PharmTech: Advancing ADCs to the Next Level

Featured Contributor: Nicolas Camper, Senior Director of Bioconjugation Chemistry

Following a long road to success with antibody-drug conjugates (ADCs), developers today are seeing regulatory approvals for ADCs as a more common occurrence. Better success in the current environment is largely due to technology improvements that have helped minimize risk and enhance therapeutic efficacy for these complicated drugs. However, the manufacturing of ADCs remains a complex process, involving requirements for both the large-molecule and small-molecule components. The linker technology joining the two pieces also has its own requirements. Because of their manufacturing complexity, ADC development and production increasingly require outsourcing services.

“There have been a lot of new developments in terms of conjugation and linker technologies,” says Nicolas Camper, Senior Director, Bioconjugation, at Abzena. “There is a definitive move towards site-specific conjugation technologies and away from stochastic conjugation approaches that allows us to prepare better-defined antibody-drug conjugates,” he says.

Camper also points out another new development that he’s observed over the past few years, which is that linker technology is becoming more sophisticated. “Quite often, when you conjugate cytotoxic drugs, they are quite hydrophobic, and that can impact the performance of your ADC. So, there has been a lot of effort put into developing more hydrophilic linkers,” he explains.

Another noticeable advancement has been in the development of branch linkers. These branch linkers give some options for preparing the ADC and modulating the drug loading. “That is something relatively new and should have an impact on the performance of ADCs and ultimately result in better ADCs and more programs,” he says.

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