Rare Daily Staff

Israel-based SpliSense, which is developing mRNA-altering therapies for cystic fibrosis and other genetic pulmonary diseases, raised $28.5 million through a series B funding round.

Orbimed, Israel Biotech Fund, Biotel Limited, Integra Holdings and the Cystic Fibrosis Foundation participated in the round.

Proceeds will be used to advance the company’s pipeline, including its lead antisense oligonucleotide (ASO) product, SPL84-23. SPL84-23 is designed to treat the 3849+10kb C->T CFTR mutation. The company said the experimental therapy has been able to completely restore cystic fibrosis transmembrane conductance regulator (CFTR) channel function in patient-derived cell cultures. SpliSense plans to initiate a phase 1/2a trial in 2022.

Cystic fibrosis (CF) is a rare, life-shortening genetic disease. It is caused by mutations in the CFTR gene that lead to a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein. Children must inherit two defective CFTR genes—one from each parent—to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

SpliSense utilizes short, precisely targeted proprietary RNA stretches called ASOs to correct various mutations in the CFTR mRNA. In particular, the ASO binds to the mutated CFTR RNA in the desired spot, leading to the elimination of the mutated region from the mRNA and allowing the cell to produce functional CFTR proteins. The ASOs are administered directly and preferentially to the lungs via inhalation where they are taken up by the lung cells and drive the production of corrected CFTR mRNA and eventually functional CFTR proteins. SpliSense utilizes proprietary algorithms to support the design of optimized ASOs, thereby maximizing efficiency and reducing the potential for undesired effects.

SpliSense’ technology is based on the research of Batsheva Kerem, a geneticist from the Hebrew University of Jerusalem, who was part of the research team that identified and cloned the CFTR gene. The technology was licensed from Yissum, the technology transfer office of Hebrew University.

“Currently available treatments focus on treating the symptoms of the disease, such as channel function and protein modulators, antibiotics to treat lung infections, or mucus thinning drugs. However, they do not treat the root cause of the disease,” said Gili Hart, CEO of SpliSense. “Our technology addresses the underlying genetic cause, thereby offering, for the first time, hope of restoring adequate lung function to CF patients.”

Photo: Gili Hart, CEO of SpliSense

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