Research boost to find treatments for 'undruggable' cancers

A research team at the University of Bath, in collaboration with biotechnology company Sapience Therapeutics, is redoubling its efforts to discover new peptide-based treatments capable of acting upon 'undruggable' targets in cancer cells.

Some cancers are notoriously resistant to treatment – it is these tumours that are the focus of the ongoing collaboration between Sapience and scientists at the Department of Biology & Biochemistry. The drug-discovery project between the two organisations began in 2018 and is now extending for another two to three years.

Discovering new peptide-based treatments to target 'undruggable' cancer cells.

Professor Jody Mason, who leads the Bath team, said: “In the first phase of our collaboration with Sapience, we generated a number of hits against high mortality cancer targets, with several of these peptides now being progressed towards clinical trials.”

Professor Mason has spent the past two decades developing and refining approaches to screen vast libraries of peptides (short chains of amino acids – the building blocks of proteins), identifying those that show the greatest promise at blocking key players within the disease, and learning more about the characteristics of these peptides.

Professor Mason is particularly interested in drug candidates that target specific interactions, known as protein-protein interactions. These interactions can be responsible either for making cells cancerous or for dampening the immune response to tumours. The proteins involved in these interactions are generally hard to treat because they lack the deep binding pockets needed for small molecule drugs to cling to. Also, they are often located inside the cell, making them difficult to treat with larger molecules, such as monoclonal antibodies used in immunotherapy.

The Bath-Sapience project is now geared towards producing new peptides that can both disrupt specific protein-protein interactions and penetrate cancer cells in order to do so.

Professor Mason said: “Protein-protein interactions represent a class of drug target conventionally considered undruggable using small-molecule approaches. We're incredibly excited by the prospect of targeting previously undruggable oncogenic protein-protein interactions with peptide-based therapeutics.”

He added: “During our initial collaboration with Sapience, we identified six promising peptides, each of which binds to a different protein target implicated in cancers that are difficult to treat. I'm delighted to be continuing with our ambitious discovery program and am looking forward to identifying new and interesting molecules.”

Dr Barry Kappel, founder and chief executive officer of Sapience Therapeutics, said: “The continuation of this drug discovery partnership with Professor Jody Mason and the University of Bath speaks to the success of our initial two-year collaboration. Although separated by distance, our teams have worked seamlessly with one another to produce promising peptide 'hits' to several important therapeutic targets within the cancer cell. The next phase of this joint effort will focus on the characterization and development of these hits into lead compounds as well as the discovery of new hits against additional promising cancer targets.”

Under the terms of the agreement, Sapience will have exclusive rights to the development and commercialisation of any novel compounds arising from this research. For molecules developed under the agreement, the University of Bath will receive milestone payments associated with clinical development and a royalty on future commercial sales.

Source: University of Bath