The trial will test the efficacy of SpliSense’s inhaled ASO drug as a potential treatment for the lungs of people with the splicing mutation 3849+10Kb C-to-T. 

RT’s Three Key Takeaways: 

  1. SpliSense received FDA clearance to start a phase 2 trial for SPL84, a potential treatment for certain cystic fibrosis patients.
  2. The treatment aims to correct a genetic mutation affecting CFTR protein function, potentially addressing an unmet need in cystic fibrosis care.
  3. The CF Foundation will provide up to $8.5 million to SpliSense to support the trial for a potential treatment for splicing mutations.

SpliSense, a clinical-stage biotechnology company focused on the development of RNA-based therapies for pulmonary diseases, announced that the US Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for the initiation of a phase 2 study for SPL84 in cystic fibrosis (CF). 

SPL84 is the company’s lead antisense oligonucleotide (ASO) product for the treatment of people with CF carrying the 3849+10 kilobase (Kb) C->T splicing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

The IND clearance for the phase 2 study initiation was granted following SPL84’s favorable safety profile, supported by phase 1 and preclinical toxicological and pharmacological data demonstrating the potential for full restoration of CFTR protein and activity, based on clinically predictive CF models.

Mechanism of Action

Splicing mutations disrupt the production of normal CFTR RNA, resulting in dysfunctional CFTR proteins. SpliSense’s drug would work by binding to the RNA molecule and correcting the instructions to create healthy, full-length CFTR proteins, helping restore the proper balance of salt and fluids in the lungs of people with CF.

The objective of the clinical trial is to generate a proof-of-concept for ASO technology in cystic fibrosis. If the clinical trial is successful, it could validate other similar therapeutic approaches in SpliSense’s pipeline that address rare CF mutations.

“We are excited to initiate the phase 2 study for SPL84 in CF with the support of the CF Foundation and other existing investors,” says Gili Hart, PhD, chief executive officer of SpliSense, in a release. “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. 

“Our lead product, SPL84, has been shown to fully restore CFTR activity in the CF gold standard pharmacological model. With the recent FDA IND clearance, we hope to be able to deliver, a life-changing treatment for people with CF carrying the 3849+10 Kb C->T mutation and expand our unique technology to additional CF mutations where there is a significant unmet need.”

Strategic Partnerships and Support

The company also secured funding from the CF Foundation and other existing investors to support the SPL84 phase 2 study and additional pulmonary programs. The CF Foundation will provide up to $8.5 million to support the clinical trial. This represents the CF Foundation’s third investment in SpliSense’s SPL84 program.

“We continue to pursue diverse strategies to develop potential treatments for people with CF who can’t benefit from existing modulator therapies,” says Steven M. Rowe, MD, executive vice president and chief scientific officer at the CF Foundation, in a release. “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.”

Future Directions

In addition, SPL84 serves as proof-of-concept for SpliSense’s platform for the treatment of additional pulmonary diseases, including muco-obstructive diseases and idiopathic pulmonary fibrosis, which are expected to enter the clinic over the next 12 months, notes Hart.

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