Achillion’s HCV approach focuses on the discovery and development of product candidates specific to a novel target, the HCV non-structural protein 4A or NS4A, a key component in viral replication. Through its in-house discovery efforts and as part of its collaboration with Gilead Sciences, Achillion has assembled a portfolio of next-generation antagonists to NS4A that are potent inhibitors of HCV replication. The Company believes these compounds have the following benefits:
Novel Mechanism of Action. Based upon extensive virology and biochemistry studies, the mechanism of action of these compounds appears to be novel and involves targeting the NS4A protein of HCV. Inhibiting this target prevents the formation of a functional replicase complex, a necessary step in viral replication that occurs before copying the viral RNA genome. Achillion believes this unique mechanism may contribute to the lack of cross resistance between its compounds and other HCV inhibitors. Click here to view an animation of how NS4A antagonism leads to inhibition of HCV replication.
Potency. Data obtained in the standard laboratory assays used to determine anti-HCV activity against the genotype 1 virus demonstrate that the Achillion compounds have potency in vitro in a range similar to the published data on Boehringer Ingelheim’s protease inhibitor under clinical development, and 14 to 21 times more potent in vitro than either the Schering-Plough or Vertex HCV protease inhibitors under clinical development.
NS4A Antagonist : Superior Potency Against Other Clinical Stage HCV Inhibitors
Lack of Cross Resistance. In laboratory studies, Achillion’s compounds have not demonstrated cross resistance to any of the polymerase inhibitors or protease inhibitors of which the Company is aware and has tested.
Ease of Administration. Based on current animal studies, compounds in this series appear to be orally bioavailable.
Evolving Treatment Paradigm
Current investigational treatment regimens combine a direct antiviral with Pegylated interferon.
Potential for Combination Treatment. Because of the lack of cross resistance in in vitro tests with all other known classes of HCV inhibitors, Achillion believes that NS4A antagonists are well positioned for evaluation as a treatment for chronic HCV in combination with the current standard of care and/or in combination with other direct-acting antivirals.
