Non-Clinical Pharmacology of CX-01

Development of radiation medical countermeasures (MCM) has become a national security priority owing to such threats as radiological dispersal devices (i.e., “dirty bomb”) and nuclear accidents, which may be caused by extreme weather (such as occurred in Fukushima, Japan in 2011). Radiation exposure can be potentially lethal via the hematopoietic-acute radiation syndrome (H-ARS) and the gastrointestinal-ARS (GI-ARS). The U.S. government has committed to supporting development of medical countermeasures (MCMs) to mitigate morbidity and mortality of these radiation syndromes. Re-purposed leukemia drugs have proven useful in treatment of the H-ARS in preclinical models, but there remains no effective MCM for GI-ARS. Ceramedix, Inc. is developing a pipeline of therapeutic candidates with the goal of preventing and mitigating illness due to radiation exposure. Our lead candidate, CX-01, is an anti-ceramide single-chain variable antibody fragment (scFv) that binds ceramide on the exocellular leaflet of the plasma membrane of radiation-injured endothelial cells in the GI tract and in other organs. By binding ceramide, ceramide-rich platforms are disrupted, thereby preventing cellular death. Extensive data in multiple species, including non- human primates (NHPs), show that disrupting the ceramide signaling pathway protects and mitigates the GI- ARS. We have demonstrated dose-dependent efficacy in NHPs as well as mortality benefits in mice. CX-01 may be administered subcutaneously, a critical advantage during mass casualty events. Ceramedix’ therapeutics may have broad application in multiple additional diseases. Ceramide-rich platform signaling is a ubiquitous damage response pathway that drives cell injury and death in response to diverse disease and environmental stimuli. Ceramedix has generated significant preclinical data supporting treatment of diabetic retinopathy and diabetic macular edema. Ceramedix is also exploring other diseases including diabetic nephropathy and pulmonary injury (fibrosis and other pulmonary syndromes). The overall goal of this work is to validate that CX-01 demonstrates equivalent potency and efficacy as a precursor non-humanized scFv molecule. We will perform in vitro and in vivo pharmacological studies to support CX-01 IND acceptance. The ability to prevent and treat GI-ARS would have profound benefits in protecting civilians and defense personnel. There is no current treatment for GI-ARS, particularly one suitable for field administration following a mass casualty event. USG has prioritized this critical unmet medical need. CX-01 represents a major breakthrough in potential treatment of the lethal GI-ARS. CX-01 has the potential to become the first and only available treatment for GI-ARS. Successful completion of this work will accelerate IND submission and clinical evaluation of Ceramedix’ transformative therapeutic platform.