PhoreMost Ltd., a next-generation targeted protein degradation company, has published validation data for its GlueSEEKER platform, marking a significant advancement in molecular glue drug discovery. The high-throughput technology represents a shift from traditional serendipitous discovery methods to systematic, rational design of molecular glue degraders.
The study, titled "Systematic molecular glue drug discovery with a high-throughput effector protein remodeling platform," was published in BioRxiv and details PhoreMost's unique approach to molecular glue discovery. The platform enables engineering of effector proteins, such as E3 ligases, at scale to expand protein surface landscapes and trigger induced degradation of target proteins.
Platform Technology and Capabilities
GlueSEEKER integrates high-throughput biological data with computational drug discovery tools to provide blueprints for small molecule development. The platform expands protein surface landscapes to induce novel protein-protein interactions, enabling the rational design of molecular glues—a class of small molecule drugs traditionally discovered through serendipity.
The methodology is applicable to a wide range of effector proteins and therapeutic areas, including oncology and inflammation. The published data supports the platform's potential to accelerate drug development programs and expand the druggable proteome through systematic approaches rather than chance discoveries.
Clinical and Commercial Significance
The therapeutic potential of molecular glues is already well-established in clinical practice. According to Dr. Neil Torbett, CEO of PhoreMost, "FDA-approved molecular glues have treated millions of patients and generated billions of dollars in revenue." This existing clinical success underscores the significant opportunity for expanding the modality through more systematic discovery approaches.
The study includes an end-to-end case study demonstrating the platform's capabilities in identifying molecular glue degraders, providing concrete validation of the technology's practical applications in drug discovery.
Scientific Innovation
Dr. Benedict Cross, CTO of PhoreMost, emphasized the platform's breakthrough potential: "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."
The approach synthesizes quantitative high-throughput biological data with recent advances in computational small molecule drug discovery. GlueSEEKER builds on PhoreMost's expertise in mini-protein engineering and high-throughput phenotypic screening to provide rich biological data that enables advancement of first-in-class drugs using AI-based molecule design tools.
Future Applications
The platform's methodology can be applied to novel E3 ligases and other effector proteins across broad therapeutic areas. Dr. Torbett noted that "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."
PhoreMost plans to leverage its leading position to progress the next generation of molecular glue degrader assets for both internal pipeline development and through alliances and partnerships, potentially expanding access to this systematic approach across the pharmaceutical industry.
