About Amphista

Amphista Therapeutics is the leading Europe-based targeted protein degradation (TPD) company. Our scientific team, which includes leading academic and drug discovery pioneers from the TPD field, has developed several completely novel mechanisms to remove disease-causing proteins from within cells.

We have shown these novel mechanisms have potential to overcome many of the limitations seen with current TPD approaches, and to deliver transformational medicines to treat a wide range of disease.

Targeted Protein Degradation.

The targeted protein degradation (TPD) approach offers a greatly improved way of treating disease, and modulating drug targets, using synthetic small molecule degraders.

Our degraders are bifunctional, or two-headed, molecules. One end is designed to selectively bind to the specific, disease-causing proteins we want to degrade while the other end binds to proteins involved in cellular protein degradation so our molecules act as magnets to attract the desired proteins to be degraded. We call our protein degrading drugs, Amphistas.

Most drug molecules transiently inhibit a single function of a disease-causing protein but TPD degraders can remove the target proteins from within cells completely. This provides much more complete and durable inhibition of biological pathways leading to more effective control of disease processes.

Effectively retrain and redirect

Degraders generate their effects through hijacking the cellular waste disposal process active within all human cells, known as the ubiquitin-proteasome system (UPS). During normal disease progression, pathogenic proteins are removed from cells inefficiently or not at all, allowing them to continue to drive undesired cellular processes which ultimately lead to illness.

TPD drugs however, effectively retrain and redirect the cellular waste disposal processes to actively seek out these disease-causing proteins, leading to their rapid and complete removal from the body.

TPD approaches offer many advantages over other drug modalities

TPD Degraders function by bringing a disease-causing target protein and a UPS protein (frequently one of a family of E3 ubiquitin ligases proteins) into close proximity within cells allowing the target to be tagged with a marker, ubiquitin (Ub), which flags it to be subsequently destroyed by the cell’s waste recycling centre, the proteasome. Due to their unique mode of action, TPD approaches offer many advantages over other drug modalities including small molecule inhibitors, monoclonal antibodies or oligonucleotide-based RNAi approaches as summarised below.

Traditional Small Molecules
Antibodies
Oligos
Targetted Small Molecule Protein Degraders
Undruggable Targets
(scaffolding, multiple funct.)
Intracellular Targets
(enzymatic activity)
Elimination
of target protein
Systemic
exposure
Oral
Catalytic
Efficient

One powerful characteristic of protein degrading drugs is their ability to act as highly efficient catalysts to accelerate the desired degradation processes within cells. This means very low doses and concentrations of active drug can deliver potent biological effects efficiently. Few other drug treatment approaches share this catalytic mode of action, allowing TPD molecules including Amphista degraders to deliver therapeutic effects impossible with other approaches.

TPD drugs therefore offer many transformational opportunities to develop new medicines though some limitations are now beginning to appear which may slow their clinical progress. Amphista focuses on maximising these opportunities while directly addressing and overcoming the limitations using our next generation TPD approaches.

Why Amphista?

Amphista takes its name from the mythical two-headed serpent the Amphisbaena (also known as an Amphista). In ancient times, Amphisbaenae were said to possess many health-giving properties.

Career Opportunities

We seek exceptional and visionary scientists to join our team working on a cutting-edge therapeutic modality focused on bringing much needed new medicines to patients with life-changing diseases.

Amphista is searching for innovative, and highly motivated individuals who enjoy teamwork and are comfortable working in a fast-paced entrepreneurial environment.

If you feel that your skills and experience are aligned to the opportunities posted, please e-mail your CV directly to recruitment@amphista.com, including the position title in the subject line of your email.