The results of a recently completed first-in-human, phase 1 clinical trial of SPL84 for the treatment of patients with cystic fibrosis (CF) indicate favorable tolerability and a good safety profile, SpliSense announced.

SPL84 is an inhaled antisense oligonucleotide product for patients with CF who carry the 3849+10 kilobase (Kb) C->T splicing mutation in the transmembrane conductance regulator (CFTR) gene.

“The encouraging phase 1 clinical trial results together with the preclinical data published in Nucleic Acid Therapeutics showing broad lung distribution of SPL84 support the further development of our wider pulmonary pipeline, including treatments for muco-obstructive diseases and idiopathic pulmonary fibrosis, both of which are expected to enter the clinic next year,” said Gili Hart, PhD, chief executive officer, SpliSense.

In this placebo-controlled, double-blind, randomized study evaluating the safety, tolerability, and pharmacokinetics of SPL84, the researchers administered SPL84 or placebo to 32 healthy male volunteers. They tested 4 doses of the experimental medication: 20, 40, 80, and 160 mg.

Read more about CF experimental therapies

According to the results, no serious adverse events or significant related adverse events were associated with SPL84. The novel drug did not cause any significant changes from baseline in vital signs, clinical laboratory values, electrocardiogram, physical examination, or pulmonary function. Systemic exposure to the inhalation formulation was very low and dose dependent.

“Although currently available treatments managed to significantly increase life expectancy in the past few decades, they are focused on symptomatic treatments and there is still a significant unmet medical need for a CF cure. In particular, CF patients carrying the 3849 +10 Kb C->T mutation have no specific approved treatment. Our lead product, SPL84, managed to completely restore CFTR activity to the CF gold standard pharmacological model, and with the results announced today supporting its safety in humans, we hope to be able to deliver in the foreseeable future a life-changing treatment for CF patients,” Hart added.

SPL84 is an RNA stretch designed to bind to the mutated CFTR RNA in the targeted sequence and modulate the mutated region in the mRNA, allowing the cell to produce fully functional CFTR proteins.


SpliSense successfully completed phase 1 study of SPL84, RNA-based therapy, for the treatment of cystic fibrosis. News release. SpliSense; September 6, 2023.