Day 1 | Day 2
THURSDAY, OCTOBER 29
8:30 Chairperson’s Remarks
Paul Chamberlain, NDA Advisory Board
8:35 Intellectual Property Issues and Landscape Surrounding Minimizing Immunogenicity
Kathleen M. Williams, Ph. D., J.D., Intellectual Property Law, Edwards Angell Palmer & Dodge LLP
Therapeutic molecules are vastly improved by minimizing their immunogenicity. What are the implications of reducing immunogenicity to the intellectual property protection for the therapeutic and its uses? Structural and functional changes to a therapeutic that already is under patent may permit one to step out from under the patent altogether. At the same time, such changes may be sufficient to permit patent protection of the non-immunogenic therapeutic itself. How is this accomplished? What are the basic rules of play?
9:05 In vitro and in silico Methods to Identify T-cell Epitopes: Interpreting the Data in a Clinically Relevant Way
Philippe Stas, M.B.A., Chief Executive Officer, Algonomics
This presentation reports on immunogenicity predicting at lead discovery, lead optimization and early pre-clinical characterization. In order to select the drug leads with the lowest immunogenicity risk, pre-clinical tools generally rely on in vitro and in silico methods focussing on T-cell epitopes. We have found the data generated to be useful in the context of an immunogenicity risk management plan, but extra care has to be taken to correctly interpret them from a clinical standpoint. Specific case studies will be presented showing the link between clinical and non-clinical data.
9:35 Engineering Antibodies for Reduced Immunogenic Potential: Humira
Fiona A. Harding, Ph.D., Associate Director, New Technologies, Facet Biotech Corp.
The immunogenic potential of therapeutic antibodies is well known. Interestingly, even antibodies derived from fully human sequence constructs can elicit anti-drug antibody responses. We studied human CD4+ T cell responses elicited by Humira to characterize and address the source of immunogenicity in this fully human antibody. We identified CD4+ T cell epitopes in the V region, and were able to select modified variants that retained the full bioactivity of the parent antibody while reducing the immunogenic potential. To this end, we developed a comprehensive mutational analysis tool, and discovered some basic understandings about immune responses to therapeutic antibodies.
10:05 Sponsored Presentation (Opportunity available, please contact Ilana Quigley, iquigley@healthtech.com)
10:25 Networking Coffee Break, Poster and Exhibit Viewing
11:00 Industrial Protein Engineering for Selection of Non-immunogenic Protein Mutations
David Estell, Vice President, Innovation, Genencor International
Reducing the immunogenicity of a protein requires the identification of T cell epitopes, and the replacement of amino acids within these epitopes. A major difficulty of this approach is the identification of amino acid substitutions that reduce immunogenicity, but maintain the protein’s activity and stability. We have created a T cell based assay that identifies T cell epitopes. We have also invented a large scale protein engineering technique that allows us to rapidly identify changes within the T cell epitopes that maintain or enhance the protein’s properties. This subset of mutations can easily be checked for reduction in T cell immunogenicity, resulting in a protein with good performance and lower immunogenicity.
11:30 Featured Presentation
Clinical Data Showing Deimmunization without Affecting Efficacy
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope Ltd.
Identification and removal of CD4+ T cell epitopes by deimmunization has lead to the development of a number of therapeutic proteins including J591 (anti-PSMA), ThromobView (anti-D dimer), Anthim (anti-anthrax protective antigen), and Bouganin which are currently in clinical trials. These products reveal no development of anti-therapeutic antibody responses in clinical studies. Data will be presented on the development of deimmunized J591 for hormone-refractory prostate cancers including methods employed to generate deimmunized mAbs and progress on the clinical development of the deimmunized anti-PSMA mAb J591.
12:00 Selective Removal of B Cell Epitopes from Bacterial Proteins
Erika Gustafsson, Ph.D., Project Manager, Alligator Bioscience
Many proteins of bacterial origin have exciting properties making them attractive to drug development. However, clinical development of proteins from common infectious organisms is hampered by pre-existing antibodies. Through removal of B-cell epitopes on the bacterial protein CHIPS (Chemotaxis Inhibitory Protein of Staphylococcus aureus), we have optimized the selectivity and affinity of the ADC-1004 antagonist of the C5a receptor. Using this mutagenesis and recombination technology, more than 99% of the binding to pre-existing human IgG was removed while full functionality was preserved. ADC-1004 is presently being subjected to proof of concept efficacy studies in a porcine model of ischemia reperfusion injury.
12:30 End of Immunogenicity Prediction and Reduction
For more information, please contact:
Nicole Lyscom, Ph.D.
Conference Producer
Cambridge Healthtech Institute (CHI)
Phone: +44-1483-826359
E-mail: nlyscom@healthtech.com
For sponsorship information, please contact:
Ilana Quigley
Manager, Business Development
Cambridge Healthtech Institute (CHI)
Phone: +1-781-978-5457
Cell: +1-857-636-2334
Email: iquigley@healthtech.com