The Optimization and Selection Strategies of ADC

1. The Optimization and Selection Strategies of ADC https://www.creative-biolabs.com/adc

2. PART ONE What is ADC

3. 01 What is ADC? • ADC (antibody-drug conjugate) is a compound molecule consisting of an antibody that is linked to a bioactive cytotoxicity (anti-cancer agent) payload or drug. Antibody-drug conjugates are currently a major research field, mainly focused on oncology, but in other areas such as infectious diseases are also limited. The success of this targeted drug delivery depends on many factors, one of which is the performance of the linker to release the active drug moiety under appropriate conditions.

4. ADCs are mandatory to improve the homogeneity and developability of the antibody to reduce the churn rate of drug candidates. Liquid chromatography, electrophoresis and mass spectrometry analysis technology, not only help to choose the best antibody with appropriate glycosylation characteristics of cloning, but also can be used for research and overall structure identification of a potential clinical candidate. Moreover, it can identify possibly harmful antibodies to the stability and pharmacokinetic properties. Mass spectrometry also helps to optimize the structure of the next generation mAb from a pharmaceutical perspective, allowing for the development of reduced CMC loads and better drug candidates (OptimAb) and ADC (OptimADC).

5. 02 The selection of antibodies 2 3 1 chimerism human antibody anthropogenic

6. 02 The selection of antibodies The second generation ADCs all are controlled mixtures of different drug load substances, with typical average DAR of 3.5 or 4. Species with DAR greater than 4 indicate lower tolerance, higher plasma clearance, and lower body efficacy. At present most ADCs have common structural features, such as the formation of thio-succinylamide connections through the maleimide reaction of sulphide and alkyl .

7. conjugation in chemistry But mostly a long time of ADC circulation will lead to the elimination of measurable maleic imide, which can be addressed by site-specific conjugation and alternative conjugation in chemistry: such as cysteine engineering, unnatural amino acids, enzyme auxiliary connections, to avoid the disintegration of retro - Michael and high payload ADC.

8. The development of ADC benefits from the general improvements in the design of therapeutic mAb, as well as specific improvements to the enhanced homogeneity of conjugated composition methods. PART TWO

9. 02 ADC linker The diversification of ADC linker and payload provides new opportunities for improving drug transport in tumors, as well as reducing exposure to normal tissue. In fact, it is important to better understand ADC's toxic determinants, whether as a single drug or in combination with other therapies. To increase the therapeutic index, ADC needs to reduce the minimum effective dose in the efficacy of cytotoxic agents, or increase the maximum tolerable dose in tumor selectivity.

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