▎藥明康德

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。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年上半年偶聯領域的最新進展，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：三款新藥獲批上市，多項超10億美元合作達成

2025年上半年，三款創新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，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。今年5月，FDA批準艾伯維（AbbVie）靶向c-Met的抗體偶聯藥物，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，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。

此外，ADC領域在2025年上半年達成了多項授權許可與研發合作，多項交易數額超過10億美元。這體現了業界對ADC治療模式的重視及對創新ADC開發技術的持續關注。除了靶點開發、連接子及載荷方面的創新外，利用雙特異性抗體開發的雙特異性ADC也正在成為下一代ADC設計的重要探索方向。

▲2025年上半年ADC領域部分許可和研發合作信息（數據來源：公開資料）

放射性偶聯藥物：諾華重磅藥再獲FDA批準，潛在“first-in-class”藥物獲突破性療法認定

RDC通過將放射性同位素與靶向特定組織的配體偶聯，將放射性物質精準遞送到腫瘤組織，同時最大限度減少對健康組織的損害。這一領域近年來增長迅速，據統計，2024年啟動的RDC臨床試驗超過30項，與5年前相比增長了3倍。

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。近日公布的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。

此外，Cellectar Biosciences開發的潛在“first-in-class”療法iopofosine I 131近日獲得FDA授予的，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。在治療WM的2期臨床試驗中，其總緩解率達83.6%。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中也達到主要終點，該公司預計今年提交新藥申請（NDA）。

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 CRDMO平臺目前正在賦能各類偶聯藥物開發，覆蓋多種疾病領域。

持續創新，多家偶聯藥物新銳完成融資

2025年上半年，偶聯藥物領域的多家新銳陸續完成融資，為持續推動這一治療模式的創新提供了強勁動力。

在抗體偶聯藥物領域，Callio Therapeutics完成了1.87億美元的。這家公司致力于開發能夠同時攜帶兩種不同載荷的雙載荷ADC，以進一步增強藥物的治療效力。映恩生物于今年3月在港交所完成約2.1億美元的首次公開募股（IPO）。該公司獨特的雙特異性抗體偶聯藥物平臺，利用雙特異性抗體精準驅動藥物載荷的靶向遞送。基于該平臺開發的EGFR/HER3靶向ADC藥物是該公司與Avenzo Therapeutics達成的超12億美元授權協議的核心。

在放射性偶聯藥物領域，AdvanCell公司于上半年完成1.12億美元的。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，共同開發針對多種癌癥類型的創新靶向α粒子療法。

在多肽偶聯藥物領域，ProteinQure公司于今年5月完成1100萬美元的A輪融資。該公司利用先進的人工智能（AI）和機器學習技術，設計并優化包含非天然氨基酸的創新多肽偶聯藥物。其主打在研療法PQ203是一款靶向SORT1的潛在“first-in-class”多肽偶聯藥物，預計在今年下半年啟動首個人體臨床試驗。該公司表示，這將是全球首款進入臨床開發階段的AI設計多肽偶聯藥物。

▲2025年上半年偶聯藥物領域部分投融資活動（數據來源：公開資料）

回顧2025年上半年，偶聯藥物領域在新藥獲批、臨床進展、授權合作以及投融資方面都取得了可圈可點的進展。期待隨著偶聯技術的持續創新和優化，催生更多造福患者的突破。WuXi TIDES團隊將繼續利用其一體化的CRDMO平臺賦能偶聯藥物的開發，幫助合作伙伴將科學創新早日轉化成讓全球患者獲益的療法。

H1 2025 Review of Conjugated Therapeutics: Three Novel ADCs Gained Regulatory Approvals

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 were initiated 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: Three Novel ADC Approvals and Multiple Billion-Dollar Deals

In H1 2025, three 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.

Moreover, multiple licensing and R&D collaborations exceeding $1 billion were signed in the ADC field in early 2025, underscoring the industry's strong interest in ADCs.

Radionuclide Drug Conjugates: Indication Expansion for Pluvicto and a Breakthrough Therapy Designation

RDCs link radioactive isotopes to tissue-targeting ligands to deliver radioactivity precisely to tumors while minimizing harm to healthy tissues. The field has grown rapidly, with more than 30 RDC clinical trials initiated in 2024—three times the number from five years ago.

In March 2025, Novartis’ blockbuster RDC, Pluvicto, received indication expansion for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Recently released Phase III data also demonstrated significant radiographic progression-free survival benefits in PSMA-positive hormone-sensitive prostate cancer.

In addition, Cellectar Biosciences’ potential first-in-class RDC iopofosine I 131 received FDA Breakthrough Therapy Designation for relapsed/refractory Waldenstr?m’s macroglobulinemia (WM). This drug links a phospholipid ether to a radioactive isotope, selectively binding to lipid-rich domains on cancer cells. In its Phase II study for WM, the overall response rate reached 83.6%. Meanwhile, ITM Isotope Technologies’ peptide-conjugated RDC, 177Lu-edotreotide, met primary endpoints in a Phase III trial for gastroenteropancreatic neuroendocrine tumors, with a New Drug Application (NDA) expected this year.

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.

Additionally, WuXi TIDES offers an integrated CRDMO platform with extensive experience in chemical synthesis, supporting the development of various conjugated drugs across multiple disease areas.

Sustained Innovation: Emerging Players Secure New Financing

In the first half of 2025, several emerging companies in the conjugated drug space secured new financing, providing a strong foundation for continued innovation in this rapidly evolving modality.

Within the ADC segment, companies developing dual- or multi-payload or dual-targeting ADC technologies are capturing growing investor interest. Dual- or multi-payload ADCs are designed to deliver combinations of cytotoxic agents and maximize therapeutic benefit. Meanwhile, bispecific ADCs are engineered to enhance tumor selectivity over healthy cells.

In the RDC field, targeted alpha-particle therapies (TAT) continue to emerge as a focal point. TAT leverages the unique properties of alpha particles—such as high linear energy transfer (LET) and short tissue penetration—to deliver potent cytotoxic effects to cancer cells while minimizing damage to surrounding healthy tissue.

In the peptide-drug conjugate (PDC) space, some emerging companies are designing innovative PDCs incorporating non-natural amino acids. A potentially first-in-class PDC is expected to enter first-in-human trials in the second half of the year.

In summary, the first half of 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 that promise to benefit patients worldwide.

WuXi TIDES remains committed to harnessing its fully integrated CRDMO platform to support the development of conjugated drugs—empowering partners to accelerate the translation of scientific innovation into transformative therapies.

參考資料：

[1] Case Study: PDC Drug R&D and Manufacturing in 9 Months. Retrieved June 3, 2025, from https://tides.wuxiapptec.com/resources/case-study-pdc-drug-rd-and-manufacturing-in-9-months/

[2] 創新多肽偶聯藥物達3期臨床主要終點，今年遞交新藥申請https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2650107324&idx=2&sn=420318d4250bf582588e9e861ca14748&chksm=831934ebc8f5e0a7a1322e83abb62c211eac8fc564211e02881a8e3f6ef8cc23fe51d138ecbc#rd

[3] Novartis Pluvicto? demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. Retrieved June 3, 2025, from https://www.novartis.com/news/media-releases/novartis-pluvictotm-demonstrates-statistically-significant-and-clinically-meaningful-rpfs-benefit-patients-psma-positive-metastatic-hormone-sensitive-prostate-cancer

[4] Global Oncology Trends 2025. Retrieved June 3, 2025, from https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-oncology-trends-2025

[5] Bicycle Therapeutics Announces Poster Presentations at the 2025 ASCO Annual Meeting. Retrieved June 17, 2025, from https://investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-announces-poster-presentations-2025-asco

[6] New Real-World Data support effectiveness and tolerability of Pepaxti in heavily pretreated Multiple Myeloma patients. Retrieved June 17, 2025, from https://oncopeptides.com/en/media/press-releases/new-real-world-data-support-effectiveness-and-tolerability-of-pepaxti-in-heavily-pretreated-multiple-myeloma-patients/

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