Date: 2016-04-20
Type of information: Initiation of preclinical development
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Emergent BioSolutions (USA - MD) Aptevo Therapeutics (USA - MD)
Product: ES425
Action
mechanism: immunotherapy product/bispecific protein. ES425 is a bispecific immunotherapeutic protein that redirects T-cell cytotoxicity to tumor cells expressing ROR1 (receptor tyrosine kinase-like orphan receptor 1), an oncofetal antigen expressed on TNBC and other solid tumor and hematologic malignancies. ES425 has bee developed using the ADAPTIR platform technology. ADAPTIR bispecific proteins are modular, single chain polypeptides that are comprised of two separate binding domains, a hinge segment, and an effector domain. They have a differentiated structure from monoclonal antibodies and can generate a unique signaling response. Some ADAPTIR molecules may mediate T-cell cytotoxicity by redirecting T cells against tumor cells and some by targeted cytokine delivery. In addition, other ADAPTIR proteins may mediate complement dependent cytotoxicity and Fc dependent cytotoxicity, similar to monoclonal antibodies.
Disease: triple-negative breast cancer (TNBC)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 20, 2016, Emergent BioSolutions announced that it presented preclinical data on its bispecific ADAPTIR™ (modular protein technology) molecule, ES425, at the American Association for Cancer Research Annual Meeting in New Orleans, Louisiana. The ES425 molecule is being developed as a potential therapeutic for triple-negative breast cancer (TNBC). This product candidate was constructed using the ADAPTIR platform technology and will be further developed by Emergent’s planned spin-off company Aptevo Therapeutics.
ES425 is a bispecific immunotherapeutic protein that redirects T-cell cytotoxicity to tumor cells expressing ROR1 (receptor tyrosine kinase-like orphan receptor 1), an oncofetal antigen expressed on TNBC and other solid tumor and hematologic malignancies.
The presentation, “Anti-ROR1 x Anti-CD3 ADAPTIR™ Molecule, ES425, Redirects T-Cell Cytotoxicity and Inhibits Tumor Growth in Preclinical Models of Triple-Negative Breast Cancer,” shared results of preclinical studies examining in vitro and in vivo activity of ES425. Results showed that ES425 efficiently redirected T-cell cytotoxicity against ROR1(+) cell lines at low picomolar concentrations in vitro. T cells were activated and proliferated in response to ES425 in the presence of ROR1(+) target cells. In vivo, pharmacokinetic analysis showed inhibition of tumor growth and an improvement in overall survival in preclinical models of TNBC.
