PARIS, September 11 Novexel, a specialty pharmaceuticalcompany focused on the discovery and development of novel antibioticsdesigned to overcome the significant global problem of microbial resistance,announces that its pipeline will be the subject of 16 posters and one slidepresentation at the 49th annual meeting of the Interscience Conference onAntimicrobial Agents and Chemotherapy (ICAAC). The ICAAC meeting, which istaking place in San Francisco, California, September 12-15 2009, is theleading global conference on anti-microbial agents globally with over 10,000participants.
Poster L1-336 covers a Phase II trial which compared NXL103 withamoxicillin in the treatment of mild to moderate community acquired pneumonia(CAP) in adults. The trial showed that 500mg or 600mg of NXL103 twice a daywas efficacious in the treatment of CAP and produced similar results to highdose amoxicillin. NXL103, which was generally well tolerated, may be aneffective oral therapy for CAP and based on its spectrum, for complicatedskin and skin structure infections (cSSSI).
Posters A1-1944, A1-1945 and A1-1946 cover the Phase I work with NXL103and show that the product was generally well tolerated, that it shows abeneficial interaction with food, and that no dosing adjustment was requiredin elderly patients. Poster A1-1943 looks at the optimization of the ratio oflinopristin and flopristin, the two components of NXL103. This studyconcludes that a dose consisting of 250mg of linopristin and 350mg offlopristin is optimal as it gives lower pharmacokinetic variability anddelivers optimal ex-vivo plasma bactericidal activity in all subjects.
Poster E-1965 provides data on the in vitro activity of NXL103 againstMRSA. The study concludes that NXL103 is highly active against importantbacterial species of cSSSIs including community acquired MRSA and hospitalacquired MRSA, supporting the further development of this novel streptograminfor indications such as cSSSI, where staphylococci are important pathogens.
NXL104, either alone or in combination with ceftazidime, is the subjectof 9 posters and one slide presentation.
Poster A1-007 covers a Phase I study in healthy volunteers looking at theeffects of age and gender on the pharmacokinetics of NXL104. The study showsthat NXL104 is well tolerated and that no dose adjustment is required basedon age or gender.
Poster C1-1374 describes the nature of inhibition of the class A TEM-1beta-lactamase by NXL104. Slide Presentation C1-1098 describes the highresolution crystal structure of NXL104 complexed with the extended spectrumbeta-lactamase CTX-M-15 to understand the molecular details of mechanism ofinhibition.
Three of the posters outline research with NXL104/ceftazidime in murinemodels of infection. Poster A1-006 shows that the NXL104/ceftazidime isefficacious in a pneumonia model using a strain of Klebsiella pneumoniaeexpressing elevated levels of AmpC beta-lactamase. Poster B-1339, shows thatNXL104/ceftazidime is very effective in two murine models of infectionagainst a strain of Klebsiella pneumoniae harboring the KPC carbapenemase,which has been shown to confer resistance to all other beta-lactams andbeta-lactamase inhibitor combinations. Poster A1-005 shows thatNXL104/ceftazidime has good parenteral efficacy against Enterobacteriaceaebearing a CTX-M beta-lactamases in a mouse septicemia model. In all threemodels, ceftazidime alone has poor activity.
The remaining 4 posters cover in vitro studies with NXL104/ceftazidime.Poster E-194 shows that the combination was active against 300 geographicallydiverse clinical isolates of Pseudomonas aeruginosa while Poster E-186 showsthat it had a broad spectrum of activity against resistant Enterobacteriaceaeisolates. Poster E-188 and Poster E-192 examines the activity ofNXL104/ceftazidime against anaerobic bacteria. In these last two posters thecombination, together with metronidazole, is shown to have potentanti-anaerobe activity against most clinical anaerobe species, making itpotentially useful in the treatment of mixed infections.
A final poster sponsored jointly by Novexel and Forest (B-1339a) showsthe efficacy of ceftaroline combined with NXL104 againstceftaroline-resistant organisms in a mouse septicaemia model. All posterswill be available for download from Novexel's web site (http://www.novexel.com) shortly after the close of ICAAC.
In addition to these Novexel sponsored posters, 4 posters will bepresented by Forest Inc on NXL104 in combination with ceftaroline. Forestlicensed North American rights to develop and commercialize NXL104 solely incombination with ceftaroline in January 2008. Novexel retains rights to theNXL104-ceftazidime combination worldwide, including in North America.
Novexel is a speciality pharmaceutical company focused on the discoveryand development of novel antibiotics designed to overcome the significantglobal problem of microbial resistance. The ever increasing resistance tomarketed antibiotics has led to a clear need for novel drugs that are activeagainst multi-drug resistant bacteria. Novexel's products are targeting theglobal hospital antibiotic market, which was worth an estimated $17bn in2008.
Novexel currently has two novel antibacterials in Phase II clinicaldevelopment. These are the injectable beta-lactamase inhibitor, NXL104, whichis being developed in combination with the cephalosporin antibioticceftazidime for serious Gram negative infections, and the oral streptograminantibiotic, NXL103, for the treatment of Gram positive infections, with afocus on treatment in the hospital setting and intravenous (IV) to oralswitch. Novexel has three further programmes in preclinical development,NXL105, a novel anti-Pseudomonal antibiotic, NXL201, a novel echinocandinantifungal agent, and NXL104 in combination with ceftaroline. This latterproduct is being developed by Novexel's partner, Forest Laboratories (NYSE:FRX), solely for North American markets.
Novexel was created in December 2004 as an independent spin-out of thesanofi-aventis (Euronext Paris: SAN, NYSE: SNY) anti-infectives unit. Novexelhas a team of 50 employees with significant experience in anti-infectiveresearch and development, who are located in Paris, France and Philadelphia,USA.The posters presented at the conference cover: - NXL103, a novel oral streptogramin, which has completed a successful Phase II study in patients with community acquired pneumonia (CAP). It has been shown to be highly active against methicillin resistant Staphylococcus aureus (MRSA) and will soon start a Phase II trial in complicated Skin and Skin Surface infections (cSSSIs). - NXL104, Novexel's broad spectrum non-beta-lactam class A and C beta-lactamase inhibitor which, in combination with the cephalosporin antibiotic ceftazidime, is currently in two Phase II trials for complicated urinary tract infections (cUTIs) and complicated intra abdominal infections(cIAIs). NXL103 NXL103 is the subject of 6 posters.