Halda Therapeutics LLC

编者按：诱导接近（induced proximity）机制通过将蛋白或核酸拉近形成复合体，从而调控靶点功能。基于这一机制开发的靶向蛋白降解剂（TPD）已成为新药研发的热点之一。与传统抑制剂不同，它们无需直接抑制靶蛋白活性，而是通过降解疾病相关蛋白，有望靶向许多长期被认为“不可成药”的靶点。药明康德在TPD技术刚刚起步时，就开始布局相关能力和技术，积累了丰富的成功经验，搭建起集发现、合成、分析纯化和测试等能力于一体的一站式赋能平台。目前，该平台已成功支持超过120款TPD分子的开发，其中20余款顺利推进至临床阶段。近年来，基于诱导接近机制的研发已不再局限于TPD，还扩展至针对难以成药靶点的抑制剂开发，以及组织特异性药物的开发。本文将回顾2025年第三季度该领域的最新进展，并介绍药明康德的一体化CRDMO平台如何高效解决诱导接近药物开发过程中的诸多挑战。 靶向蛋白降解：FDA受理PROTAC®疗法新药申请 Arvinas与辉瑞（Pfizer）宣布，美国FDA已受理为PROTAC®疗法vepdegestrant递交的新药申请（NDA），用于治疗既往接受过内分泌治疗、雌激素受体阳性（ER+）/人表皮生长因子受体2阴性（HER2-）且伴有ESR1突变的晚期或转移性乳腺癌患者。根据新闻稿，vepdegestrant是首个在乳腺癌患者中展现临床获益的PROTAC®疗法。若获批，该药物将成为首个获美国FDA批准的PROTAC®雌激素受体降解剂。 除了Arvinas公司，C4 Therapeutics公司还公布了靶向IKZF1/3的在研蛋白降解疗法cemsidomide治疗多发性骨髓瘤患者的1期临床试验结果。截至2025年7月23日，75 µg剂量组的客观缓解率（ORR）为40%，100 µg剂量组的ORR为50%。该公司计划在2026年初启动注册性临床试验。 Monte Rosa Therapeutics公司开发的靶向NEK7的分子胶蛋白降解剂MRT-8102，在1期临床试验中已完成首例患者给药。这款口服选择性分子胶降解剂有望用于治疗与NLRP3、IL-1β和IL-6失调相关的炎症性疾病。值得注意的是，该公司还在《科学》杂志发表论文，详细介绍了其自主开发的人工智能（AI）和机器学习（ML）引擎如何发现可通过CRBN介导降解的人体蛋白，涵盖多种不同的蛋白结构域与类别。这一突破显著拓展了分子胶蛋白降解药物的可操作靶点空间。该公司还在9月15日宣布与诺华（Novartis）达成57亿美元的新研发合作协议，携手推动针对免疫介导疾病的创新降解剂研发。 TPD药物虽具广阔前景，但其开发也面临独特挑战。例如，PROTAC®分子由于分子量大、结构复杂，通常存在溶解度差和药代动力学性质不佳的问题。以下案例展示了药明康德旗下合全药业（WuXi STA）如何与合作伙伴携手，有效应对这些挑战。 解决TPD药物开发痛点，加速创新疗法进入临床试验 几年前，一家公司因PROTAC®分子的生产难题，选择与合全药业合作，希望在14个月内完成候选药物的生产，以支持IND申请及首次人体临床试验。然而，该候选分子的初始合成路线非常复杂，需要多达24个步骤，且最终产率仅为0.3%。此外，PROTAC®特定的分子结构进一步增加了产品结晶和纯化难度。 同时，由于候选化合物分子量较大且水溶性低，其口服生物利用度只有0.9%。值得注意的是，在合成过程中还有三步涉及使用罕见金属钯（Pd）作为催化剂，这不仅带来潜在安全隐患，更显著提高了生产成本。 针对上述问题，合全药业的工艺研发、生物催化及结晶工艺等团队协同攻关，重新设计了一条合成路线，将合成步骤从原来的24步缩减至16步，并在其中两个步骤中用生物催化剂替代了钯催化剂。为攻克结晶难题，团队采用高通量结晶筛选技术，迅速确定了符合纯度与产量要求的结晶工艺，并通过优化大幅提升了生产过程的总产率。这些改进不但极大提高了整体合成工艺的可放大性，也提升了合成效率并降低了成本。 与此同时，合全药业的制剂研发团队针对药物口服生物利用度低的问题，进行了全面的生物利用度增强技术筛选，最终选定喷雾干燥制备固体分散体（SDD）技术进行制剂制备。这种技术将难溶药物以无定形状态高度分散在聚合物中，目前已成功应用于多种上市药物的制剂开发中。借助SDD技术，候选化合物药片制剂的口服生物利用度提高了约30倍，为后续临床应用奠定了坚实基础。 合全药业一体化CRDMO平台的整合能力，使多个团队能够并行推进原料药与制剂开发，高效协作，加速破解PROTAC®分子开发中的难题。最终，团队仅用了12个月就完成了支持IND申请所需的候选药物生产和制剂制备，顺利供应首次人体临床研究用药，比合作伙伴原定时间提前了2个月。 超越蛋白降解：分子胶抑制剂获突破性疗法认定 TPD只是诱导接近机制在新药开发中的一种应用。分子胶通过将靶点蛋白与呈递蛋白（presenter proteins）结合，形成复合表面，从而突破传统药物对活性位点的依赖，让小分子能够靶向更多“不可成药”的靶点，显著拓展了治疗可能性。 例如，Revolution Medicines公司研发的RAS抑制剂elironrasib成功招募了cyclophilin这一呈递蛋白，实现了对激活状态下KRAS G12C蛋白的特异性靶向与抑制。今年7月，该药物获得FDA授予的突破性疗法认定，用于治疗携带KRAS G12C突变的非小细胞肺癌（NSCLC）患者。Elironrasib单药治疗在既往未接受KRAS抑制剂的经治NSCLC患者中达到56%的ORR和94%的疾病控制率（DCR）；与pembrolizumab联用时，一线治疗的ORR更是高达100%，显示出可喜的初步疗效。 Halda Therapeutics公司的调节诱导接近靶向嵌合体（RIPTAC）则代表另一种新策略。这类异双功能分子的一端结合富集于癌细胞中的靶点蛋白，另一端结合细胞生存必需的关键蛋白。当细胞同时表达这两种蛋白时，RIPTAC分子将两者结合形成复合体，使关键蛋白失活，从而诱导癌细胞死亡。 今年8月，Halda Therapeutics宣布与VantAI达成研发合作，利用VantAI的人工智能和结构蛋白组学发现平台，开发治疗癌症和免疫疾病的下一代RIPTAC药物。 越来越多开发诱导接近药物的公司开始利用人工智能技术加速新药发现，除了Halda Therapeutics与VantAI的合作，Revolution Medicines在7月与Iambic Therapeutics也达成研发合作，利用Iambic公司基于AI的蛋白-配体结构预测模型和图像神经网络模型来发现创新候选药物。今年8月，致力于分子胶药物开发的Proxygen宣布与洛桑联邦理工学院（EPFL）建立战略研究合作关系。这一合作旨在将高通量体外筛选与先进计算设计相结合，以系统性地预测和验证新底物-连接酶相互作用，并设计能够诱导靶向蛋白降解的化学分子。 非降解性分子胶的开发也得到投资人的关注。今年9月，Rapafusyn Pharmaceuticals宣布完成4400万美元A轮融资。该公司的RapaGlue平台已展现出生成高协同非降解型分子胶的能力，这些分子胶具有较高的细胞膜通透性，可用于调控蛋白-蛋白相互作用、转录因子、转运蛋白、离子通道、酶等多种难以成药靶点。 一体化平台助力分子胶早期发现 药明康德一体化平台的能力不但涵盖PROTAC®，还包括分子胶、以及多种新兴双功能分子。以分子胶药物发现为例，其早期研发阶段中无偏倚药物筛选的低命中率始终是一大挑战。为助力合作伙伴有效应对这一难题，药明康德采取了“双轨并进”的策略，构建起一套兼顾广度与深度的化合物库体系：一方面，通过多样化的DNA编码化合物库（DEL）大范围探索新靶点；另一方面，借助聚焦化合物库精细化研究已知蛋白体系，提升发现效率。 ▲药明康德分子胶发现平台（图片来源：参考资料[15]） 在分子胶药物的早期发现过程中，药明康德不仅依赖DNA编码化合物库进行筛选，还不断引入并整合多种先进技术，以助力合作伙伴拓展分子胶药物的发现能力。其中，亲和筛选质谱（ASMS）提供无标记筛选手段。药明康德构建了一个涵盖超过37万个小分子的广谱化合物库，通过比较这些分子在单蛋白与双蛋白条件下的质谱信号差异，精准识别出能够促进蛋白–蛋白相互作用的潜在分子胶候选物，从而识别出潜在促互作的小分子。 与此同时，公司还部署高通量筛选（HTS）技术。在“一孔一化合物”的自动化运行模式下，结合蛋白结合能力或降解能力等功能性实验，HTS能迅速锁定具备生物活性的候选分子，大幅提升筛选效率与准确性。通过将ASMS与HTS等多维筛选工具与DEL平台深度融合，药明康德打破了单一筛选方式的限制，让更多不同类型的靶点进入分子胶研究视野，进一步拓宽了分子胶在多类靶点上的研发空间。 展望未来 Broad研究所联合创始人Stuart Schreiber博士在2024年发表的一篇评论文章中指出，基于诱导接近作用的分子胶和双功能化合物为药物发现提供了创新模式。这一模式可以通过新颖的方式调控具有挑战性的靶点，包括稳定、降解、易位、激活，以及重塑转录回路。对于精准医疗而言，这可能提供了一个独特的机会，将“合适的药物在合适的时间、用于合适的患者，在合适的组织中生效”这一理念变为现实。 药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，以独特的一体化、端到端的CRDMO模式，助力包括靶向蛋白降解剂在内的诱导接近药物的开发，帮助合作伙伴将科学创新转化为惠及全球患者的变革性药物。 CRDMO: Q3 2025 Review of Induced Proximity Drugs The induced proximity mechanism regulates target function by bringing proteins or nucleic acids into close proximity to form complexes. Targeted protein degraders (TPDs) developed on this basis have become one of the hottest areas in drug discovery. Unlike traditional inhibitors, TPDs do not need to block target activity directly; instead, they eliminate disease-related proteins, opening opportunities to tackle many proteins once deemed “undruggable.” When TPD technology was still in its infancy, WuXi AppTec started building relevant capabilities. Since then, the company has established a comprehensive, integrated platform encompassing discovery, synthesis, purification, analysis, and testing. To date, this platform has supported the development of more than 120 TPD molecules, with over 20 advancing to clinical stages. In recent years, induced proximity has extended beyond TPDs to include inhibitors for hard-to-drug targets and tissue-specific therapies. This article reviews the latest developments in Q3 2025 and highlights how WuXi AppTec’s integrated CRDMO platform helps overcome the unique challenges of developing induced-proximity medicines. Targeted Protein Degradation: FDA Accepts NDA for a PROTAC® Therapy In a major regulatory milestone, Arvinas and Pfizer announced that the U.S. FDA has accepted the New Drug Application (NDA) for the PROTAC® therapy vepdegestrant. The application covers patients with advanced or metastatic breast cancer who have received prior endocrine therapy and are ER+/HER2− with ESR1 mutations. According to the companies, vepdegestrant is the first PROTAC® therapy to demonstrate clinical benefit in breast cancer. If approved, it will become the first FDA-approved PROTAC® estrogen receptor degrader. Other companies are also making progress. C4 Therapeutics reported Phase 1 clinical results for its protein degrader cemsidomide in multiple myeloma. As of July 23, 2025, the objective response rate (ORR) was 40% in the 75 µg cohort and 50% in the 100 µg cohort. A registrational trial is planned for early 2026. Meanwhile, Monte Rosa Therapeutics announced that the first subjects have been dosed in a Phase 1 study evaluating MRT-8102, a NEK7-directed molecular glue degrader being developed for the treatment of inflammatory conditions driven by the NLRP3 inflammasome, IL-1β, and IL-6. Adding to this progress, Monte Rosa published a paper in Science describing how its proprietary AI and ML engine identified human proteins potentially amenable to CRBN-mediated degradation. The findings, spanning diverse protein domains and classes, significantly broaden the actionable target space for molecular glue degrader discovery. On September 15, the company also announced an agreement to collaborate with Novartis to develop novel degraders for immune-mediated diseases. While clinical advances are encouraging, TPDs still pose unique development hurdles. For example, due to their large molecular weight and structural complexity, PROTAC® compounds often suffer from poor solubility and suboptimal pharmacokinetics. The following case study illustrates how WuXi STA, an integral part of WuXi AppTec, collaborated with a partner to address these challenges effectively. Addressing Key Bottlenecks in TPD Drug Development Several years ago, a biotech company developing a PROTAC® candidate faced synthetic challenges and turned to WuXi STA for support. The goal was to complete the production of drug substance and clinical trial material within 14 months to support an IND filing and FIH trial. However, the original synthesis route involved 24 steps and yielded only 0.3%. Crystallization and purification proved difficult due to the compound’s unique structure. Compounding the challenge, the candidate’s high molecular weight and poor solubility resulted in oral bioavailability of only 0.9%. Moreover, three steps in the synthesis relied on a palladium (Pd) catalyst, raising safety concerns and increasing production costs. To resolve these issues, WuXi STA’s process chemistry, biocatalysis, and crystallization teams worked in concert to redesign the synthesis route, reducing the number of steps from 24 to 16 and replacing palladium with biocatalysts in two steps. To tackle crystallization bottlenecks, high-throughput crystallization screening identified suitable conditions that met both purity and yield requirements. These changes significantly improved the scalability and efficiency of the synthetic route while reducing costs. Simultaneously, WuXi STA’s formulation team addressed the low oral bioavailability by exploring a range of enabling technologies and ultimately selected spray-dried dispersion (SDD) to prepare a solid dosage form. SDD disperses poorly soluble compounds in an amorphous state within a polymer matrix and has been successfully used in several approved drugs. With this approach, the candidate’s oral bioavailability improved by approximately 30-fold—supporting further clinical advancement. Thanks to WuXi STA’s integrated CRDMO model, API process development and formulation were advanced in parallel by multiple teams working seamlessly together. Ultimately, they delivered IND-enabling materials and clinical trial materials within just 12 months—two months ahead of schedule. Beyond Protein Degradation: Molecular Glue Inhibitor Receives Breakthrough Designation Induced proximity is not limited to protein degradation. Molecular glues, which bind a target protein and a presenter protein to form composite binding surfaces, bypass the need to interact with active sites. This allows small molecules to reach a broader range of targets, including those once considered undruggable. A notable example comes from Revolution Medicines. Its RAS inhibitor elironrasib recruited cyclophilin as a presenter protein to selectively target and inhibit active-state KRAS G12C. In July, the FDA granted Breakthrough Therapy Designation for elironrasib in KRAS G12C-mutant NSCLC. Phase 1 data were compelling: in previously treated patients without prior KRAS inhibitors, monotherapy achieved a 56% ORR and 94% disease control rate (DCR). In combination with pembrolizumab as first-line therapy, the ORR reached 100%, signaling strong early potential. Halda Therapeutics is advancing another strategy with Regulated Induced Proximity Targeting Chimeras (RIPTACs). These heterobifunctional molecules bind a cancer-enriched target protein on one end and an essential survival protein on the other. By bringing the two together, RIPTACs inactivate the survival protein, triggering cancer cell death. In August, Halda announced a partnership with VantAI to apply AI and structural proteomics in the discovery of next-generation RIPTACs for cancer and immune diseases. Revolution Medicines also entered a collaboration with Iambic Therapeutics in July, leveraging AI-based protein-ligand prediction and neural network models to accelerate novel candidate discovery. In August, Proxygen announced a strategic research collaboration with EPFL (the Swiss Federal Institute of Technology in Lausanne). The collaboration aims to build a next-generation discovery paradigm that bridges high-throughput in vitro screening with state-of-the-art in silico design. Non-degrading molecular glues also attracted investors’ attention. In September, Rapafusyn Pharmaceuticals announced the closing of its oversubscribed Series A financing round ($44 million). Its RapaGlue platform has demonstrated the ability to create highly cooperative non-degrading molecular glues with high cell membrane permeability to modulate protein–protein interactions, transcription factors, transporters, ion channels, enzymes, and others. WuXi AppTec’s integrated platform supports not only PROTAC® development but also molecular glues and other bifunctional modalities. By uniting cutting-edge screening technologies, tailored library design, and deep scientific expertise, WuXi AppTec offers a fully integrated platform for molecular glue discovery. This approach supports partners across: Hit identification and validation Mechanistic characterization and degradation profiling Lead optimization and SAR development Outlook Looking ahead, the potential of induced proximity continues to grow. In a 2024 commentary, Dr. Stuart Schreiber, co-founder of the Broad Institute, highlighted molecular glues and bifunctional compounds as an innovative paradigm in drug discovery—capable of stabilizing, degrading, translocating, activating targets, as well as rewiring transcriptional circuits. For precision medicine, this may enable the long-sought goal of delivering “the right drug to the right patient at the right time—and in the right tissue.” Guided by its vision that “every drug can be made and every disease can be treated”, WuXi AppTec remains committed to leveraging its unique, fully integrated, end-to-end CRDMO model to help partners transform scientific innovation into transformative therapies for patients worldwide. 参考资料： [1] Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer. Retrieved August 20, 2025, from https://www.globenewswire.com/news-release/2025/08/08/3130368/0/en/Arvinas-Announces-FDA-Acceptance-of-the-New-Drug-Application-for-Vepdegestrant-for-the-Treatment-of-ESR1m-ER-HER2-Advanced-Breast-Cancer.html [2] C4 Therapeutics Reports Second Quarter 2025 Financial Results and Recent Business Highlights. Retrieved August 20, 2025, from https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-reports-second-quarter-2025-financial-results [3] Monte Rosa Announces Publication in Science of Key Insights that Enable Next Generation Molecular Glue Degrader Medicines. Retrieved August 20, 2025, from https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-announces-publication-science-key-insights-enable [4] Monte Rosa Therapeutics Announces First Subjects Dosed in Phase 1 Study of MRT-8102, a NEK7-Directed Molecular Glue Degrader for the Treatment of Multiple Inflammatory Diseases. Retrieved August 20, 2025, from https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-first-subjects-dosed-phase-1 [5] SEED Therapeutics Named Finalist for 2025 Prix Galien USA “Best Start-Up” Award. Retrieved August 20, 2025, from https://seedtherapeutics.com/seed-therapeutics-named-finalist-for-2025-prix-galien-usa-best-start-up-award/ [6] Revolution Medicines Announces FDA Breakthrough Therapy Designation for Elironrasib. Retrieved August 20, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-fda-breakthrough-therapy-0 [7] Revolution Medicines Announces Publication of a Peer-Reviewed Research Paper in Science on the Discovery and Development of Zoldonrasib, a RAS(ON) G12D-Selective Inhibitor. Retrieved August 20, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-publication-peer-reviewed [8] VantAI and Halda Therapeutics Forge Alliance to Discover Next-Generation RIPTAC Medicines. Retrieved August 20, 2025, from https://haldatx.com/vantai-and-halda-therapeutics-forge-alliance-to-discover-next-generation-riptac-medicines/ [9] Arvinas Reports Second Quarter 2025 Financial Results and Provides Corporate Update. Retrieved August 20, 2025, from https://ir.arvinas.com/news-releases/news-release-details/arvinas-reports-second-quarter-2025-financial-results-and [10] Targeted Protein Degrader. Retrieved August 20, 2025, from https://rcs.wuxiapptec.com/wp-content/uploads/RCS_Targeted-Protein-Degrader_20250818.pdf [11] Revolution Medicines and Iambic Announce Technology and Research Collaboration Using Iambic’s AI Discovery Tools to Pursue New Drug Candidates. Retrieved August 27, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-and-iambic-announce-technology-and-research [12] Schreiber (2024). Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity. Cell Chemical Biology, DOI: 10.1016/j.chembiol.2024.05.004 [13] Rapafusyn Pharmaceuticals Closes Over-Subscribed $44 Million Series A Financing to Advance Its Non-Degrading Molecular Glue Drug Discovery Platform. Retrieved September 11, 2025, from https://www.globenewswire.com/news-release/2025/09/04/3144896/0/en/Rapafusyn-Pharmaceuticals-Closes-Over-Subscribed-44-Million-Series-A-Financing-to-Advance-Its-Non-Degrading-Molecular-Glue-Drug-Discovery-Platform.html [14] Proxygen and EPFL Launch Strategic Collaboration to Advance AI-Driven Glue Discovery. Retrieved September 11, 2025, from https://www.globenewswire.com/news-release/2025/08/26/3139189/0/en/Proxygen-and-EPFL-Launch-Strategic-Collaboration-to-Advance-AI-Driven-Glue-Discovery.html [15] Molecular Glues Discovery: Challenges and Opportunities. Retrieved July 4, 2025 from https://wuxibiology.com/resource/discovery-of-molecular-glues-challenges-and-opportunities/ 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

8月，全球小分子药物交易市场展现出强劲的活跃度，尤其是在神经科学和肿瘤学领域。仅上周，发生3起超10亿美元的小分子药物交易合作：Skyhawk Therapeutics与德国默克达成超20亿美元合作聚焦RNA靶向小分子，用于治疗神经系统疾病；Jazz Pharmaceuticals则以10.35亿美元获得Saniona的癫痫候选药物SAN2355的全球权益。此外，VantAI与Halda Therapeutics的合作（价值超10亿美元）结合AI技术与RIPTAC平台，推动肿瘤和免疫疗法的突破。这些交易凸显了小分子药物在解决复杂疾病机制中的持续潜力。 从宏观趋势看，8月至今，全球小分子药物交易合作数量至少26起，潜在交易总额超140亿美元，涉及神经、肿瘤、代谢等多个领域。亮点包括： AI技术与小分子药物开发的结合成为显著趋势：除前文提到的VantAI超10亿美元合作外，晶泰科技与DoveTree合作达成约470亿港元合作，结合AI推动多款处于临床前阶段的大分子及小分子创新药资产研发（也是8月潜在最高额小分子药物交易合作）；礼来达成13亿美元合作，结合AI推进治疗心脏代谢疾病和肥胖症的小分子疗法。此外，还有MetaVia、MAX Biopharma等公司达成AI小分子药物研发合作。 神经科学领域成为小分子药物交易热点：上周3起超10亿美元小分子药物交易合作中，2起聚焦神经系统疾病，包括德国默克达成的超20亿美元合作、Jazz公司10.35亿美元引进癫痫候选药物。此外，还有至少7起交易合作涉及该领域，进一步印证了神经科学领域的高需求。 值得关注的交易合作： 晶泰科技与DoveTree合作推进AI驱动的创新药资产开发 8月5日，晶泰科技宣布与DoveTree完成总订单规模约470亿港元的管线合作签约，并已收到协议约定的首付款约4亿港元。根据协议条款，晶泰科技与DoveTree就多款处于临床前阶段的大分子及小分子创新药资产达成合作，并将针对一系列 DoveTree指定的靶点进行新药研发，DoveTree独家享有相关药物全球范围的独家开发和商业化权利。 此次合作中，双方将深度融合DoveTree公司生物学机制研究、靶点选择和商业化开发能力，与晶泰科技AI驱动的药物研发技术优势，共同推进肿瘤学、免疫及炎症疾病、神经系统疾病及代谢失调领域的高潜力管线项目。 Skyhawk Therapeutics与德国默克合作开发RNA靶向小分子药物 8月18日，Skyhawk Therapeutics宣布与德国默克达成一项价值超过20亿美元的战略合作，专注于开发RNA靶向小分子药物，用于治疗神经系统疾病。根据协议，Skyhawk将利用其专有的SkySTAR平台筛选候选药物，而德国默克将负责后续开发和商业化。 Skyhawk的SkySTAR平台通过调节RNA剪接技术，针对传统方法难以攻克的疾病靶点。此次合作聚焦于神经系统疾病，如阿尔茨海默病和帕金森病，旨在通过RNA靶向技术解决未满足的临床需求。德国默克的加入进一步验证了RNA靶向小分子在神经科学领域的潜力。 拜耳与Kumquat在精准肿瘤学领域获得全球独家许可和合作 8月12日，拜耳和Kumquat Biosciences宣布达成全球独家许可和合作，以开发和商业化Kumquat的KRAS G12D抑制剂。根据协议，Kumquat负责启动和完成1a期研究，而拜耳将完成开发和商业活动。根据协议条款，Kumquat将获得达13亿美元的资金，包括前期、临床和商业里程碑，以及净销售额的额外分级特许权使用费。 KRAS突变发生在近25%的癌症中，最普遍和致癌的KRAS（G12D）变体仍然缺乏有效的治疗方案。本次合作重点是开发KRAS G12D抑制剂，补充拜耳在胰腺癌、结直肠癌和肺癌领域的精准肿瘤学开发组合。 Superluminal与礼来合作推进针对心脏代谢疾病和肥胖症的小分子疗法 8月14日，Superluminal Medicines宣布与礼来合作，共同推进针对与心脏代谢疾病和肥胖症相关的未公开GPCR靶点的小分子疗法。根据协议条款，在Superluminal交付符合预定标准的候选药物后，礼来将获得合作中产生的化合物的独家开发和商业化权利。Superluminal最多可获得13亿美元的协议，其中包括首付款和短期付款、股权投资、开发和商业里程碑付款，以及净销售额的分级特许权使用费。 此次合作将利用Superluminal基于结构的药物发现平台，结合礼来在小分子药物开发和商业化方面的专长，快速推进可能改变生命的疗法。Superluminal的平台整合了深度结构生物学、机器学习以及专有的药代动力学和毒理学预测工具，以加速候选小分子的发现。最初的研究重点是GPCR，这是一个历来具有挑战性的靶点类别，其功能选择性和结构复杂性需要下一代计算解决方案。 Jazz Pharmaceuticals获得Saniona的癫痫候选药物SAN2355全球权益 8月20日，Jazz Pharmaceuticals与Saniona达成独家许可协议，以10.35亿美元的总交易额获得SAN2355的全球开发和商业化权利。Saniona将获得4250万美元的首付款，并有机会获得后续里程碑付款和销售分成。 SAN2355是一种选择性Kv7.2/Kv7.3钾通道激活剂，用于治疗癫痫。其独特的设计避免了非选择性Kv7靶向药物的副作用，有望成为癫痫治疗领域的重要候选药物。Jazz Pharmaceuticals在神经科学领域的商业化能力将为SAN2355的临床开发提供支持。 VantAI与Halda Therapeutics合作开发RIPTAC疗法 8月19日，VantAI与Halda Therapeutics宣布达成一项价值超10亿美元的合作，结合VantAI的AI驱动药物发现平台与Halda的RIPTAC技术，开发针对肿瘤和免疫疾病的精准疗法。 Halda的RIPTAC技术通过“hold-and-kill”机制选择性杀伤肿瘤细胞，其候选药物HLD-0915已进入临床阶段。VantAI的Neo-1模型和NeoLink平台将加速靶点发现和验证，推动新型小分子药物的开发。此次合作展示了AI技术与新型作用机制结合的潜力。 读者们请星标⭐创鉴汇，第一时间收到推送 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。 更多数据内容推荐 点击“在看”，分享创鉴汇健康新动态

Collaboration integrates VantAI’s frontier AI and structural proteomics discovery platform with Halda’s novel and clinically validated RIPTAC™ modality to unlock novel, cell-selective approaches in oncology and immunology NEW YORK, NA & NEW HAVEN, CT, USA I August 19, 2025 I VantAI, the leader in generative AI for proximity drug discovery, and Halda Therapeutics, the pioneer of RIPTAC (Regulated Induced Proximity Targeting Chimeras) therapeutics, today announced a strategic research collaboration worth over $1 billion in total potential value, inclusive of upfront and milestone payments across multiple targets. This landmark alliance combines two category-defining platforms to accelerate the discovery and development of selective proximity-based therapies across cancer and immunology indications. The agreement includes upfront payments, research support, success-based development and commercial milestones, and tiered royalties on net sales, with a path to expand the collaboration over time. Under the partnership, VantAI will leverage its Neo-1 foundation model and NeoLink high-throughput structural proteomics platform to rapidly identify and validate novel, context-specific target–effector pairs . These pairs—across both oncology and immunology—will feed directly into Halda’s proprietary RIPTAC development pipeline , which harnesses a distinctive “hold-and-kill” mechanism to achieve potent, cell-selective effects in disease-relevant tissues. By pairing Halda’s validated modality with VantAI’s AI-driven rational drug design engine, the partnership is poised to deliver the next generation of selective, proximity-based therapeutics tailored to disease-specific signatures. “Induced proximity is poised to unlock a new and exciting chapter of medicine, including but also beyond protein degradation,” said Zachary Carpenter, Co-Founder and CEO of VantAI. “Halda is leading this next wave, already demonstrating its potential in the clinic. Together, we’re advancing a new generation of RIPTACs—leveraging the unique properties of this modality to address previously inaccessible targets, with the potential to meaningfully impact patients underserved by current treatment options.” “VantAI’s proprietary platform enables the systematic rewiring of protein interactions with precision,” said Christian Schade, President and CEO of Halda Therapeutics. “By pairing Halda’s novel RIPTAC modality with VantAI’s AI-driven rational drug design engine, the partnership will complement platform discovery efforts and will help deliver the next generation of selective, proximity-based therapeutics tailored to disease-specific signatures.” Halda’s lead candidate, HLD-0915, is currently advancing through Phase 1/2 clinical trials in metastatic castration-resistant prostate cancer (mCRPC). About VantAI VantAI is pioneering a transformative approach to drug discovery by illuminating the dynamic networks of protein interactions that drive biological function. Leveraging our groundbreaking NeoLink structural proteomics platform and next generation foundation models, VantAI generates unprecedented interactomics data at scale, revealing how molecules connect, interact, and shape cellular behavior—in 3D. Alongside a robust and mechanistically differentiated internal pipeline, VantAI collaborates extensively with external partners to accelerate the delivery of innovative therapies. VantAI’s cross-disciplinary team of scientists and engineers is uniquely positioned to unlock novel therapeutic strategies that induce, modulate, or block protein interfaces—making previously undruggable targets accessible and providing powerful new ways to target diseases by rewiring cellular circuitry. For more information, please visit www.vant.ai . About HLD-0915 HLD-0915 is an innovative bifunctional small molecule therapy designed to selectively target prostate cancer tumors cells by holding together, with defined orientation and purpose, androgen receptor (a tumor-specific intracellular targeting protein) and a protein with essential function (effector protein). The ternary complex drives the formation of new, or neomorphic, protein-protein interactions, abrogating an essential function within cancer cells which results in an antitumor effect. HLD-0915 is designed to drive specific interactions between selected proteins to achieve optimal activity and pharmacology, as demonstrated in Halda’s preclinical studies. In preclinical prostate cancer models, orally delivered HLD-0915 treatment resulted in tumor shrinkage and declines in prostate-specific antigen (PSA), while delivering a favorable therapeutic index including in models of drug resistance. About Halda Therapeutics Halda Therapeutics is a clinical-stage biotechnology company that has developed a proprietary RIPTAC™ (Regulated Induced Proximity Targeting Chimeras) modality that works by a novel “hold and kill” mechanism for the precision treatment of cancer and other diseases. The novel mechanism of action of RIPTAC therapeutics is uniquely designed to address cancer’s ability to evolve bypass mechanisms of resistance, a common limitation of today’s precision oncology medicines. Our lead RIPTAC programs are in clinical and pre-clinical development for major solid tumor types with additional RIPTAC therapeutic programs in our pipeline to treat serious disease. Halda is led by a leadership team with deep expertise in biotechnology, drug discovery, platform innovation, and clinical development, and is located in New Haven, CT. For more information, please visit www.haldatx.com and follow us on LinkedIn . SOURCE: VantAI