Development, scale-up and manufacturing strategies to deliver novel antibody drug conjugates (ADCs)

Mersana Therapeutics is a clinical-stage biopharmaceutical company with an innovative and differentiated antibody drug conjugates (ADCs) pipeline that is built upon novel linker platforms such as Dolaflexin® and Dolasynthen that deliver proprietary auristatin-based payloads via the state-of-the-art bioconjugation strategies. The unique hydrophilicity of the Dolaflexin platform enables the engineering of ADC therapies with high drug to antibody ratios (DAR) with an enhanced therapeutic window for the treatment of multiple cancers. In addition to managing a relatively complex supply chain architecture against aggressive timelines for process development, scale-up and technology transfer activities, dedicated CMC efforts led to the successful completion of several at-scale cGMP campaigns for the synthesis and manufacturing of key process intermediates. In order to deliver robust manufacturing processes with well-defined process controls in-place, we have conducted thorough product and process risk assessments to identify the development gaps and areas of focus to further process understanding and characterization scope, leveraging synergies between synthetic chemistry, small molecule, antibody production, and bioconjugation processes. This presentation will provide an overview of Mersana’s novel ADC platform and discuss the QbD-based process development and scale-up strategies via case studies focusing on purification and separation unit ops.