FogPharma’s key program aims to discover and develop direct-acting antagonists of β-catenin. β-catenin is a key signaling hub in the Wnt pathway, which is activated by pathway mutations in nearly all colorectal cancers and a significant number of cancers of the liver, breast, prostate, endometrium and lung, among others. In these cancers, the activations are all upstream of or in β-catenin; our antagonists are expected to block all Wnt-driven cancers, irrespective of their specific pathway mutation.
Recently, the laboratory of our scientific advisory board member Dr. Thomas Gajewski showed that Wnt pathway activation also plays an important role in tumors going “cold”, avoiding invasion by cytotoxic T lymphocytes. β-catenin antagonist might be useful in two distinct and potentially synergistic ways; as an anti-oncogene to block tumor cell proliferation and as an immuno-oncology drug to promote tumor clearance by cytotoxic T cells. FogPharma is actively pursuing both of these indications in pre-clinical models.
β-catenin has multiple interacting partners and interference with any one of them may be therapeutically beneficial. FogPharma is developing multiple series of drugs, each of which binds β-catenin at a unique site and blocks a particular interaction. These series will be developed initially as single agents, but the company’s long-term goal is to use them in combination to stave off the emergence of resistance.