Eloxx Pharmaceuticals presented additional positive preclinical and clinical data for ELX-02, its lead treatment candidate for cystic fibrosis (CF), reinforcing the therapy’s safety and tolerability in humans and its ability to increase the levels of CFTR protein in preclinical models of the disease.
Findings were presented in three posters and an oral workshop at the North American Cystic Fibrosis Foundation Conference (NACFC), held recently in Nashville, Tennessee.
“We are extremely pleased with the emerging profile of ELX-02,” Matthew Goddeeris, PhD, Eloxx’ executive director of research, said in a press release, adding that “the consistency of our data with those from previous studies with already approved drugs for cystic fibrosis” showing that increases in CFTR protein were associated with improvements in lung function, suggest that ELX-02 may lead to significant improvements in the company’s ongoing Phase 2 studies.
ELX-02 is a small molecule being developed for the treatment of CF caused by nonsense mutations in the CFTR gene, which represent about 10% of CF cases worldwide. These mutations cause a premature stop in protein synthesis, resulting in a shorter, incomplete, and non-functional CFTR protein.
ELX-02 works by preventing the premature stop in protein synthesis, potentially enabling the production of sufficient amounts of full-length CFTR protein and lowering CF burden.
Goddeeris presented preclinical data — in a poster titled “Investigational Drug ELX-02 Mediates CFTR Nonsense Mutation Read-through to Increase CFTR MRNA, CFTR Protein Translation and CFTR Function” — showing that ELX-02 treatment resulted in a considerable increase in the levels of full-length CFTR protein in several preclinical models of the disease, including patient-derived organoids.
These organoids are 3D “mini-organs” that mimic diseased tissue, and are thus considered a potentially valuable tool to predict a therapy’s clinical benefit.
The increase in CFTR levels was observed in organoids derived from CF patients with the five most common nonsense mutations, which represent more than 75% of all CF patients with nonsense mutations, according to the company. Goddeeris also noted they are continuing to identify new ELX-02-responsive nonsense mutations.
Gregory Williams, MD, Eloxx’s chief operating officer, presented clinical data of the two Phase 1 safety studies of ELX-02 treatment in healthy volunteers: a single ascending dose study in 60 people in Israel (NCT02807961) and Belgium (NCT03292302), and a multiple ascending dose study in 45 people in Belgium (NCT03309605).
The studies showed positive and consistent results regarding ELX-02’s safety, tolerability, and pharmacokinetics (uptake, distribution, and elimination in the body).
Single, under-the-skin (subcutaneous) doses of ELX-02 from 0.3–7.5 mg/kg were safe. ELX-02 was rapidly absorbed, highly available, did not accumulate in the blood, and was mainly excreted through the kidneys into the urine. To date, it has been well tolerated, and there are no reports of serious adverse events or kidney damage among the 105 healthy volunteers analyzed.
The posters reporting these findings are titled “Pharmacokinetics, Safety, and Tolerability of Multiple Ascending Doses of ELX-02 in Healthy Volunteers, a Potential Treatment for Cystic Fibrosis Caused by Nonsense Mutations,” and “Pharmacokinetics, Safety, and Tolerability of Single Ascending Doses of ELX-02 in Healthy Volunteers, a Potential Treatment for Cystic Fibrosis Caused by Nonsense Mutations.“
Collectively, the overall preclinical and clinical data supported the ongoing evaluation of ELX-02 in Phase 2 studies.
“With the successful completion of our Phase 1 programs, we are pleased to have advanced ELX-02 into Phase 2 clinical trials,” Williams said.
Eloxx’s Phase 2 clinical trial program consists of two open-label, dose-escalation studies that are evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (the therapy’s effects on the body) of multiple doses of ELX-02 in patients with CF who carry the G542X mutation, the most common nonsense mutation.
Given that the Cystic Fibrosis Foundation will provide up to $1.6 million and additional resources to support the EL-012 study in the U.S., Williams also emphasized that the company is grateful to the foundation for their continued support.