Enanta Pharmaceuticals could receive up to $42.7 million from the NIAID over five years to develop antibiotics to be used as medical countermeasures against multiple biodefense Category A and B bacteria. The award will fund preclinical and clinical development of a new class of bridged bicyclic antibiotics known as bicyclolides.
Enanta has focused on bicyclolides for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and resistant streptococci. Enanta has bicyclolides that are active against top priority Gram-positive and Gram-negative biodefense pathogens like anthrax (Bacillus anthracis), plague (Yersinia pestis), tularemia (Francisella tularensis), and glanders (Burkholderia mallei).
Due to a unique binding site on the bacterial ribosome, bicyclolides are very effective against resistant pathogens, according to Enanta. "Bicyclolide antibiotics discovered by Enanta offer a new broad spectrum approach to treating lethal infections including those caused by biothreat pathogens," says Jay Luly, Ph.D., president and CEO, Enanta.
"We have new bicyclolides with both oral and IV dosage forms to provide flexible treatment options for the hospital and community setting. This contract will enable us to advance additional bicyclolide candidates into clinical development."
Enanta has applied several research strategies to develop its antibiotics, including innovative medicinal chemistry approaches to create novel and proprietary chemical structures; conformational engineering of macrolides so that the molecular shape is no longer recognized by the bacterial efflux pumps; and structural design to add chemical moieties that interact with additional binding elements of the bacterial ribosomal RNA to overcome targeted superbugs.
Enanta is also developing protease, NS5A, nucleoside(tide) polymerase, and cyclophilin-based inhibitors targeted against the hepatitis C virus (HCV). The company says that it has established a SAR strategy to create novel and proprietary series and leads that demonstrate significant antiviral potency in the enzyme and cell-based replicon assay.
Enanta reports that it has identified promising lead series and several lead candidates that have sub nM potency in the replicon assay, good bioavailability, attractive drug levels at the site of infection, and potential for QD dosing. Enanta has announced the advancement of this program into Phase II trials. Enanta has a worldwide collaboration agreement with Abbott Laboratories for the development of protease inhibitors, under which Enanta retains a 40% profit share option in the U.S. and has royalty streams in non-U.S. territories.