In the US, there are approximately 30,000 people living with CF. It is a disease characterized by a defect in the CFTR protein that results in impaired or absent mucus clearance of copious amounts of thick, sticky mucus. CF lungs are chronically inundated with neutrophilic inflammation and chronic bacterial infection. Over time, the combination of inflammation and infection result in obstruction of the airways, thereby resulting inflammation and infection throughout the lungs that eventually leads to clinical decline. Despite advances in CF, there remains a critical need for therapies that will decrease mucus viscosity and improve mucus transport out of the airways.
Ex vivo and in vitro data demonstrates that ARINA-1 completely restores mucus clearance in dF508 homozygous airway epithelial cells by significantly and profoundly decreasing mucus viscosity. Further, ARINA-1 has both direct anti-inflammatory and antibacterial properties. Thus, by clearing the airway and downregulating inflammation caused by neutrophils and inhibiting the growth of immunostimulating bacteria, ARINA-1 has a high probability of success in this difficult-to-treat patient population.
ARINA-1 has been used in one patient with CF (dF508 homozygous) for over 13 years with great success. The patient has experienced stabilized pulmonary function and decreased exacerbation rates since using ARINA-1 twice daily. Currently, Renovion is working with key opinion leaders to begin a Phase 2b proof-of-concept clinical trial in 2020.
PRIMARY CILIARY DYSKINESIA
In the US, there are approximately 3,000 people living with primary ciliary dyskinesia (PCD). It is a disease characterized by a defect in cilia throughout the body, including the cilia that line the respiratory tract and sweep inflammatory and infectious material from the lungs. Impaired lung cilia results in excessive mucus that is unable to be cleared from the airway and causes accumulation of inflammatory and infectious material in the lungs that can lead to pulmonary infections, decreased pulmonary function and eventual clinical decline. Despite advances in similar airway diseases, there remains a critical need for therapies that will improve mucus clearance and protect the lungs in PCD.
Ex vivo data in cells that are genetically lack mucus clearance function demonstrate that ARINA-1 completely restores mucus clearance by significantly and profoundly decreasing mucus viscosity. Further, ARINA-1 has both direct anti-inflammatory and antibacterial properties. Thus, by clearing the airway and protecting the lungs from inflammation and infection, ARINA-1 has a high probability of success in PCD. Renovion plans to start a small proof-of-concept study in PCD in early 2020.
ALPHA-1 ANTI-TRYPSIN DEFICIENCY
About 100,000 people in the US are living with alpha-1 anti-trypsin deficiency (A1AD) lung disease, which is characterized by progressive destruction of the lungs due to uncontrolled inflammatory processes. Alpha-1 anti-trypsin is an enzyme involved in regulating inflammatory responses, and when it is deficient, neutrophilic inflammation causes pulmonary decline. Often described as "genetic COPD," patients experience a variety of symptoms including chronic cough, mucus production and frequent pulmonary infections. The current treatment for A1AD is systemic enzyme replacement. However, patients with A1AD still experience coughing, excess mucus and pulmonary damage.
Data from neutrophils collected from volunteers demonstrate that ARINA-1 downregulates inflammation- and damage-causing cytokine release from neutrophils. Additionally, its potent mucus clearance and anti-bacterial functions clear the airways of thick mucus and inflammatory debris while protecting the lungs from infection. Given these data, ARINA-1 is a logical and safe therapy for use in patients with A1AD. Renovion plans to start a small proof-of-concept study in A1AD in mid-2020.