Replies to post #57069 on Biotech Values

[DewDiligence]

>VRUS – they shouldn't have too much trouble enrolling future trials!<

However, they may have trouble accommodating everyone who wants to attend the JPM presentation on Thursday (5 pm ET).

[DewDiligence]

VRUS Adds Two Cohorts to R7128 HCV Combination Study

[The two new cohorts are 1000mg BID in treatment-naïve genotype-1 and 1500mg BID is treatment-refractory gentotype-2/3. Four-week data from the two prior cohorts in this trial (500mg and 1500mg BID in treatment-naïve genotype-1) were reported in January (#msg-25785397) and caused a huge pop in the share price.]

http://biz.yahoo.com/prnews/080424/clth073.html

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Thursday April 24, 8:45 am ET

-- Two 4-week cohorts will be enrolled to evaluate R7128 1500mg BID in HCV genotypes 2 and 3 prior non-responders and R7128 1000mg BID in HCV genotype 1 treatment-naive patients --

-- Conference call scheduled for Friday, April 25, 2008 at 1:00 PM ET (US) and 7:00 PM CEST (Milan) --

PRINCETON, N.J. and MILAN, Italy, April 24 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS ) will enroll two additional cohorts in the ongoing Phase 1 study protocol to evaluate 4 weeks of combination therapy with R7128. R7128, a prodrug of PSI-6130, is a nucleoside analogue polymerase inhibitor of hepatitis c virus (HCV) that is being developed through Pharmasset's collaboration with Roche.

Cohort 3 will study R7128 1000mg BID in treatment-naive patients with HCV genotype 1. This cohort is intended to provide clinical antiviral activity data in support of pharmacokinetic models from earlier studies.

Cohort 4 will study R7128 1500mg BID in patients with HCV genotypes 2 and 3 who did not achieve a sustained virologic response (SVR) with previous interferon-based therapy. Cohorts 3 and 4 will both be dosed in combination with Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin).

Patients in Cohorts 3 and 4 are scheduled to begin dosing by the end of May 2008. Preliminary safety and antiviral activity data from the 4-week combination studies are anticipated during the 3rd quarter of 2008.

Cohorts 3 and 4 will be conducted in parallel with the global Phase 2b study preparation activities for R7128. The timing of the Phase 2b study is not dependent upon data from Cohorts 3 and 4.

"Our pharmacokinetic modeling of the 500mg and 1500mg cohorts of R7128 in combination with Pegasys plus Copegus suggests that the 1000mg dose could deliver a rapid virologic response (RVR) rate similar to the 1500mg dose," stated Dr. Michelle Berrey, Pharmasset's Chief Medical Officer. "The confirmatory results from this additional cohort will aid us in selecting the appropriate doses to evaluate in the global Phase 2b study that is being planned to evaluate R7128 in triple combination for up to 12 weeks."

"R7128 is equally potent in vitro against HCV genotypes 1, 2, 3 and 4, and we believe it is clinically and commercially important to test R7128 in patients with these HCV genotypes," stated Schaefer Price, Pharmasset's Chief Executive Officer. "Twenty percent of U.S. HCV-infected patients and approximately 30% of European and Latin American HCV-infected patients have genotypes 2 and 3. These patients are currently treated with 24 weeks of pegylated-interferon plus ribavirin, but 20% of this population fails to achieve an SVR. By potentially addressing this unmet medical need in a patient population for whom the standard of care is only 24 weeks, we could possibly design shorter clinical trials that may provide a quicker path to the market for R7128."

Separately, the results of the 4-week Phase 1 clinical trial evaluating two oral dose levels of R7128 (500mg and 1500mg) in combination with Pegasys plus Copegus in 50 treatment-naive patients chronically infected with HCV genotype 1 will be presented at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL) in Milan, Italy on Friday, April 25, 2008 at 11:15 AM ET (US) and 5:15 PM CEST (Milan). The scientific presentation will be available for download in PDF format immediately following the EASL presentation in the "Events & Presentations" section of the Investor Center on Pharmasset's website at http://investor.pharmasset.com/events.cfm.

Please see www.clinicaltrials.gov or e-mail [e-mail] for more information.

Conference Call

Pharmasset will host a conference call at 1:00 PM ET (US) and 7:00 PM CEST (Milan) on Friday, April 25, 2008 to discuss the addition of two R7128 cohorts, as well as the results of the 4-week combination study of R7128 presented at EASL.

Dial-in Information:

US/Canada Toll-Free callers: [phone]

US/Canada Toll or International Toll callers: [phone]

Live audio of the conference call will be simultaneously broadcast over the internet via a webcast. To access the live webcast, log on to the "Events & Presentations" section of the Investor Center on Pharmasset's corporate website at http://investor.pharmasset.com/events.cfm.

Please connect to the company's website at least ten minutes prior to the start of the presentation to ensure adequate time for a reliable connection and any software download that may be necessary to listen to the webcast. The archived replay of the webcast will be available on the Pharmasset website for two weeks following the conference call.

About R7128

R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analog inhibitor of HCV RNA polymerase. A prodrug is a chemically modified form of a molecule designed to enhance the absorption, distribution and metabolic properties of that molecule. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.

R7128 demonstrated potent, dose-dependent antiviral activity across four prior treatment-failure patient cohorts (n=40) receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. The greatest mean decrease in HCV RNA from baseline was demonstrated in the patient cohort that received 1500 mg twice-daily, the highest dose of R7128 administered in the study. These patients demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of the development of viral resistance in any dose cohort after 14 days of dosing.

In a 4-week Phase 1 combination study that was conducted in 50 treatment- naive patients chronically infected with HCV genotype 1, R7128 demonstrated potent short-term antiviral activity and was generally safe and well tolerated. Eighty-five percent (85%) of patients receiving R7128 1500mg twice- daily (BID) with Pegasys plus Copegus for 4 weeks achieved undetectable HCV RNA levels with safety and tolerability comparable to placebo with Pegasys plus Copegus.
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[DewDiligence]

VRUS Presents 4-Week R7128 Data from Phase-1 Combination Study

[This PR contains the full 4-week results from the first two dosing cohorts: 500mg and 1500mg BID in treatment-naïve genotype-1 patients. Some of these data were presented in a January PR (#msg-25785397), which caused a 30% pop in the share price. Two additional doses have since been added to the study, as described in #msg- 28783125.]

http://biz.yahoo.com/prnews/080425/clf006.html

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Friday April 25, 11:30 am ET

- 85% of patients achieve undetectable HCV RNA levels following 4 weeks of treatment with R7128 1500mg BID with Pegasys(R) plus Copegus(R) -

- Safety and tolerability comparable to placebo administered with Pegasys plus Copegus -

- EASL presentation available on Pharmasset website -

- Conference call scheduled for Friday, April 25, 2008 at 1:00 PM ET (US) and 7:00 PM CEST (Milan) -

PRINCETON, N.J. and MILAN, Italy, April 25 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS ) announces the results of a 4-week Phase 1 clinical trial evaluating two oral dose levels of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in 50 treatment-naive patients chronically infected with hepatitis C virus (HCV) genotype 1. R7128, a prodrug of PSI-6130, is a nucleoside analogue polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. The results of this study were presented today at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL) being held from April 23-27, 2008 in Milan, Italy.

In this study, R7128 demonstrated potent short-term antiviral activity and was generally safe and well tolerated. Eighty-five percent (85%) of patients receiving R7128 1500mg twice-daily (BID) with Pegasys plus Copegus for 4 weeks achieved undetectable HCV RNA levels with safety and tolerability comparable to placebo with Pegasys plus Copegus.

Dr. John McHutchison, professor of medicine at Duke University Medical Center and a clinical investigator for this study, stated, "R7128, in combination with Pegasys plus Copegus, has demonstrated Rapid Virologic Response (RVR) percentages in a 4-week study that are similar to HCV protease inhibitors and has an encouraging short-term clinical safety profile. Longer-term studies of R7128 with Pegasys plus Copegus are needed to provide additional information about its potential to improve sustained virologic response (SVR) rates for HCV patients."

R7128 4-week Combination Study Overview

The 4-week Phase 1 combination clinical trial was a multiple center, observer-blinded, randomized and placebo-controlled study that was conducted in 50 treatment-naive patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability and pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The secondary objective was to evaluate the change in HCV RNA after 4 weeks of treatment.

The study investigated two oral dose levels of R7128, 500mg and 1500mg, each administered twice-daily (BID) with once-weekly injections of Pegasys plus Copegus BID. Each cohort of 25 patients was comprised of 20 patients receiving R7128 and 5 patients receiving placebo with Pegasys plus Copegus.

Antiviral Activity Summary

Placebo + R7128 500mg + R7128 1500mg +
Pegasys plus Pegasys plus Pegasys plus
Copegus Copegus Copegus
(n=10) (n=20) (n=20)
Mean Decrease in
HCV RNA (log10 IU/mL)
at 4 Weeks -2.95 -3.82 -5.12
Percentage of Patients
with Undetectable
HCV RNA (<15 IU/mL)
at 4 Weeks (RVR) 10% 30% 85%

Potent antiviral activity was demonstrated following 4 weeks of treatment with R7128 1500mg BID with Pegasys plus Copegus. These patients achieved a mean 5.12 log10 IU/mL decrease in HCV RNA and 85% (17 of 20) had undetectable levels of HCV RNA (<15 IU/mL), or RVR. Following 4 weeks of treatment with R7128 500mg BID with Pegasys plus Copegus, patients achieved a mean 3.82 log10 IU/mL decrease in HCV RNA and 30% (6 of 20) had RVR. Following 4 weeks of treatment with placebo with Pegasys plus Copegus, patients achieved a mean 2.95 log10 IU/mL decrease in HCV RNA and 10% (1 of 10) had RVR. The baseline HCV RNA levels for all patients in the study were greater than 6.3 log10 IU/mL and were similar across all study groups.

Safety Summary

Safety and tolerability for the 4-week treatment period were similar for R7128 with Pegasys plus Copegus compared to placebo with Pegasys plus Copegus. There were no serious adverse events reported during the 4-week treatment period, and most of the adverse events reported were of mild to moderate intensity. The most common adverse events, reported in 15% or greater of patients in any treatment group during the 4-week treatment period, were headache, injection site reaction, myalgia, fatigue, chills, rash, nausea, diarrhea, arthralgia, pyrexia, dizziness, dyspepsia and pruritis. The frequency and severity of these adverse events, as well as any general body system observations, were generally similar to clinical experience with the standard of care for HCV, pegylated interferon plus ribavirin.

Grade 3/4 neutropenia was observed in 30% of the placebo patients and in 10% to 15% of the R7128 patients in each active dosing cohort. Grade 3 changes in hemoglobin were observed in 10% of the placebo patients and in 15% of the R7128 patients. There were no clinically significant changes in other hepatic, renal, or other safety laboratory parameters, vital signs, or electrocardiograms.

Overall, there was no clinical evidence of any major organ toxicities related to R7128. One patient in the active treatment group discontinued the study during the 4 week treatment period due to lower-gastrointestinal adverse events. At the time of study discontinuation, this patient had undetectable HCV RNA. R7128 was generally safe and well-tolerated when administered for 4 weeks in combination with Pegasus plus Copegus in patients with HCV genotype 1.

Please see www.clinicaltrials.gov or e-mail [e-mail] for more information.

Conference Call

Pharmasset will host a conference call at 1:00 PM ET (US) and 7:00 PM CEST (Milan) on Friday, April 25, 2008 to discuss the R7128 500mg and 1500mg combination study results, as well as the addition of two R7128 cohorts to the on-going Phase 1 protocol.

Dial-in Information:

US/Canada Toll-Free callers: [phone]

US/Canada Toll or International Toll callers: [phone]

Live audio of the conference call will be simultaneously broadcast over the internet via a webcast. To access the live webcast, log on to the "Events & Presentations" section of the Investor Center on Pharmasset's corporate website at http://investor.pharmasset.com/events.cfm .

Please connect to the company's website at least ten minutes prior to the start of the presentation to ensure adequate time for a reliable connection and any software download that may be necessary to listen to the webcast. The archived replay of the webcast will be available on the Pharmasset website for two weeks following the conference call.
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