ELX-02 shows significant increases in CFTR protein expression and localization correlating with functional activity in Cystic Fibrosis patient-derived organoids bearing CFTR nonsense mutations
In previous studies, the increased CFTR functional activity associated with ELX-02 was shown to correlate with increases in CFTR mRNA with elevations to wild-type levels
ELX-02 appears to increase CFTR mRNA stability, suggesting that ELX-02 may be modulating nonsense mediated decay
“ELX-02 is the first read-through agent to demonstrate significant increases in CFTR protein expression, localization on the apical surface, and functional activity in a dose responsive manner in organoids derived from cystic fibrosis patients with nonsense mutations” said Dr.
Recent work with cystic fibrosis patient-derived organoids have extended the potential applications of the FIS assay to include use in stratifying patient disease severity (1) and as a potential predictor of CF patient response to drug therapy (2). On
Eloxx is on track to report top line results in 2019 from a Phase 2 study in cystic fibrosis patients carrying at least one G542X mutation in the U.S., and
In a Poster presentation at the
- Consistent with increased CFTR activity observed in the organoid swelling assay, ELX-02 mediates a significant restoration of CFTR protein expression as measured via a capillary-based immunoassay approach in multiple G542X or W1282X nonsense carrying organoids.
- G542X organoids treated with ELX-02 demonstrate proper cell surface CFTR localization on the apical surface, which is consistent with increased CFTR, mRNA, and CFTR function in the swelling assay.
While ELX-02 mediated protein increases have been previously demonstrated, this is the first demonstration reported in cystic fibrosis patient organoids. Within this translational CF organoid model, ELX-02 dose-dependent increases in CFTR mRNA stability and function can now be extended to the demonstration of accompanying increases of CFTR protein.
Previously, Eloxx presented positive data for ELX-02 at the
These data demonstrate that ELX-02 promotes translation of functional CFTR and we believe, de-risks our planned Phase 2 clinical trial of ELX-02 in cystic fibrosis patients with the G542X CFTR mutation on one or both alleles, which is the second most common mutation globally and accounts for about 5% of the cystic fibrosis population.
Eloxx has continued to generate new data for ELX-02 activity from a growing number of patient-derived organoids which represent multiple nonsense mutations across a variety of genotypes representing the top 5 nonsense mutations in the cystic fibrosis population, which cover over 75% of the nonsense bearing cystic fibrosis patients.
ELX-02 is an investigational agent not approved by any regulatory agency for therapeutic use.
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Contact:
Barbarar@eloxxpharma.com
(203) 274-2825
SOURCE:
Source: Eloxx Pharmaceuticals