SpliSense Ltd.

JERUSALEM, May 29, 2024 /PRNewswire/ -- SpliSense, a clinical-stage biotechnology company focused on the development of transformative RNA-based therapies for pulmonary diseases including cystic fibrosis (CF), muco-obstructive diseases like COPD, asthma and NCFB and idiopathic pulmonary fibrosis (IPF), today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to SPL84 for CF. SPL84 is the Company's lead antisense 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. "Fast Track Designation for SPL84 is an important acknowledgement by the FDA of the critical need to find an effective treatment for CF patients carrying the 3849+10 kilobase (Kb) C->T mutation, a serious and life-threatening condition with very poor treatment options," said Gili Hart, PhD, CEO of SpliSense. "The recent IND clearance we received from the FDA together with this Fast Track designation for SPL84, currently being evaluated in a global Phase 2 study, will allow us to expedite the development of a potentially life-changing treatment for people with CF carrying the 3849+10 Kb C->T mutation, and expand our unique technology to additional pulmonary indication where there is a significant unmet need." About Fast Track Designation The FDA grants Fast Track designation to facilitate the development and expedite the review of medicines to treat serious conditions and fill an unmet medical need. Fast Track status allows for enhanced communication and collaboration between the FDA and drug developers, potentially speeding up the delivery of life-saving treatments to patients. About Cystic Fibrosis (CF) 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 CFTR modulators. However, approved CFTR modulators do not support all people with CF and do not offer a cure for the disease. Thus, new strategies of therapeutic development are essential to address partially responsive and non-responsive people with CF, specifically those carrying the 3849+10 Kb C->T splicing mutation. About SPL84 SpliSense utilizes short, precisely targeted proprietary RNA stretches called Antisense Oligonucleotides (ASOs) to modulate specific mRNA sequences or correct various mutations in the target mRNA. SPL84 binds specifically to the mutated CFTR RNA in the targeted sequence, leading to the modulation of the mutated region in the mRNA, potentially allowing the cell to produce fully functional CFTR proteins. SPL84 is administered directly and preferentially to the lungs via inhalation, where it is designed to be taken up by the lung cells and to drive the production of corrected CFTR mRNA and eventually fully functional CFTR proteins. SPL84, has been shown to fully restore CFTR activity in the CF gold standard pharmacological model. SPL84 is currently being evaluated in a global Phase 2 study for the treatment of patients with CF carrying the 3849+10 kilobase (Kb) C->T by weekly inhalation regimen. About SpliSense SpliSense is a biotechnology company focused on the development of 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 address specific genetic mutations or deficiencies, by restoring or reducing protein function, thus targeting the root cause of the disease. For additional information, please visit our website at: Company contact: Tsipi Haitovsky Global Media Liaison +972-52-5989-892 [email protected] SOURCE SpliSense

- Funding secured from CF Foundation and current investors for SPL84 Phase 2 study - - Two additional early-stage candidates expected to commence Phase 1-2a studies over the next 12 months – JERUSALEM, April 3, 2024 /PRNewswire/ -- SpliSense, a clinical-stage biotechnology company focused on the development of transformative RNA-based therapies for pulmonary diseases including cystic fibrosis (CF), muco-obstructive diseases like COPD, asthma, non-CF bronchiectasis (NCFB) and idiopathic pulmonary fibrosis (IPF), today announced that the U.S. Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for the initiation of a Phase 2 study for SPL84 in 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. The Company has also announced today that it has secured funding from the CF Foundation and other existing investors to support the SPL84 Phase 2 study and additional pulmonary programs. This represents the CF Foundation's third investment in SpliSense's SPL84 program. "We are excited to initiate the Phase 2 study for SPL84 in CF with the support of the CF Foundation and other existing investors," said Gili Hart, PhD, Chief Executive Officer of SpliSense. " 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." "In addition, SPL84 serves as proof-of-concept for our platform for the treatment of additional pulmonary diseases, including muco-obstructive diseases and IPF, which are expected to enter the clinic over the next 12 months," added Dr. Hart. About Cystic Fibrosis (CF) 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 CFTR modulators. However, approved CFTR modulators do not support all people with CF and do not offer a cure for the disease. Thus, new strategies of therapeutic development are essential to address partially responsive and non-responsive people with CF, specifically those carrying the 3849+10 Kb C->T splicing mutation. About SPL84 SpliSense utilizes short, precisely targeted proprietary RNA stretches called Antisense Oligonucleotides (ASOs) to modulate specific mRNA sequences or correct various mutations in the target mRNA. SPL84 binds specifically to the mutated CFTR RNA in the targeted sequence, leading to the modulation of the mutated region in the mRNA, potentially allowing the cell to produce fully functional CFTR proteins. SPL84 is administered directly and preferentially to the lungs via inhalation where it is designed to be taken up by the lung cells and to drive the production of corrected CFTR mRNA and eventually fully functional CFTR proteins. About SPL5AC (Muco-Obstructive Diseases) and SPL5B (IPF) SpliSense is advancing two preclinical ASO assets for the treatment of additional pulmonary diseases, including muco-obstructive diseases and IPF. Patients with muco-obstructive lung disease are susceptible to severe mortality and morbidity, creating an unmet need for the development of an effective and potent agent in the treatment of mucin induced lung disease. SPL5AC is an ASO that specifically lowers the level of MUC5AC expression and production in mucus, decreases mucus viscosity, eliminates accumulation in the airways, and reduces infection and inflammation as demonstrated in three proof of-concept disease animal models. Chronic overexpression of MUC5B is suggested to be the single greatest risk factor for the development of IPF. SPL5B is an ASO that lowers MUC5B expression and production avoiding accumulation of MUC5B mucin and plugs in the distil regions of the lungs. By lowering MUC5B levels and plugs formation, SpliSense aims to slow or delay IPF progression and improve patient's clinical condition and quality of life. About SpliSense SpliSense is a biotechnology company focused on the development of 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 address specific genetic mutations or deficiencies, by restoring or reducing protein function, thus targeting the root cause of the disease. The Company's investors include Cystic Fibrosis Foundation, OrbiMed, Israel Biotech Fund, Integra Holdings and Biotel Limited. For additional information, please visit our website at: Company contact: Tsipi Haitovsky Global Media Liaison +972-52-5989-892 [email protected] SOURCE SpliSense

The additional funding will support a Phase 2 clinical trial for an inhaled antisense oligonucleotide drug for people with cystic fibrosis who have the splicing mutation 3849+10Kb C-to-T BETHESDA, Md.--(BUSINESS WIRE)-- The Cystic Fibrosis Foundation is investing up to $8.5 million in additional funds in SpliSense to continue clinical trials for its inhaled antisense oligonucleotide (ASO) drug for people with cystic fibrosis who have certain splicing mutations and potentially other rare mutations. The Foundation's funding will support a planned Phase 2 clinical trial to 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. A recent Phase 1a study indicated the drug was safe and well tolerated. “We continue to pursue diverse strategies to develop potential treatments for people with CF who can’t benefit from existing modulator therapies,” said Steven M. Rowe, MD, executive vice president and chief scientific officer at the Foundation. “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.” Splicing mutations disrupt the production of normal cystic fibrosis transmembrane conductance regulator (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. In 2021, the Foundation invested $8.4 million in SpliSense to develop a therapy for splicing mutations, in addition to $400,000 the Foundation provided in 2017. All these investments are part of the Foundation’s $500 million Path to a Cure, an ambitious research initiative to accelerate treatments for everyone with CF and ultimately deliver a cure. About the Cystic Fibrosis Foundation The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization, and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The CF Foundation is a donor-supported nonprofit organization. For more information, visit cff.org.