Currently, Centrose has seven EDC drug candidates and 32 additional prescreened leads in its pipeline. The first class of EDCs targets the sodium/potassium ATPase, which is usually considered an ion channel and is highly expressed in multiple cancers. However, research at Centrose and elsewhere suggests that this cell surface protein functions as more than an ion pump.
“It’s a membrane spanning protein that complexes with proteins inside and is involved in cell proliferation and death. We don’t fully understand all of its implications, but the target appears to be a central player in multiple disease states,” says Dr. Prudent.
A main target of the sodium/potassium ATPase is Src kinase. When an EDC binds and changes the conformation of the ATPase, Src kinase is activated, which, in turn, phosphorylates proteins that trigger cell death. Other proteins are likely involved, such as IP3 (inositol triphosphate) and PI3Ks, a family of intracellular signal transducers involved in cancer.
Centrose’s lead candidate, EDC1, is effective against non-small-cell lung cancer (NSCLC), one of the most aggressive tumor types known, the firm notes. NSCLC accounts for 85% of lung cancer, and more than half of cases present at an advanced stage with little hope for survival.
EDC1 complexes to FXYD5 (also known as dysadherin), a recognized subunit of the sodium/potassium ATPase. Late-stage metastatic cancer cells express high levels of FXYD5, and it is considered a sole prognostic indicator for poor cancer outcomes.
The second program, EDC2, complexes with CD147, a protein highly expressed on the cell surface of carcinoma cells. EDC2 shows strong efficacy against several cancer types. Other EDCs found to date are selective for a variety of specific disease complexes. “We typically use antibodies with some disease significance, mainly oncology,” says Dr. Prudent.
Centrose is building a portfolio of EDCs to license to pharmaceutical companies for further testing. The revenue raised will be used to develop, test, and move to market other EDCs in house.
“We’re in negotiations with several pharmaceutical companies for access to our lead programs and core technology,” says Dr. Prudent. The EDC system could be a way to resurrect drugs that were shelved because they lack specificity or efficacy.