pre|CISIONTM drug conjugate (PDC)

 

The warhead is linked to a peptide specifically cleaved by fibroblast activation protein-α (FAP), thus releasing the warhead in the extracellular space of the TME.

The Avacta pre|CISIONTM platform is a proprietary warhead delivery system based on a tumour-specific protease that is designed to concentrate highly potent warheads in the tumour microenvironment while sparing normal tissues.

Fibroblast activation protein α (FAP) is an extracellular post-proline protease that is upregulated in many solid tumours in a membrane-bound form on cancer associated fibroblasts as well as tumour cells. FAP activity is also observed as a soluble protease to a low degree in plasma.

AVA6000 is the first clinical-stage pre|CISIONTM drug. It is a peptide drug conjugate that leverages the tumour-specific expression of FAP to target the release of doxorubicin to tumour tissue.  It has two key properties:

  1. It prevents doxorubicin from entering cells.
  2. It is specifically cleaved by FAP to release active doxorubicin in the tumour.

 

Peptide Drug Conjugates – Multiple advantages over traditional ADC

 

 

pre|CISIONTM can be utilised in multiple drug formats:

pre|CISION peptide drug conjugate (PDC)

The warhead is linked to a peptide specifically cleaved by FAP which prevents cell entry until released by FAP in the extracellular TME. t1/2: mins to hours

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pre|CISION+ half-life optimised conjugate

The peptide-warhead conjugate is linked to the Fc region, producing a pre|CISIONTM molecule with prolonged half-life and DAR~10. t1/2: ~hours – days

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pre|CISION ADC drug conjugate (AffDC)

The peptide-warhead conjugate is linked  to a tumour antigen-targeted monoclonal antibody or Affimer®, creating a highly tumour-specific ADC. t1/2: ~days – weeks

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