Abstract:
Industry atlas research is a sub-topic of the team's research on the transformation of scientific and technological achievements. The goal is to clearly understand the technical core of cutting-edge scientific and technological achievements, the technical competitiveness of scientific and technological enterprises, and the research progress of scientific researchers, so as to help improve the efficiency of scientific and technological achievement transformation. The industry atlas research will be carried out in a series, selecting commercial application scenarios in key national strategic science and technology fields one by one, with strong timeliness.
This report is the Atlas of Antibody-drug conjugates (ADCs). ADCs have emerged as a promising therapeutic modality in oncology, and made great improvements in the patients prognosis of different cancer types. Spanning over 40 years of development, 13 ADCs have approved by the FDA/EMA/NMDA and more than 200 ADCs are currently being tested in clinical trials. Based on market analysis, revenue from approved ADCs and those in phase III development is forecasted to reach $26 billion by 2028.
As the most representative drug classes in oncology, an ADC typically consists of a monoclonal antibodies (Monoclonal antibodys, mAbs) covalently attached to a potent cytotoxic payload through a chemical linker. This innovative design harnesses the precision of mAbs and the potency of cytotoxic payloads. ADCs have been defined as “magic bullets” or “biological missiles”, it can selectively deliver cytotoxic payload exclusively to tumor cells while sparing normal cells, make precise and efficient eradication of cancer cells.
Herein, we have conducted an atlas detailed the concept, composition, history and mechanism of action (MOA) of ADCs, and then emphatically introduced the molecular aspects of key elements of ADCs and the conjugation techniques by which influence the properties of ADCs. From a technical perspective, the key components of ADCs—antibodies, linkers, cytotoxic payloads, and conjugation methods—each significantly influence the physicochemical properties and clinical efficacy, and provided detailed elaboration on these given aspects. The efficacy and safety of ADCs strictly depend on their MOA. Consequently, it is esstional to carefully select and balance the various components in accordance with the biological characteristics of specific tumor types, which means there is no “one-size-fits-all” approach to ADC construction. Ongoing innovation, grounded in accumulated clinical experience, not only drive the ADC field toward its ultimate goal of providing precise medicines for patients, but also perpetually pioneers the expansion of this therapy into novel disease territories.
From sector perspective, research on ADCs began earlier in international markets, with leading companies such as Daiichi Sankyo, Pfizer, Seagen, AbbVie, Genentech, Roche, and ADC Therapeutics at the forefront. These corporations benefit from strong R&D platforms, sustained investment in research and development, extensive product pipelines, robust clinical development and trial capabilities, sophisticated commercialization systems, and strategic partnerships and acquisitions that position them for long-term success.
Compared to international giants, ADC research in China started relatively later but is now experiencing rapid growth. Over 100 companies are currently active in the field, including RemeGen, LaNova Medicines, DualityBio, MediLink Therapeutics, KELUN-BIOTECH, GeneQuantum, ALPHAMAB, Hengrui Pharma, BIO-THERA, CSPC, ProfoundBio, BeiGene, and others. Chinese ADC companies are primarily concentrated in geographical regions, with a diverse range of backgrounds in terms of company establishment. They are also highly active in the capital markets, with varying degrees of commercialization. Regarding R&D region, there has been a shift from the early attention on specific targets to more differentiated strategies. Companies are increasingly developing proprietary technology platforms with core competitive advantages, ensuring sustained growth.
Domestic universities and research institutes, leveraging their talent and resource strengths, have also made significant contributions to the advancement of the ADC. Notably, institutions such as Tsinghua University, Peking University, Peking Union Medical College, Fudan University, Zhejiang University, Nanjing University, Sun Yat-sen University, Xiamen University, and the Shanghai Institute of Materia Medica at the Chinese Academy of Sciences have made considerable contributions in ADC technological innovation. Chinese academic institutions engage in interdisciplinary research across multiple fields and are increasingly successful in translating academical research into practical applications. However, the stability of technical teams in universities can be a challenge, often leading to delays in the progress of projects. Additionally, incomplete patent portfolios and other factors hinder the commercialization of these advancements. Overall, the innovative research and technological progress made by these companies and academic institutions have not only driven industry development but also provided valuable insights and experience that will shape future applications and commercialization.
Building on the information presented, we have used the classic example of DS-8201a to illustrate the development process of traditional ADC. Confronted with multiple clinical challenges such as drug resistance, tumor heterogeneity and treatment-related adverse effects，several rising ADC formats have emerged, including multiple payload ADC, bispecific or biparatopic ADCs, immunostimulatory antibody conjugates, peptibody, antibody-oligonucleotide conjugates, antibody cell conjugates, conditionally active ADCs (also known as probody–drug conjugates) and protein-degrader ADCs, and each offers unique capabilities for tackling these various challenges and improves cancer treatments.
ADCs are a promising and rapidly evolving class of therapeutics with significant potential for cancer treatment. By combining the precision of targeted therapy with the potent efficacy of chemotherapy, ADCs represent a major advancement in oncology. However, challenges such as toxicity, tumor heterogeneity, and high treatment costs persist. Ongoing research and development are expected to enhance the safety, efficacy, and accessibility of ADCs, solidifying their role as a cornerstone of future cancer therapies. Moreover, the clinical applications of ADCs are beginning to expand beyond oncology, with promising developments in the treatment of other diseases, including autoimmune disorders.
Full text: Atlas of the antibody-drug conjugates
