Next generation protein degrading technologies.

Using our extensive experience developing the basic understanding of TPD approaches, we have identified a number of completely novel approaches with potential to overcome some of the intrinsic limitations of current approaches to power the next generation of TPD medicines and bring new therapies to patients in a wide range of diseases.

Amphista’s degraders use a completely novel set of mechanisms which make use of a wider range of the body’s own innate protein degrading proteins instead of the very narrow set of ubiquitin E3 ligase-based mechanisms used by most other TPD companies (for example degraders based on recruiting the ubiquitin E3 ligase proteins VHL and cereblon).

Our unique approach

The field of targeted protein degradation offers many opportunities to develop exciting new drugs for a range of diseases, but limitations to current TPD strategies are now starting to appear, driving a need for improved approaches. We achieve degradation using an expanded set of UPS proteins which can include deubiquitinases (DUBs), members of Cullin RING Ligase complexes (CRLs) and the proteasome itself. Our unique approaches give us new ways to tackle known limitations of TPD approaches. Potential advantages of our approach include:

1

Efficient degradation

Allowing the efficient degradation of a broad range of disease-causing proteins from within a wider range of cells throughout the body compared to existing TPD approaches which often work poorly in many cells.
2

Improved druglike properties

Allowing the design of degrading molecules with improved druglike properties including the ability to be orally active as well as being able to enter the brain for use in neurological disorders.
3

Lower resistance risk

Our unique mechanisms mean our approach has a lower risk of tumours developing resistance to Amphista degraders relative to other degradation approaches where innate and acquired resistance is a significant issue.