From breakthrough therapy approval to over $1 billion in collaboration, the latest progress in the field of conjugation in the first half of 2025 | Going Far

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 Waldenström’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.