The following is a summary of data from the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which is being held through Thursday in Chicago.

• Ambrilia Biopharma Inc., of Montreal, said data from its series of HIV integrase inhibitors (pyrazolopyridine inhibitors) demonstrated their synergistic potential with some of the known integrase inhibitors (diketo acid inhibitors) in clinical development and also indicated that its inhibitors bind to a different site on the HIV integrase enzyme from that of known competitors. The company said that could lead to a different resistance profile than drugs currently in development.

• Ardea Biosciences Inc., of Carlsbad, Calif., presented promising preclinical data suggesting that RDEA806, its HIV non-nucleoside reverse transcriptase inhibitor, has the potential to be used in both naïve and treatment-experienced patients, including those harboring the K103N mutation, the most abundant mutation observed in patients failing Sustiva (efavirenz, Bristol-Myers Squibb Co.) therapy and in some newly infected patients. RDEA806 was designed to accommodate the amino-acid changes associated with NNRTI resistance and has demonstrated activity in vitro against wild-type and the majority of HIV strains carrying key reverse transcriptase mutations. The compound recently completed Phase I trials.

• Basilea Pharmaceutica Ltd., of Basel, Switzerland, reported data from ceftobiprole's Phase III program demonstrating the drug's potential range of activity in complicated skin infections involving Gram-positive and Gram-negative infections. A microbiological analysis of two pivotal studies demonstrated the drug's activity against infections involving pathogens ranging from methicillin-resistant Staphylococcus aureus to Pseudomonas aeruginosa, and showed that microbiological eradication for ceftobiprole alone (88 percent) was comparable to that of combination therapy (89 percent). Results from the second pivotal study in patients with complicated skin and skin structure infections showed that ceftobiprole demonstrated non-inferiority within the 10 percent margin in that patient population, with clinical cure rates of 91 percent for Gram-positive infections and 87 percent in Gram-negative infections. Ceftobiprole is a broad-spectrum cephalosporin in development with Johnson & Johnson Pharmaceutical Research and Development LLC, a unit of New Brunswick, N.J.-based Johnson & Johnson.

• Ceragenix Pharmaceuticals Inc., of Denver, reported that one of its lead Ceragenin compounds, CSA-13, showed promise as an alternative therapy against Pseudomonas aeruginosa bacterial infections in cystic fibrosis patients and was active against both multidrug-resistant isolates and the transmissible virulent LES clone. The drug also appears to lend itself to aerosolized administration to deliver bactericidal concentrations directly to the lungs. Ceragenins are synthetically produced small-molecule, positively charged compounds comprised of a sterol backbone with amino acids and other chemical groups attached to them and are designed to attach to the negatively charged cell membranes of certain viruses, fungi and bacteria.

• Incyte Corp., of Wilmington, Del., presented in vitro data showing INCB9471, an oral CCR5 antagonist, demonstrated synergistic or additive effects, rather than antagonistic effects, when combined with four major classes of antiretroviral agents. Experiments also showed that de novo mutations that result in resistance to INCB9471 do not appear rapidly in cell culture. The drug is being developed as a once-daily treatment for HIV and has been studied at 100-mg, 200-mg and 300-mg once-daily doses in a 14-day Phase IIa trial, in which the compound provided potent and prolonged antiviral effects in patients with R5-tropic virus. INCB9471 was well tolerated at all three doses and is being evaluated in several drug-interaction trials to support the initiating of two six-month Phase IIb studies in treatment-experienced HIV patients.

• Monogram Biosciences Inc., of South San Francisco, said its collaborator, New York-based Pfizer Inc., reported data reinforcing the long-term safety and efficacy of Pfizer's oral CCR5 antagonist, Selzentry (maraviroc), which recently gained FDA approval in HIV. Results from a planned 48-week analysis showed that nearly three times as many patients receiving Selzentry in addition to an optimized background regimen achieved undetectable levels of virus compared to those receiving an optimized regimen alone. Selzentry, administered along with an optimized background regimen, also significantly increased CD4 cells compared to patients who did not receive Selzentry as part of their treatment. Monogram's co-receptor tropism assay, Trofile, was used for patient selection during Selzentry's clinical development program and is being marketed by Monogram's sales force for use with Pfizer's drug.

• Paratek Pharmaceuticals Inc., of Boston, reported preclinical results from its multiple adaptation response (MAR) inhibitor program, showing that small-molecule agents that block the activity of ExsA, a MAR protein, in Pseudomonas aeruginosa significantly reduced bacterial virulence and were protective in an animal model from pneumonia. Paratek describes MAR proteins as the "master switches" in bacteria that control virulence and antibiotic resistance and believes that shutting down the switch disables virulence and prevents the bacteria from causing infection. The company also reported a recent publication showing efficacy of its MAR inhibitors against E. coli in urinary tract infection in another animal model. Those data appear in the August issue of Bioorganic & Medicinal Chemistry Letters.

• Sangamo BioSciences Inc., of Richmond, Calif., reported data demonstrating that human CD4 T cells can be made permanently resistant to HIV infection by treatment with zinc finger DNA-binding protein nucleases and that they can preferentially survive and expand in an animal after HIV infection. Findings show that a one-time exposure to CCR5-specific ZFNs resulted in the generation of an HIV-resistant population of primary T cells that permanently expressed disrupted CCR5 proteins, and that those ZFN-modified CD4 T cells expanded stably in HIV-infected cultures for several weeks and appeared to behave identically to untreated T cells except for their resistance to HIV. Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system.

• Tibotec Pharmaceuticals Ltd., of Cork, Ireland, said results from a new, ongoing Phase III study showed that 84 percent of treatment-naïve HIV-1 infected adults taking an investigational dose of its Prezista (darunavir) 800 mg in combination with 100 mg ritonavir once-daily with Truvada (emtricitabine and tenofovir disoproxil fumarate, Gilead Sciences Inc.) reached an undetectable viral load (<50 copies/mL) at week 48, compared with 78 percent of patients taking Kaletra (lopinavir/ritonavir, Abbott Laboratories) 800 mg/200 mg once daily with Truvada. The mean difference in response between the treatment groups was 5.3 percent, and the study met the primary endpoint of non-inferiority. Those data will be submitted to the FDA later this year as part of the company's postmarketing plan for Prezista.

• Virxsys Corp., of Gaithersburg, Md., said a new analysis of safety data from Phase I and II studies of VRX496, an HIV-based lentiviral vector gene delivery system, confirmed previous safety findings. In ongoing Phase II trials of VRX496, the company has treated a total of 24 patients with multiple doses of the drug, with half the patients receiving four doses of the therapy and the other half receiving eight, and to date, the trial has demonstrated the safety and tolerability of multiple infusions and larger bolus infusions. Patients currently are being monitored to determine the optimal treatment regimen.

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