Collaborative Workshop hosted by the Centers of Excellence in Regulatory Science and Innovation (CERSIs) and the Food and Drug Administration (FDA)
Full Agenda
Wednesday, October 3, 2018: 8:30 a.m. - 5:00 p.m.
Thursday, October 4, 2018: 8:30 a.m. - 5:00 p.m.
FDA's White Oak Campus
10903 New Hampshire Avenue
Building #31 - The Great Room
Silver Spring, MD 20903
Goals and Objectives:
Protein therapeutics have continued to gain an increasing share of the pharmaceutical market and now provide medical interventions for some of the most complex and intractable diseases. Immunogenicity, the propensity of a therapeutic protein to induce immune responses, principally by development of antibodies, may affect safety and/or efficacy, and is thus an important concern in the development and regulation of protein therapeutics. Patients, regulators and the biopharmaceutical industry are all affected by immunogenicity. Recently, both the US Food and Drug Administration and the European Medicines Agency have released Guidance Documents for industry focusing on immunogenicity.
This timely public workshop will present advances in the development of technological tools for predictions of immunogenicity and discussions on how to engage relevant stakeholders in application of these tools during drug development.
The specific objectives of this workshop are to:
- Communicate to stakeholders the “state of the science” regarding technological approaches for prediction of immunogenicity including non-clinical (in silico) studies for detection of neo-antigens, the use of novel animal models, and strategies to de-immunize protein molecules.
- Explore strategies for choosing appropriate tools and interpreting the results since the novel tools and information available in this field are complex and not amenable to simple prescriptive approaches during drug development.
For speakers who have given permission, the workshop slides are posted below on this webpage (see hyperlinks). For speakers who have given permission, the workshop webcast recordings will be posted in the near future on this webpage.
Wednesday, October 3rd |
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8:30 - 8:45 a.m. |
Welcome |
James Polli, Ph.D. |
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8:45 - 9:00 a.m. |
Opening Remarks from the FDA Center for Drug Evaluation and Research (CDER) |
Patrizia Cavazzoni, M.D. (CDER) |
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9:00 - 9:15 a.m. |
Opening Remarks from the FDA Center for Biologics Evaluation and Research (CBER) |
Carolyn Wilson, Ph.D. (CBER) |
Session 1 |
Advances in understanding the biology of T- & B-cell responses as it applies to the immunogenicity of therapeutic proteins |
Moderator: Amit Golding, M.D., Ph.D. (University of Maryland School of Pharmacy) |
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9:15 - 9:20 a.m. |
Introduction |
Dr. Amit Golding |
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9:20 - 10:00 a.m. |
Interplay of Cells involved in Therapeutic Agent Immunogenicity |
Robert G. Hamilton, Ph.D. (Johns Hopkins University School of Medicine) |
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10:00 - 10:25 a.m. |
Coffee Break |
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Session 2 |
New analytical techniques and improvements in existing technologies to predict immune response to therapeutic proteins
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Moderator: Daniela Verthelyi, M.D., Ph.D. (OPQ/CDER/ FDA) |
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10:30 - 11:00 a.m. |
MHC binding and immunogenicity of eluted ligands - benchmarking and predictions |
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11:00 - 11:30 a.m. |
Vibha Jawa, Ph.D. (Merck and Co. USA) |
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11:30 - 12:00 p.m. |
The ABIRISK integrated approach to identify and evaluate predictive markers of immunogenicity |
Sophie Tourdot, Ph.D. (Pfizer Inc.) |
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12:00 - 1:10 p.m. |
Lunch |
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Session 3 |
The human cost and the economic burden: How immunogenicity affects patients and the economic burden on the healthcare system
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Moderator: Frank F. Weichold, M.D., Ph.D. (FDA) |
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1:10 - 1:15 p.m. |
Introduction |
Dr. Frank F. Weichold |
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1:15 - 1:45 p.m. |
Immunogenicity economic impacts from gene therapy development to biosimilar markets: inconvenient biology truths for all |
Mark Trusheim (MIT) |
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1:45 - 2:15 p.m. |
A patient-centered approach to understanding the burden of inhibitors |
Mark W. Skinner, J.D. (Institute for Policy Advancement Ltd) |
Session 4 |
Mathematical models that can integrate seemingly disparate measurements related to immunogenicity |
Moderator: Million A. Tegenge, RPh, Ph.D. (CBER/FDA) |
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2:15 - 2:20 p.m. |
Introduction |
Dr. Million A. Tegenge |
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2:20 - 2:50 p.m. |
Piet H. van der Graaf, Pharm.D., Ph.D. (Certara QSP) Andrzej M. Kierzek, Ph.D. (Certara QSP) |
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2:50 - 3:20 p.m. |
Do differences make a difference: human immune responsiveness and single-cell variations |
John Tsang, Ph.D. (NIH) |
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3:20 - 3:40 p.m. |
Break |
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Session 5 |
Panel Discussion with Day 1 Speakers
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Moderator: Zuben E. Sauna, Ph.D. (CBER) |
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3:40 - 4:45 p.m. |
Expert Panel |
Dan Sikkema, Robert Hamilton, Alessandro Sette, Vibha Jawa, Sophie Tourdot, Mark Trusheim, Mark Skinner, Piet van der Graff, John Tsang |
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4:45 - 5:00 p.m. |
Dr. Zuben E. Sauna
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Thursday, October 4th |
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Session 6 |
Big data and immunogenicity: How “omics” workflows can be used to generate and analyze large data sets as they relate to immunogenicity
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Moderator: Joseph McGill (FDA/OMPT/CBER/OTAT/DPPT/HB) |
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8:35 - 8:40 a.m. |
Introduction |
Joseph McGill |
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8:40 - 9:10 a.m. |
Tonsil organoid cultures as a model system to study human adaptive immune responses in vitro |
Mark M. Davis, Ph.D. (Stanford) |
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9:10 - 9:40 a.m. |
Massively parallel screening of natively paired human antibody repertoires for antibody response analysis |
Brandon J. DeKosky, Ph.D. (University of Kansas) |
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9:40 - 10:10 a.m. |
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Laura Santambrogio, M.D., Ph.D. (Albert Einstein College of Medicine) |
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10:10 - 10:25 a.m. |
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Session 7 |
Identification and application of biomarkers for predicting immunogenicity
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Moderator: João A. Pedras-Vasconcelos, Ph.D. (FDA/CDER/OBP/DBRR3) |
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10:25 - 10:30 a.m. |
Introduction |
Dr. João A. Pedras-Vasconcelos
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10:30 - 11:00 a.m. |
De-risking Protein Therapeutics: Should You Delete that T cell Epitope or Keep it? And Why |
Annie De Groot, M.D. (University of Rhode Island) |
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11:00 - 11:30 a.m. |
Amplitude and peptidespecificity of CD4 T-cell response to therapeutic antibodies in healthy donors and in patients |
Bernard Maillere, Ph.D. (University Paris-Saclay, France) |
Session 8 |
Update NHLBI State of the Science Workshop: Inhibitors in Hemophilia |
Moderator: Basil Golding, M.D. (DPPT, OTAT/CBER/FDA) |
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11:30 - 11:35 a.m. |
Introduction |
Dr. Basil Golding |
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11:35 - 12:05 p.m. |
Factor VIII Inhibitors: Generating a National Blueprint for Future Research |
Donna DiMichele, M.D. (NIH) |
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12:05 - 1:05 p.m. |
Lunch |
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Session 9 |
The Holy Grail: Deimmunizing protein therapeutics
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Moderator: Amy S. Rosenberg, M.D. (CDER) |
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1:05 - 1:10 p.m. |
Introduction |
Dr. Amy S. Rosenberg |
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1:10 - 1:40 p.m. |
Recombinant Immunotoxins: Efficacy and Immunogenicity |
Ira Pastan, M.D. |
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1:40 - 2:10 p.m. |
Computationally-driven deimmunization of therapeutic proteins |
Chris Bailey-Kellogg, Ph.D. (Stealth Biologics, LLC) |
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2:10 - 2:40 p.m. |
Toward de novo design of immune silent protein and peptide therapeutics |
Lance J. Stewart, Ph.D. (University of Washington) |
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2:40 - 3:00 p.m. |
Break |
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Session 10 |
Panel Discussion with Day 2 Speakers
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3:00 - 4:45 p.m. |
Expert Panel |
Mark Davis, Brandon DeKosky, Laura Santambrogio, Anne DeGroot, Bernard Maillere, Ira Pastan, Chris Bailey-Kellogg, Lance Stewart, Donna DiMichele |
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4:45 - 4:55 p.m. |
Dr. Amy S. Rosenberg |
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4:55 - 5:00 p.m. |
Acknowledgements & Wrap-up Declaring the workshop closed |
Dr. Zuben E. Sauna |
** Collaborative Workshop hosted by:
Centers of Excellence in Regulatory Science and Innovation (CERSIs):
The Food and Drug Administration:
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