Precisely targeting potent warheads to the tumor microenvironment
The Avacta pre|CISION® platform is a proprietary warhead delivery system based on a tumor-specific protease that is designed to concentrate highly potent warheads in the tumor microenvironment while sparing normal tissues.
Fibroblast activation protein-α (FAP) is an extracellular post-proline protease that is upregulated in many solid tumors 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|CISION® molecule has two key properties:
- It prevents the warhead from entering cells.
- It is specifically cleaved by FAP to release active warhead in the tumor.
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 tumors.
The first of the pre|CISION® molecules, AVA6000, has achieved clinical proof-of-concept.
- Download the ESMO conference poster
1st Gen – No spacer or PK extensions
AVA6000 (FAP-enabled doxorubicin)
> No PK extension: the half-life (t1/2) of first-gen compounds is 30-90 minutes, with extension of released warhead t1/2
> No spacer to modulate the kcat/Km (baseline is high efficiencykcat/Km)
Read more2nd Gen – Extended chemistry and increased half life
Enhanced plasma protein binding
> Alternate capping group with PEG links to enhance plasma protein binding and extend half-life of the preCISION® molecule (t1/2of hours in plasma)
> Self-immolativelinker allows additional warheadchemistry to link to the D-Ala-Pro peptide
Read more3rd Gen – Biologic Conjugate Drug
FAP-enabled MMAE with PEG Cap / Maleimide / Cysteine conjugation to Affimer®
> Capping group enables conjugation to biologics. This significantly extends half-life (t1/2 of days to weeks)
> Warhead is delivered intratumorally in a sustained release mechanism
Read moreWatch the video presentations from our R&D Spotlight Live Science Day event.
Discover pre|CISION® technology – watch the Mechanism of Action video below.
Explore our pipeline of pre|CISION® assets.