Sovaprevir Fall 2012 About Sovaprevir

SOVAPREVIR FALL 2012 ABOUT SOVAPREVIR

Achillion is a leader in the development of small molecule therapeutics for the treatment of HCV infection. Goals for New Sovaprevir (formerly ACH-1625) is a potent inhibitor of HCV NS3 protease which, based upon its preliminary HCV Therapeutic safety and tolerability, unique pharmacokinetic profile and demonstrated once-daily dosing, has the potential Development to be a best-in-class protease inhibitor for the treatment of chronic HCV infection. Sovaprevir is currently • Improving efficacy against the genotype being clinically tested in Phase 2 and is poised to begin studies as part of an all-oral, interferon-free regimen 1 virus for the treatment of HCV. • Offering a treatment response in patients who have failed an SOVAPREVIR AT-A-GLANCE interferon and ribavirin- • Pharmacokinetics. With its rapid and extensive partitioning to the liver, as well as high liver/plasma rations, based treatment sovaprevir has been clinically demonstrated to allow once-daily dosing. • Reducing treatment- • Virology. Sovaprevir has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent related adverse effects against HCV genotypes 1a and 1b (IC50 ~ 1nM). Further, no virology breakthrough during treatment with • Offering a more con- sovaprevir has been observed to date. venient, orally available, • Safety. High safety margins established during Phase 1 development have been replicated during Phase 2 treatment option development. Overall, the compound has been safe and well-tolerated to date. • Efficacy. Sovaprevir has achieved high rates of clinical cures in combination with pegylated-interferon and ribavirin and is expected to produce robust activity as part of an all-oral regimen for the treatment of HCV.

THE HCV MARKET OPPORTUNITY

It is estimated that over 170 million people are infected with HCV worldwide. The American Association of Liver Disease estimates that up to 85% of individuals become chronically infected following exposure to the virus. The current standard of care (SOC) for patients with chronic HCV infection is treatment with a combination of long acting, pegylated forms of interferon alpha (IFN-alpha) administered through weekly injections coupled with twice daily, oral doses of ribavirin. The duration of treatment for HCV patients infected with the genotype 1 virus is 12 months and is successful in only approximately 50% of patients receiving a full course of treatment. Up to 40% of those patients modify or discontinue therapy due to adverse side effects, including flu-like symptoms, anemia, depression, fatigue, suicidal tendencies and abnormal fetal development.

PROTEASE INHIBITOR PROGRAM OVERVIEW

Our proprietary HCV protease inhibitors were designed and synthesized based on crystal structures of enzyme/inhibitor complex. Comprehensive in vitro and in vivo profiling was utilized for progression of potent inhibitors. Sovaprevir is an “open chain,” non-covalent, reversible inhibitor of NS3 protease. It was selected for development based on an optimal target profile for its high potency, unique pharmacokinetic properties and excellent safety profile at high drug exposures.

Preclinical Data Sovaprevir demonstrated high potency against HCV genotypes 1a and 1b, unique pharmacokinetic properties and an excellent safety profile at high drug exposures in two animal species through 9 months of evaluation. In addition, sovaprevir demonstrated rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. Clinical Data Achillion initiated clinical trials with sovaprevir in 2009 and has steadily advanced the program into Phase 2 development. In Phase 1 clinical studies, subjects receiving both single and multiple ascending doses of sovaprevir, ranging from 50 mg to 2000 mg, for periods up to 5 days and demonstrated that it was well tolerated at all doses with no serious adverse events. In Phase 1b clinical studies, HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.11log10 to

4.25log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 1.01log10 from baseline through day 12, the last day of viral load measurement in the study. Phase 2 development of sovaprevir began in Sovaprevir (ACH-1625): Phase 2a (segment 2) September 2010 with the initiation of a random- Mean Change in GT1 HCV RNA ized, double-blind, placebo-controlled trial evaluating the safety, tolerability and antiviral activity of once daily sovaprevir in combination with SOC after 28 days of dosing (segment 1) and after 12 weeks of dosing (segment 2) in genotype 1 treatment naïve HCV- infected patients. In segment 1, a rapid viral response (RVR) of 75 – 81% was reported following 4 weeks of therapy with no serious adverse events reported and a side-effect profile similar to that previously seen in Phase 1. Segment 2, evaluating 12–weeks of combination therapy demonstrated robust continued early virologic response (cEVR) of up to 100% with sustained viral responses (SVR), or cures, of approximately 90% across all dose groups. Achillion is poised to advance sovaprevir into all-oral, interferon-free trials that will evaluate sovaprevir in combination with one or more direct-acting antiviral agents and anticipates reporting initial results from these studies during the first quarter of 2013.

ABOUT ACHILLION Achillion is an innovative biopharmaceutical company dedicated to Achillion Pharmaceuticals, Inc. bringing important new treatments to patients with infectious disease. The Company’s 300 George Street highly skilled and experienced discover and development teams have identified and New Haven, CT 06511 advanced multiple therapeutic compounds, many with novel mechanisms or attributes. Main phone: 203.624.7000 Achillion is focused on solutions for the most challenging problems in infectious disease Email: [email protected] including hepatitis C (HCV) and resistant bacterial infections. www.achillion.com