Rib-X Pharmaceuticals presents positive preclinical data for delafloxacin at ICAAC Conference

Sep 14 2010

Rib-X Pharmaceuticals, Inc., a development-stage antibiotics company with a broad product pipeline based on its innovative discovery platform, today announced the presentation of positive preclinical data for delafloxacin in four poster sessions at the 50^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

“Delafloxacin has consistently demonstrated outstanding clinical efficacy and an excellent safety profile that does not further compromise an already vulnerable patient population presenting with difficult-to-treat, complicated infections”

Delafloxacin is a novel fluoroquinolone antibiotic that offers both IV and oral versatility. According to details from the poster presentations, delafloxacin's unique chemical structure and molecular properties lead to an increase in potency in acidic environments—which are typically found at the site of infection. In addition, the data support the selected dose for further study of delafloxacin in future trials. Delafloxacin has successfully completed three Phase 2 clinical studies in approximately 1,000 subjects.

"Across multiple studies presented at ICAAC, delafloxacin demonstrated increased potency at the site of infection as compared to the leading approved agents—including the most difficult-to-treat fluoroquinolone resistant Gram-positive and resistant Gram-negative pathogens," said Scott Hopkins, M.D., Chief Medical Officer at Rib-X. "We believe delafloxacin's unique chemical structure allows the drug to more readily cross the bacterial membrane resulting in increased potency. These properties should translate to both improved efficacy and a greater barrier to resistance development in the clinical setting. The results of these studies support a superior profile for delafloxacin in the fluoroquinolone class and, more importantly, as a well-tolerated, broad spectrum antibiotic candidate that can effectively target key pathogens that cause hospital-treated infections."

"Delafloxacin has consistently demonstrated outstanding clinical efficacy and an excellent safety profile that does not further compromise an already vulnerable patient population presenting with difficult-to-treat, complicated infections," said Mark Leuchtenberger, President and Chief Executive Officer at Rib-X. "The data presented at ICAAC continue to support delafloxacin's potential as a new best-in-class antibiotic, which includes MRSA coverage. The next key steps for delafloxacin's development are the initiation of a Phase 1 study to assess a new oral formulation and the design and implementation of a Phase 2 study to evaluate objective endpoints for complicated skin infections."

In a poster presentation entitled "Delafloxacin Chemical Properties Lead to Increased Potency Against Quinolone-Resistant Pathogens (I)" by E. Burak, J. Devito, J. Remy and E. Duffy, the impact of increasing acidity on the minimum inhibitory concentrations (MICs) of delafloxacin in comparison to the leading approved agents levofloxacin, ciprofloxacin and moxifloxacin was explored. Each drug was tested at varying pH levels against clinical isolates of a number of Gram-positive and Gram-negative bacteria. Results demonstrated that delafloxacin MICs were reduced as a function of acidity 2- to 32-fold at pH concentrations typically found at most sites of infection (pH 5.5 and 6.5) whereas levofloxacin, ciprofloxacin and moxifloxacin MICs increased from those seen at neutral pH. For instance, delafloxacin's MIC dropped 5.8 fold against Pseudomonas aeruginosa when the pH dropped from 7.2 to 5.5 while ciprofloxacin's increased by 3.4 fold over the same pHs. Against fluoroquinolone resistant strains, delafloxacin demonstrated more pronounced reduction in MICs which were approximately 2-fold greater than those observed with quinolone-susceptible strains.

A second poster presentation entitled "Delafloxacin Chemical Properties Lead to Increased Potency Against Gram-positive Pathogens, Including Quinolone-Resistant Pathogens (II)" by E. Duffy, J. Devito, J. Remy and E. Burak further suggests that delafloxacin's novel chemical structure and molecular properties support increased potency in Gram-positive pathogens, including quinolone resistant pathogens such as MRSA. Specifically, the study identified through computational analysis a set of molecular features unique to delafloxacin that deliver enhanced potency as compared to other quinolones.

Combined, these two chemical property studies support the hypothesis that the unique chemical structure and molecular features of delafloxacin provide increased potency at neutral pH and enhance the candidate's ability to permeate the bacterial membrane, resulting in even greater potency at lower concentrations in acidic environments. It is believed that this increased potency may translate to an enhanced clinical benefit with regard to both improved efficacy and an improved resistance profile.

Two separate pharmacokinetic (PK) and pharmacodynamic (PD) studies were also conducted to confirm the optimal dose selection for further study of delafloxacin, including in MRSA. The first study "Delafloxacin Population Pharmacokinetics (PPK) and Covariate Exploration" by C. Rubino, A. Forrest, S. Bhavnani, E. Burak and P. Ambrose presented a population model used to support target attainment. The second study "Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment (TA) Analyses Supporting Delafloxacin (DFX) Phase 3 Dose Regimen Decisions" by C. Rubino, S. Bhavnani, E. Burak and P. Ambrose utilized the model and demonstrated low variability in the pharmacokinetics of delafloxacin. Specifically, given the current MIC distribution for MRSA, excellent overall PK-PD target attainment (TA) rates were achieved for the evaluated regimens and, going forward, the Company has identified the optimal delafloxacin dose as 300 mg administered intravenously every 12 hours. This dose was previously shown to be safe and effective in a Phase 2 study of complicated skin and skin structure infections.