5-year contracts could total $150 million, support research with emerging infectious disease and biodefense applications
Four companies are to develop broad-spectrum therapeutics-antibiotics, antivirals and an antitoxin-to prevent or treat diseases caused by multiple types of bacteria or viruses, under contracts awarded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Total funding for the four contracts could reach $150 million over a maximum five-year period.
The contracts are designed to support essential research and development activities to enable promising investigational therapies to move toward early-phase clinical studies and, if successful in clinical studies, on to eventual licensure. The ultimate goal is to develop products that the U.S. government can stockpile to protect the public in the event of a bioterror attack or public health crisis.
In line with NIAID's strategic plan for biodefense and emerging infectious diseases research, these contracts move beyond the paradigm of drug development that is sometimes called "one-bug, one-drug." (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/biosp2007.pdf)The contracts are to focus on candidate therapies that can be used against classes of pathogens rather than being agent-specific. Such broad-spectrum therapeutics would improve preparedness for all infectious threats, whether they occur naturally or are deliberately introduced.
The following companies are recipients of the new contracts:
CUBRC Inc., Buffalo, N.Y., in partnership with Tetraphase Pharmaceuticals, Watertown, Mass.-Researchers will develop a fully synthetic tetracycline product, TP-271, to treat the bacterial disease tularemia, and respiratory infections such as community-acquired bacterial pneumonia. Both intravenous and oral formulations of the drug will be evaluated in preclinical studies for safety and efficacy, and several preliminary 1 clinical trials are planned. The compound will also be tested in nonclinical studies for activity against anthrax and plague. The initial award is for $5.7 million, with the potential for up to $35 million over five years.
Enanta Pharmaceuticals Inc., Watertown, Mass.-Researchers will develop and evaluate a candidate from a novel class of next-generation broad-spectrum antibiotics known as bicyclolides. Bicyclolides are small-molecule anti-infectives. Enanta's bicyclolide has demonstrated potential for activity against anthrax, plague and tularemia in cell culture studies, as well as efficacy against anthrax and tularemia in mice. The compound will be evaluated for effectiveness against multiple bacteria that might be used as agents of bioterror, and several Phase 1 clinical trials are planned. Bicyclolides represent a promising new class of broad-spectrum antibiotics that have demonstrated activity against the two major groups of bacteria, known as gram-negative and gram-positive bacteria. These groups of bacteria are distinguished by the presence or absence of peptidoglycan, which is visible in lab specimens when the bacteria are stained using the Gram method. In general, the two types of bacteria are treated using different types of drugs.The initial award is for $14.3 million with the potential for a five-year total of up to $43 million.
Unither Virology LLC, Silver Spring, Md.-Unither will develop and evaluate UV-4, an investigational antiviral drug with potential as a treatment for influenza and dengue fever and possible applications for viral hemorrhagic fever, smallpox and hepatitis. The drug is derived from a class of compounds known as iminosugars that includes drugs approved for other indications, such as diabetes and Gaucher's disease. UV-4, which may also reduce the potential for drug resistance, is expected to undergo toxicity studies, a preliminary safety study and a Phase 2 clinical trial for dengue fever. Unither has received an initial award of $10.5 million with the potential for up to $45 million over five years.
XOMA (US) LLC, Berkeley, Calif.-The company will develop an intravenous antitoxin to treat human botulism poisoning. XOMA's monoclonal antibody product will target serotypes C and D of Clostridium botulinum neurotoxin and would also neutralize C/D and D/c mosaic/hybrid toxins. The development of human botulinum monoclonal antibodies would replace existing horse-based antitoxin products that are difficult to make and pose safety concerns for humans. A preliminary clinical trial is planned for XOMA's anti-C/D toxin product. The company received $7 million in its initial NIAID award with the potential for up to $28 million in five years.