近一年已有4款新型偶聯(lián)藥物獲批上市，用于乳腺癌、肺癌、鼻咽癌！當(dāng)下這類療法還有哪些熱點(diǎn)？

編者按：偶聯(lián)藥物通過將與靶蛋白結(jié)合的配體與功能性載荷連接，實(shí)現(xiàn)向特定組織或細(xì)胞精準(zhǔn)遞送載荷的效果。近年來，這一領(lǐng)域快速發(fā)展，據(jù)統(tǒng)計(jì)，2024年全球啟動了284項(xiàng)抗體偶聯(lián)藥物（ADC）臨床試驗(yàn)，比2023年增加了100多項(xiàng)，彰顯了偶聯(lián)藥物領(lǐng)域的迅猛增長。ADC之外，放射性偶聯(lián)藥物（RDC）、多肽偶聯(lián)藥物（PDC）以及寡核苷酸偶聯(lián)藥物等新興偶聯(lián)模式也不斷涌現(xiàn)。在2025年，多款創(chuàng)新ADC療法獲批上市，雙特異性ADC獲得臨床進(jìn)展，RDC療法也成為產(chǎn)業(yè)融資熱點(diǎn)之一。藥明康德旗下WuXi TIDES搭建了為寡核苷酸、多肽及復(fù)雜化學(xué)偶聯(lián)藥物開發(fā)提供一體化服務(wù)的CRDMO平臺，覆蓋從藥物發(fā)現(xiàn)、CMC開發(fā)及商業(yè)化生產(chǎn)的全生命周期，尤其借助藥明康德在化學(xué)業(yè)務(wù)方面的豐富經(jīng)驗(yàn)，為賦能新一代偶聯(lián)療法奠定了堅(jiān)實(shí)基礎(chǔ)。本文將盤點(diǎn)2025年偶聯(lián)領(lǐng)域的重要進(jìn)展，并介紹WuXi TIDES一體化CRDMO平臺賦能多肽偶聯(lián)藥物開發(fā)的能力。

抗體偶聯(lián)藥物：多款療法獲批上市，雙特異性ADC嶄露頭角

2025年，4款創(chuàng)新ADC獲得監(jiān)管機(jī)構(gòu)批準(zhǔn)上市。阿斯利康（AstraZeneca）與第一三共（Daiichi Sankyo）聯(lián)合開發(fā)的Datroway獲批，用于治療無法切除或轉(zhuǎn)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(yè)媒體Evaluate列為潛在重磅療法。2025年5月，F(xiàn)DA批準(zhǔn)艾伯維（AbbVie）靶向c-Met的抗體偶聯(lián)藥物Emrelis上市，用于治療c-Met蛋白高度表達(dá)的局部晚期或轉(zhuǎn)移性非鱗狀非小細(xì)胞肺癌（NSCLC）成年患者。恒瑞醫(yī)藥的HER2靶向ADC瑞康曲妥珠單抗獲得批準(zhǔn)，單藥治療存在HER2激活突變且既往接受過至少一種系統(tǒng)治療的不可切除的局部晚期或轉(zhuǎn)移性NSCLC成人患者。樂普生物開發(fā)的靶向EGFR的ADC維貝柯妥塔單抗也獲得批準(zhǔn)，用于治療復(fù)發(fā)性或轉(zhuǎn)移性鼻咽癌。

雙特異性ADC通過靶向兩個(gè)不同靶點(diǎn)，或者同一靶點(diǎn)上的兩個(gè)不同表位，與只與單個(gè)靶點(diǎn)結(jié)合的ADC相比，可能增加與靶細(xì)胞結(jié)合的特異性，從而提高療效并降低脫靶效應(yīng)帶來的潛在毒性。此外，靶向不同靶點(diǎn)蛋白可能讓雙特異性ADC與更為廣泛的細(xì)胞群體結(jié)合，從而克服腫瘤的異質(zhì)性。

圖片來源：123RF

2025年，雙特異性ADC獲得業(yè)界越來越多的關(guān)注，多家公司在這一領(lǐng)域獲得臨床進(jìn)展。例如，百利天恒與百時(shí)美施貴寶（Bristol Myers Squibb）聯(lián)合開發(fā)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(yàn)中獲得積極結(jié)果。數(shù)據(jù)顯示，患者的確認(rèn)客觀緩解率（ORR）達(dá)54.6%，而對照組這一數(shù)值為27.0%。此外，治療組的中位無進(jìn)展生存期（PFS）為8.38個(gè)月，幾乎是對照組（4.34個(gè)月）的兩倍。

Iza-bren與EGFR抑制劑Tagrisso聯(lián)用作為一線組合療法，在治療攜帶EGFR突變的非小細(xì)胞肺癌患者的2期臨床試驗(yàn)中，達(dá)到95%的確認(rèn)ORR，12個(gè)月無進(jìn)展生存率為92.1%。這一療法也被FDA授予突破性療法認(rèn)定。

此外，Avenzo Therapeutics和映恩生物聯(lián)合開發(fā)的EGFR/HER3靶向ADC AVZO-1418完成1/2期臨床試驗(yàn)的首位患者給藥，用于治療晚期實(shí)體瘤。康方生物的AK146D1是一款靶向Trop2和Nectin4的雙特異性ADC，它在2025年7月也完成1a期臨床試驗(yàn)的首例患者給藥。

在2025年，雙特異性ADC也成為研發(fā)合作的熱點(diǎn)之一，至少有6項(xiàng)研發(fā)合作涉及雙特異性ADC項(xiàng)目的開發(fā)。

▲2025年雙特異性ADC領(lǐng)域的研發(fā)合作（數(shù)據(jù)截至2025年12月17日）

放射性偶聯(lián)藥物：諾華重磅藥再獲FDA批準(zhǔn)，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(zhǔn)，用于治療PSMA陽性轉(zhuǎn)移性去勢抵抗性前列腺癌患者。此外，3期臨床試驗(yàn)結(jié)果顯示，它在治療PSMA陽性激素敏感性前列腺癌患者時(shí)，也顯示出具有臨床意義和統(tǒng)計(jì)學(xué)顯著性的放射學(xué)無進(jìn)展生存期獲益。

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

Cellectar Biosciences開發(fā)的潛在“first-in-class”療法iopofosine I 131獲得FDA授予的突破性療法認(rèn)定，用于治療復(fù)發(fā)/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(lián)，能夠特異性結(jié)合癌細(xì)胞表面的特定脂質(zhì)區(qū)域。

在2025年，多家致力于開發(fā)放射性偶聯(lián)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(yàn)中用于治療轉(zhuǎn)移性前列腺癌患者。此外，該公司2025年還與禮來公司達(dá)成研發(fā)合作協(xié)議，共同開發(fā)針對多種癌癥類型的創(chuàng)新靶向α粒子療法。

ARTBIO在2025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(xiàng)目的開發(fā)進(jìn)程，重點(diǎn)推動其主打候選藥物AB001在轉(zhuǎn)移性去勢抵抗性前列腺癌（mCRPC）患者中的2期臨床試驗(yàn)。

▲2025年放射性偶聯(lián)藥物領(lǐng)域部分融資活動（數(shù)據(jù)截至2025年12月17日）

雖然RDC在早期腫瘤成像和治療方面均展現(xiàn)巨大潛力，但其藥物結(jié)構(gòu)復(fù)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(chǎn)過程需要多學(xué)科的專業(yè)技術(shù)支持。藥明康德綜合性的放射性藥物發(fā)現(xiàn)平臺整合了多肽發(fā)現(xiàn)和放射性藥物開發(fā)能力，提供包括多肽合成、螯合劑合成、放射性標(biāo)記、成像、藥理學(xué)研究和監(jiān)管申報(bào)支持等完善的服務(wù)。一體化平臺讓多個(gè)團(tuán)隊(duì)并行攻堅(jiān)、高度協(xié)作，幫助合作伙伴快速推動RDC項(xiàng)目，節(jié)省寶貴的開發(fā)時(shí)間。

藥明康德旗下WuXi TIDES搭建了獨(dú)特的CRDMO平臺，為全球合作伙伴開發(fā)寡核苷酸、多肽藥物及相關(guān)化學(xué)偶聯(lián)物（TIDES藥物）提供高效、靈活和高質(zhì)量解決方案。

比如，在多肽偶聯(lián)藥物開發(fā)方面，WuXi TIDES全面的多肽平臺結(jié)合了小分子化學(xué)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(lián)藥物等偶聯(lián)藥物的開發(fā)。WuXi TIDES的一體化平臺讓多個(gè)團(tuán)隊(duì)能夠并行攻關(guān)，密切合作，顯著提高項(xiàng)目推進(jìn)速度。

未來，WuXi TIDES將繼續(xù)依托其一體化、端到端的CRDMO平臺，支持合作伙伴推進(jìn)包括多肽偶聯(lián)藥物、寡核苷酸偶聯(lián)藥物在內(nèi)的多類偶聯(lián)藥物研發(fā)，助力前沿科技轉(zhuǎn)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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