LAUSR

ABSTRACT Introduction ELX-02, an investigational compound that is structurally an aminoglycoside analog, induces read-through of nonsense mutations through interaction with the ribosome, through which full-length functional proteins can be produced. It is being developed as a therapy for genetic diseases caused by nonsense mutations such as cystic fibrosis (CF) and nephropathic cystinosis. In Phase 1 clinical trials, 105 volunteers were exposed to ELX-02. To date, ELX-02 is well tolerated and there has been no reported treatment-related serious adverse events or deaths. Areas Covered The development of this molecule, from its pharmacology to the ongoing Phase 2 clinical trials is discussed. Expert Opinion Globally, nonsense mutations account for ~11% of all described gene lesions causing inherited monogenetic diseases. In CF and nephropathic cystinosis, they comprise from 10% to 12% of the disease-causative alleles. ELX-02 is in development as a therapeutic for patients with these alleles as in vitro and in vivo data demonstrated dose-dependent read-through of nonsense mutations to produce full-length, functional proteins. Since read-through efficiency varies between alleles and mRNA context, careful consideration of target patient populations is required. The results to date support the ongoing Phase 2 clinical evaluations of ELX-02 as a read-through agent.