1. Overview of ADC Drugs
Antibody-drug conjugates (ADCs) are referred to as the ‘magic bullets’ for cancer treatment. They are a new type of biotherapeutic drug that combines monoclonal antibodies with cytotoxic drugs through a chemical linker. The core concept is to combine the specific targeting ability of antibodies with the powerful killing effect of cytotoxic drugs. Once inside the cell, the linker undergoes cleavage in a specific intracellular environment, releasing the cytotoxic drug to kill tumor cells. The aim is to achieve precise targeting of tumor cells, reduce damage to normal cells, and improve the effectiveness and safety of cancer treatment.
2. Key Factors in ADC Drug Development
The development of ADC drugs requires comprehensive consideration of several key factors: – Target selection: Focus on high expression specificity in tumor cells and relevance to tumor biological processes. – Antibody design: Ensure low immunogenicity, strong specificity, high internalization efficiency, and long half-life to achieve effective delivery of ADCs in the body. – Linker design: Balance stability and cleavability, as well as chemical compatibility, while avoiding ADC aggregation, preventing premature release of the active payload in the bloodstream, and ensuring precise release of the active drug at the target site. – Cytotoxic drugs: Ensure stability under physiological conditions and the presence of functional groups that can bind to the antibody. – Conjugation method: The method of attaching small molecular components to the antibody is a key factor in successfully constructing ADCs, and the choice of conjugation method significantly impacts the stability and efficacy of the ADC.
3. Development History of ADC Drugs
– Concept Introduction: The concept of ADCs was first proposed by German physician and Nobel laureate Paul Ehrlich in the early 20th century. – Research Initiation: It wasn’t until the 1970s, with the advent of monoclonal antibodies and the maturity of recombinant protein engineering technology, that ADC research gradually became a hot area in antibody drug development. – First Approval: In 2000, Mylotarg, developed by Wyeth Pharmaceuticals, received accelerated approval from the FDA for the treatment of CD33-positive acute myeloid leukemia (AML) patients, becoming the world’s first commercialized ADC drug. – Period of Silence: Following this, the ADC field experienced a long period of silence, during which only four new products—Adcetris, Kadcyla, Besponsa, and Lumoxiti—were approved over eight years, leading to slow growth in the ADC market. – Resurgence and Development: In 2019, three ADCs—Polivy, Padcev, and Enhertu—were approved, with Enhertu, developed in collaboration between Daiichi Sankyo and AstraZeneca, being seen as the biggest catalyst for the rapid resurgence in the ADC field. After 2019, the ADC sector saw a flurry of approvals for products like Trodelvy, Blenrep, and Zynlonta, leading to exponential market growth.
4. Current Market Status
Currently, 15 ADCs have been approved, with over 210 in clinical trials. In recent years, ADC drug development has entered a phase of flourishing diversity, particularly demonstrating significant efficacy and good safety on targets such as HER2, EGFR, Trop2, CLDN18.2, and Nectin-4. Combination therapies and bispecific ADCs have shown remarkable results, providing patients with more treatment options. However, the ADC drug market also faces challenges, such as the termination of collaborations between companies and potential resistance issues. Overall, the growth trend is evident, and the market potential is enormous.
5. Status of Some Popular Targeted ADC Drugs
1. HER2 Target: Since the first HER2 monoclonal antibody drug was approved, the HER2 target has received significant attention in the field of tumor treatment. Currently, approved HER2 ADC drugs include trastuzumab emtansine, trastuzumab deruxtecan, and trastuzumab duocarmazine, with many more HER2 ADCs in clinical research, such as SHR-A1811 from Hengrui Medicine and DP303c from CSPC. Trastuzumab deruxtecan (DS-8201, Enhertu) has become a major breakthrough in the HER2 ADC field due to its unique structure and high anti-tumor activity. Since its first approval in 2019, it has been approved in multiple countries and regions, including the USA, Japan, the EU, and China, for indications covering HER2-positive breast cancer, HER2-positive gastric cancer, HER2-low expressing breast cancer, HER2-mutated non-small cell lung cancer, and HER2-positive solid tumors, with annual sales increasing, reaching approximately 395.9 billion yen (about 3 billion USD) in 2023, a year-on-year increase of about 78%. 2. Trop2 Target: The development status of Trop2 ADCs in lung cancer is multifaceted. In terms of efficacy, products from different companies show varying effectiveness in different subpopulations. The products from Daiichi Sankyo and Kelun Biotech are effective in EGFR-positive and non-squamous populations but limited in efficacy for EGFR wild-type or squamous patients; Gilead’s products show good efficacy in populations with driver gene mutations, with comparable effectiveness in non-squamous and squamous cancers. There are significant differences in clinical layouts among companies. On June 11, 2025, Kelun Pharmaceutical’s subsidiary Kelun Biotech’s Trop2-targeting ADC, sacituzumab govitecan (Jiatilai®), in combination with the PD-L1 monoclonal antibody, was granted breakthrough therapy designation by the NMPA for first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without driver gene mutations.
7. ADC Drugs Granted Breakthrough Therapy Designation by CDE in 2025
Xinovate Biopharmaceuticals’ injectable XNW28012
Proposed for inclusion as a breakthrough therapy, with the intended indication for metastatic pancreatic cancer that has failed previous second-line systemic treatment (based on gemcitabine and fluorouracil chemotherapy). It is an innovative ADC that targets tissue factor (TF) for the treatment of various solid tumors with high TF expression. Preclinical experiments have confirmed its good anti-tumor efficacy in solid tumors with high TF expression, providing a new treatment option for patients with high TF expression solid tumors. Non-clinical studies have shown good anti-tumor activity in various solid tumor models with high TF expression, and the overall safety profile is controllable.
Hengrui Medicine’s injectable SHR-A1811 (RuiKang Trastuzumab)
Received breakthrough therapy designation from CDE on March 27. The intended indication is for recurrent or metastatic cervical cancer with HER2 expression (IHC≥1+) that has failed previous platinum-based chemotherapy and immune checkpoint inhibitor treatment. This is the eighth breakthrough therapy designation for this product. It is an HER2 ADC independently developed by Hengrui Medicine, composed of trastuzumab, a cleavable linker, and the topoisomerase I inhibitor payload SHR169265. The payload SHR169265 not only has higher membrane penetration ability but also significantly enhances the cell-killing effect. More importantly, this drug innovatively introduces a chiral cyclopropyl design between the linker and the toxin, greatly improving the chemical stability of the drug, effectively controlling the precise release of the toxin, and significantly reducing the side effects that may arise from early release.
Maiwei Biopharmaceuticals’ 9MW2821
Proposed for inclusion in the breakthrough therapy list in early January, with the intended indication for use in combination with toripalimab for the treatment of previously untreated, unresectable locally advanced or metastatic urothelial carcinoma. This product is a targeted ADC new drug aimed at Nectin-4, developed by Maiwei Biopharmaceuticals using their ADC drug development platform, achieving site-specific modification of the antibody through proprietary linker technology and optimized ADC conjugation processes. After injection into the body, it can bind to Nectin-4 on the surface of tumor cells and enter the cells, releasing cytotoxins through enzymatic action, thereby killing the tumor. The company is currently conducting multiple clinical studies for various indications, including urothelial carcinoma, cervical cancer, esophageal cancer, and breast cancer.
Innovent Biologics’ Class 1 New Drug IBI343
Proposed for inclusion in the breakthrough therapy list in early January, it is a recombinant humanized anti-CLDN18.2 ADC that, upon binding to CLDN18.2-expressing tumor cells, can undergo CLDN18.2-dependent ADC internalization and release toxic drugs that cause DNA damage, leading to tumor cell apoptosis.