Replies to post #82498 on Biotech Values

[ghmm]

ITMN:

The 191 Phase 2B Clinical Trials.gov entry is up for those interested.

http://clinicaltrials.gov/ct2/show/NCT00963885

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ITMN/VRUS/Roche:

INFORM-1 Results: Robust Antiviral Suppression Achieved with Combination of Nucleoside Analog Polymerase Inhibitor RG7128 and Protease Inhibitor RG7227

Pharmasset had a webcast yesterday night (7pm) http://investor.pharmasset.com/events.cfm I didn't catch it yet. InterMune's Q3 call is thursday 4:30pm also they present at Oppenheimer tomorrow at 3:20pm.

- Significant antiviral potency in both naive and treatment-failure patients -

BOSTON, Nov. 3 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) and Pharmasset, Inc. (Nasdaq: VRUS) today announced results from all patient cohorts of the INFORM-1 trial, an innovative Phase 1 study of two direct-acting antiviral (DAA) compounds administered without interferon or ribavirin for the treatment of patients chronically infected with the hepatitis C virus (HCV).(i) The study, conducted by Roche as part of its collaborations with InterMune and Pharmasset, combined the oral NS3 protease inhibitor RG7227 (also known as ITMN-191) and the oral nucleoside analog polymerase inhibitor RG7128.

The results announced today focused on the recently completed final three cohorts of the INFORM-1 study, consisting of higher-dose, twice-daily regimens, presented during the Presidential Plenary Session at the 60th Annual Meeting of the American Association for the Study of the Liver (AASLD) in Boston by Edward Gane, M.D., Associate Professor, University of Auckland, and Director, Auckland Clinical Studies Limited, and Prinicipal Investigator in the INFORM-1 study. The initial four lower-dose cohorts of patients from INFORM-1 were previously reported at the European Association for the Study of the Liver (EASL) meeting in Copenhagen in April, 2009.

INFORM-1 Results

Viral Kinetic Performance of Twice-Daily Regimens

The full dose combination of RG7128 1000mg and RG7227 900mg administered twice-daily without pegylated interferon or ribavirin, the current standard of care for HCV, for 13 days resulted in 88% of HCV-positive treatment-naive patients achieving HCV RNA below the lower limit of quantification (LLOQ; <43 IU/mL), and 63% of patients having HCV RNA below the lower limit of detection (LLOD; <15 IU/mL). The same regimen in "null responders" resulted in 50% of patients with HCV RNA below LLOQ and 25% of patients with HCV RNA below LLOD. Null responders were defined as patients with an HCV RNA reduction of <1 log10 IU/mL in 4 weeks or <2 log10 IU/mL in 12 weeks of prior treatment with pegylated interferon and ribavirin. At the twice-daily dose of 600mg of RG7227 in combination with 1000mg of RG7128 twice-daily for 13 days in treatment-experienced patients, somewhat lower viral load reduction and categorical responses were observed, an observation that will guide dosing in future studies in these patients.

All patients receiving a twice-daily regimen experienced a continual decline in HCV RNA during the study period. Viral decline displayed a biphasic pattern with a rate of HCV RNA decline in the second phase that was similar to that observed when a single direct acting antiviral is added to pegylated interferon and ribavirin. No treatment-emergent resistance to RG7227 or RG7128 was observed in the study.

 
         Day 13 Viral Kinetic Results: Higher-Dose Twice-Daily Regimens 
  
                                           HCV RNA            HCV RNA 
        Regimen                           <LLOQ(1)           <LLOD(2) 
       (RG7128 /           Patient       (<43 IU/mL)       (<15 IU/mL) 
       RG7227 mg)    N    Population        N (%)              N (%) 
        ---------    -   -------------     ----              ---- 
       1000/600 BID  8  TF-Non-Null         4/8 (50%)            1/8 (13%) 
      -------------- -  -----------   --------------  ------------------- 
       1000/900 BID  8    TF-Null           4/8 (50%)            2/8 (25%) 
      -------------- -    -------     --------------  ------------------- 
       1000/900 BID  8     Naive            7/8 (88%)            5/8 (63%) 
      -------------- -     -----      --------------  ------------------- 
  
     (1) LLOQ = lower limit of quantification by Roche TaqMan Assay 
         (<43 IU/mL) 
     (2) LLOD = lower limit of detection by Roche TaqMan Assay (<15 IU/mL) 
  
 

Safety and Tolerability

The all-oral, interferon-free combination showed promising safety and tolerability. No treatment-related serious adverse events (SAEs), dose reductions or discontinuations were reported in any patient in INFORM-1, including previously reported lower dose cohorts. The most commonly reported adverse events (AEs) were headache, nausea and diarrhea and these had a similar incidence to previously reported lower-dose cohorts.

Dr. Gane commented, "The results from this study of the RG7227/RG7128 combination raise hopes that we can deliver an interferon-free regimen for our patients in the future. Current HCV therapy includes up to 12 months of weekly interferon injections which can be associated with significant side effects. In addition, not all patients can take interferon due to intolerance or contraindications. We look forward to the results of additional studies with these potent compounds."

FURTHER INFORM STUDIES - PROGRAM ADVANCING RAPIDLY

The companies announced today that a Phase 2 program of multiple studies will be initiated by Roche in the first quarter of 2010. "INFORM-2" will investigate rapid virologic response (RVR) provided by twice-daily dosing of RG7128 and RG7227 alone, in combination with pegylated interferon alfa-2a, ribavirin, and in combination with both pegylated interferon alfa-2a and ribavirin. Longer term studies evaluating sustained virologic response (SVR) are anticipated for the first half of 2010.

About RG7227

RG7227 (ITMN-191) is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log10 reductions in levels of HCV in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin, USP). ITMN-191 was safe and well-tolerated in these studies.

About RG7128

RG7128, a cytidine nucleoside analog inhibitor of HCV RNA polymerase, is being developed for the treatment of chronic HCV infection. RG7128 has shown potent in vivo activity against all of the most common HCV genotypes (1, 2 and 3). RG7128 has been studied in combination with PEGASYS® and COPEGUS® for up to 28 days, and is currently in a Phase 2b clinical trial in combination with PEGASYS® plus COPEGUS®.

About INFORM-1

INFORM-1 is a randomized, double-blind, ascending-dose Phase 1b trial which enrolled a total of 86 patients. The prinicipal objectives were to evaluate safety, tolerability and antiviral activity of RG7227 and RG7128 administered in combination at increasing doses for up to 13 days. The study was conducted in centers in New Zealand and Australia and was the first to investigate the combination of two oral antiviral medicines in the absence of interferon and ribavirin.

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone for which a Phase 3 program in patients with IPF (CAPACITY) has been completed and the compound is currently in the pre-registration stage. The hepatology portfolio includes the HCV protease inhibitor ITMN-191 (referred to as RG7227 at Roche) that entered Phase 2b in August of 2009 and a second-generation HCV protease inhibitor research program. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV) and, secondarily, on the development of Racivir(TM) for the treatment of human immunodeficiency virus (HIV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase thus inhibiting viral replication. We currently have three clinical-stage product candidates. RG7128, a nucleoside analog for chronic HCV infections, is in a Phase 2b clinical trial in combination with PEGASYS® plus COPEGUS® and is also in INFORM studies, the first studies designed to assess the potential of combinations of small molecules without interferon and ribavirin to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage candidates are PSI-7851, an unpartnered, next generation HCV nucleotide analog which has completed two Phase 1 clinical studies and Racivir(TM), for the treatment of HIV, which has completed a Phase 2 clinical trial. We have also recently announced the nomination of two purine nucleotide analogs, PSI-938 and PSI-879, for preclinical development.

Forward-Looking Statements

This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect the companies' judgments and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines. All forward-looking statements and other information included in this press release are based on information available to the companies as of the date hereof, and the companies assume no obligation to update any such forward-looking statements or information. Actual results could differ materially from those described in the forward-looking statements.

Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in the companies' most recent annual reports on Form 10-K filed with the SEC and in other periodic reports filed with the SEC. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the respective Forms 10-K and in the companies' other periodic reports filed with the SEC, all of which are available via their respective web sites at www.intermune.com and www.pharmasset.com.

All trademarks used or mentioned in this release are protected by law.

About INFORM-1: www.clinicaltrials.gov

(i) "Combination Therapy with a Nucleoside Polymerase (RG7128) and Protease (RG7227/ITMN-191) Inhibitor Combination in HCV: Safety, Pharmacokinetics, and Virologic Results from INFORM-1," Abstract #193: to be presented at the Meeting of the American Association for the Study of the Liver (AASLD) in Boston, Massachusetts, October 30 - November 3, 2009

SOURCE InterMune, Inc.

Jim Goff , Sr. Director, Corp. Comm. & IR of InterMune, Inc., [phone], [e-mail]; or Richard E. T. Smith, Ph.D., VP, Investor Relations and Corporate Communications of Pharmasset, [phone], [e-mail]

[ghmm]

ITMN/VRUS et al Protease/Polymerase combo trials:

I was going back over the oppenheimer call earlier this month and (reading between the lines) one could infer that starting longer duration studies of two antivirals in combination would first require an equivalent dosing period of each individually in patients at least in Europe and the US. ITMN/VRUS/Roche have two trials planned (according to InterMune) and perhaps there are additional reasons for doing so but certainly the timeline for when each starts would go along with this plan.

Vertex has stated they plan to start combo trials perhaps as early as this year. Well one of a couple things could be inferred:
1-The trials are not in the US or Europe
2-They have unpublished (and unannounced) results of their polymerase in longer duration studies.
3-They are misleading investors
4-They believe they can be granted a lower bar then Roche/ITMN/VRUS.

Somehow I see 2 and 4 as extremely unlikely so lets see what happens.

[genisi]

ITMN-191 presentation at the HepDart conference:

http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MjIzNjF8Q2hpbGRJRD0tMXxUeXBlPTM=&t=1

(in the ritonavir + 191 trial, boosted doses are 100 and 200mg, slides 18-19)

[ghmm]

InterMune Provides Program Update and 2010 Milestones for RG7227 (ITMN-191)

A mixture of news IMO. The bad is that the timeline for 2B results is basically pushed back 1+ years (for the Protease + SOC) with the new ritonvair boosting Phase 2B. The programs saving grace is the potential for QD dosing and much lower dose to hopefully alleviate any safety concerns. However IMO I think progress in the INFORM series is much more important from both a valuation perspective and for future market share in HCV treatment.


http://finance.yahoo.com/news/InterMune-Provides-Program-prnews-2158168794.html?x=0&.v=1

Press Release Source: InterMune, Inc. On Monday January 11, 2010, 7:00 am EST

BRISBANE, Calif., Jan. 11 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) today provided an update on its development program for protease inhibitor RG7227 (formerly referred to as ITMN-191) for the treatment of patients chronically infected with the hepatitis C virus (HCV). The company also reported guidance for the 2010 milestones and key events for RG7227.

Dan Welch, Chairman, Chief Executive Officer and President of InterMune, said, "Today we reported preliminary, top-line results from two cohorts of the Phase 1b, 15-day study of low-dose RG7227 co-administered with low-dose ritonavir and standard of care (SOC) in patients with chronic HCV. The majority of patients given ritonavir with 100mg RG7227 twice-daily or 200mg RG7227 once-daily were HCV RNA negative at the end of therapy. The ritonavir-boosted regimen provided a more favorable pharmacokinetic profile than what has been previously observed for 900mg RG7227 administered twice-daily with SOC but without ritonavir. In view of these data, our plan is that the development of RG7227 will be in combination with ritonavir."

Clinical Development Highlights and Recent Events

(RG7227)

* Enrollment began in August 2009 of the company’s Phase 2b study of
RG7227 in combination with PEGASYS(R) (pegylated interferon alfa-2a)
and COPEGUS(R) (ribavirin), one of the options for the current
standard of care (SOC) in HCV. The Phase 2b trial was designed to
study both twice-daily (600mg and 900mg q12h) and three-times-daily
regimens (300mg q8h) and both 12-week and 24-week treatment durations.
On November 17, 2009, InterMune announced that three patients in the
blinded 900mg q12h dosage cohort experienced an ACTG Grade 4 elevation
in ALT levels, one of whom experienced an elevation of total bilirubin
while also receiving concomitant allopurinol. After their review of
un-blinded data from these patients, the study’s independent Data
Monitoring Committee (DMC) recommended that the 900mg q12h cohort be
discontinued and that all other cohorts of the study continue. The
companies accepted the DMC’s recommendations. Enrollment of all
remaining cohorts was completed in November of 2009.

* The company reported top-line results of a Phase 1 study of
ritonavir-boosted RG7227 in healthy volunteers. Ritonavir is an
antiviral compound commonly used at low, sub-therapeutic doses to
enhance or "boost" the pharmacokinetic (PK) profiles of protease
inhibitors. The results of this study demonstrated that the co-
administration of low-dose ritonavir increased RG7227 concentration 12
hours post dose by 18 times, with the effect on Cmin being roughly 6
times and 3 times greater than the effect on Cmax and AUC,
respectively. These results guided the selection of the substantially
lower doses of RG7227 investigated in the Phase 1b MAD study in HCV
patients.

* The company reported preliminary, top-line results of a Phase 1b
multiple-ascending-dose (MAD) study that was initiated in September
2009 to evaluate low doses of once-daily and twice-daily RG7227
co-administered with low-dose ritonavir in combination with SOC for 15
days in treatment-naive HCV-infected patients. This study is examining
the following three dosage regimens of RG7227, each with SOC and 100mg
twice-daily ritonavir:
o 100mg twice-daily RG7227
o 200mg once-daily RG7227
o 200mg twice-daily RG7227

Preliminary viral kinetic data from the first two cohorts of this
study indicate that in the presence of SOC, the majority of patients
achieved an undetectable level of HCV RNA after 15 days of treatment.
The pharmacokinetic profile of ritonavir-boosted RG7227 was more
favorable and less variable than that observed in previously reported
studies conducted with much higher doses of un-boosted RG7227. No
drug related serious adverse events have been reported to date. The
companies hope to present the results from this study at a medical
conference in the first half of 2010.

* Based upon these results, the company’s plan is that the development
of RG7227 will be in combination with low-dose ritonavir.
Accordingly, the previously planned 24-week un-boosted part of the
on-going Phase 2b triple combination study will now be replaced with a
Phase 2b ritonavir-boosted study that is expected to begin in Q3 of
2010. As a result of not conducting Part B of the Phase 2b study, the
company will un-blind the Part A 12-week cohorts earlier than
originally planned and expects to provide both 4-week RVR data and
12-week EVR data late in the first quarter or early in the second
quarter of 2010. In addition, the companies plan to amend the
on-going Phase 1b MAD 15-day ritonavir boosting study to evaluate 12
weeks of RG7227 ritonavir-boosted therapy plus SOC.

2010 Key Project Guidance

The company provided the following guidance on the development timelines for RG7227.


Milestones and Key Events


Expected Date


Un-blinded rapid virologic response (RVR) and early virologic response (EVR) data from the on-going Phase 2b study of RG7227 plus SOC (un-boosted 12-week regimens)


Late Q1 or early Q2 2010 (updated guidance with additional data reported)


Initiation of INFORM-2 program (ritonavir-boosted RG7227 plus RG7128)


Q1 2010: Timing subject to change due to integration of new ritonavir boosting strategy


Initiation of longer duration DAA study to evaluate SVR (ritonavir boosted)


Q2 2010: Timing subject to change due to integration of new ritonavir boosting strategy


Initiation of Phase 2b study of ritonavir-boosted RG7227 plus SOC


Q3 2010 (new study)





About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone for which InterMune has completed a Phase 3 program in patients with IPF (CAPACITY) and a New Drug Application (NDA) is currently under Priority Review by the FDA. The hepatology portfolio includes the HCV protease inhibitor compound RG7227 (ITMN-191) which entered Phase 2b in August of 2009 and a second-generation HCV protease inhibitor research program. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

Forward-Looking Statements

This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect InterMune's judgment and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines, the dates on which clinical data will be released and intended changes to certain of InterMune's clinical studies. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune's actual results could differ materially from those described in InterMune's forward-looking statements.

Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in InterMune's most recent annual report on Form 10-K filed with the SEC on March 16, 2009 (the "Form 10-K") and other periodic reports filed with the SEC, including the following: (i) risks related to the long, expensive and uncertain clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues or delays in anticipated timing of the regulatory approval process; (ii) risks related to failure to achieve the clinical trial results required to commercialize our product candidates; and (iii) risks related to timely patient enrollment and retention in clinical trials. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the Form 10-K and InterMune's other periodic reports filed with the SEC, all of which are available via InterMune's web site at www.intermune.com.

All trademarks used or mentioned in this release are protected by law.