Cempra Pharmaceutical's CEM-101 Demonstrates Potent Anti-Inflammatory Activity, Compared to Other Macrolide Antibiotics, in an Inflammation Cell Model at the American Thoracic Society 2010 International Conference
CHAPEL HILL, N.C., May 18 /PRNewswire/ -- Cempra Pharmaceuticals today announced the results from two poster presentations on its novel antibiotic CEM-101, a next-generation macrolide, at the American Thoracic Society 2010 International Conference, May 14 to 19, 2010, in New Orleans. Both presentations are scheduled for 8:15 a.m. to 4 p.m. CDT on Tuesday, May 18.
The two posters by Kobayashi et al. compared the anti-inflammatory activity of CEM-101 to several available macrolide antibiotics in an in vitro inflammation model for chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic and progressive airway inflammation and oxidative stress. Macrolides have previously been reported to reduce COPD exacerbations and show anti-inflammatory effects in vitro.
In the presentation entitled "Superior Anti-Inflammatory Effects of a Novel Macrolide/Fluoroketolide, CEM-101 in Monocytic cells (Poster #3527)," the investigators found that CEM-101 significantly reduced the levels of three inflammatory markers tested - matrix metalloproteinase 9 (MMP9), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF alpha) – as compared to the macrolides clarithromycin, azithromycin and telithromycin. CEM-101's IC(50) value, a measure of the effectiveness of a compound to inhibit a biological or biochemical function, was 10 times greater than the three other active macrolides. The fifth macrolide tested, erythromycin, did not reduce any inflammatory markers.
In "A Novel Macrolide/Fluoroketolide, CEM-101, Reverses Corticosteroid Insensitivity Under Oxidative Stress via PI3K Pathway Inhibition (Poster #3506)," the authors demonstrated that CEM-101 restored corticosteroid sensitivity by restoring HDAC activity and HDAC2 expression and preventing protein kinase B (Akt) phosphorylation by inhibiting the phosphoinositide 3 kinase (PI3K) pathway in human monocytic U937 cells in vitro. Oxidative stress in the lungs of COPD patients can result in corticosteroid insensitivity due to oxidative stress-induced down regulation of histone deactylase 2 (HDAC2) expression and activity caused by activation of PI3K. CEM-101's ability to restore corticosteroid sensitivity was superior to the other macrolides tested (erythromycin, clarythromycin and azithromycin).
"COPD is a debilitating and progressive disease with few therapeutic options," Peter J. Barnes FMedSci, FRS, professor of thoracic medicine, the Airway Disease Section, NHLI, Imperial College London and co-author of the studies, "The anti-inflammatory potential of CEM-101 seen in these studies suggests a role for the compound or for new anti-inflammatory-specific members of the macrolide class in COPD patients."
Prabhavathi Fernandes, Ph.D., chief executive officer of Cempra said, "CEM-101 is a macrolide anti-bacterial candidate that has shown potent and broad spectrum activity in in vitro studies and in animal infection models and has been found to be well tolerated in Phase 1 trials. We are very encouraged by the results from these two studies demonstrating the compound's potent anti-inflammatory activity as well. Previous studies have shown that anti-inflammatory activity aids macrolide antibacterial efficacy. Therefore, these results add to the very interesting and promising therapeutic profile of CEM-101."
CEM-101 is a next generation macrolide with a number of attributes that may provide clinically important advantages over several comparator products:
- Potent activity, in vitro and in vivo, against all important pathogens that cause community-acquired bacterial pneumonia, including pneumococci, as well as potent activity against a broad spectrum of other serious pathogens including CA-MRSA, M. avium, malaria, atypical bacteria such as Legionella, Mycoplasma, Chlamydophila, and Neisseria
- CEM-101 is generally 8 to 16 times more potent than azithromycin and is active against organisms that have become resistant to azithromycin
- Novel structure with additional binding sites on the bacterial ribosome that confers activity against erm- and mef-resistant strains
- Good tolerability and oral bioavailability in phase 1 trials
- Low resistance frequency in vitro
- Excellent tissue distribution and intracellular tissue concentrations
- Oral and IV formulations
- Once-daily dosing
- Potential for indications beyond CABP, including urethritis and other urogenital infections, bioterrorism targets, malaria, M. avium infections and tuberculosis
The annual incidence for pneumonia in the United States is over 5 million patients each year. There is a growing need for new drugs to address the issues of drug resistance, tolerability, and administration associated with currently available treatments. Cempra has licensed exclusive worldwide rights from Optimer Pharmaceuticals, Inc., except in the Association of Southeast Asian Nations (ASEAN) countries, to discover, develop and commercialize macrolides from a library of more than 500 compounds from Optimer's OPopS drug discovery platform.
About Cempra Pharmaceuticals
Founded in 2006, Cempra Pharmaceuticals is a privately-held, clinical-stage pharmaceutical company focused on developing antibacterials to address critical medical needs. Two lead products, both in late-stage clinical trials, address the urgent and increasing need for new treatments targeting drug-resistant bacterial infections in the hospital and in the community. Cempra is well-funded and is committed to developing commercially and medically differentiated and novel products that reduce development risk and provide a high financial return. The company is also utilizing its proprietary compound library and chemistry technology to develop novel macrolides without antibacterial activity for non-antibiotic uses such as COPD, chronic inflammatory and GI disorders. Additional information about Cempra can be found at www.cempra.com.
SOURCE Cempra Pharmaceuticals
Posted: May 2010