The next wave of biologics such as bispecifics, ADCs, biosimilars, immunotherapies and combinations presents significant new challenges for today’s immunogenicity scientists, from both a technical, clinical and regulatory perspective. The 10th Annual Immunogenicity Assessment and Clinical Relevance conference brings industry, regulatory and scientific experts together to share best practices in immunogenicity risk assessment, the reporting of immunogenicity to regulators and determining the link between immunogenicity and clinical relevance. The session will also discuss predictive models, risk assessment, mitigation and control strategies, as well as latest developments in de-immunization and tolerance.
Final Agenda
Recommended Short Course*
SC8: In silico Immunogenicity Predictions – A Hands-On Workshop - Detailed Agenda
*Separate registration required
MONDAY, MAY 1
7:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
LiNa Loo, Ph.D., Principal Scientist, Non-Clinical Safety, Celgene
8:40 Current Regulatory Updates and Expectations
Bonnie Rup, Ph.D., Independent Consultant
As the number of biotherapeutics in development continues to grow and diversify, it is important for immunogenicity scientists and related departments to prepare themselves for the unique challenges associated with diverse pipelines. This presentation will review the key challenges in developing immunogenicity assessment and risk mitigation strategies with emphasis on supporting this increasing level of diversity and complexity.
9:10 KEYNOTE PRESENTATION: Immunogenicity of Avelumab - An Immune Checkpoint Inhibitor for Oncology
Theresa J. Goletz, Ph.D., Global Head, NBE Drug Disposition, QPD, EMD Serono
Avelumab binds PD-L1, blocking the interaction with PD-1 to subsequently potentiate T-cell cytotoxicity against tumor cells. Avelumab is in clinical development for the treatment of metastatic Merkel cell carcinoma, a rare form of skin cancer. The incidence of immunogenicity with avelumab was found to be low with no apparent impact on clinical pharmacokinetics, safety, or efficacy. Progress towards obtaining neutralizing antibody data will also be presented.
9:40 Preclinical Testing Strategies in IO and Complex Biologics
Sofie Pattijn, Ph.D., CTO at ImmunXperts, Member, European Immunogenicity Platform
During the last decade, the field of early immunogenicity assessment has significantly matured and progressed. With the new wave of immuno-oncology drugs and new modalities, new approaches and assays will be required to deal with the complex mechanisms and mode of actions of this class of therapeutics.
10:10 Coffee Break
10:45 Chairperson’s Remarks
LiNa Loo, Ph.D., Principal Scientist, Non-Clinical Safety, Celgene
10:50 Developing Tools for De-Risking Immune Mediated Drug Hypersensitivity: Humanized Mice
Michael Oropallo, Ph.D., Associate Scientist, Postdoctoral Fellow, Safety Assessment & Laboratory Animal Resources, Merck
Drug induced hypersensitivity reactions pose a significant safety risk, yet pre-clinical animal models often fail to detect the potential of drugs to cause these reactions. This discussion will summarize current first and second generation humanized mouse models and their potential to predict clinically relevant immunogenicity. It will share methods to determine if these mice recapitulate human physiology, as well as data comparing various commercially available 1st and 2nd generation models. It will also discuss the potential of humanized mice to be combined with other techniques in the pre-clinical pipeline.
11:20 Latest Advances in T Cell and B Cell Epitope Prediction
Paolo Marcatili, Ph.D., Assistant Professor, Bio and Health Informatics, Technical University of Denmark
The prediction of B and T cell epitopes has substantially improved in the last few years, thanks to novel machine learning algorithms and larger datasets. We will go through the latest advances in the field, see the strengths and limitations of the available computational tools, and describe the latest developments concerning the inclusion of antibody and TCR information in epitope prediction.
11:50 Broad Mapping of the Immunome with Peptide Phage Display and NGS
Michael Szardenings, Ph.D., Group Head, Ligand Development, Fraunhofer Institute for Cell Therapy and Immunology
A new way to analyse the NGS data from peptide phage display experiments in combination with a proprietary library allows the identification of multiple potential epitopes from a single selection experiment. This is allowing to efficiently map and compare antibodies from different patient sera by in silico data analyses.
12:20 pm An Integrated Approach to Managing Immunogenicity Risk and Drug Immune Modulation
Emilee Knowlton, Ph.D., Immunology Sales Specialist, ProImmune
12:50 Luncheon Presentation: Predicting, Avoiding and Mitigating Risk of Failure when Developing Biotherapeutics
Yvette Stallwood, Ph.D., Head, Applied Protein Services, Lonza Biologics
In silico methods can be used to evaluate protein sequence and structure to assess the likelihood of immunogenic responses and potential critical quality attributes. Ex vivo T and B-Cell responses enable the assessment of overall immunogenicity risks and to identify processed and presented epitopes. This presentation will discuss how such methodologies are employed to perform a manufacturability and immunogenicity risk assessment in order to highlight potential risks of failure early in the development of biotherapeutics.
1:50 Session Break
2:20 Problem-Solving Breakout Discussions
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Regulatory feedback on Immunogenicity Incidences
Tiago de Oliveira Menezes, PhD., Specialist on Health Surveillance, Biologics Drugs Office – ANVISA (National Surveillance Regulatory Agency- BRAZIL)
- Examples of products (or calls or products) that require major concern of immunogenicity
- Some products that don’t need a specific study on anti-drug antibodies (ADA)
- Antibodies against Host cells proteins
Immunogenicity for IO Therapies
Sofie Pattijn, Ph.D., Member, European Immunogenicity Platform, CTO at ImmunXperts
- Unique considerations for IO products?
- Preclinical testing strategies
- Available Tools and technologies
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Chairperson’s Remarks
4:10 Bicycles and Bicycle Drug Conjugates: Next Generation Therapeutics
Sir Gregory Winter, Ph.D., FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics
Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs); a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. This presentation will describe both the Bicycle® and BDC platforms.
4:55 Young Scientist Keynote: Programming Proteins by Deep Sequencing and Design
Tim Whitehead, Ph.D., Assistant Professor, Chemical Engineering and Materials Science, Michigan State University
Next-generation sequencing has presented protein scientists with the ability to observe entire populations of molecules before, during, and after a high-throughput screen or selection for function. My group leverages this unprecedented wealth of sequence-function information to design and engineer protein affinity, specificity, and function and to infer structural complexes of proteins. My talk will present an overview of the above and detail methodological improvements that enable the engineering work.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing
6:55 End of Day
TUESDAY, MAY 2
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Remarks
Darshana Jani, Ph.D., Senior Manager, Global Assay Lead, Pfizer
8:30 Preclinical Immunogenicity Assessment of Engineered Lysins: Next-Gen Antibiotics
Chris Bailey-Kellogg, Ph.D., Professor, Computer Science, Dartmouth
Lysostaphin is a highly potent antibacterial lysin and a promising lead in the search for next generation therapies to treat infections by MRSA superbugs. Like most lysins, however, lysostaphin has proven to be immunogenic due to its microbial origins. Using advanced biotherapeutic design algorithms, we have reengineered lysostaphin to evade T cell mediated immune recognition in human subjects. Here we describe preclinical efficacy and immunogenicity analysis of one high-performance variant.
9:00 Preclinical Assessments of Immunogenicity
Zuben Sauna, Ph.D., Principal Investigator, Division of Plasma Protein Therapeutics and Office of Tissues and Advances Therapies, FDA/CBER
Immunogenicity (development of anti-drug antibodies) is a significant impediment to development and licensure of any therapeutic-protein. Recent progress in the development and use of pre-clinical assessments of immunogenicity will be presented along with examples demonstrating good predictive outcomes. I will illustrate how judicious application of these tools can permit better decision making during drug-development, licensure, and clinical-trials.
9:30 Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory
Julio Delgado, MD, Medical Director and Section Chief, Immunology Division, ARUP Laboratories; Associate Professor, Pathology, University of Utah School of Medicine
TNF antagonists are used for the treatment of inflammatory diseases. Development of antibodies against these drugs is a major impediment that contributes to therapeutic failure. Rational and cost-effective evaluation of therapeutic failure includes measurement of drug levels, and detection of drugspecific antibodies. A functional, cell-based reporter gene assay (RGA) was developed in the clinical laboratory for measuring the biological activity and neutralizing antibody response to TNF antagonists.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Implementation of Therapeutic Drug Monitoring in Clinical Practice as a Reactive or Proactive Tool to Optimize Treatment Outcomes of Biologics
Niels Vande Casteele, Pharm.D., Ph.D., Postdoctoral Fellow, Gastroenterology, University of California, San Diego
Anti-drug antibodies (ADA) can impair the treatment effect of biologics and have been associated with adverse events. However, it is important to distinguish transient from persistent ADA and how this covariate (continuous or categorical) is included in pharmacological models. ADA are typically used in a reactive setting to support treatment decisions, whereas drug concentrations can be used in a proactive setting to guide dosing based on exposure.
11:20 Immunogenicity In Haemophilia Patients – A Case Study With BAY86-6150 (Rfviia) And Development Of An Integrated Peptide-MHC-Tcr Modelling For Immunogenicity Prediction
Pedro E. Paz, Senior Scientist and Head of Immunoprofiling Group, Biologics Research, Bayer Healthcare
The leading complication of haemophilia treatment is development of inhibitors to replacement factors. BAY86-6150 is a modified rFVIIA containing 6 amino acid substitutions that increased circulation half-life and enhanced procoagulant activity. Inhibitor development in one patient led to the premature stop of the BAY86-6150 clinical trial although in silico immunogenicity assessment did not indicate increased immunogenic risk with the rFVIIA modifications. Indeed, in vitro testing post-trial did not show patient T cell reactivity to potential neo-epitopes in BAY86-6150 but rather to two WT FVIIA T cell epitopes. An integrated peptide-MHC-TcR modelling approach is discussed as a possible improvement in predicting immunogenic response in patients.
11:50 Engineering Less Immunogenic and Antigenic FVIII Proteins
Kathleen Pratt, Ph.D., Associate Professor, Department of Medicine, Uniformed Services University
Development of antibodies that interfere with factor VIII (FVIII) pro-coagulant activity (“inhibitors”) can complicate the treatment of hemophilia A. Our laboratory has identified an immunodominant epitope in FVIII, tested its potential promiscuity, and generated amino acid substitutions in FVIII peptides and proteins to abrogate or reduce its immunogenicity. This proof-of-principle study presents a strategy for designing less immunogenic FVIII proteins targeted to specific hemophilia A subpopulations.
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
2:00 Chairperson’s Remarks
Darshana Jani, Ph.D., Senior Manager, Global Assay Lead, Pfizer
2:05 Strategies to Reduce the ADA Response to Immunotoxin Therapy of Cancer
Ira Pastan, Co-Chief, Molecular Biology, National Cancer Institute, NIH
Recombinant immunotoxins are anti-cancer agents composed of an Fv targeting a protein on a cancer cell fused to a bacterial toxin. They have good anti-cancer activity in hematologic malignancies, where the immune system is suppressed and neutralizing antibodies do not develop. SS1P is an immunotoxin targeting mesothelin expressing tumors. We have pursued several strategies to reduce the immunogenicity of SS1P, which include identification and removal of B and T cell epitopes and the induction of tolerance using novel approaches.
2:35 Challenges and Solutions in Immunogenicity Assessment of Moxetumomab Pasudotox, a Recombinant Immunotoxin with Two Functional Domains
Inna Vainshtein, Ph.D., Principal Scientist, Clinical Pharmacology & DMP, MedImmune LLC
Immunogenicity is an important part of clinical development for biologics as it impacts drug PK, efficacy and safety. Immunogenicity assessment of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, was challenging because of pre-existing anti-toxin antibodies of high prevalence. In addition, two domain structure of the drug required characterization of anti-drug antibodies for domain specificity. This talk will present challenges and solutions to obtain the most accurate assessment of drug immunogenicity.
3:05 Considerations for Development Projects: Combination Therapy
Josefin-Beate Holz, Ph.D., Bioneer-Consulting, part of NDA Group Network Considerations of an integrated development plan for a product as part of a combination regimen impact on candidate selection impact on non-clinical development impact on translational research impact on first-in-human strategy impact on assessment of “clinical Proof-of-Concept”.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 and Early Clinical Development of Synthetic Vaccine Particles (SVP) to Prevent the Formation of Anti-Drug Antibodies
Takashi Kei Kishimoto, Ph.D., CSO, Selecta Biosciences
The development of ADAs is a common cause for treatment failure and adverse events, such as hypersensitivity reactions, associated with biologic therapies. We have recently engineered nanoparticles to provide a tolerogenic signal to antigen-presenting cells to induce antigen-specific immune tolerance. We have demonstrated the ability to mitigate immunogenicity against a broad array of biologic therapies, including coagulation factor VIII in a model of hemophilia A, anti-TNF monoclonal antibody in a model of spontaneous arthritis, immunotoxins in tumor models, pegylated uricase in uricase deficient mice and in nonhuman primates, and adeno-associated vectors used in gene therapy. Tolerogenic nanoparticle therapy for the prevention of ADAs against pegylated uricase in the treatment of gout is currently being evaluated in Phase 2 clinical trials.
4:55 Are Antidrug Antibodies Indicative for Clinical Exposure? - Lessons Learned from a Biosimilar Program
Niklas Czeloth, Ph.D., Head, Biosciences, Biosimilars, Boehringer Ingelheim GmbH
Testing of immunogenicity is an important aspect in biosimilar programs. Here we show the assessment of immunogenicity of BI 695501, a proposed biosimilar to Humira, in a healthy volunteer trial with highly sensitive methodology. During the study ADA responses developed that impacted exposure of the drug. A similar development of ADA rates and titers and a similar impact on exposure was observed equally for BI 695501, US-licensed and EU-approved Humira.
5:25 End of Immunogenicity: Regulatory and Clinical Relevance
5:30 Registration for Dinner Short Courses
Recommended Dinner Short Course*
SC14: Overcoming the Challenges of Immunogenicity Assays, Risk Assessment and Regulatory Requirements - Detailed Agenda
*Separate registration required