Strong rationale for development for Alport syndrome as ELOX-02 has demonstrated significant readthrough in COL4A5 nonsense mutations in preclinical studies and is preferentially transported to kidney
Initiation of proof-of-concept clinical trial expected in second half of 2022; topline results expected in first half of 2023
Alport syndrome is a genetic disorder characterized by kidney disease with high levels of proteinuria, hearing loss and eye abnormalities caused by mutations in the genes (COL4A3, COL4A4, and COL4A5) needed for production of type 4 collagen. Approximately 6% to 7% of Alport syndrome patients, or approximately 9,400 to 12,750 individuals, are estimated to have nonsense mutations. These patients have significantly worse clinical outcomes than other Alport patients and have no disease modifying treatment options.
Eloxx believes there is a strong rationale to pursue clinical development of ELX-02 in Alport syndrome, based on encouraging preclinical results demonstrating potentially therapeutic levels of readthrough, ability to deliver high drug concentrations in the kidney relative to plasma at clinically tolerable dose levels, and the clinical readthrough results seen in our Phase 2 cystic fibrosis trial.
“We are beginning to fully capture the potential of ELX-02 as a novel readthrough agent in rare diseases with significant need with the addition of a new program in Alport syndrome,” said
"For the global patient community, this study represents a groundbreaking and hopeful step as the first to explore a potential curative therapy in a specific genetic mutation of our rare disease,” notes
ELX-02 is preferentially taken up in the kidney, resulting in an expected greater than 50-fold exposure in the kidneys compared to plasma. In recently published preclinical studies, ELX-02 has demonstrated readthrough in COL4A5 mutations, which represent 85% of nonsense mutations in this population. We believe that the results of the treatment of Class 1 CF patients with ELX-02 monotherapy and its high local kidney drug levels make it well suited to potentially deliver transformative results in these patients.
Eloxx intends to initiate a proof-of-concept clinical trial in up to eight Alport syndrome patients with nonsense mutations in the second half of 2022. Patients will be dosed for two months with a three month follow-up. Trial primary endpoints will include safety, while secondary endpoints will include reduction in proteinuria and induction of COL4A5 protein expression in the kidney. Topline results are expected in the first half of 2023.
About nonsense mutations
Nonsense mutations cause a premature stop codon in the mRNA resulting in less than full length or los of function proteins. These remain highly underserved with no approved disease modifying therapies. An estimated 10-12% patients across over 8,000 inherited genetic rare diseases harbor nonsense mutations in one or both alleles harboring nonsense mutations.
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This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of present and historical facts contained in this press release, including without limitation, statements regarding the expected timing of trials and results from clinical studies of our product candidates and the potential of our product candidate to treat nonsense mutations are forward-looking statements. Forward-looking statements can be identified by the words “aim,” “may,” “will,” “would,” “should,” “expect,” “explore,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “seeks,” or “continue” or the negative of these terms similar expressions, although not all forward-looking statements contain these words.
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Source: Eloxx Pharmaceuticals