下一代ADC要换打法了？不只是换“弹头”，而是改变整个递送系统 | Bilingual

编者按：2026年第三季度，偶联药物领域迎来多项重要进展。两款靶向B7-H3的抗体偶联药物（ADC）在3期研究中取得积极生存数据，已上市ADC和放射性配体疗法的应用也向更早治疗阶段拓展。与此同时，新型载荷、多靶点识别和条件激活技术不断涌现，多项重磅收购与授权合作反映了行业对这些技术的持续投入。

在这一过程中，递送系统与载荷是决定ADC能否从分子构想走向可开发候选药物的关键因素之一。药明康德研发化学服务部（Research Chemistry Services，RCS）构建了覆盖连接子与载荷合成、分析及纯化的一体化技术平台，为ADC关键小分子组件开发提供系统化支持。依托超过10年的项目经验、580余名专业化学家团队，以及包含1000余种连接子、30多类抗体连接位点和超过30种新型载荷及其类似物的可定制化体系，RCS能够帮助合作伙伴高效推进ADC连接子与载荷开发，加速创新偶联疗法从早期研究迈向可开发阶段。

临床验证：ADC取得积极生存数据，治疗阶段进一步前移

多项后期临床研究和监管审批为ADC领域带来了重要进展。其中，两款靶向B7-H3的ADC在3期研究中均达到总生存期（OS）主要终点，成为9月世界肺癌大会（WCLC）的重要看点。B7-H3是一种在多种肿瘤组织中表达的蛋白，近年来受到ADC研发领域的广泛关注。9月13日公布的ARTEMIS-008和TAISHAN-302研究，均针对复发性小细胞肺癌患者，以拓扑替康作为活性对照药物。

在纳入461例患者的ARTEMIS-008研究中，risvutatug rezetecan（Ris-Rez，HS-20093/GSK5764227）达到OS主要终点。治疗组中位OS为18.5个月，活性对照组为10.3个月，死亡风险比（HR）为0.46（95% CI：0.35～0.62）。研究同时达到无进展生存期（PFS）等关键次要终点。

另一款B7-H3靶向ADC tambotatug pelitecan（Tam-Peli，YL201）在TAISHAN-302研究中也取得积极结果。该研究共纳入451例患者，治疗组中位OS为13.3个月，活性对照组为9.4个月，HR为0.46（95% CI：0.35～0.62），同样达到OS主要终点。

两项随机对照3期研究为B7-H3靶向ADC治疗复发性小细胞肺癌提供了重要临床证据，进一步支持了这一靶点的开发潜力。

除了新靶点ADC获得积极临床数据，已经上市的ADC也在向更早治疗阶段拓展。9月14日，阿斯利康（AstraZeneca）与第一三共（Daiichi Sankyo）公布Enhertu（trastuzumab deruxtecan）在3期DESTINY-Lung04研究中的详细数据。该研究评估了Enhertu作为一线疗法治疗携带人表皮生长因子受体2（HER2）基因突变的不可切除局部晚期或转移性非鳞状非小细胞肺癌患者的效果。

研究达到PFS主要终点。Enhertu治疗组的中位PFS为14.3个月，活性对照组为8.3个月，HR为0.63（95% CI：0.50～0.79）。此前，Enhertu已获批用于特定既往接受过治疗的HER2突变晚期非小细胞肺癌患者。此次研究的积极结果为其进一步拓展至一线治疗提供了支持。

7月10日，美国FDA批准扩大Padcev（enfortumab vedotin）与帕博利珠单抗联合方案在肌层浸润性膀胱癌围手术期治疗中的适用人群，从不适合接受顺铂治疗的患者扩大至所有符合根治性膀胱切除术条件的成年患者。该方案在术前采用新辅助治疗，并在膀胱切除术后继续辅助治疗。

此次扩大批准基于纳入808例患者的3期KEYNOTE-B15/EV-304研究，结果显示，该方案在无事件生存期（EFS）和OS方面均取得积极结果。这一进展进一步体现了ADC联合免疫疗法在围手术期治疗中的潜力。

双特异性ADC也迎来了新的监管进展。7月17日，百利天恒宣布，其靶向表皮生长因子受体（EGFR）和人表皮生长因子受体3（HER3）的双特异性ADC伦康依隆妥单抗（iza-bren，商品名：宜泽康）在中国获批第二项适应症，用于治疗既往经PD-1/PD-L1抑制剂联合含铂化疗治疗失败的复发性或转移性食管鳞状细胞癌成人患者。

伦康依隆妥单抗通过同时识别EGFR和HER3，并利用偶联的拓扑异构酶1（TOPO1）抑制剂载荷发挥抗肿瘤作用。此次获批基于3期PANKU-Esophagus01研究的积极结果，该研究达到PFS和OS两项主要终点。

这些进展表明，ADC正在更多癌症类型和治疗阶段积累临床证据，其应用范围有望进一步拓展。

创新载荷：让靶向递送承载更多作用机制

随着更多ADC进入临床应用，如何应对耐药、扩大治疗窗口，成为研发人员关注的重要问题。2026年第三季度，多项收购与授权合作显示，医药企业正在探索新的载荷作用机制，将酶抑制、信号通路阻断和靶向蛋白降解等策略引入偶联药物设计。

7月6日，诺华（Novartis）宣布拟以11亿美元首付款及最高4亿美元潜在里程碑付款收购Myricx Bio，获得其以N-肉豆蔻酰转移酶抑制剂（NMTi）为载荷的ADC技术平台。该交易已于8月28日完成。N-肉豆蔻酰转移酶（NMT）参与蛋白质的脂质修饰，对多种蛋白质的正常功能具有重要作用。与临床常用的TOPO1抑制剂载荷不同，NMTi可通过干扰蛋白质修饰过程产生抗肿瘤作用。在临床前研究中，Myricx Bio的候选药物在部分TOPO1抑制剂耐药模型中仍表现出抗肿瘤活性，为应对现有ADC载荷耐药提供了新的探索方向。

8月28日，罗氏（Roche）旗下基因泰克（Genentech）与映恩生物（DualityBio）达成全球合作协议，共同开发基于DUPAC新型载荷平台的下一代ADC。根据协议，映恩生物将获得4500万美元首付款，以及超过10亿美元的潜在里程碑付款。

DUPAC平台目前包括DUP5、DUP9和DUP10等多种载荷。其中，DUP5通过抑制真核翻译起始因子eIF4A，干扰癌细胞内的蛋白质合成；DUP9则是一种鲁比卡丁（lurbinectedin）衍生物，可通过干扰RNA聚合酶II介导的转录过程诱导DNA损伤。在2025年公布的临床前研究中，基于DUP5或DUP9的ADC在部分对DXd类ADC反应不佳的肿瘤模型中仍表现出抗肿瘤活性。

该平台还可用于双载荷ADC开发。例如，映恩生物在2026年美国癌症研究协会（AACR）年会上公布的DB-1326，将TOPO1抑制剂和DUP9两种载荷连接至靶向TA-MUC1的抗体，在临床前肿瘤模型中取得积极结果。另一项合作则尝试将靶向信号通路的小分子抑制剂与抗体递送相结合。

9月3日，和黄医药与GSK就HMPL-A830达成授权许可协议，首付款为1.1亿美元，另有最高11.85亿美元潜在里程碑付款。HMPL-A830将KRAS小分子抑制剂作为载荷，与靶向EGFR的抗体相连接。该药物旨在利用抗EGFR抗体将KRAS抑制剂递送至EGFR表达的肿瘤组织，同时发挥对EGFR与KRAS信号通路的阻断作用。该项目计划于2026年下半年启动1期临床研究。与传统细胞毒性ADC不同，这一设计尝试将抗体靶向作用与小分子通路抑制相结合。

靶向蛋白降解同样成为偶联药物探索的新方向。7月29日，强生（Johnson & Johnson）宣布完成对Firefly Bio的收购，交易金额为10亿美元，获得其Firelink降解剂抗体偶联物（DAC）平台。该平台利用抗体将具有选择性的蛋白降解剂递送至肿瘤细胞，旨在降解疾病相关蛋白，同时减少正常组织暴露。强生计划利用该技术探索包括KRAS驱动肿瘤在内的实体瘤治疗机会。

从NMT抑制剂到KRAS抑制剂，再到蛋白降解剂，偶联药物正在尝试利用靶向递送技术承载更多类型的药理机制。

放射性偶联药物：治疗阶段前移，产业整合加速

放射性配体疗法是偶联药物领域的另一重要方向。与通过化学载荷发挥作用的ADC不同，这类药物将靶向分子与放射性核素相结合，利用其衰变释放的辐射杀伤肿瘤细胞。

7月31日，美国FDA批准Pluvicto（lutetium Lu 177 vipivotide tetraxetan）与雄激素受体通路抑制剂（ARPI）联合，用于治疗前列腺特异性膜抗原（PSMA）阳性的转移性雄激素通路调节初治或敏感性前列腺癌患者，即此前通常所称的转移性激素敏感性前列腺癌。此次批准基于纳入1144例患者的3期PSMAddition研究。研究达到影像学无进展生存期（rPFS）主要终点，HR为0.72（95% CI：0.58～0.90）。Pluvicto此前已获批用于治疗转移性去势抵抗性前列腺癌，此次新适应症将其应用拓展至更早治疗阶段。

与此同时，放射性配体疗法的靶点探索也在向肿瘤微环境延伸。7月20日，Immunome宣布，其靶向成纤维细胞活化蛋白（FAP）的镥177放射性配体疗法IM-3050在1期临床研究中完成首例患者给药。IM-3050主要靶向肿瘤微环境中的癌症相关成纤维细胞（CAF），旨在将放射性载荷递送至肿瘤区域，利用β射线的作用影响邻近癌细胞。该研究将评价其安全性、剂量学、药代动力学（PK）及初步抗肿瘤活性。

除临床进展外，放射性药物领域在第三季度也迎来了多项重大交易。8月3日，Curium与Lantheus宣布达成最终合并协议，此次交易涉及的对Lantheus股东的总对价最高约80亿美元。双方计划通过合并整合放射性诊疗产品组合、研发管线及全球制造网络，进一步完善放射性药物的开发与供应体系。

9月21日，Telix与ITM宣布达成战略合并协议。ITM在镥177、锕225和铽161等治疗性放射性同位素生产方面具有布局，同时拥有已完成3期临床开发的ITM-11等放射性药物项目。此次拟议合并将整合Telix的临床管线和商业化能力，以及ITM的同位素生产与供应资源。

此外，9月22日，博锐创合（BoomRay）宣布与诺华达成全球独家许可协议，涉及一项临床前放射性配体疗法，首付款与潜在里程碑付款合计最高9亿美元。

精准识别与条件激活：如何让载荷更有效地到达肿瘤？

如果说载荷决定药物发挥什么作用，那么靶点识别、细胞摄取和局部释放则影响这些作用发生的位置。与传统单靶点ADC相比，靶向两种不同抗原的双特异性ADC有望覆盖具有不同抗原表达特征的肿瘤细胞，并通过优化靶点结合与细胞内吞，提高载荷递送效率。除了前文介绍的伦康依隆妥单抗，更多双特异性ADC也正在推进临床开发。

8月3日，Pathos AI宣布与康宁杰瑞旗下子公司就JSKN016达成许可协议。根据协议，Pathos AI获得该药在大中华区以外的开发和商业化权益，首付款为1.25亿美元，另有最高20.93亿美元潜在里程碑付款。JSKN016是一款靶向TROP2/HER3的双特异性ADC，通过糖基位点特异性偶联形成药物抗体比（DAR）为4的均一结构，利用双靶点识别与细胞内吞机制递送TOPO1抑制剂载荷。该药物针对三阴性乳腺癌的3期临床研究正在进行。

多特异性识别也不限于抗体。9月9日，TwoStep Therapeutics宣布完成6250万美元A轮融资，其多特异性多肽偶联药物TS-104的IND同时获得美国FDA许可。TS-104利用能够结合5种肿瘤相关整合素的多肽作为靶向部分，并连接细胞毒性载荷MMAE。通过同时识别多个肿瘤相关靶点，该药物旨在降低递送过程对单一抗原高表达的依赖，提高对肿瘤异质性的适应能力。

与增加识别靶点不同，条件激活技术尝试利用肿瘤局部的生物学特征，控制载荷释放。

9月16日，Avacta公布FAP激活型多肽偶联药物AVA6103的1期FOCUS-01研究初步结果。该药物利用FAP相关酶活性，在特定环境中触发exatecan载荷释放。根据前3个剂量水平、共19例患者的初步安全性及PK数据，研究人员观察到符合预期的持续释放特征，载荷释放可延续至给药后数天。这为该平台的作用机制提供了早期人体研究依据。

这些设计策略说明，偶联药物的创新不仅在于选择合适的靶点，还需要考虑载荷如何进入目标细胞、何时释放，以及释放方式能否与药物作用机制相匹配。随着偶联药物结构日益复杂，连接子、载荷及其他小分子构建模块的开发也面临更高要求。除了设计具有特定释放机制的连接子和新型载荷，研发人员还需要解决复杂分子的合成、结构确认、纯化放大以及高活性载荷的安全处理等问题。

药明康德研发化学服务部构建了覆盖连接子与载荷合成、分析及纯化的一体化技术平台，为ADC关键小分子组件开发提供系统化支持。依托超过10年的项目经验与580余名专业化学家团队，RCS已累计交付超过27000种相关化合物，在多类型连接子合成方面积累了丰富实践经验。平台采用模块化设计理念，建立了包含1000余种连接子、30多类抗体连接位点及超过30种新型载荷及其类似物的可定制化体系。

在载荷与构建模块方面，RCS覆盖多类主流细胞毒性分子体系，包括camptothecin类、auristatin类、maytansinoid类、PBD及duocarmycin类等，并建立了完善的构建模块库与快速物料调用体系，实现从仓储到实验室小于4小时的高效响应。同时，平台支持毫克级至百克级的灵活合成规模，可满足不同阶段项目需求。配套的先进分析与分离能力涵盖LC-MS/HPLC、CAD/ELSD检测、高场核磁（400/500 MHz）、Prep-HPLC-MS及Prep-SFC-MS等技术，可针对稳定性差、紫外响应弱或分离困难的连接子及载荷分子开发专用纯化方案，确保结构确证与高回收率。

此外，RCS配备符合规范的高活性化合物操作实验室，通过隔离器系统、严格去污染流程及完善的人员防护与废弃物管理体系，实现高毒性载荷的安全合规处理。通过将模块化化学设计、规模化合成能力与高标准安全体系相结合，RCS能够帮助合作伙伴高效推进ADC连接子与载荷开发，加速创新偶联疗法从早期研究迈向可开发阶段。

结语

2026年第三季度，偶联药物在临床应用和技术创新两方面取得了重要进展。B7-H3 ADC的积极3期结果，以及ADC和放射性配体疗法向更早治疗阶段拓展，展现了这一领域不断积累的临床证据。与此同时，新型载荷、多靶点识别和条件激活技术，也为未来偶联药物的开发提供了更多可能。这些进展对分子设计、合成、分析、制造及临床开发提出了新的要求。药明康德将持续依托其一体化、端到端的CRDMO平台，支持全球合作伙伴推进创新偶联药物研发，为患者带来更多治疗选择。

Q3 2026 Review of Conjugate Therapeutics

The third quarter of 2026 brought significant advances in conjugate therapeutics. Two B7-H3-targeted antibody-drug conjugates (ADCs) reported positive survival results in Phase 3 trials, while approved ADCs and radioligand therapies continued to move into earlier treatment settings. Meanwhile, novel payloads, multispecific targeting strategies, and conditionally activated drug delivery technologies opened new avenues for conjugate design. Major acquisitions and licensing agreements further underscored the industry's investment in these approaches.

As ADC designs become more complex, linkers and payloads play a critical role in turning molecular concepts into developable drug candidates. WuXi AppTec's Research Chemistry Services (RCS) has established an integrated platform for linker and payload synthesis, analysis, and purification. Backed by more than a decade of project experience, over 580 specialized chemists, and an extensive portfolio of customizable linkers and payloads, RCS helps partners address key development challenges and advance innovative conjugate therapeutics beyond early-stage research.

Clinical Validation: Positive Survival Results and Expansion into Earlier Treatment Settings

The third quarter brought several important clinical and regulatory milestones for ADCs. Among the highlights were two B7-H3-targeted ADCs that met their primary overall survival (OS) endpoints in Phase 3 trials, with results presented at the September World Conference on Lung Cancer (WCLC).

B7-H3, a protein expressed in a range of tumors, has attracted considerable interest as an ADC target. On September 13, results from the ARTEMIS-008 and TAISHAN-302 trials were presented. Both studies evaluated B7-H3-targeted ADCs in patients with relapsed small-cell lung cancer, using topotecan as the active comparator.

In the ARTEMIS-008 trial, which enrolled 461 patients, the investigational ADC risvutatug rezetecan (Ris-Rez, HS-20093/GSK5764227) met its primary OS endpoint. Median OS was 18.5 months in the investigational treatment group versus 10.3 months in the active comparator group, with a hazard ratio (HR) for death of 0.46 (95% CI: 0.35–0.62). The study also met key secondary endpoints, including progression-free survival (PFS).

Another B7-H3-targeted ADC, tambotatug pelitecan (Tam-Peli, YL201), delivered positive results in the TAISHAN-302 trial. Among 451 enrolled patients, median OS was 13.3 months in the investigational treatment group versus 9.4 months in the active comparator group, with an HR of 0.46 (95% CI: 0.35–0.62). This trial also met its primary OS endpoint.

Together, these randomized Phase 3 studies provide important clinical evidence supporting further development of B7-H3-targeted ADCs for relapsed small-cell lung cancer.

Beyond progress with emerging ADC targets, established therapies are also being evaluated earlier in the treatment course.

On September 14, AstraZeneca and Daiichi Sankyo announced detailed results from the Phase 3 DESTINY-Lung04 trial of Enhertu (trastuzumab deruxtecan). The study evaluated Enhertu as a first-line treatment for patients with unresectable locally advanced or metastatic nonsquamous non-small-cell lung cancer harboring HER2 mutations. The trial met its primary PFS endpoint. Median PFS was 14.3 months with Enhertu versus 8.3 months with the active comparator, with an HR of 0.63 (95% CI: 0.50–0.79). Enhertu had previously been approved for certain patients with previously treated HER2-mutant advanced non-small-cell lung cancer. These positive findings support the potential use of Enhertu in the first-line setting.

On July 10, the U.S. FDA expanded the approved perioperative use of Padcev (enfortumab vedotin) in combination with pembrolizumab for muscle-invasive bladder cancer. The expanded indication covers adults eligible for radical cystectomy, regardless of cisplatin eligibility.

The regimen includes neoadjuvant treatment before surgery, followed by adjuvant treatment after radical cystectomy. The expanded approval was based on results from the Phase 3 KEYNOTE-B15/EV-304 trial, which enrolled 808 patients and demonstrated positive results for both event-free survival (EFS) and OS. This milestone further highlights the potential of combining ADCs with immunotherapy in the perioperative setting.

Bispecific ADCs also reached a new regulatory milestone. On July 17, Sichuan Biokin Pharmaceutical (Biokin) announced that izalontamab brengitecan (iza-bren) had received approval for its second indication in China. The approval covers adults with recurrent or metastatic esophageal squamous cell carcinoma whose disease had progressed following treatment with a PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy.

Iza-bren simultaneously targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), delivering a topoisomerase I (TOP1) inhibitor payload. The approval was based on positive findings from the Phase 3 PANKU-Esophagus01 trial, which met both its PFS and OS primary endpoints.

These developments add to the evidence supporting ADCs across different cancer types and treatment settings, while creating opportunities for broader therapeutic applications.

Novel Payloads: Expanding the Mechanisms of Action of Targeted Therapies

As more ADCs enter clinical use, overcoming resistance and improving the therapeutic window have become important priorities. During the third quarter, several acquisitions and licensing agreements highlighted efforts to move beyond conventional ADC payloads by incorporating mechanisms such as enzyme inhibition, signaling pathway blockade, and targeted protein degradation.

On July 6, Novartis announced an agreement to acquire Myricx Bio for $1.1 billion upfront and up to $400 million in potential milestone payments. The acquisition, completed on August 28, gave Novartis access to Myricx Bio's ADC platform featuring N-myristoyltransferase inhibitor (NMTi) payloads.

N-myristoyltransferase (NMT) catalyzes the myristoylation of proteins, a lipid modification involved in regulating protein function. Unlike commonly used TOP1 inhibitor payloads, NMT inhibitors may exert antitumor effects by disrupting this process. In preclinical studies, Myricx Bio's candidates demonstrated antitumor activity in certain models resistant to TOP1 inhibitors, suggesting a potential approach to addressing resistance to existing ADC payloads.

On August 28, Genentech, a member of the Roche Group, entered a global collaboration with DualityBio to develop next-generation ADCs using DualityBio's novel-payload DUPAC platform. Under the agreement, DualityBio will receive $45 million upfront and is eligible for more than $1 billion in potential milestone payments.

The DUPAC platform includes several payload classes, including DUP5, DUP9, and DUP10. DUP5 inhibits eukaryotic translation initiation factor eIF4A, disrupting protein synthesis in cancer cells. DUP9, a derivative of lurbinectedin, interferes with RNA polymerase II-mediated transcription and induces DNA damage. Preclinical studies reported in 2025 showed that ADCs incorporating DUP5 or DUP9 demonstrated antitumor activity in certain tumor models that responded poorly to DXd-based ADCs.

The platform also supports dual-payload ADC development. For example, at the 2026 American Association for Cancer Research (AACR) Annual Meeting, DualityBio presented preclinical findings for DB-1326, a TA-MUC1-targeted ADC incorporating both a TOP1 inhibitor and DUP9 payload. The candidate demonstrated promising antitumor activity in preclinical tumor models.

Another collaboration explored the combination of small-molecule signaling pathway inhibitors with antibody-mediated delivery.

On September 3, HUTCHMED entered a licensing agreement with GSK for HMPL-A830, receiving $110 million upfront and becoming eligible for up to $1.185 billion in additional milestone payments. HMPL-A830 is an antibody-targeted therapy conjugate (ATTC) that combines a KRAS inhibitor payload with an EGFR-targeting antibody. The candidate is designed to deliver a KRAS inhibitor to EGFR-expressing tumors, combining antibody-mediated tumor targeting and EGFR signaling inhibition with the pharmacological activity of the KRAS inhibitor payload. At the time of the announcement, a Phase 1 trial was expected to begin in the second half of 2026. Unlike conventional cytotoxic ADCs, this approach explores how antibody-mediated delivery can be combined with small-molecule pathway inhibition.

Targeted protein degradation is another emerging direction in conjugate therapeutics. On July 29, Johnson & Johnson announced the completion of its $1 billion acquisition of Firefly Bio, gaining access to the company's Firelink degrader-antibody conjugate (DAC) platform. The platform uses antibodies to deliver selective protein degraders into target cells, with the goal of degrading disease-associated proteins while limiting exposure in healthy tissues. Johnson & Johnson plans to explore the technology for solid tumors, including those driven by KRAS alterations.

From NMT inhibitors and KRAS inhibitors to targeted protein degraders, researchers are exploring how antibody-mediated delivery can be applied to an increasingly diverse range of payload mechanisms.

Radioligand Therapies: Earlier Treatment and Accelerating Industry Consolidation

Radioligand therapy represents another important area of conjugate therapeutics. Unlike ADCs, which rely on chemical payloads, radioligand therapies combine targeting molecules with radionuclides, using radiation emitted by the radionuclide to kill cancer cells.

On July 31, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in combination with androgen receptor pathway inhibitor (ARPI) therapy for patients with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer, a disease category previously referred to as metastatic hormone-sensitive prostate cancer.

The approval was based on the Phase 3 PSMAddition trial, which enrolled 1,144 patients and met its primary radiographic progression-free survival (rPFS) endpoint, with an HR of 0.72 (95% CI: 0.58–0.90). Pluvicto was previously approved for metastatic castration-resistant prostate cancer. The new indication extends its use to an earlier treatment setting.

Meanwhile, radioligand development is expanding beyond tumor-cell targets to components of the tumor microenvironment.

On July 20, Immunome announced that the first patient had been dosed in a Phase 1 trial of IM-3050, a fibroblast activation protein (FAP)-targeted lutetium-177 radioligand therapy. IM-3050 targets cancer-associated fibroblasts (CAFs) within the tumor microenvironment. It is designed to deliver radioactivity to tumor regions and potentially damage nearby cancer cells through crossfire irradiation. The ongoing study will evaluate safety, dosimetry, pharmacokinetics (PK), and preliminary antitumor activity.

In addition to clinical progress, the radiopharmaceutical sector saw several major transactions during the quarter. On August 3, Curium and Lantheus announced a definitive merger agreement, with total consideration to Lantheus shareholders of up to approximately $8 billion. The proposed transaction aims to combine the companies' radiopharmaceutical diagnostic and therapeutic portfolios, development pipelines, and global manufacturing networks to strengthen drug development and supply capabilities.

On September 21, Telix and ITM announced a strategic merger agreement. ITM has established production capabilities for therapeutic radioisotopes, including lutetium-177, actinium-225, and terbium-161, as well as radiopharmaceutical candidates such as ITM-11, which has completed Phase 3 clinical development. The proposed combination would bring together Telix's clinical pipeline and commercialization capabilities with ITM's isotope production and supply infrastructure.

On September 22, BoomRay also announced an exclusive global licensing agreement with Novartis involving a preclinical radioligand therapy asset. The agreement includes upfront and potential milestone payments totaling up to $900 million. These developments illustrate how progress in radioligand therapies depends not only on clinical evidence but also on reliable isotope production, manufacturing, and distribution capabilities.

Precision Targeting and Conditional Activation: Improving Payload Delivery to Tumors

While the payload determines a conjugate's pharmacological activity, target recognition, cellular uptake, and local drug release influence where those effects occur. Compared with conventional monospecific ADCs, bispecific ADCs targeting two distinct antigens may bind to tumor cells with different antigen expression profiles. By optimizing target engagement and cellular internalization, these designs could also improve payload delivery. Beyond iza-bren, discussed earlier, additional bispecific ADC candidates are advancing through clinical development.

On August 3, Pathos AI entered a licensing agreement with a subsidiary of Alphamab Oncology for JSKN016. Under the agreement, Pathos AI secured development and commercialization rights outside Greater China, with an upfront payment of $125 million and up to $2.093 billion in potential milestone payments.

JSKN016 is a TROP2/HER3-targeted bispecific ADC that uses glycosite-specific conjugation to achieve a homogeneous drug-to-antibody ratio (DAR) of 4. The candidate is designed to deliver a TOP1 inhibitor payload following binding to TROP2 and/or HER3 and subsequent cellular internalization. A Phase 3 trial in triple-negative breast cancer is underway.

Multispecific targeting strategies are not limited to antibodies. On September 9, TwoStep Therapeutics announced the completion of a $62.5 million Series A financing round, along with FDA clearance of the investigational new drug (IND) application for TS-104, its multispecific peptide-drug conjugate. TS-104 uses a targeting peptide capable of binding five tumor-associated integrins and is conjugated to the cytotoxic payload monomethyl auristatin E (MMAE). By recognizing multiple tumor-associated targets, the candidate aims to reduce dependence on high expression of a single antigen and improve drug delivery across tumors with heterogeneous antigen expression.

In contrast to multispecific targeting, conditionally activated conjugates seek to control payload release by exploiting biological characteristics of the tumor microenvironment.

On September 16, Avacta reported preliminary results from the Phase 1 FOCUS-01 trial of AVA6103, an FAP-activated peptide-drug conjugate. The candidate is designed to use FAP-associated enzymatic activity to trigger the release of its exatecan payload in specific biological environments.

Based on initial safety and PK data from 19 patients across the first three dose levels, researchers observed sustained payload release consistent with the proposed mechanism, with release continuing for several days after administration. These findings provide early clinical evidence supporting the platform's proposed mechanism of action.

Together, these strategies highlight the importance of looking beyond target selection alone. Effective conjugate design also requires an understanding of how payloads enter target cells, when they are released, and whether payload release is appropriately matched to the intended mechanism of action.

As conjugate therapeutics become increasingly complex, developing linkers, payloads, and other small-molecule building blocks is becoming more demanding. Beyond designing novel payloads and linkers with tailored release properties, researchers must address complex synthesis, structural characterization, purification and scale-up, and the safe handling of highly potent compounds.

WuXi AppTec RCS has established a comprehensive ADC linker-payload synthesis platform, designed to support the growing demand for highly specialized cytotoxic conjugation components in next-generation targeted therapies. Built upon more than a decade of experience in complex small-molecule and high-potency chemistry, the platform integrates customized linker-payload synthesis, analytical characterization, and safe handling capabilities into a flexible and scalable workflow. Supported by a team of over 580 experienced chemists, RCS has delivered more than 27,000 compounds and accumulated extensive expertise across diverse linker-payload chemistries, enabling partners to efficiently advance ADC programs from early discovery through development. The platform provides access to a highly modular linker–payload toolbox comprising over 1,000 linkers, more than 30 antibody attachment sites, and over 30 novel payloads and analogs.

RCS supports a broad spectrum of cytotoxic payload classes, including camptothecins, auristatins, maytansinoids, pyrrolobenzodiazepines (PBD), and duocarmycins, alongside a well-established modular building-block warehousing system featuring hundreds of linker and payload intermediates. This infrastructure allows rapid material supply, often transferring compounds from warehouse to laboratory within 4 hours. Meanwhile, the RCS platform supports synthesis scales ranging from milligrams to hundreds of grams, facilitated by advanced analytical and purification capabilities, including LC-MS/HPLC, CAD/ELSD detection, high-field NMR, Prep-HPLC-MS, and Prep-SFC-MS. These tools enable efficient impurity identification, challenging separations, and precise structural validation, particularly for unstable or weakly UV-active linker-payload molecules.

Complementing technical expertise, RCS has dedicated high-potency laboratories equipped with isolators, strict containment protocols, and comprehensive personnel protection procedures to ensure safe and compliant handling of cytotoxic compounds. By combining modular chemistry design, scalable synthesis, advanced analytics, and robust safety infrastructure, WuXi AppTec RCS provides partners with an integrated and reliable solution for ADC linker-payload development, accelerating the creation of innovative conjugate therapeutics with enhanced efficiency and confidence.

Looking Ahead

In Q3 2026, conjugate therapeutics advanced on both clinical and technological fronts. Positive Phase 3 results for B7-H3-targeted ADCs, together with the expansion of ADCs and radioligand therapies into earlier treatment settings, provided further evidence of the therapeutic potential of these modalities. At the same time, novel payloads, multispecific targeting strategies, and conditionally activated delivery technologies created new opportunities for drug development.

These advances are also placing new demands on molecular design, synthesis, analytical characterization, manufacturing, and clinical development. WuXi AppTec will continue to leverage its integrated, end-to-end CRDMO platform to help global partners accelerate the development of more innovative conjugate therapeutics and bring more precise and effective therapies to patients.

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