Preparations Underway for Launch of Multinational Phase 2 Study
DURHAM, N.C., May 23, 2017 – Spyryx Biosciences, Inc., a clinical-stage biopharmaceutical company developing innovative therapeutics to address severe lung diseases, shared positive data highlighting clinical safety and pharmacokinetics in healthy volunteers and the preclinical mechanism of action of SPX-101, the Company’s pipeline therapeutic treatment for cystic fibrosis (CF), at the American Thoracic Society International Conference in Washington, DC. Based on this positive data, the Company is preparing to launch a Phase 2 study in CF patients later this year.
SPX-101 is an inhaled peptide with a novel mechanism for regulating epithelial sodium channel (ENaC) density in the airway. The drug is designed to restore a cellular pathway in the lung that promotes airway hydration and mucociliary clearance, which are dysfunctional in CF.
The mechanism of action of SPX-101 is independent of the genetic mutations that cause CF, which makes it a potential therapy for all CF patients.
“The strong clinical and preclinical data presented at ATS helps support the potential of SPX-101 to safely promote airway hydration and mucociliary clearance,” said John Taylor, President and CEO, Spyryx Biosciences. “We will be thoroughly investigating the clinical potential of SPX-101 in our HOPE-1 study, a Phase 2 trial in CF patients, which we anticipate getting underway around the middle of this year.”
Poster # P105
A7674 “SPX-101 Is a Novel ENaC-Targeted Therapeutic for Cystic Fibrosis that Restores Mucus Transport”
This study, which was also published earlier this month in the American Journal of Respiratory and Critical Care Medicine, investigates the preclinical in vitro and in vivo efficacy of SPX-101.
The authors used biochemical approaches to demonstrate that SPX-101 binds specifically to ENaC, but not structurally similar proteins, inducing ENaC internalization in human bronchial epithelial cells from healthy and CF donors. Removal of ENaC from the plasma membrane caused a significant reduction in amiloride sensitive current and increased hydration of the airway epithelial cell cultures. When tested in vivo, SPX-101 fully corrected mucus transport in a sheep model of CF. SPX-101 also increased mucous movement, corrected leukocyte distribution in broncho-aveolar lavage fluid, and increased survival in the βENaC transgenic mouse model of CF.
The authors concluded that via this unique biological mechanism of action in removing ENaC from the cell surface, SPX-101 promotes a durable inhibition of sodium absorption resulting in increased mucus transport.
“We appreciate the opportunity to share our findings with the global respiratory care community at ATS,” said Timm Crowder, PhD, Senior Vice President, Technical Operations, Spyryx Biosciences and one of the authors of the paper. “We believe our findings highlight the opportunity for a treatment pathway that extends beyond mutation specific therapies, with the potential to deliver clinically meaningful benefit to all CF patients.”
Poster # 114
A4736 “Safety and Pharmacokinetics of SPX-101 in Healthy Human Subjects”
This study established the clinical safety and tolerability of SPX-101in healthy, non-smoking adults age 18-50 with no history of respiratory disease and with normal lung function. Each of the 32 participants received one of four doses (20 mg, 60 mg, 120 mg or 240 mg) of SPX-101 or placebo via an investigational eFlow nebulizer system (PARI Pharma, Starnberg, Germany) in a single, ascending dose design. There were no clinically meaningful changes in lung function as measured by forced expiratory volume in one second (FEV1) in any overall dose group. No subject had an abnormal serum potassium value at any time in the study. There were no incidences of bronchoconstriction and no serious adverse events (SAEs) observed in the study. Marginal and transient systemic exposure was evident at low levels only at the first measurement after dosing (5 minutes) and only in 4 of 6 subjects receiving the highest dose.
“We believe the results shared in the preclinical studies, combined with the absence of dose-limiting adverse effects in our 28-day toxicology and Phase 1 clinical testing, provide a strong scientific rationale for the investigation of SPX-101 in a randomized controlled clinical trial of all CF patients, regardless of their CFTR mutation,” said Alistair Wheeler, MD, Chief Medical Officer, Spyryx Biosciences.
About Cystic Fibrosis
CF is an autosomal recessive genetic disorder affecting approximately 75,000 individuals worldwide. The disease is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF profoundly affects the lungs and respiratory tract and is characterized by dehydration of the airway surface, resulting in reduced mucus clearance, the lung’s principle mechanism for maintaining a clean environment. The mucus becomes thick and sticky, progressively accumulating into obstructions that block airflow and result in recurrent colonization of the airways by viruses and bacteria. These pathogens lead to frequent, acute lung infections, chronic inflammation, exacerbations, and impaired lung function. The long-term result of the disease is progressive, permanent tissue damage and scarring (fibrosis) in the lung. No cure for cystic fibrosis is known, although several treatments have been approved to address the underlying cause of the disease in some patients. Despite currently available treatment, the median age of survival for CF patients is approximately 40 years of age.
About Spyryx Biosciences
Spyryx Biosciences is a privately held, clinical-stage biopharmaceutical company developing innovative therapeutics to address severe lung diseases. Spyryx’s lead clinical candidate, SPX-101, is a novel treatment for cystic fibrosis that has successfully completed a Phase 1 study in healthy volunteers and is advancing into Phase 2 in CF patients. The product has demonstrated a robust ability to restore mucociliary clearance in animal models of the disease and has the potential to improve lung function in all CF patients independent of their CFTR mutation. The Spyryx leadership team and scientific staff have extensive experience in the development of respiratory medicines and work closely with a broad group of clinical and scientific experts in the pulmonary field. Spyryx is funded by a first tier syndicate of life science investors, including Canaan Partners, 5AM Ventures and Hatteras Venture Partners. Further information regarding Spyryx Biosciences is available at www.spyryxbio.com.