pHLIP, Inc. is a Delaware corporation founded in 2014. It has the general objective of applying its pHLIP® platform technology for targeting cargoes to acidic tissues in order to detect, treat or prevent diseases in human. The current uses are focused on the fact that cancer cells and activated macrophages within tumors or inflamed tissues acidify their environments, and hence are targeted by pHLIP® agents. How did the technology evolve? How is the company organized? What might the future hold?
The original pHLIP® peptide was discovered in the course of studies of ideas concerning how membrane proteins enter the lipid bilayers that form the basic structures of biological membranes. Most proteins that are located across membranes have one or more helical segments that cross the lipid bilayer, and studies of these helical parts in a highly researched protein, bacteriorhodopsin, revealed that one of the helices could fold from a disorganized state outside of a membrane to form a helix across the membrane in response to local acidity. Because tumor cell surfaces are acidic as a result of their active metabolism, versions of pHLIP® peptides were extensively investigated and tested as possible tumor targeting agents over the course of 15 years of work at Yale, the University of Rhode Island, and the Memorial Sloan Kettering Cancer Center. These studies showed that an extensive variety of cargoes can be targeted to cell surfaces and that a surprising range of cargoes can be delivered across membranes into cells if their surfaces are acidic, creating opportunities to detect and treat tumors.
Because it is evident that marking and treating tumors are major objectives in contemporary medicine, pHLIP, Inc. was formed, and the technology was licensed from the universities where the work was done. The licenses include exclusive rights to the pH peptide patent families (more than 20 issued patents and patent applications), as well as the pHLIP® trademark. Research and intellectual property protection are ongoing efforts as new versions and applications of pHLIP® peptides are found.
With a large range of possible approaches in view, it rapidly became apparent that it would be impossible to pursue all of them in a timely fashion, so the company has adopted a business approach based on collaborative licensing of particular applications to other companies, where pHLIP, Inc. receives various payments and provides expert guidance for the applications in the company of the licensee. In some cases, pHLIP, Inc. is taking the early steps toward the clinic in order to enhance the value of a product before it is licensed, in other cases the path toward the clinic is pursued by a partner starting at an earlier stage. Two imaging products developed within the company are now entering clinical trials, and two licensed areas are rapidly nearing the point where candidates will be advanced to clinical trials.
The future of applications in the cancer field is bright. Because acidity is a feature of cancer cells that is more pronounced in aggressive cases, and because very small tumors can be targeted, the resistance that has limited many current approaches should not arise, and successful therapy can be anticipated for metastatic cancer. Moreover, other areas of medicine may be amenable to successful applications of the pHLIP® technology, including arthritis, atherosclerosis, gene therapy, and others. An exciting set of directions is in view!