A first-in-human, phase 1/2 clinical trial of the antisense oligonucleotide (ASO) SPL84 is being investigated as a promising treatment for patients with cystic fibrosis (CF) who carry the 3849+10 kilobase (Kb) C->T splicing mutation in the CF transmembrane conductance regulator (CFTR) gene.

The current placebo-controlled, randomized, double-blind study, which is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of SPL84, is being conducted in 2 parts.

The first part of the analysis is a single ascending dose study conducted in healthy volunteers. The second part of the analysis is a multiple ascending dose study conducted in patients with CF who carry the 3849 +10 Kb C->T mutation. SPL84 will be given via inhalation in either a weekly or an every-other-week regimen.

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SPL84 is being developed by the biopharmaceutical company SpliSense, located in Jerusalem, Israel. SpliSense has been involved in the development of transformative RNA-based therapies for pulmonary diseases, including CF, muco-obstructive diseases, and idiopathic pulmonary fibrosis.

According to Dr. Gili Hart, Chief Executive Officer of SpliSense, “CF is a debilitating disease, leading to frequent lung infections, breathing difficulties and reduced life expectancy. Currently available treatments focus on treating the symptoms of the disease, while we address the underlying cause of the disease…”

Currently, patients with CF who carry the 3849 +10 Kb C->T mutation have no specific available treatment. CF is a multisystem genetic disorder that originates from various mutations in the CFTR gene. The CFTR gene is responsible for production of the CFTR protein—a chloride channel that is expressed in the lungs, as well as in other tissues.

New strategies for the development of medication are critical for addressing the unmet needs of nonresponsive patients with CF—in particular, those who carry the 3849 +10 Kb C->T splicing mutation.

SpliSense uses short, precisely targeted proprietary RNA stretches, known as ASOs, to correct various mutations in the CFTR mRNA. The ASOs are administered directly to the lungs via inhalation, where they are taken up by the lung cells, thus driving the production of corrected CFTR mRNA and eventually fully functional CFTR proteins.

Whereas currently available treatments focus on treating the symptoms of CF, this treatment plan addresses the underlying genetic cause of the disease, thereby offering the hope of restoring the defective protein and generating adequate lung function in patients with CF.

Reference

Cision PR Newswire. SpliSense initiates phase 1/2 study of SPL84, RNA-based therapy, for the treatment of cystic fibrosis. December 14, 2022. Accessed December 15, 2022.