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  • Writer's pictureUSACFA

Research Corner: Zero Percent Left Behind – Eloxx Pharmaceuticals Nonsense Target Therapy

By Ella Balasa

The treatment advances for our community in just these short few years have been phenomenal. But sadly, as we know, not all of us have been able to rejoice in the feeling of deeper, clearer breaths resulting from the changes in the cells in our lungs, hydrating our airways, and leading to sustained improvement in our quality of life. No, some in our community are still waiting to join us.

Fortunately, many companies are working in fervor to bring such therapy options to the remaining population – those with nonsense mutations. This is just what Eloxx Pharmaceuticals is working on - restoring the production of functional proteins overcoming the nonsense mutation impairment with novel small molecules.

For those that are interested in understanding the science behind how this works, here is a little breakdown.

In every genetic disease, a subset of patients has nonsense mutations that impair the production of essential proteins. This is the CFTR protein in CF. This mutation acts as a stop sign when the RNA is being read through the ribosome to create the CFTR proteins. Before the protein assembly even begins, this mutation halts the process so no protein is created. The treatment Eloxx is developing will allow the production and delivery of clinically meaningful levels of functional proteins by bypassing this stop sign called a stop codon. This protein, when working correctly, allows the proper chloride and water ratios in and out of our cells, creating more normal conditions. If you were wondering, currently available modulator therapies do not work for those with nonsense mutations because modulator therapies require at least some production of CFTR proteins which do occur in other mutations of CF. These proteins, however, are deformed and defective, but existing, so they can then be modulated and corrected to perform.

Now, back to this treatment advancement. What has Eloxx’s research and clinical trial results yielded so far and what will be the upcoming trial’s goals?

In the phase 1 trial of healthy adults, in both single and multiple ascending doses, there were no reported significant adverse events or kidney function issues. It was generally well tolerated. Collectively, these data support the evaluation of ELX-02 in Phase 2 trials.

The current phase 2 trial is the first in cystic fibrosis patients which will evaluate the safety, tolerability, concentration, and biochemical and physiological effects of the drug in the body of CF patients with at least one G542X mutation.

In total, up to eight patients will be enrolled in the trial; up to four patients will be homozygotes, meaning two copies of the G542X mutation, and the remaining patients will have one copy of G542X and another Class 1 or Class 2 mutation, excluding those with the most common F508del mutation. Each patient will receive four escalating doses of 0.3 mg/kg, 0.75 mg/kg, and 1.5mg/kg which were chosen to determine the optimal dose to get the maximum benefit with the least possibility for adverse events. They will be examining concentrations of the medication in the blood, tracking adverse events, measuring the observed change in FEV1, as well as sweat chloride concentrations.

Are you interested in participating? They are now enrolling patients with at least one copy of nonsense mutation G542X in this phase 2 trial. This is one of the most common nonsense mutations in CF, so having patients with the same mutation enrolled reduces potential variability. There are some exclusion criteria, however. If you have been on any CFTR modulators within the last 2 months you are ineligible. Additionally, as mentioned above, if you have an F508del mutation (even if you have a G542X mutation) you are ineligible. There are trial sites throughout Europe and in the US. If you think you qualify and are interested in learning more and participating, visit the site. You can find participating CF centers listed toward the bottom of the page, or discuss with your CF center team. You can also contact the Eloxx team directly at

Tune into the North American Cystic Fibrosis Conference (NACFC) later this week starting Wednesday to hear about Eloxx’s clinical updates as well as learn about other new and exciting research developments in the CF space!

“We are pleased to be presenting additional preclinical study results in cystic fibrosis at the 2020 NACFC virtual conference which demonstrate ELX-02’s selectivity for read-through of premature stop codons versus native stop codons and its ability to restore production of functional CFTR in patient-derived organoids,” said Dr. Gregory Williams, Chief Executive Officer of Eloxx Pharmaceuticals. “We are advancing our Phase 2 clinical trials for ELX-02 in cystic fibrosis in Europe, Israel and the U.S., and we believe the data from our preclinical programs substantially de-risk this program. We look forward to reporting top line data from our proof of concept Phase 2 clinical trials as quickly as possible.”


About the Author: Ella is a director for USACFA. She is 28 years old and was diagnosed with CF at 18 months old. She has a B.S. in biology and has worked in an environmental microbiology lab. She serves on various research committees, planning virtual events, and writes to provide a scientific voice and encourage empowerment to the CF community as well as introspectively writing about the hardship yet triumph that comes along with a chronic disease. When she is not taking care of her health, she enjoys cooking, drawing, and spending time with friends. Follow her life experiences on Instagram @thisgirlella.

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