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PUBLIC RELEASE DATE:
17-Jul-2014

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Contact: David Sheon
dsheon@whitecoatstrategies.com
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WHITECOAT STRATEGIES, LLC

Biomarker discovery may lead to new HIV treatment

Median HIV viral load reduction more than doubled among participants with high anti-C5/gp41732-744 antibody levels who received therapeutic HIV vaccine candidate Vacc-4x in exploratory, ad hoc, subset analysis by St George's and Bionor Pharma

Further analysis of a Phase II study of therapeutic HIV vaccine candidate Vacc-4x revealed a potential biomarker associated with participants who experienced a more profound viral load reduction after receiving the vaccine. The results of this exploratory, ad hoc, subset analysis by St George's, University of London and Bionor Pharma were announced today at the AIDS 2014 Conference in Melbourne, Australia.

If confirmed, the biomarker may be able to predict which patients will benefit most from the therapeutic HIV vaccine candidate Vacc-4x, which is being developed by the Norwegian vaccine company Bionor Pharma.

St George's, University of London has had a long-standing collaboration with Bionor Pharma in a project to study HIV-associated immune activation that drives disease progression. Based on St George's work within this field, Bionor Pharma has developed a peptide (C5/gp41732-744 ) that can be used to detect antibodies against a part of the HIV envelope glycoprotein. The presence of antibodies to this part of HIV has been associated with slowed disease progression in the absence of combination antiretroviral therapy (ART).

Analysis of antibody responses to C5/gp41732-744 among patients who participated in a large Phase II clinical study has revealed that participants with baseline anti-C5/gp41732-744 antibody levels above 4μg/ml who received Vacc-4x had a statistically significant reduction in median viral load setpoint of log 0.94 (88%) compared to their median pre-ART viral load setpoint (p=0.005, n=12). Participants with anti-C5/gp41732-744 antibody levels below 4μg/ml who received Vacc-4x had a median viral load reduction of log 0.20 or 37% (p=0.019, n=27) compared to their median pre-ART viral load setpoint. The earlier Phase II study on which this subset analysis was based found a statistically significant 60% reduction in median viral load setpoint compared to historic viral load levels among participants who received Vacc-4x, interrupted ART for six months, and had pre-ART viral load data available. In contrast, those who received placebo did not experience a statistically significant change in viral load compared to pre-ART viral load setpoint.

Therapeutic HIV vaccines are designed to train the immune system to seek out and kill virus-producing cells in order to control the patient's HIV for prolonged periods of time. A successful therapeutic vaccine may negate the need for daily antiretroviral therapy (ART) for some people with HIV or provide an option for those who do not respond to ART.

Professor Angus Dalgleish, of St George's, University of London, said: "In spite of very effective drugs against HIV these need to be taken daily and have significant side-effects.

"The ability to replace this daily medication with a vaccine that allows several months of being off medication, not to mention the enormous financial gains that would be delivered to health services, is a step closer with these preliminary results."

Further study will be needed to confirm anti-C5/gp41732-744 antibody levels as a biomarker for improved response to Vacc-4x. Approximately 21% of participants in the Phase II study had antibody levels above 4g/ml prior to Vacc-4x vaccination.

Vacc-4x is also being studied in a clinical trial to assess whether a 'kick-kill' strategy, which is designed to reverse HIV latency using HDAC inhibitor romidepsin and to train the immune system to kill virus-producing cells using Vacc-4x, may be effective in reducing the HIV reservoir.

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About Vacc-4x

Vacc-4x is designed as a therapeutic HIV vaccine candidate aimed at generating immune responses to "conserved domains", or parts of HIV that are consistently present, even if the virus mutates. Sustained immune responses to this part of the virus (on the HIV protein p24) have been shown to delay HIV disease progression. Vacc-4x, which is being developed by Bionor Pharma, is made from modified, synthetic peptides, targeting these conserved regions on HIV p24. By immunizing with Vacc-4x, potentially followed by reboosting immunizations, researchers seek to control the virus infection for a prolonged period of time by training the patient's own immune system to seek out and kill virus-producing cells.

About the Phase II Vacc-4x clinical trial

The study was a Phase II randomized, multicenter, double-blind, placebo-controlled multinational clinical trial of Vacc-4x. The trial enrolled 137 participants and was conducted at clinical trial sites in the UK, the US, Germany, Italy and Spain between July 2008 and June 2010. The 52-week follow-up period was completed in June 2011. The study is registered with Clinicaltrials.gov with the identifier NCT00659789 and was published in The Lancet Infectious Diseases 2014; 14: 291-300. For study participants who completed a six-month treatment interruption of ART, there was a 64% reduction in median viral load set point between the two groups, which was statistically significant (Vacc-4x 22300 copies/mL, n=56; and placebo 61900 copies/mL, n=25; p=0.040) corresponding to a 0.44 log reduction. For participants with a pre-ART value available, a reduction in the median viral load set point of 0.40 log compared to pre-ART values was observed (24150 compared to 60470 copies/mL, p=0.0001) in the Vacc-4x group (n=45). This result was in contrast to the placebo group, in which no reduction was observed (n=18) (50400 compared to 52731 copies/mL, log 0.02, p=0.980).

About St George's, University of London

St George's, University of London, is the UK's only university dedicated to medical and health sciences education, training and research. Sharing a clinical environment with a major London teaching hospital, our innovative approach to education results in well-rounded, highly skilled clinicians, scientists, and health and social care professionals.

Our internationally recognised research programme delivers cutting-edge scientific discovery through three specialist Research Institutes, directly helping patients through our close links to the clinical frontline and London's diverse community.

Our Institutes focus on biomedical and scientific discovery, advancing the prevention and treatment of disease in the fields of population health, heart disease and infection three of the greatest challenges to global health in the 21st Century.



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