#Israel #Jerusalem #cystic fibrosis #SpliSense #SPL84

SpliSense Launches Phase 2b Clinical Trial of SPL84

SpliSense, a notable player in biotechnology, has announced the beginning of a Phase 2b clinical trial for its lead product, SPL84. This investigational therapy, classified as an inhaled antisense oligonucleotide (ASO), targets a specific genetic mutation related to cystic fibrosis (CF). The trial is particularly focused on patients who have the 3849+10kb C→T splicing mutation in the CFTR gene.

Study Highlights

SpliSense's SPL84–002 study aims to demonstrate the clinical benefits of adding SPL84 to standard CF treatment regimens. In its earlier phase (Phase 2a), findings suggested that patients experienced a significant improvement in lung function, with nearly 70% of treated participants showing positive outcomes. The new phase of the study will dive deeper into safety and further clinical effectiveness against the backdrop of existing CFTR modulator therapies.

According to Dr. Gili Hart, CEO of SpliSense, the initiation of this trial marks an important step in evaluating whether SPL84 can effectively enhance treatment results for individuals already undergoing standard therapy with CFTR modulators. The data gathered from Phase 2a has informed their confidence in proceeding with Phase 2b, suggested by a favorable safety profile and promising clinical activity noted at the selected dosage of 50 mg.

Trial Design

The Phase 2b study will be a randomized, double-blind, placebo-controlled trial involving approximately 40 patients with cystic fibrosis. Participants will be divided into two groups; one will receive the SPL84 treatment while the other will receive a placebo. The therapy will be administered once weekly for a total of 12 weeks. The primary focus will be on assessing safety and tolerability, while secondary outcomes will include pulmonary function metrics and patient-reported respiratory symptoms.

This structured approach seeks to mitigate common concerns associated with drug trials in sensitive populations, particularly those living with chronic conditions like cystic fibrosis. Data is expected to be available in the second half of 2027, and additional information can be tracked on ClinicalTrials.gov under the identifier NCT06429176.

Mechanism of Action

SPL84 functions on a molecular level by correcting the splicing defect caused by the identified mutation, which disrupts the production of functional CFTR protein, crucial for lung function. This therapy works distinctly from CFTR modulators, positioning it as a potential additive treatment for individuals who have seen only moderate effect from existing therapies.

In preclinical studies, SPL84 demonstrated a full restoration of CFTR activity in test systems, reinforcing the biological rationale for combining SPL84 alongside existing standard treatments such as Trikafta®/Kaftrio® or Alyftrek™. Its design is tailored to modulate RNA directly to address the root causes of CF, highlighting SpliSense's innovative approach towards pulmonary disease therapeutics.

The Future of Cystic Fibrosis Treatment

Given the complexity of cystic fibrosis, characterized by variable patient responses to existing therapies, the introduction of SPL84 could herald enhanced treatment options for those affected by specific mutations. SpliSense is committed to exploring the full potential of SPL84, alongside their broader pipeline that includes treatments targeting other pulmonary conditions.

The move not only represents a significant advancement in cystic fibrosis treatment strategies but also underscores the potential of RNA-based therapies in transforming the healthcare landscape. Patients, advocates, and healthcare providers alike are eager to see how this clinical trial unfolds, hoping for promising outcomes that could redefine care standards in cystic fibrosis.