预约演示
更新于：2025-11-15
Trastuzumab Imbotolimod
更新于：2025-11-15
概要
基本信息
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最高研发阶段临床1期 |
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最高研发阶段(中国)- |
特殊审评孤儿药 (美国) |
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结构/序列
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Sequence Code 18481L
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关联
2
项与 Trastuzumab Imbotolimod 相关的临床试验NCT05954143
Phase 2, Multi-Center, Randomized, Open-Label Trial of BDC-1001 as a Single Agent and in Combination With Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer Previously Treated With Trastuzumab Deruxtecan
This is an open-label, Phase 2 study to evaluate preliminary anti-tumor activity, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of BDC-1001 administered as a single agent and in combination with pertuzumab in subjects with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) previously treated with trastuzumab deruxtecan (Enhertu®).
开始日期2023-11-30 |
申办/合作机构 |
NCT04278144
Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Nivolumab in Patients With Advanced HER2-Expressing Solid Tumors
A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in HER2 expressing advanced malignancies
开始日期2020-02-24 |
申办/合作机构 |
100 项与 Trastuzumab Imbotolimod 相关的临床结果
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100 项与 Trastuzumab Imbotolimod 相关的转化医学
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100 项与 Trastuzumab Imbotolimod 相关的专利（医药）
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93
项与 Trastuzumab Imbotolimod 相关的新闻（医药）2025-11-12
Initial clinical data for BDC-4182 Phase 1 dose escalation study expected in 3Q 2026 Cash balance of $38.8 million as of September 30, 2025 anticipated to fund key milestones into 2027
REDWOOD CITY, Calif., Nov. 12, 2025 (GLOBE NEWSWIRE) -- Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today reported financial results for the third quarter ended September 30, 2025, and provided a business update.
“In the third quarter, we focused on developing BDC-4182, the first next-generation Boltbody™ ISAC in our pipeline. We are actively enrolling patients with gastric and gastroesophageal cancer in the Phase 1 dose-escalation study. We now look forward to presenting initial data in the third quarter of 2026,” said Willie Quinn, President and Chief Executive Officer. “With our cash runway now expected to extend into 2027, we are in a financial position to create long-term value for our shareholders and fulfill our mission of bringing new treatment options to patients with cancer.”
Recent Highlights and Anticipated Milestones
Initial clinical data for BDC-4182 Phase 1 study for patients with gastric and gastroesophageal cancer expected in the third quarter of 2026. BDC-4182 is a next-generation Boltbody™ ISAC clinical candidate targeting claudin 18.2, a clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. Following a strong immune response that was observed at the initial dose levels, Bolt modified the clinical trial protocol to allow for step-up dosing, which has been successfully used commercially for T-cell engagers. The clinical trial is ongoing and the Company expects to present initial clinical data in the third quarter of 2026. In November at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), Bolt presented preclinical data supporting the clinical development of BDC-4182. The data indicate that the claudin 18.2 ISAC stimulates a powerful, tumor-dependent immune response that culminates in complete tumor regression and the establishment of immunological memory. The ensuing T cell-dependent immunity was robust enough to prevent the growth of tumors lacking claudin 18.2 expression during rechallenge experiments. Furthermore, the ISAC demonstrated superior anti-tumor activity compared to both Topo1- and MMAE-based ADCs, particularly in a low-antigen model of claudin 18.2-expressing cancer. Taken together, these findings provide a strong rationale for the ongoing clinical development of BDC-4182. Presented updated preclinical results for next-generation Boltbody™ ISACs targeting CEA and PD-L1 at SITC. Bolt’s CEACAM5 (CEA) ISAC features a novel, fully human antibody with high affinity and selectivity for membrane-bound CEA while minimizing binding to other CEACAMs and soluble CEA. Our CEA ISAC is conjugated to a proprietary TLR7/8 agonist via a non-cleavable linker and drives enhanced phagocytosis of CEA-positive tumor cells and immune activation relative to an ISAC created with an alternative CEA antibody, tusamitamab. Bolt’s CEA ISAC induced complete and durable anti-tumor responses in preclinical models and was more effective than a Topo1-based ADC at lower doses and in a lower antigen density tumor model. Bolt’s CEA ISAC was well tolerated in a non-GLP toxicology study and is available for partnering. Bolt’s PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a TLR7/8 agonist via a non-cleavable linker. This ISAC leverages a unique mechanism of action due to its ability to target both tumor and immune cells that express PD-L1. Preclinical results demonstrated that PD-L1 ISACs represent a compelling new approach to treat cancer, leveraging mechanisms that are distinct from and potentially complementary to conventional PD-1/PD-L1 blockade with the potential for enhanced immune activation and antitumor activity. The poster also highlights the potential advantage of using an active Fc and a dual TLR7 and TLR8 agonist, design choices that may confer a competitive advantage versus other PD-L1 ISACs in development. Collaborations with Genmab and Toray ongoing. Genmab and Bolt’s collaboration continues to explore research and development of additional next-generation ISAC programs for the treatment of cancer. The Toray collaboration combines the Company’s immunostimulatory linker-payloads with Toray antibodies targeting Caprin-1, a tumor-specific antigen that is strongly expressed on the cell membrane in multiple solid tumor types. Seeking a partner for further BDC-3042 development. BDC-3042 is a proprietary agonist antibody that targets dectin-2, an immune-activating receptor expressed by tumor-associated macrophages (TAMs). Bolt completed the Phase 1 dose escalation study and presented the clinical results at the American Associates for Cancer Research (AACR) Annual Meeting that took place in April 2025. BDC-3042 is available for partnering. Cash, cash equivalents, and marketable securities were $38.8 million as of September 30, 2025. Cash position is expected to fund multiple milestones and operations into 2027.
In November at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), Bolt presented preclinical data supporting the clinical development of BDC-4182. The data indicate that the claudin 18.2 ISAC stimulates a powerful, tumor-dependent immune response that culminates in complete tumor regression and the establishment of immunological memory. The ensuing T cell-dependent immunity was robust enough to prevent the growth of tumors lacking claudin 18.2 expression during rechallenge experiments. Furthermore, the ISAC demonstrated superior anti-tumor activity compared to both Topo1- and MMAE-based ADCs, particularly in a low-antigen model of claudin 18.2-expressing cancer. Taken together, these findings provide a strong rationale for the ongoing clinical development of BDC-4182.
Bolt’s CEACAM5 (CEA) ISAC features a novel, fully human antibody with high affinity and selectivity for membrane-bound CEA while minimizing binding to other CEACAMs and soluble CEA. Our CEA ISAC is conjugated to a proprietary TLR7/8 agonist via a non-cleavable linker and drives enhanced phagocytosis of CEA-positive tumor cells and immune activation relative to an ISAC created with an alternative CEA antibody, tusamitamab. Bolt’s CEA ISAC induced complete and durable anti-tumor responses in preclinical models and was more effective than a Topo1-based ADC at lower doses and in a lower antigen density tumor model. Bolt’s CEA ISAC was well tolerated in a non-GLP toxicology study and is available for partnering. Bolt’s PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a TLR7/8 agonist via a non-cleavable linker. This ISAC leverages a unique mechanism of action due to its ability to target both tumor and immune cells that express PD-L1. Preclinical results demonstrated that PD-L1 ISACs represent a compelling new approach to treat cancer, leveraging mechanisms that are distinct from and potentially complementary to conventional PD-1/PD-L1 blockade with the potential for enhanced immune activation and antitumor activity. The poster also highlights the potential advantage of using an active Fc and a dual TLR7 and TLR8 agonist, design choices that may confer a competitive advantage versus other PD-L1 ISACs in development.
Third Quarter 2025 Financial Results
Collaboration Revenue – Total collaboration revenue was $2.2 million for the quarter ended September 30, 2025, compared to $1.1 million for the same quarter in 2024. Revenue in the comparative periods was generated from services performed under the R&D collaborations as we fulfill our performance obligations. Research and Development (R&D) Expenses – R&D expenses were $6.5 million for the quarter ended September 30, 2025, compared to $13.8 million for the same quarter in 2024. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses, a decrease in clinical expenses primarily related to the discontinued development of trastuzumab imbotolimod, formerly known as BDC-1001 in May 2024. General and Administrative (G&A) Expenses – G&A expenses were $3.3 million for the quarter ended September 30, 2025, compared to $3.8 million for the same quarter in 2024. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring. Loss from Operations – Loss from operations was $7.7 million for the quarter ended September 30, 2025, compared to $16.4 million for the same quarter in 2024.
About the Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) PlatformBolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc. Bolt Biotherapeutics is a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer. Bolt Biotherapeutics’ pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development. The Company’s pipeline includes BDC-4182, a next-generation Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) clinical candidate targeting claudin 18.2. BDC-4182 is currently in a Phase 1 dose escalation trial that includes patients with gastric and gastroesophageal cancer. The Company has strategic collaborations with Genmab and Toray built around the Company’s Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) platform technology and its expertise in myeloid biology. The Company is seeking to partner its Dectin-2 agonist, BDC-3042, that recently completed a first-in-human Phase 1 dose escalation trial. For more information, please visit https://www.boltbio.com/.
Forward-Looking StatementsThis press release contains forward-looking statements about us and our industry that involve substantial risks and uncertainties and are based on our beliefs and assumptions and on information currently available to us. All statements other than statements of historical facts contained in this press release, including statements regarding our ability to partner BDC-3042, the advancement and success of our BDC-4182 clinical trials, the timing of initial data from our Phase 1 dose-escalation study of BDC-4182, the anti-tumor potency, safety and tolerability, and characteristics of our product candidates, the initiation of future clinical trials, the potential value of collaborations, and the expected duration of our cash runway and ability to fund key milestones into 2027, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “on track,” “plan,” “potential,” “predict,” “project,” “should,” “will,” or “would,” or the negative of these words or other similar terms or expressions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our current beliefs, estimates and assumptions only as of the date of this press release and information contained in this press release should not be relied upon as representing our estimates as of any subsequent date. These statements, and related risks, uncertainties, factors and assumptions, include, but are not limited to: the potential product candidates that we develop may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; such product candidates may not be beneficial to patients or become commercialized; and our ability to maintain our current collaborations and establish further collaborations. These risks are not exhaustive. Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Further information on factors that could cause actual results to differ materially from the results anticipated by our forward-looking statements is included in the reports we have filed or will file with the Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. These filings, when available, are available on the investor relations section of our website at investors.boltbio.com and on the SEC’s website at www.sec.gov.
Investor Relations and Media Contact: Matthew DeYoung Argot Partners (212) 600-1902 boltbio@argotpartners.com
临床1期免疫疗法AACR会议财报
2025-11-04
·医药速览
竺宝琳
普华资本 投资副总裁
除了比较成熟的ADC、FDC、RDC外，随着偶联技术和对分子类型认知的提升，有望实现突破性发展的领域有蛋白降解偶联药物和抗体-核苷偶联药物等。当然除了科学性考量外还需要考虑市场情况和竞争优势，但下一代“ADC”仍然有很大的机会出现。
文丨竺宝琳
2023年3月，辉瑞以430亿美元并购Seagen；4月初，映恩生物成为继荣昌生物、科伦药业之后又一个获得超亿美元首付款的国内ADC创新药企。回顾过去几年，ADC在全球市场交易持续火热，该领域何以吸引巨头重金下场，除了ADC自身各组分迭代优化外，下一个“ADC”在何方？
01.
ADC交易回顾
ADC的交易数量和交易方式：
自2018年以来，ADC相关资产的交易量增长了三倍多，授权模式和共同开发模式占比最高。
ADC不同临床阶段的交易数量：
ADC交易经常在产品开发生命周期的早期达成。可见人们对早期的技术/资产有明显的兴趣，特别是在发现阶段，涉及单抗选择、优化链接子和毒素选取等方面。
ADC与其他不同分子形式平均交易首付款和里程碑付款对比：
虽然ADC的交易频率低于某些分子形式，但ADC获得的交易价值最高。平均而言，所有阶段的首付款为8.51亿美元 (基于42项已披露的交易)，其中5项交易的首付款为10亿美元。在评估总交易金额中位值时，ADC的总体价值为8.48亿美元，比多/双特异性抗体的中位值5.12亿美元高出3亿美元。
ADC不同临床阶段的交易规模：
ADC的交易版图中最引人注目的是各个开发阶段的整体交易价值。虽然从临床前到3期临床的整体交易价值也在持续增加（从临床前的约25亿美元到3期临床的约40亿美元），但首付款显著增加（从临床前的5200万美元到I期临床的5.2亿美元），这表明了通过临床数据实现的成药性风险消除价值。
02.
为何是ADC?
ADC 药物自开发至今已有接近 100 多年历史，其首次真正尝试源于 1958 年，Mathe 将抗鼠白细胞免疫球蛋白与甲氨蝶呤偶联用于白血病的治疗。但这次尝试以失败告终，直到 2000 年第一款 ADC 药物 -吉妥珠单抗才正式上市；2011 年第二款 ADC 药物维布妥昔单抗上市，自此之后的 11 年接连上市了 10多款药物。总体来说，ADC 药物从 2011 年开始才真正意义上进入了发展的快车道。不同于大多数前沿疗法叫好不叫座，近5年来ADC凭借颠覆性的临床疗效及广覆盖的适应应用，正在释放巨大商业价值。DS-8201在2019年底以末线疗法上市以来，不断往前线和Her2低表达攻克，商业上气势如虹，2022年全球销售额12.6亿美元，《Nature》预计其 2026年销售额将达到62亿美元。
(一）结构决定性质
抗体偶联药物（ADC，Antibody Drug Conjugate）由三部份组成，分别是能够对癌细胞靶向的单克隆抗体、高生物活性的小分子药物以及能够将单抗和小分子药物连接的连接子。
抗体与癌细胞表面抗原结合后介导ADC通过内吞作用进入细胞，经内体运输进入溶酶体，在溶酶体中ADC的连接子或抗体部分降解，并释放细胞毒性小分子药物杀死肿瘤细胞。
ADC药物研发核心在于抗体、连接子、小分子毒素、偶联技术等四大基本要素。
1.1抗体方面涉及靶标选择和抗体类型选择
靶标（Target）选择：
理想的靶点可以获得更低的非特异性毒副作用以及更好的治疗指数。通常可选择的靶抗原有在肿瘤组织表达的特异性抗原（TSA）和在肿瘤组织中高表达而在正常组织中低表达的肿瘤相关抗原（TAA）。除了特异性表达要求外，这些这些靶点还需要有介导内吞作用，从而实现小分子药物在胞内起效。研究发现，ADC 活性与细胞表面的抗原数量相关，至少需要 10 4的表面抗原才能确保致死剂量的细胞毒性药物被递送到细胞内部实现ADC药物的起效，但DS-8201在her2低表达适应症的临床成功也给未来靶点选择拓宽了思路。
ADC有丰富的靶点选择空间：
− 已成药的抗体靶点（如Her2）；
− 靶部位高表达可内吞且机理较清晰的尚未成药靶点（如叶酸受体-α/FR-α）；
− 机理尚未完全验证的未成药靶点
15款上市的ADC药物对应11个靶点，分别为CD33、CD30、HER2、CD22、CD79b、Nectin-4、BCMA、EGFR、CD19、TissueFactor和FRα。
据药智网和医药魔方数据库统计在研的425款ADC药物中较为热门的靶点包括HER2、EGFR、CLDN18.2、TROP2、c-Met、CD19、PSMA、Muc1、BCMA和PDL1，大多数为验证成熟的靶点。
更进一步待验证的ADC靶点有：
注：由义翘神州公开资料整理
抗体（Antibody）选择：
抗体可变区选择和靶点高度相关，本身要求其满足高特异性、强靶点结合能力；恒定区选择要求低免疫原性、低交叉反应活性，以达到肿瘤细胞对ADC药物更高效的摄入和ADC药物在血清中更长的半衰期。
− ADC中抗体来源选择经历了大致四个阶段，即鼠源、嵌合体、人源化以及全人源抗体。由于鼠源、嵌合体抗体在不同程度上受到高免疫排异、低效性以及较短的循环半衰期影响，随着抗体和基因工程技术的发展，人源化以及全人源抗体成为ADC药物设计中的第一选择，现在绝大多数临床和临床前研究都采用后两种抗体。
− 除了抗体来源外，人的抗体还有多种亚型，其中IgG1在血清中丰富最高，也能够较好地平衡长半衰期和强免疫激活的关系，是被研究和采用最多的ADC抗体。除IgG1之外，IgG4由于较低的免疫激活效应也经常被采用在一些对免疫原性反应要求较高的ADC药物设计中。IgG1和IgG4都具有12个链内二硫键和4个链间二硫键，其中链间二硫键具有较高反应活性常被作为连接子反应位点。但是由于IgG4具有较高的Fab段交换性质会引起脱靶效应，所以在ADC药物设计在使用IgG4抗体时还需采取S228P 位点变异的策略来降低Fab段交换。
− 此外由于抗体本身具有某些信号作用，如抗体依赖性细胞毒性（ADCC）、抗体依赖的细胞吞噬（ADCP）和补体依赖性细胞毒性（CDC）也应被慎重考虑。ADCC和ADCP会介导免疫系统参与杀伤肿瘤细胞过程，对最终ADC的治疗效果产生影响，因此在设计ADC药物时必须对抗体的ADCC、ADCP效应有充分的研究。
1.2小分子毒素（Payloads）的选择：
毒素分子是 ADC 药物研发成功的关键因素，直接决定对靶细胞的杀伤效果。
早期ADC药物研究一般选择包括阿霉素在内的传统小分子化疗药物，但是注射入体内的抗体仅仅只有很小的一部分聚集在实体瘤组织中，且单个抗体偶联小分子药物数量有限，导致那些半数抑制浓度（IC50）在微摩尔级别的小分子药物并不能达到很好的治疗效果。现在在选择小分子药物时往往要求小分子药物IC50值低至纳摩尔级别乃至皮摩尔级别。这些小分子药物主要包括两类，即微管蛋白抑制剂和DNA 损伤剂。另外，毒性分子必须具有可偶联的合适的功能基团，强大的细胞毒性，具有疏水性，且在生理条件下要非常稳定。
除需要较低的IC50值以外，通常还要求小分子药物有以下属性：1)在与抗体偶联后不易引起ADC药物发生聚集以保证在体内拥有较长的循环时间；2)本身以及构成ADC药物后较低的免疫原性；3)在水溶液、血液中足够稳定且具有合适的反应位点；4）通过连接子与抗体偶联，偶联后仍然能够保证其生物活性；5）可以通过相对经济的过程合成。
1.3连接子（Linker）的选择：
尽管根据肿瘤细胞的类型选择特异性抗体和 payloads 很重要，但就药代动力学，药理学和治疗窗口来说，连接子能够对最终获得ADC药物的毒性、稳定性、特异性等性质产生巨大影响，通过选择合适的 linker 来约束抗体和 payloads 是成功构建 ADC 的关键。理想的 linker 必须满足以下条件：1）linker 需要在血液循环系统中稳定存在，当定位到肿瘤细胞内或附近时能快速释放活性 payloads，linker 的不稳定性会导致 payloads 的过早释放，造成对正常组织细胞的损伤；2）ADC 一旦被内化到靶肿瘤组织中，linker 需要具有被快速裂解并释放毒性分子的能力；3）亲疏水性也是 linker 考虑的一个重要特性，疏水性连接基团和疏水性 payloads 通常会导致 ADC 小分子的聚集，从而引起免疫原性。
连接子大体上可以分为第一代ADC药物采用的不可裂解型和第二、三代ADC药物采用较多的可裂解型。
不可裂解型：
不可裂解型连接子主要包括马来酰型以及含硫醇己酰胺型连接子，通过形成酰胺键以及硫醚键将小分子药物与抗体偶联。
不可裂解型连接子能够保证ADC药物在体内循环中保持较高的稳定性，经抗体-抗原介导进入细胞后通过内体运输进入溶酶体，然后抗体在溶酶体中各种生物酶的作用下裂解释放小分子药物进而产生细胞毒性。但通常采用不可裂解型连接子的ADC药物一般针对性靶向具有高抗原表达肿瘤细胞而很少影响周边低抗原表达的肿瘤细胞，这是由于ADC药物在溶酶体中酶解后的小分子药物通常带有具有电荷的氨基酸残留物，这些带电氨基酸-小分子复合物不能够进出细胞膜进而通过旁观者效应杀伤周围肿瘤细胞。
可裂解型：
可裂解型连接子利用其在血液系统和肿瘤细胞的环境差异，主要分为pH敏感型（腙类、碳酸酯类）、酶敏感型（多肽类、β-葡萄糖醛酸苷类）以及可还原型（二硫键），分别利用进入肿瘤组织酸性内体（PH=5.0-6.0）或溶酶体（PH=4.8）中较低的pH值、肿瘤细胞内蛋白酶、肿瘤细胞内较高的还原性来裂解连接子。采用这一类型连接子的ADC药物在通过抗体靶向定位肿瘤细胞，在肿瘤区域富集并利用肿瘤细胞特殊的微环境的刺激使连接子断裂释放小分子药物，从而产生抑制细胞增殖和杀伤细胞的效果。与不可裂解型连接子相比对肿瘤细胞内吞的依赖性较低，有利于ADC的旁杀伤效应。
可见，选择何种类型的 linker 与靶标选择密切相关。在具有可切割 linker 的 ADC 药物中，靶标为 B 细胞抗原(CD19，CD20，CD21，CD22，CD79B，CD180) 的，被证实在体内非常有效。相反，带有不可切割 linker 的 ADC 药物中，被证实在体内内吞并快速转运到溶酶体的靶标如CD22，CD79b有效。
1.4偶联技术
偶联方法可分为化学偶联和酶偶联，也可分为定点偶联和非定点偶联。
化学偶联包括：赖氨酸酰胺偶联、半胱氨酸偶联、引入非天然氨基酸偶联。
赖氨酸酰胺偶联：
赖氨酸残基上的氨基可以与含有活性羧酸酯的连接子以酰胺键连接，进一步实现与药物偶联。由于抗体表面赖氨酸残基数量众多，该方法得到的ADC中将包含不同DAR和多种偶联部位的偶联物，优化后得到的最佳均值DAR为3.5-4，实际分布为0-7，均一性差。同时，一些赖氨酸残基在抗原抗体相互作用中很重要，该方法会降低抗体的亲和性。
半胱氨酸偶联包括：
1）传统半胱氨酸偶联：一般情况下，抗体中半胱氨酸残基链间和链内都有巯基，以二硫键形式存在，链间的二硫键对抗体性质基本没有影响，可以采用温和的还原方法使其断裂，得到游离巯基。在IgG1中，有4个链间二硫键和12个链内二硫键，可以将链间二硫键选择还原为2、4、6或8个二硫键，进一步进行偶联。由于可偶联部位少，该方法优于赖氨酸酰胺偶联，但均一性仍有待提升；
2）工程化突变半胱氨酸偶联（Thiomab技术）：通过定点诱变，在单抗中人工引入半胱氨酸残基用于偶联。这样得到的ADC的DAR均值为1.9，抗体均一性大于90%，体内外都有活性；
3）半胱氨酸二硫键重架桥偶联：利用二溴马来酰亚胺等试剂，可以在还原后的链间巯基之间形成重架桥，实现定点偶联，得到的DAR主要为4；
4）芳基钯高选择性偶联：利用芳基钯进行高选择性偶联，得到的DAR主要为4.4。该方法不需要连接子，产物对酸、碱、氧化稳定，但是用到钯催化剂，需要考虑毒性、价格、钯残留等问题。
第一种方法为非定点偶联，后三种方法为定点偶联。
插入非天然氨基酸偶联：
引入非天然氨基酸，利用其上的特征官能团进行偶联，方法包括：
1）通过一种特殊的密码子-tRNA合成酶可以在蛋白质中引入含有羰基的p-乙酰基苯丙胺残基，利用该羰基与烷氧胺生成肟，进一步与药物偶联；
2）引入含有叠氮基团的非天然氨基酸残基，如p-叠氮甲基苯丙胺等可以与炔基通过叠氮-炔环化反应连接，通过改变炔的结构，该反应在铜催化条件存在与否的情况下都可以进行。
插入非天然氨基酸偶联属于定点偶联技术，得到的ADC具有较好的均一性，但该方法需要特殊的技术，且这些非天然氨基酸的免疫原性未知，需要考虑安全性。
酶偶联包括：
转肽酶催化转肽反应偶联、细菌谷氨酰胺转氨酶催化转氨反应偶联、N-聚糖工程偶联、甲酰甘氨酸生成酶催化反应偶联等。
(二） 技术迭代助力临床优效
从ADC药物发展至今，从技术迭代的角度看，可以分为三代。
2.1 同靶点HER2-ADC的对比
ADC的三要素抗体、连接子、载荷，每一项都是影响最终药物安全性和有效性的关键。无论是罗氏的Kadcyla（T-DM1）、第一三共的Enhertu （DS-8201）还是荣昌生物的RC48，都在各自的系统中，做到了三要素的平衡。
Kadcyla 作为先行者，开拓了ADC治疗实体瘤领域。而Enhertu和RC48，作为后来者不仅是致敬T-DM1，也通过自身技术的积累和更新，升级HER-2 ADC，挑战T-DM1的治疗效果。
靶点选择：
HER2在肿瘤细胞的表达量较正常细胞有100倍以上的差异，且HER2已经有成熟抗体药物，使其成为ADC治疗实体瘤一个较为理想的靶点。三家药企都选择了HER2作为ADC药物开发的靶点。这样在验证ADC平台时可避免生物学机理不清晰的挑战。
抗体：
T-DM1凭借曲妥珠单抗强内吞活性，将DM1递送至细胞内发挥肿瘤细胞的杀伤作用。DS-8201，与T-DM1同样使用了曲妥珠单抗，其亮点是独特的linker-payload系统大大增强了其药效。RC48, 使用了自主研发新型抗体-Disitamab，与曲妥珠单抗具有不同HER2表位，对HER2具有高度选择性。Disitamab具有更高的亲和力，EC50 为6.4pM, 曲妥珠单抗的EC50为20.1pM。
Linker：
T-DM1使用MCC的不可裂解 linker。而DS-8201和RC48 则采用GGFG 和VC的可裂解linker，可裂解 linker有利于ADC的旁杀伤效应。减小ADC药物的疏水性有利于减少ADC体内清除，增强ADC药效。DAR值也直接关联着ADC的药效。而增加DAR值和减少疏水性存在一定的矛盾，因此，linker的亲水性就显得十分重要。DS-8201通过优化筛选上百种linker，建立起自其独特的linker-payload系统，使得DAR值可以高达8，且仍然保持较好的亲水性。独有的linker技术贡献了第一三共ADC成功的关键。
载荷：
由于肿瘤细胞表面上抗原的数量有限（平均每个细胞表面约 5,000 至 106的抗原），而且大多数临床阶段的 ADC 药物平均 DAR 为 3.5 至 4，所以 ADC 药物传递到肿瘤细胞内的很少。这也被认为 ADC 中偶联常规细胞毒性药物如甲氨蝶呤、紫杉醇和蒽环类抗生素等临床失败的主要原因之一。T-DM1采用了低通透性DM1毒素，而随着科学研究深入，第一三共研发了高通透性的DXd毒素，荣昌生物使用了较好的MMAE毒素，两者都比DM1 具有更高的膜通透性。毒素释放后，可穿透相邻细胞产生旁杀效应。从荣昌招股书中动物实验发现，3.3mg/kg RC48对靶细胞的旁观者效应明显强于10mg/kg T-DM1。此外，有研究表明不可裂解linker和细胞膜低通透性的DM1毒素，导致T-DM1在溶酶体中的大量积累，使得长时间的药物暴露，是造成T-DM1耐药的一个重要原因。
2.2 ADC成功的必然性和偶然性
必然性：
生物学确定性。肿瘤治疗的终极目标是选择性杀死肿瘤细胞而不损伤正常细胞。化疗药物这么多年之所以一直能够占据肿瘤治疗的一线疗法，正式因为其确切几乎无差别的杀伤效果，但也伴随着耐药和显著副作用问题。ADC药物从科学性上最简单的逻辑就是将化疗药物或比化疗药物毒性更大的毒素靶向递送到肿瘤细胞，没有生物学和科学性疑问。如果能够精准递送，则必然成功。
偶然性：
技术创新性。由于ADC涉及抗体、毒素、连接子、偶联方式等多个关键因素，哪一个团队能够在某一方面形成突破或迭代进化有很大的不确定。随着抗体技术日渐成熟，DS-8201通过对毒素、连接子的筛选，创新偶联方式，形成了对Her2靶点的重大突破。但其也仍面临间质性肺炎发生率较高的问题，未来还有新的ADC产品有机会在药物连接设计，甚至抗体全新靶点选择上实现新的迭代。
03.
下一个"ADC"?
跨国药企纷纷重金押注ADC赛道，势头不亚于早些年的PD-1，过去几年全球科学家也在寻找下一个PD-1，但是肿瘤免疫治疗领域的TIGIT、TGFβ、偏向性IL-2纷纷折戟。那有下一个“ADC”么？
对比肿瘤免疫治疗（IO）赛道和ADC，从生物学确定性和技术创新看有很大的不同。IO赛道的创新药研发可能更侧重基础生物学的突破，新靶点、新机理、新通路，但是ADC领域目前看到主要突破在分子设计和偶联技术，其构成有确定机理的靶点以及确定起效的载荷，相比IO在科学性上的风险更小，对技术可实现性要求更高。
从ADC的结构出发探索可成药的分子结构，就配体、连接子和载荷方向做了可能的延伸：
除了 抗体+linker+小分子毒素 的ADC设计外，通过排列组合，我们还可以看到：抗体片段偶联药物（FDC）、多肽偶联药物（PDC）、小分子偶联药物（SMDC）、核素偶联药物（RDC）、抗体免疫刺激偶联药物（ISAC）、抗体降解偶联药物（ADeC）、抗体细胞偶联药物（ACC）、病毒样药物偶联物（VDC）、抗体寡核苷酸偶联物（AOC）、抗体生物聚合物偶联物（ABC）等。
从配体类型分类：
抗体片段偶联药物（FDC）和ADC的主要差别在于将全长的抗体换成抗体片段，主要依托于新的抗体工程技术发展，更小的抗体结构在肿瘤渗透上可能也有更好的疗效，同时由于结构缩小连接位点的选择也可能更为受限，药物代谢上可能与全长抗体也有区别。
多肽偶联药物（Peptide-Drug Conjugates，PDC）主要是将靶头从ADC的抗体换成归巢肽，相比于目前ADC 药物，PDC 药物具有分子量小、肿瘤穿透性强、免疫原性低、利用固相合成法可大规模合成、生产成本较低、相对较好的药代动力学等特点。但目前多肽药物主要为内源性多肽的衍生物，如奥曲肽、GLP-1、胰岛素等，如何开发高亲和力的靶向多肽可能比ADC中的抗体要做更多的研究。
小分子偶联药物（Small molecule-drug conjugates，SMDC）采取小分子定向，小分子之间的定点偶联技术可以实现相对准确的药物抗体比（DAR）。SMDC由纯小分子构成容易控制成本；理论上不会具有免疫原性，安全性控制更容易实现；分子量相较于ADC要低很多，从而在实体瘤中能够具有更好的细胞通透性以及更好的体外和体内稳定性。同时，也要考虑到SMDC的小分子配体选择并没有ADC抗体那样直接，筛选合适配体的难度较大。此外分子量小有优势也需要考虑半衰期和口服给药可实现性。
从广义上看蛋白降解靶向联合体（PROTAC）也属于SMDC，通过小分子实现靶向将E3连接酶带到靶标实现目标分子的降解。但是PROTAC要求linker是不可断裂的，SMDC的linker是可裂解的。从可裂解的角度看，小分子前药设计也可以归入SMDC，但前药可能不一定要求有可靶向性的配体。
同理核酸适配体偶联物（ApDC）、DNA嵌合体偶联物（如DNA嵌合体靶向水解，DENTAC）、病毒样颗粒偶联物（VDC）等主要将抗体变换为全新的配体成分。从筛选难度上看，也许抗体是最容易获得和做靶点差异化选择的配体。
从载荷类型分类：
核素偶联药物（Radionuclide Drug Conjugates，RDC）是利用抗体（Antibody-radionuclide Conjugate，ARC）或小分子（包括多肽，Peptide-radionuclide Conjugate，PRC）介导的靶向定位作用将细胞毒/成像因子（放射性核素放射性同位素，Radionuclide radioisotope）精准定位至靶位置，避免全身暴露的潜在危害。不同之处是，RDC载荷是放射性核素，既可用于诊断也能实现治疗功能；组成上与ADC也略有差异，需要添加螯合毒素的特定官能团结构。代表药物有诺华的镥177氧奥曲肽、177Lu-PSMA-617等。
抗体-免疫刺激偶联物（Immune stimulating antibody conjugate，ISAC）和抗体-免疫调节偶联物（Immune modulating antibody conjugate，IMAC）主要是将免疫激动剂或免疫抑制剂连接到抗体上，实现起效成分的靶向释放。这两类有效成分由于其下游效应细胞在体内分布广，如果不能实现有效靶向的话一方面会限制其使用剂量影响疗效，另外一方面会因为全身分布导致靶毒性，故通过抗体实现靶向是比较理想的方式。涉及此类机制的药物主要包括Toll样受体激动剂（TLR）类ISAC药物BDC-1001；STING激动剂ISAC药物XMT-2056，Treg细胞调节IMAC药物ADCT-301等。
抗体-降解剂偶联物（Antibody degrader Conjugate，ADeC），它的技术原理是将蛋白降解剂如分子胶或Protac作为payload，兼具抗体的肿瘤特异性和PROTAC分子在催化剂量下对低表达的适用性。代表药物是有Orum Therapeutics开发的ORM-5029。与降解剂相反的药物设计有蛋白稳定剂，DUBTACs也是类似Protac的双功能性分子，它们的一端是与致病蛋白相结合的化合物，通过连接子与能够募集去泛素化酶（DUB）的化合物连接在一起。去泛素化酶能够去除即将被降解的蛋白表面的泛素链，从而防止它们的降解并稳定蛋白水平。2022年这个领域Stablix 、Vicinitas等多家靶蛋白稳定的公司完成早期融资，但尚未看到抗体-稳定剂偶联物（Antibody stabilizer Conjugate，ASC）相关公司。
抗体-寡核苷酸偶联物（Antibody oligonucleotide Conjugate，AOC）和 抗体-siRNA偶联物（Antibody-siRNA conjugates, AsiRC）的设计是将寡核苷酸或siRNA连接到抗体上。目前RNA类药物面临着肝外靶向性不足的问题，通过抗体实现组织靶向也许是核酸递送的突破方向。相比于ADC携带的毒素，核酸片段的分子量要大很多，其电负性对药物设计也有非常不同的要求。目前代表药物是由Avidity 开发的AOC-1001。Avidity是研发AOC的先驱，该设计结合了单克隆抗体的组织选择性和基于寡核苷酸治疗方法的精确性，从而克服了阻碍寡核苷酸传递的障碍并实现疾病的遗传驱动因素靶向，用于治疗罕见的肌肉疾病和其他严重疾病。率先进入临床的AOC-1001由3部分组成：靶向转铁蛋白受体1的全长单抗、linker、靶向DMPK mRNA的siRNA，适应症为强直性肌营养不良症1型。
抗体-生物聚合物偶联物（Antibody-biopolymer Conjugate，ABC）由抗体与生物多聚物通过连接子偶联得到。代表药物是由Kodiak 开发的KSI-301。公司采用800kDa分支状磷酸胆碱多聚物为生物多聚物，该多聚物可以与水结合，与抗体通过不可裂解连接子定点偶联，在抗体外形成一层水屏障，避免其受到非特异性相互作用干扰直达靶点。该平台被设计用于VEGF靶点，提高药物在眼组织内的持续时间，以此提高疗效、减少注射次数，目前正被开发用于治疗视网膜血管疾病和预防糖尿性眼病患者的视力丧失。2022年2月，Kodiak Sciences公布湿性年龄相关黄斑变性KSI-301首个注册临床试验DAZZLE 数据，显示视力矫正较阿柏西普未显示非劣，未达到临床终点；公司分析认为，此次失败的一个重要原因是方案用药间隔过长。
抗体-细胞偶联物（Antibody-cell Conjugate，ACC）与CAR-T的作用类似，更偏向于细胞治疗，抗体起到为细胞疗法提供靶向的作用，如CAR-NK，CAR-血小板等。但抗体细胞偶联药物通过化学反应偶联，不需要基因改造，免疫细胞仍保留天然的激活信号系统，抗体仅起到靶向作用。代表药物有Acepodia公司开发的ACE1702。
将上述排列组合所得创新平台，根据以下几点考虑，以生物学确定性和技术成熟度为横纵坐标作图：
1.抗体偶联药物（ADC）和抗体片段偶联药物（FDC）相比其他偶联平台相似度最高，随着抗体工程的演进都有比较好的技术成熟度；
2.多肽偶联药物（PDC）、小分子偶联药物（SMDC）和核酸适配体偶联药物（ApDC）由于理想配体筛选难度较抗体更大，故参与企业数量比ADC少，技术成熟度相对较低，同靶点比ADC作出优效的科学性确定性也许要弱一些，但如果找到合适的靶点也有差异化的发展机会；
3.抗体偶联免疫激活剂（ISAC）从技术层面看与ADC有比较相似的设计方法，但目前激活剂单药成药难点比较大，载荷的生物学机理还有很多尚未研究清楚；
4.核素偶联药物（RDC）目前基于多肽和小分子的靶向基础已经有一些药物上市，相对技术成熟度和科学确定性比较高。由于核素管控要求更高，开发企业需要克服的相应技术难点，较ADC的技术普及性稍低；
5.蛋白降解体系的偶联药物有单纯的Protac、以及抗体介导的ADeC和DNA嵌合体介导的DNEtac，这些都依托体内的泛素降解体系，生物学机理已经有相对比较多的研究，但在药物分子结构设计和起效过程中体内三元复合物形成上还有很多技术问题待克服。目前Pretac已有相关分子进入临床研究阶段，其他尚处于临床前；
6.蛋白稳定剂与蛋白降解剂的作用机理相反，抑制泛素降解体系，与体内天然的泛素化系统运作相反，相比降解剂在基础生物学和分子设计上还都有更多要研究的，目前一些企业尚处于临床前阶段；
7.抗体偶联核酸（AOC）解决了目前核酸药物靶向性的核心难题，与ADC相比在连接上会有一些区别和待探索技术。生物学确定性上由于载荷涉及核酸全新序列设计，但这些序列的设计可参考基因组学，类似其他高开发成功率的RNA药物，在生物学成熟度上会有一些挑战但相对可控。
8. 病毒样药物偶联物（VDC）和抗体生物聚合物偶联物（ABC）在药物分子更大，结构更复杂，整体生物学确定性和目前的技术发展都还更早期些。
注：1.在坐标中将ADC定位生物学确定性、技术成熟度最高，将新靶点的成熟分子形式（如抗体、小分子）定位生物学确定性最低、技术成熟度最高。2.不同色块对应有较大不同的技术平台，相同色块指相应平台在技术路径或实际应用上有比较好的可替换性。
上图中我们可以看到除了比较成熟的ADC、FDC、RDC外，随着偶联技术和对分子类型认知的提升，有望实现突破性发展的领域有蛋白降解偶联药物和抗体-核苷偶联药物等。当然除了科学性考量外还需要考虑市场情况和竞争优势，但下一代“ADC”仍然有很大的机会出现。
参考文献：
1.A Payday For Payloads: The Transactional Landscape Of ADCs.
2.Site-selective modification strategies in antibody–drug conjugates.
3.Cleavable linkers in antibody–drug conjugates.
4.Strategies and challenges for the next generation of antibody-drug conjugates.
5. Antibody–Drug Conjugates for Cancer Therapy.
6.Antibody-drug conjugates: recent advances in conjugation and linker chemistries.
7.Characterization of antibody-drug conjugates by mass spectrometry: advances and future trends.
8.Antibody–drug conjugates in solid tumors: a look into novel targets.
9.荣昌生物制药招股书。
10. HER2-ADC的迭代进阶。
11.Antibody–Drug Conjugates: A Comprehensive Review.
12.Antibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.
13.Collaboration on trastuzumab deruxtecan Investor conference call presentation.
14.Avidity、Stablix、Vicinitas、Kodiak、Acepodia等官网.
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抗体药物偶联物引进/卖出临床3期临床2期并购
2025-08-14
Next-generation claudin 18.2 ISAC BDC-4182 now in Phase 1 dose-escalation study Cash balance of $48.5 million as of June 30, 2025 anticipated to fund key milestones through mid-2026
REDWOOD CITY, Calif., Aug. 14, 2025 (GLOBE NEWSWIRE) -- Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today reported financial results for the second quarter ended June 30, 2025, and provided a business update. “In the second quarter we focused on advancing BDC-4182, the first next-generation Boltbody™ ISAC in our pipeline,” said Willie Quinn, President and Chief Executive Officer. “We are now conducting a Phase 1 dose-escalation study for patients with gastric and gastroesophageal cancer in Australia, and will expand to other countries in the second half of 2025. We look forward to presenting initial data in the first half of 2026. We also continue to seek a partner for further development of our dectin-2 agonist antibody BDC-3042, which demonstrated activity in lung cancer patients in the form of a partial response (PR) at the highest dose tested. Patients at the highest doses also had a strong immune response consistent with our expectations based on preclinical data.”
Recent Highlights and Anticipated Milestones
Our BDC-4182 Phase 1 study opened for enrollment for patients with gastric and gastroesophageal cancer in the first half of 2025. BDC-4182 is a next-generation Boltbody™ ISAC clinical candidate targeting claudin 18.2, a clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. Preclinically, monotherapy treatment with BDC-4182 generated complete regressions in multiple models and BDC-4182 was tolerated in toxicology studies. BDC-4182 outperformed cytotoxic claudin 18.2 ADCs, using MMAE or Topo1, in multiple preclinical studies. Collaborations with Genmab and Toray continue to progress. Genmab and Bolt are advancing multiple development candidates, while the companies also continue research and development on additional programs. The Toray collaboration combines the Company’s immunostimulatory linker-payloads with Toray antibodies targeting Caprin-1, a tumor-specific antigen that is strongly expressed on the cell membrane in multiple solid tumor types. Seeking a partner for further BDC-3042 development. In May, Bolt hosted a KOL conference call with BDC-3042 investigator Dr. Dumbrava to discuss the results from the Phase 1 dose-escalation clinical study of BDC-3042 that were presented at the American Associates for Cancer Research (AACR) Annual Meeting that took place in April 2025. Bolt completed the dose escalation and is seeking a partner. Cash, cash equivalents, and marketable securities were $48.5 million as of June 30, 2025. Cash on hand is expected to fund multiple milestones and operations through mid-2026.
Second Quarter 2025 Financial Results
Collaboration Revenue – Total collaboration revenue was $1.8 million for the quarter ended June 30, 2025, compared to $1.3 million for the same quarter in 2024. Revenue in the comparative periods was generated from services performed under the R&D collaborations as we fulfill our performance obligations. Research and Development (R&D) Expenses – R&D expenses were $7.5 million for the quarter ended June 30, 2025, compared to $15.4 million for the same quarter in 2024. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses, a decrease in clinical expenses primarily related to the discontinued development of trastuzumab imbotolimod, formerly known as BDC-1001 in May 2024. General and Administrative (G&A) Expenses – G&A expenses were $3.5 million for the quarter ended June 30, 2025, compared to $4.9 million for the same quarter in 2024. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring. Restructuring Charges – Restructuring charges were zero for the quarter ended June 30, 2025, compared to $3.6 million for the same quarter in 2024, consisting of $2.9 million of one-time termination benefits such as severance costs and related benefits and $0.7 million of non-cash stock-based compensation expense as a result of the restructuring plan. Loss from Operations – Loss from operations was $9.2 million for the quarter ended June 30, 2025, compared to $22.6 million for the same quarter in 2024.
Other Developments
Reverse Stock Split
On June 6, 2025, we effected a one-for-twenty (1:20) reverse stock split of its outstanding common stock, effective as of June 6, 2025 (the “Reverse Stock Split”). As a result of the Reverse Stock Split, every 20 shares of the Company’s issued and outstanding common stock automatically converted into one issued and outstanding share of common stock, without any change in par value per share. In part, due to the Reverse Stock Split, on June 24, 2025, Nasdaq notified the Company that it had regained compliance with Nasdaq’s minimum bid price requirement.
About the Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) PlatformBolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc. Bolt Biotherapeutics is a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer. Bolt Biotherapeutics’ pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development. The Company’s pipeline includes BDC-4182, a next-generation Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) clinical candidate targeting claudin 18.2. BDC-4182 is currently in a Phase 1 dose escalation trial that includes patients with gastric and gastroesophageal cancer. The Company has strategic collaborations with Genmab and Toray built around the Company’s Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) platform technology and its expertise in myeloid biology. The Company is seeking to partner its Dectin-2 agonist, BDC-3042, that recently completed a first-in-human Phase 1 dose escalation trial. For more information, please visit https://www.boltbio.com/.
Forward-Looking StatementsThis press release contains forward-looking statements about us and our industry that involve substantial risks and uncertainties and are based on our beliefs and assumptions and on information currently available to us. All statements other than statements of historical facts contained in this press release, including statements regarding our ability to partner BDC-3042, the advancement and success of our BDC-4182 clinical trials, the anti-tumor potency, safety and tolerability, and characteristics of our product candidates, the initiation of future clinical trials, the potential value of collaborations, and the expected duration of our cash runway, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “on track,” “plan,” “potential,” “predict,” “project,” “should,” “will,” or “would,” or the negative of these words or other similar terms or expressions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our current beliefs, estimates and assumptions only as of the date of this press release and information contained in this press release should not be relied upon as representing our estimates as of any subsequent date. These statements, and related risks, uncertainties, factors and assumptions, include, but are not limited to: the potential product candidates that we develop may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; such product candidates may not be beneficial to patients or become commercialized; and our ability to maintain our current collaborations and establish further collaborations. These risks are not exhaustive. Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Further information on factors that could cause actual results to differ materially from the results anticipated by our forward-looking statements is included in the reports we have filed or will file with the Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. These filings, when available, are available on the investor relations section of our website at investors.boltbio.com and on the SEC’s website at www.sec.gov.
Investor Relations and Media Contact: Matthew DeYoung Argot Partners (212) 600-1902 boltbio@argotpartners.com
临床1期免疫疗法财报AACR会议
100 项与 Trastuzumab Imbotolimod 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| HER2阳性转移性乳腺癌 | 临床2期 | 美国 | 2023-11-30 | |
| HER2阳性转移性乳腺癌 | 临床2期 | 西班牙 | 2023-11-30 | |
| 晚期恶性实体瘤 | 临床2期 | 美国 | 2020-02-24 | |
| 晚期恶性实体瘤 | 临床2期 | 法国 | 2020-02-24 | |
| 晚期恶性实体瘤 | 临床2期 | 韩国 | 2020-02-24 | |
| 晚期恶性实体瘤 | 临床2期 | 西班牙 | 2020-02-24 | |
| HER2阳性乳腺癌 | 临床2期 | 美国 | 2020-02-24 | |
| HER2阳性乳腺癌 | 临床2期 | 法国 | 2020-02-24 | |
| HER2阳性乳腺癌 | 临床2期 | 韩国 | 2020-02-24 | |
| HER2阳性乳腺癌 | 临床2期 | 西班牙 | 2020-02-24 |
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床2期 | 231 | 憲鹽選廠蓋鏇積遞構糧(廠壓網衊構膚積蓋衊夢) = 鹹製鹹遞餘餘夢淵網鑰 範觸廠築襯鹹鏇願鑰鏇 (願鹹鑰壓範範鏇壓醖憲 ) 更多 | 积极 | 2023-11-02 | |||
憲鹽選廠蓋鏇積遞構糧(廠壓網衊構膚積蓋衊夢) = 淵鏇衊築襯鏇餘網襯憲 範觸廠築襯鹹鏇願鑰鏇 (願鹹鑰壓範範鏇壓醖憲 ) 更多 | |||||||
临床1/2期 | 实体瘤 HER2 Expression | 131 | 壓鏇積積繭選鏇製鑰膚(鹹壓壓淵觸餘鹽襯鬱餘) = 鬱願鹹遞餘製艱餘膚築 鑰範鏇糧構淵築齋網襯 (顧遞選淵鏇窪顧願窪糧 ) 更多 | 积极 | 2023-10-23 | ||
壓鏇積積繭選鏇製鑰膚(鹹壓壓淵觸餘鹽襯鬱餘) = 繭餘觸鹹鹹繭襯鑰鏇觸 鑰範鏇糧構淵築齋網襯 (顧遞選淵鏇窪顧願窪糧 ) 更多 | |||||||
临床1/2期 | HER2阳性实体瘤 HER2 Expressing | 118 | 淵鹽網壓蓋夢膚鹽選鹹(鑰顧淵簾餘範選築壓齋) = A related SAE (Gr4, bronchopulmonary hemorrhage) was seen in 1 pt (mono, 1.1%). 積艱窪構築鬱蓋獵鑰餘 (廠遞窪襯積顧繭齋廠獵 ) 更多 | 积极 | 2023-05-26 | ||
临床1/2期 | 20 | 鹽襯餘蓋積顧夢鬱範憲(餘淵廠醖獵鬱積獵襯醖) = mild to moderate 築壓蓋窪範鹹繭願鬱遞 (築鬱顧膚鏇醖鹽願蓋觸 ) | - | 2021-05-28 |
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