Analysts weigh in on takeover odds of Achillion and Idenix...

Posted on Weds from Market Watch.com : It drives me nuts when 'nucs',  the popular shortened term for 'nucleoside analogs', is spelled 'n-u-k-e-s' instead. We're talking drug development, not nuclear arms proliferation in unstable Middle East nations. Probably a good indicator I need something else to take out my frustrations on. 

An article here from Market Watch talking to several analysts about possible mergers of Achillion and Idenix. No doubt that the slack of easing sales of Incivek and Victrelis will definitely be picked up by the 2nd and 3rd generation molecules, especially if developers can manage an interferon-free regimen. The HCV drug development space is incredibly hot right now, and with an estimated 170 million people infected, successful drugs are probable cash cows for many years to come.

Feb. 1, 2012, 12:01 a.m. EST

Achillion, Idenix could miss hep-C merger bonanza

By Val Brickates Kennedy, MarketWatch

BOSTON (MarketWatch) -- Investors tantalized by a recent string of lucrative takeover offers for hepatitis C drug-developers shouldn’t assume that an eye-popping bid for Idenix Pharmaceuticals and Achillion Pharmaceuticals is just around the corner, according to biotech analysts.

Both Idenix  were put in play earlier this month by news that Bristol-Myers Squibb intends to buy Inhibitex Inc for $2.5 billion in cash.The offer represents a dazzling 163% premium over Inhibitex’s pre-bid closing price.

Bristol’s bid also comes on the heels of two other lucrative takeovers in the hepatitis C virus, or HCV, arena. In October, Roche announced it was paying a stunning 256% premium, or $230 million, for tiny Anadys Pharmaceuticals. That was followed by Gilead Sciences’s whopping $11 bid for Pharmasset Inc., which carried an 89% premium.

Rumors have since swirled that other Big Pharma players are likewise eyeing the HCV space. And that speculation has helped push up Idenix shares by a hefty 80% and Achillion shares by 45% since the beginning of the year.

At stake is a market filled with a backlog of under-treated HCV patients that many analysts believe could reach $10 billion a year within the next five years.

But here’s the kicker -- because the new HCV drugs can actually cure the disease, their demand will likely drop over time after the backlog of patients is treated. Despite this, most analysts agree the market should be able to coast along at the $10 billion level for at least ten years. And because time is of the essence, companies with HCV drug candidates in mid-to-late stage development have been considered the hottest takeover targets.

Of the two companies, Idenix’s stock has seen the most action largely because its lead drug candidate hails from a highly-touted class of drugs called nucleotides, or “nukes.” Both Inhibitex’s and Pharmasset’s lead drug candidates are nukes, which is what made them particularly attractive acquisitions.

“I don’t think Idenix’s stock’s bid too high,” said Wedbush Securities analyst Duane Nash, who tracks Idenix. “But the caveat is that acquisitions generally take longer than most people anticipate.”
While Wedbush currently has Idenix’s fair market value listed at $15 a share, Nash believes that Idenix could fetch a takeout price of between $20 and $25 a share. The stock closed at $13.39 on Tuesday.

William Blair analyst Katherine Xu, meanwhile, said she believes Idenix’s current takeout range is probably between $15 and $20 a share. Xu currently has a price target of $10 on the stock.

Xu added that she could be raising her target into the mid-to-high teens if and when U.S. regulators give the green light to an Idenix’s clinical trial that has been placed on partial hold over safety concerns. The decision is expected within the next few weeks.

“I doubt people will take it out before the hold is removed,” she said.

But analysts also point out that Novartis AG’s roughly 30% equity stake in Idenix could hinder a takeover bid, especially as the Swiss pharmaceutical giant reportedly has options to some key drug candidates. Meanwhile, JMP Securities analyst Liisa Bayko thinks that investors have overvalued Idenix’s nuke drug candidate, which she says isn’t as potent as those being developed by Inhibitex and Pharmasset. Because of this, Bayko has a sell rating on the stock.

As for Achillion, the reason its shares haven’t been bid up as high as Idenix’s is largely because its lead drug candidate is a protease inhibitor, a class of drugs that includes Merck & Co.’s Victrelis and Vertex Pharmaceuticals’s Incivek, which were both launched last year. Several other drug developers already have protease inhibitors in their pipelines.

Xu said that while she currently has Achillion’s price target at $15 a share, its takeout range is probably between $15 and $20. The stock closed at $11.09 on Tuesday.

“I think it’s still undervalued at the moment,” she said.

Wells Fargo Securities analyst Brian Abrahams said that even though Achillion’s lead drug candidate isn’t a nucleotide, that doesn’t mean it isn’t an attractive acquisition target.

“Certainly nucleotides are an exciting class but they’re not the only class we believe will be used in HCV treatment,” said Abrahams, adding that doctors will be looking to use the drugs in combination to get the best results.

Roche Pharmaceuticals buys Anadys Pharmaceuticals in $230 million deal...

Looks like Roche is gearing itself up for the HCV Wars by potentially bolstering it's long-standing presence in HCV with Anadys's non-nuc Setrobuvir, which currently in Phase II clinical trials.

Roche to Acquire Anadys Pharmaceuticals
Oct 20, 2011
By: Rich Whitworth
ePT--the Electronic Newsletter of Pharmaceutical Technology


In a deal worth approximately $230 million, Roche has signed an agreement to acquire Anadys Pharmaceuticals according to a Roche press release issued Oct. 17, 2011. Citing aims to bolster future treatment options for hepatitis C, the merger will see Roche fully acquiring Anadys at a share price of $3.70 in an all-cash transaction.

Anadys, a US-based company, develops oral, small-molecule therapeutics for the hepatitis C virus (HCV), the most advanced of which is a direct-acting antiviral compound (Setrobuvir, a non-nucleoside polymerase inhibitor) that is being evaluated in Phase II studies in combination with Roche’s pegylated interferon (Pegasys) and ribavirin (Copegus).

Also in development at Anadys is an oral, small-molecule inducer of innate immunity. Currently in Phase I trials, it may prove useful for treating HCV as well as other chronic infections and oncology, another strong focus for Roche.

“This acquisition augments our already strong HCV portfolio. Our aim is to offer physicians and hepatitis patients a powerful combination of therapies that bring us closer to a cure, even without the use of interferon. Anadys’ compounds provide additional modes of action that could lead to interferon-free treatment regimens without viral resistance,” said Jen-Jacques Garaud, global head of Roche Pharma research and early development.

Steve Worland, president and CEO of Anadys, said, “With Roche’s considerable capabilities and experience in HCV, we believe this acquisition provides the best chance of success for the new potential treatments to reach patients.”

Anadys added in its own press statement that Anadys’ directors and executive officers have agreed to tender their own shares in the offer, which is expected to close in the fourth quarter of 2011.

Anadys Announces Positive 12-Week Data for Setrobuvir in Phase 2b Hepatitis C Study

Positive interim (12 week) Phase IIb data for Anadys's non nuc Setrobuvir + p/r in both treatment naive and non-responders to previous P/R. Looks to be comparable to P/R in side effect profile, except for the amount of rash (39%) (98% mild to moderate)

Anadys Announces Positive 12-Week Data for Setrobuvir in Phase 2b Hepatitis C Study

- Strong Antiviral Response in Prior Partial Responders and Relapsers - Favorable Safety Data with AE Profile Comparable to Control Group - High Barrier to Resistance Confirmed --Conference Call at 8:00 AM EDT Today

SAN DIEGO, Oct. 13, 2011 Anadys Pharmaceuticals today released interim antiviral response and safety data from an ongoing Phase IIb study of setrobuvir in combination with pegylated interferon and ribavirin (P/R) in genotype 1 hepatitis C patients. Setrobuvir is the Company's direct-acting antiviral being developed for the treatment of chronic hepatitis C, or HCV.

"We are pleased with today's data, which we believe demonstrate a compelling profile for setrobuvir in significantly more patients," said Steve Worland, Ph.D., President and CEO of Anadys. "The antiviral response in patients who had failed prior treatment is a particularly encouraging benchmark of setrobuvir's potency and high barrier to resistance. Coupled with a favorable safety profile to date, we believe today's data position setrobuvir as a very attractive agent to be included in future DAA combination regimens."

78% of treatment-naive patients and 76% of patients who had responded inadequately to, or relapsed after, prior treatment with P/R had undetectable virus at week 12 (cEVR) while receiving setrobuvir plus P/R, compared to 56% and 44%, respectively, for patients who received placebo plus P/R. 71% of treatment-naive patients who received setrobuvir plus P/R had undetectable virus at week 8 and met the initial response-guided criteria for shortening treatment in this study to 28 weeks from the traditional 48 weeks for treatment with P/R alone.

29% of patients who had no appreciable response to prior treatment with P/R (null responders) achieved cEVR with setrobuvir plus P/R, and the percentage of patients with undetectable virus continued to climb in this hard-to-treat population to 36% at week 18. No prior null responders received placebo plus P/R in this trial.

The viral breakthrough rate through 12 weeks on setrobuvir plus P/R was low in both treatment-naïve patients (2.9%) and patients who had responded inadequately to, or relapsed after, prior treatment with P/R (3.6%). The Company believes this low incidence of viral breakthrough exhibited to date in a larger patient population further characterizes setrobuvir's high barrier to resistance.

Setrobuvir has been generally well-tolerated in the study. Safety data for patients receiving setrobuvir plus P/R, and comparison to the control group that received placebo plus P/R, are being reported through a time period that reflects a median dosing duration of 19 weeks. The rate of discontinuing treatment in the study due to adverse events has been similar in patients receiving setrobuvir plus P/R (5.6%) or P/R alone (5.9%). The profile of adverse events has been similar between the setrobuvir and control groups, with reported adverse events being typical for patients treated with interferon and ribavirin. In the setrobuvir group, 39% of patients (84/215) developed a rash while 22% (15/68) of patients in the control group developed a rash. 98% of the rashes in the setrobuvir group were mild or moderate (grade 1 or grade 2), compared to 93% in the control group. There were no Grade 4 rashes in either group. The incidence of rash in the setrobuvir group is consistent with prior reports of rash due to interferon and ribavirin through 19 weeks of treatment.



Proportion of patients with undetectable virus at Week 12 (cEVR)
setrobuvir + P/R placebo + P/R
--------------------- ---------------------
Treatment-naive patients 78% 56%
----------------------------------- --------------------- ---------------------
Treatment-experienced patients
prior partial responder or relapser 76% 44%
prior null responder 29% ---
----------------------------------- --------------------- ---------------------




Phase 2b Protocol Design

283 patients were dosed in this study. Patients received either setrobuvir 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) (P/R) with a loading dose of setrobuvir 800 mg bid on day 1, or placebo plus P/R. Patients who had a prior null response to P/R, defined as less than a 1 log10 decline in viral load at week 4 or less than a 2 log10 decline at week 12 during prior treatment, were not randomized to receive placebo. All other patients were stratified by IL28B genotype (CC/non-CC) between setrobuvir and placebo groups. The interim antiviral response data is being reported as the proportion of patients with undetectable virus (< 15 IU/mL) using the Roche COBAS HCV TaqMan assay. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. In addition to the interim data released today, data through 24 weeks of dosing are expected around year-end. The study is being conducted at sites in the United States, Canada, Australia and New Zealand.

Treatment-Naive Group

102 treatment-naive patients received setrobuvir plus P/R

36 treatment-naive patients received placebo plus P/R

Treatment-naive patients who achieved undetectable levels of virus by Week 8 and maintain undetectable levels of virus are scheduled to conclude all treatment at Week 28

For treatment-naive patients with detectable virus at Week 8, treatment with setrobuvir or placebo and P/R is scheduled to continue through Week 48

Treatment-Experienced Group (including prior null responders)

82 patients who were partial responders during, or relapsers after, a prior course of therapy with P/R alone received setrobuvir plus P/R

32 corresponding patients received placebo plus P/R

31 prior null responder patients received setrobuvir plus P/R

All treatment-experienced patients are scheduled to be treated for 48 weeks

About Setrobuvir

Setrobuvir is an HCV RNA polymerase inhibitor that belongs to a chemical class referred to as non-nucleosides. Setrobuvir has a well-characterized safety database in which more than 350 subjects have received the agent to date. Setrobuvir has received Fast Track Status from the FDA for the treatment of chronic hepatitis C. Earlier this year, Anadys announced a cross-company clinical trial agreement with a large, commercial-stage biopharmaceutical company to study setrobuvir in combination with another DAA in healthy volunteers.

Conference Call Webcast and Slides

Anadys will hold a conference call and webcast today, October 13, 2011 at 8:00 a.m. Eastern Daylight Time to discuss interim antiviral response and safety data from an ongoing Phase IIb study of setrobuvir in combination with P/R. A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com . A telephone replay with slides 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 21814367. The webcast and telephone replay will be available through October 27, 2011.

Safe Harbor Statement

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such forward-looking statements include, but are not limited to, references to (i) the belief that the interim data described in this press release, coupled with a very favorable safety profile to date, position setrobuvir as a very attractive agent to be included in future DAA combination regimens, (ii) Anadys' belief that the low incidence of viral breakthrough exhibited to date further characterizes setrobuvir's high barrier to resistance, and (iii) setrobuvir's potency and adverse event profile based on the interim data reported in this press release. Such 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 may not be predictive of future results, and Anadys cannot provide any assurances that setrobuvir will not have unforeseen safety issues, will have favorable results in ongoing or future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its non-clinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments 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-Q for the quarter ended June 30, 2011. 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.

Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.

SOURCE Anadys Pharmaceuticals, Inc.

Copyright (C) 2011 PR Newswire. All rights reserved

Anadys Pharmaceuticals' Steve Worland on the future of HCV drug development....

An excellent read here. Anadys Pharmaceuticals President and CEO Steve Worland gives us his take on the evolving HCV antiviral drug developmental landscape in this recent article published online in Xconomy. It's amazing how analogousness this development space is becoming to the early days of HIV. There are many notables in this article, including the mention of mathematical modeling that suggests that interferon-free regimens might be possible, but will need to contain three or four distinct antiviral mechanisms to result in a SVR without the emergence of resistance. I found his comparison of Anadys's HCV non-nuc setrobuvir to to the HIV non-nuc efavirenz to be interesting - his feeling is that, like efavirenz, setrobuvir's superior pharmacokinetics may be the answer to the inherent low barrier of resistance issues with the non-nuc class that have plagued other compounds such as Vertex's VX-222.

Dramatic Changes in Hepatitis C Treatment Expected to Continue
Steve Worland 9/6/11

Earlier this year the FDA approved telaprevir (Incivek) from Vertex Pharmaceuticals and boceprevir (Victrelis) from Merck for the treatment of hepatitis C. Both agents are protease inhibitors and represent the first approvals of direct acting antivirals for hepatitis C. Direct acting antivirals are a broad class of agents that act to block the growth of viruses by directly disrupting essential viral functions. The benefit of these drugs for hepatitis C follows the dramatic success of this class over the last 15 years in HIV. Now the future advances of direct acting antiviral therapy for hepatitis C is expected to follow a central theme of their use in HIV: that combination of multiple antivirals in a single treatment regimen will provide greater benefit than use of any one antiviral drug alone.

The new protease inhibitors were approved for use only in combination with two previously approved agents, pegylated interferon and ribavirin. The addition of either protease inhibitor increased clinical cure rates, known formally as sustained viral response (SVR) rates, by 30 to 40 percentage points over control groups receiving the standard pegylated interferon and ribavirin alone. As dramatic as these improvements are, there is a good chance for even more dramatic improvements if all-oral regimens, assembled by combining multiple direct acting antivirals, are able to maintain high cure rates while eliminating injectable interferon and its associated flu-like side effects that patients have long sought to avoid.

Next in the development queue are three agents that entered Phase III development this year, including two additional protease inhibitors (TMC435 from Johnson & Johnson’s Tibotec unit and BI201335 from Boehringer Ingelheim) and a cyclophilin inhibitor that disrupts a host function required for viral replication (alisporivir from Novartis). All three Phase III programs are exploring a modality similar to the approved agents, i.e. addition of a single new agent to the standard pegylated interferon/ribavirin. The ongoing Phase III programs will hope to demonstrate one or more advantage over the recently approved agents, potentially including better tolerability, further increases in cure rates, shorter duration of therapy and/or an increased proportion of patients successfully treated with shortened therapy. While such improvements may well be achieved, they may become less important or even irrelevant if the rapidly expanding number of direct acting antiviral combination trials leads to identification of new regimens that surpass all regimens that are based on a single antiviral drug added to the old standard regimen.

Investigation of direct acting antiviral combination regimens has exploded in the last 12 months. This advance has become possible because of the diversity of antiviral mechanisms distinct from protease inhibitors that are now represented in the pipeline of hepatitis C drugs in Phase II development across the industry. Diverse mechanisms are important because they typically provide distinct resistance profiles, and antiviral combinations are being assembled using new compounds with non-overlapping resistance profiles to provide a greater barrier to the development of antiviral resistance. Additional factors that are considered important in assembling optimal combinations include the safety and tolerability profile of each agent, compatible pharmacokinetic profiles and a low potential for unfavorable drug-drug interactions. The more extensively characterized each individual antiviral drug is, the lower the risk of an unanticipated negative interaction between the drugs once combined.

New mechanisms other than protease inhibitors that have entered large Phase IIb studies include non-nucleoside polymerase inhibitors (setrobuvir from my company, Anadys Pharmaceuticals, as well as tegobuvir from Gilead Sciences and filibuvir from Pfizer). Another class is composed of nucleoside/tide polymerase inhibitors (mericitabine from Roche and PSI-7997 from Pharmasset). There’s also an NS5a inhibitor in Phase IIb development (BMS-790052 from Bristol-Myers Squibb).

At Anadys, we chose to focus on the non-nucleoside class of polymerase inhibitors for several reasons. We recognized an inherent potential for an excellent safety profile, given the absence of structurally related host targets and the ability to generate inhibitors without relying on close analogs of host metabolites. The excellent safety record to date for setrobuvir is consistent with our initial expectations regarding safety. The diversity of applicable chemotypes also led us to expect a clear path to patent-protected intellectual property, exemplified by our recently issued U.S. patent covering setrobuvir. In other antiviral drug classes, especially nucleosides/tides and NS5a inhibitors, the range of useful chemical space discovered to date is considerably more narrow, leading to the potential for more interference on the IP side. Lastly, we recognized that a potential liability of the non-nucleoside class, a lower genetic barrier to resistance, could likely be addressed if we were able to engineer a high pharmacological barrier to resistance into candidate molecules. This recognition was based on the lessons learned about non-nucleosides in the 1990s in HIV. Specifically, there were two disappointing product introductions of non-nucleoside products for HIV that were plagued with rapid emergence of resistance—nevirapine (Viramune) from Boehinger Ingelheim and delavirdine (Rescriptor), now marketed by Pfizer. After that came efavirenz (Sustiva) from Bristol-Myers Squibb, so named for its ability to last longer in the bloodstream, which demonstrated that a non-nucleoside with good potency and a prolonged plasma half-life could demonstrate a dramatically improved resistance profile. While we reasoned that a similar solution would be applicable in hepatitis C, we also understood the significant medicinal chemistry challenge to accomplish this objective and furthermore understood that the technology platform at Anadys was exquisitely well matched to the molecular engineering challenge of simultaneously optimizing potency and pharmacokinetics. The excellent resistance profile of setrobuvir observed to date demonstrates the high pharmacological resistance barrier achieved with setrobuvir, and data to date is consistent with our idea that a high pharmacological barrier to resistance could serve in place of a high genetic barrier to resistance.

As the hepatitis C development landscape continues to advance, we expect to see an increasing number of direct acting antiviral combination trials and subsequent approval of new agents based on data derived from such trials. The FDA as well as patient advocacy groups have been strong proponents of investigating antiviral drug combinations prior to approval of individual components, and I expect an ongoing favorable regulatory environment towards combination trials provided that each individual agent is sufficiently well-characterized.

Companies that believe in the importance of antiviral combinations for future commercial relevance in hepatitis C are likely to have opinions as to how many drugs they believe will be needed in antiviral combination regimens, and are likely to pursue strategies directed at accessing at least that number of compounds if not a greater number as insurance against attrition. Mathematical modeling from Perelson and colleagues suggests that interferon-free regimens will need to contain three or four distinct antiviral mechanisms to result in viral eradication (SVR) prior to emergence of resistance. To access the required number of drugs, companies have several business alternatives available. They can rely on maturation of their internal pipelines, although few if any companies appear today to have sufficiently robust internal pipelines to rely exclusively on this approach. Companies can rely on cross-company clinical collaboration agreements to gain initial data on particular antiviral combinations, although this approach doesn’t directly answer the question of how to seek approval and launch effective marketing efforts for the individual components studied in a cross-company antiviral drug combination trial. Companies with antiviral drugs other than protease inhibitors can look to utilize one of the approved protease inhibitors as one other mechanism, analogous to the use of interferon and ribavirin in the development of the protease inhibitors to date, but this will only be a partial solution if three or more DAAs are required. Lastly, companies can gain exclusive access to antiviral drugs outside their current pipelines through a variety of business deals, allowing them to quickly assemble a pipeline with sufficient depth to increase the chances of being early to market with a successful combination regimen. To date, examples of all these strategies except combination with one of the approved protease inhibitors have been pursued by one or more companies. Going forward, these efforts across the industry are likely to culminate in approval of direct acting antiviral combination regimens, with the ultimate goal of assembling combinations powerful enough to eliminate interferon and perhaps ribavirin from hepatitis C therapy. These advancements may occur within the next few years, and if realized, would represent yet another dramatic improvement in hepatitis C therapy, at least as dramatic as the advances recently realized with the approval of the first protease inhibitors.

Steve Worland is the president and CEO of San Diego-based Anadys Pharmaceuticals.

Anadys Initiates Dosing in Phase IIb Study of ANA598

The race for next gen DAA compounds continues. Given the AE's, dosing difficulty and the sequential therapy void associated with the upcoming Telaprevir and Boceprevir compounds, the market looks lucrative.

SAN DIEGO, Jan. 26, 2011 /PRNewswire/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that dosing has begun in the Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin in hepatitis C patients. ANA598, the Company's direct-acting antiviral, is being tested in both treatment-naive patients and patients who failed a prior course of HCV therapy with interferon and ribavirin. Approximately 275 patients are expected to be enrolled in the study. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients complete treatment, known as SVR24.

The Company expects to receive Week 8 antiviral response data for treatment-naive patients by the end of the second quarter of 2011, Week 12 antiviral response data for treatment-experienced patients in the third quarter of 2011 and Week 24 antiviral response data for both groups in the fourth quarter of 2011.

About Anadys

Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is conducting a Phase IIb study of ANA598, the Company's DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.

Safe Harbor Statement

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 Anadys' expectations regarding the timing of receipt of data from the study and the ability to achieve the primary endpoint of the study. 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 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 ongoing or future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its non-clinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments 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-Q for the quarter ended September 30, 2010. 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.


SOURCE Anadys Pharmaceuticals, Inc.

Anadys Pharmaceuticals intiates Phase IIb study of HCV Polymerase Inhibitor ANA598

Anadys getting it's non-nuc to Phase IIb, that's a pretty big hurdle for this company. If this gets to Phase III, they will have done what many drug developers previously have not. The Phase II graveyard for the DAA's is huge. Interesting that no week 4 (RVR) timepoint is mentioned for this protocol - Chris

SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.

“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design

In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm

Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.

Treatment-Experienced Arm, Including Prior Null Responders

Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.

Rash scare & potential crowded marketplace keeps ANA598 partnerless...

BioWorld Today - Oct. 18, 2010

Financings Roundup

Having yet to sign a partnership for hepatitis C drug ANA598, Anadys Pharmaceuticals Inc. is pulling in $25 million in a public offering to support an upcoming Phase IIb study of the non-nucleoside polymerase inhibitor.

The San Diego-based firm priced the offering of about 13.9 million shares at $1.80 apiece, marking a 13.5 percent discount to Thursday's closing price.

That discount, plus the added dilution to the company's stock, sent shares (NASDAQ:ANDS) tumbling 33 cents, or 15.9 percent, to close Friday at $1.75.

In May, Anadys raised $12.5 million in a registered direct offering and hired Lazard Freres & Co. LLC to help pursue strategic alternatives such as sale of the company or out-licensing assets.

That includes ANA598, which, despite promising early efficacy data, has been dinged by reports of rash in a Phase Ib trial, followed by a higher-than-expected placebo effect that diminished 12-week virological response data in a Phase II study. (See BioWorld Today, April 24, 2009, and Feb. 26, 2010.)

Add to that the increasing competition in the HCV space, and it's no surprise that prospective partners might be skeptical.

Leerink Swann analyst Howard Liang noted last month that recent Phase III data on HCV protease inhibitors, especially Vertex Pharmaceuticals Inc.'s telaprevir "set a high efficacy bar" while early data for NS5A inhibitor BMS-790052 from Bristol-Myers Squibb Co. and nucleoside polymerase inhibitors for Roche AG (RG7128) and Pharmasset Inc. (PSI-7977) also have been impressive.

"In comparison, ANA598's early data do not look compelling," Liang wrote in a Sept. 27 research report.

Anadys is hoping that further Phase II data and results from the Phase IIb study slated to start early next year might prove tempting enough to snag a partner to help with the costly Phase III program.

The ongoing Phase II study is testing ANA598 in combination with the standard-of-care regimen pegylated interferon and ribavirin in treatment-naive HCV patients with genotype 1 disease.

Anadys has data for three of the six patients in the 200-mg twice-daily group, treated for 24 weeks and then had HCV levels measured 24 weeks after all treatment stopped. All three of those patients achieved sustained viral response.

The planned 48-week Phase IIb trial will test ANA598, again in combination with pegylated interferon and ribavirin, in about 200 patients, including both treatment-naive and treatment-experienced subjects.

Anadys is working to finalize the design with the FDA.

Elsewhere in its pipeline, the company has ANA773, an HCV drug designed to induce endogenous interferon that acts via the Toll-like receptor 7 pathway.

Work on that program was suspended in 2009 to concentrate resources on ANA598, but data from a monotherapy trial, plus recent developments suggesting that interferon-based treatment might continue to have a place in the HCV landscape, prompted the firm to restart ANA773. A 28-day combination study of the drug plus ribavirin is expected to begin dosing in the second quarter of 2011 . (See BioWorld Today, June 5, 2009.)

Proceeds from the latest financing, which will add to the $22. 1 million Anadys had in the bank as of June 30, also will be used for general corporate purposes, including working capital.

The firm could pull in an additional $3.7 million if underwriter Lazard Capital Markets LLC exercises its full overallotment option of about 2. 1 million shares.

Prior to the offering, Anadys had about 46.2 million shares outstanding.

Anadys Pharmaceuticals ANA598 update - SVR 12 in Phase II looking good!

SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.

The Company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36.  In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24.  ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin. 

"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, Ph.D., President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today." 

The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (<15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes.  Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48.  The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.

Conference Call Webcast and Slides

Anadys will hold a conference call and webcast today, Thursday, July 29, 2010 at 8:30 a.m. Eastern Daylight Time to discuss the post-treatment results from the ongoing Phase II combination study and Anadys' second quarter 2010 financial results. A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com.  A telephone replay with slides 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 28631163.  The webcast and telephone replay will be available through August 12, 2010.

Phase II Combination Study

In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one.  After week 12, patients are to continue receiving SOC.  Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48.  The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR).  Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR.  Approximately 90 patients have been enrolled in this study â?? with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC.  The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.

About ANA598

ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys.  In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile.  In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naive genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.

Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey.  The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.

Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors.  In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates.  Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.

ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.