SPL24 – N

Treatment for N1303K CF Mutation

Background

N1303K is a missense mutation  which leads to a folding defect resulting in a reduced number of N1303K CFTR channels in the cell membrane , it also have channel gating defects. There is no available and effective therapy for this mutation.

Prevalence

About 2500 patients carrying the N1303K mutation listed in the US Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) patient registries. About 50% of N1303K CF patients carry non-F508del mutation on the second allele.

Challenge

N1303K mutation does not respond to CFTR modulator drugs. Heterozygous patients carrying the F508del mutation and a minimal function mutation are responsive to Vertex triple combination therapy (Trikafta®). Significantly, around 50% of CF patients carrying N1303K also carry a non-F508del mutation on the second allele. For those patients, no effective treatment is available.

SpliSense Solution

SPL24-N ASO  given by inhalation, penetrates the cells  and skips over exon 24 CFTR transcript. Skipping exon 24 will avoid the maturation defect and proteasomal degradation of misfolded proteins generated by the N1303K mutation generating mature and active CFTR. The activity of these CFTR channels can be further augmented by CFTR modulators.

The program is in pre-clinical stage.

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