By Invitation Only

“Westin Immunogenicity Seminar” 2011

Tuesday, March 29, 2011

9:45 am – 6:10 pm
KUSUNOKI Room
The Westin Tokyo
1-4-1 Mita Meguro-ku, Tokyo 153-8580 Japan

Speakers:
Annie De Groot M.D.
Director and Professor, Institute of Immunology and Informatics, University of Rhode Island, Associate Professor, Brown University Medical School, CEO/CSO EpiVax;
Leslie Cousens, Director of Protein Therapeutics, EpiVax, Inc.
Keizo Yoshida Ph.D., EpiVax Asia
Matthew Ardito, Frances Terry, EpiVax, Inc.

9: 00 AM Registration / Breakfast

9: 45 AM              Opening Remarks –  Dr. Keizo Yoshida

10: 00 AM            Immunogenicity: Determinants & Correlates – Dr. Cousens

11:15 AM –Morning Break – Coffee / Tea

11: 30 AM            Predicting and Confirming Immunogenicity  – Dr. A. De Groot

12: 30 PM — Box Lunch Provided

1: 00 PM               ISPRI Demonstration – M. Ardito / F. Terry, EpiVax

2: 00 PM              Tregitope Update: Application to Biologics – Dr. A. De Groot

3: 30 PM Afternoon Break – Coffee / Tea

5: 00 PM FDA and EMEA Panel Discussion – Interpreting the guidelines

6: 00 PM            Closing Remarks – Keizo Yoshida, Ph.

We will address the following important questions:

(1) What drives the immunogenicity problem for protein drugs?
(2) How can regulatory T cells be engaged to control immunogenicity through Tregitopes?
(3) What are the best means to predict and prevent immunogenicity?

Expert immunologist and Biotech CEO Dr. Annie De Groot of EpiVax, Inc. who is also faculty member of the Brown University Medical School and Professor at the University of Rhode Island, will provide a detailed discussion of immunogenicity and tolerance for a highly selected audience.

Seating is limited. Please reserve your seat now by emailing EpiVax representative Dr. Keizo Yoshida, yoshidakeizo@gmail.com.

Seminar Topic:

Immune Response to Protein Medicines: Prediction and Mitigation.

Modulation of T cell response in the context of protein therapy and inflammation may contribute to the design of improved biologic therapeutics for a wide range of clinical conditions. Preclinical efforts to reduce immunogenicity have until now been directed at reducing the presence of T cell epitopes or T cell response to protein therapeutics by screening for epitopes and deimmunizing (removing T cell epitopes) prior to further development of the protein for clinical use. The seminar speakers are experts in the field of immunogenicity; they will discuss case studies and provide information about current trends and future directions regarding FDA and EMEA guidelines.

Modulation of T cell responses by blocking upregulatory receptors, or concomitant treatment with cytotoxic drugs has also been attempted with varying degrees of success. Adaptation or incorporation of Tregitopes, which are natural T regulatory epitopes derived from IgG (“Tregitopes”, described in Blood, 2008; 112: 3303-3311) also may aid in the design of safer, more effective protein therapeutics, whether these proteins are monoclonal antibodies, novel scaffolds, replacement therapies or biosimilars.

The discovery of Tregitopes also has broad reaching implications for the fields of allergy, autoimmunity and transplantation.

New data on Tregitopes will be presented at this seminar, including information on the following studies: Co-administration of natural T regulatory epitopes with a range of proteins (such as protein therapeutics, allergens, autoimmune disease antigens such as GAD65) in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. Diabetes is delayed and suppressed in NOD mice treated with the Tregitopes (Scott, Su); pulmonary infiltrates and serum IgE are suppressed following Tregitope administration in the OVA model of allergy. T cell staining demonstrates significant expansion of adoptive Tregs in gene therapy (Mingozzi) and MLR studies conducted with human PBMCs, and transplant rejection (skin, heart) is delayed (Najafian). The mechanism of suppression appears to be due to the induction of antigen-specific adaptive tolerance induction (Khoury, Najafian, De Groot and Cousens).

In this presentation, we will review the evidence that consideration of regulatory T cell induction represents a new paradigm for the suppression of immune response to protein therapeutics, gene therapy vectors, transplanted organs, and for treatment of autoimmune disease.

For Dr. De Groot’s CV see here: http://tinyurl.com/AnnieD

Selected References:

• De Groot A.S., L. Moise, J.A. McMurry, Erik Wambre, Laurence Van Overvelt, Philippe Moingeon, W. Scott, W. Martin, Activation of Natural Regulatory T cells by IgG Fc-derived Peptide “Tregitopes”. Blood, 2008,112: 3303. http://tinyurl.com/ASDeGroot-Blood-2008.

• Anne S. De Groot and Bill Martin. Reducing Risk, Improving Outcomes: Bioengineering less immunogenic protein therapeutics. (Andy Saxon, Ed.). Clin Immunol. 2009 May;131(2):189-201. http://tinyurl.com/ASDeGroot-Clin-Immunol-2009

• David W. Scott, Anne S. De Groot. Can we prevent the immunogenicity of Protein Drugs. Annals of Rheumatology. Ann Rheum Dis. 2010 Jan;69 Suppl 1:i72-76.

• Cohen T, Moise L, Ardito M, Martin W, De Groot AS. A method for individualizing the prediction of immunogenicity of protein vaccines and biologic therapeutics: iTEM (individualized T Cell Epitope Measure). J Biomed Biotechnol. 2010: 961752.  doi: 10.1155/2010/961752.

Websites:  http://www.EpiVax.com
http://www.immunome.org