—RX-04 compounds also demonstrate potent in vivo activity against the deadly superbug, Klebsiella pneumoniae, including against carbapenem- and colistin-resistant strains —
Rib-X Pharmaceuticals, Inc. announced today the presentation of five posters featuring completely new antibiotic compounds from the company’s RX-04 program at the 52 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), taking place September 9-12, 2012 in San Francisco, CA. The reported data from multiple preclinical studies emphasized the potent, broad spectrum activity of RX-04 compounds, including at single, low doses. A study conducted in a lung infection model established the potential for this class of compounds to address respiratory pathogens. Additionally, studies demonstrated the unique activity of these novel antibiotics across a diverse array of bacterial pathogens, including against carbapenem- and colistin-resistant strains of and five major biodefense pathogens.
RX-04 is Rib-X’s most advanced preclinical program focused on using a discrete, novel binding site within the bacterial ribosome to design and develop completely new classes of antibiotics to treat some of the most deadly and difficult-to-treat, multi-drug resistant Gram-positive and Gram-negative infections. Since its unveiling at last year’s ICAAC, the program has progressed to late lead optimization. In June, 2011, Rib-X signed a collaborative and licensing agreement with Sanofi, giving Sanofi the right to develop multiple product candidates targeting this distinct binding site within the ribosome.
"These studies continue to highlight the potent activity of compounds in our RX-04 program, including efficacy at low, single doses, against deadly species that have acquired resistance to most compounds on the market, including last-resort classes with safety issues like colistin," said Erin Duffy, Ph.D., Chief Scientific Officer at Rib-X. "The activity of RX-04 compounds against all five of the major biodefense pathogens, including the most difficult-to-treat species, sets these new classes of compounds apart from other currently available therapies and development compounds. We believe that the RX-04 program has significant potential to produce drug candidates representing completely novel classes of bacterial protein synthesis inhibitors that directly address urgent public health threats caused by the most difficult to treat pathogens.”
In a late breaking abstract (F-2072a) presented today titled, “Pharmacodynamic Assessments of RX-P873 Against Using the Murine Thigh Infection Model,” researchers from the Hartford Hospital Center for Anti-Infective Research and Development reported pharmacodynamic results of an study of RX-P873, one of several RX-04 compounds in preclinical evaluation, against . RX-P873 exhibited potent and rapid antibacterial activity against in the neutropenic thigh infection model, a target infection site, at very low, single doses of the compound. In the last few years have emerged as significant nosocomial threats due to their resistance to current marketed drugs, resulting in high patient morbidity and mortality.
RX-04 was also featured in the following posters:
Poster Session 177: “Novel Antimicrobial Approaches and Agents,” 11:15am-1:15pm Pacific Time
F-1521 “Anti-Staphylococcal and Anti-Enterococcal Activity of Novel Protein Synthesis Inhibitors from the RX-04 Program” – demonstrated potency against a diverse collection of gram-positive clinical isolates including those with resistant phenotypes such as methicillin-resistant (MRSA) and vancomycin-resistant (VRE).
F-1522 “Antibacterial Activity of Novel RX-04 Compounds Against Biodefense Pathogens” – The antibacterial activity demonstrated against the five most difficult to treat biodefense pathogens, coupled with previously shown efficacies in multiple murine models of infection, demonstrate a level of activity unmatched by other compounds at this time. The five pathogens studied were , , , and .
F-1523 “Novel Ribosome Inhibitors are Efficacious in a Murine Respiratory Tract Infection Model Caused by ” – Representative RX-04 compounds effectively reduced colony-forming units in lung tissues and conferred protection with a single dose. These results establish the credentials for this class of compounds for respiratory infections, adding to their demonstrated efficacy in murine models of peritonitis, kidney and thigh abscess infection against key bacterial pathogens.
Poster Session 249: “Targeting Gram-negative Pathogens,” 9:15am-11:15am Pacific Time
F-2059 “Activity of Novel Pyrrolocytosine Agents Against Multidrug- and Carbapenem-Resistant ” - Two agents from the pyrrolocytosine class of RX-04 compounds showed potent activity against , including MDR, carbapenem, tigecycline and colistin resistant isolates. With carbapenemases nearly eliminating carbapenem as an option for treating in addition to the safety challenges posed by colistin, this level of activity shows potential for RX-04 to fulfill a growing need.
Based on preclinical data and on studies published in Antimicrobial Agents and Chemotherapy, RX-04 is believed to be the only drug development program that has produced compounds with demonstrated coverage of all of the following multi-drug resistant Gram-positive bacteria: , including MRSA; and multi-drug resistant and extremely drug resistant Gram-negative bacteria: and . These pathogens account for a majority of hospital-acquired infections, are associated with high rates of morbidity and mortality and are increasingly multi-drug resistant, meaning that they are resistant to more than three classes of antibiotics. The RX-04 compounds bind to a novel site on the ribosome that has never before been exploited by marketed antibiotics and have proprietary chemical characteristics distinct from all current classes of broad-spectrum or Gram-negative therapies; indeed, Rib-X has shown that the activity of these compounds is unaffected by cross-resistance to current therapies, and lower resistance development is expected compared to current therapies. These compounds are also small molecules, thereby providing the potential to ultimately offer an IV-to-oral switch for maximum flexibility. Furthermore, these compounds have strong and packages, including 7-day rat toxicology studies, and are progressing well in preclinical studies.
Rib-X Pharmaceuticals, Inc. is a biopharmaceutical company developing new antibiotics to provide superior coverage, safety and convenience for the treatment of serious and life-threatening infections. The Company's proprietary drug discovery platform provides an atomic-level, three-dimensional understanding of interactions between drug candidates and their bacterial targets and enables design of antibiotics with enhanced characteristics. Rib-X has two antibiotic candidates in clinical development. Delafloxacin is an enhanced spectrum IV/oral antibiotic intended for use as first-line monotherapy primarily in hospitals and recently completed a Phase 2b clinical trial for the treatment of acute bacterial skin and skin structure infections. Radezolid is a next-generation IV/oral oxazolidinone designed to be a potent antibiotic with a safety profile permitting long-term treatment of resistant infections. The Company's pipeline also includes its preclinical RX-04 program, partnered with Sanofi, S.A., and other discovery stage anti-infective programs.