Replies to post #65195 on Biotech Values

[DewDiligence]

Non-Nucleoside HIV Drugs Show Promise in Early Trials

[The two protagonists here are IDX899 from IDIX and RDEA806 from RDEA, both of which are candidates to supersede Sustiva as the sole non-nuke in 3-drug SoC cocktails. Both drugs performed well in terms of tolerability and antiviral activity.]

http://www.medpagetoday.com/MeetingCoverage/IAC/tb/10504

›By Ed Susman
August 11, 2008

MEXICO CITY, Aug. 11 -- Two investigational non-nucleoside reverse transcriptase inhibitors have showed promising results in suppressing HIV, found preliminary trials.

The two new drugs, IDX899, made by Idenix Pharmaceuticals of Cambridge, Mass., and RDEA806, made by Ardea Biosciences of Carlsbad, Calif., both showed potent activity in seven-day data, presented at the 17th International AIDS Conference here.

IDX899 resulted in a 1.8 log10 decline in HIV at three different doses, reported Carlos Zala, M.D., of the University of Buenos Aires.

Dr. Zala and colleagues at the Hospital Privado Modelo in Buenos Aires recruited 30 patients with no history of an AIDS-defining illness who registered a plasma HIV viral load equal to greater than 5,000 copies/mL and who were naive to treatment with antiretroviral medications.

Eight participants were assigned to each of three doses of IDX899 -- 800 mg, 400 mg and 200 mg -- all of which were taken once daily. Six patients were randomly assigned to a placebo arm.

In all the dose ranges, the fall in HIV levels was similar, Dr. Zala said. In all three doses, CD4-positive cell counts increased about 62 cells/mm3 while the cell count dropped by 80 among placebo patients. Dr. Zala said, however, that he was uncomfortable in considering those changes a treatment effect because of normal fluctuations in CD4-cell counts that one might see in a week.

"We did not see any treatment-emergent serious side effects and there were no premature discontinuations," Dr. Zala said. "The laboratory profiles were similar between IDX899 and placebo."

In the second study, Graeme Moyle, M.D., M.B.B.S, director of HIV Research Strategy at Chelsea and Westminster Hospital in London, described a similar seven-day study with RDEA806 in a phase IIa trial, which showed similar results as IDX899.

He recruited 48 patients. Nine were assigned to RDEA806 at a dose of 400 mg twice a day; nine were assigned to RDEA806 at 600 mg once daily; nine were assigned to RDEA806 at 800 mg once daily; nine were assigned to RDEA806 at 1,000 mg once daily. Twelve patients (three per cohort) were assigned placebo.

With the exception of the 600 mg dose, all other active-treatment groups showed a mean drop of 1.8log10 in viral load -- but the decrease was maintained through day 10 of the trial, despite the patients being off treatment. After day 10, HIV viral levels rebounded to baseline. Changes in HIV levels among the placebo patients were minor, Dr. Moyle said. Patients on the 600 mg once daily dose achieved a 1.3 log10 decline in viral load. [The 600mg qD dose has been discontinued.]

"We saw no clinically significant laboratory findings and no clinically relevant electrocardiography findings," he said.

Both RDEA806 and IDX899, in preclinical trials, appeared to be effective against strains of HIV that have gained resistance against efavirenz (Sustiva), the non-nucleoside reverse transcriptase inhibitor that is the standard of care for first-line treatment of HIV infection.

"RDEA806 was well tolerated and showed robust antiviral effect at all doses," Dr. Moyle said.

"These drugs look promising," commented John Mellors, M.D., of the University of Pittsburgh. "But no drug gets better with time. We need to see how these drugs fare in later trials."

He speculated that if they continue to show activity and lack of serious side effects he could imagine them being co-formulated with other drugs, "possibly creating a better Atripla (the fixed dose combination of emtricitabine, tenofovir, and efavirenz)." [exactly what IDIX intends to do with IDX899: #msg-26800695].‹



“The efficient-market hypothesis may be
the foremost piece of B.S. ever promulgated
in any area of human knowledge!”

[DewDiligence]

RDEA Awarded US CoM Patent for RDEA806

http://biz.yahoo.com/bw/081020/20081020005578.html

›Monday October 20, 8:00 am ET

SAN DIEGO--(BUSINESS WIRE)--Ardea Biosciences, Inc. (Nasdaq:RDEA - News) announced today that the United States Patent and Trademark Office has issued a patent covering the composition of matter of RDEA806, the Company’s lead non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of patients with human immunodeficiency virus (HIV), and related analogs. U.S. Patent No. 7,435,752 was issued on October 14, 2008.

“We are very pleased with the continued expansion of our proprietary position in the NNRTI area. This issued patent significantly enhances the value of RDEA806 and strengthens our ability to enter into future strategic alliances for its further development,” commented Barry D. Quart, PharmD, Ardea’s president and chief executive officer. “We look forward to further expanding the proprietary position of RDEA806 and our other product candidates through additional future patent issuances.”

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, we believe that RDEA806 may have important competitive advantages compared to currently available NNRTIs. These include the potential for potent antiviral activity against a wide range of HIV viral isolates, including those that are resistant to Sustiva® (efavirenz) and other currently available NNRTIs; a high genetic barrier to resistance; no reproductive toxicity based on animal studies; 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, Inc., of San Diego, California, is a biotechnology company focused on the discovery and development of small-molecule therapeutics for the treatment of HIV, gout, cancer and inflammatory diseases. We have five product candidates in clinical trials and others in preclinical development and discovery. Our most advanced product candidate is RDEA806, a non-nucleoside reverse transcriptase inhibitor (NNRTI), which has successfully completed a Phase 2a study for the treatment of patients with HIV. We have evaluated our second-generation NNRTI for the treatment of HIV, RDEA427, in a human micro-dose pharmacokinetic study and have selected it for clinical development. RDEA594, our lead product candidate for the treatment of gout, is being evaluated in a Phase 1 clinical trial and is believed to be an inhibitor of the URAT1 transporter in the kidney, which is responsible for regulation of uric acid levels. We are evaluating our lead MEK inhibitor, RDEA119, in a Phase 1/2 study in combination with Nexavar® (sorafenib) and as a single agent in a Phase 1 study, both in advanced cancer patients, and have completed a Phase 1 study in normal healthy volunteers as a precursor to trials in patients with inflammatory diseases. Lastly, we have evaluated our second-generation MEK inhibitor for the treatment of cancer and inflammatory diseases, RDEA436, in a human micro-dose pharmacokinetic study and have selected it for clinical development.‹

[DewDiligence]

RDEA Advances RDEA806 to Phase-2b in HIV

[RDEA806 is one of the contenders to supersede Sustiva as the sole non-nuke in a 3-drug cocktail including Truvada. (IDX899 from IDIX is another contender for this slot.) The phase-2b trial will test RDEA806 at 600mg, 800mg, and 1000mg qD vs Sustiva as addends to backbone treatment with Truvada in treatment-naïve patients. Please see #msg-31380545 for a brief write-up on the RDEA806 and IDX899 data presented at the recent AIDS conference in Mexico City.]

http://biz.yahoo.com/bw/081027/20081027005292.html

›Ardea Biosciences Presents Additional Phase 2a and Preclinical Data on its Lead HIV Product Candidate, RDEA806, at the 48th Annual ICAAC/IDSA 46th Annual Meeting

Monday October 27, 8:00 am ET

SAN DIEGO--(BUSINESS WIRE)--Ardea Biosciences, Inc. (Nasdaq: RDEA ) announced today that additional data from a Phase 2a monotherapy study of RDEA806, our lead non-nucleoside reverse transcriptase inhibitor (NNRTI) in development for the treatment of human immunodeficiency virus (HIV), were presented at the 48th Annual ICAAC/IDSA 46th Annual Meeting in Washington, DC.

Dr. Graeme Moyle, Director of HIV Research, Chelsea and Westminster Hospital, gave an oral presentation showing that in the Phase 2a study, RDEA806 demonstrated robust antiviral activity with a well-tolerated profile and confirmed a low potential for drug interactions. Data from the study also showed that 800mg of RDEA806 administered once daily produced similar viral load reductions as 400mg of RDEA806 administered twice daily, supporting initiation of a Phase 2b study using once daily doses of RDEA806. In addition, Dr. Moyle presented preliminary data from a Phase 1 drug-drug interaction study of RDEA806 and Truvada® (Gilead Sciences) showing no interaction with either of its components (emtricitabine or tenofovir disoproxil fumarate).

Ardea recently received regulatory approval from the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom to conduct a Phase 2b study comparing RDEA806 to efavirenz (SUSTIVA®/Stocrin®, Bristol-Myers Squibb/Merck) in anti-retroviral treatment of naïve patients without transmitted resistance, receiving background treatment with Truvada.

In addition, Dr. Anneke Raney, director, virology, presented preclinical virology data (poster H-1222) showing RDEA806 has a high genetic barrier to resistance and limited cross-resistance to other NNRTIs [as does IDX899]. Consistent with these in vitro data, no genotypic or phenotypic changes were observed during the Phase 2a study following one week of monotherapy with RDEA806.

“We look forward to initiating the Phase 2b study of RDEA806, an important step forward in the development of this product candidate for the treatment of HIV-infected patients,” commented Barry D. Quart, PharmD, Ardea’s president and chief executive officer.

The presentation and poster are available on the Company website (http://www.ardeabio.com) under the titles, “RDEA806, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Shows Positive Outcome in Treatment of Naïve HIV Patients,” and “Resistance to RDEA806 Requires Multiple Mutations Which Have Limited Cross-Resistance to Other NNRTI’s,” respectively.

About RDEA806

RDEA806 is a novel NNRTI for the potential treatment of HIV infection. Based on preclinical and clinical studies to-date, we believe that RDEA806 may have important competitive advantages compared to currently available NNRTIs. These include the potential for potent antiviral activity against a wide range of HIV viral isolates, including those that are resistant to efavirenz and other currently available NNRTIs; a high genetic barrier to resistance; no reproductive toxicity based on animal studies; 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.‹


<font size=3><font color=red> “The efficient-market hypothesis may be
the foremost piece of B.S. ever promulgated
in any area of human knowledge!”