HK）宣布，PD-L1xVEGF双特异性抗体IMM2510联合替达派西普(Timdarpacept，IMM01) 的Ib/II期临床研究申请 (IND) 获得国家药品监督管理局 (NMPA) 受理。 替达派西普(IMM01)是中国首个进入临床阶段的SIRPα-Fc融合蛋白，计划开发用于与其他药物联合治疗多种血液肿瘤和实体瘤。目前分别针对初治的CMML和既往PD-1抗体治疗失败后的cHL 适应症的III期注册研究正在积极推进中。 宜明昂科产品管线 关于替达派西普（Timdarpacept，IMM01） IMM01是基于宜明昂科自有研发平台研发、经基因修饰，并具有全球自主知识产权的新一代CD47靶向分子。IMM01具有双重机制，能够同时阻断来自肿瘤的“别吃我”信号，并通过IgG1激活患者免疫系统的“吃我”信号。IMM01在体内具有强大的抗肿瘤活性，临床上可以观察到单药的有效性。同时，在临床前体内药效试验中，IMM01与靶向药物或免疫治疗药物联用，显示了针对血液肿瘤还有实体瘤的强大的抑瘤活性。IMM01完美解决了CD47靶点药物研发中的核心痛点，相比之下具有较大的差异化优势，并具有“Best-In-Class”的潜力。IMM01目前已分别在中国、日本、美国和欧盟获批发明专利。 关于IMM2510 IMM2510项目是基于宜明昂科“mAb-Trap”技术平台研发的、具有自主知识产权的双抗类药物，通过靶向免疫调节靶点PD-L1，阻断了PD-L1和PD-1的结合，解除了肿瘤细胞免疫逃逸，并通过Fc介导的ADCC/ADCP激活NK细胞及巨噬细胞从而发挥强大的肿瘤免疫治疗作用；同时，通过阻断VEGF/VEGFR信号通路，抑制肿瘤血管生成从而抑制肿瘤的生长和转移。临床前研究证实，IMM2510在多种肿瘤模型中均取得显著的治疗效果，IMM2510优于对应靶点的单药或针对两个靶点的联合用药，安全性上具有明显的优势。IMM2510主要的适应症包括多种晚期实体瘤。 免责声明： 文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部责任。本公众号发布的各类文章重在分享，如有侵权请联系我们，我们将会删除。 国内唯一！ 深度聚焦自免药物开发的峰会 联系我们 AIM 2025 展位火热预定中！ 扫码立即咨询 电话：13816031174 （同微信） 赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。 点击此处“阅读全文”咨询更多！