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ANA598 Demonstrates Potent Antiviral Activity in an Early Clinical Study in HCV-Infected Patients

SAN DIEGO, Jan. 8 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. today announced results from the first cohort of an ongoing Phase Ib clinical trial of ANA598, the Company's investigational non-nucleoside polymerase inhibitor. ANA598 was very well-tolerated and demonstrated potent antiviral activity in patients infected with chronic Hepatitis C virus (HCV) in this first cohort of the study.

Patients in the first cohort received 200 mg ANA598 (n=8) or placebo (n=2), twice-daily (bid) for three days. At the end of the treatment period, the median viral load decline was 2.5 log10 (>99%), with a range of 1.4-3.4 log10, for the eight patients who received ANA598. Three patients who received ANA598 were genotype 1a and demonstrated a median viral load decline of 1.6 log10, while five patients who received ANA598 were genotype 1b and demonstrated a median viral load decline of 2.6 log10. All eight patients who received ANA598 demonstrated a rapid decline in viral load, and no patients demonstrated viral rebound while on study drug. In addition to the robust viral load decline, ANA598 was very well-tolerated and there were no serious adverse events in the first dose cohort, although conclusions regarding longer-term safety and tolerability cannot be made until the results of future clinical trials of longer duration in more patients are known. Patients are currently being enrolled in the second cohort (400 mg bid) of the study. Anadys expects to report detailed data from multiple cohorts of the study at an upcoming medical conference.

"We are very pleased with the antiviral activity and safety of ANA598 at this first dose tested in the Phase Ib study," commented James Freddo, M.D., Anadys' Senior Vice President, Drug Development and Chief Medical Officer. "We believe this early data continues to position ANA598 as a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV and we look forward to investigating ANA598 in longer-term studies in combination with current standard of care."

"The clinical and preclinical profile of ANA598 observed to date is very impressive," said Steve Worland, Ph.D., President and CEO of Anadys. "The magnitude of viral load drop reported today for ANA598 is greater than has been reported for any other non-nucleoside HCV inhibitor in a monotherapy study. Furthermore, the rate of initial viral load decline, believed to be associated with direct inhibition of viral replication, is greater than has been reported previously for all classes of HCV polymerase inhibitors, including nucleosides. This demonstrated antiviral potency holds significant promise for the future use of ANA598 in combination with other anti-HCV agents."

Anadys retains worldwide rights to ANA598, which was fully discovered at the Company. Preclinical evaluation of ANA598 was completed in the first quarter of 2008, leading to submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA), subsequent allowance of the IND by the FDA and initiation of clinical investigation in the second quarter of 2008. In December 2008, Anadys announced that the FDA granted fast track designation to ANA598 for the treatment of chronic HCV.

In October 2008, Anadys initiated patient dosing in the Phase Ib study of ANA598 in HCV patients. In the double-blind, randomized placebo-controlled Phase Ib study, treatment-naive genotype 1a and 1b patients are to receive oral capsules of ANA598 over three days at doses of 200 mg bid (twice-a-day), 400 mg bid or 800 mg bid. Ten patients are to be enrolled at each dose level, eight receiving active drug and two receiving placebo.

In a Phase I study in healthy volunteers, ANA598 was administered as capsules at single oral doses of 400 mg, 800 mg, 1400 mg, 2000 mg (fed and fasted) and 3000 mg. In addition, a separate cohort received two 800 mg doses 12 hours apart. ANA598 was well tolerated at all doses and there were no serious adverse events or withdrawals from the study. All reported adverse events were classified as mild or moderate, with no apparent dose relationship. The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 consistent with the potential for once-daily or twice-daily oral dosing.

In the preclinical program, ANA598 was well tolerated at all doses tested in 28-day GLP toxicology studies. In September 2008, Anadys initiated long-term, chronic toxicology studies of ANA598.

If ANA598 is successful in early stage development, the Company anticipates completion of the clinical, toxicology and manufacturing activities required to initiate Phase II studies of ANA598 in combination with current standard of care in mid-2009.

Anadys will host a conference call today, January 08, 2009, 2009 at 8:30 a.m. Eastern Standard Time (5:30 a.m. Pacific Standard Time) to discuss the results from the first cohort of the ongoing Phase Ib clinical trial of ANA598. A live webcast of the call will be available online at A telephone replay will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 99568266.The webcast and telephone replay will be available through January 22, 2009.

Chronic HCV infection is a serious public health concern affecting approximately 3.2 million people in the United States and approximately 170 million people worldwide. HCV causes inflammation of the liver, which can lead to fibrosis and cirrhosis, and may ultimately lead to liver failure and/or liver cancer if not successfully treated. Cirrhosis of the liver resulting from chronic HCV infection is the leading indication for liver transplantation in the U.S. Due to the asymptomatic nature of HCV infection, it often goes undetected for up to 20 years following initial infection. Each year, 8,000 to 10,000 people in the U.S. die from complications of HCV.

The current standard of care is a combination of pegylated interferon and ribavirin. Inadequate response rates, in particular for patients infected with genotype 1 HCV, along with significant side effects of approved therapy, support the medical need for improved treatment options. It is estimated that fewer than 5% of people with chronic HCV infection living in the U.S. are under treatment today. Most infected individuals are unaware of their infection status and the large majority of individuals who know their condition do not currently receive drug therapy. There is also a growing number of individuals who have failed interferon-based regimens who may be successfully treated with combinations of two or more direct antivirals. It is expected that the next generation of therapies for treatment of HCV will include small molecules, such as ANA598, that directly act upon specific viral enzymes to inhibit viral replication. These new therapies are expected to improve overall therapy by increasing cure rates and potentially improving tolerability and convenience of treatment if doses of currently used agents can be reduced or eliminated.

Anadys Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to improving patient care by developing novel medicines in the areas of hepatitis C and oncology. For the treatment of chronic hepatitis C, the Company is developing two potentially complementary agents, ANA598, a non-nucleoside polymerase inhibitor and ANA773, an oral TLR7 agonist prodrug. The Company is also developing ANA773 for the treatment of cancer.

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the potency, safety and tolerability profile of ANA598, which may not be duplicated in future cohorts at higher doses or future clinical studies of longer duration; (ii) the belief that ANA598 is a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV and the ability to use ANA598 in combination with other anti-HCV agents in the future; (iii) the potential for once-daily or twice-daily oral dosing of ANA598; (iv) the ability of Anadys to transition into Phase II studies of ANA598 during 2009; and (v) expectations regarding the evolution of the market for HCV therapies. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies (including those described in this press release) may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues, will have favorable results in future cohorts of the Phase Ib study or future clinical trials, will maintain fast track designation or will receive regulatory approval. In addition, Anadys' results may be affected by risks related to competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into collaborations around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its product candidates, regulatory developments involving its product candidates and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2007 and Anadys' Form 10-Q for the quarter ended September 30, 2008. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

Posted: January 2009