Amdoxovir plus Zidovudine Demonstrates Potent Antiviral Activity in HIV-Infected Patients

RFS Pharma Announces a 2 Log Plasma Viral Load Decline Following 10 Day Treatment with a Dual Combination of Amdoxovir (DAPD) and Retrovir (AZT) in HIV-1 Infected Individuals

ATLANTA, GA, February 6, 2008 -- RFS Pharma, LLC, announced positive results from a Phase 2 clinical study evaluating Amdoxovir® (DAPD) and Retrovir® (AZT) in 24 HIV-infected individuals. The results from this study were presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) held in Boston, MA. DAPD 500 mg bid was administered alone or in combination with AZT 200 mg or 300 mg bid for 10 days. DAPD and AZT combination produced a 2 log viral load decline, suggesting synergy. There was markedly decreased viral load variability with DAPD and AZT combination compared with DAPD alone. Furthermore, there was no significant difference in viral load decline when DAPD was combined with AZT 200 or 300 mg bid, indicating that the two doses of AZT in combination with DAPD were equivalent in terms of effectiveness. Adverse events were mild to moderate and transient.

“The results from this study are very promising and warrant confirmation and further development of coformulated DAPD with AZT for second line therapy,” stated Dr. Robert L. Murphy, Professor of Medicine in the Division of Infectious Diseases at Northwestern University and the presenting author of the study.

“We are particularly encouraged by the consistent 2 log drop obtained with this combination. The potency, durability and broad resistance profile for DAPD and AZT combination will provide a robust regimen in the HIV treatment armamentarium,” said Nancy Kivel, MD, Chief Medical Officer of RFS Pharma.

DAPD plus AZT 200 mg was significantly more potent compared with DAPD alone (p < 0.04), suggesting synergy. AZT 300 mg bid was equivalent in potency to AZT 200 mg bid, when combined with DAPD. Viral load decline was significantly improved with DAPD plus AZT 200 mg and plus AZT 300 mg compared with AZT monotherapy (p < 0.0001). There were no apparent pharmacological drug-drug interactions observed.

Study Design
This was a Phase 2a, randomized, double-blind, placebo-controlled 20 day study evaluating the tolerability, safety, efficacy, post-treatment effect and pharmacokinetics of DAPD and AZT. Twenty-four subjects, who were not receiving antiretroviral therapy and had a plasma HIV-1 RNA viral load ? 5,000 copies/ml, were randomized to DAPD 500 mg bid/placebo, DAPD 500 mg/placebo plus AZT 200 mg bid or DAPD 500 mg/placebo plus AZT 300 mg bid administered for 10 days. In each arm, subjects were randomized 3:1 to DAPD or placebo. Subjects enrolled in the study had a baseline mean viral load of 4.5 log and mean CD4+ cell count of 417 cells/mm3.

About Amdoxovir
Amdoxovir is a nucleoside analog prodrug that is metabolized to its 2’-deoxyguanosine analog, DXG, which is a potent and selective inhibitor of HIV-1, including drug resistant viruses harboring M184V/I and thymidine analog mutations (TAMS). Resistance to DAPD develops slowly in MT-2 cells and is associated with K65R or L74V. Mutations associated with DAPD resistance have not been identified in humans. Virus containing the K65R mutation show moderate to high cross resistance to the approved drugs, Ziagen® (abacavir, ABC), Videx® (didanosine, ddI), Viread® (tenofovir disoproxil fumarate, TDF) and Epivir® (lamivudine, 3TC), but increased sensitivity to Retrovir® (zidovudine, AZT). DAPD has been safely administered to over 200 adults in seven Phase 1 and 2 studies.

About RFS Pharma, LLC
RFS Pharma, LLC, was founded in September 2004 and is located in a 26,500 sq. ft. state-of-the-art research facility in Tucker, Georgia. RFS Pharma is a privately owned biotech company committed to the discovery and development of antiviral agents and other human therapeutics. The company capitalizes on its expertise in nucleoside chemistry to develop drugs to combat infections caused by drug-resistant HIV and hepatitis viruses. RFS Pharma’s lead product candidate is Amdoxovir, which is in advanced Phase 2 clinical studies for the treatment of HIV-1 infections under a US IND. For further information about RFS Pharma, please refer to http://www.rfspharma.com

Forward-looking Statements
“Safe Harbor" Statement: Any statements in this press release that relate to the Companies’ expectations are forward-looking statements, within the meaning of the US Private Securities Litigation Reform Act of 1995. Since this information may involve risks and uncertainties and be subject to change at any time, the Companies’ actual results may differ materially from expected results. The Companies disclaim any obligation to update the statements contained in this press release.

Retrovir, Ziagen and Epivir are registered trademarks of GlaxoSmithKline. Videx is a registered trademark of Bristol-Myers Squibb. Viread is a registered trademark of Gilead Sciences, Inc.
SOURCE: RFS Pharma, LLC

Posted: February 2008

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