Disease Area Focus and Pipeline

Anemia

Several recombinant versions of human erythropoietin (EPO) have been approved for treating patients with chronic anemia conditions with low endogenous EPO production, including chronic kidney disease (CKD) patients, cancer patients on chemotherapy, and those on HIV treatments and other diseases. These biological agents target the EPO receptor (EPOR), and this has been the only approved mechanism effective in treating anemia due to low EPO. Due to the ubiquitous presence of EPOR, the actions of recombinant EPO are not restricted to erythropoiesis. Recently, the US FDA has approved an oral inhibitor targeting hypoxia-inducible factor-prolyl hydroxylase domain (HIF-PHIs) for treating anemia in dialysis patients. Safety concerns have challenged this approach due to the wide distribution of HIF and the promiscuous nature of the mechanism of action of HIF-PHIs. However, no other mechanisms have emerged as alternatives for developing treatments for low-EPO anemia.

Erythropoiesis-stimulating agents based on EPO have been the standard of care for over three decades, with no other safer mechanism approved for broader use since then. The EPOK development candidate focuses on negating the drawbacks of the approved EPO-based ESAs: the need for dosing once or multiple times a week, instability at room temperature, high cost, and oncogenic potential due to the documented activity of EPO through other receptors distinct from the EPOR.   EPOK Therapeutics’ lead candidate, EPRA-0322, is a mono-specific antibody with potent erythropoietin receptor agonist activity currently in GMP cell-line development. Pre-clinical studies demonstrated the potential for low (<1 ug /kg), 4 - 6 doses a year subcutaneous dosing in humans, and low cost of goods. Moreover, unlike the approved anemia treatment agents, EPRA-0322 does not activate other human receptors, which may offer a better safety profile.  

Phosphate Wasting Disorders

Genetic and acquired hypophosphatemic rickets result from the overexpression of the phosphaturic hormone fibroblast growth factor 23 (FGF23). These disorders include X-linked dominant hypophosphatemic rickets (XLH), Autosomal dominant hypophosphatemic rickets (ADHR), Autosomal recessive hypophosphatemic rickets Type 1, 2 and 3 (ARHR1, 2, 3), and Tumor-induced osteomalacia (TIO). The anti-FGF23 neutralizing monoclonal antibody burosumab is the only agent approved for treating XLH and TIO. Considering that FGF23 has myriad effects beyond regulating phosphate balance, simply obliterating FGF23 from the circulation with neutralizing antibodies likely causes unintended effects.

EPOK Therapeutics’ second leading program is KLOT-1123, a novel proprietary antibody to treat hypophosphatemic disorders and CKD due to high FGF23 bioactivity, currently in pre-clinical development. Thanks to its novel and unique mechanism of action, KLOT-1123 does not directly target FGF23 but blocks its signaling. This targeted approach does not impact the circulating levels of FGF23 while blocking its function on targeted cells. Such selective blocking of the phosphaturic activity of FGF23 yields a better safety profile, with a potential for broader use than neutralizing circulating FGF23.