ELX-02 is an experimental treatment being developed by Eloxx Pharmaceuticals to treat cystic fibrosis (CF) caused by nonsense mutations.

How ELX-02 works

CF is a heritable disease caused by mutations in the CFTR gene, which results in the CFTR protein being made incorrectly or not at all. The protein functions as a channel at the cell membrane to allow salts to travel in and out of cells. The absence or malfunction of the protein leads to insufficient salt being transported across cell membranes, which causes a buildup of sticky mucus in organs, interfering with their function. The most common mutation in the CFTR gene is called the F508del mutation, which causes the CFTR protein to misfold.

ELX-02 targets a less common mutation known as a nonsense mutation where there is a premature stop signal in the CFTR gene. This premature stop signal causes the cellular machinery to stop making the CFTR protein midway. The resulting incomplete protein is quickly degraded by the cell.

The treatment binds to ribosome, a protein in the cell responsible for synthesizing proteins, and changes how it reads the instructions of the CFTR genetic template. It’s designed to increase the read-through of nonsense mutations, in essence telling the ribosome to skip over the stop signal. In this way, ELX-02 helps ensure that sufficient quantities of full-length CFTR protein are made in order to lessen the burden of CF.

ELX-02 in clinical trials

A Phase 1 clinical trial (NCT03292302) to assess the safety, tolerability, and pharmacokinetics (movement in the body) of ELX-02 in healthy volunteers has been completed. A total of 18 healthy volunteers were randomly assigned to receive a single dose of ELX-02 or a placebo. Participants were assessed before treatment and 10 days after.

The results were published in the journal Clinical Pharmacology in Drug Development and showed that 62.5 percent of participants experienced at least one side effect following treatment with ELX-02. However, 45 percent of participants also experienced at least one side effect following treatment with a placebo. All of the side effects reported were mild. Medications that work like ELX-02 have been known to cause damage to kidneys or hearing, so this was assessed in the trial. No toxicity in either area was reported for volunteers treated with ELX-02.

Another Phase 1 clinical trial (NCT03309605) is currently recruiting healthy adults in Belgium to further assess the safety, tolerability, and pharmacokinetics of ELX-02. An estimated 45 participants will receive either ELX-02 or a placebo. Side effects from the start of treatment until 40 days afterwards will be recorded.

A Phase 1 clinical trial (NCT03776539) is currently recruiting volunteers with kidney problems in Florida to assess the pharmacokinetics of ELX-02. An estimated 26 participants will be grouped based on their degree of kidney impairment (mild, moderate, severe, or no impairment) and receive a single dose of ELX-02.

Eloxx Pharmaceuticals is expected to report results of the Phase 1 clinical trials and begin Phase 2 clinical trials in 2019. The Phase 2 program for ELX-02 has been given a score of “high priority” by the European Cystic Fibrosis Society-Clinical Trial Network.

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