SpliSense Achieves First Positive Phase 2 Results for Inhaled Antisense Therapy in Cystic Fibrosis
Key Insights
SpliSense (search) reported positive Phase 2 results for SPL84, marking the first evidence of potential clinical benefit from an inhaled antisense oligonucleotide therapy in pulmonary disease.
The study demonstrated improvement in lung function in up to 70% of participants with cystic fibrosis (search) carrying the 3849+10 Kb C->T CFTR (search) mutation, with no safety signals identified.
The results validate SpliSense (search)'s ASO platform and support advancement of additional pulmonary programs for COPD (search), asthma (search), and idiopathic pulmonary fibrosis (search) into clinical trials by early 2026.
SpliSense (search) has announced positive results from its Phase 2 study of SPL84, an inhaled antisense oligonucleotide therapy for cystic fibrosis (search), representing a significant milestone as the first demonstration of potential clinical benefit from an inhaled ASO in pulmonary disease. The SPL84-002 study evaluated the treatment in patients with cystic fibrosis carrying the 3849+10 kilobase C->T splicing mutation in the CFTR (search) gene.
Study Design and Patient Population
The SPL84-002 study is a global randomized, double-blind, placebo-controlled Phase 2 trial conducted across multiple centers in the US and Europe. The study was designed with three sequential cohorts assessing different dose levels of inhaled SPL84 at 25, 50, and 100mg, administered once weekly for 9 weeks. The reported data is based on the complete evaluation of Cohorts 1 and 2, encompassing 12 participants.
Safety and Efficacy Results
The study demonstrated an encouraging safety profile with no identified safety signals or trends of concern among participants. Notably, no treatment-related Severe Adverse Events (SAEs) were observed during the evaluation period.
In terms of efficacy, improvement in lung function as measured by percent predicted FEV1 (ppFEV1) was observed in up to 70% of SPL84-treated participants compared with placebo. The estimated mean absolute change in ppFEV1 for SPL84 compared with placebo was 10 percentage points.
"The SPL84-002 data mark an important milestone, not only for SpliSense (search) but for the entire field of pulmonary ASO therapeutics," said Gili Hart, PhD, CEO of SpliSense. "They represent the first time an antisense oligonucleotide administered directly to the lungs by inhalation has demonstrated potential efficacy in treating a pulmonary disease."
Mechanism of Action and Drug Development
SPL84 is an inhaled antisense oligonucleotide designed to correct the splicing defect caused by the 3849+10 Kb C->T mutation in the CFTR (search) gene. By binding to the mutated CFTR RNA, SPL84 enables the production of a functional CFTR protein. In preclinical studies, SPL84 fully restored CFTR activity in gold-standard pharmacological models.
The therapy is delivered via inhalation on a weekly basis to directly target the lungs, which represents the primary site of cystic fibrosis (search) pathology. SPL84 has been granted both Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration for the treatment of people with cystic fibrosis carrying the 3849+10 Kb C->T mutation.
Pipeline Expansion and Future Development
The positive results provide clinical validation of SpliSense (search)'s ASO platform and support the advancement of additional pipeline programs. The company is developing SPL5AC for muco-obstructive diseases including Chronic Obstructive Pulmonary Disease (COPD (search)), asthma (search), Non-Cystic Fibrosis (search) Bronchiectasis (NCFB), and cystic fibrosis, as well as SPL5B for Idiopathic Pulmonary Fibrosis (search) (IPF).
"The favorable safety and efficacy profile emerging from our SPL84 program provides clinical validation of our ASO platform," added Dr. Hart. "Importantly, this readout supports advancement of our additional pipeline programs with first-in-human studies expected to begin in early 2026."
SpliSense (search) is currently finalizing enrollment for the third cohort of the SPL84-002 study, with plans to share a complete data set with the cystic fibrosis (search) community. The company's pioneering ASO platform is designed to target the root cause of pulmonary disease by restoring or reducing protein function, addressing a significant unmet medical need in respiratory medicine.