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Actilon, New HCV Drug Reduces HCV RNA

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  • Shshonee (Alley)
    doctors at natap.org doctors at natap.org Sun Jan 9 08:49:13 EST 2005 NATAP - www.natap.org New HCV Drug Reduces HCV RNA
    Message 1 of 1 , Jan 10, 2005
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      doctors at natap.org doctors at natap.org
      Sun Jan 9 08:49:13 EST 2005

      NATAP - www.natap.org

      New HCV Drug Reduces HCV RNA
      http://natap.org/pipermail/doctors_natap.org/2005-January/000450.html

      Actilon (CPG 10101), Coley's lead clinical product for the treatment of viral
      disease, induces high levels of endogenous type I interferons and restores
      immune function that may be compromised by viral infection. Actilon is currently
      in Phase I/II trials for the treatment of chronic hepatitis C (HCV)
      infection.

      Actilon induces high levels of endogenous type I interferons and restores
      immune function that may be compromised by viral infection.

      Actilon is a synthetic agonist of the Toll-like receptor 9 (TLR9). By
      stimulating TLR9 in vitro, Actilon works directly and selectively on dendritic cells
      and B cells, inducing high levels of IFN-a to drive antiviral activities.
      Actilon achieves effective control of viral replication and induces viral
      clearance by:

      * activating natural killer cells and stimulating endogenous type I IFN
      production for control of viral replication (innate immunity)
      * enhancing dendritic cell function and reversing tolerance to viral
      antigens.
      * inducing the generation of antigen-specific cytotoxic T cells and
      antibodies (adaptive immunity).

      Coley is independently developing its Actilon products and will seek partners
      for select markets. Complete Phase I/II data, including viral load reduction
      data, will be available in late 2004. Controlled Phase II trials are planned
      for the second half of 2004. Additional viral disease indications are under
      consideration.

      Coley Reports Results from Phase I Studies of ActilonTM for Hepatitis C

      Antiviral Activity Demonstrated in Interim Phase Ib and Consistent with Phase
      Ia Dose Tolerance, Pharmacokinetics and Immune Response Findings

      Wellesley, MA - January 06, 2005

      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 ActilonTM (CPG10101), the company's lead antiviral TLR TherapeuticTM.
      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 forty 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, M.D., 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 forty healthy volunteers within five
      sequential dosing cohorts (0.25, 1, 4, 10, or 20 mg). Two subcutaneous
      injections were administered double-blind fourteen 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-a) 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-a 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-a 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 DC., USA.
      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, MA, USA.

      About Actilon
      Actilon is one of Coley's TLR TherapeuticTM family of compounds, a new class
      of investigational pharmaceutical products which activate and direct the
      immune system. Actilon is designed to act through the toll-like receptor 9 (TLR9)
      found in dendritic cells and B cells to induce a durable and natural immune
      response against the Hepatitis C virus. The compound is also designed to not only
      stimulate the body's own production of anti-viral interferons, but to also
      drive both early and sustained virus-specific memory immune responses to help
      clear the viral infection.

      About Hepatitis C
      According to the Center for Disease Control (CDC), approximately 200 million
      people worldwide are infected with the Hepatitis C virus (HCV), a blood-borne
      infectious disease of the liver and the leading cause of cirrhosis and a cause
      of liver cancer. An estimated four million people in the United States carry
      the Hepatitis C virus, and approximately 85 percent of those infected with the
      virus will progress to chronic infection. Further, 70 percent of those who
      are infected will develop chronic liver disease, making HCV the leading cause of
      liver transplants in the U.S. Currently, the most common treatments for
      Hepatitis C are recombinant forms of interferon alpha (IFN-a) intended to mimic the
      body's natural immune response in suppressing the virus. These therapies may
      be limited by toxicities and by viral resistance among some patients.



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