Hepatitis C Therapeutic Vaccine, GI-5005, Improves EVR Rates to 94 Percent in Phase 2

GlobeImmune's Hepatitis C Therapeutic Vaccine, GI-5005, Improves EVR Rates to 94 Percent in Phase 2

Poster Presentations

Presentation Date: Apr 24, 2009

GI-5005 IMMUNOTHERAPY PLUS PEG-IFN/RIBAVIRIN VERSUS PEG-IFN/RIBAVIRIN IN GENOTYPE 1 CHRONIC HCV SUBJECTS; PRELIMINARY PHASE 2 EVR ANALYSES

E.J. Lawitz1, T.D. Boyer2, G.T. Everson3, I.M. Jacobson4, W. Lee5, J.G. McHutchison6, P.J. Pockros7, M.L. Shiffman8, J.M. Vierling9, S. Cruickshank10, T.C. Rodell11, D. Apelian11

1Alamo Medical Research, San Antonio, TX, 2University of Arizona, Tucson, AZ, 3Department of Medicine, University of Colorado Denver, Aurora, CO, 4Department of Medicine, Weill Cornell Medical College, New York, NY, 5Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 6Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, 7The Scripps Clinical Research Center, La Jolla, CA, 8Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, 9Department of Medicine and Surgery, Baylor College of Medicine, Houston, TX, 10Cruickshank and Associates, Santa Barbara, CA, 11GlobeImmune, Inc., Louisville, CO, USA

Background and aims: GI-5005 is a whole heat-killed S. cerevisiae immunotherapy expressing HCV NS3 and Core antigens. GI-5005 has been designed to elicit antigen-specific T-cell responses with the goal of improving the rate of immune clearance of HCV. HCV genotype 1 patients enrolled in a trial comparing pegylated interferon plus ribavirin with and without GI-5005 were compared in a prior interim analysis; RVRs for triple therapy compared to SOC alone were >2 fold more frequent (Hepatology 2008; 48: 1023A). Interim EVR data are presented here.

Methods: Naïve and non-responder chronic HCV genotype 1 patients were eligible (null responders and relapsers were excluded), and were randomized 1:1 and stratified by prior virologic response in this open label trial; Arm 1- GI-5005 monotherapy run-in consisting of five weekly followed by 2 monthly subcutaneous (SC) doses of 40YU (1 YU = 10,000,000 yeast) GI-5005 over 12 weeks, followed by triple therapy consisting of monthly 40YU GI-5005 doses plus 48 weeks pegIFN/ribavirin (SOC), Arm 2- SOC alone.

Results: At this time, 52/72 triple therapy subjects and 65/68 SOC subjects were evaluable for EVR (≥ 2 log10 reduction in HCV RNA at week 12, with last observation carried forward). Triple therapy showed a trend for improved EVR in all naïve subjects (34/36 {94.4%} vs. 40/46 {87%} p=0.23) and naïve subjects with high baseline viral load (>600,000IU/mL) (28/30 {93.3%} vs. 35/41 {85.4%} p=0.26). EVR was comparable for triple therapy and SOC in the small subset of prior non-responder subjects. GI-5005 has been well-tolerated, with no GI-5005 related serious adverse events or dose limiting toxicities to date.

Conclusions: Triple therapy with GI-5005 plus pegIFN/ribavirin was well tolerated and preliminary data indicate improved EVR rates, despite an unusually high EVR rate in the SOC group. These data are consistent with the HCV-specific cellular immune responses observed in the GI-5005-01 phase 1 trial and the improved week 4 RVR in the current trial. This therapeutic approach and the mechanism of GI-5005 support further investigation and development of combination therapy strategies in chronic HCV infection. Complete cohort data for naives and non-responders will be included at the time of presentation.

Monday, 27 April 2009

http://pr-canada.net

Twelve-week Phase 2 clinical trial data show that patients treated with GI-5005, GlobeImmune's targeted molecular immunogen (Tarmogen®) for the treatment of hepatitis C virus infection, had 94 percent early virologic response (EVR) rate in treatment naïve patients. The study compared GI-5005 plus standard of care (SOC) -- pegylated interferon and ribavirin -- versus SOC alone in patients with chronic genotype 1 hepatitis C infection.

The study data will be presented in a poster presentation tomorrow by Eric Lawitz, M.D., of Alamo Medical Research Center, San Antonio, Tex. at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark. The 94 percent EVR rate in naïve subgroups including those with high baseline viral loads, is defined as a greater than 100-fold reduction of HCV RNA from baseline at 12 weeks and is an eight to twelve percent improvement over the SOC alone arm.

"We were pleased to see a 94 percent EVR rate in the treatment naïve patient population," said Dr. Lawitz, the study's lead author. "We believe that this increase in EVR over standard of care alone may indicate that the GI-5005 mechanism of action is complementary to the current standard care."

Additional exploratory analyses of serum fibrosis (Fibrotest) and necrosis (Actitest) markers showed a two-fold improvement in the proportion of patients with improved serum Fibrotest, and a fifty percent reduction in the number of patients with worsening Fibrotest scores after 24 weeks in the group receiving the triple therapy. At the 24 week time point, the triple therapy improved serum Actitest scores by up to 14 percent in treatment naïve patients when compared to SOC alone. The treatment naïve group with high viral load receiving the triple therapy also saw a 14 percent advantage over the SOC group in normalization of alanine transaminase (ALT), a marker of liver damage.

"We believe that the improvement in ALT, Actitest and Fibrotest scores seen in patients in the triple therapy arm of the study suggests that triple therapy with GI-5005 may lead to improvements in liver inflammation, necrosis and fibrosis compared to standard of care alone," said David Apelian, M.D., Ph.D., GlobeImmune's Chief Medical Officer. "At this interim stage of our Phase 2 program, we are encouraged by the data as we believe they suggest that triple therapy including GI-5005 may improve sustained virologic response as well as liver histology, both of which will be measured in the current study and could serve as primary or co-primary efficacy endpoints in a future Phase 3 HCV program."

The GI-5005-02 clinical trial is a randomized, multi-center, Phase 2 study evaluating 140 patients, all with genotype 1 HCV infection. In the trial, 74 percent of patients had never received prior treatment, and the remaining 26 percent had failed prior treatment.

About GlobeImmune

GlobeImmune Inc. is a private company developing targeted molecular immunogens, Tarmogens, for the treatment of cancer and infectious diseases. The company's lead product candidate, GI-5005, is a Tarmogen for the treatment of chronic hepatitis C infection (HCV). GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer.

For additional information, please visit the company's Web site at www.globeimmune.com.

This news release and the anticipated presentation contain forward-looking statements that involve risks and uncertainties, including statements relating to initiation and progress of the Company's clinical trial programs and the preliminary results from the clinical trials. Actual results could differ materially from those projected and the Company cautions readers not to place undue reliance on the forward-looking statements contained in the release and anticipated presentation.