Catabasis Pharmaceuticals Research on CAT-5571, a Novel Activator of Autophagy and Potential Oral Treatment for Cystic Fibrosis, Published in Journal of Medicinal Chemistry
-- Preclinical Data Demonstrate that Fatty Acid Cysteamine Conjugates Are Autophagy Activators that Enhance the Correction of Misfolded F508del-CFTR --
The publication describes the synthesis and biology of the CAT-5000 series of molecules developed using the proprietary Catabasis SMART linker drug discovery platform. The data demonstrate that CAT-5571 is a novel autophagy activator which, in combination with the current standard of care therapy, increased the cell surface expression and function of CFTR in bronchial epithelial cells isolated from multiple CF patients with the F508del mutation. When CAT-5571 was used in combination with lumacaftor and ivacaftor, it significantly enhanced the effects on the cells of the standard of care combination, both in the amount of the more mature C-band form of the CFTR protein with complex glycosylation, and in the amount of the CFTR protein reaching the cell surface. Importantly, CAT-5571 significantly enhanced the lumacaftor/ivacaftor-mediated chloride current increase in cultured primary homozygous F508del human bronchial epithelial cells.
“We are excited about these preclinical results and the potential of
autophagy activation by CAT-5571 as a treatment for CF that is able to
improve CFTR trafficking and function. We look forward to progressing
CAT-5571 in preclinical development and toward clinical development,”
Catabasis expects to initiate a Phase 1 clinical trial with CAT-5571 for the potential treatment of CF in Q4 2017 or Q1 2018. CAT-5571 is a novel molecule comprising cysteamine covalently conjugated to docosahexaenoic acid (DHA) using the company’s SMART linker drug discovery platform to enhance the intracellular activity of the bioactive components. CAT-5571 allows sustained intracellular delivery of the two bioactive components leading to activation of autophagy through two different pathways. Autophagy is a process that maintains cellular homeostasis and host defense mechanisms, and is known to be impaired in CF. We have found that the level of autophagy activation achieved with CAT-5571 cannot be replicated by administering the bioactive components either individually or in combination, even at much higher concentrations.
Catabasis is developing CAT-5571 as a potential oral treatment for cystic fibrosis (CF) with potential effects on both the cystic fibrosis transmembrane conductance regulator (CFTR) and on the clearance of Pseudomonas aeruginosa. CAT-5571 is a small molecule that activates autophagy, a process that maintains cellular homeostasis and host defense mechanisms, and is known to be impaired in CF. Catabasis has shown in preclinical studies that CAT-5571, in combination with lumacaftor/ivacaftor, enhances cell-surface trafficking and function of CFTR with the F508del mutation. Catabasis has also shown that CAT-5571 enhances the clearance of P. aeruginosa infection in preclinical models of CF, regardless of CFTR mutation status.
About Cystic Fibrosis
Cystic fibrosis (CF) is a rare, chronic, genetic, life-shortening disease that affects over 70,000 patients worldwide, predominantly in the Caucasian population. In CF, a malfunctioning cystic fibrosis transmembrane conductance regulator (CFTR) ion channel impairs chloride secretion, with deleterious effects on multiple organs, and particularly devastating effects on pulmonary, intestinal and pancreatic function. Patients affected with CF are also predisposed to respiratory failure caused by persistent lung infections that are difficult to treat with standard antibiotics. Advancements in research and treatments have extended the life expectancy for those living with CF, however there is currently no cure.
Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including statements about future clinical trial plans and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “may” and similar expressions, constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company’s product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial potential of the Company’s product candidates; and general economic and market conditions and other factors discussed in the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q for the period ended
Catabasis Pharmaceuticals, Inc.
Andrea Matthews, 617-349-1971