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On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.

点击图片查看IDC2014第六届创新化学药会后报告，IDC2025合作热线：181 1603 6798 美国西部时间7月29日，勃林格殷格翰公司宣布，以最高13亿美元交易收购由维亚生物参与投资孵化的Nerio Therapeutics（“Nerio”）。 Nerio的核心管线为小分子PTPN1/2抑制剂，一款处于临床前阶段的肿瘤管线。该抑制剂通过抑制蛋白酪氨酸磷酸酶N1和N2（“PTPN1”和“PTPN2”），激活免疫系统，对抗癌细胞。此次收购将极大增强勃林格殷格翰公司的肿瘤免疫管线，目标是改善癌症患者的治疗效果。 顶级VC创立，维亚参与孵化 Nerio是一家专注于磷酸酶的药物发现及开发公司，由 Avalon Ventures 创立，并获得了包括 Bregua Corporation、Correlation Ventures、Alexandria Venture Investments 及维亚生物创新中心在内的投资机构支持。 Nerio是依托Avalon BioVentures加速器发展而来，受益于Avalon BioVentures加速器在早期药物开发方面的专长和全面的公司支持。Avalon Ventures 是一家长期专注于种子和早期公司的风险投资公司，成立于1983年，创立和资助了100多家信息技术和生命科学公司。 对于此次收购，Avalon BioVentures合伙人及Nerio Therapeutics联合创始人兼首席执行官Sanford Madigan表示：“我们相信Nerio的小分子PTPN1/N2抑制剂具有优越的药物特性，并提供了成为first-in-class的机会。” Sanford Madigan 拥有深厚的科学背景，且在企业融资、运营、业务开发和并购方面有超过 25 年的从业经验。除了上述两个职位外，他目前还是 Ankasa Rogenic Therapeutics 的首席执行官，也是 Strategic Enzyme Applications 的创始人兼首席执行官。不仅如此，Avalon Ventures的所有合伙人都是经验丰富的企业家，在生命科学和技术领域拥有丰富的公司组建、运营和价值创造的经验。 作为一家初创企业，Nerio不仅有Avalon Ventures这一强大的背书，其背后的其他孵化机构和投资机构同样实力不容小觑。其中，维亚生物创新中心作为一家国内孵化中心引人注目。其2017年由维亚生物正式成立，是公司三大业务板块之一。 维亚生物创新中心（Viva BioInnovator ，简称“VBI”）是维亚生物投资孵化和以服务换股权（EFS）业务的核心部门。维亚生物结合原有的以技术服务换取现金（CFS）和独创的技术服务换取股权（EFS）的创新型商业模式，既能实现稳定现金流入，又能实现长期药物孵化投资带来的高额收益。 凭借维亚生物在新药研发领域多年积累的丰富经验和技术优势，维亚生物创新中心根据新药研发及公司成长阶段的各类需求，提供投资并不断优化研发、场地和后勤支持、产业对接、投融资等一系列投后增值的平台化服务。 截至目前，维亚生物创新中心共计投资、孵化超过90家早期生物医药创新企业，孵化公司产品管线超200条，维眸生物、索智生物、璧辰医药都是其孵化投资的企业。 背后各大资本雄厚且资源丰富，想必也是Nerio能够快速发展，并且获得顶级药企认可的重要原因。 另有顶级MNC也在抢滩这一蓝海 除了背后资本背景雄厚之外，Nerio关注的不可成药领域同样具有价值。近年来，放疗、化疗等治疗手段快速发展，虽然这些治疗方式对肿瘤有一定杀伤作用，但其无差别的杀伤也会对患者健康的组织造成损害。许多患者由于无法耐受副作用选择停药，导致病情严重复发。 在此基础上，以PD-1及其配体PD-L1阻断剂为代表的靶向治疗快速发展。但是，目前只有约10%的靶点被成功开发出靶向药物用于治疗。另有约10%的靶点正在研发中，被开发出靶向药物。而剩下的约80%的靶点在现有抑制剂药物研发技术看来则是不可靶向性靶点，无法被开发为靶向抑制剂药物。 仅针对20%可靶向性的靶点，每年产生的抑制剂靶向药物的市场就达2000亿美金，如果能够将剩下80%的不可靶向性靶点用于研发药物，市场不可估量。 磷酸酶由于具有高度极性活性位点，被公认是一类具有潜在高价值的“不可成药”靶点。 其中，蛋白酪氨酸磷酸酶PTPN2（也称TC-PTP）及其旁系同源物PTPN1（也称PTP-1B）在肿瘤细胞或免疫细胞中的基因缺失可促进抗肿瘤的免疫反应。因此，与目前的治疗方法不同，PTPN2/ N1靶向治疗可以通过直接作用于肿瘤细胞和增加免疫细胞的抗肿瘤活性来实现双重抗癌机制。 对此，Nerio已开发出新型、强效且高度选择性的PTPN2/N1抑制剂，具有卓越的药物特性。Nerio的PTPN2/ N1抑制剂为同类首创，可增强免疫功能，使肿瘤对促炎信号更敏感，从而促进强大的抗肿瘤活性。Nerio的小分子抑制剂不仅能作为单药治疗，还能与公司内部开发的多种癌症疗法联合使用，成为其治疗组合的重要补充。 目前，Nerio的PTPN2/N1抑制剂肿瘤管线尚处于临床前阶段，预计将在今年晚些时候向美国食品和药物管理局（Food and Drug Administration）申请批准开始临床试验。 此次收购是勃林格殷格翰向改变癌症治疗格局迈出的大胆一步。这进一步增强了其在癌症细胞靶向和免疫肿瘤学研究疗法方面的产品管线，旨在通过巧妙的产品组合为癌症患者提供最大获益。勃林格殷格翰董事会成员Paola Casarosa表示，“获得Nerio Therapeutics的创新免疫检查点抑制剂，为勃林格殷格翰创造了广泛而令人兴奋的新癌症治疗药物组合机会。这使我们离实现变革癌症患者生活的愿景更近了一步。” 值得一提的是，艾伯维也布局了相同靶点。其通过与Calico Life Sciences合作，设计出一种能进入细胞并与PTPN2和PTPN1磷酸酶结合的小分子，可有效通过免疫调控实现肿瘤治疗。该管线名为ABBV-CLS-484，目前处于临床1期实验阶段。 在国内，英矽智能通过其生成性AI平台Chemistry42，也开发了一种新型的具有药物相似特性和体内口服吸收的PTPN2/N1抑制剂。其具有纳米级的抑制效力，良好的体内口服生物利用度，以及强大的体内抗肿瘤功效。这项研究于今年4月发表在《欧洲药物化学杂志》上，相关研究目前则处于临床前开发阶段。 * 参考资料：维亚生物，《VIVA朋友圈丨13亿美元交易，维亚生物投资孵化公司Nerio与勃林格殷格翰达成收购》 *封面来源：pexels 点击图片查看IDC2014第六届创新化学药会后报告，IDC2025合作热线：181 1603 6798