FDA clears Phase 2 clinical trial of inhalation therapy SPL84 for CF

CF Foundation helps fund study of treatment for 3849+10 kb C-to-T mutation

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has given the go-ahead for a Phase 2 trial testing the inhalation therapy SPL84 in people with cystic fibrosis (CF) caused by a specific mutation called 3849+10 kb C-to-T.

Therapy developer Splisense welcomed the FDA’s clearance of the clinical trial, and announced it had secured new funding from its investors for the study — including up to $8.5 million in additional monies from the Cystic Fibrosis Foundation. The nonprofit has invested nearly $9 million in the company since 2017.

“Although currently available CF therapies have managed to significantly increase life expectancy over the past few decades, there is still a significant unmet medical need for disease modifying treatments,” Gili Hart, PhD, CEO of Splisense, said in a company press release.

“We are excited to initiate the Phase 2 study for SPL84 in CF with the support of the CF Foundation and other existing investors,” Hart said.

The investigational therapy, given via inhalation, aims to target a specific disease-causing mutation in the CFTR gene.

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Several mutations in the CFTR gene can cause CF by resulting in a lack of functional CFTR protein.

In many people with the disease, such mutations lead to the production of a version of the CFTR protein that doesn’t work correctly. A recently developed class of medications called CFTR modulators are able to increase protein functionality in CF patients with many of these mutations. But not all patients are eligible for treatment with CFTR modulators.

Like other protein-coding genes, the CFTR gene contains exons — the parts of the gene that provide instructions for making proteins — as well as introns, which are sequences that don’t provide instructions for the protein but help regulate the activity of the gene.

When the CFTR gene is read to make the protein, the entire sequence is copied into a temporary molecule called messenger RNA (mRNA). The mRNA then undergoes a process called splicing, where the introns are removed and the exons are strung together to form a mature sequence that can be used as a template to make protein.

The splicing mutation here, 3849+10Kb C-to-T, makes alterations to the splicing process, with the end result that cells produce a shorter and dysfunctional CFTR protein. SPL84, previously known as SPL84-23, is an RNA-based medicine that’s designed to correct this splicing deficit, allowing for the production of a fully functional CFTR protein.

The experimental inhalation therapy guides the medication directly into the lungs. It’s shown promise in lab models of CF, and recent data from a first-in-human study in healthy volunteers suggested a favorable safety profile.

With the recent FDA IND [investigational new drug application] clearance, we hope to be able to deliver … a life-changing treatment for people with CF carrying the 3849+10 Kb C->T mutation.

According to Hart, SPL84 “has been shown to fully restore CFTR activity in the CF gold standard pharmacological model.”

“With the recent FDA IND [investigational new drug application] clearance, we hope to be able to deliver … a life-changing treatment for people with CF carrying the 3849+10 Kb C->T mutation,” Hart said.

Steven M. Rowe, MD, executive vice president and chief scientific officer at the CF Foundation, said the nonprofit is keen to support the development of potential treatments that can help patients with any of a range of mutations.

“Information from this study is key to advancing those efforts with a novel technology and will also provide valuable insight into the development of therapies for people with rare mutations,”Rowe said in a foundation press release.

The CF Foundation has been a major investor in Splisense’s tech — between a smaller initial investment and a larger one in 2021, the foundation has invested nearly $9 million in the company. These previous investments, as well as the new one to support the Phase 2 study, are part of the foundation’s $500 million Path to a Cure project.

“We continue to pursue diverse strategies to develop potential treatments for people with CF who can’t benefit from existing modulator therapies,” Rowe said.