The Division of Monoclonal Antibodies

1. The Division of Monoclonal Antibodies Kathleen A. Clouse, Ph.D., Director CTGTAC - July 26, 2007

2. Mission of the DMA … to ensure that safe, efficacious, and high quality monoclonal antibody and related products are available to the American people to diagnose, prevent and treat the illnesses that afflict them. … to maintain and retain a diverse, knowledgeable, scientifically based and dedicated staff actively involved in research and regulatory review

3. Clinical Success of Monoclonal Antibodies “Monoclonal antibodies now comprise the majority of recombinant proteins currently in the clinic, with more than 150 products in studies sponsored by companies located worldwide.” Janice Reichert, Tufts University Center for the Study of Drug Development Nature Biotechnology, September 2005

4. The Division of Monoclonal Antibodies

5. Dr. David Frucht • Established an independent research program to characterize • the activity of anthrax lethal toxin in vitro and in vivo • Reviews products for infectious diseases, including antibodies • under consideration for inclusion in the SNS under Emergency • Use Authorization • Reviews monoclonal antibodies or related molecules that • function as agonists or antagonists for hematologic indications • Participates in pre-approval inspections for MoAb products • Serves on working groups for guidance document development • (anthrax therapeutics development, drug-drug interactions) • Co-Chair, CDER/CBER Inter-Center Biotechnology Counter- • Terrorism Working Group • Chair, CMC session of the FDA-sponsored workshop on • “Immune Therapies for Anthrax Infection”

6. Dr. David Frucht • Board certified in Internal Medicine & Infectious Diseases • Performs weekly clinical rounds at NIH • Serves on Editorial Boards for The Journal of Immunology and • The Journalof Biological Chemistry • Awarded competitive HHS grants (2006 & 2007) and • CBER/FDA grants (2002 & 2003) for CBT research efforts • Duties as a Commissioned Officer, U.S. Public Health Service • - Incident Response Coordination Team, on-call every 5 • months for deployment (six deployments in 3 years) • - Selected for the Physicians’ Professional Advisory Committee • to the Surgeon General

7. David Frucht, M.D. Research Program Objectives • Identify biological markers for the activity of anthrax lethal toxin • (LT) in humans and animal models • Assess the biological significance of these markers in the • pathology of toxemia and/or anthrax infection • Establish the scientific basis for development of more relevant • bioassays to assess product potency • *Important for addressing issues relevant to seeking approval for • these products under the “Animal Rule” (i.e., efficacy testing in • animal models and not in humans)

8. David Frucht, M.D. Research Program Milestones • Anthrax LT activates murine macrophages, leading to release of • IL-1b and IL-18 (J Biol Chem, 2004) - Identification of new • biomarkers & strain susceptibility factors • Anthrax LT targets human T cells, leading to a blockade in • proliferation and cytokine production (J Immunol, 2005) - A • pathogenic mechanism and basis for new bioassays • Anthrax LT blocks B cell proliferation and immunoglobulin • production (J Immunol, 2006) - A pathogenic mechanism and • basis for new bioassay