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:

  1. It prevents the warhead from entering cells.
  2. 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.

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)

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2nd 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

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3rd 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

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Watch the video presentations from our R&D Spotlight Live event.

Discover pre|CISION® technology – watch the Mechanism of Action video below.

Explore our pipeline of pre|CISION® assets.