2023, PhoreMost’s year of Drugging the Undruggable®

20th December 2023

It has been a year of significant progress for PhoreMost across target finding and drug discovery operations, with some major scientific milestones reached. Building on our SITESEEKER® phenotypic target discovery platform, we have now also established a pipeline of novel degrader-focussed drug discovery programmes and continue to collaborate broadly across pharma and biotech. Here, our CEO, Neil Torbett, gives an overview of the Company’s progress and looks ahead to what lies in store for 2024.

Target Discovery Alliance Success
PhoreMost had an excellent start to the year with the announcement that we achieved a significant milestone within our target discovery alliance with Boehringer Ingelheim. Our other target discovery partnerships across diverse therapeutic areas continue to make excellent progress, and we look forward to making further milestone announcements on these, together with new partnership deals, in the coming year.

Internally, PhoreMost is dedicated to applying its SITESEEKER® technology towards the discovery and development of ‘next-generation’ degrader therapeutics.

Degradation-based therapies, such as bifunctional small molecules, are becoming an integral approach to tackling previously undruggable targets. They act by recruiting an E3 ligase to destroy (rather than inhibit) a therapeutic protein of interest (POI) and hold many advantages over traditional modalities. Despite there being over 600 E3 ligases, clinical stage degraders are predominatly reliant on using just a single ligase, Cereblon. At PhoreMost, we are changing this key limitation.

We have deployed our SITESEEKER® technology towards the discovery of functionally active ‘degrader’ PROTEINi® which operate through a wide variety of E3 ligases to degrade recruitable POIs. From these insights, we have now successfully developed small molecule ligands to a number of unprecedented E3 ligases, and further optimised these through to bifunctional degraders.

Our novel E3 ligase-based degraders are poised to unlock ‘undruggable’ targets.
We are tremendously excited about the therapeutic opportunities that our novel ligase-based degraders will bring, in terms of target scope, safety, and overcoming resistance to first generation therapeutics. We plan to move several degrader assets towards preclinical development over the coming year.

Our unique SITESEEKER®-based approach to discover and translate novel mechanisms of targeted protein degradation is now focussed towards identifying selective degrader mechanisms. Here, we are interested in progressing cancer-selective ligases arising from our platform, in addition to identifying the optimal ligases to degrade high value targets. This is an important opportunity that our platform is systematically addressing.

Team PhoreMost
The progress we have made throughout 2023 would not have been possible without the dedication and inspiration of our incredible team. We are very proud of our science-focussed, vibrant, and caring culture. Working hard and having fun has been the theme of 2023, and we are committed to ensuring PhoreMost continues to be a Great Place to Work.

We also remain ever conscious of the environmental impact of our scientific endeavours, and continue to participate in the Furthr carbon offsetting schemes alongside a host of other measures which have led to us gaining the National Union of Students Platinum Green Impact Award.

In support of our continued growth, we have strengthened our leadership team over the past year by making some key executive appointments with Dr Charli Batley and Dr Rich Boyce being promoted to COO and Senior VP of Drug Discovery respectively. We have also bolstered our SAB with the appointments of Prof Peter Parker and Dr Jason Imbriglio; who join our existing members, Dr Simon Cook, Dr Lorenz Mayr, and Dr Catherine Beech.

Externally, we continue our strong participation at major international targeted protein degradation conferences, and have also been recognised through nominations for key industry awards including the MSD’s Innovation Award at the SCRIP Awards, Life Science Innovation and Life Science Scale-up at the Business Weekly Awards, and the 2nd Annual TPD Awards.

‘PhoreWard’ into 2024!
In the coming year, it is our belief that the field of targeted protein degradation is going to go from strength to strength, within increasing attention being placed on differentiated ‘beyond cereblon’ approaches.

PhoreMost is in an excellent position to be a key player in this exciting and evolving field with our novel ligase drug discovery poised to deliver degrader assets, and our ongoing SITESEEKER® activities delivering differentiated and selective degrader mechanisms. We also look forward to further advances with both new and existing partnerships.

2024 is shaping up to be a big year for PhoreMost!
I would like to thank our amazing PhoreMost team, collaborators, and partners, wishing all a happy holiday period and a wonderful new year.