AKB-6899 is our second hypoxia inducible factor-prolyl hydroxylase (HIF-PH) inhibitor product candidate, which we believe, based on preclinical testing, has the ability to increase erythropoietin (EPO) levels while reducing vascular endothelial growth factor, or VEGF, levels. We intend to file an Investigational New Drug, or IND, application and begin phase 1 trials to determine its potential use in oncology and ophthalmology.
In screening AKB-6899 for its HIF-related properties, it was discovered that, in cells cultured at low oxygen levels, AKB-6899 significantly inhibited the expression of VEGF and phosphoglycerate kinase, or PGK, messenger RNA, both of which are associated with the growth of cancerous tumors. In addition, AKB-6899 was found to significantly stimulate the production of soluble vascular endothelial growth factor receptor 1, or sVEGFr1. sVEGFr1 is known to be a potent inhibitor of VEGF signaling by sequestering VEGF and inhibiting its interaction with transmembrane receptors—in so doing, sVEGFr1 can inhibit the growth of certain types of cancer cells. AKB-6899 was also found to stimulate the production of EPO in a manner similar to vadadustat (also known as AKB-6548).
These properties, and others, indicate that AKB-6899 may be an excellent treatment for certain cancers (ovarian, breast, colon, and possibly lung), and could be given in combination with other types of chemotherapy. In addition, AKB-6899 may also be a candidate compound for the treatment of chemotherapy-induced anemia and for VEGF-related eye diseases. AKB-6899 has been used effectively in several animal models of cancer, both alone and in combination. In addition, it has been shown to be effective in animal models of colitis.