10:00am-1:00pm
(SC2) PRECLINICAL SAFETY ASSESSMENT OF BIOLOGICS – UNEXPECTED SAFETY FINDINGS
Moderator:
Thomas Monticello, DVM, Ph.D., Diplomate ACVP, Executive Director, Toxicology, Amgen
This short course provides an overview of the most common reasons for encountering unexpected preclinical safety issues during development of monoclonal antibodies in particular. These unexpected issues can arise from:
* Binding to the intended target
* Binding to unanticipated targets
* Anti-drug antibody formation in preclinical species
* Fc- and Fab-mediated interactions
Course instructors:
Thomas Monticello, DVM, Ph.D., Diplomate ACVP, Executive Director, Toxicology, Amgen
Jeanine Bussiere, Ph.D., DABT, Executive Director, Toxicology, Amgen
Nancy Everds, DVM, Diplomate ACVP, Pathology Director, Clinical Pathology, Amgen
10:00-11:00am
Thomas Monticello, DVM, Ph.D., Diplomate ACVP, Executive Director, Toxicology, Amgen
11:00-12:00pm
Jeanine Bussiere, Ph.D., DABT, Exec. Dir., Toxicology, Amgen
12:00-1:00pm
Nancy Everds, DVM, Diplomate ACVP, Pathology Director, Clinical Pathology, Amgen
2:00-5:00pm
(SC5) ANTIBODY DRUG CONJUGATES
Moderator:
Pamela A. Trail, Ph.D., Vice President, Oncology, MedImmune, Inc.
- Linker technology and drug characteristics
- Site-specific antibody modifications
- Use of alternative scaffolds for delivery
- Recent clinical proof of concept data
2:00 Introduction and Opening Comments
Pamela A. Trail, Ph.D., Vice President, Oncology, MedImmune, Inc.
2:15 Antibody-Drug Conjugates: Technology Advances in Linkers and Cytotoxic Agents
Ravi V.J. Chari, Ph.D., Exective Director, Chemistry & Biochemistry, ImmunoGen, Inc.
Multiple antibody-drug conjugates (ADCs) made with ImmunoGen’s tubulin interacting maytansinoid cell killing agents are undergoing clinical evaluation. ImmunoGen has developed approaches to tailor the design of each maytansinoid conjugate to achieve the best performance for the specific cancer target. My talk will discuss ImmunoGen’s technology and also highlight advances in linker design and new effector molecules for use in ADCs.
3:00 Cysteine Engineered Antibodies for Site-Specific Antibody-Drug Conjugates
Changshou Gao, Ph.D., Principal Scientist, Antibody Discovery & Protein Engineering, MedImmune
Significant progress has been made most recently in using recombinant strategies to generate antibody-drug conjugates with predetermined sites and stoichiometries for drug attachment. Here, I discuss our recent effort in cysteine engineered antibodies with reactive thiol groups for site-specific labeling in order to improve conjugation efficiency and product homogeneity. Changshou Gao, Nazzareno Dimasi, and Herren Wu
3:45 Refreshment Break
4:00 Antibody-Drug Conjugates Targeting the Tumor Neo-Vasculature
Dario Neri, Ph.D., Professor, Chemistry & Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich
In collaboration with Philogen (www.philogen.com), my laboratory has developed seven antibody derivatives which are currently being investigated in Phase I and Phase II clinical trials. In this lecture, I will present preclinical data on antibody-drug conjugates, which selectively target the tumor neo-vasculature with residence times of weeks and which release potent drugs at the site of disease without the need for antibody internalization.
4:30 Safety Assessment of Antibody Drug Conjugates
Kirsten Achilles Poon, Senior Toxicology Research Associate, Development Sciences Safety Assessment, Genentech, Inc.
Antibody drug conjugates (ADCs), or immunoconjugates, are hybrid molecules usually comprised of monoclonal antibodies conjugated with potent cytotoxins that are being developed for the treatment of a variety of cancers. Since ADCs contain both biologic and small molecule components, standard approaches for pre-clinical safety evaluation for either component may not be
appropriate or adequate and regulatory expectations are not well defined. This presentation will highlight safety assessment challenges, development strategies and case examples of the toxicology associated with certain ADCs.
5:00 Close of Short Course
*Separate Registration Required
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