Company says that compounds inhibit DNA gyrase, a key bacterial enzyme.
Achillion Pharmaceuticals won a phase 1 SBIR grant from the NIAID to evaluate a series of antibacterial compounds related to ACH-702, which is in late preclinical development. The firm claims the new compounds are potent inhibitors of the essential bacterial enzyme DNA gyrase and have shown early promise against drug-resistant strains of Mycobacterium tuberculosis.
The tuberculosis research will be carried out in collaboration with Michael Cynamon, M.D, at the Syracuse Veterans Administration Medical Center. Dr Cynamon will conduct antibacterial testing of compounds against M. Tuberculosis clinical isolates including drug-resistant strains.
“We believe that this compound series has the potential to deliver a new oral and intravenous agent for the treatment of tuberculosis infections including those caused by multidrug-resistant and extremely drug-resistant strains for which there are currently limited treatment options,” states Michael Pucci, Ph.D., senior director of microbiology at Achillion and principal investigator for the NIH grant. “Over the next few months we plan to profile and optimize several additional analogs prior to potential selection of a lead candidate for further development.”
ACH-702 is an internally discovered compound targeting serious nosocomial bacterial infections. The firm claims that it has demonstrated a broad spectrum of activity including inhibition of the DNA replication enzymes gyrase, topoisomerase IV, and primase. The molecule has also shown activity against multidrug-resistant bacteria in a laboratory evaluation of clinical isolates obtained from infected patients as well as in preclinical models of infection, Achillion adds.
The company’s two lead internally discovered candidates target chronic hepatitis C infection. ACH-1625 is an NS3 protease inhibitor currently in early clinical development. ACH-1095 is an NS4A antagonist, which the company claims is in a class of compounds that has demonstrated synergistic or additive effects in combination with other inhibitors of HCV. ACH-1095 is poised to start clinical development.
Achillion has also finalized a 96-week Phase II program for elvucitabine, a novel L-cytosine nucleoside analog reverse transcriptase inhibitor in Phase II development for the treatment of HIV. The compound has also completed Phase II trials as a potential treatment for HBV.
The firm sublicensed elvucitabine from Vion Pharmaceuticals (which had licensed the relevant patents and intellectual property from Yale University) and initiated development activities in 2000. In February the firm reported positive 96-week safety and efficacy data from a Phase II trial. The study evaluated the safety, tolerability, and antiviral activity of a once daily dose of elvucitabine in comparison with 3TC (lamivudine) as part of a standard triple-combination regimen.
Also in February Achillion signed an elvucitabine license agreement with GCA Therapeutics. The deal gives GCA an exclusive license, through its Chinese joint venture with Tianjin Institute of Pharmaceutical Research, to develop and commercialize elvucitabine for the treatment of both HIV and HBV in mainland China, Hong Kong, and Taiwan.