The biotech firm SpliSense is making significant strides in the development of a novel therapy for cystic fibrosis, announcing a substantial funding injection from the Cystic Fibrosis Foundation and the commencement of its Phase IIb clinical trial. This development marks a critical juncture for the company’s antisense oligonucleotide (ASO) candidate, SPL84, which targets a specific genetic mutation prevalent in a subset of cystic fibrosis patients. The $13 million in funding from the Cystic Fibrosis Foundation is poised to accelerate the progression of SPL84, an inhaled drug designed to address the underlying cause of the disease in a unique way.
Background: The Challenge of Cystic Fibrosis
Cystic fibrosis (CF) is a debilitating genetic disorder that affects tens of thousands of individuals worldwide, with nearly 40,000 children and adults in the United States alone living with the condition. It stems from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein responsible for regulating the movement of salt and water across cell membranes. When the CFTR gene is faulty, it leads to the production of abnormally thick and sticky mucus, which accumulates in various organs, most notably the lungs and digestive system. This mucus buildup obstructs airways, impedes nutrient absorption, and creates a breeding ground for persistent bacterial infections, ultimately leading to progressive lung damage and a shortened lifespan.
For decades, the treatment landscape for CF has focused on managing symptoms and complications. This has included therapies to thin mucus, antibiotics to combat infections, and nutritional support. More recently, a class of drugs known as CFTR modulators has revolutionized treatment for many patients. These oral medications work by targeting specific CFTR mutations to improve the function of the defective protein. Vertex Pharmaceuticals’ Trikafta (elexacaftor/tezacaftor/ivacaftor) has emerged as a leading therapy in this category, achieving significant commercial success with $10.31 billion in sales in 2025, underscoring the substantial unmet need and market potential within the CF space. However, existing CFTR modulators are not effective for all patients, particularly those with certain rare or complex mutations, highlighting the ongoing need for diverse therapeutic approaches.
SpliSense’s Innovative Approach: SPL84 and Antisense Oligonucleotides
SpliSense’s SPL84 represents a distinct therapeutic strategy. It is an antisense oligonucleotide (ASO) therapy, a type of drug that uses short, synthetic strands of nucleic acids to target and modify gene expression. Specifically, SPL84 is engineered to correct a splicing defect caused by the 3849+10kb C→T mutation in the CFTR gene. This particular mutation is significant because it leads to an abnormal splicing of the CFTR messenger RNA (mRNA), resulting in a truncated and non-functional protein. ASOs like SPL84 work by binding to the aberrant mRNA sequence, thereby preventing the incorrect splicing and allowing for the production of a more functional CFTR protein.
A key differentiating factor of SPL84 is its administration route. It is designed to be inhaled directly into the lungs. This targeted delivery system aims to maximize the drug’s concentration at the site of disease pathology, potentially enhancing efficacy and minimizing systemic exposure and associated side effects. This contrasts with the oral administration of most current CFTR modulators.
Promising Phase IIa Results Pave the Way for Further Development
The recent positive outcomes from SpliSense’s Phase IIa trial (NCT06429176) have provided a strong foundation for the advancement of SPL84. This trial enrolled patients who carried the specific 3849+10kb C→T mutation. Notably, some cohorts within the study included patients who were already receiving standard-of-care (SoC) CFTR modulators. The results demonstrated a favorable safety profile for SPL84, coupled with encouraging signs of efficacy. According to SpliSense, up to 70% of treated patients exhibited an improvement in lung function, a critical measure of disease progression and treatment effectiveness in cystic fibrosis.
These Phase IIa findings are particularly significant as SpliSense reports them as the first demonstration of proof-of-concept for an inhaled ASO therapy in cystic fibrosis. This suggests that the inhaled delivery mechanism is viable and that the ASO approach can indeed yield therapeutic benefits for patients with this specific genetic defect.
Regulatory Recognition and Accelerated Pathway
The potential of SPL84 has not gone unnoticed by regulatory bodies. The therapy has garnered important designations from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA has granted SPL84 Fast Track designation and Orphan Drug designation. Fast Track designation is intended to expedite the development and review of drugs for serious conditions that fill an unmet medical need, while Orphan Drug designation provides incentives for the development of drugs for rare diseases. In Europe, the EMA has awarded SPL84 PRIME (PRIority MEdicines) designation, which offers similar benefits by providing early and enhanced dialogue with regulators and a potential for a faster marketing authorization. These designations are crucial as they can streamline the regulatory process, potentially bringing the therapy to patients sooner.
The Cystic Fibrosis Foundation’s Investment: Fueling the Next Stage
The $13 million in funding from the Cystic Fibrosis Foundation represents a substantial endorsement of SpliSense’s technology and the potential of SPL84. This investment is crucial for advancing the drug into the next critical phase of clinical development. The Cystic Fibrosis Foundation is a leading organization dedicated to driving research and innovation to improve the lives of people with CF. Their financial support often signifies a belief in the scientific merit and therapeutic promise of a candidate.
This funding will directly support SpliSense’s ongoing Phase IIb clinical trial. This study is designed as a randomized, placebo-controlled trial, the gold standard for evaluating drug efficacy and safety. It is expected to enroll approximately 40 patients and will be conducted across multiple sites in the United States, Europe, and Israel. The geographical diversity of the trial sites aims to ensure that the findings are representative of a broader patient population. Topline results from this pivotal Phase IIb study are anticipated in the second half of 2027.
Leadership Perspective: Optimism and Future Potential
Gili Hart, CEO of SpliSense, expressed gratitude and optimism regarding the funding and the ongoing development. "We are honored to receive this investment from the Cystic Fibrosis Foundation, one of the world’s leading organizations advancing innovative therapies for people with cystic fibrosis," Hart stated. "We believe this commitment reflects both the strength of our Phase II clinical data and the potential of SPL84 to become a transformative treatment option for patients, paving the way also for earlier candidates in our pipeline developed for additional lung diseases to advance into the clinic."
Hart’s statement highlights not only the immediate focus on SPL84 for cystic fibrosis but also the broader implications for SpliSense’s pipeline. The success of SPL84 could validate the company’s ASO technology platform and its inhaled delivery approach, potentially enabling the development of therapies for other lung diseases.
Broader Ecosystem of Innovation in Cystic Fibrosis Research
SpliSense is not alone in its efforts to combat cystic fibrosis through innovative research. The Cystic Fibrosis Foundation actively collaborates with and supports a range of organizations and companies working on new therapeutic strategies. For instance, in March of the same year, the foundation entered into a research agreement with Antiverse, an AI-driven techbio company. This collaboration aims to develop antibodies that target the extracellular region of the CFTR protein, representing another distinct approach to addressing the disease. Such partnerships underscore the dynamic and multi-faceted nature of research aimed at finding cures and better treatments for cystic fibrosis.
Analysis of Implications: A Targeted Approach and Future Outlook
The progression of SPL84 into Phase IIb trials, bolstered by significant funding, carries several important implications for the cystic fibrosis therapeutic landscape. Firstly, it reinforces the value of targeted therapies that address specific genetic mutations. While broad-acting CFTR modulators have been successful, there remains a substantial patient population with mutations not covered by existing therapies. SPL84 offers hope for this underserved group.
Secondly, the success of an inhaled ASO therapy could open new avenues for drug delivery in respiratory diseases. Targeted delivery to the lungs can potentially improve efficacy and patient experience compared to systemic treatments, especially for chronic conditions requiring long-term management.
Thirdly, the regulatory designations received by SPL84 suggest that regulatory agencies recognize the unmet need and the potential of this novel approach. This expedited pathway could lead to a quicker market approval if the Phase IIb and subsequent Phase III trials yield positive results.
The timeline for SPL84’s development is now clearly defined, with topline data from the Phase IIb trial expected in the latter half of 2027. This provides a concrete milestone for investors, patients, and the broader medical community to watch. The ultimate success of SPL84 will depend on the outcomes of these rigorous clinical trials, but the current momentum, fueled by strong clinical data and substantial financial backing, positions SpliSense as a significant player in the ongoing fight against cystic fibrosis. The company’s progress underscores the relentless pursuit of innovative solutions for genetic diseases and the critical role of organizations like the Cystic Fibrosis Foundation in translating scientific discovery into tangible patient benefits.
