Eloxx Pharmaceuticals, Inc. announced the submission of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration for ZKN-013 for the treatment of recessive Dystrophic Epidermolysis Bullosa (RDEB) with nonsense mutations. RDEB is a rare skin disease characterized by mutations in Collagen7 gene. Recent preclinical results demonstrated read-through activity of ZKN-013 in multiple COL7 genotypes across multiple RDEB patient derived fibroblasts and keratinocytes.

Read-through activity resulted in up to an 18-fold increase in full-length COL VII protein levels. Prolonged treatment with ZKN-013 further increased COL VII protein levels. Functionality of the restored full-length COL VII protein was confirmed.

These results have been accepted for presentation at an upcoming medical conference. An additional IND filing for ZKN-013 for the treatment of familial adenomatous polyposis (FAP) is planned in the first half of 2023. FAP, a rare inherited disease with no approved drug therapies, is characterized by proliferation of colon polyps.

Eloxx is targeting a subset of patients that have nonsense mutations in the Adenomatous Polyposis Coli (APC) gene that is truncated in these patients. In January 2023, Eloxx published positive results from a study in the APCMin (multiple intestinal neoplasia) model evaluating the potential of ZKN-013 to treat FAP. The APCMin mouse is a translationally validated model for drug development for FAP.

In the APCMin model, treatment with ZKN-013 demonstrated a decrease in intestinal polyps and adenomas, resulting in increased survival. The publication also included in vitro and in vivo demonstrating that ZKN-013 inhibited the growth of human colon carcinoma cells with APC nonsense mutations, and promoted read through of premature stop codons in the APC gene, leading to functional restoration of full-length APC protein.