创新放射性偶联药物有望今年获批，新一代ADC迎来多项进展 | Bilingual

编者按：偶联药物通过将与靶蛋白结合的配体与功能性载荷连接，实现向特定组织或细胞精准递送载荷的效果。近年来，这一领域快速发展，2025年，共有4款创新抗体偶联药物（ADC）获得监管机构批准上市。ADC之外，放射性偶联药物（RDC）、多肽偶联药物（PDC）等新兴偶联模式也不断涌现。本文将盘点2026年第一季度偶联领域的重要进展，并介绍药明康德一体化CRDMO平台赋能抗体偶联药物开发的能力。

两款疗法获FDA优先审评资格，ADC领域创新不断

在2026年第一季度，由阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo）共同开发的两款ADC的补充生物制品许可申请（sBLA）获得美国FDA授予的优先审评资格。其中，Trop2靶向抗体偶联药物Datroway（datopotamab deruxtecan）旨在用于治疗不可切除或转移性三阴性乳腺癌（TNBC）成人患者，这些患者不适合接受PD-1/PD-L1抑制剂治疗。HER2靶向ADC Enhertu（trastuzumab deruxtecan）旨在作为手术之后的辅助疗法，用于治疗在接受新辅助治疗之后，乳房和/或淋巴结仍存在残留侵袭性疾病的HER2阳性早期乳腺癌患者。

此外，礼来（Eli Lilly and Company）开发的叶酸受体α（FRα）靶向ADC sofetabart mipitecan获得FDA授予，用于治疗既往接受过贝伐珠单抗和ADC疗法mirvetuximab soravtansine的铂耐药性上皮性卵巢癌、输卵管癌或原发性腹膜癌成年患者。

百利天恒与百时美施贵宝（Bristol Myers Squibb）联合开发的靶向EGFR和HER3的潜在“first-in-class”双特异性ADC izalontamab brengitecan（iza-bren），在既往接受过紫杉烷类药物治疗后疾病出现进展的三阴性乳腺癌患者中进行的3期临床试验获得积极顶线结果。期中分析结果显示，iza-bren达到了无进展生存期（PFS）和总生存期（OS）的双重主要终点。

PDS Biotechnology公布了其在研白细胞介素-12（IL-12）肿瘤靶向免疫细胞因子PDS01ADC在一项2期临床试验中的研究结果。PDS01ADC将能够与肿瘤内坏死DNA结合的抗体与IL-12偶联。该抗体能够特异性靶向并将IL-12递送至肿瘤内部微环境，从而抑制肿瘤抵御T细胞攻击的能力。同时，IL-12还可促进T细胞向肿瘤浸润并激活T细胞。研究显示，在晚期去势抵抗性前列腺癌患者中，接受PDS01ADC与多西他赛联合治疗的患者的中位无进展生存期为9.6个月。此外，还观察到具有潜力的前列腺特异性抗原（PSA）中位下降幅度为40%，在16名患者中，有6名患者PSA下降超过50%。

在这些临床进展之外，多家开发新一代ADC的新锐公司完成融资或者达成研发合作。这些公司致力于通过不同策略，进一步改进ADC的安全性、有效性和肿瘤选择性。例如，InduPro公司与礼来公司达成战略研发合作，基于其专有平台开发双特异性或三特异性ADC或T细胞衔接器。InduPro的技术平台能够发现在肿瘤细胞表面与肿瘤相关抗原共同表达的肿瘤相关邻近抗原（TAPA）。利用这一技术可以发现具有肿瘤特异性的创新靶点蛋白对，用于设计双特异性ADC或多特异性T细胞衔接器，提高疗法的安全性、效力和肿瘤选择性。

今年完成1300万美元种子轮融资的Fortitude Biomedicines专注于开发携带创新载荷的ADC。该公司的GLUE-DAC平台将抗体与其独有的分子胶载荷偶联，整合ADC的精准靶向能力与分子胶的靶向蛋白降解能力，具有克服耐药机制，解锁创新靶点，以及扩展ADC治疗窗口的潜力。

放射性偶联药物：创新疗法有望今年获批

ITM Isotope Technologies公布了在研放射性偶联药物（RDC）177Lu-edotreotide在3期临床试验COMPETE中的亚组分析结果。在生长抑素受体（SSTR）阳性的胰腺神经内分泌瘤患者（P-NETs）中，177Lu-edotreotide治疗组的中位PFS为24.5个月，活性对照组为14.7个月。177Lu-edotreotide治疗组的客观缓解率为33.3%，活性对照组为3.6%。FDA已经接受177Lu-edotreotide用于治疗胃肠胰神经内分泌肿瘤的新药申请，预计在今年8月28日之前完成审评。

ITM公司之外，Aktis Oncology公司今年通过IPO募集约3.65亿美元，用于进一步推进其放射性偶联药物研发。公司拟将募集资金用于支持核心候选药物AKY-1189（以锕-225为放射同位素）的1b期临床研究，该药物主要针对表达nectin-4的肿瘤患者。

Starget Pharma公司完成1800万美元的A轮融资，加速基于其AI驱动药物发现平台设计的多肽放射性偶联药物的开发。

Curium Group、PeptiDream和PDRadiopharma公司共同宣布，在研疗法177Lu-PSMA-I&T在日本进行的注册性2期临床试验已经完成首例患者给药。177Lu-PSMA-I&T是一款靶向前列腺特异性膜蛋白（PSMA）的多肽放射性偶联药物，用于治疗PSMA阳性转移性去势抵抗性前列腺癌患者。

一体化平台助力创新抗体偶联药物开发

在抗体偶联药物持续迭代的过程中，开发具有更高效力和差异化作用机制的创新载荷已成为推动下一代ADC突破的重要方向。然而，创新载荷往往具有高活性、复杂代谢路径以及独特体内行为，对药物代谢与药代动力学（DMPK）研究提出了更高要求。依托完善的DMPK研究体系与丰富的ADC研究经验，药明康德DMPK可在早期阶段开展针对创新载荷开发的一系列关键体外与体内研究，以全面解析载荷的ADME特征并降低后续开发风险。

例如，在体外研究方面，可开展低浓度条件下的血浆蛋白结合（PPB）评估、代谢稳定性与代谢物鉴定、药物代谢酶表型研究以及转运体相关研究，从而系统解析载荷在体内的代谢途径、潜在药物相互作用风险及组织分布机制。在体内研究方面，通过放射性标记技术结合定量全身放射自显影（QWBA）等方法，可深入研究载荷的组织分布、排泄路径及质量平衡特征，并评估其在体内的清除能力。此外，针对ADC疗效主要由载荷在肿瘤组织中的暴露驱动的特点，药明康德还可开展肿瘤组织药代与PK/PD研究，系统评估肿瘤内载荷暴露与抗肿瘤活性之间的关系。

通过整合多维度生物分析技术与体内外研究体系，药明康德DMPK团队能够为创新ADC载荷的筛选、结构优化及安全性评价提供关键数据支持，加速具有新机制载荷的开发与转化，并持续赋能下一代ADC药物的创新研发。

Innovative Radiopharmaceutical Conjugates May Gain Approval This Year; Next-Generation ADCs See Multiple Advances

Conjugated therapeutics achieve targeted delivery of functional payloads to specific tissues or cells by linking ligands that bind target proteins with therapeutic cargos. In recent years, this field has advanced rapidly. In 2025, four innovative antibody-drug conjugates (ADCs) received regulatory approval. Beyond ADCs, emerging conjugate modalities such as radiopharmaceutical drug conjugates (RDCs), peptide-drug conjugates (PDCs), and oligonucleotide conjugates have also continued to emerge. This article reviews key developments in the conjugate therapeutics field in the first quarter of 2026 and introduces how WuXi AppTec’s integrated CRDMO platform enables the development of antibody-drug conjugates.

Two therapies receive FDA Priority Review as ADC innovation continues

In the first quarter of 2026,supplemental biologics license applications (sBLAs) for two ADCs jointly developed by AstraZeneca and Daiichi Sankyo were granted Priority Review by the U.S. Food and Drug Administration (FDA).

Among them, the TROP2-targeting ADC Datroway (datopotamab deruxtecan) is intended for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not eligible to receive PD-1/PD-L1 inhibitor therapy. The HER2-targeted ADC Enhertu (trastuzumab deruxtecan) is intended as an adjuvant therapy after surgery for patients with HER2-positive early breast cancer who have residual invasive disease in the breast and/or lymph nodes following neoadjuvant treatment.

In addition,the folate receptor-alpha (FRα)-targeting ADC sofetabart mipitecan developed by Eli Lilly and Company received Breakthrough Therapy Designation from the FDAfor the treatment of adult patients with platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have previously received bevacizumab and the ADC mirvetuximab soravtansine.

The potential first-in-class bispecific ADC izalontamab brengitecan (iza-bren), targeting EGFR and HER3 and jointly developed by SystImmune and Bristol Myers Squibb, achieved positive topline results in a Phase 3 clinical trial in patients with triple-negative breast cancer whose disease progressed after prior taxane therapy. An interim analysis showed that iza-bren met its dual primary endpoints of progression-free survival (PFS) and overall survival (OS).

PDS Biotechnology Corporation announced results from a Phase 2 clinical study of its investigational Interleukin-12 (IL-12) tumor-targeted immunocytokine PDS01ADC.PDS01ADC conjugates IL-12 with an antibody capable of binding to necrotic DNA within tumors. This antibody can specifically target and deliver IL-12 into the inner tumor microenvironment, thereby suppressing the tumor’s ability to protect itself from T-cell attack.At the same time, IL-12 also promotes T-cell infiltration into the tumor and activates T cells.

The study showed that in patients with advanced castration-resistant prostate cancer, the median progression-free survival for patients receiving the combination of PDS01ADC and docetaxel was 9.6 months. In addition, a promising median decline in prostate-specific antigen (PSA) of 40% was observed, with 6 of 16 patients achieving a PSA reduction of more than 50%.

Beyond these clinical advances, several emerging companies focused on developing next-generation ADCs completed financing rounds or established R&D collaborations. These companies aim to further improve the safety, efficacy, and tumor selectivity of ADCs through various strategies. For example, InduPro entered into a strategic research collaboration with Eli Lilly to develop bispecific or trispecific ADCs or T-cell engagers based on its proprietary platform. InduPro’s technology platform identifies tumor-associated proximity antigens (TAPAs) that are co-expressed with tumor-associated antigens on tumor cell surfaces. This approach enables the discovery of tumor-specific target protein pairs for the design of bispecific ADCs or multispecific T-cell engagers, improving the safety, potency, and tumor selectivity of therapies.

Fortitude Biomedicines, which recently completed a $13 million seed financing round, is focused on developing ADCs carrying novel payloads. Its GLUE-DAC platform conjugates antibodies with proprietary molecular-glue payloads, integrating the precise targeting capability of ADCs with the targeted protein degradation capability of molecular glues. This approach has the potential to overcome resistance mechanisms, unlock novel targets, and expand the therapeutic window of ADCs.

Radiopharmaceutical drug conjugates: innovative therapies may gain approval this year

ITM Isotope Technologies Munich reported subgroup analysis results from the Phase 3 COMPETE trial of the investigational radiopharmaceutical drug conjugate (RDC) 177Lu-edotreotide. In patients with somatostatin receptor (SSTR)-positive pancreatic neuroendocrine tumors (P-NETs), the median PFS was 24.5 months in the 177Lu-edotreotide treatment group compared with 14.7 months in the active control group. The objective response rate was 33.3% in the treatment group versus 3.6% in the active control group.The FDA has accepted the new drug application for 177Lu-edotreotide for the treatment of gastroenteropancreatic neuroendocrine tumors, with a review decision expected by August 28 this year.

In addition to ITM, Aktis Oncology raised approximately $365 million through an IPO this year to further advance its radiopharmaceutical drug development programs. The company plans to use the proceeds to support the Phase 1b clinical study of its lead candidate AKY-1189, which uses actinium-225 as the radioisotope and targets tumors expressing nectin-4.

Starget Pharma completed an $18 million Series A financing to accelerate the development of peptide radiopharmaceutical drug conjugates designed using its AI-driven drug discovery platform.

Curium Group, PeptiDream, and PDRadiopharma jointly announced that the first patient has been dosed in a registrational Phase 2 clinical trial in Japan evaluating the investigational therapy 177Lu-PSMA-I&T. This peptide radiopharmaceutical drug conjugate targets prostate-specific membrane antigen (PSMA) and is intended for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer.

Integrated Platform Enables the Development of Innovative ADCs

As ADCs continue to evolve, the development of novel payloads with greater potency and differentiated mechanisms of action has become a key driver for next-generation ADC innovation. However, these innovative payloads often exhibit high biological activity, complex metabolic pathways, and unique in vivo behaviors, placing greater demands on drug metabolism and pharmacokinetics (DMPK) evaluation. Leveraging its comprehensive DMPK research platform and extensive experience in ADC development, WuXi AppTec provides a range of critical in vitro and in vivo studies to support the early development of novel ADC payloads and to systematically characterize their ADME properties while mitigating downstream development risks.

For in vitro studies, WuXi AppTec DMPK can conduct plasma protein binding (PPB) assays at low payload concentrations that better reflect in vivo exposure levels, along with metabolic stability assessment, metabolite identification, drug-metabolizing enzyme phenotyping, and transporter interaction studies. These evaluations help elucidate payload metabolic pathways, potential drug–drug interaction risks, and mechanisms governing tissue distribution. For in vivo studies, radiolabeled payload approaches combined with techniques such as quantitative whole-body autoradiography (QWBA) can be applied to investigate tissue distribution, excretion pathways, and mass balance, providing a comprehensive understanding of payload disposition and clearance. In addition, given that ADC efficacy is largely driven by payload exposure within tumor tissues, WuXi AppTec can perform tumor pharmacokinetics and PK/PD studies in relevant animal models to evaluate the relationship between intratumoral payload exposure and antitumor activity.

By integrating multidimensional bioanalytical capabilities with robust in vitro and in vivo DMPK study systems, WuXi AppTec enables partners to generate critical insights for payload screening, structural optimization, and safety evaluation, ultimately accelerating the development and translation of next-generation ADCs with innovative payload mechanisms.

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