Antibody–drug conjugates (ADCs) have become a major class of cancer biopharmaceuticals and traditional ADCs have a stochastic distribution of cytotoxic drugs linked across several different sites of the antibody. The heterogeneous nature of resulting stochastic ADCs can cause diminished efficacy and increased toxicity, thus limiting the corresponding therapeutic index. To improve on traditional ADC technology, we developed a novel chemical conjugation platform termed “AJICAP™” for the site-specific modification of native antibodies through the use of a class of IgG Fc-affinity reagents. Here we report the in vitro and in vivo activity of these resulting ADCs and assessed compared to the state-of-the-art ADC conjugation technology.<br/>Furthermore, we also report process optimization for the preparation of a “Gram-Scale” AJICAP™ conjugation batch by utilizing scale-down manufacturing and purification approaches. The minimum yield of each step was 91% and more than 1.4 g AJICAP™-ADC was synthesized to support the rodent safety studies. Toxicology studies revealed an enhancement of the maximum tolerated dose of AJICAP™-ADC, indicating an expansion of the comparative therapeutic index when compared to stochastic technology.<br/>These results presented herein indicate that AJICAP™ technology is an effective platform to enable next generation ADCs through the enhancement of dosing therapeutic index and this approach is amenable to relevant manufacturing production scales.

Process development and biological evaluation of antibody drug conjugate (ADC) based on a novel site-specific chemical conjugation platform

2019 Fall National Meeting

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