RDEA806, A Potent, New HIV NNRTI With a High Genetic Barrier to Resistance and a Broad Spectrum of Activity

Even as the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine nears the end of the development process, there are other drugs in this class further back in the development pipeline.

At the recent 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, researchers from Ardea Biosciences presented early preclinical data on the company's NNRTI candidate RDEA806. In laboratory studies, RDEA806 demonstrated activity against both wild-type HIV and virus that has developed resistance to other NNRTIs.

Below is an excerpt from Ardea's press release announcing the findings:

RDEA806, A Potent, New HIV NNRTI With a High Genetic Barrier to Resistance and a Broad Spectrum of Activity, Introduced at 47th ICAAC

• RDEA806 is highly active in vitro against wild-type and the majority of HIV strains carrying key reverse transcriptase mutations

• RDEA806 has the potential to be used in both naive and treatment-experienced patients

• RDEA806 has a much higher barrier to resistance than currently approved NNRTIs, which could translate into delayed onset of resistance

CHICAGO, Sept. 18 -- PRNewswire-FirstCall -- Ardea Biosciences, Inc. (Pink Sheets: ARDC) today presented promising preclinical data on RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) posters H-1040 and H-1041, Poster Session 101, HIV: New Drugs.

To view the posters on-line, go to http://www.ardeabio.com.

Preclinical data suggest that RDEA806 has the potential to be used in both naive and treatment-experienced patients, including those harboring the K103N mutation, the most abundant mutation observed in patients failing therapy with efavirenz (Sustiva(R), Bristol-Myers Squibb) and in some newly infected patients.

RDEA806 was designed to accommodate the amino acid changes associated with NNRTI resistance and is highly active in vitro against wild-type and the majority of HIV strains carrying key reverse transcriptase mutations, including potent coverage of the 10 most prevalent strains of HIV found in patients failing therapy with efavirenz.* These include viral strains with both single and double mutations, e.g., K103N-L100I.

RDEA806 also has a much higher barrier to resistance than currently approved NNRTIs, which could translate into more durable viral suppression. In parallel serial passage studies with wild-type and K103N virus, high-level resistance to RDEA806 was not obtained for almost one year, compared to 3 months for efavirenz with wild-type virus and one month for efavirenz with virus with the K103N mutation.

"To discover RDEA806, our medicinal chemists synthesized over 1,000 analogues in a structure-activity relationship (SAR) effort to optimize potency and pharmacokinetic properties, while ensuring potent antiviral activity against the majority of the HIV strains associated with NNRTI treatment failure. These promising preclinical results led us to conduct Phase 1 clinical trials, the results of which will be presented at ICAAC tomorrow at Poster Session 160 on Antiviral Agents," said Barry D. Quart, PharmD, President and CEO.

About RDEA806

RDEA806 is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for the potential treatment of HIV infection. Based on preclinical and clinical studies to-date, Ardea believes that RDEA806 possesses several attractive properties. These include: potent antiviral activity against a wide range of HIV viral isolates, including those that are resistant to efavirenz (Sustiva, Bristol-Myers Squibb) and other currently available NNRTIs; a high genetic barrier to resistance; the potential to be administered in a patient-friendly, oral dosing regimen; limited pharmacokinetic interactions with other drugs; and the ability to be co-formulated with other HIV antiviral drugs.

About Ardea Biosciences, Inc.

Ardea Biosciences is focused on the discovery and development of small-molecule therapeutics for the treatment of viral diseases, cancer and inflammatory diseases. The company plans to initiate clinical studies on four compounds this year. These include RDEA806, the company's lead non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV, which recently completed Phase 1 clinical trials, RDEA119, a mitogen-activated ERK kinase (MEK) inhibitor for the treatment of cancer and inflammatory diseases, scheduled to enter Phase 1 clinical trials in the second half of 2007, and a follow-on NNRTI and a follow-on MEK inhibitor, both of which are scheduled to enter first-in-human studies in
the fourth quarter of 2007.

*Potent coverage is defined as less than a 10-fold shift in antiviral activity versus wild-type virus. Prevalence of resistant strains based on Bachelor et al. Antimicrob Agents Chemother. 2000 Sep; 44(9): 2475-2484.

10/02/07

Source
Ardea Biosciences. RDEA806, A Potent, New HIV NNRTI With a High Genetic Barrier to Resistance and a Broad Spectrum of Activity, Introduced at 47th ICAAC. Press release. September 18, 2007.