First and PhoreMost

Newly founded company will apply Site-Seeker platform to identify drug targets considered ‘undruggable’

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CAMBRIDGE, U.K.—A new company joined the biopharmaceutical ranks last month with the founding of PhoreMost Ltd., which launched with £2.5 million ($3.8 million) in seed funding from Cambridge-based angel investors Jonathan Milner, Amadeus Capital, Sunil Shah and Prashant Shah (O2H Ventures), Cambridge Enterprise and Dr. Chris Torrance, PhoreMost’s founder and CEO.
PhoreMost’s goal is to focus on increasing the diversity and affordability of novel therapeutics. The company will use the funding to build its commercial operations based on a drug discovery platform developed by the lab of Dr. Ashok Venkitaraman of the University of Cambridge. The platform can unmask cryptic drug sites in disease targets and pathways that are currently considered “undruggable.” Based on PhoreMost’s proprietary Protein Interference technology, Site-Seeker is a next-generation phenotypic screening platform that can identify the best targets for drug development and how to drug them.
Venkitaraman, a PhoreMost co-founder, is the Ursula Zoellner Professor of Cancer Research at the University of Cambridge, and the director of the Medical Research Council Cancer Unit. He is currently leading a multidisciplinary initiative to pioneer new approaches for drug discovery in both Cambridge and as director of the Centre for Chemical Biology and Therapeutics at the National Centre for Biological Sciences, Bangalore. Torrance, who is also one of the founders of Horizon Discovery and served as its chief scientific officer for seven years, brings with him experience in oncology R&D and management.
“I’m delighted that an influential group of experienced investors has chosen to support PhoreMost, enabling the commercialization of research in my laboratory that has developed the Site-Seeker platform,” said Venkitaraman. “We are well positioned to exploit our disruptive new approaches for drug discovery at a time when the pharmaceutical industry seeks to widen its pipelines.”
The Site-Seeker platform is capable of defining key disease-impacting steps in cellular pathways that can’t be predicted a priori, through the use of empirical live cell phenotypic assays, and can simultaneously identify hidden druggable sites within those targets. This reportedly allows it to offer a seamless assay system to “de-orphan” newly identified target sites with small-molecule drug candidates.
“The other platforms on the market that would be used to identify targets on a genome-wide scale that are linked to specific disease operate at the genetic level; the level of DNA, RNA, i.e., the genes themselves; whereas we are uniquely screening at the protein level. Our SiteSeeker platform is therefore able to provide another important layer of information; not just 'is this the best target in that disease,' but also tell you how to drug that target,” Torrance explains to DDNews.
“There are 30,000 genes in the human genome, and most of these pharma companies would look at it and say 'you know what? I don't see any obvious way of developing a drug for that.' Druggable targets, such as kinases, have very obvious clefts to them and naturally bind small molecules in them, so it is very easy to design a better small-molecule drug that goes into the cleft. However, most proteins don't look like that, appearing as featureless entities in a static X-ray crystal structure, which is like a photographic snapshot taken of a protein outside of a cellular environment,” he continues. “What Site-Seeker does, however, is screen the entire proteome for thousands of druggable pockets that are opening and closing all the time in a dynamic live-cell environment and then simultaneously link them to a useful effect in a specific disease. These important dual aims can only be achieved by screening live cells at the protein level rather than the genetic level.”
PhoreMost will aim to identify new druggable targets for cancer and other diseases with high unmet needs, and Torrance says the company will initially be focusing on cancer, noting that “Of all the genes that have been linked to cancer—there's about 300—about 250 of those are considered undruggable; these are the ones we are systematically going after.” He says PhoreMost addresses “a real need to fill pharma pipelines with validated targets and get drugs designed to them into clinical trials faster.”
“If you can identify, as a part of the screening process, how to drug a target, as well as find the right targets, I think you could speed up drug discovery quite significantly,” Torrance tells DDNews. “Moreover, in the U.K., with its National Healthcare Service, you could access the genetic diversity of an entire country quite easily; and if they would also start to work with biotech as a co-invested partner in the future to develop new medicines in a very personalized and stratified way, the U.K. could be a good place to pursue a more efficient drug discovery model.”
“Everybody behind this company really buys into the longer-term mission of using this technology to accelerate drug discovery and ultimately pass those cost savings onto patients. If we're going to achieve personalized medicine, we're firstly going to need a lot more drugs, so we need to start drugging what most people think are undruggable targets,” he adds. “But we also need to find a way to discover and provide those new medicines more cheaply. That is the longer-term social mission that I'm really excited by, and everybody who's part of the company is excited by too.”

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