PhoreMost: Meet the Team – Rich Boyce, Senior VP Drug Discovery

When did you join PhoreMost, and what attracted you to the company?
Prior to joining PhoreMost, I worked in the medicinal chemistry space for over 20 years. I completed my post-doctoral studies as an organic chemist with Professor Steve Ley at the University of Cambridge before beginning my career as a medicinal chemist at Cambridge Combinatorial. Following its acquisition by Millennium Pharmaceuticals, I was the chemistry lead for several kinase inhibition programs in the oncology and inflammation disease areas. In 2003, I moved to Inpharmatica, where I worked on nuclear receptor drug discovery programs targeting metabolic diseases. I then spent three years as a medicinal chemistry consultant before joining Sentinel Oncology returning to work on kinase inhibitors to treat cancer.

It was here that I met Dr Chris Torrance, founder and Chair of PhoreMost, who later approached me to join PhoreMost to lead the small molecule drug discovery projects. I was excited by the SITESEEKER platform that had been developed to deliver interesting and novel therapeutic targets, and looked forward to the challenge of developing PROTEINi mini-protein hits into traditional small molecule drugs. Having gotten to know Chris personally while working on collaborative projects at Sentinel, I was confident that I had joined a company that was destined to carry out great science and would grow to be hugely successful.

How has the TPD space advanced in the last few years, and how is PhoreMost working to unlock the full potential of this crucial new tool?
The therapeutic approach of targeted protein degradation has gained more and more momentum over the recent years, with several heterobifunctional molecules now in human clinical trials, and some showing promising clinical results. Most assets hijack cereblon as the E3 ligase, and while there are many good things about using cereblon-based degraders, there are issues around potential resistance and toxicity, and the fact that cereblon simply doesn’t work to effectively degrade all therapeutic targets. The idea of expanding beyond cereblon has therefore been gaining huge amounts of interest more recently, and we at PhoreMost have an advanced collection of new functional E3 ligase ligands, discovered using our SITESEEKER platform, that we are progressing in the oncology and inflammatory disease space.

What differentiates PhoreMost from other companies working in the Targeted Protein Degradation space?
Using our unique and highly differentiated target ID approach, we are able to identify novel functional E3 ligases, which have now transitioned into heterobifunctional drug discovery and development. The next generation of screens has successfully identified tissue sparing and cancer selective E3 ligases, which has been a significant goal for the industry over recent years and sets us apart from many companies working in the targeted protein degradation field. Recent in vivo proof of concept degradation has demonstrated the power of the SITESEEKER platform to deliver high quality E3 ligases to move the field beyond Cereblon and Von Hippel Lindau (VHL) based degrader molecules, which are the mainstay of other degrader therapeutic portfolios.

Tell us more about the TPD Summit Europe you recently attended and presented at – what was the topic of your presentation?
The 4^th Annual Targeted Protein Degradation Europe meeting took place in London in March 2024, bringing together TPD professionals from across the world to explore novel degrader development. I presented a talk entitled “Bifunctional Degrader Discovery with PROTEINi Screening” where I outlined how our lead degrader programme was identified using the SITESEEKER platform, translated initially into small molecule binders of the novel E3 ligase and then into fully elaborated heterobifunctional degraders. These degraders have the capability to degrade a number of different proteins of interest and have appropriate drug properties to show efficacy in in vivo models of cancer.

What innovations or development do you think we will see in the TPD space in the next few years?
A new approach I think we will see emerging in the next few years is the rational design and discovery of molecular glues. Molecular glues enhance the affinity between proteins to induce a therapeutic effect, opening up new opportunities for drug development. However, discovery of new molecular glue degraders requires a highly systematic biology-led technology – a challenge PhoreMost is uniquely positioned to pursue. We recently adapted our discovery platform to enable molecular glue discovery, and are very excited about the progress we have made already in contributing to the advancement of this field.