Overview | Day 1 | Day 2 | Day 3 | Download Brochure | Breakout Discussions

FRIDAY, FEBRUARY 27

SELECTION AND DEVELOPMENT OF NON-CLINICAL 
SAFETY PROGRAMS FOR NEW THERAPIES

(combined with Preclinical Drug Safety track)

8:30 Chairperson’s Remarks
Barbara Mounho, Ph.D., Scientific Director, Toxicology, Comparative Biology and Safety Sciences, Amgen

8:35 Scientific Challenges in Preclinical Toxicology Studies to Support the Clinical Development of Biologics
Barbara Mounho, Ph.D., Scientific Director, Toxicology, Comparative Biology and Safety Sciences, Amgen
The therapeutic advantage of biologics is their specificity, which provides them with a highly targeted therapeutic action. Due to the complex structural and biological nature of biologics, these molecules have several distinctive properties making them fundamentally different from conventional (small molecule) pharmaceuticals. The unique properties associated with biologics can create certain scientific challenges in conducting preclinical toxicology studies that typically are not issues for small molecules. The alternative approaches that toxicologists often use for the preclinical safety evaluation of these molecules will be discussed. 

9:05 Safety of Molecularly-Targeted Biologics Versus Cytoxic Oncology Drugs: Utility and Limitations of Nonclinical Safety Assessment
Rakesh Dixit, Ph.D., D.A.B.T. Senior Director & Head, Biologics Safety Assessment, MedImmune, Gaithersburg, MD
The molecularly-targeted biologic (MTB) therapies have greatly improved the treatment of debilitating cancers. While MTB therapies are generally well tolerated, many MTB therapies with unique targets have also resulted in a wide spectrum of previously unrecognized and ill-defined toxicities in sensitive cancer patients. This presentation will discuss the potential mechanisms of toxicity of MTB versus standard cytoxic therapies in cancer treatment. The value and limitations of nonclinical safety assessment using animal models in identifying toxicities of newer MTBs versus cytoxics will also be presented. 

9:35 Streamlined Custom Non-Clinical Safety Programs for Biological Therapies 
Lauren E. Black, Ph.D., Senior Scientific Advisor, Navigator Services, Charles River Laboratories 
There is no “one size fits all standard” for biologic toxicology programs. For novel biologics, there may be more “gap” than “knowledge” of the treatment’s or the targets’ effects. To define appropriate safety programs but avoid excess studies, some processes can be cross applied. Knowing target structure, distribution, and function, we can anticipate many safety events. Historical cases, successful strategies for streamlining preclinical programs, and common hurdles to success will be discussed.

10:05 Sponsored Presentation (Opportunity Available)

10:20 Coffee Break 

11:00 Qualification of New Safety Biomarkers for
Use in Drug Development: Experience of the Predictive Safety Testing Consortium
Elizabeth Gribble Walker, Ph.D., Assistant Director, Toxicology, Predictive Safety Testing Consortium, Critical Path Institute 
Establishing a process for putting new biomarkers into routine practice for regulatory submission in drug development is a complex undertaking. While safety biomarkers that reflect injury to a particular target organ are applicable to developing both small- and large-molecule therapeutics, biologics possess unique considerations for safety testing. This talk will give an overview of the process and accomplishments of the Predictive Safety Testing Consortium, and highlight case studies and opportunities where such a collaborative consortium approach might advance biologic drug safety. 

11:30 Panel with Speakers: Developing Non-Clinical Safety Programs
Moderator: Vivek Kadambi, Ph.D., Director of Drug Safety Evaluation, Millennium: The Takeda Oncology Company

• Lessons learned from in-vivo small molecules toxicology testing that can be applied to biologics or vis-a-vis

• Points of intersection for nonclinical toxicology testing of biologics and small molecule therapies

12:00 Luncheon Presentation (Opportunity Available) or Lunch on your own

FIRST IN HUMAN DOSE

1:00 Chairperson’s remarks
Mary Haak-Frendscho, Ph.D., President and CSO, Takeda San Francisco

1:05 Overview: FIH Dose Selection for Biologics
Kathy A. Elias, Ph.D., Director, Pharmacology & Experimental Pathology, Takeda San Francisco
An overview will be provided including recent perspectives aimed at determining the starting dose for first in human clinical trials of biologic drug candidates. This introductory presentation is designed to set the context for the case studies in this session. Definitions and methods also will be discussed.

1:35 Preclinical Studies to Support FIH Dose Selection of XOMA 052, A Novel Monoclonal Antibody Targeting IL-1 beta
Kathleen Meyer, M.P.H., Ph.D., D.A.B.T, Director Preclinical Safety Evaluation, XOMA US LLC
This presentation will discuss the preclinical studies and PK/PD modeling used to support FIH dosing of XOMA 052, a potent antibody that binds to IL-1b. XOMA 052 is currently in phase 1 studies in patients with Type 2 Diabetes (T2D) as inhibiting IL-1b may satisfy the unmet medical needs in a variety of autoimmune and inflammatory diseases, including T2D.

2:05 Preclinical Markers Relevant for FIH Dose Selection with an Anti-Integrin Monoclonal Antibody
Dale Johnson, Ph.D., President and CEO, Emiliem, Inc.; Adjunct Professor of Molecular Toxicology, UC Berkeley
Mechanistic studies in a preclinical macular degeneration model, binding saturation in circulating monocytes, and pharmacokinetic modeling provided the rationale for FIH dosing of an anti-integrin monoclonal antibody in cancer patients.

2:35 Dose Selection Case Study #3
Robert Bauer, Ph.D., Vice President, Pharmacometrics, ICON Development Solutions
Pharmacokinetic (PK) and pharmacodynamic (PD) models developed based on known and putative biological mechanisms and preclinical data can be very useful in anticipating PK/PD profiles that are likely to be observed in humans. This knowledge can help drug developers more effectively design their phase I clinical trials and capture the needed information in humans. An example is given of such a PK/PD model developed for the anti-Psoriasis product Raptiva, developed jointly by XOMA and Genentech.

3:05 Close of Conference
Scientific Advisors
Matt Devalaraja, D.V.M, Ph.D., Director, Pharmacology, PK and Toxicology, Human Genome Sciences
Jeanine Bussiere, Ph.D., Executive Director, Toxicology, Amgen, Inc.
Barbara Mounho, Ph.D., Scientific Director, Toxicology, Comparative
Biology and Safety Sciences, Amgen
Mary Haak-Frendscho, Ph.D., President and CSO, Takeda San Francisco

Overview | Day 1 | Day 2 | Day 3 | Download Brochure | Breakout Discussions

For more information, please contact:
Leslie C. Lilly, BSN, RN 
Conference Director
Cambridge Healthtech Institute
250 First Avenue, Suite #300
Needham, MA 02494
Phone: 978 371 5942
Fax: 781-972-5425
email: llilly@healthtech.com 

For sales information, contact:
Carol Dinerstein
Tel: 781-972-5471 
email: Dinerstein@healthtech.com