主要目的：评估AST-3424静脉给药的安全性和耐受性；评估AST-3424及其代谢产物的药代动力学特征；评估ALL受试者接受AST-3424单药治疗的给药方案；次要目的：初步评估AST-3424单药治疗复发或难治性ALL的血液学缓解情况，判定标准为ORR= CR+PR（其中CR包括CR和CRi）；评估患者的总生存期（OS）；评估患者的无进展生存期（PFS）（PFS定义为从首次用药开始到疾病进展或任何原因导致的死亡的时间）；评估CR/CRi患者的微小残存病变（MRD）的阴性率（MRD阴性定义为流式细胞术检测< 0.01%）；评估CR/CRi患者微小残存病变（MRD）首次达到阴性的时间；评估CR/CRi患者MRD阴性持续的时间（从达到CR/CRi后MRD首次评估阴性到MRD转为阳性或CR/CRi后复发的最早日期时间）；探讨患者外周血和骨髓中经PCR-荧光探针法确定的AKR1C3酶的表达与疗效之间的关系。探索性目的：探索DNA损伤修复相关基因突变的表达。

开始日期2021-04-06

申办/合作机构

深圳艾欣达伟医药科技有限公司

NCT04315324

/ Recruiting临床1/2期IIT

A Phase I/II Study of AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) In Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)/T-Cell Lymphoblastic Lymphoma (T-LBL)

This phase I/II trial studies the safety, side effects and best dose of OBI-3424 and how well it works in treating patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.

开始日期2021-02-08

申办/合作机构

National Cancer Institute

NCT06239155

/ Active, not recruiting临床1/2期

Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of AST-3424 in Treatment of Patients With Advanced Solid Tumors and Its Correlation With AKR1C3 Enzyme Expression

An open-label, Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of AST-3424 administered as a single agent

开始日期2019-09-03

申办/合作机构

深圳艾欣达伟医药科技有限公司

100 项与 AST-3424 相关的临床结果

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100 项与 AST-3424 相关的转化医学

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100 项与 AST-3424 相关的专利（医药）

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项与 AST-3424 相关的文献（医药）

2025-01-15·INTERNATIONAL JOURNAL OF CANCER

Enhanced pharmacological activities of AKR1C3‐activated prodrug AST‐3424 in cancer cells with defective DNA repair

Article

作者: Duan, Jianxin ; Meng, Fanying ; Liu, Xing ; Jung, Don ; Li, Anrong ; Qi, Tianyang ; Wang, Yizhi ; Cai, Xiaohong ; Lu, Zhaoqiang ; Yu, Jibing

Abstract:

AST‐3424 is a novel and highly tumor‐selective prodrug. AST‐3424 is activated by AKR1C3 to release a toxic bis‐alkylating moiety, AST 2660. In this study, we have investigated the essential role of DNA repair in AST‐3424 mediated pharmacological activities in vitro and in vivo. We show here that AST‐3424 is effective as a single therapeutic agent against cancer cells to induce cytotoxicity, DNA damage, apoptosis and cell cycle arrest at G2 phase in a dose‐ and AKR1C3‐dependent manner in both p53‐proficient H460 (RRID:CVCL_0459) and p53‐deficient HT‐29 cells (RRID:CVCL_0320). The combination of abrogators of G2 checkpoint with AST‐3424 was only synergistic in HT‐29 but not in H460 cells. The enhanced activity of AST‐3424 in HT‐29 cells was due to impaired DNA repair ability via the attenuation of cell cycle G2 arrest and reduced RAD51 expression. Furthermore, we utilized a BRCA2 deficient cell line and two PDX models with BRCA deleterious mutations to study the increased activity of AST‐3424. The results showed that AST‐3424 exhibited enhanced in vitro cytotoxicity and superior and durable in vivo anti‐tumor effects in cells deficient of DNA repair protein BRCA2. In summary, we report here that when DNA repair capacity is reduced, the in vitro and in vivo activity of AST‐3424 can be further enhanced, thus providing supporting evidence for the further evaluation of AST‐3424 in the clinic.

2023-08-01·British journal of cancer

Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors.

Article

作者: Hsu, Pei ; Pearce, Tillman E. ; Wesolowski, Robert ; Verschraegen, Claire F. ; Shia, Chi-Sheng ; Tsimberidou, Apostolia Maria

BACKGROUND:

Report of a Phase 1 dose-escalation study of OBI-3424 monotherapy in patients with advanced solid tumors (NCT03592264).

METHODS:

A classic 3 + 3 design was used to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of OBI-3424 administered intravenously, as a single agent, at doses of 1, 2, 4, 6, 8, or 12 mg/m² (days 1 and 8 of a 21-day cycle, Schedule A) or 8, 10, 12, or 14 mg/m² (day 1 of a 21-day cycle, Schedule B).

RESULTS:

Dose-limiting hematologic toxicities at 12 mg/m² in Schedule A led to dose and schedule modifications (Schedule B). In Schedule B, maximum tolerated dose was not reached at the maximum dose tested (14 mg/m²). Grade ≥3 anemia was noted in 3/6 patients treated at 14 mg/m²; the RP2D was 12 mg/m² (Schedule B). Grade ≥3 treatment-emergent adverse events were experienced by 19/39 (49%) and included anemia (41%) and thrombocytopenia (26%); three patients experienced serious treatment-emergent adverse events (grade ≥3 anemia and thrombocytopenia). One patient had a partial response and 21/33 (64%) had stable disease.

CONCLUSIONS:

The RP2D is 12 mg/m² once every 3 weeks. OBI-3424 was well tolerated; dose-dependent, noncumulative thrombocytopenia and anemia were dose-limiting.

2023-06-01·Journal of pharmacological sciences

A novel AKR1C3 specific prodrug AST-3424 and its combination therapy in hepatocellular carcinoma

Article

作者: Qin, Shukui ; Zheng, Xia ; Zhang, Yu ; Xun, Chen

OBJECTIVE:

AST-3424 is a novel specific aldo-keto reductase 1C3 (AKR1C3) prodrug that releases a DNA alkylating reagent upon reduction by AKR1C3. This study aimed to evaluate the efficacy and safety of AST-3424 in patient-derived tumor xenograft (PDTX) model and orthotopic model against hepatocellular carcinoma (HCC).

MATERIALS AND METHOD:

PDTX models derived from three HCC patients and orthotopic mice models using HepG2 cells were developed. The mice were treated with AST-3424 alone or combined with other drugs (oxaliplatin, apatinib, sorafenib and elemene in PDTX models, oxaliplatin and 5- fluorouracil in orthotopic models). The tumor volume and weight, as well as the mice weight were assessed. The liver tumor and transplanted tumor were removed for histological, immunohistochemical and Western blot detection in orthotopic model experiments.

RESULTS:

AST-3424 could inhibit tumor growth in HCC PDTX models and orthotopic models, with no difference in safety compared with other marketed drugs, and the drug combination did not increase toxicity. The inhibitory effect of combination treatment was more obvious than which used alone. The reduction of AKR1C3 expression was negatively correlated with AST-3424 dose.

CONCLUSION:

AST-3424 had a promising effect against HCC in PDTX model and orthotopic model with good safety. It could promote the sensitivity of other drugs without increasing toxicity. Clinical trials are warranted to further certify its antitumor effect and safety.

项与 AST-3424 相关的新闻（医药）

2025-06-06

·PipelineReview

OBI Pharma Enters ADC Collaboration with TegMine Therapeutics utilizing GlycOBI® and TegMiner™ Enabling Technologies

TAIPEI, Taiwan I June 06, 2025 I OBI Pharma, Inc. (OBI), a clinical-stage global oncology company specialized in the development of novel cancer therapies such as antibody-drug conjugates (ADCs) (4174. TWO), and TegMine Therapeutics, Inc. (TegMine), a US Biopharma specialized in developing best-in-class antibodies targeting cancer glycans and glycoproteins, have entered into an ADC-related Master Services Agreement (MSA). Under the terms of the MSA, OBI grants TegMine rights to utilize OBI’s GlycOBI ® ADC enabling technologies, powered by EndoSymeOBI ® and HYPrOBI ® , to identify ADC therapeutics candidates for potential clinical development. If an ADC product candidate(s) is ensued, OBI and TegMine would enter into a formal licensing agreement. “This strategic collaboration leverages the synergistic strengths of both organizations,” noted Heidi Wang, Ph.D., OBI Pharma’s Chief Executive Officer. “In addition to advancing OBI’s compelling ADC products, we are focused on leveraging the innovative ADC enabling technologies, like GlycOBI ® , for strategic partnership. We look forward to working closely with TegMine to generate novel ADC candidates to treat patients with unmet medical need.” “This collaboration reflects the exciting convergence of two innovative platforms,” said Jeff Bernstein, Ph.D., Chief Executive Officer of TegMine Therapeutics. “OBI’s ADC technology is an ideal complement to our efforts to target cancer-specific glycans. Together, we have the opportunity to develop ADCs with unprecedented tumor specificity and therapeutic impact.” About GlycOBI ® OBI has developed a unique glycan-based ADC technology (GlycOBI ® ), which is in a ‘Plug and Play’ format and compatible with any antibodies, linkers, and payloads in various Drug antibody ratio (DAR). Utilizing OBI’s proprietary enzymatic technology (EndoSymeOBI ® ) and linker technology (HYPrOBI TM ), GlycOBI ® generates site-specific homogenous ADCs with an efficient and scalable process under GMP conditions. The conjugation process of GlycOBI ® avoids disrupting the antibody structure and ensures the ADC has similar biophysical characteristics to the native antibody. Furthermore, OBI’s linker technology has improved conjugation efficiency of the payload, reduced aggregation propensity, which provides advantages on manufacturing ADC products. GlycOBI ® has overcome the limitations of traditional ADCs and achieved better antitumor activity and stability in various in vivo animal studies. About OBI Pharma OBI is a clinical stage global oncology company that is headquartered in Taiwan and established in 2002. Its mission, together with its wholly owned subsidiary OBI Pharma USA, Inc., is to develop novel cancer therapeutic agents for patients with high unmet medical needs. OBI’s primary focus is the development of novel ADCs, including the first-generation cysteine-based TROP2 ADC, OBI-992. Using the company’s proprietary ADC enabling technology, GlycOBI ® , powered by EndoSymeOBI ® and HYPrOBI™; OBI has created its second generation novel ADC pipeline, including monospecific: OBI-902 (TROP2), OBI-904 (Nectin-4), Trastuzumab-ADC (HER2), bi-specifics and dual payload ADCs. To broaden the applicability of the linker technology, HYPrOBI™, OBI further developed a next-generation ThiOBI ® platform to enable cysteine-based conjugation. Additionally, OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 (AKR1C3) enzyme that is highly expressed in tumors. Additional information can be found at www.obipharma.com . GlycOBI ® , EndoSymeOBI ® , ThiOBI ® are registered trademarks of OBI. HYPrOBI™ is a trademark under registration. About TegMine Therapeutics TegMine Therapeutics is a privately held biotechnology company based in San Francisco, California, USA focused on developing next-generation antibody-based therapies that target cancer-associated glycans and glycoproteins. Founded in 2017, TegMine is pioneering a highly selective approach to cancer treatment by exploiting tumor-specific carbohydrate antigens that are largely absent from healthy tissues. These novel targets are being developed into a diverse pipeline of antibody-drug conjugates (ADCs), bispecific antibodies, and cell therapies. TegMine’s proprietary TegMiner™ platform enables the discovery and development of therapeutic antibodies against previously inaccessible glycan epitopes, opening new frontiers in oncology for patients with high unmet medical needs. Additional information can be found at www.tegminetx.com SOURCE: OBI Pharma

引进/卖出抗体药物偶联物

2025-05-01

·PipelineReview

OBI Pharma Announces U.S. FDA Clearance of IND Application for a Phase 1/2 Study of OBI-902, a Trop-2 Targeting ADC

OBI-902 is the first ADC utilizing OBI’s proprietary GlycOBI® ADC enabling technology TAIPEI, Taiwan I May 01, 2025 I OBI Pharma, Inc. (“OBI”), a clinical stage oncology company（4174.TWO), today announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug （IND） application for OBI-902, to conduct a Phase 1/2 study. OBI plans to enroll patients with advanced solid tumors. This IND clearance represents a significant milestone for OBI-902, bringing forward a potentially best-in-class Trop-2 -targeted cancer therapy for patients with high unmet medical needs. OBI’s Chief Executive Officer, Heidi Wang, Ph.D. noted, “The impending OBI-902-001 clinical trial intends to evaluate the safety, pharmacokinetics, and preliminary efficacy of OBI-902 in patients with advanced solid tumors. We are very excited to begin dosing patients in our Phase 1/2 clinical study of OBI-902 later this year.” OBI-902 is a novel Trop-2 ADC utilizing OBI’s proprietary GlycOBI ® ADC enabling technology. At the 2025 American Association for Cancer Research (AACR) meeting, OBI presented data demonstrating enhanced linker-payload stability, favorable pharmacokinetics with superior and durable antitumor activities of OBI-902 in numerous in-vitro and animal studies compared to other Trop-2 ADCs 1 , 2 . The Phase 1/2 clinical study is planned to begin enrolling patients in 2H 2025. 1 OBI-902, a novel TROP-2 targeted antibody-drug conjugate via GlycOBI ® platform, has favorable pharmacokinetics and sustained antitumor activities in challenging solid tumors. AACR Annual Meeting 2025 Abstracts online https://www.abstractsonline.com/pp8/#!/20273/presentation/1103 2 Harnessing the GlycOBI® enabling technologies: next-generation site-specific glycan ADCs with versatile DAR to enhance therapeutic index. AACR Annual Meeting 2025 Abstracts online https://www.abstractsonline.com/pp8/#!/20273/presentation/3007 About OBI-902 OBI-902 is a Trop-2-targeted antibody-drug conjugate （ADC） that carries a potent topoisomerase I inhibitor payload to kill tumor cells and with a drug-antibody ratio （DAR） of 4. Trop-2 is highly expressed in a variety of solid tumors such as breast, ovarian, gastric, and many other cancer types, rendering it an ideal target for cancer therapy. OBI-902 is a novel site-specific glycan-conjugated ADC using OBI’s proprietary GlycOBI ® platform, which provides improved stability and enhanced hydrophilicity. OBI-902 demonstrated remarkable antitumor efficacy, improved pharmacokinetic characteristics, and a favorable safety profile in various animal models. IND of OBI-902 was submitted to the U.S. FDA on March 31, 2025, and the IND was cleared on April 30, 2025. OBI has licensed Trop-2 targeting antibody from Biosion, Inc. ( www.biosion.com ) since December 2021, holding exclusive rights worldwide except in China. OBI holds worldwide commercial rights to OBI-902, to the exception of the rights pertaining to the antibody in China. About GlycOBI ® OBI has developed a unique glycan-based ADC technology (GlycOBI ® ), which is in a ‘Plug and Play’ format and compatible with any antibodies, linkers, and payloads in various DAR. Utilizing OBI’s proprietary enzymatic technology（EndoSymeOBI®） and linker technology（HYPrOBI™), GlycOBI ® generates site-specific homogenous ADCs with an efficient and scalable process under GMP conditions. The conjugation process of GlycOBI ® avoids disrupting the antibody structure and ensures the ADC has similar biophysical characteristics to the native antibody. Furthermore, OBI’s linker technology has improved conjugation efficiency of the payload, reduced aggregation propensity, which provides advantages on manufacturing ADC products. GlycOBI ® has overcome the limitations of traditional ADCs and achieved better antitumor activity and stability in various in vivo animal studies. About OBI Pharma OBI is a clinical stage global oncology company that is headquartered in Taiwan and established in 2002. Its mission, together with its wholly owned subsidiary OBI Pharma USA, Inc., is to develop novel cancer therapeutic agents for patients with high unmet medical needs. OBI’s primary focus is the development of novel ADCs, including the first-generation cysteine-based TROP-2 ADC, OBI-992. Using the company’s proprietary ADC enabling technology, GlycOBI ® , powered by EndoSymeOBI ® and HYPrOBI™; OBI has created its second generation novel ADC pipeline, including monospecific: OBI-902 （Trop-2), OBI-904 (Nectin-4), Trastuzumab-ADC (HER2), bi-specifics and dual payload ADCs. To broaden the applicability of the linker technology, HYPrOBI™, OBI further developed a next-generation ThiOBI ® platform to enable irreversible cysteine-based conjugation. Additionally, OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 （AKR1C3） enzyme that is highly expressed in tumors. Additional information can be found at www.obipharma.com . SOURCE: OBI Pharma

临床申请抗体药物偶联物引进/卖出AACR会议

2025-03-01

·药时代

小分子偶联药物（SMDC）：结构机制、临床优势、机遇与挑战

引言小分子偶联药物（SMDC）是一种新型靶向治疗药物，始于对传统化疗及抗体偶联药物（ADC）的优化探索，旨在通过精准递送提高疗效并降低系统毒性，在靶向性、安全性与成本等方面具备优势。目前全球尚无SMDC获批上市，约10款候选药物处于临床阶段，适应症集中于实体瘤，为耐药性肿瘤提供新策略，并有望拓展至其他疾病领域。 SMDC结合小分子药物的灵活性与偶联技术的增效潜力，推动肿瘤治疗向高效低毒方向演进，成为偶联药物赛道中具潜力的分支。 SMDC的作用机制小分子偶联药物（SMDC）由三部分组成：小分子靶向配体、连接子和载荷药物。其作用机制与ADC药物基本一致，是通过小分子配体特异性识别肿瘤细胞表面过表达的受体或转运蛋白，经内吞作用将细胞毒性药物递送至靶细胞内，实现精准杀伤[1]。图：SMDC药物结构来源：公开资料，药智咨询整理小分子靶向配体 SMDC的靶向配体为小分子化合物，在SMDC中发挥的作用类似ADC抗体的作用。SMDC配体的选择需要考虑到结合亲和力、选择性和化合物大小等问题，因此主要来自天然来源配体的衍生物，如叶酸、前列腺特异性膜抗原（PSMA）抑制剂或整合素拮抗剂等，相比ADC配体选择面较小，是目前SMDC发展的主要限制。目前靶向叶酸受体的SMDC药物研究最多，叶酸受体在多种实体瘤（如卵巢癌、肺癌）中高表达，以叶酸为配体的SMDC可通过受体介导的内吞作用高效富集于肿瘤组织。连接子 SMDC的连接子与ADC类似，是连接小分子靶向配体与载荷药物的纽带，其设计决定SMDC的稳定性和药物释放效率。目前在研的SMDC药物主要采用酶敏感型连接子和基于二硫键的连接子两种技术路线。载荷药物目前在研的SMDC的载荷药物以细胞毒性化疗药物为主，如喜树碱衍生物（SN-38）、微管抑制剂（MMAE）及拓扑异构酶抑制剂等。此外，部分研究尝试将放射性核素（如锕-225）或免疫调节剂作为载荷，以扩展其治疗范围。 SMDC的临床优势首先，SMDC的临床优势主要基于其小分子特性。小分子靶向配体使SMDC容易渗透并能更均匀地扩散到肿瘤组织内部，使其有更高的肿瘤穿透性；并且小分子不会在肿瘤及其他正常细胞中聚集，少数脱靶的药物也会被快速排出体外，从而减少对正常细胞的毒性；同时SMDC理论上不会具有免疫原性，安全性控制更容易实现。此外，相较于抗体药物，SMDC容易控制合成工艺和成本，工业化操作简单。更高的肿瘤穿透性相比ADC（分子量约150kDa）和PDC（分子量约5-10kDa），SMDC的分子量通常低于1kDa，能够通过被动扩散快速穿透实体瘤组织，克服传统大分子药物的递送瓶颈，在实体瘤中能够具有更好的细胞通透性。肾脏代谢与低免疫原性 SMDC主要通过肾脏代谢，半衰期较短，减少了药物在肝脏和骨髓中的蓄积，少数脱靶的药物也会被快速排出体外，减少对正常细胞的毒性，具有更好的体外和体内稳定性。例如叶酸受体SMDC 长春夫利 Vintafolide在临床试验中表现出较低的肝毒性[2]。同时，SMDC理论上不具有免疫原性，使其安全性控制更容易实现。更低的生产成本小分子的化学合成工艺成熟，生产成本显著低于抗体或多肽，更易于规模化生产，成本控制更容易。精准的有效载荷 ADC药物分子的有效载荷与抗体之比通常不能确定，因此细胞内有效载荷也会出现上下浮动；SMDC的小分子靶向配体和有效载荷通常有准确比例。 SMDC全球及中国在研管线分析相比ADC赛道的火热以及PDC、RDC在技术和市场上陆续取得的突破，SMDC的研发尚未能取得令人眼前一亮的成绩。目前国内外尚未有SMDC获批准上市，但约十余款药物进入临床研究阶段，其中进入临床II期研究的约有7款，整体处于临床研发早期。相比其他新型偶联药物来看，RDC已有11款药物获批上市，其中Lutathera在2023年销售额达到6.05亿美元，270余款RDC新药处于临床试验及申请上市阶段；PDC已有两款药物获批，全球进入临床试验阶段的管线约有20条，多条管线进入临床后期。目前SMDC在研管线中的靶点多样性也较低，主要集中在AKR1C3、 KRAS G12D、Tubulin等几个靶点。表全球在研SMDC药物（部分）药品名称靶点适应症最新状态研发单位长春夫利 Vintafolide FOLR,Tubulin 三阴性乳腺癌，非小细胞肺癌，子宫内膜癌，卵巢癌，实体瘤，肺腺癌注册申请 (2014年终止) Endocyte Inc 长春夫利 Vintafolide FOLR,Tubulin 三阴性乳腺癌，非小细胞肺癌，子宫内膜癌，卵巢癌，实体瘤，肺腺癌注册申请 (2014年终止) Endocyte Inc NUV-1511 DDC 实体瘤临床Ⅱ期 (2024-02-12) Nuvation Bio CBP-1019 Topo 实体瘤临床Ⅱ期 (2023-03-29) 同宜医药 AST-001 KRAS 实体瘤，胰腺癌临床Ⅱ期 (2022-04-29) 艾欣达伟 AST-3424 AKR1C3 实体瘤;急性淋巴细胞白血病;癌症;肝细胞癌临床Ⅱ期 (2019-07-15) 艾欣达伟 ELU001 FOLR1 x Top I 肿瘤临床Ⅱ期 (2021-07-14) Elucida Oncology Inc OBI-3424 AKR1C3,DNA T细胞急性淋巴细胞白血病; 临床Ⅱ期 (2018-05-21) Molecular Templates PEN-866 HSP90;Topo I 实体瘤临床Ⅱ期 (2017-07-13) Madrigal Pharmaceuticals Tarveda Therapeutics VIP236 Integrin αVβ3 癌症临床Ⅰ期 (2022-10-18) Vincerx Pharma 拜耳制药 Legutaxel Tubulin 实体瘤;胃癌临床Ⅰ期 (2022-08-10) 亲合力生物 T-1201 PS;Topo I 实体瘤临床Ⅰ期 (2021-04-23) 泰纬生命 PSMA-targeted tubulysin B conjugates FOLH;Tubulin 前列腺癌临床Ⅰ期 (2014-07-21) Endocyte Inc AST-006 - 乳腺癌;卵巢癌临床Ⅰ期艾欣达伟来源：药智数据，药智咨询整理海外布局企业中，虽布局企业相对较少，但几款领域内具有代表意义的产品也值得一讲： Vintafolide（Endocyte）：作为全球临床阶段最靠前产品，早在2014年就进入注册申请阶段，并于2014年获欧洲药品管理局的有条件批准，但最终却因未达到主要终点无进展生存期而宣告失败，Endocyte之后也彻底放弃SMDC领域，转向其他种类偶联药物的研究，大名鼎鼎的Lutathera就是转战成果，2024年全球销售额达7.24亿美元。国内布局企业方面，布局SMDC领域的企业相对海外，则相对更多，竞争也更大，比较有代表意义的有艾欣达伟、同宜医药等。艾欣达伟专注于SMDC创新药研发，目前已有2条SMDC药物管线进入II期临床研究，其中AST-001作为其重点管线，在一项Ⅰ期实体肿瘤的临床研究中，广泛入组的10余类不同瘤种的晚期实体瘤患者，符合靶点要求的患者中疾病控制率达到66.7%，ORR为33.3%。充分展现出AST-001广谱抗肿瘤的特性。安全性方面，大部分治疗相关的不良事件（TRAE）为1-2级，均可控可管理。AST-3424是全球首创的依赖AKR1C3酶活化的SMDC，其II期临床试验结果显示作为后线药物，AST-3424用于治疗晚期肝细胞癌具有较好的有效性，特别是用于曾经接受免疫治疗后进展的HCC受试者，仍然可以延长其生存期。同宜医药同样也拥有多款SMDC药物在研，其中CBP-1008与CBP-1019最被寄予厚望，其中CBP-1019在一项全球多中心、开放标签的I/II期临床试验中，入组的10名晚期/转移性EC患者，研究结果显示，在3.0 mg/kg剂量水平，9名晚期/转移性EC患者中有7名有给药后至少一次肿瘤评估，客观缓解率（ORR）达42.9%，疾病控制率（DCR）为100%。 CBP-1008是一款靶向叶酸受体α（FRα）/瞬时受体电位阳离子通道6 蛋白（TRPV6）的全球双配体SMDC，其在晚期实体瘤患者开展的I期试验包括铂耐药性高级别浆液性卵巢癌 (HGSOC)、透明细胞卵巢癌 (OCCC)、转移性三阴性乳腺癌 (TNBC) 和其他实体肿瘤患者。2024年10月被FDA授予快速通道资格。数据来源：公开数据整理（点击查看大图）而针对上述SMDC系列管线的临床有效性数据而言，除了SMDC领域之内的数据观测外，其实针对SMDC与化疗、小分子靶向抑制剂与ADC等其他技术领域的对比反而更显重要。目前来看，由于SMDC的临床阶段尚处于前期，很多数据还不具备统计意义，但就整体而言，部分产品目前所展示的ORR、DCR数据并不逊色于ADC或新一代PARP抑制剂，甚至因其生产成本、肿瘤穿透性等特点，想象空间反而更大。 SMDC的发展前景 SMDC药物的研发目前处于早期探索阶段，小分子配体的选择是目前SMDC开发中主要难点。 SMDC配体主要来自天然来源配体的衍生物，相比ADC配体选择面较小，合适的受体和配体难以获得，靶点和适应症都比较狭窄。因此，优化现有设计、拓展小分子配体的选择范围，并扩大靶点及适应症的覆盖领域，是SMDC突破发展瓶颈的关键策略。小结 SMDC凭借其小分子特性，在肿瘤穿透性、生产成本和安全性方面展现显著优势，已成为偶联药物领域的重要分支。目前SMDC临床研发面临小分子靶向配体选择面窄的限制，药物研发整体还处于早期探索阶段，相比其他种类的偶联药物研发进程滞后，国内企业已有数条SMDC管线进入II期临床研究，具有成为SMDC领域FIC的潜力。未来可能有更多公司参与SMDC的研发，不断改善现有产品的技术瓶颈，使SMDC有望为实体瘤和难治性癌症提供更精准的治疗方案。参考文献 1.Zhang J, Hu F, Aras O, Chai Y, An F. Small Molecule-Drug Conjugates: Opportunities for the Development of Targeted Anticancer Drugs. ChemMedChem. 2024 Jun 3;19(11):e202300720. doi: 10.1002/cmdc.202300720. Epub 2024 Mar 11. PMID: 38396351. 2.Vergote, I., & Leamon, C. P. (2015). Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors. Therapeutic advances in medical oncology, 7(4), 206–218. 3.评价AST-001治疗恶性肿瘤患者的安全性、耐受性、药代动力学、初步疗效以及疗效与AKR1C3表达相关性的临床研究封面图来源：123rf 查处"政治遗产"？疫苗药企迎来“至暗时刻”！ 2025-02-28 一代传奇K药：大劫降至 2025-02-27 不止有DeepSeek，中国生物制药正在崛起！ 2025-02-26 版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击，查看更多精彩！

抗体药物偶联物多肽偶联药物免疫疗法

100 项与 AST-3424 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16057

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
急性髓性白血病	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
膀胱癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
结直肠癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
子宫内膜癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
食管癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
结外NK-T细胞淋巴瘤	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
肝细胞癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
高危骨髓增生异常综合征	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
非小细胞肺癌	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23
外周T细胞淋巴瘤	临床2期	中国	深圳艾欣达伟医药科技有限公司	2022-06-23

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临床结果

适应症

分期

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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


Pediatric Preclinical In Vivo Testing Consortium (PIVOT) (AACR2025)	临床2期	肝母细胞瘤 AKR1C3	-	OBI-3424	築遞鏇獵簾鏇鹽製築壓(鏇鏇鑰憲網繭鑰網鹹製) = 廠憲夢築艱鹽鏇窪製顧顧艱選選鏇選廠遞選齋 (蓋繭廠簾壓遞艱窪艱鹹 )	积极	2025-04-30
	临床2期	肝母细胞瘤 AKR1C3	-	Vehicle	築遞鏇獵簾鏇鹽製築壓(鏇鏇鑰憲網繭鑰網鹹製) = 鏇顧齋窪廠顧選膚願艱顧艱選選鏇選廠遞選齋 (蓋繭廠簾壓遞艱窪艱鹹 )	积极	2025-04-30
NCT06239155 (ASCO2024)	临床1期	晚期恶性实体瘤 AKR1C3 expression	21	AST-3424 8 mg/m2	壓願餘鹽製襯艱齋顧鏇(積遞廠醖鬱餘夢壓艱憲) = 遞遞憲壓鹹遞選淵構選鹽觸壓齋襯糧壓遞鑰觸 (膚積構鏇網壓艱夢鏇醖 ) 更多	积极	2024-05-24
NCT03592264 (Pubmed)	临床1期	转移性实体瘤	39	OBI-3424	範憲選鏇齋衊繭蓋顧簾(簾鹽糧襯築觸廠壓襯構) = 繭鏇遞憲鬱範餘淵淵蓋鏇顧範艱顧繭蓋願構衊 (鑰衊膚憲遞獵顧壓膚繭 )	-	2023-05-12
NCT03592264 \| NCT04315324 (AACR2022)	临床1/2期	胰腺腺癌 \| HR阳性/HER2低表达实体瘤 \| 难治性 T 急性淋巴细胞白血病	-	OBI-3424	選壓蓋選餘選艱範鬱鑰(淵構鹽糧糧築餘淵繭膚) = 鹹糧膚襯鏇衊簾壓範壓膚蓋簾醖網網觸糧醖醖 (遞醖遞築襯襯艱醖簾顧 )	-	2022-06-15
NCT03592264 \| NCT04315324 (AACR2022)	临床1/2期	胰腺腺癌 \| HR阳性/HER2低表达实体瘤 \| 难治性 T 急性淋巴细胞白血病	-	Pembrolizumab	選壓蓋選餘選艱範鬱鑰(淵構鹽糧糧築餘淵繭膚) = 廠築顧製膚淵構膚廠醖膚蓋簾醖網網觸糧醖醖 (遞醖遞築襯襯艱醖簾顧 )	-	2022-06-15
NCT03592264 (ASCO2022)	临床1期	转移性实体瘤	39	OBI-3424	築衊願繭鹽願網願顧鏇(鏇蓋醖網鑰鏇繭構衊觸) = 鹹築衊膚觸鹽獵淵艱簾製窪網顧製願顧構壓遞 (獵鏇醖顧顧壓獵選觸積 ) 更多	-	2022-06-02