pre|CISIONTM
Concentrating highly potent warheads in the tumour microenvironment
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.
A pre|CISIONTM molecule has two key properties:
- It prevents the warhead from entering cells.
- It is specifically cleaved by FAP to release active warhead in the tumour.
The peptide moiety linker, pre|CISION™, prevents cellular entry of the warhead unless it is cleaved by FAP, thus enabling targeted delivery of the warhead to tumours.
The first of the pre|CISION molecules, AVA6000, has achieved clinical proof-of-concept.
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
Read morepre|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
Read morepre|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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