The first healthy subject was dosed in a Phase 1b clinical trial evaluating the safety, tolerability and drug properties of ELX-02 as a candidate for the treatment of multiple conditions, including Duchenne muscular dystrophy (DMD).
The study is dose-escalating, double-blinded and placebo-controlled to evaluate the safety, tolerability and pharmacokinetics (drug response in the body) of ELX-02 across four dose levels. The trial is being conducted in Belgium and data are expected by the end of 2018.
“We are very pleased to continue our clinical development program for ELX-02 and are excited about its potential to treat many genetic diseases caused by nonsense mutations,” Pedro Huertas, MD, PhD, chief medical officer of Eloxx Pharmaceuticals, said in a press release. “We look forward to continue achieving our key clinical milestones.”
DMD is caused by mutations in the gene “dystrophin.” DMD-causing mutations may vary in nature and account for deletion, replications, duplications or single-point mutations, which disrupt the coding reading frame of the dystrophin gene. The result is nonexistent dystrophin expression in skeletal and cardiac muscles.
About 10 to 15 percent of the single point mutations are so-called nonsense mutations. When nonsense mutations are observed, the result is the expression of non-functional proteins.
A nonsense mutation is a genetic mutation in a DNA sequence that results in shorter, unfinished proteins, that are often nonfunctional. Nonsense mutations occur when a premature stop codon is introduced in the DNA sequence. When the mutated sequence begins to be translated into a protein, the stop codon stops the process prematurely.
ELX-02 is a lead molecule-targeting nonsense mutation in rare diseases. The lead product candidate is an optimized molecule designed to restore full-length functional proteins.
ELX-02 is a translation read-through inducing drug (TRID). Read-through therapy is a treatment strategy for genetic diseases caused by nonsense mutations to increase translation and restoring of the activity of the mutated proteins.
In addition to DMD, nonsense mutations covered by ELX-02 include cystic fibrosis (CF), cystinosis, mucopolysaccharidosis Type I (MPS I) and Rett Syndrome.