In late September and early October, the North American Cystic Fibrosis Conference (NACFC) went virtual, as many conferences and symposia this year have been forced to do. However, that does not mean the insights stopped. The NACFC explored drug development, care, and research related to cystic fibrosis (CF). During the conference, biopharmaceutical company Eloxx Pharmaceuticals (“Eloxx”) presented two poster presentations on their therapeutic candidate ELX-02. In addition to the presentations, Eloxx announced that their findings would also be published in other journals.

ELX-02 Presentations

According to Eloxx, ELX-02:

is a eukaryotic ribosomal selective glycoside (ERSG) designed to increase the read-through activity in patients with nonsense mutations and enable the production of sufficient amounts of full-length functional protein to restore activity. Currently, ELX-02 is in Phase 2 clinical trials in cystic fibrosis patients with diagnosed nonsense mutations on one or both alleles.

The National Human Genome Research Institute defines a nonsense mutation as:

a change in DNA that causes a protein to terminate or end its translation earlier than expected

Currently, nonsense mutations and the stop codons they elicit are believed to play a role in over 1,800 rare conditions.

Posters

In the first poster presentation, Dr. Dan Crawford discussed how ELX-02 helps read-through premature stop codons, prompting the developing of full-length and functional proteins. Through his team’s research, Dr. Crawford also discovered that ELX-02 improved protein expression and reduced RNA degradation. See the full findings published in The Journal of Pharmacology and Experimental Therapeutics.

The second poster presentation, presented by Dr. Matthew Goddeeris, PhD, discussed how Eloxx utilized organoids to test how specific CFTR gene mutations responded to ELX-02. According to the Harvard Stem Cell Institute (HSCI):

Organoids are tiny, self-organized three-dimensional tissue cultures that are derived from stem cells. Such cultures can be crafted to replicate much of the complexity of an organ, or to express selected aspects of it like producing only certain types of cells.

So researchers used these organoids to screen for around 75% or more of nonsense CFTR mutations relating to cystic fibrosis. Next, they discovered that ELX-02 increased CFTR mRNA levels. As a result, mRNA can create and express additional proteins, reducing cystic fibrosis symptoms and damage.

Ultimately, ELX-02 seems to be a promising solution for patients with cystic fibrosis.

Cystic Fibrosis

Cystic fibrosis is a recessive genetic disorder. To inherit this condition, both parents must have at least one gene mutation. Patients with cystic fibrosis do not have “healthy” and slippery mucus. Instead, their mucus is thick and sticky, often accumulating through the respiratory and digestive systems. As this mucus accumulates, airways become clogged. Additionally, patients are unable to release digestive enzymes or properly absorb nutrients. Cystic fibrosis occurs more often in Caucasian infants than those of other racial backgrounds. Symptoms include:

• Shortness of breath or difficulty breathing
• Exercise intolerance
• Stuffy nose
• Frequent coughing or wheezing
• Lung infections
• Fatigue
• Inability to gain weight
• Infertility (males)
• Salty skin
• Constipation or diarrhea
• Pulmonary hypertension

Learn more about cystic fibrosis.