SPL23 / SpliSense - LARVOL DELTA

SPL23, an Exon-Skipping Antisense Oligonucleotide for PwCF Carrying the W1282X Variant (NACFC 2026) - " The effects of SPL23 following basal or apical free uptake, either alone or in combination with modulators (Elexacaftor/tezacaftor/ivacaftor - ETI or Vanzacaftor/Tezacaftor/Ivacaftor - VTI), were evaluated in human nasal epithelial (HNE) and human bronchial epithelial (HBE) cells derived from pwCF carrying the W1282X variant. These results highlight the therapeutic potential of SPL23, part of the clinically validated SpliSense ASO platform, in combination with CFTR modulators for pwCF carrying the W1282X nonsense variant - addressing a critical unmet need for patients who do not benefit from existing modulator therapies. SPL23 is a potent and safe preclinical lead, and these data support initiation of clinical studies in the near future."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR

Antisense Oligonucleotide Splicing Modulation as a Novel Cystic Fibrosis Therapeutic Approach for the W1282X Nonsense Mutation (NACFC 2022) - "CFTR activity was analyzed with the chronic addition of VX-661, VX-445 for 48 hours and acute addition of VX-770 using the Ussingchamber system.Cumulative results indicate that exon skipping generated bySPL23-2 leads to production of mature CFTR proteins. These results highlight the potential therapeutic and clinicalbenefit of ASO-based exon 23–skipping SPL23-2, supplemented by CFTRmodulators, for people with CF carrying the W1282X nonsense mutation.We aim to initiate a clinical study by next year.620 Antisense oligonucleotide splicing modulation as a novel cystic fibrosistherapeutic approach for the N1303 K nonsense mutation"

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Antisense oligonucleotide splicing modulation as a novel cystic fibrosis therapeutic approach for the W1282X nonsense mutation (ECFS 2022) - "These results highlight the potential therapeutic and clinical benefit of ASO-based exon 23 skipping SPL23–2, supplemented by CFTR modulators, for CF patients carrying the W1282X nonsense mutation aiming to enable the initiation of clinical study by next year."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Antisense oligonucleotide splicing modulation as a novel Cystic Fibrosis therapeutic approach for the W1282X nonsense mutation. (PubMed, J Cyst Fibros) - "The highly efficient exon 23 skipping induced by free uptake of the lead ASO and the resulting levels of mature CFTR protein exhibiting channel function in the presence of modulators, demonstrate the ASO therapeutic potential benefit for CF patients carrying the W1282X mutation with the objective to advance the lead candidate SPL23-2 to proof-of-concept clinical study."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

SpliSense Presents Preclinical Data for SPL23-ASO, mRNA-Altering Drug Candidate for the Treatment of Cystic Fibrosis, at the European Cystic Fibrosis Conference (PRNewswire) - "SpliSense...announced preclinical data for SPL23-ASO, an antisense oligonucleotide (ASO) targeting the W1282X nonsense mutation associated with a severe form of the CF, showing that the ASO enables production of a functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein...We are therefore excited to see that our technology has the potential to treat people with such mutations and look forward to advancing both SPL23-ASO and SPL84-23, which is designed to treat the 3849+10kb C->T CFTR mutation, into the clinic next year."

Preclinical • Cystic Fibrosis