SpliSense Raises $28.5M to Advance Treatments for Rare CF Mutations

SpliSense has raised $28.5 million in funding to advance its antisense oligonucleotide (ASO) platform for the treatment of cystic fibrosis (CF) caused by certain rare mutations, and of other genetic lung diseases.

ASOs are molecules designed to target the messenger RNA (mRNA), the intermediate molecule derived from DNA that guides protein production.

Money raised came through a series B financing round featuring Orbimed, Israel Biotech Fund, Biotel Limited, Integra Holdings, and the Cystic Fibrosis Foundation (CFF).

The CFF invested up to $8.4 million as part of its Path to a Cure, a $500 million initiative to promote the development of new treatments tackling CF’s underlying cause for every person with CF. The foundation also awarded SpliSense $400,000 in 2017 to develop this type of ASO-based therapy.

“This successful funding round is a vote of confidence of in our platform technology and early-stage therapeutic pipeline,” Gili Hart, PhD, SpliSense’s CEO, said in a press release.

“Currently available [CF] treatments focus on treating the symptoms of the disease,” while “our technology addresses the underlying genetic cause, thereby offering, for the first time, hope of restoring adequate lung function to CF patients,” Hart said.

“We look forward to using this funding and the support of the Cystic Fibrosis Foundation to advance our pipeline for the benefit of CF patients,” Hart added.

The funding “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,” William Skach, MD, CFF’s executive vice president and chief scientific officer, said in a separate press release.

“As such, these studies will provide important information for the future development of these potential therapies for additional people with rare mutations,” Skach added.

Genes consist of alternating pieces, exons and introns, with exons alone containing the information necessary to build proteins. The conversion of genetic information into proteins involves the production of an intermediate mRNA molecule that cuts out introns and pieces exons together, as in a puzzle, to produce a functional protein. This process is called splicing.

CF is caused by mutations in the CFTR gene, which provides the instructions to produce a protein channel of the same name that controls the flow of water salts through cells. Defects in CFTR result in the production of mucus and salty sweat.

More than 1,700 CF-causing mutations identified to date affect CFTR production in different ways.

Some of these mutations are called splicing mutations, meaning that they change CFTR’s splicing process, affecting production of a working protein. ASOs have the potential to correct this type of mutation by masking the mutated region, so that splicing can be restored and a fully functional protein produced.

SpliSense is working to develop inhalation-delivered ASOs targeting rare CFTR mutations, which show no response to approved CFTR modulators.

The Israel-based company uses its proprietary algorithm to design highly efficient ASOs, with a lesser risk of off-target effects (additional genes that are targeted) and of immune reactions.

Its technology is based on the research of Batsheva Kerem, PhD, a professor of genetics at the Hebrew University of Jerusalem who was part of the team that identified and characterized the CFTR gene.

Proceeds will be used to advance the company’s pipeline, such as its lead ASO, SPL84-23, designed to correct a rare CF-causing splicing mutation called 3849+10kb C-to-T. The therapy was found to completely restore CFTR channel function in lab-grown cells derived from patients carrying that mutation, according to SpliSense.

SpliSense plans to launch a Phase 1/2 clinical trial of SPL84-23 in 2022.

Other earlier-stage CF therapies being developed by the company include SPL23-2 and SPL24-N.

SPL23-2 is designed to treat CF patients with the W1282X mutation, which leads to a shorter mRNA that is targeted for degradation, while SPL24-N aims to treat those carrying the N1303K mutation, which results in the production of a misfolded protein.

“SpliSense couples Prof. Kerem’s pioneering research on the genetic underpinnings of CF together with a strong track record in developing ASO therapies and inhaled treatments,” said Nissim Darvish, MD, chairman of SpliSense’s board. “We have great faith in SpliSense’s transformative technology … and await with interest the advancement of its pipeline into the clinic.”