PNU anthracycline payload
NBE-Therapeutics' highly-potent anthracycline-based toxin platform
Many of the ADCs currently in clinical development, including the FDA-approved ADC products, Adcetris® and Kadcyla®, comprise tubulin-polymerization inhibiting toxins. Due to the abundance of the cellular target tubulin, these drugs need to internalize into the cytoplasm of cells at relatively high concentrations, and cancer targets expressed a low levels cannot be addressed with such tubulin-targeting ADCs. Therefore, ADCs based on more potent, particularly DNA-damaging and intercalating toxins, such as pyrrolo-benzodiazepines (PBDs) or duocarmycines are currently in development.
NBE-Therapeutics has developed its own DNA-targeting, highly potent toxin platform based on the PNU anthracycline payload, related to the established cancer drug doxorubicine. The PNU anthracycline payload is about 3 logs more potent than tubulin-targeting ADC payloads, and thus requires a highly stable linker to covalently attach it to the antibody. Using NBE-Therapeutics' SMAC-TechnologyTM, best-in-class serum stability is achieved, while at the same time maintaining high potency of ADCs with this toxin. Furthermore, unlike tubulin-polymerization inhibitors and other payloads, the PNU anthracycline payload is not a substrate for the multidrug resistance pump P-gp, further underscoring the attractiveness of NBE's payload platform.
- Highly-potent anthracycline based DNA-alkylating toxin platform
- High serum stability of SMAC-TechnologyTM manufactured ADCs
- Toxin is not a substrate for P-gp multidrug efflux pump
- Low toxicity of ADCs at dose levels showing high efficacy in mouse tumor models