Novel targets identified will be further validated and characterized by Roche’s R&D organization, and any SITESEEKER-based probes would become the starting point for drug discovery efforts across a set of disease pathways in immunology and hematology, explained the parties.
The companies are not disclosing the financial details, only revealing that, under the terms of the agreement, PhoreMost will receive an upfront payment and is eligible for preclinical success-based milestones.
PhoreMost says its next-generation phenotypic screening platform called SITESEEKER can discern the best new targets for future therapy and crucially, how to drug them. It explained how it systematically unmasks cryptic druggable sites across the entire human genome and directly links them to useful therapeutic functions in a live-cell context.
The company claims the technology has the potential to significantly increase the diversity and affordability of novel therapeutics for cancer and other unmet diseases.
Dr Neil Torbett, CEO of PhoreMost, told us how the technology works: “The SITESEEKER phenotypic screening platform, uses proprietary PROTEINi or protein interference libraries of ‘mini-proteins’ that are delivered into cells and examined under pooled phenotypic screening conditions. The company’s NGS based informatics platform is then used to identify the most phenotypically active mini-proteins and these undergo extensive validation work. The most promising mini-proteins are then passed to target identification after-which novel drug sites can be discovered via mini-protein – target interaction confirmation. This represents a springboard to the progression of first-in-class small molecule programs.
“The live cell phenotypic screening context essentially means that we are interrogating our PROTEINi libraries for their effects on a particular disease relevant phenotype. This can be as simple as screening for PROTEINi that kill cancer cells and not WT cells but of course can be deployed in multiple therapeutic areas. This aspect is essential for us to identify and progress drug targets with disease relevance.”
Addressing unmet diseases
Using this platform, PhoreMost is building a pipeline of novel drug discovery programs aimed at addressing a range of unmet diseases.
“Using the SITESEEKER technology, PhoreMost is taking an innovative approach to degradation-based therapies. These are bifunctional small molecules, which recruit an E3 ligase to destroy (rather than inhibit) a therapeutic protein of interest (POI). This approach has become an integral strategy for tackling previously undruggable targets. However, despite there being over 600 E3 ligases, industry is still heavily reliant on using a single ligase, Cereblon, within degrader-based drug development.
"At PhoreMost, we are seeking to change 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 are progressing small molecule drug discovery towards novel E3 ligases with a view to developing a range of next generation degrader therapeutics,” continued Torbett.
Beyond Roche, Phoremost has also established SITESEEKER partnerships with Otsuka, Boehringer Ingelheim and Oxford Biomedica, with the CEO adding that the company anticipates signing further alliances in the near future.
