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Innovators in the field of immunogenicity are constantly furthering our understanding of factors that contribute to immunogenicity and developing new and advanced approaches for predicting immunogenicity, for reducing immunogenicity, and for tolerance induction. Presentations at Immunogenicity Prediction and Mitigation will enable attendees to make informed decisions on candidate selection, dosing and formulation, with a view to producing safe and efficacious products in the clinic and beyond.


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Recommended Pre-Conference Short Course* 

SC7: Immunogenicity Risk Assessment and Regulatory Strategies 

*Separate registration required.


MONDAY, MAY 4

7:00 am Registration and Morning Coffee


plenary keynote session

8:30 Chairperson’s Opening Plenary Remarks

8:40 Building an Antibody Discovery Company in a Crowded Field – the Adimab Story

Tillman Gerngross, Ph.D., CEO, Co-Founder, Adimab

The presentation will cover the evolution of Adimab from its founding in 2007 to becoming one of the few privately held profitable biotech companies in the last decade. Industry trends and specific strategic decisions along the way will be discussed and used to illustrate the importance of integrating finance and scientific information to build successful capital efficient biotech companies.

9:25 Cancer Stem Cells and Mechanisms of Malignant Progression

Robert A. Weinberg, Ph.D., Founding Member, Whitehead Institute for Biomedical Research; Professor, Biology, Massachusetts Institute of Technology

The cell-biological program termed the epithelial-mesenchymal transition (EMT) plays a role in conferring aggressive traits on carcinoma cells. In addition, it generates cancer stem cells (CSCs) that have the ability, following dissemination, to serve as founders of new metastatic colonies. The relationship between these CSCs and the SCs residing in normal tissues, and the participation of the CSCs in metastatic dissemination will be described.

10:10 Coffee Break


Risk Assessment and Predictive Strategies 

10:45 Chairperson’s Remarks

Ronit Mazor, Ph.D., Post Doctoral Fellow, Molecular Biology, National Cancer Institute (NCI)


10:50 KEYNOTE PRESENTATIONS

Immunogenicity Risk Assessment

Steven J. Swanson, Ph.D., Immunogenicity Consultant, Steven J Swanson Consulting

An important consideration when developing a new protein therapeutic is the potential and consequences of the therapeutic inducing an immune response. A careful analysis of the amino acid sequence can identify the presence of regions that are associated with higher rates of immunogenicity. Other tools are available to further help predict if a therapeutic will induce an immune response. Risk assessment includes deciding if any of the available prediction tools should be utilized. The possible consequences of an immune response are also evaluated when completing a risk assessment.

11:20 Case Studies on Immunogenicity Prediction Strategies for Early Decision-Making in Therapeutic Protein Development

Case StudyTim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.

Identification of immunogenicity risk is performed for all therapeutic proteins. However, not all proteins undergo a complete investigation of risk potential through the suite of assays available. I will present case studies of risk assessment, including application of in silico and in vitro methods to contribute to protein engineering and the selection of clinical candidates. Strategies for low immunogenicity risk and de-immunization will be discussed.

11:50 Presentation to be Announced

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:20 Session Break


Risk Factors that Contribute to Immunogenicity 

1:50 Chairperson’s Remarks

Tim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.

1:55 The Role of the Target in Antibody Biodisposition

Enrique Escandon, Ph.D., Principal Scientist, DMPK and Disposition, Merck Research Laboratories

For therapeutic antibodies, proximal target engagement is equivalent to immune complex formation; therefore, depending on the nature of the target (valence, abundance, location, metabolism, and its intrinsic biology), antibody-target and off-target mediated mechanisms of disposition and clearance will be affected by interactions with the Fc Gamma family of receptors. Here we present specific experimental examples where dramatic changes in exposure and biodisposition relate to target engagement.

2:25 Impact of Different Types of Aggregate on Immunogenicity

Narendra Chirmule, Ph.D., 7immune Consulting

Aggregation of proteins presents a significant safety concern in the development of this class of therapeutics. In recent years, there have been several elegant studies on delineating potential mechanism of action of aggregate induced immune activation. This presentation will focus on comparing the impact of different types of aggregates on immune activation. These observations may inform the monitoring approaches of these aggregates during process development.

2:55 Particulate Matter in Injectable Drug Products-A Regulatory Perspective and Reflections from the Draft Immunogenicity Guidance

Jack Ragheb, Ph.D., Principal Investigator, Laboratory of Immunology, Division of Therapeutic Proteins, CDER/FDA

3:25 A Systems Pharmacology Approach to Immunogenicity – A Multi-Scale, Mechanistic Mathematical Model and Its Applications

Xiaoping Chen, Ph.D., Principal Scientist Pharmacokinetics, Dynamics, and Metabolism (PDM) Pfizer, Inc.

We have developed a mechanistic, multi-scale mathematical model by recapitulating fundamental biological mechanisms. The key strength of this model lies in its capacity to integrate various risk factors, e.g., T- and B- epitopes, patients’ HLA background, and naïve T and B cell numbers into the underlying biology. The model can provide many clinical-relevant predictions. An example to illustrate potential applications in drug development will be provided.

3:55 Refreshment Break in the Exhibit Hall with Poster Viewing

4:35 Problem-Solving Breakout Discussions

5:35 Welcome Reception in the Exhibit Hall with Poster Viewing

6:50 End of Day


Day 1 | Day 2 | Download Brochure | Register 

TUESDAY, MAY 5

8:00 am Morning Coffee


Tools for Immunogenicity Risk Prediction 

8:25 Chairperson’s Remarks

Vibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Amgen, Inc.

8:30 Development of Humanized Mouse Models for the Study of Immunogenicity

Unpublished DataMichael A. Brehm, Ph.D., Assistant Professor, Diabetes Center of Excellence, Program in Molecular Medicine, University of Massachusetts Medical School

The development of severely immunodeficient IL2rγnull mice that support engraftment of functional human immune systems has enabled the in vivo study of human immunity. This presentation will include a general overview of these humanized mouse models, describing currently available strains, the protocols to generate humanized mice, the strengths of each system and a discussion of the application of these models to study immunogenicity.

9:00 Predictive Studies with Factors VII and VIII based on Genetic Analyses of Patients

Zuben E. Sauna, Ph.D., Principal Investigator, Department of Haematology, Research and Review, CDER/FDA

Based on genetic analyses of individual hemophilia A patients, we developed a predictive algorithm for immunogenicity (Receiver-operator-characteristic curve analysis, AUC, 0.890, P=0.001). The algorithm can be applied to determine the putative immunogenicity-risk of neo-epitopes introduced in bioengineered protein-therapeutics. A poof-of-principle study will be presented using a bio-engineered analog of Factor VIIa as an example. The development of this molecule was discontinued due to the development of ADAs in some patients in a phase 3 clinical trial.

9:30 Immunogenicity-Driven Late-Onset Hypersensitivity and Ways to Mitigate the Risk

Harald Kropshofer, Ph.D., Director, Senior Personalized Healthcare Leader, Pharmaceutical Development, F. Hoffmann- La Roche Ltd.

Type 2 diabetes patients experienced drug-related hypersensitivity during weekly s.c. treatment with a peptide drug. All allergic patients tested persistently positive for anti-drug antibodies, some tested IgE-positive. Competitor drugs of the same class did not give rise to allergic reactions. The results of an extensive root cause analysis program and options of how to minimize the risk of failure due to hypersensitivity will be discussed.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


Controlling Immunogenicity/Immunosuppressive Mechanisms 

10:50 Anti-Drug Antibody – A Challenge in the Field of Therapeutic Proteins, Lessons Learned from Pompe Disease

Unpublished Data and Case Study Priya Kishnani, M.D., C.L. and Su Chen Professor of Pediatrics, Division Chief, Medical Genetics, Pediatrics, Duke University Medical Center

Cross-Reactive Immunological Material (CRIM)-negative (CN) and a subset of CRIM-positive (CP) Infantile Pompe disease (IPD) mount an immune response against enzyme replacement therapy (ERT) resulting in clinical decline. Prophylactic immune tolerance induction (ITI) protocol has prevented immune response in CN patients treated with ERT. We will present data on the safety and efficacy of ITI approaches for CP and CN IPD receiving ERT.

11:20 Modulation of Immunogenicity by T Regulatory Cells

Ethan M. Shevach, M.D., Chief, Cellular Immunology Section, Laboratory of Immunology, NIAID/NIH

Foxp3+ T regulatory cells (Treg) are essential for immunological tolerance and immune homeostasis. T follicular helper (TFH) cells provide help to B cells, while a new Treg subset (TFR) has been shown to suppress germinal center B cell responses. Both TFH and TFR express the follicular homing receptor CXCR5, PD-1, and the transcription factors Bcl6. Enhancement of TFR function represents an attractive target for decreasing immunogenicity.

11:50 Design of Immunotoxins with Reduced Immunogenicity

Unpublished DataRonit Mazor, Ph.D., Postdoctoral Fellow, Molecular Biology, National Cancer Institute (NCI)

Immunotoxins are highly immunogenic recombinant proteins designed to treat cancer. We identified and removed the T cell epitopes in immunotoxins in order to reduce its immunogenicity. In this talk we will discuss the methods we used to identify and eliminate the T cell epitopes, show a comparison of in silico predicted and experimental T cell epitopes in PE38 and lastly show a proof of concept using a mouse model that shares the immune-dominant epitopes.

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing


Immune Suppression and Deimmunization 

2:00 Chairperson’s Remarks

Michael A. Brehm, Ph.D., Assistant Professor, Diabetes Center of Excellence, Program in Molecular Medicine, University of Massachusetts Medical School

2:05 Biotherapeutic Deimmunization Using Computationally Designed, Combinatorial Libraries

Unpublished DataKarl E. Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth

Biotherapeutic deimmunization via T cell epitope deletion can enable therapeutic applications for otherwise highly immunogenic proteins. Here, we demonstrate the use of computationally designed, combinatorial libraries for aggressive epitope deletion in challenging biotherapeutic candidates. Highly engineered variants of exogenous therapeutic enzymes were evaluated in humanized murine models where they mitigated immune cell responses, suppressed development of anti-biotherapeutic antibodies, and enhanced efficacy in repeat dosing therapeutic regimes.

2:35 Immune Suppression of Humanized Antibodies

Case StudyVibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Amgen, Inc.

Fully human biotherapeutics such as mAbs may be potentially immunogenic when administered to preclinical animal models and in the clinic and are associated with the formation of anti-drug antibodies (ADA). In this work we assessed the impact of various immunosuppressive regimens on ADA formation and the consequent impact on the PK profile of a fully human mAb in a rodent study . A better understanding of the mechanisms behind induction of tolerance with chronic dosing of a biotherapeutic and the impact of different immune suppressive regimens will also be discussed.

3:05 Sponsored Presentation (Opportunity Available)

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing


New Approaches to Tolerance Induction  

4:25 Improving the Efficacy Profile of Biologic Drugs by Addressing Product Immunogenicity with Tolerogenic Nanoparticles

Kei Kishimoto, Ph.D., Chief Scientific Officer, Selecta Biosciences

A case example will be presented with adalimumab in a mouse model of a spontaneous arthritis. Co-administration of the tolerogenic nanoparticles with adalimumab at the beginning of therapy prevent the formation of ADAs, resulting in normalized adalimumab PK and greatly enhanced protection from joint erosion. Other applications will also be discussed.

4:55 Induction of Immunological Tolerance to E. Coli Asparaginase by Engineering Erythrocyte Binding

Stephan Kontos, Ph.D., Co-Founder, Director, Research, Anokion SA

We report the application of an antigen-specific immune tolerance technology that harnesses natural immune regulation mechanisms of apoptotic cells to induce tolerance to the E. coli chemotherapeutic enzyme L-asparaginase. We demonstrate that engineering an erythrocyte-binding variant of asparaginase (ERY1-ASNase) allows for repeated dosing in mice without the development of anti-asparaginase antibodies, while additionally driving prophylactic immune tolerance that enables non-immunogenic follow-on therapy with wild-type ASNase.

5:25 End of Conference

5:30 Registration for Dinner Short Courses



Recommended Dinner Short Course* 

SC11: Overcoming the Challenges of Immunogenicity Assessment 

*Separate registration required.


Day 1 | Day 2 | Download Brochure | Register