Coley Reports Results from Phase I Studies of Actilon(TM) for Hepatitis C

WELLESLEY, Mass. -- Coley Pharmaceutical Group, Inc. today announced results from the company's phase Ia study in normal volunteers and phase Ib dosing of hepatitis C patients with Actilon(TM) (CPG10101), the company's lead antiviral TLR Therapeutic(TM). Actilon is a first-in-class Toll-like receptor 9 (TLR9) agonist initially being developed for the treatment of hepatitis C.

The phase Ia trial of Actilon in 40 healthy volunteers demonstrated that the compound is well-tolerated over a wide dose range, and that small subcutaneous doses induce measurable, dose-related immune responses consistent with the known pharmacologic mechanisms of this new class of antiviral activity drugs. The same range of doses were administrated twice weekly for four weeks to adults with chronic hepatitis C virus (HCV) infection who had relapsed after, or were intolerant of, prior interferon therapy. One-third of these patients showed at least a 1.0 log reduction in HCV RNA (range 1.0 to 2.6).

"Coley staff is very pleased by the consistent and clear results in these randomized phase I studies. The data confirm our expectations regarding Actilon's TLR9-mediated antiviral activity which was observed over a wide range of tolerable dose levels," said John Whisnant, MD, Coley's senior vice president, drug development. "I am also encouraged by the fact that Actilon demonstrated antiviral activity even among patients with genotype 1 HCV, the viral genotype which is most difficult to treat. These results provide us with important insights on dosing regimens for further development."

"Actilon showed the predicted two phases of drug activity now characteristic of TLR9 Therapeutics. The early phase helps restore innate immune functions which are commonly dysfunctional in hepatitis C infected hosts. This occurs through TLR9 activation of dendritic cells, leading to early antiviral cytokine and cellular changes. Actilon is designed then to drive long-term adaptive immune response, also through TLR9 and dendritic cells, to sustain the virus reduction," Dr. Whisnant added.

Detailed Study Results

The phase Ia study, designed to assess the compound's safety, dose tolerability and immunological activity, randomized 40 healthy volunteers within five sequential dosing cohorts (0.25, 1, 4, 10, or 20 mg). Two subcutaneous injections were administered double-blind 14 days apart and subjects were evaluated for a total of 29 days. Researchers observed an immune system response demonstrating drug-related increases in interferon alpha (IFN-alpha) levels and other markers indicative of antiviral activity. Volunteers had no drug-related serious adverse events or dose-limiting toxicities. Mild injection site reactions and mild to moderate flu-like symptoms were consistent with the pharmacological mode of action of Actilon.

The ongoing phase Ib study is evaluating anti-viral responses among chronic hepatitis C patients as well as the safety and tolerability of twice weekly Actilon over the same dose range (0.25, 1, 4, 10, and 20 mg). Adult patients who had relapsed after or were intolerant of prior IFN-alpha therapy were randomized to receive Actilon or a placebo two times weekly for four weeks with monitoring for up to four additional weeks (eight weeks total). Of 18 patients evaluated to date at the 1, 4, and 10 mg dose levels, six (33 percent) have demonstrated early viral level reduction equal to or better than 1.0 log decrease (or 90 percent) during the four weeks of treatment. The viral level reduction observed was consistent with the elevation of IFN-alpha and other markers associated with an antiviral immune response. Dose tolerance and laboratory safety were the same in HCV patients as in normal volunteers.

Both the phase Ia and interim phase Ib data were presented at national scientific meetings last fall. phase Ia dose tolerance, pharmacokinetic (PK) and immune response data were presented at the 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in Washington. Phase Ib data, including antiviral response, were reported at The American Association of Liver Disease (AASLD) meeting (November 2004) in a poster entitled "Human Pharmacologic Activity of a New TLR9 Agonist Antiviral, CPG 10101" in Boston.

Source: Coley Pharmaceutical Group

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