XMT-1522 and XMT-1536 are antibody drug conjugates (ADCs) in Phase 1 clinical trials that target cancer cells containing HER2 and NaPi2b antigens, respectively.  These ADCs are comprised of a novel linker platform, Dolaflexin, in which 10-15 auristatin F-hydroxypropylamide (AF-HPA) payload molecules are bound to the antibody via a polymer backbone.  The hydrophilicity of the Dolaflexin polymer allows for the high drug to antibody ratio (DAR) while maintaining antibody pharmacokinetics and drug-like properties of the ADC.  The Dolaflexin platform has inherent heterogeneity that can be minimized and controlled to provide critical quality attributes, which have led to good batch-to-batch reproducibility.  The conjugation of Dolaflexin to the antibody has controls in place to produce ADCs with defined and consistent key quality attributes.  The process development and controls of Dolaflexin based ADCs having high DAR ratios will be discussed.<br/>

Development and manufacturing of high DAR (10-15) ADCs utilizing the Dolaflexin® platform

256th National Meeting (2018)

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