The biotech company SpliSense received an investment of up to $8.4 million from the Cystic Fibrosis Foundation to develop an antisense oligonucleotide (ASO) therapy for people with cystic fibrosis who have splicing mutations and potentially other rare mutations.
The CF Foundation’s funding will support SpliSense’s splicing mutation correction program, including preclinical development and a Phase 1/2a clinical trial to test the safety and tolerability of the ASO as a potential treatment for people with the splicing mutation 3849+10Kb C-to-T. The objective is to generate a proof-of-concept for the ASO technology in cystic fibrosis. If the trial is successful, it could potentially validate other similar therapeutic approaches in SpliSense’s pipeline that address rare mutations in cystic fibrosis which do not respond to current therapies that target the underlying cause of CF.
“This agreement will enable the exploration of synthetic antisense oligonucelotides as a potential treatment for CF in the clinic, opening exciting new opportunities for therapeutic development and further diversifying the approaches we are pursuing as part of our Path to a Cure,” said William Skach, MD, executive vice president and chief scientific officer for the CF Foundation. “As such, these studies will provide important information for the future development of these potential therapies for additional people with rare mutations.”
Splicing mutations disrupt the production of functional CFTR messenger RNA (mRNA), which is needed to make CFTR proteins. As a result, splicing mutations block the synthesis of normal CFTR proteins. If successful, this potential therapy would enable the creation of a full-length normal CFTR protein, helping restore the proper balance of salt and fluids in the lungs to improve lung function.
A splicing mutation occurs when there is an alteration in the DNA sequence that changes the instructions needed to properly generate mRNA. Oligonucleotides work by binding to the RNA molecule and correcting these instructions. Oligonucleotides, including ASOs, provide a potential therapeutic approach for several types of CFTR mutations and are already used in the treatment of spinal muscular atrophy, certain forms of muscular dystrophy, and other genetic diseases.
SpliSense’s technology is based on the research of professor Batsheva Kerem from the Hebrew University of Jerusalem. Kerem was part of the team that identified and cloned the CFTR gene which, when mutated, is responsible for causing cystic fibrosis.