[January 05, 2017] |
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Catabasis Pharmaceuticals Research on CAT-5571, a Novel Activator of Autophagy and Potential Oral Treatment for Cystic Fibrosis, Published in Journal of Medicinal Chemistry
Catabasis
Pharmaceuticals, Inc. (NASDAQ:CATB), a clinical-stage
biopharmaceutical company, today announced the publication of
preclinical data on CAT-5571, a novel activator of autophagy and
potential oral treatment for cystic fibrosis (CF). The preclinical data
demonstrate an increase in CF transmembrane conductance regulator (CFTR)
activity and trafficking which are detailed in an article titled "Fatty
Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators that
Enhance the Correction of Misfolded F508del-CFTR" in the Journal of
Medicinal Chemistry (J Med Chem. 2016 Dec 23. doi:
10.1021/acs.jmedchem.6b01539).
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,"
said Andrew Nichols, Ph.D., Chief Scientific Officer of Catabasis. "This
program further builds our rare disease pipeline and shows the
capability of the proprietary Catabasis SMART linker drug discovery
platform."
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 inracellular 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.
About CAT-5571 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.
About Catabasis At Catabasis Pharmaceuticals, our mission is
to bring hope and life-changing therapies to patients and their
families. Our SMART (Safely Metabolized And Rationally Targeted) linker
drug discovery platform enables us to engineer molecules that
simultaneously modulate multiple targets in a disease. We are applying
our SMART linker platform to build an internal pipeline of product
candidates for rare diseases and plan to pursue partnerships to develop
additional product candidates. For more information on the Company's
drug discovery platform and pipeline of drug candidates, please visit www.catabasis.com.
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 September
30, 2016, which is on file with the Securities and Exchange Commission,
and in other filings that the Company may make with the Securities and
Exchange Commission in the future. In addition, the forward-looking
statements included in this press release represent the Company's views
as of the date of this press release. The Company anticipates that
subsequent events and developments will cause the Company's views to
change. However, while the Company may elect to update these
forward-looking statements at some point in the future, the Company
specifically disclaims any obligation to do so. These forward-looking
statements should not be relied upon as representing the Company's views
as of any date subsequent to the date of this release.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170105005452/en/
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