Unlocking the potential of ADCs
Cancer continues to be a leading cause of death, and there is an unmet need for additional treatment options.1-3 Antibody drug conjugates, or ADCs, are a fast-evolving class of agents being studied in oncology therapy.2-6 ADCs have the potential to deliver potent cytotoxic therapy directly to tumor cells, while reducing systemic exposure to this payload.3,4,7
Optimizing the 3 components of ADCs
ADCs contain 3 components: An antibody, a linker, and a payload. Depending on their characteristics, these 3 components may influence the ADC’s ability to safely deliver potent therapy to cancer cells.3,5-7
DXd ADC Technology
Linker
The tumor cell internalizes the ADC and cleaves the linker, releasing the payload.5,6 The linker*
- Is plasma-stable to ensure minimal release of payload in circulation3,7
- Is a tumor-selective cleavable linker, cleaved by lysosomal enzymes typically upregulated in tumor cells, promoting delivery of a potent payload to cancer cells5,7
*The clinical relevance of these features is still under investigation.
DXd ADC Technology
Payload
Linker cleavage releases payload into the tumor cell and leads to tumor cell death.5,6 The payload*
- Is potent and cytotoxic to induce tumor cell death2,4,6
- Has a short half-life3,6,†
- Is cell-membrane permeable, enabling a bystander antitumor effect. After ADC internalization and linker cleavage, the released payload results in elimination of both target and neighboring cells present in the tumor microenvironment3
*The clinical relevance of these
features is still under investigation.
†Based on animal studies.
Antibody
The antibody component directs the ADC to cell-surface antigens highly upregulated in tumor cells.5,6 The antibody
- Is tumor-selective, binding to antigens highly expressed in tumor cells, allowing more targeted delivery of the payload1,6
DXd ADC Technology is connected to a monoclonal antibody for a tumor-selective antigen.1,5,6
Unlocking the potential of ADCs
Cancer continues to be a leading cause of death, and there is an unmet need for additional treatment options.1-3 Antibody drug conjugates, or ADCs, are a fast-evolving class of agents being studied in oncology therapy.2-6 ADCs have the potential to deliver potent cytotoxic therapy directly to tumor cells, while reducing systemic exposure to this payload.3,4,7
Optimizing the 3 components of ADCs
ADCs contain 3 components: An antibody, a linker, and a payload. Depending on their characteristics, these 3 components may influence the ADC’s ability to safely deliver potent therapy to cancer cells.3,5-7
DXd ADC Technology
Linker
The tumor cell internalizes the ADC and cleaves the linker, releasing the payload.5,6 The linker*
- Is plasma-stable to ensure minimal release of payload in circulation3,7
- Is a tumor-selective cleavable linker, cleaved by lysosomal enzymes typically upregulated in tumor cells, promoting delivery of a potent payload to cancer cells5,7
*The clinical relevance of these features is still under investigation.
DXd ADC Technology
Payload
Linker cleavage releases payload into the tumor cell and leads to tumor cell death.5,6 The payload*
- Is potent and cytotoxic to induce tumor cell death2,4,6
- Has a short half-life3,6,†
- Is cell-membrane permeable, enabling a bystander antitumor effect. After ADC internalization and linker cleavage, the released payload results in elimination of both target and neighboring cells present in the tumor microenvironment3
*The clinical relevance of these
features is still under investigation.
†Based on animal studies.
Antibody
The antibody component directs the ADC to cell-surface antigens highly upregulated in tumor cells.5,6 The antibody
- Is tumor-selective, binding to antigens highly expressed in tumor cells, allowing more targeted delivery of the payload1,6
DXd ADC Technology is connected to a monoclonal antibody for a tumor-selective antigen.1,5,6
Striving to create optimized ADC technology
At Daiichi Sankyo we strive to create optimized ADCs. Our DXd ADC Technology, found in all our DXd ADCs, has 7 key attributes.8,*
An optimized drug-to-antibody ratio
A plasma-stable linker-payload
A tumor-selective cleavable linker
A topoisomerase I inhibitor payload
A highly potent payload
A payload with a short systemic half-life†
A bystander antitumor effect
*The clinical relevance of these features is still
under investigation.
†Based on animal studies.
With our DXd ADC Technology, we strive to meet new challenges with continuous innovation.
Explore the science
Watch our videos that dive into the proposed mechanism of action of our DXd ADC Technology, as well as a video series from our leadership on the development of DXd ADC Technology.
Advancing Drug Capabilities
4:48
We delve into the components of an antibody drug conjugate and the unique characteristics of our proprietary DXd ADC Technology.
How Daiichi Sankyo’s DXd ADCs Came to Be
4:34
Toshinori Agatsuma, Executive Officer, Head of Research, and Yuki Abe, VP of Research Innovation Planning discuss the process of thoughtful questioning that led to the development of a groundbreaking ADC platform.
Discover the Design Behind DXd Antibody Drug Conjugates (ADCs)
2:15
Mark Rutstein, Global Head of Oncology Clinical Development, discusses the linker-payload, the core of Daiichi Sankyo’s DXd ADC Technology. He discusses how the traits of DXd ADC Technology aim to help patients with unmet medical needs.
Looking Towards the Future of Oncology
2:30
Ken Keller, Global Head of the Oncology Business, explores the organization’s goals with DXd ADC Technology and how Daiichi Sankyo seeks to go beyond making incremental differences, by striving to create new standards of care for people with cancer around the world.
Discover
DXd ADCs
Visit our website to learn more about our investigational products, such as DXd ADCs, that seek to provide hope for patients with unmet medical needs.
References: 1. Lucas AT, Moody A, Schorzman AN, Zamboni WC. Importance and considerations of antibody engineering in antibody-drug conjugates development from a clinical pharmacologist’s perspective. Antibodies (Basel). 2021;10(3):30. doi:10.3390/antib10030030 2. Baah S, Laws M, Rahman KM. Antibody-drug conjugates—a tutorial review. Molecules. 2021;26(10):2943. doi:10.3390/molecules26102943 3. Tarantino P, Ricciuti B, Pradhan SM, Tolaney SM. Optimizing the safety of antibody-drug conjugates for patients with solid tumours. Nat Rev Clin Oncol. 2023;20(8):558-576. doi:10.1038/s41571-023-00783-w 4. Makawita S, Meric-Bernstam F. Antibody-drug conjugates: patient and treatment selection. Am Soc Clin Oncol Educ Book. 2020;40:1-10. doi:10.1200/EDBK_280775 5. Liao MZ, Lu D, Kågedal M, et al. Model-informed therapeutic dose optimization strategies for antibody-drug conjugates in oncology: what can we learn from US Food and Drug Administration-approved antibody-drug conjugates? Clin Pharmacol Ther. 2021;110(5):1216-1230. doi:10.1002/cpt.2278 6. Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-drug conjugates: a comprehensive review. Mol Cancer Res. 2020;18(1):3-19. doi:10.1158/1541-7786.MCR-19-0582 7. Rosner S, Valdivia A, Hoe HJ, et al. Antibody-drug conjugates for lung cancer: payloads and progress. Am Soc Clin Oncol Educ Book. 2023;43:e389968. doi:10.1200/EDBK_389968 8. Data on file. 2023.
This information reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products have not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
