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Oritavancin Demonstrates Potent and Rapid In Vitro Activity Against MRSA, VRE and Other Strains of Resistant Bacteria
Date:9/19/2007

CHICAGO, Sept. 19 /PRNewswire/ -- Targanta Therapeutics Corporation today released detailed data from completed studies comparing the in vitro activity of its lead antibiotic drug candidate, oritavancin, to that of other antibiotics against a variety of susceptible and resistant strains of gram- positive bacteria. Results are being presented today at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) taking place in Chicago, IL. All posters highlighted below are being presented at 12:15 pm CDT.

Poster E-1617 is entitled "In Vitro Activity Profile of Oritavancin (ORI) Against Resistant Staphylococcal Populations From a Recent Surveillance Initiative." In this study, researchers examined clinical isolates of Staphylococcus aureus (n=5,008) and coagulase-negative staphylococci (n=862) collected in 2005-2006 from hospital sites in the U.S., Europe and Israel. Oritavancin was active against all staphylococcal isolates, including those with specific resistance phenotypes and including multi-drug resistant S. aureus, which were resistant to three or more of the following agents: ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin, quinupristin- dalfopristin, trimethoprim-sulfa, vancomycin, daptomycin, and linezolid. Results from this study demonstrated that oritavancin had potent in vitro activity against a wide spectrum of staphylococci likely to be encountered in a variety of clinical settings.

Poster E-1613, entitled "In Vitro Activity Profile of Oritavancin (ORI) Against Organisms Demonstrating Key Resistance Profiles to Other Antimicrobial Agents," compared the activity of oritavancin to vancomycin and teicoplanin against a diverse collection of staphylococci and enterococci, including strains with elevated MICs to linezolid, daptomycin, and/or vancomycin, as well as strains of streptococci. Bacterial isolates included S. aureus (n=35), coagulase-negative staphylococci (n=21), Enterococcus faecalis (n=11), Enterococcus faecium (n=32), Streptococcus pneumoniae (n=20) and Streptococcus pyogenes (n=20). Data from the study revealed that oritavancin demonstrated potent in vitro activity against geographically diverse, contemporary gram- positive pathogens with important resistance phenotypes and genotypes.

The study presented in poster E-1615, entitled "Anti-Enterococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections," established a current in vitro activity profile of oritavancin against both E. faecalis and E. faecium populations, including strains resistant to linezolid, daptomycin, and vancomycin. In the study, oritavancin showed potent in vitro activity against all enterococci encountered in this study, including strains non-susceptible to vancomycin (both VanA and VanB phenotypes), linezolid or daptomycin.

Poster E-1619, entitled "Synergistic Effects of Oritavancin Tested in Combination with Other Agents," details a study that tested for synergistic activity of oritavancin when combined with other antibiotics against S. aureus and enterococci of different resistance phenotypes. Oritavancin was tested in combination with daptomycin, gentamicin, linezolid, moxifloxacin or rifampicin against methicillin-sensitive S. aureus (MSSA), a clinical isolate of vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), vancomycin-resistant E. faecium (VanA VRE), and vancomycin-resistant E. faecalis (VanB VRE). The study demonstrated that oritavancin has promising activity in vitro in combination as it synergizes with antibiotics of different classes against gram-positive pathogens of clinically important resistance phenotypes.

In poster E-1620, entitled "Pharmacokinetic Concentrations of Oritavancin Kill Stationary-Phase and Biofilm Staphylococcus aureus In Vitro," researchers detailed the antibacterial efficacy of physiologically attainable concentrations of oritavancin and other comparators tested against in vitro models of slow-growing and biofilm S. aureus. Slow-growing bacteria and biofilms are notoriously tolerant to antibiotics. In this study, time-kill studies were performed using oritavancin, linezolid and vancomycin on stationary-phase MSSA, methicillin-resistant S. aureus (MRSA) and VRSA. Under the conditions of these in vitro assays, oritavancin displayed concentration- dependent bactericidal activity against all three S. aureus inocula whereas comparator agents vancomycin and linezolid displayed bacteriostatic activity. Against the S. aureus biofilms, oritavancin exhibited minimal biofilm eradication concentrations (MBEC) values between 0.5 and 2 microgram/mL, whereas linezolid and vancomycin were ineffective (MBEC greater than 128 microgram/mL). The study concluded that pharmacokinetic concentrations of oritavancin show promising activity in vitro against stationary-phase and biofilm S. aureus of clinically important resistance phenotypes.

Poster E-1614 is entitled "In vitro Time Kill Studies of Oritavancin against Drug-resistant Isolates of Staphylococcus aureus and Enterococci." To understand the time dependence of oritavancin activity, in vitro time-kill experiments were completed against clinically important strains of S. aureus, E. faecalis, and E. faecium, including recently identified antibiotic- resistant isolates. In this study, oritavancin displayed concentration- dependent killing of MSSA, MRSA, VRSA, VISA, VSE and both VanA and VanB strains of VRE in vitro. In addition, oritavancin was more rapidly bactericidal in this in vitro study against all bacteria tested than were vancomycin, teicoplanin, linezolid or daptomycin at their respective physiologically relevant concentrations.

Additional oritavancin-related posters presented today at ICAAC include:

-- In Vitro Activity Profile of Oritavancin against a Broad Spectrum of

Aerobic and Anaerobic Bacterial Pathogens (E-1612, 12:15 p.m. CDT)

-- Anti-Streptococcal Activity Profile of Oritavancin, a Potent

Lipoglycopeptide under Development for Use Against Gram-Positive

Infections (E-1616, 12:15 p.m. CDT)

-- Comparative Intracellular Activity of 10 Anti-Staphylococcal

Antibiotics (AABs) Against a Stable Small Colony Variant (SCV) of S.

aureus in a Model of Human THP-1 Macrophages (A-1437, 1:15 p.m. CDT)

About Oritavancin

Oritavancin is a novel semi-synthetic lipoglycopeptide antibiotic candidate with potent bactericidal (killing) activity against a broad spectrum of gram-positive bacteria. The product candidate has been tested in over 1500 patients and has completed two Phase 3 studies for the treatment of complicated skin and skin structure infections (cSSSI) in which the primary endpoints were met. Targanta believes oritavancin's properties may give it distinct advantages over currently marketed therapies and expects to submit a New Drug Application to the U.S. Food and Drug Administration in the first quarter of 2008 seeking to commercialize oritavancin for the treatment of cSSSI.

About Targanta Therapeutics

Targanta Therapeutics Corporation is a privately held biopharmaceutical company focused on developing and commercializing innovative antibiotics to treat serious infections in the hospital and other institutional settings. The Company's pipeline includes oritavancin, a semi-synthetic lipoglycopeptide antibiotic, for which Targanta intends to seek U.S. regulatory approval in early 2008, as well as a number of antibacterial agents in pre-clinical development. The company has operations in Cambridge, MA, Indianapolis, IN, Montreal, Quebec, Canada and Toronto, Ontario, Canada. For further information about Targanta, visit the company's website at http://www.targanta.com.

Disclaimer

All forward-looking statements and other information included in this press release are based on information available to Targanta as of the date hereof, and Targanta assumes no obligation to update any such forward-looking statements or information. Targanta's actual results could differ materially from those described in Targanta's forward-looking statements.


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SOURCE Targanta Therapeutics Corporation
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