同行致遠 | 4款創新ADC獲批，放射性偶聯藥物和雙特異性ADC獲得產業關注 | Bilingual

編者按：偶聯藥物通過將與靶蛋白結合的配體與功能性載荷連接，實現向特定組織或細胞精準遞送載荷的效果。近年來，這一領域快速發展，據統計，2024年全球啟動了284項抗體偶聯藥物（ADC）臨床試驗，比2023年增加了100多項，彰顯了偶聯藥物領域的迅猛增長。ADC之外，放射性偶聯藥物（RDC）、多肽偶聯藥物（PDC）以及寡核苷酸偶聯藥物等新興偶聯模式也不斷涌現。在2025年，多款創新ADC療法獲批上市，雙特異性ADC獲得臨床進展，RDC療法也成為產業融資熱點之一。藥明康德旗下WuXi TIDES搭建了為寡核苷酸、多肽及復雜化學偶聯藥物開發提供一體化服務的CRDMO平臺，覆蓋從藥物發現、CMC開發及商業化生產的全生命周期，尤其借助藥明康德在化學業務方面的豐富經驗，為賦能新一代偶聯療法奠定了堅實基礎。本文將盤點2025年偶聯領域的重要進展，并介紹WuXi TIDES一體化CRDMO平臺賦能多肽偶聯藥物開發的能力。

抗體偶聯藥物：多款療法獲批上市，雙特異性ADC嶄露頭角

2025年，4款創新ADC獲得監管機構批準上市。阿斯利康（AstraZeneca）與第一三共（Daiichi Sankyo）聯合開發的Datroway獲批，用于治療無法切除或轉移性HR陽性、HER2陰性乳腺癌成人患者。這款靶向Trop2的ADC曾被行業媒體Evaluate列為潛在重磅療法。今年5月，FDA批準艾伯維（AbbVie）靶向c-Met的抗體偶聯藥物Emrelis上市，用于治療c-Met蛋白高度表達的局部晚期或轉移性非鱗狀非小細胞肺癌（NSCLC）成年患者。恒瑞醫藥的HER2靶向ADC瑞康曲妥珠單抗獲得批準，單藥治療存在HER2激活突變且既往接受過至少一種系統治療的不可切除的局部晚期或轉移性NSCLC成人患者。樂普生物開發的靶向EGFR的ADC維貝柯妥塔單抗也獲得批準，用于治療復發性或轉移性鼻咽癌。

雙特異性ADC通過靶向兩個不同靶點，或者同一靶點上的兩個不同表位，與只與單個靶點結合的ADC相比，可能增加與靶細胞結合的特異性，從而提高療效并降低脫靶效應帶來的潛在毒性。此外，靶向不同靶點蛋白可能讓雙特異性ADC與更為廣泛的細胞群體結合，從而克服腫瘤的異質性。

2025年，雙特異性ADC獲得業界越來越多的關注，多家公司在這一領域獲得臨床進展。例如，百利天恒與百時美施貴寶（Bristol Myers Squibb）聯合開發的靶向EGFR和HER3的潛在“first-in-class”雙特異性ADC izalontamab brengitecan（iza-bren）在治療鼻咽癌的3期臨床試驗中獲得積極結果。數據顯示，患者的確認客觀緩解率（ORR）達54.6%，而對照組這一數值為27.0%。此外，治療組的中位無進展生存期（PFS）為8.38個月，幾乎是對照組（4.34個月）的兩倍。

Iza-bren與EGFR抑制劑Tagrisso聯用作為一線組合療法，在治療攜帶EGFR突變的非小細胞肺癌患者的2期臨床試驗中，達到95%的確認ORR，12個月無進展生存率為92.1%。這一療法也被FDA授予突破性療法認定。

此外，Avenzo Therapeutics和映恩生物聯合開發的EGFR/HER3靶向ADC AVZO-1418完成1/2期臨床試驗的首位患者給藥，用于治療晚期實體瘤。康方生物的AK146D1是一款靶向Trop2和Nectin4的雙特異性ADC，它在今年7月也完成1a期臨床試驗的首例患者給藥。

在2025年，雙特異性ADC也成為研發合作的熱點之一，至少有6項研發合作涉及雙特異性ADC項目的開發。

▲2025年雙特異性ADC領域的研發合作（數據截至12月17日）

放射性偶聯藥物：諾華重磅藥再獲FDA批準，多家新銳完成融資

2025年，諾華的重磅RDC療法Pluvicto再次獲得FDA批準，用于治療PSMA陽性轉移性去勢抵抗性前列腺癌患者。此外，3期臨床試驗結果顯示，它在治療PSMA陽性激素敏感性前列腺癌患者時，也顯示出具有臨床意義和統計學顯著性的放射學無進展生存期獲益。

ITM Isotope Technologies開發的基于多肽偶聯的靶向RDC療法177Lu-edotreotide，在治療胃腸胰神經內分泌腫瘤的3期臨床試驗中也達到主要終點。FDA已接受該公司提交的新藥申請（NDA）。

Cellectar Biosciences開發的潛在“first-in-class”療法iopofosine I 131獲得FDA授予的突破性療法認定，用于治療復發/難治性華氏巨球蛋白血癥（WM）。該藥物將磷酸酯與放射性同位素偶聯，能夠特異性結合癌細胞表面的特定脂質區域。

在2025年，多家致力于開發放射性偶聯藥物的新銳完成融資。例如，AdvanCell公司于上半年完成1.12億美元的C輪融資。該公司基于Pb212的靶向α粒子放射性療法ADVC001具有“best-in-class”潛力，目前正在1/2期臨床試驗中用于治療轉移性前列腺癌患者。此外，該公司今年還與禮來公司達成研發合作協議，共同開發針對多種癌癥類型的創新靶向α粒子療法。

ARTBIO在今年7月完成1.32億美元B輪融資，加速該公司α粒子放射性配體療法項目的開發進程，重點推動其主打候選藥物AB001在轉移性去勢抵抗性前列腺癌（mCRPC）患者中的2期臨床試驗。

▲2025年放射性偶聯藥物領域部分融資活動（數據截至12月17日）

雖然RDC在早期腫瘤成像和治療方面均展現巨大潛力，但其藥物結構復雜，通常由靶向配體、連接子、螯合劑和放射性同位素組成。其生產過程需要多學科的專業技術支持。藥明康德綜合性的放射性藥物發現平臺整合了多肽發現和放射性藥物開發能力，提供包括多肽合成、螯合劑合成、放射性標記、成像、藥理學研究和監管申報支持等完善的服務。一體化平臺讓多個團隊并行攻堅、高度協作，幫助合作伙伴快速推動RDC項目，節省寶貴的開發時間。

藥明康德旗下WuXi TIDES搭建了獨特的CRDMO平臺，為全球合作伙伴開發寡核苷酸、多肽藥物及相關化學偶聯物（TIDES藥物）提供高效、靈活和高質量解決方案。

比如，在多肽偶聯藥物開發方面，WuXi TIDES全面的多肽平臺結合了小分子化學能力，支持多肽-毒素、多肽-金屬、多肽-GalNAc、多肽-寡核苷酸和放射性核素偶聯藥物等偶聯藥物的開發。WuXi TIDES的一體化平臺讓多個團隊能夠并行攻關，密切合作，顯著提高項目推進速度。

未來，WuXi TIDES將繼續依托其一體化、端到端的CRDMO平臺，支持合作伙伴推進包括多肽偶聯藥物、寡核苷酸偶聯藥物在內的多類偶聯藥物研發，助力前沿科技轉化為惠及全球患者的突破性療法。

CRDMO: 2025 Review of Conjugated Therapeutics

Conjugated drugs enable the precise delivery of therapeutic payloads to specific tissues or cells by linking target-binding ligands with functional payloads. In recent years, this field has advanced rapidly. According to a recent report, 284 antibody-drug conjugate (ADC) clinical trials were initiated globally in 2024—over 100 more than in 2023.Alongside ADCs, new conjugated modalities have also gained momentum, including radionuclide-drug conjugates (RDCs), peptide-drug conjugates (PDCs), and oligonucleotide-drug conjugates.This growing momentum underscores the expanding potential of conjugated therapeutics in addressing a broad range of diseases.

Backed by extensive experience in chemistry and integrated drug development expertise, WuXi TIDES is supporting next-generation conjugated therapies. As an integral part of WuXi AppTec, WuXi TIDES has built an integrated CRDMO platform focused on oligonucleotides, peptides and related synthetic conjugates. This platform simplifies TIDES drug development by providing all discovery, CMC development and the entire manufacturing supply chain under one roof.

Antibody-Drug Conjugates: Multiple Approvals and the Rise of Bispecific ADCs

In 2025,four novel ADCs received their first regulatory approvals in key markets.Datroway (datopotamab deruxtecan), jointly developed by AstraZeneca and Daiichi Sankyo, was approved for the treatment of adults with unresectable or metastatic HR-positive, HER2-negative breast cancer. In May, AbbVie’s Emrelis (telisotuzumab vedotin), a c-Met-targeting ADC, received approval for treating adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met expression. Also in May, the HER2-targeting trastuzumab rezetecan, developed by Hengrui Pharma, was approved for the treatment of adult patients with unresectable locally advanced or metastatic NSCLC harboring activating HER2 mutations who have previously received at least one systemic therapy. Lepu Biopharma’s EGFR-targeting ADC, becotatug vedotin, was also approved for the treatment of recurrent or metastatic nasopharyngeal carcinoma.

Beyond conventional ADCs, bispecific ADCs—designed to target either two distinct antigens or two different epitopes on the same antigen—are emerging as a promising next generation of conjugated therapies.Compared with ADCs that bind a single target, bispecific ADCs may enhance binding specificity to target cells, thereby improving therapeutic efficacy while reducing potential off-target toxicity. Moreover, by engaging different target proteins, bispecific ADCs may interact with a broader population of tumor cells, offering a potential strategy to address tumor heterogeneity.

Accordingly, bispecific ADCs have attracted increasing attention across the industry in 2025, with several programs reporting meaningful clinical progress. Notably, izalontamab brengitecan (iza-bren), a potential first-in-class bispecific ADC targeting EGFR and HER3 developed by Biotheus in collaboration with Bristol Myers Squibb, demonstrated positive results in a Phase 3 clinical trial in nasopharyngeal carcinoma. The confirmed objective response rate (ORR) reached 54.6% in the treatment group, compared with 27.0% in the control group. In addition, the median progression-free survival (PFS) was 8.38 months, nearly double that observed in the control arm (4.34 months).

Further reinforcing its clinical potential, iza-bren in combination with the EGFR inhibitor Tagrisso, used as a first-line regimen, achieved a confirmed ORR of 95% in a Phase 2 trial in patients with EGFR-mutant NSCLC. The 12-month progression-free survival rate reached 92.1%, and the combination therapy was granted Breakthrough Therapy Designation by the FDA.

In addition, a Trop2/Nectin-4 bispecific ADC and an EGFR/HER3-targeting ADC both completed the dosing of first patients in their first-in-human clinical trials.

Reflecting this growing momentum, bispecific ADCs have also become a focal point for strategic collaborations.In 2025 alone, at least six R&D partnerships were established around the development of bispecific ADC programs, highlighting strong industry confidence in this emerging modality.

Radionuclide-Drug Conjugates: A Blockbuster Secures Another FDA Approval as Emerging Players Complete Major Financings

In 2025, Novartis’ blockbuster RDC therapy Pluvicto received another FDA approval for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer. In addition, results from a Phase 3 clinical trial showed that Pluvicto also delivered clinically meaningful and statistically significant improvements in radiographic progression-free survival in patients with PSMA-positive hormone-sensitive prostate cancer, further expanding its clinical potential.

Meanwhile, ITM Isotope Technologies reported positive Phase 3 results for its peptide-based targeted RDC therapy 1??Lu-edotreotide in patients with gastroenteropancreatic neuroendocrine tumors, meeting the trial’s primary endpoint. The FDA has accepted the company’s New Drug Application (NDA) for this candidate, marking an important regulatory milestone.

Progress has also been made with novel mechanisms in the field. Cellectar Biosciences’ potential first-in-class therapy iopofosine I 131 was granted Breakthrough Therapy Designation by the FDA for the treatment of relapsed or refractory Waldenstr?m macroglobulinemia (WM). This drug conjugates a phospholipid ether with a radioactive isotope, enabling selective binding to specific lipid domains on the surface of cancer cells.

Alongside these clinical and regulatory advances,2025 has also been an active year for financing among emerging RDC developers.For example, AdvanCell completed a $112 million Series C financing in the first half of the year. Its Pb-212-based targeted alpha-particle radiotherapy candidate ADVC001, which has demonstrated best-in-class potential, is currently being evaluated in a Phase 1/2 clinical trial for patients with metastatic prostate cancer. In addition, AdvanCell entered into a research collaboration with Eli Lilly this year to jointly develop innovative targeted alpha-particle therapies across multiple cancer indications.

Similarly, ARTBIO closed a $132 million Series B financing in July, accelerating the development of its alpha-particle radioligand therapy programs. The funding will primarily support advancement of its lead candidate AB001 into a Phase 2 clinical trial in patients with metastatic castration-resistant prostate cancer (mCRPC).

Although RDCs have demonstrated potential in early tumor imaging and treatment, their complex drug structures—typically composed of a targeting ligand, linker, chelator, and radionuclide—require multidisciplinary technical expertise for development and manufacturing.WuXi AppTec offers a comprehensive radiopharmaceutical discovery platform that combines peptide discovery with radiopharmaceutical development, covering peptide synthesis, chelator synthesis, radiolabeling, imaging, pharmacology studies, and regulatory filing support.This integrated model enables parallel, highly collaborative efforts across multiple teams, helping partners accelerate RDC programs and save valuable development time.

In addition to RDC, WuXi TIDES, a specialized CRDMO platform under WuXi AppTec, provides efficient, flexible, and high-quality solutions for the development of oligonucleotides, peptides, and related chemically conjugated molecules—collectively known as "TIDES" drugs. The platform integrates advanced peptide capabilities with small molecule chemistry, supporting various peptide conjugates, including but not limited to: peptide-toxin, peptide-metal, peptide-GalNAc, peptide-PMO, peptide-oligonucleotide, etc. The platform’s integrated nature enables cross-functional teams to collaborate in parallel, significantly accelerating project timelines.

In summary, 2025 has seen remarkable progress in the conjugated drug field across new drug approvals, clinical milestones, strategic partnerships, and financing activity. As innovation and optimization in conjugation technologies advance, the field is poised for even more breakthroughs. WuXi AppTec will continue to leverage its fully integrated, end-to-end CRDMO platform to support partners in advancing diverse classes of conjugated drugs—including peptide- and oligonucleotide-based conjugates—ultimately helping to transform scientific breakthroughs into life-changing therapies for patients worldwide.

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