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ADC (Antibody-Drug Conjugates)

ADC is a targeted anti-cancer drug designed to induce tumor cell death after being selectively internalized in the tumor cell and released potent cytotoxic payloads with less toxicity in normal cells or blood vessels.

The importance of ADC linker

ADC linker determines the chemical structure, ease of CMC, PK property (stability) and TI of ADCs.

  • When conjugated to Ab, payloads are generally not active and their PK property depends on Ab.
  • After released from Ab, payloads become active to work as therapeutics or toxins
  • The time and space of payload releasing are very important for the value of ADC therapeutics

AbClick® : Principles of Site-selective Ab Conjugation

AbTis cyclic peptide (AbClick®) tightly binds to the IgG Fc domain. K248 ε-amine and the carbonyl group in AbClick® are in a proximity to undergo an amide bond formation reaction. The site selectivity depends on the reactivity of carbonyl group: react with amine mainly in a pseudo first order type.

AbClick® : Application

AbClick® has two different types of technologies: AbClick® Standard & AbClick® Pro

  • AbClick® Standard reduces the FcRn binding affinity, which can decrease the half-life of the antibody, while AbClick® Pro allows to maintain the inherent half-life of the antibody. 
  • By adjusting the half-life of the antibody, AbClick® Standard can be used for companion diagnostics of tumor and RIT(radio-immunotherapy) due to short half-life whereas AbClick® Pro is applicable to treat solid tumors due to its long half-life.

AbClick® : Core Competency

Site-selective Conjugation to Unmodified Ab with a Defined DAR

   - Metabolically stable isopeptide bond to Lys248 only

   - Simple process with high yield (advantages of CMC)

Available to adjust PK Property of ADC Products

   - Available to prepare therapeutics with a short or long biological half-life when necessary

   - Short half-life is a big advantage for companion diagnostics using in vivo radio imaging

Diversity of Payloads

   - Drug antibody ratio control (2, 4, 6, 8)

   - Diverse payloads / in vivo diagnostics

Stable in Serum

   - Stable in serum but release payload through enzyme action mainly in cancer cells