As the immunogenicity field is moving forward, closing the gap between clinicians and assay developers is essential in the success of biologic development and accelerates the adoption of new biologic therapies
in patient treatments. This year, CHI’s Immunogenicity Case Studies and Clinical Management conference will focus on new case studies of novel biologics and emphasize on closing this gap by providing multiple viewpoints
from clinicians, technology developers and regulators on how to use immunogenicity data in clinical settings.
Final Agenda
SUNDAY, APRIL 7
Recommended Short Course(s)*
SC1: Preclinical and Clinical Assessment of Immunogenicity: Focus on New Modalities Including Bi- and Tri-Specific Antibodies, Oligonucleotides, Gene Therapy
and CAR-T
Darshana Jani, MSc, Associate Director, Global Lead Biologics, Clinical Assay Group, Global Product Development, Pfizer, Inc.
SC5: In silico Immunogenicity Predictions (Hands-on) Workshop
Vinodh B. Kurella,
PhD, Principal Scientist, Protein Engineering, Merrimack Pharmaceuticals
Daron Forman,
PhD, Principal Scientist, Molecular Discovery Technologies, Bristol-Myers Squibb
*Separate registration required.
MONDAY, APRIL 8
7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Opening Remarks
Sandra Garces, MD,
PhD, Senior Medical Advisor for Immunogenicity, GPS Medical and Benefit-Risk Management, Eli Lilly
8:40 KEYNOTE
PREESENTATION: How to Characterize ADA Responses and Assess Their Clinical Impact to Better Inform the Clinical Relevance of ADA Using a Risk-Based Approach
Sandra Garces,
MD,
PhD, Senior Medical Advisor for Immunogenicity, GPS Medical and Benefit-Risk Management, Eli Lilly
Practical cases will be used to better illustrate the specific questions and some of the limitations we sometimes face and to discuss potential ways to overcome challenges in pre-clinical risk assessment of expected clinical consequences according to
type of biologic, disease population, drug MoA. Study designs to incorporate specific immunogenicity questions, characterization of ADA responses, type of analyses to characterize the impact on PK, on PD, efficacy
and safety and risk-benefit perspective to decide if further mitigation strategies are needed will also be discussed.
9:10 Relationship Between ADA and PK Assays: Is There an Impact?
Marcela M. Araya,
PhD, Principal Scientist, Group Leader, BioMedicine Design, Pfizer
The assessment of immunogenicity of
therapeutics drugs is a requirement for regulatory filings. The ADA formation may have an impact on the efficacy, dosing schedules and sampling schedules. Current gaps include
a limited knowledge of the effect of endogenous ADA on PK/PD profiles, and the inconsistency of reported types of ADA responses (e.g., titers, concentration, isotypes, etc). The presentation will cover the impact of immunogenicity induction on
PK assays.
9:40 Applying Modeling Methodologies to Analyze the Impact of Immunogenicity on Exposure and Efficacy
Vibha Jawa,
PhD, Director and Lead, Predictive and Clinical Immunogenicity, PPDM, Merck & Co Inc
Understanding immunogenicity’s effect on the PK and PD of a therapeutic protein is important during drug discovery, as it allows for the identification of clinically relevant anti-drug antibody reactions. The goal of this work is to use modeling
methodologies to understand the effect of immunogenicity, streamlining the early drug discovery process and informing clinical decisions.
10:10 Networking Coffee Break (Harbor & Mezzanine Level)
10:45 Chairperson’s Remarks
Vibha Jawa,
PhD, Director and Lead, Predictive and Clinical Immunogenicity, PPDM, Merck & Co Inc
10:50 Increased Immunogenicity Associated with Combination Regimens with Immune Modulatory Biologics
Jad Maamary, PhD, Associate Principal Scientist, Predictive and Clinical Immunogenicity, PPDM, Merck
& Co Inc
The use of immune modulatory biologics to augment
functionality of immune cells can also augment the risk of immunogenicity. The quality of such an immune response and its clinical relevance will be explored through this talk. Whether the activation of immune cells can break tolerance to otherwise
tolerant sequences will also be explored.
11:20 ADA Testing in Clinical Routine: Where Are We and Where Are We Heading?
Anna Fogdell-Hahn, PhD, Associate Professor, Karolinska Institutet, Clinical Neuroscience, Clinical Neuroimmunology, Center for Molecular Medicine (CMM), Stockholm, Sweden
Whereas ADA testing is now a requirement for drugs to be approved, the use of them in clinical settings are only partially applied. This is unfortunate since it would enable identification of patients that have reacted and become tolerant against their
treatment before clinical symptoms appear. In this
talk I will present a feasible process for translating the ADA testing from the industry, through
academy to applied clinical routine.
11:50 Towards Translational Immunogenicity
Jochem
Gokemeijer, Associate Director, Molecular Discovery Technologies, Bristol Myers Squibb
In Vitro and In Silico tools can be utilized during biologics drug development to select clones with decreased immunogenicity risk. Here we will discuss how these tools are used in drug development as well as ongoing efforts to harmonize methods and
establish clinical validation.
12:20 pm Bioanalytical Strategy to support CAR-T Therapies: Where are the Challenges?
Corinna Fiorotti, PhD, CSO, BioAgilytix
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:50 Session Break
2:20 Problem-Solving Breakout Discussions - Click here for details (Commonwealth
Hall)
3:20 Networking Refreshment Break (Harbor & Mezzanine Levels)
4:00 Chairperson’s Remarks
Rakesh Dixit,
PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
PLENARY KEYNOTE SPEAKER
4:10 Vision for How Immunotherapy Will Shape Future of Cancer Care
Leena Gandhi, MD,
PhD, Vice President, Immuno-Oncology Medical Development, Lilly Oncology
Immunotherapy is considered by many as a pillar of cancer care today, but in many
ways we have only scratched the surface. Our knowledge and understanding of the complexities of immunotherapy and its mechanisms continue to evolve. The future of cancer care will be defined by our ability to systematically identify and implement
opportunities for combination therapy to improve and standardize patient response.
YOUNG SCIENTIST KEYNOTE
4:55 The Lassa Virus Glycoprotein: Stopping a Moving Target
Kathryn Hastie,
PhD, Staff Scientist, Immunology and Microbiology, The Scripps Research Institute
Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. The trimeric surface glycoprotein, termed GPC, is critical for infection, is the target for neutralizing antibodies, and a major component of vaccines. Structural
analysis of Lassa GPC bound to antibodies from human survivors reveals a major Achilles heel for the virus and provides the needed template for
development of immunotherapeutics and improved vaccines.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:15 End of Day
TUESDAY, APRIL 9
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Darshana Jani,
PhD, Associate Director & Global Lead Biologics, Pfizer Inc
8:30 Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms
Robin E. Walsh, MS, Toxicologist, Toxicology and Immunosafety Lab, Eli Lilliy & Co
In this study, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in clinic. Two of the three antibodies were capable of eliciting a CD4[+] T cell proliferative response with multiple donors in a peripheral blood
mononuclear cell (PBMC) assay, but required different experimental conditions to induce these responses. The third antibody did not trigger any T cell response in this assay. These distinct capacities to promote CD4[+] T cell responses in vitro
were mirrored by different capacities to stimulate innate immune cells. Only one out of the three antibodies was capable of inducing human monocyte-derived dendritic cell (moDC) maturation; the second antibody promoted monocyte activation while
the third one did not induce any innate cell activation in vitro. However, all three antibodies exhibited a moderate to high internalization by human moDCs and MHC-associated peptide proteomics (MAPPs) analysis revealed the presence of potential
T cell epitopes that were later confirmed by PBMC T cell proliferation assay using peptides instead of whole antibodies. Collectively, these findings highlight the existence of distinct immune stimulatory mechanisms of immunogenic antibodies.
These approaches and findings might have implications for the preclinical screening of therapeutic proteins and help lower the immunogenicity risk of therapeutic proteins.
9:00 Nonclinical and Clinical Immunogenicity Assessment of Bispecific Protein Therapeutics
Eric Wakshull,
PhD, Principal Scientist/Group Leader, Bioanalytical Sciences, Genentech
The advent of increasingly complex and novel protein therapeutic modalities requires non-standard approaches to assessing immunogenic responses. Bispecific antibodies are one such novel modality in which two different target specificities are engineered
into a single protein. This presentation will discuss our bioanalytical strategy and its implementation using two such molecule programs. These case studies will illustrate how these strategies were implemented, their outcome and impact on clinical
development.
9:30 Case Study: Clinical Immunogenicity and Its Impact
Deborah Finco,
PhD, President, Deborah Finco Consulting LLC
Multiple companies developed therapeutic monoclonal antibodies to the same target for lowering low-density lipoprotein (LDL). However, the immunogenicity profiles varied considerably between the different companies monoclonal antibodies. This talk
will discuss the different therapeutic antibodies, the immunogenicity assays, clinical results, and the impact of immunogenicity and efficacy on one program.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
CASE STUDIES OF BIOLOGICS (CONT.)
10:45 Chairperson’s Remarks
Darshana Jani,
PhD, Associate Director & Global Lead Biologics, Pfizer Inc
10:50 Immunogenicity Assessment of an Enzyme Replacement Therapy Administered via the Intracerebroventricular Route in Patients with CLN2 Disease
Anu Cherukuri,
PhD, Associate Director, Immunogenicity Assessment, BioMarin Pharmaceutical Inc.
We have characterized immunogenicity of a novel ERT directly delivered to the CNS in patients with a life-threatening neurodegenerative disease. The consequences of both a systemic and CNS-specific immune response on the safety and efficacy profiles
of the drug will be presented. Implications of ADA impact on systemic and CSF PK will be included. Lastly, regulatory feedback on the risk assessment approach and learnings from the program that can be applied to assess immunogenicity risks of
future ICV-delivered ERT therapeutics will be presented.
11:20 Immunogenicity Testing – The Next Frontier: Gene Therapies, Nanoparticles and Beyond
Renuka Pillutla,
PhD, Executive Director, Lead, Bioanalytical Sciences, Bristol-Myers Squibb
Advances in molecular engineering and our understanding of biological mechanisms are resulting in increasingly novel therapeutics. In the realm of large molecules, we have gone beyond the traditional antibody and protein therapeutics to unique modalities
with innovative delivery systems.
Increasing complexity of novel modalities has led to increases in the complexity of immunogenicity testing strategies. This presentation will discuss the challenges of assessing immunogenicity risk and developing appropriate testing strategies
as we move into this next frontier. Two case studies will be used to illustrate some of the challenges. In one example, the therapeutic is a lipid nanoparticle that encapsulates siRNA as the active pharmaceutical ingredient. Based on a thorough
assessment and careful consideration, an immunogenicity assay development strategy was developed and implemented for this complex molecule. In another example, immunogenicity considerations in gene therapy and the potential impact of pre-existing
antibodies to the vector will be discussed.
11:50 PANEL DISCUSSION: Characterization and Impact of Post Marketing Commitment Requirements for New Biologics Approved by the FDA
Moderator: Susan Richards,
PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D
Panelists:
Eric Wakshull,
PhD, Principal Scientist/Group Leader, Bioanalytical Sciences, Genentech
Jack A. Ragheb, MD,
PhD, Co-Chair, Immunogenicity/Immunosafety Working Group, Senior Medical Fellow for Immunogenicity, Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center
Darshana Jani,
PhD, Associate Director & Global Lead Biologics, Pfizer Inc
- Gain an awareness of postmarketing requirements and commitments, how they differ and what gaps are generally addressed?
- Discuss the various immunogenicity-related commitments that have been issued by the FDA. Are there common themes? Will they provide learnings for future biologics development?
- How will the newer guidances and incorporating a risk-based immunogenic assessment approach in programs impact future PMR/PMCs?
12:20 pm Enjoy Lunch on Your Own
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
2:00 Chairperson’s Remarks
Sophie Tourdot,
PhD, Senior Principal Scientist, Immunogenicity, Pfizer
2:05 Impact of
Presence of Pre-Existing Antibodies on Immunogenicity Assessment Strategy
Joleen White, PhD, Director and Head, NBE DMPK Project Support, EMD Serono Research & Development Institute Inc.
While all biotherapeutics have the potential to induce an antidrug antibody response (ADA), for some, pre-existing ADAs are observed in drug-naïve matrix. The presence of pre-existing ADAs may influence the bioanalytical approach
and data analysis, both preclinically and clinically. Clinical case studies of biotherapeutic candidates in development for Oncology or non-Oncology indications for which pre-existing ADA were detected will be presented.
2:35 The Origin of Antidrug Antibodies
Jack A. Ragheb,
MD, PhD, Co-Chair, Immunogenicity/Immunosafety Working Group, Senior Medical Fellow for Immunogenicity, Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center
Many factors influence the immunogenicity of therapeutic proteins. This presentation will review basic aspects of immune tolerance and discuss the implications for the development of ADA to therapeutic monoclonal antibodies.
3:05 Attend Concurrent Track
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:25 New Updates on the Use of Low Dose Transient Methotrexate
NEW: Lauren Bailey Flueckinger, MS, CGC, Genetic Counselor, Medical Genetics, Duke University Medical Center
Prophylactic immune tolerance induction (ITI) has been standard of care in CRIM-negative infantile Pompe disease (IPD) patients. However, the side effects and cost of rituximab has resulted in its use on in CRIM-negative IPD. We have developed
an immune modulation protocol using transient low-dose methotrexate. We will present data on our experience with transient low-dose methotrexate in infantile Pompe disease.
4:55 Immune Tolerance Induction Approaches for Immunogenicity Mitigation
Sophie Tourdot, PhD, Senior Principal Scientist, Immunogenicity, Pfizer
I will talk about rationale for mitigating immunogenicity through tolerance induction (the case of ERT and gene therapy, and beyond). Current practice in the clinic (ITI, methotrexate, … ) and new approaches such as antigen- specific and
non-antigen specific (nanoparticles, proteasome inhibitors, anti-CD20, …) will also be discussed.
5:25 End of Immunogenicity Case Studies and Clinical Management
5:30 Registration for Dinner Short Courses (Commonwealth Hall)
Recommended Dinner Short Course*
SC14: Subvisible Protein Particles in Immunogenicity: Measurement, Characterization
and Impact
Björn Boll,
PhD, Head, Particle Lab
and Higher Order Structure Protein Analytics, Physical Chemical Analytics, Novartis Pharma AG
Antonio Iglesias,
PhD, Expert Scientist, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd. Basel
*Separate registration required.