Immunacia's ViroStatics Reports Phase II Data on VS411, an AV-HALT for Treating HIV/AIDS, During the XVIII International AIDS Conference

Significant Reductions in Both Immune Hyperactivation and Viral Load in HIV Therapy-naïve Individuals After 28 Days of Therapy

SASSARI, Italy & PRINCETON, N.J.--(BUSINESS WIRE)--Jul 19, 2010 - ViroStatics, a US/Italian biopharmaceutical company developing innovative immunotherapies for HIV/AIDS and other chronic diseases, is releasing Phase II data from a randomized, dose-ranging trial of VS411, the Company's novel combination product for treating HIV/AIDS, during the XVII International AIDS Conference this week in Vienna, Austria.

“We are developing VS411, a two-drug combination product that accomplishes two distinctive goals,” said Franco Lori, MD and CEO of ViroStatics. “The first is the reduction of circulating virus, something that the currently approved HIV/AIDS medications also do. What is exceptional about the ViroStatics approach is that our products are designed to also reduce the inappropriately elevated level of immune system activation experienced by HIV-infected people. This excessive activation of the immune system begins within the first weeks of HIV infection, lasts throughout the disease, and is now recognized as the driver behind immune system exhaustion, the loss of CD4+ T cells, and the onset of AIDS.”

This second mechanism is so unique that drugs effectively accomplishing both goals are now known as a new class – the AV-HALTs (Antiviral-HyperActivation Limiting Therapeutics). To test the Proof-of-Concept that VS411, an AV-HALT containing an antiviral (low-dose, slow-release 2´,3´-dideoxyinosine) and an anti-proliferative drug (low-dose hydroxycarbamide), can both inhibit viral replication and directly reduce markers of excessive immune system activation, a 28-day Phase IIa study followed traditional safety and efficacy parameters as well as measurements of four accepted markers of immune system hyperactivation – PD-1 (exhaustion), Ki-67 (proliferation), CD38 (activation), and HLA-DR (activation).

“We are presenting Phase II data from our multinational study in which four key markers of chronically elevated immune hyperactivation were significantly reduced after only 28 days of treatment with once-daily VS411, the first agent to demonstrate true AV-HALT activity in HIV/AIDS,” said Study Investigator Elly Katabira, MD, Associate Professor of Medicine at Makerere Medical School in Kampala, Uganda. “In this five-arm, dose-ranging study, the two-drug AV-HALT VS411 achieved proof-of-concept for this novel anti-HIV class. VS411 was well tolerated and increased CD4+ counts while also reducing HIV viral load, T cell activation and the number of proliferating CD4+ T cells without suppressing HIV-specific immune responses. These unique results were achieved in a population of 58 subjects mirroring the global pandemic: 50% female and 50% black from both the northern and southern hemispheres.”

Over the 28 days of the study, VS411 safely lowered HIV replication by 1.5 logs (96.8%) without inducing drug resistance, significantly increased CD4+ T cells by up to 135 cells/mm3 in the dideoxyinosine 200 mg/hydroxycarbamide 900 mg cohort (doses lower than traditionally investigated), while also rapidly and significantly reducing markers of excessive immune activation. “It is encouraging to note that the reduction in excessive immune activation was achieved in only 28 days without complete viral load suppression,” added Dr Lori, “confirming the HALT activity of the VS411 formulation. With the AV-HALT proof-of-concept now established, work is underway at ViroStatics to develop a newly identified family of compounds combining both antiviral and HALT activities in a single molecule.”

In a companion presentation, ViroStatics' scientists explored whether Ki-67 or other immune-activation markers can be used to predict the outcome of AV-HALT treatment. Viral load data as well as pre- and post-therapy blood analyses from 32 subjects receiving VS411 were analyzed. A similar, confirmatory analysis of 7 subjects treated with the same drugs administered independently in the previously published RIGHT 702 study was also performed.

“Using 10-color flow cytometry to measure activation and proliferation markers, we compared AV-HALT-induced changes in pre- and post-therapy T cells with the degree of viral suppression achieved,” explained Denis Baev, PhD of ViroStatics. “We found individuals with a greater percentage of T cells expressing Ki-67 before treatment had greater reductions in HIV viral load after both short- and long-term anti-HIV AV-HALT therapy. This relationship was not seen with the other markers. Thus, we concluded the Ki-67 marker appears to be a valuable new tool to predict the efficacy of anti-HIV therapy.”

About the Companies:

US/Italian ViroStatics and US/Hungarian Genetic Immunity, both spin-offs of the non-profit Research Institute for Human and Genetic Therapy (RIGHT), are developing novel treatments for HIV/AIDS and other chronic diseases. The two companies are in the process of merging to form Immunacia – a multinational biopharmaceutical company with Business, Medical and Legal operations in the United States and research facilities in Hungary and Italy. Together as Immunacia, they are dedicated to developing novel treatments that partner with the human immune system to improve human health.

Posted: July 2010

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