PALO ALTO, Calif.—Anacor Pharmaceuticals has announced thatGlaxoSmithKline (GSK), its business partner, has been awarded a contract withthe U.S. Department of Health and Human Services' (HHS) Biomedical AdvancedResearch and Development Authority (BARDA). The contract will support thecontinuing development of GSK2251052 (also known as GSK '052, formerly AN3665),a novel boron-based Gram-negative systemic antibiotic discovered by Anacor. Thecontract will provide GSK will up to $94 million in funding for up to fouryears as the company moves forward in studies to evaluate the compound'sefficacy against bioterrorism threats, Phase II clinical trials ofventilator-associated pneumonia and Phase III trials for complicatedintra-abdominal infections.
GSK will receive $38.5 million in the first two years, andthe contract can be extended for a total of four years. BARDA will also providetechnical support and will share the cost and drug development risk. Ifsuccessful, the drug would represent the first new class of antibacterial agentto treat Gram-negative infections in 30 years.
"To help providers protect health and save lives in anemergency and every day, we will need to develop the next generation ofantibiotics," BARDA Director Robin Robinson, Ph.D., said in a press release."This commercial-plus-biodefense strategy creates a sustainable, cost-effectivebusiness model for private industry and taxpayers, and it promotes a warm basemanufacturing capability for use in a public health emergency."
GSK '052 targets the bacterial enzyme leucyl-transfer RNAsynthetase, or LeuRS, which is necessary for protein synthesis. Inhibitingprotein synthesis terminates cell growth and leads to apoptosis. An added bonusis that since there are no commercially available antibiotics that targetLeuRS, there is no known pre-existing bacterial resistance. Preclinical andPhase I studies have shown that NAME has potential as a treatment forinfections caused by a broad range of Gram-negative bacteria, including E.coli, K. pneumoniae, S. marcescens, Citrobacter spp., Providencia spp., Proteusspp., Pseudomonas aeruginosa and Enterobacter spp. It also has displayedpotential for treating pathogens responsible for complicated urinary tractinfections, complicated intra-abdominal infections, ventilator-associatedpneumonia and hospital-acquired pneumonia.
The compound was licensed to GSK by Anacor last July as partof the companies' ongoing research and development collaboration. Anacorreceived an option exercise fee of $15 million for the license and is eligiblefor future development milestones up to $75.5 million, commercial milestones ofup to $175 million and double-digit tiered royalties with the potential toreach the high teens on annual net sales, according to a company press release.For its part, GSK is responsible for all further development andcommercialization of the compound.
"BARDA's financial support for the development of GSK '052will help ensure the rapid development of this compound toward its approval inall relevant indications," David Perry, Chief Executive Officer of Anacor, saidin a press release. "With its novel mechanism of action, and potential to beadministered both orally and intravenously, we believe GSK '052 has thepotential to improve the lives of patients suffering from Gram-negativebacterial infections which have grown increasingly resistant to existingantibiotics."
BARDA's contract also supports initial lab testing toestablish the drug's potential in providing protection against multi-drugresistant pathogens, including those containing the New DelhiMetallo-beta-lactamase-1 (NDM-1) resistance gene. The NDM-1 gene makes bacteriathat carry it resistant to almost all routine antibiotics used for suchinfections.
The contract is part of a new approach to developing medicalcountermeasures, which was recommended last year in a review by KathleenSebelius, HHS Secretary. One facet is the development of broad-spectrumcountermeasures for biological threat agents that can also treat regular publichealth threats, such as multi-drug resistant bacterial infections. It is thethird contract funded under BARDA's new Broad Spectrum Antimicrobials Program.
