Taking on the undruggables

CAMBRIDGE, U.K.—A new partnership between an American research institute and a British startup is aimed at making biological targets that have been deemed “undruggable” druggable. PhoreMost, a newly founded biopharmaceutical company focused on increasing the diversity and affordability of novel therapeutics, is teaming up with the Wistar Institute, a Philadelphia-based biomedical research institute that specializes in cancer research and vaccine development. Their goal is to de-orphan new targets in cancer, aging and the immune system, potentially opening up a range of therapeutic options for areas of unmet medical need.

The collaboration calls for PhoreMost to use its phenotypic screening platform called Siteseeker to uncover hidden druggable target sites among apparently undruggable targets that Wistar researchers identify with high-throughput phenotypic assays. Wistar will also provide PhoreMost with specialist disease biology knowledge and drug mode-of-action studies on a project-by-project basis to support downstream drug discovery efforts.

An overwhelming majority of disease targets appear to be structurally resistant to chemical intervention, especially when viewed outside of a cell in a static crystallized form. PhoreMost CEO Chris Torrance tells DDNews that roughly 80 percent of potential cancer targets are considered undruggable. “Either no targets are known, or, more pointedly, targets or pathways may be known, but none of the proteins involved conform to classes of protein have been drugged previously,” he says. “Moreover, their structures do not give any immediate insights on how to break new ground from a small-molecule drug perspective.”

Torrance believes that PhoreMost’s Siteseeker offers a genuinely new approach to finding the best targets in previously elusive areas. The technology’s function is to use the dynamics of a live-cell environment to uncover hidden druggable target sites throughout the human genome. The company says Siteseeker offers an assay system to de-orphan these newly identified target sites with small-molecule drug candidates, quickly identifying the promising starting points for future drug development. “All other methods to define good targets are genetic-based, and so do not directly identify how to find novel druggable sites as part of the process,” he says. “Siteseeker screens cells directly at the protein level, identifying good targets and novel druggable sites.”

PhoreMost was founded last spring, boosted by $3.8 million in seed-funding from Cambridge-based angel investors. The company’s strategy is centered around Siteseeker, which was developed from a drug discovery platform originating in the laboratory of University of Cambridge cancer researcher Ashok Venkitaraman, who now serves as PhoreMost’s chief scientific officer. Torrance became CEO of PhoreMost after another company he founded, Horizon Discovery, completed an initial public offering in 2014.

Torrance tells DDNews that partnerships with research institutions like the Wistar Institute are central to PhoreMost’s business strategy. “We have a key screening approach to find ways of drugging ‘undruggable’ targets, but the knowledge of good diseases that allows us to apply this technology with good benefit needs to come from academia,” he says.

In addition to launching more collaborations aimed at identifying potential targets, PhoreMost is also looking toward cultivating partners for the drug development process. Torrance says that the company will work with chemistry partners to develop the targets it identifies and, eventually, with clinical partners. “While we will grow to some degree, it is really the collaborative networks we aim to grow the most, so as to be able to provide a truly new model of drug discovery,” he says.

Wistar’s vice president for business development, Heather Steinman, called PhoreMost a “cutting-edge discovery partner” in a public statement about the new partnership. “We are eager to be partnering with PhoreMost to fully utilize their phenotype-based screening platform technology to rapidly identify new therapeutic candidates,” she said.