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Pursuing new paths in targeted protein degradation drug development

Targeted protein degradation (TPD) therapy has grown rapidly as a field, with transformational potential. TPD is poised to be successful in delivering marketed products, but limitations are now starting to emerge, including tumour resistance, a lack of mechanisms for oral dosing, and the inability to penetrate tissues such as the CNS. Here, Ian Churcher, Chief Science Officer at Amphista, highlights opportunities and the need for new mechanisms to overcome these limitations, which are being addressed by the next generation of TPD development.

DRUG DEVELOPMENT based on targeted protein degradation (TPD) has progressed rapidly since the publication in 2015 of three landmark papers1-3 that highlighted important early-stage breakthroughs with drug-like molecules in this area of research. Since that time, the field has advanced to the point where there are now more than two dozen companies dedicated to working on the development of TPD drugs, some of which have advanced to later-stage clinical development. Additionally, several large pharmaceutical companies are very active in the field, including Merck and Bristol Myers Squibb, who have just partnered with us at Amphista, signalling wider recognition of the potential of this research to deliver a new generation of innovative drugs. The unique targeting properties of TPD therapies are acknowledged to have potential applications in a range of therapeutic indications that represent significant areas of unmet need in healthcare.