ADC Franchise page edits 12 2017
Investigational ADC Franchise
The investigational Antibody Drug Conjugate (ADC) Franchise of the Daiichi Sankyo Cancer Enterprise is built around our proprietary DXd ADC technology, which is being researched across multiple types of cancer. Our proprietary linker and payload technologies have been specifically designed to potentially address various limitations of two critical components of an ADC: the payload and linker.
Daiichi Sankyo Proprietary DXd ADC Technology
ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy directly to cancer cells. An ADC consists of three components:
1) a monoclonal antibody
2) a cytotoxic chemotherapy payload
3) a linker that joins the two together
Using expertise in both protein engineering and medicinal chemistry, our team of exceptional scientists has methodically designed our proprietary DXd ADC technology to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way that chemotherapy is commonly delivered. The cornerstone of our investigational ADC Franchise is a proprietary payload and linker-payload technology, which consists of:
- Payload: DXd, an investigational novel topoisomerase I inhibitor
- Linker: A proprietary tetrapeptide-based linker that joins the antibody and payload together, and is designed to be broken down by lysosomal enzymes such as cathepsins, which are highly expressed in tumor cells
Our investigational ADC Franchise currently consists of seven novel ADCs, including [fam-] trastuzumab deruxtecan (DS-8201) in pivotal phase 2 and 3 clinical development; U3-1402 in phase 1/2 clinical development, DS-1062 in phase 1 development; DS-7300, DS-6157 and DS-6000 in preclinical development; and TA-MUC1 in discovery.
We are open to partnership opportunities with external companies to combine our linker-payload technology with other monoclonal antibodies as well as collaborations with other compounds to study in combination with our ADC assets.
These are investigational agents and have not been approved by the FDA or any other worldwide regulatory agency as a treatment for any indication. Safety and efficacy have not been established.
Antibody Drug Conjugate (ADC) Franchise
|[Fam-]Trastuzumab Deruxtecan (DS-8201):
[Fam-] trastuzumab deruxtecan (DS-8201) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise.
In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize [fam-] trastuzumab deruxtecan as a medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.
A broad and comprehensive clinical development program is currently underway with [fam-] trastuzumab deruxtecan, including five pivotal trials:
Phase 3 Clinical Studies
•DESTINY-Breast04: [Fam-] trastuzumab deruxtecan versus investigator’s choice in patients with HER2 low, unresectable and/or metastatic breast cancer previously treated with one to two prior lines of chemotherapy (US, EU, Japan and Asia)
•DESTINY-Breast03 – [Fam-] trastuzumab deruxtecan versus ado-trastuzumab emtasine (T-DM1) in HER2 positive unresectable and/or metastatic brest cancer previously treated with trastuzumab and a taxane (US, EU, Japan and Asia)
• DESTINY-Breast02 – [Fam-] trastuzumab deruxtecan versus investigators’s choice in HER2 positive unresectable and/or metastatic breast cancer previously treated with standard of care HER2 therapies includng T-DM1 (US, EU, Japan and Asia)
Pivotal Phase 2 Clinical Studies
• DESTINY-Breast01 – [Fam-] trastuzumab deruxtecan for HER2 positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (US, EU, Japan and Asia)
Phase 2 Clinical Studies
Phase 1 Clinical Studies
• Breast and Bladder Cancers: [Fam-] trastuzumab deruxtecan in combination with nivolumab in HER2 expressing breast and bladder cancers in the US and EU
[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA).
[Fam-] trastuzumab deruxtecan has also been granted SAKIGAKE Designation by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer.
U3-1402 is an investigational and potential first-in-class HER3 targeting ADC currently in phase 1/2 development for HER3 expressing metastatic or unresectable breast cancer in the US and Japan and phase 1 development for metastatic or unresectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer in the U.S.
DS-1062 is an investigational TROP2 targeting ADC currently in phase 1 development for unresectable advanced non-small cell lung cancer in the US and Japan.