Cempra pharmaceuticals presents new data on its multi-drug resistant anti-infective portfolio

Cempra pharmaceuticals presents new data on its multi-drug resistant anti-infective portfolio, cem-101 and takstatm (cem-102), at the 20th european congress of clinical microbiology and infectious disease

Phase 1 multi-dose study of oral CEM-101, a macrolide, shows excellent tolerability and potential for once-daily dosing

Data on in vitro activity of CEM-101 show broad spectrum of activity and high potency against respiratory, skin and other serious bacterial pathogens including resistant strains
Data on in vitro activity of sodium fusidate (TAKSTA, CEM-102) demonstrated high activity against European gram positive bacterial isolates, including MRSA, despite several decades of use

Chapel Hill, N.C., Apr. 10, 2010 - Cempra Pharmaceuticals today announced poster presentations on its novel antibiotic CEM-101, a next-generation macrolide, and CEM-102 (TAKSTA), the company's proprietary front-loading oral dosing regimen of sodium fusidate, at the 20th European Congress of Clinical Microbiology and Infectious Disease (ECCMID), April 10 to 13, 2010, in Vienna Austria. All presentations are scheduled for 12:30 to 1:30 p.m. CET on Sunday, April 11.

CEM-101 has shown a broad spectrum of activity and high potency against respiratory and other serious pathogens in in vitro and in vivo studies. Data presented at the conference showed results from a Phase 1 multi-dose, dose escalation study in healthy subjects and data from several in vitro activity studies demonstrating the high potency and broad activity spectrum of CEM-101.


The results from the first Phase 1 dose escalation study demonstrated that doses of CEM-101 from 200 to 600 mg were safe and well tolerated in healthy subjects and that the compound's pharmacokinetic profile is supportive of once-daily dosing (Poster #902). CEM-101 was administered once-daily for seven days at 200, 400 and 600 mg. The compound showed moderate accumulation over the seven days of dosing indicating no induction of cytochrome enzymes as is seen with some other macrolides. Mild, clinically insignificant gastrointestinal side effects were the most common adverse events observed in each dose group. There were no clinically significant adverse events.


CEM-101's in vitro spectrum of activity and potency were examined against a variety of respiratory and non-respiratory bacterial pathogens. Jones et al. (Poster #901) tested CEM-101 against European clinical isolates including S. aureus, coagulase negative staphylococci, enteroccoci and S. pneumoniae. They found that CEM-101 exhibited equal to or greater potency, compared to telithromycin, and superior potency, compared to other macrolides against most pathogens causing community-acquired bacterial pneumonia (CABP) and acute bacterial skin structure infections (aBSSI). In another study (Poster #903) CEM-101 demonstrated superior activity against several serotypes of Legionella pneumophila compared to other macrolides, particularly erythromycin and azithromycin, which are commonly used to treat Legionellosis. Only levofloxacin showed comparable activity to CEM-101 in these assays.


CEM-101's increased potency results from the molecule binding to three sites on the bacterial ribosome compared to two sites for other macrolides. It has been hypothesized that the additional binding site would engender activity against pathogens resistant to available macrolides. Dubois and Fernandes (Poster #904) evaluated CEM-101's activity against drug resistant respiratory pathogens, including strains of S. pneumoniae and H. influenza. CEM-101 demonstrated superior activity against S. pneumoniae drug resistant strains including erythromycin-R mef E, erythromycin-R erm B and ciprofloxacin-R gyrA, parC. CEM-101 also demonstrated superior activity, compared to other macrolides, against erythromycin-R erm A, B, C H. influenzae.


Prophylactic treatment with antibiotics is recommended for individuals exposed to bacterial meningitis patients infected with Neisseria meningitides. Unfortunately, resistance or reduced susceptibility to antibiotics used for prophylaxis has been reported. In vitro activity of CEM-101 against invasive N. meningitides isolates, including resistant strains, was investigated (Poster #905), CEM-101 demonstrated activity comparable to ceftriaxone and the fluoroquinolones and had two to 16-fold greater activity compared to other macrolides. CEM-101 may be a potent alternative to current prophylactic therapies.


TAKSTA (CEM-102, sodium fusidate)
TAKSTA is sodium fusidate delivered with a proprietary front-loading dosing regimen to enhance spectrum of activity, optimize efficacy and reduce resistance development. Sodium fusidate has a long and established record of safety and efficacy outside the U.S. It has been reported that bacteria tend to develop resistance to sodium fusidate so the drug is usually used in combination with other drugs outside the U.S. However, this premise has been challenged. Adequate dosing determined by PK/PD calculations could be used to decrease the development of resistance. In vitro activity was analyzed in several thousand strains collected in 13 European countries (Poster #929). Despite being available for over 40 years in Europe sodium fusidate demonstrated sustained activity against S. aureus including methicillin-resistant strains indicating that the compound is not highly susceptible to resistance development. Sodium fusidate appears to provide a valuable oral treatment alternative to other anti-MRSA agents in the management of serious S. aureus infections.


"The in vitro data on CEM-101 that we presented at this year's ECCMID is very consistent with results from earlier work. The completion of the multi-dose Phase 1 study, in which the compound was very well tolerated confirms the substantial therapeutic potential of CEM-101," said Prabhavathi Fernandes, Ph.D., chief executive officer of Cempra. "The tolerability matches the profile we observed in an earlier Phase 1 single-dose study. In addition, CEM-101 continues to demonstrate high potency and a broad spectrum of activity against respiratory pathogens, including drug-resistant strains, as well as other serious pathogens. The CEM-102 data from the in vitro European isolates study is particularly gratifying because it confirms our analysis of the low resistance development potential of sodium fusidate. TAKSTA is an exceptionally promising oral anti-MRSA agent that we are developing for a high unmet clinical need in the U.S. market."


About 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.


TAKSTA, (sodium fusidate) is a novel class of antibiotic with an established history of safety and efficacy outside the United States. TAKSTA is being developed as an NCE in the U.S for aBSSI. Clinical trials with TAKSTA employ a proprietary front-loading oral regimen designed to increase potency, increase coverage and minimize resistance development. Cempra believes that TAKSTA will be an important addition to anti-MRSA therapies based on the following:

Sodium fusidate is orally active against gram-positive bacteria, including all S. aureus strains such as HA-MRSA and CA-MRSA
TAKSTA employs a novel and proprietary PK-PD-based dosing regimen of sodium fusidate that optimizes efficacy and minimizes the risk of resistance development
Sodium fusidate is the only compound within the fusidane class and therefore is unlikely to select for cross-resistance to other classes of antibiotics
Sodium fusidate's safety has been well documented even when used for long periods of time (over one year) to treat osteomyelitis and other serious infections
Sodium fusidate has been used safely in children including neonates in countries where it is marketed
About 60 to 80 percent of the 13 million acute skin structure infections that occur in the U.S. each year are infected with MRSA. There is a growing need for an oral anti-MRSA drug that is safe, effective and is capable of long-term administration.

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.