The following data were presented at the joint Interscience Conference of Antimicrobial Agents and Chemotherapy and International Congress of Chemotherapy and Infection meeting in San Diego.

Ampliphi Biosciences Corp., of Richmond, Va., reported experimental results highlighting that its prototype bacteriophage cocktail demonstrated comparable efficacy to vancomycin in reduction of Staphylococcus aureus in a murine lung infection model. At two hours post infection, scaled dosing of the bacteriophage cocktail was administered intranasally to three dosage groups of neutropenic immunocompromised mice inoculated nasally with S. aureus, with a second identical dose administered at six hours post infection. Vancomycin was administered subcutaneously at two and six hours post infection to a fourth, positive control group. Two control groups were infected, but untreated. The groups treated with the bacteriophage cocktail at the two highest doses (1 x 109 and 1 x 108 PFU per phage per dose) showed a 3-log reduction in bacterial cell counts relative to untreated controls at the same time point, which was comparable to the efficacy seen in the positive control group treated with vancomycin.

Arno Therapeutics Inc., of Flemington, N.J., reported preclinical data from its broad-spectrum, antimicrobial candidate, AR-12, showing in vitro inhibition of chikungunya virus replication. Activity of AR-12 was evaluated against the wild-type and T-705-resistant chikungunya virus strains, and its mechanism of action was shown to down-regulate a number of protein chaperones, thus targeting the unfolded protein response. Results indicate that the combination of AR-12 with T-705 resulted in an additive antiviral effect against either the wild-type or T-705-resistant strain. The drug previously demonstrated activity against pathogenic viruses such as influenza A, Epstein-Barr virus, and hemorrhagic fever viruses, including Ebola, Marburg, Nipah, Lasa, Junin and Yellow fever.

Chimerix Inc., of Durham, N.C., reported findings showing that hospital readmissions related to opportunistic infections are common among patients following autologous and allogeneic hematopoietic cell transplant, with data indicating that of hospital readmissions related to opportunistic infections (25.8 percent of all readmissions), about one in three readmissions were due to double-stranded DNA viral infections.

Cidara Therapeutics Inc., of San Diego, presented preclinical data from a number of studies suggesting that its lead antifungal candidate, CD101, is associated with high stability and solubility along with potent antifungal activity with high efficacy in animal models, with no toxicity signals. In a study that compared the toxicity of CD101 to a first-generation echinocandin, CD101 was administered by intravenous infusion in doses comparable to its estimated human plasma exposures and was shown to be metabolically stable, without exhibiting chemical-driven liver damage, at doses up to 20 mg/kg for two weeks. CD101 also was effective in treating both echinocandin-susceptible and -resistant invasive candidiasis in mice at equivalent human-exposure levels of CD101 and micafungin.

Dipexium Pharmaceuticals Inc., of New York, and collaborators presented microbiology data on Locilex (pexiganan cream 0.8 percent), showing that pexiganan, the agent's active pharmaceutical ingredient, demonstrated in vitro activity against a broad spectrum of gram-positive and gram-negative bacteria selected as having elevated minimum inhibitory concentration (MIC90) values to topical antibiotics, including bacitracin, polymyxin B, neomycin, mupirocin, retapamulin and fusidic acid. Pexiganan also demonstrated activity against gentamicin-susceptible and gentamicin-resistant isolates. Pexiganan's MIC90 values for each of the organism groups studied, including difficult-to-treat gram-positive staphylococci, beta-hemolytic streptococci, enterococci and viridans group streptococci as well as gram-negative Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Acinetobacter baumannii, were below the concentration of pexiganan in Locilex's topical cream formulation.

Matinas Biopharma Holdings Inc., of Bedminster, N.J., presented preclinical data suggesting that MAT2501, its orally administered encochleated formulation of amikacin, showed antibacterial activity against Mycobacterium avium (M. avium) without apparent toxicity. Researchers said 20 and 100 mcg/mL doses of oral MAT2501 were studied in an in vitro model of M. avium lung infection and an in vivo model of M. avium respiratory lung infection, with MAT2501 shown as an effective bactericide in both settings. The company plans to file an investigational new drug application for MAT2501 in the fourth quarter and move the product into human studies next year.

The Medicines Co., of Parsippany, N.J., presented data from a multinational cohort demonstrating mortality, morbidity and poor outcomes associated with existing therapies in patients with infections due to carbapenem-resistant Enterobacteriaceae (CRE). The study reviewed the treatment of 257 adults at 22 major medical centers in the U.S., UK, Italy and Greece over a six-month period, including patients with complicated urinary tract infection, acute pyelonephritis, hospital acquired bacterial pneumonia (HABP), ventilator associated bacterial pneumonia (VABP) and bacteremia due to CRE pathogens. Findings showed an average 28-day mortality of 28 percent with current treatment options, rising to 35 percent in patients with HABP and 33 percent in patients with VABP. Only 57 percent of patients achieved a clinical cure and 52 percent achieved microbiological eradication. The analysis was conducted in patients with severe infections due to CRE to assess outcomes with current treatment options and to guide the design of the company's ongoing phase III program for Carbavance (meropenem/RPX7009).

Melinta Therapeutics Inc., of New Haven, Conn., said in vitro results showed activity by delafloxacin against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis bacteria commonly associated with respiratory tract infections. The fluoroquinolone candidate was tested against more than 500 related isolates from the U.S. and Europe, including some that had shown resistance to levofloxacin, penicillin and ceftriaxone. When compared to antibiotics covering multiple classes, including the currently marketed quinolones ciprofloxacin, levofloxacin and moxifloxacin, delafloxacin was the most potent compound tested against S. pneumoniae, H. influenza and M. catarrhalis. Delafloxacin was active against all resistant S. pneumoniae isolates and was not affected by beta-lactamase status in H. influenza and M. catarrhalis. Melinta's candidate is in late-stage development to treat acute bacterial skin and skin structure infections. (See BioWorld Today, June 11, 2015.)

Merlion Pharmaceuticals Pte. Ltd., of Singapore, said data from a phase II study showed that patients treated with a five-day course of its antibacterial, finafloxacin, had a higher, more rapid and more sustained level of microbiological eradication and improved clinical outcomes over those treated with ciprofloxacin twice daily for 10 days. Finafloxacin also was found to be safe and tolerable. The double-blind, double-dummy study at 18 sites in Poland and Germany enrolled 225 adults diagnosed with complicated urinary tract infections and acute pyelonephritis, who were randomized to finafloxacin (800 mg once daily intravenously or orally) for five or 10 days or to ciprofloxacin (400 mg IV twice a day or 500 mg orally twice a day) for 10 days. The most common pathogens in the study were the gram-negative Escherichia coli and Klebsiella pneumoniae. For finafloxacin, the test of cure was 70 percent when dosed for five days or 68 percent when dosed for 10 days, compared to 57 percent for ciprofloxacin dosed for 10 days. In addition, five-day dosing with finafloxacin did not result in an increased rate of relapses on day 24 compared to the other study arms.

Paratek Pharmaceuticals Inc., of San Diego, said that, across seven microbiology studies, its lead candidate, omadacycline, showed in vitro activity against gram-positive, gram-negative and atypical bacteria, including those with resistance to currently available antibiotics. Microbiology testing of omadacycline suggested the compound offers potential therapeutic value against Staphylococcus aureus, Streptococcus pneumoniae (including resistant strains) and Enterobacteriaceae compared to commonly prescribed antibiotics. Additional in vitro data suggested omadacycline may be useful in infections caused by Legionella pneumophila, lending support to the compound's potential utility as an oral and intravenous monotherapy agent to treat community-acquired bacterial pneumonia.

Sangamo Biosciences Inc., of Richmond, Calif., presented data showing sustained functional control of viral load in the absence of antiretroviral drugs in two of three HIV-infected subjects treated in cohort 3 of the phase I/II study of its ZFP therapeutic (SB-728-T) to treat HIV/AIDS. The patients received an SB-728 product that included CCR5-modified CD8 T cells, and their regimen differed from subjects treated in other cohorts in the study, who received only CCR5-modified CD4 T cells after Cytoxan preconditioning. The cohort 3 regimen was designed to test whether inclusion of CCR5-modified CD8 T-cells – immune cells responsible for controlling viral infections – could improve HIV viral load control. Sangamo said the patients remain on extended treatment interruption (TI) beyond the initial 16-week TI period.

Scynexis Inc., of Jersey City, N.J., reported results from three nonclinical studies of lead candidate, SCY-078, a glucan synthesis inhibitor in phase II development to treat invasive fungal infections. Intravenous administration of SCY-078 in preclinical models resulted in plasma exposures that exceeded by 16-fold those associated with efficacy in murine models of invasive candidiasis. SCY-078 also was distributed extensively to key tissues commonly associated with invasive fungal infections, including lung epithelial lining fluid, and was well-tolerated when delivered intravenously in multiple species. The company said its phase II study in invasive candidiasis is in progress, with the amendments to the study protocol in place. Top-line data are expected in the first half of 2016.

Symbiomix Therapeutics LLC, of Newark, N.J., presented data showing that the pharmacokinetics of lead candidate, SYM-1219, were bioequivalent when administered orally with or without a high-fat meal. The single dose, oral antibiotic is in development to treat bacterial vaginosis. The company recently completed enrollment in a phase III study – a second pivotal trial for SYM-1219. (See BioWorld Today, May 6, 2015.)

Synthetic Biologics Inc., of Rockville, Md., presented data from its SYN-004 program that demonstrated SYN-004 protected the gut microbiome from damage often caused by intravenous beta-lactam antibiotic, ceftriaxone, in a pilot study of humanized pigs. SYN-004 is currently in phase II clinical trials designed to degrade certain IV beta-lactam antibiotics within the gastrointestinal tract and maintain the natural balance of the gut microbiome for the prevention of C. difficile infection, antibiotic-associated diarrhea and secondary antibiotic-resistant infections.

Theravance Biopharma Inc., of Dublin, reported data from several studies of Vibativ (telavancin) that confirmed in vitro potency against isolates from a range of difficult-to-treat infections. Vibativ showed the greatest in vitro activity among antibiotics evaluated against gram-positive clinical isolates that caused complicated skin and skin structure infections in U.S. hospitals, with minimum inhibitory concentrations for Vibativ eight-fold lower than for daptomycin and 16-fold lower than for vancomycin and linezolid against Staphylococcus aureus strains, including methicillin-resistant and methicillin-susceptible S. aureus (MRSA/MSSA) subsets. Vibativ also possessed the greatest in vitro activity among antibiotics evaluated against gram-positive cocci from Canadian hospitals. In addition, Vibativ showed greater in vitro activity against biofilm-producing MRSA compared to vancomycin, daptomycin, teicoplanin and ceftaroline.