Breakthrough data validates capabilities of GlueSEEKER platform to identify novel induced protein-protein interactions and expand druggable space

PhoreMost Ltd., a next-generation targeted protein degradation (TPD) company progressing a pipeline of degrader therapeutics within oncology and inflammation, announced the publication of a study demonstrating the capabilities of its high-throughput GlueSEEKER platform to accelerate the design and development of novel molecular glue degraders.

The paper, titled “Systematic molecular glue drug discovery with a high-throughput effector protein remodeling platform”, was published in BioRxiv and describes PhoreMost’s unique approach to molecular glue discovery, wherein effector proteins, such as E3 ligases, can be engineered at scale to expand protein surface landscapes and trigger induced degradation of target proteins. GlueSEEKER is used to develop a high-resolution understanding of the physical and chemical requirements for molecular glue development, and provides the blueprints to enable small molecule drug discovery. The approach synthesises quantitative high-throughput biological data with the most recent advances in computational small molecule drug discovery.

The study describes PhoreMost’s GlueSEEKER in detail and documents an end-to-end case study for small molecule molecular glue discovery with the technology. The potential of the platform to accelerate programmes is validated by the published data and methodology, which can also be applied to novel E3 ligases and other effector proteins across broad therapeutic areas.

Dr Benedict Cross, CTO, PhoreMost, said: “Molecular glues have now been established as an effective therapeutic modality, but these small molecule drugs have still largely only been found through serendipity. Our GlueSEEKER platform overcomes the challenges associated with monovalent glue discovery, enabling their rational and systematic design from almost any E3 ligase or target. This paper marks a significant milestone by showcasing one of our case-studies and validating our deep mutational scanning approach for prospective drug discovery.”

Dr Neil Torbett, CEO, PhoreMost, commented: “FDA-approved molecular glues have treated millions of patients and generated billions of dollars in revenue. The advances disclosed within this manuscript demonstrate how GlueSEEKER can radically enable the discovery of new molecular glue therapies, directing this modality towards specific targets across a broad array of E3 ligases.”

Neil added: “GlueSEEKER builds on PhoreMost’s long-standing expertise in mini-protein engineering and high-throughput phenotypic screening to provide rich biological data which is deeply enabling for the advancement of first-in-class drugs using AI-based molecule design tools. We are excited to build upon our leading position to progress the next generation of molecular glue degrader assets for both our internal pipeline and though alliances and partnerships.”

About PhoreMost Ltd

PhoreMost is a next-generation targeted protein degradation (TPD) company developing a pipeline of first-in-class and best-in-class degrader therapeutics within oncology and inflammation.

TPD is a promising new way to eliminate toxic or disease-associated targets from cells, with degradation-based therapies now becoming an integral approach to tackling undruggable targets. However, despite there being over 600 known E3 ligases, the pharma industry is currently reliant upon a very small number, such as Cereblon, for degrader-based drug development.

PhoreMost is unlocking the full potential of TPD and has pioneered the use of mini-protein based engineering via its proprietary platforms, SITESEEKER® and GlueSEEKER™,towards developing novel therapeutic approaches to TPD.

The Company has progressed multiple next-generation ligase programmes through proof-of-concept and is advancing multiple degrader assets towards preclinical studies. PhoreMost also has a number of disclosed alliances with partners, including Roche, Boehringer Ingelheim and Sentinel Oncology.