ADC Cascade - Abzena

ADC Cascade: a new clinically based approach to development

ADC Cascade and Biologics Cascade are ex-vivo platform approaches allow efficacy and safety studies against clinically characterized on and off-target tissues.

Clinical failure of ADCs and biologics remain high, and candidate lead selection is associated with significant risk for translation into clinical development. Pre-clinical testing evaluates target expression and toxicity in animal models but does not optimally link human tissue with clinical history and potential binding to healthy tissue, which may predict safety issues.

There is an opportunity to improve this approach. The patient population expressing the target of interest can be defined, and safety liabilities assessed, prior to candidate nomination.

ADC and Biologics Cascade is a new approach to ADC and biologics development, with a clinically oriented focus on the early design and developability of lead candidates. Abzena already has market leading developability and conjugation chemistry services and has now established a collaboration with a leading global provider of high-quality biological specimens to allow access to their 175,000 clinically characterized human tissue samples. Abzena’s Cascades will:

  1. Augment target validation with biobank derived patient tissues to identify relevant patient subgroups
  2. Enhance lead selection through rational design and cascade approach to evaluate linker and payload (or other conjugated moiety such as RNA) combinations. These can be bound to clinically characterized on and off-target tissues.
  3. Candidate selection can include augmented ex-vivo safety and efficacy profiles.

Abzena Solution ADC Cascade

  • 175,000 very well clinically characterized tissues / fluids
  • Select samples of interest (avoid single site academic tissue bias)
    • Presence of target in disease and absence normal tissues (local and remote)
    • Confirm binding of ADC or Mab
  • Select lead candidate of interest
  • Use toolbox and conjugation expertise to create range of Antibody or peptide linker/payload combinations
  • Then test these conjugates maximal binding to target on diseased tissue and minimal binding to normal tissues

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