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7:00am Registration (Open until 5:30pm)

8:30am Chairperson's Remarks
Mary Haak-Frendscho, Ph.D., Vice President, Preclinical Research & Development, XOMA (US) LLC

8:35 Defining and Finding Relevant Animal Models: The Evolution of "Relevant" During Development
Nancy Wehner, Ph.D., Senior Director, Non-clinical Safety Evaluation, Elan Pharmaceuticals)
Defining and finding relevant animal models for biopharmaceutical toxicity testing is a major challenge for drug development due the the generally limited species reactivity of these compounds. This challenge can be greatly heightened when specific safety concerns exist that can稚 be easily tested due to this limited reactivity or when clinical events reveal issues that were not identified preclinically in the chosen "relevant" species. These circumstances can and should lead to a reevaluation of the animal models being used and a willingness to examine/utilize less traditional models and methodologies when appropriate. This talk will examine this evolution of relevance through case studies.

9:05 Predicting Cardiac Toxicity with Adjuant Trastuzumab Therapy
Ellie Guardino, M.D., Ph.D., Assistant Professor of Medicine, Breast Oncology, Stanford University
Trastuzumab, a monoclonal antibody, has been incorporated into the adjuvant treatment of HER2-positive breast cancer. I will discuss cardiotoxicity found in the major adjuvant trastuzumab trials reported to date including NSABP B-31, NCCTG N9831, HERA, Breast Cancer International Research Group (BCIRG) trial 0069 and the Finland Herceptin (FinHER) trial. Attempts at reducing the risk of cardiotoxicity and selecting appropriate patients for treatment will be discussed.

9:35 Translating Safety from Animals to FIH Studies of Biologics: Science or Art?
Lauren E. Black, Ph.D., Senior Scientific Advisor, Navigators, Preclinical Services, Charles River Laboratories
After TGN1412, IL-12, and thrombopoietin, does the future for biologics seem insecure? Do biologics have to be a perfect "magic bullet" to be a successful therapeutic advance? No, long term clinical experience with monoclonal antibodies show how risk and benefit can be balanced. But we have to acknowledge that sometimes, startling things can happen when protein drugs enter human trials - why can稚 we prevent every risk? Why aren稚 animals always perfect models of human response? As regulators and large pharma push for complete risk prevention, the biologics community can only fight for risk mitigation. The answer is not "more [animals] is better". To move forward in these times, we have to use every muscle - our interdisciplinary experts, new technologies and history- to craft unique approaches for each biologic IND. There are simple steps that we can take to mitigate risks that are couched in traditional science - like the ancient quote from Paracelsus, "the dose makes the poison." The FDA "Starting Doses" guidance hold some little-known clues and is discussed by one of it's authors. The last page lists the factors which lead to larger safety margins - among them is a hint that if you can稚 ferret out the dose/response relationship, all bet's are off (read: "kill the drug"). But if you can, the Pharmacologically Active Dose can be used as a conservative index for FIH dosing, a method which is very pertinent to biologics and other receptor-targeted drugs. This dose extrapolation index can offer a moderate dose estimate approach that will appease reviewers without either caving to paranoia or ignoring the frailties in pre-clinical testing.

10:05 Technology Spotlight (Sponsorship Available)

10:20 Coffee Break in the Foyer

11:00 Development of an in Vitro Cytokine Release Assay and its Predicative Value
Jing Min, Ph.D., Principal Scientist, Biotherapeutics, Pfizer
In light of the tragic FIH clinic outcome of TGN1412, a predictive cytokine release assay would be beneficial for the early safety assessment of any future immunomodulators. Using a synthesized anti-CD28 superagonist mAb as a positive control a human PBMC-based in vitro cytokine release assay has been developed. The predicative value of the assay has been further assessed with various control antibodies.

11:30 The Early Development of Raptivaｮ (efalizumab) for Plaque Psoriasis
Kathleen Meyer, Ph.D., Director of Toxicology, XOMA (US) LLC
The early nonclinical safety evaluation and clinical development of Raptivaｮ (efalizamub) will be discussed, focusing on the predictive value of animal studies to the clinical situation. Raptiva is an immunosuppressive recombinant humanized IgG1 kappa isotype monoclonal antibody that binds a human CD11a, thus reducing T cell activation, adhesion and migration. Raptiva is indicated for the treatment of adult patients with chronic moderate to severe plaque psoriasis.

12:00pm Luncheon Workshop (Sponsorship Available) or Lunch on Your Own

1:00 Chairperson's Remarks
Kohkan Shamsi, M.D., Ph.D., President & CEO, Acunova Life
Sciences Inc. and Director, Symbiotic Pharma Research

1:05 Imaging Biomarkers in Early Clinical Development of Novel Therapeutic Agents
Jeffrey L. Evelhoch, Ph.D., Executive Director, Medical Sciences, Imaging, Amgen Inc.
Over the past decade, biomarkers (objectively measured indicators of a biological/ pathobiological process or pharmacologic response to treatment) have been recognized as a critical element to improve predictability and efficiency in the process of developing more effective, more affordable, and safer therapeutics for patients. In the early clinical development of novel therapeutics, biomarkers can provide information critical to internal decision-making (i.e., establish presence of target, evaluate biological/clinical activity, dose selection for later phase trials, stratify study populations, conduct interim analysis of efficacy and/or safety). Imaging is a powerful biomarker that can provide information about genetic, biochemical, physiological and anatomic processes in many diseases including multiple sclerosis, cancer, arthritis, atherosclerosis, Alzheimer's disease, and others. This talk will explain how imaging is used as a biomarker and give several examples of how it can impact decision-making in early clinical development.

1:35 Imaging in Phase II/III Clinical Development
Haren Rupani, M.D, FACR, FACNP, Global Head, Oncology Imaging, Novartis Pharmaceuticals Corporation

• Standard or Validated Imaging Modalities

• RECIST and McDonald Criterias

• Role of Exploratory Imaging in Phase II/III

2:05 Imaging as a Biomarker in Oncology Drug Trials and Improving Cancer Patient Care
Gary Kelloff, M.D., Advisor, Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute
New promising imaging tools for measuring biomarkers have also been developed and are based on direct visualization by microscopy, nanotechnologies, and direct and remote imaging. Definitions and classifications of these biomarkers for use in oncology drug development are presented, as are activities of the NCI/FDA Interagency Oncology Task Force; opportunities under the Oncologic Biomarker Qualification Initiative (OBQI) and Biomarkers Consortium for establishing public/private partnerships; and validation/qualification studies of imaging-based biomarkers.

2:35 The Promises and Realities of Imaging as a Translational Biomarker in Drug Development
Timothy J. McCarthy, Ph.D., Senior Director and Head of Imaging, Translational and Molecular Medicine, Pfizer Global R&D

• Overview of the use of non-invasive imaging in drug development

• Identification of issues around translational imaging

• Opportunities for future technical innovations

3:05 Close of Conference