January 9, 2012

Pharma giants buy up hepatitis C hopefuls

Nature News Blog

09 Jan 2012 | 13:22 GMT | Posted by Richard Van Noorden

Therapies that target the hepatitis C virus (HCV) are predicted to generate a multi-billion-dollar market in the next few years. And drug firms are rushing to stock their pipelines with potential treatments. On 7 January, Bristol-Myers Squibb of New York said that it would spend US$2.5 billion to acquire Inhibitex of Alpharetta, Georgia, with the main focus being Inhibitex’s INX-189 a potential hepatitis C treatment that is now in phase II clinical trials.

INX-189 is a nucleoside polymerase inhibitor, meaning that it prevents HCV from copying its genome. In November of last year, Gilead Sciences in Foster City, California, splashed out $11 billion on biotech firm Pharmasset, of Princeton, New Jersey. Pharmasset has three treatments for hepatitis C in clinical trials — including some nucleoside polymerase inhibitors.

All told, there are perhaps 60 compounds in preclinical and clinical development against HCV, using a variety of methods to disrupt the virus’s biology. Two drugs approved by the US Food and Drug Administration last year — boceprevir, made by Merck of Rahway, New Jersey, and telaprevir, made by Vertex Pharmaceuticals in Cambridge, Massachusetts — target an HCV protein called the NS3 protease, which is crucial for proper processing of the virus’s proteins.

Both Gilead and Bristol-Myers Squibb also have runners in the NS3 race, and additionally are developing treatments that disrupt an HCV protein called NS5A, essential for the assembly of infectious viral particles and the amplification of viral RNA. Other drugs block the virus’s entry into human cells.

Not all of these drugs can be winners. But the virus, which infects liver cells and can cause cirrhosis and liver cancer, affects around 3% of the world’s population. So there’s plenty of scope for new targeted treatments, which might be more effective and cause fewer side effects than the course of generic antivirals and immune-boosting interferon proteins now used. For more on HCV treatments, see Nature‘s article ‘New drug targets raise hopes for hepatitis C cure‘ and the more detailed (but not free) pipeline update in Nature Reviews Drug Discovery from last February.

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Idenix Reports Advancement of HCV Development Pipeline

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January 9, 2012

-- Idenix advances HCV clinical development pipeline with initiation of phase I study of pan-genotypic NS5A inhibitor, IDX719

-- Idenix selects next-generation HCV nucleotide inhibitors, IDX19368 and IDX19370, to enter IND-enabling studies

-- Management to host conference call webcast at 5:30 a.m. PT/8:30 a.m. ET today

CAMBRIDGE, Mass., Jan. 9, 2012 /PRNewswire/ -- Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced the advancement of its hepatitis C virus (HCV) development pipeline.

IDX719: NS5A Program
Idenix announced today the initiation of a phase I clinical trial of the Company's NS5A inhibitor, IDX719. The first part of the study will evaluate safety, pharmacokinetics and food effect of IDX719 in 48 healthy volunteers. A subsequent part of the study will evaluate three days of IDX719 treatment in treatment-naïve genotype 1 HCV-infected patients and is expected to begin in the second quarter of 2012. Preclinical studies have shown that IDX719 has potent, pan-genotypic activity in vitro with the potential for once-daily dosing.

IDX19368 and IDX19370: Nucleotide Prodrug Program
Further, the Company has selected two additional nucleotide inhibitors, IDX19368 and IDX19370, as potential clinical candidates. The Company anticipates Investigational New Drug (IND) filings in mid-2012.

"Over the past year, Idenix has made significant progress in both our core nucleotide and NS5A programs," commented Ron Renaud, President and Chief Executive Officer of Idenix. "The preclinical profile of IDX719 is very competitive, and we are leveraging the Company's significant nucleotide chemistry expertise to discover novel nucleotides with promising properties as well as continuing to strengthen our IP position. We are excited about the potential of our novel antiviral compounds in the evolving HCV field in the coming year."

2011 Year-end Cash Balance
Idenix today reported that it ended 2011 with approximately $118.3 million of cash and cash equivalents. The Company's 2011 financial results have not yet been audited.

ABOUT IDENIX
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

CONFERENCE CALL AND WEBCAST INFORMATION
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 40631574. A slide presentation will accompany the conference call and can be accessed on the Investor section of the Idenix website at www.idenix.com. Please log on approximately 10 minutes prior to the start of the call to ensure adequate time for any downloads that may be necessary.

A replay of the conference call and webcast will be available until January 23, 2012, by dialing (855) 859-2056 (U.S./Canada) or (404) 537-3406 (International) and enter the passcode 40631574.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of hepatitis C; the likelihood and success of any future clinical trials involving our drug candidates; and expectations with respect to funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the Company's dependence on its collaboration with Novartis Pharma AG; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2011, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

Idenix Pharmaceuticals Contacts:
Kelly Barry (617) 995-9033 (media)
Teri Dahlman (617) 995-9807 (investors)

SOURCE Idenix Pharmaceuticals, Inc.

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Also See: Interim IDX184 Phase IIb Data and Development Pipeline Update

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January 9, 2012

- No serious adverse events observed in phase IIb study of IDX184; Data Safety Monitoring Board (DSMB) recommends continuation of the clinical trial

- In the 100 mg IDX184 arm, 73% of patients achieved a rapid virologic response (RVR) and 87% were undetectable at most recent visit; In the 50 mg IDX184 arm, 63% of patients achieved an RVR and 94% were undetectable at most recent visit

- Management to host conference call webcast at 5:30 a.m. PT/8:30 a.m. ET today

CAMBRIDGE, Mass., Jan. 9, 2012 /PRNewswire/ -- Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced interim data from a 12-week phase IIb clinical trial of IDX184, the Company's lead product candidate for the treatment of hepatitis C virus (HCV) infection. IDX184, a pan-genotypic oral nucleotide polymerase inhibitor, has demonstrated a high barrier to resistance in vitro and potent antiviral activity in both preclinical and clinical studies.

IDX184 Phase IIb Study Design
In July 2011, the Company initiated enrollment of treatment-naive genotype 1 HCV-infected patients into a randomized, double-blind, parallel group phase IIb clinical trial of IDX184. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with pegylated interferon and ribavirin (PegIFN/RBV). Study objectives include safety and tolerability, and antiviral activity endpoints.

IDX184 Phase IIb Interim Study Results
The first 31 patients have completed 28 days of treatment, and the interim data have shown that IDX184 was well-tolerated and that there were no serious adverse events associated with therapy. The side effect profile was consistent with that seen with PegIFN/RBV. The independent DSMB has reviewed the data for the first 31 patients and has recommended continuing enrollment of the study. The Company has submitted the interim data, along with the DSMB's recommendations, to the U.S. Food and Drug Administration (FDA) and is requesting the continuation of this study and removal of the partial clinical hold for IDX184.

RVR findings demonstrated that 73% of patients in the 100 mg IDX184 arm (n=15) and 63% in the 50 mg arm (n=16) had undetectable virus (LLOQ < 25 IU/ml) at 28 days. Currently 87% of patients in the 100 mg arm and 94% in the 50 mg arm had undetectable virus at a median of 8 weeks of treatment. There have been no virologic breakthroughs observed in the study to date.

"These interim results are encouraging as they confirm the antiviral activity and safety of IDX184 in combination with pegylated interferon and ribavirin," Eric Lawitz, M.D., of Alamo Medical Research, Camden Medical Center, stated. "Nucleotide drugs such as IDX184 are becoming an important component in the rapidly evolving treatment regimens for HCV. Eventually, the goal for treatment will be to reduce or eliminate reliance on interferon and to shift to all oral combinations of direct-acting antiviral agents that can reduce potential side effects and decrease the amount of time on therapy."

Ron Renaud, President and Chief Executive Officer of Idenix, commented, "We are very pleased with the interim results for IDX184 and with the progress we made in 2011 across our programs. In 2012, we will build on this progress and believe we are well positioned to play a major role in treating HCV patients for the foreseeable future."

ABOUT IDX184
IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. IDX184 is currently being developed under a partial clinical hold.

ABOUT IDENIX
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

CONFERENCE CALL AND WEBCAST INFORMATION
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 40631574. A slide presentation will accompany the conference call and can be accessed on the Investor section of the Idenix website at www.idenix.com. Please log on approximately 10 minutes prior to the start of the call to ensure adequate time for any downloads that may be necessary.

A replay of the conference call and webcast will be available until January 23, 2012, by dialing (855) 859-2056 (U.S./Canada) or (404) 537-3406 (International) and enter the passcode 40631574.

FORWARD-LOOKING STATEMENTS
This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of hepatitis C; the likelihood and success of any future clinical trials involving our drug candidates; and expectations with respect to funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the Company's dependence on its collaboration with Novartis Pharma AG; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2011, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

Idenix Pharmaceuticals Contacts:
Kelly Barry (617) 995-9033
Teri Dahlman (617) 995-9807

SOURCE Idenix Pharmaceuticals, Inc.

News Provided by Acquire Media

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Also See: Interim IDX184 Phase IIb Data and Development Pipeline Update

Semin Liver Dis. 2011 Nov;31(4):387-98. Epub 2011 Dec 21.

Gutierrez JA, Parikh N, Branch AD.

Source

Division of Gastroenterology, University of California, San Diego, California.

Abstract

According to the Institute of Medicine, the risk of clinically significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL. By this standard, most cirrhotic hepatitis C virus- (HCV-) positive patients and many noncirrhotic patients are vitamin D-deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. Information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients is provided.

© Thieme Medical Publishers.

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Achillion Reports Clinical Data on Portfolio of Protease Inhibitors

Jan 9, 2012 (GlobeNewswire via COMTEX) --
       
Once-daily ACH-1625 safe, well-tolerated and achieves 100% cEVR after 12 weeks of treatment

Pilot study of ACH-1625 in HCV genotype 3 achieves maximal 3.68 log10 reduction

ACH-2684 safe, well tolerated and achieves HCV genotype 1 maximal 4.63 log10 reduction; Additional dosing on-going

NEW HAVEN, Conn., Jan. 9, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today reported new clinical trial results on its portfolio of protease inhibitors including: Phase 2 interim 12-week treatment results with ACH-1625 for the treatment of genotype 1 treatment-naive hepatitis C virus (HCV), exploratory data on ACH-1625 for the treatment of HCV genotype 3, and initial proof-of-concept data for ACH-2684. Based upon these results, Achillion is planning further exploration of ACH-1625 in combination with other oral antiviral agents for the treatment of all HCV genotypes and continues to evaluate ACH-2684 in a Phase 1 clinical trial.

Michael D. Kishbauch, President and Chief Executive Officer of Achillion commented, "ACH-1625 is emerging as a fascinating and potentially superior, once-daily protease inhibitor that competes well against all other DAAs in development, regardless of their mechanism, based upon ACH-1625's safety, efficacy, genotypic coverage and emerging resistance mutation profile. Further, ACH-2684 shows preliminary promise in its ability to treat HCV, with a safety profile that looks very good, and over the next few months we will expand our clinical experience to define the dose response for its use across all HCV genotypes."

ACH-1625: Phase 2 12-Week Study Design and Interim Results

In the second segment of this ongoing Phase 2a trial, three doses of once-daily ACH-1625 (200 mg, 400 mg or 800 mg) in combination with pegylated interferon alfa-2a and ribavirin (P/R) were dosed over 12 weeks of therapy in patients with treatment-naive HCV genotype 1. Subjects were randomized and stratified by IL28B genotype, including CT and TT, which is a marker of a patient's diminished response to interferon.

Enrollment in this study of approximately 60 patients has been completed, and data on the first 35 patients enrolled were evaluated in this interim analysis. Of the patients enrolled, the majority had HCV genotype 1a (n=23/35 (66%)), with remaining patients having HCV genotype 1b (n=10) or genotype 1 (n=2). Approximately 66% of the patients were IL28B genotype CT/TT, the more difficult to treat mutation, 74% were male and approximately 14% were African American. No viral breakthroughs were observed during treatment. Preliminary results for the first 35 patients enrolled demonstrated rapid virological response (RVR) at week 4, and complete early virologic response (cEVR) and viral load reduction at week 12 as follows:

(Click on pictures to enlarge)

Ach1

Ach2

"We were pleased to note that regardless of IL28B status, 100% of patients treated through 12 weeks achieved cEVR and remained undetectable at this point in the study, and the potency and unique pharmacokinetic properties of ACH-1625 appear to provide very potent antiviral coverage for all of these genotype 1 patients," commented Dr. Elizabeth A. Olek, Chief Medical Officer of Achillion. "Patients appear to have continued on-treatment viral suppression, and we therefore look forward to determining end-of-treatment response rates for the fully enrolled study and to presenting complete study results in April."

Safety results from this segment of the trial were similar to those observed in the previously reported clinical trials of ACH-1625. Over 12 weeks of co-administration of ACH-1625 plus P/R, there was one reported serious adverse event (SAE) that was deemed unrelated to ACH-1625. Most reported adverse events (AEs) in patients receiving ACH-1625 were classified as mild to moderate and were transient. The most common AEs were consistent with pegylated interferon alfa-2a and ribavirin treatment.

ACH-1625: Pilot Phase 1 Study Evaluating Antiviral Activity against HCV Genotype 3 and Clinical Virology Assessment of HCV Genotype 1

Based upon in vitro virology, as well as evolving clinical pharmacokinetic and pharmacodynamic data, a Phase 1 pilot study was conducted to evaluate the antiviral activity of ACH-1625 for the treatment of HCV genotype 3. A total of seven patients infected with HCV genotype 3 were enrolled and treated with monotherapy consisting of 400 mg ACH-1625 twice daily for 4.5 days. In this exploratory study, ACH-1625 was safe and well tolerated. The maximum HCV genotype 3 RNA viral load reduction achieved was 3.68 log10 among the six out of seven patients that achieved an antiviral response.

In addition, clinical virology analysis of patient samples obtained during the first Phase 2 28-day study segment of ACH-1625 in combination with P/R examined the resistance mutation profile following treatment. The results indicated that following 28 days of treatment with ACH-1625 the presence of highly resistant variants were not detected.

"These findings suggest that ACH-1625 maintains high concentrations in the liver, the site of infection, resulting in a unique pharmacokinetic drug profile. These positive clinical results in genotype 3, along with the strong virologic profile of ACH-1625, have led us to take a broad look at the role of ACH-1625 in our future proprietary combination regimen," commented Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer.

ACH-2684: Phase 1 Healthy Volunteers and HCV Genotype 1 and 3 Segments

This Phase 1 clinical study is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2684. Healthy volunteers in the single ascending dose (SAD) segment received doses of ACH-2684 ranging from 10 mg once daily to 300 mg twice daily. The first cohorts of HCV-infected patients were enrolled and treated with ACH-2684 administered as 400 mg twice daily for 2.5 days.

ACH-2684 was well tolerated at all doses and there were no serious adverse events, no clinically significant changes in vital signs, ECGs, or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.

Proof-of-concept was achieved with ACH-2684 in HCV genotype 1 demonstrating a maximum HCV RNA viral load reduction of 4.63 log10. Antiviral activity with ACH-2684 in HCV genotype 3 was seen with a maximum HCV RVA viral load reduction of 2.03 log10. Additional cohorts of patients with either HCV genotype 1 or HCV genotype 3 are currently being enrolled to further explore doses and viral kinetics for ACH-2684.

All-Oral Protease Inhibitor and NS5A Inhibitor Combination Will Play an Important Role

During 2012 Achillion plans to conduct a number of clinical trials to further characterize its portfolio of protease inhibitors, including ACH-1625 and ACH-2684, and its NS5A inhibitors, including ACH-2928 and ACH-3102. In addition to the ongoing Phase 1 trials with ACH-2684 and ACH-2928, Achillion plans to submit an investigational new drug (IND) application and initiate a Phase 1 clinical trial with ACH-3102 during the second quarter of 2012. During the second half of 2012, Achillion plans to initiate an all-oral interferon-free combination study which will evaluate a protease inhibitor and a NS5A inhibitor, with or without ribavirin, for the treatment of HCV.

"We believe that the protease and NS5A inhibitor combination will play an important role in the future treatment of HCV across all genotypes," commented Mr. Kishbauch. "With the robust portfolio we have discovered and developed here at Achillion, we believe we are uniquely positioned to advance a potentially best-in-class all-oral, interferon-free combination and are looking forward to initiating clinical development with this regimen later in the year."

About ACH-1625

ACH-1625 is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. ACH-1625 has rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 of approximately 1nM. ACH-1625 is currently in a Phase 2 clinical trial and has shown clinical antiviral activity against genotypes 1 and 3. Fast Track status was granted to ACH-1625 in 2012 for the treatment of chronic HCV.

About ACH-2684

ACH-2684 is a next-generation HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It has preclinical activity against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pico-molar. The drug candidate was discovered internally and is being advanced by Achillion.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including nearly 4 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potency, safety, tolerability, effectiveness and other characteristics of Achillion's protease inhibitors and NS5A inhibitors; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of drug candidates in its protease inhibitor and NS5A inhibitor programs; the potential for its protease and NS5A inhibitor combination to play an important role in the future treatment of HCV across all genotypes; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination protease and NS5A inhibitor. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage clinical trials of ACH-1625, ACH-2684 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates, and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.

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[Date: 2012-01-09]

An event entitled 'International symposium on stem cells and human liver disease' will take place from 12 to 13 March 2012 in Paris, France.

Many forms of human liver disease can currently be treated only with orthotopic liver transplant. Biological and technical advances related with human embryonic stem cells suggest that pluripotency may provide an alternative cell-based therapy for liver disease. The development of methods and tools to engineer stem cells is necessary to generate renewable cultures for clinical-grade, cell therapies.

The conference will highlight recent progress in liver development and stem cell differentiation in the context of cell therapy for chronic liver disease. Among the topics on the agenda will be:

- liver development ;
- differentiation of stem cells to hepatocytes;
- stem cell bioengineering;
- perspectives: clinical applications;
- perspectives: phamaco/toxicology;
- use of stem cells in regenerative strategies.

This event is sponsored by the EU-funded 'Development of culture conditions for the differentiation of hES cells into hepatocytes' (LIV-ES) project, which is looking at ways of developing innovative conditions and standardised protocols to provide a renewable source of human hepatocytes (liver cells) for the treatment of liver diseases.

For further information on the event, please visit: here
For further information on the project, please visit: http://www.liv-es.eu/

Category: Events
Data Source Provider: Inserm Transfert -ADR Inserm
Document Reference: Based on an event announcement
Subject Index: Biotechnology; Healthcare delivery/services; Medicine, Health; Social Aspects

RCN: 34199

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Chimp Research: The Beginning Of The End? (VIDEO)

First Posted: 1/9/12 08:56 AM ET Updated: 1/9/12 08:58 AM ET                                   



Hi everybody. Cara Santa Maria here.

In 1961, we blasted two chimps into space. Twenty-five years later, we bred them like crazy to study the AIDS epidemic. When we realized that, oops, chimps can't get AIDS, we ended up with a surplus of research animals.

Today, most chimp research is done on monoclonal antibodies and Hepatitis C. But new methods are allowing us to develop human antibodies outside of the animal, and most Hep C research can be safely performed in humans. Even the private pharmaceutical industry is making the shift to higher-tech, less expensive technologies. But there are still almost a thousand research chimps living at five major facilities across the country.

Last month, the Institute of Medicine released a bold statement: "Most current use of chimpanzees for biomedical research is unnecessary." Within the hour, the director of the National Institutes of Health agreed to massively scale down the use of chimps in government-funded laboratory research.
Under the new guidelines, future chimp research would receive federal funding only if no other suitable model is available, if the experiments can't be ethically performed on humans, and if without the experiments, important advancements in the prevention or treatment of life-threatening conditions would be slowed or stopped.

Other than the West African nation of Gabon, we are the only country in the entire world that still experiments on chimps. And although I haven't been talking about a ban here, there are people trying to make that happen. The Great Ape Protection and Cost Savings Act of 2011 would prevent invasive research from being performed on chimps, bonobos, orangutans, gorillas, or gibbons. There's also a petition circulating that would put captive chimpanzees on the endangered species list, just like their wild counterparts. Until then, they can legally be used in lab research, show business, and kept as pets.

Now, I advocate animal research. I have personally performed lab experiments on mice and birds, knowing that the work I did was a tiny stepping stone toward understanding how the brain works, and would, down the line, contribute to medical advances in the treatment of Parkinson's disease and traumatic brain injury.

But I am also a strong animal welfare advocate. Animals DO feel pain. They experience psychological distress. Chimpanzees are our closest genetic relatives; we share 99% of the same DNA. Chimps are highly social beings. They have the capacity to form intense bonds. They feel pleasure and empathy. They also feel grief, depression, and anxiety.

In the words of Carl Sagan, "How smart does a chimpanzee have to be before killing him constitutes murder? If chimpanzees have consciousness, do they not have what until now has been described as "human" rights?" What do you think? You can weigh in on Twitter, Facebook, or right here on the Huffington Post. Come on, talk nerdy to me!

Source
Jan. 9, 2012, 6:00 a.m. EST

SAN FRANCISCO, Jan 09, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc. announced today the successful completion of a Phase 1a dose-ranging assessment of PPI-668, a potent, pan-genotypic second-generation hepatitis C virus (HCV) NS5A inhibitor, in healthy volunteers and subsequent advancement to a Phase 1b assessment of the dose-related efficacy in hepatitis C patients.

The Phase 1a dose-ranging assessment of PPI-668 was conducted with 32 healthy volunteers in New Zealand. The trial was a randomized, double-blind, placebo-controlled assessment of the safety and pharmacokinetics of three oral doses of PPI-668, initially assessed as single doses and subsequently as a multi-day regimen, in which the highest PPI-668 dose was given once daily for five successive days. The trial results indicated that all dose regimens of PPI-668 were well-tolerated. There were no serious or severe clinical adverse events, no patterns of treatment-related adverse events or laboratory abnormalities, and all subjects completed the trial successfully.

Pharmacokinetic (PK) analyses of subjects' plasma samples in the Phase 1a trial indicated that substantial blood levels of PPI-668 were rapidly and consistently achieved and dose proportional. PPI-668 plasma concentrations were orders of magnitude above those shown to inhibit HCV replication in vitro and were maintained at predicted effective concentrations for more than 24 hours. These PK results support once-daily dosing for PPI-668 in future studies. Also important was the observation that in the 5-day multi-dose regimen, steady-state PK was achieved rapidly (by Day 2), with no evidence of subsequent accumulation or changes in the clearance profile of PPI-668.

"These first clinical data for PPI-668 indicate excellent tolerance in healthy subjects for up to five days," said Nathaniel A. Brown, M.D., Presidio's Chief Medical Officer. "Equally important, the pharmacokinetic profile of PPI-668 is very encouraging, suggesting that effective plasma concentrations can be obtained with relatively low, once-daily doses of PPI-668 - which will facilitate co-formulation of PPI-668 with other HCV antivirals in future combination therapies for hepatitis C."

Patient screening for the Phase 1b evaluation of PPI-668 in hepatitis C patients has begun in New Zealand and the United States and will soon include Australia. Dosing of the first cohort of hepatitis C patients will begin this week. Presidio expects to have results regarding the antiviral efficacy of PPI-668 in HCV patients in the second quarter of 2012.

In a second HCV research program focused on inhibitors of the HCV NS5B polymerase, Presidio has discovered a lead chemical series of non-nucleosidic NS5B inhibitors with potent activity against all major HCV genotypes. Preclinical profiling is ongoing with a goal of nominating a candidate for clinical development in the coming months.

With its novel NS5A and NS5B inhibitors, Presidio's objective is to provide two complementary HCV antivirals that will be appropriate for broad use in optimized future combination therapies for patients with HCV infection. Presidio anticipates that such therapies will have a convenient oral dosing regimen (once or twice daily), will exhibit rapid pan-genotypic efficacy and will be well-tolerated.

ABOUT HEPATITIS C AND NS5A INHIBITORS

Chronic hepatitis C is a persistent, potentially progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Worldwide there are an estimated 130 to 170 million persons with chronic HCV infection. There are 7 major genotypes (strains) of HCV, which have differing geographic distributions. Globally, about 40-60% of patients are infected with HCV genotype-1, with the remaining patients infected with HCV genotypes 2 through 7.

Patients with advanced hepatitis C can develop potentially fatal liver failure or liver cancer, and hepatitis C is estimated to account for over 350,000 deaths per year worldwide (WHO estimate). The current standard-of-care treatment for hepatitis C in the United States, for patients with HCV genotype-1 infection, is combined administration of pegylated-interferon, ribavirin, and first-generation HCV protease inhibitors. This multi-drug treatment is characterized by incomplete efficacy for HCV genotype-1 patients, variations in efficacy according to patients' underlying human genetic factors, no established efficacy for patients infected with other HCV genotypes, substantial tolerance issues, and dosing inconveniences. Thus, there is a continuing need for more consistently effective and better tolerated HCV inhibitors that can be orally administered in future combination therapies for hepatitis C patients worldwide, regardless of HCV genotype, patient genetic factors, or disease stage.

Inhibitors of the HCV NS5A protein represent an exciting, relatively new class of HCV inhibitors that, when optimized, exhibit potent activity across all HCV genotypes, with a mechanism that is distinct from other classes of HCV antivirals, which commonly target the HCV protease or polymerase. PPI-668 is a novel, optimized, second-generation HCV NS5A inhibitor, which exhibits highly potent and selective activity against all HCV genotypes in replicon assays, with favorable toxicology and pharmacology profiles in preclinical assessments.

ABOUT PRESIDIO

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics for hepatitis C virus (HCV). For more information, please visit our website at: www.presidiopharma.com.

SOURCE: Presidio Pharmaceuticals, Inc.

Source

Interim IDX184 Phase IIb Data and Development Pipeline Update

Interim IDX184 Phase IIb Data and Development Pipeline Update Conference Call January 9, 2012

(Click on each picture to enlarge)

Safe Harbor Statement

This presentation includes forward-looking statements about Idenix and its business, including without limitation, statements regarding drug discovery, research and clinical development, regulatory approval processes and market opportunities. These forward-looking statements are subject to risks and uncertainties that may cause actual events or results to differ materially from our current expectations. These risks and uncertainties are detailed in our filings with the Securities and Exchange Commission. All forward-looking statements speak only as of the date of this presentation and, except as required by law, we undertake no obligation to update such statements.

IDX184 Phase IIb Interim Results






IDX184 Phase IIb Status and Next Steps
  • DSMB concluded that there was no evidence of hepatoxicity and recommended that the study continue after review of the interim data of first 31 patients
  • Interim data of 31 patients and DSMB’s recommendations were submitted to FDA in January 2012 to support potential removal of partial clinical hold
  • Additional future phase IIb clinical studies also proposed in FDA submission
HCV Development Pipeline Update


NS5A Inhibitor IDX719 Promising Profile for Combination Therapy
  • Clean preclinical safety profile to date
  • Potential for low mg doses and QD dosing in humans
  • No in vitro interaction with 7 human CYP 450 enzymes at 10 μM (well above physiologic concentrations)
  • No significant interaction with human transporters at physiologic concentrations
  • Additive antiviral effects with other HCV DAAs (e.g., PIs and IDX184)
  • No in vitro DDIs with common HBV and HIV therapeutic agents
Novel Nucleotide Prodrug Program
  • Intensive program in place
    - Robust synthetic and screening efforts ongoing, focus on single diastereomers
  • Diverse spectrum of nucleotides
    -Purines and pyrimidines
    -Known prodrugs and novel prodrugs
    - 2’ Me sugars and some novel sugars
  • Identify promising compounds in vitro and in mouse and monkey
    - Level of triphosphate production, kinetics of metabolism, cytotoxicity, etc
    - Levels of triphosphate in the liver after oral administration in vivo
  • Lead nucleotide inhibitor candidates, IDX19368 and IDX19370, selected
    - IND-enabling studies underway with IND filings expected mid-year
    - In preclinical studies, IDX19368 generates high triphosphate levels
  • Many new potential clinical candidates currently being evaluated
2012: An Eventful Year Expected to Create Value
  • IDX184: Nucleotide HCV Polymerase Inhibitor
    - Potential removal of the partial clinical hold
    - Combine with one or more DAAs for combination regimen and initiate broad Phase IIb trials
    - Establish non-exclusive/exclusive collaboration
  • IDX719: HCV NS5A Program
    - Successful completion of Phase I and proof-of-concept studies including evaluation in multiple genotypes
  • Next-Generation Nucleotide HCV Polymerase Inhibitors
    - File INDs for lead candidates, IDX19368 and IDX19370, and initiate Phase I and proof-of-concept studies
    - Continue robust nucleotide prodrug discovery efforts
We believe we are well positioned to play a major role in the evolving HCV field.
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