SpliSense Successfully Completed Phase 1 Study of SPL84, RNA-Based Therapy, for the Treatment of Cystic Fibrosis

Phase 2 efficacy study to be initiated in H1 2024

New data published in Nucleic Acid Therapeutics demonstrate broad distribution, as well as cell and nucleus penetration of SPL84 in lungs of animal models, overcoming hyper-concentrated mucus barriers, thus leading to specific and targeted RNA modulation

JERUSALEM, Sept. 6, 2023 /PRNewswire/ -- SpliSense, a biopharmaceutical company developing transformative RNA-based therapies for pulmonary diseases including  cystic fibrosis (CF), muco-obstructive diseases and idiopathic pulmonary fibrosis (IPF), today announced that it has successfully completed a first-in-human, Phase 1 clinical trial of SPL84, the Company's lead inhaled anti sense oligonucleotide (ASO) product for the treatment of patients with CF carrying the 3849+10 kilobase (Kb) C->T splicing mutation in the transmembrane conductance regulator (CFTR) gene. SPL84 was shown to be safe and well tolerated.

In the Phase 1 study, 32 healthy male volunteers received a single dose of SPL84 or placebo and 4 doses were tested: 20, 40, 80, and 160 mg (active: placebo 3:1). SPL84 was shown to be safe and well tolerated, and no serious adverse events or significant related adverse events were identified. There were no significant changes from baseline in vital signs, clinical laboratory values, ECG, physical examination, or pulmonary function. Systemic exposure to SPL84 was very low and dose dependent. The first-in-human Phase 1 placebo-controlled, double–blind, randomized study evaluating the safety, tolerability, and pharmacokinetics of SPL84 was a single ascending dose study in healthy volunteers, administered via inhalation.

"We are extremely excited with the safety profile of SPL84 as demonstrated in this Phase 1 study, paving the way to our Phase 2 efficacy study, that we plan to initiate in the first half of next year," said Gili Hart, PhD, Chief Executive Officer, SpliSense. "CF is one of the most common genetic diseases, leading to frequent lung infections, breathing difficulties and reduced life expectancy. Although currently available treatments managed to significantly increase life expectancy in the past few decades, they are focused on symptomatic treatments and there is still a significant unmet medical need for a CF cure. In particular CF patients carrying the 3849 +10 Kb C->T mutation have no specific approved treatment. Our lead product, SPL84, managed to completely restore CFTR activity the CF gold standard pharmacological model, and with the results announced today supporting its safety in humans, we hope to be able to deliver in the foreseeable future a life-changing treatment for CF patients."

In addition, SpliSense annouced the publication of a paper titled "Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849 + 10 kb C- > T Cystic Fibrosis Patients" in Nucleic Acid Therapeutics. The data demonstrate broad distribution, as well as cell and nucleus penetration of SPL84 in mouse and monkey lungs. In vivo and in vitro studies confirmed the stability of the inhaled drug in CF patient-derived mucus and in lung lysosomal extracts. The mobility of SPL8 through CF Patients hyper-concentrated mucus was also demonstrated. The results, supported by a promising preclinical pharmacological effect of full restoration of CFTR channel activity, emphasize the high potential of SPL84 as an effective drug for the treatment of CF patients.

"The encouraging Phase 1 clinical trial results together with the preclinical data published in Nucleic Acid Therapeutics showing broad lung distribution of SPL84 support the further development of our wider pulmonary pipeline, including treatments for muco-obstructive diseases and idiopathic pulmonary fibrosis, both of which are expected to enter the clinic next year," added Dr. Hart.

CF is a genetic multisystem disorder that originates from various mutations in the CFTR gene, which is responsible for the production of the CFTR protein, a chloride channel expressed in the lungs as well as in other tissues. The past decade has seen a dramatic change in CF care with the approval of new therapies (CFTR modulators). However, approved CFTR modulators do not support all patients with CF and do not offer a cure for the disease. Thus, new strategies of medication development are essential to address non-responsive CF patients, and specifically patients carrying the 3849 +10 Kb C->T splicing mutation.

SpliSense utilizes short, precisely targeted proprietary RNA stretches called ASOs to correct various mutations in the CFTR mRNA. In particular, the ASO binds specifically to the mutated CFTR RNA in the targeted sequence, leading to the modulation of the mutated region in the mRNA, allowing the cell to produce fully functional CFTR proteins. The ASOs are administered directly and preferentially to the lungs via inhalation which lasts less than 10 minutes and is given weekly or every other week. The ASOs were shown to be efficiently taken up by the lung cells and drive the production of corrected CFTR mRNA and eventually fully functional CFTR proteins.

About SpliSense

SpliSense is a biopharmaceutical company focused on RNA-based treatments for pulmonary diseases. The Company's pioneering platform harnesses ASOs for treatment of unmet cystic fibrosis mutations and large pulmonary diseases including muco-obstructive diseases and IPF. Through its novel ASO pulmonary approach, SpliSense aims to overcome specific genetic mutations, restore or reduce protein expression and function, thus targeting the root cause of the disease.  SpliSense' technology is based on the research of Prof. Batsheva Kerem, PhD, a renowned geneticist from the Hebrew University of Jerusalem, who was part of the research team that identified and cloned the CFTR gene. Investors in the Company include Orbimed, Israel Biotech Fund, Biotel Limited, Integra Holdings and the Cystic Fibrosis Foundation. For additional information, please visit our website at SpliSense.com.

Company contact:

Tsipi Haitovsky, Global Media Liaison; +972-52-5989-892; [email protected]

SOURCE SpliSense