SpliSense, a biopharmaceutical company focused on RNA-based therapies for pulmonary diseases, has announced the completion of a Phase 1 clinical trial for SPL84, its lead inhaled antisense oligonucleotide (ASO) product. SPL84 is being developed as a treatment for patients with cystic fibrosis (CF) who carry the 3849+10 kb C->T splicing mutation in the CFTR gene. The trial demonstrated that SPL84 is safe and well tolerated, with no serious adverse events or significant related adverse events identified.

In the trial, 32 healthy male volunteers received a single dose of SPL84 or a placebo across four different doses. The results showed no significant changes from baseline in vital signs, clinical laboratory values, ECG, physical examination, or pulmonary function. Systemic exposure to SPL84 was very low and dose dependent. The Phase 1 trial was a single ascending dose study conducted in healthy volunteers, administered via inhalation.

Gili Hart, PhD, Chief Executive Officer of SpliSense, expressed excitement about the safety profile of SPL84 and announced plans to initiate a Phase 2 efficacy study in the first half of next year. CF is a common genetic disease that leads to frequent lung infections, breathing difficulties, and reduced life expectancy. While current treatments have increased life expectancy, there is still a significant unmet medical need for a cure, especially for CF patients carrying the 3849+10 kb C->T mutation. SPL84 has shown promising preclinical results in restoring CFTR activity and now demonstrates safety in humans.

In addition to the Phase 1 trial, SpliSense published a paper in Nucleic Acid Therapeutics that highlights the delivery characterization of SPL84. The data showed broad distribution, as well as cell and nucleus penetration of SPL84 in mouse and monkey lungs. The drug also demonstrated stability in CF patient-derived mucus and in lung lysosomal extracts. These results, combined with the promising preclinical pharmacological effect of fully restoring CFTR channel activity, indicate the potential of SPL84 as an effective treatment for CF.

SpliSense aims to develop RNA-based treatments for pulmonary diseases by utilizing antisense oligonucleotides (ASOs) to correct mutations in the CFTR mRNA. The ASOs specifically bind to the mutated CFTR RNA, leading to the modulation of the mutated region and the production of fully functional CFTR proteins. The ASOs are administered directly to the lungs via inhalation and have shown efficient uptake by lung cells.

This Phase 1 trial success paves the way for further development of SpliSense’s pulmonary pipeline, including treatments for muco-obstructive diseases and idiopathic pulmonary fibrosis, which are expected to enter the clinic next year. SpliSense’s technology is based on the research of Prof. Batsheva Kerem, a renowned geneticist from the Hebrew University of Jerusalem, who was part of the team that identified and cloned the CFTR gene.

– Nucleic Acid Therapeutics publication: “Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849 + 10 kb C->T Cystic Fibrosis Patients”
– SpliSense website: splisense.com/

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