IBC Asia (S) Pte Ltd, Singapore
15-17 October 2012
08.30
Registration 09.00
Welcome and opening remarks from the Chair Harald Kropshofer, PhD, Senior Personalized Healthcare Leader, F.Hoffmann-La Roche Ltd., Switzerland | Overview of Immunobiology and Immunogenicity |
09.10
Understanding the immunobiology of immunogenicity This refresher on immunobiology will provide you with an overview of immune recognition and characteristics of protein antigens and their impact on immunogenicity; the humor and cellular immune system as it relates to immunogenicity; immunoglobulin class switching and how it influences ADA and immunogenicity and the basics of HLA and genetic differences in immune recognition. Charles Gullo, Deputy Director, Immunology, Duke/NUS Graduate Medical School, Singapore 09.50
KEYNOTE: Understanding the role of protein aggregates in unwanted immunogenicity Large protein aggregates are known to be produced during the pharmaceutical manufacturing of therapeutic protein products. However, our understanding of how protein aggregate attributes such as size contribute to immunogenicity is limited. This talk will focus on subvisible protein aggregates, how they may interact with the immune system, their potential impact on product safety and efficacy, as well as current regulatory considerations pertaining to the control of these particulates. Dr Jack Ragheb, Chief Medical Research Officer, Laboratory of Immunology, Food & Drug Administration, USA 10.30 Morning refreshments and networking 11.00
CASE STUDY: New concepts in immunogenicity: Induced-self antigens Lucia Mori, Ph.D., Senior Principal Investigator, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 11.40
Risk factors, clinical consequence and mitigation of immunogenicity In the past 20 years, an increasing number of recombinant therapeutic proteins have received approval, and many more are under drug development. However, all recombinant therapeutic proteins have the potential to be immunogenic to some degree. Their general immunologic or safety concerns include the loss of efficacy, general immune and hypersensitivity reactions, serum sickness and neutralization of the natural counterpart, resulting in autoimmune disorder. There are several factors involved in the immunogenicity including host cell-derived impurities, aggregates generated during formulation and storage, immunogenic amino acid sequence, dosing frequency, period and routes, dose, immunological state and genetic background of patients. To overcome the adverse clinical consequences, the risk factors should be eliminated as much as possible. And alternative treatment strategy such as concomitant use of appropriate immune suppressor should be also developed. In the presentation, I would like to introduce the case studies of risk factors, clinical consequence and mitigation of immunogenicity aiming at the less immunogenic therapy. Dr Shingo Niimi, Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Japan 12.20
Round-table discussions: Immunogenicity considerations for the Asian market In this interactive session, participants will have the opportunity to share and discuss their experiences. Topics of discussion will include: - Requirements for immunogenicity data across the region
- Are there Asian-specific immunogenicity concerns?
- Ethnic difference, do we really need it for biosimilars? Is global immunogenicity data enough?
- Interface between Asian and international guidelines
- Local regulatory considerations in designing clinical trials
- Assessing how different populations will behave in assays: Is there a documented difference between the Asian and Caucasian audience?
- Methods for comparing
- How to manage differences
Led by: Sofie Pattjin, Senior Group Leader Immunology, Applied Protein Services, Lonza, UK 13.00 Lunch | Immunogenicity in Pre-Clinical & Clinical Development |
14.00
Using new transgenic mouse models for preclinical assessment of immunogenicity Katharina Steinitz, Ph.D., Scientist, Department of Immunology, Baxter Innovations GmbH, Austria 14.40
Lessons learned from translational immunogenicity Translational immunogenicity is a new field of increasing importance after experiencing cases of poor correlation of pre-clinical versus clinical immunogenicity findings. While it is generally accepted that immunogenicity data obtained in animal models normally are not predictive for the findings in man, it is still the belief that immunogenicity-related safety events in animals may translate into humans. The scope of translational immunogenicity considerations is to deepen our understanding in two directions: (i) help define which immunosafety findings in which animal models are predictive for which patients, (ii) define which immunosafety findings observed in clinical trials; e.g. the Tegenero case, are worth-while being followed-up in the future in new pre-clinical models. Lessons learned on how translational immunogenicity may add benefit to R&D of drugs will be discussed. Harald Kropshofer, PhD, Senior Personalized Healthcare Leader, F.Hoffmann-La Roche Ltd., Switzerland 15.20
Spotlight Presentation This session may be hosted by a leading company who operates in the field of immunogenicity and will offer the opportunity to learn about the latest development and technical advancements in the industry. For details about speaking in this session or other sponsorship opportunities at this conference, please contact Yvonne Leong, Tel: +65 6508 2489 begin_of_the_skype_highlighting +65 6508 2489 end_of_the_skype_highlighting, Email: Yvonne.Leong@ibcasia.com.sg 15.40
Afternoon refreshments and networking | New Developments in Immunogenicity Assays |
16.10
Using technology and innovation to overcome immunogenicity assays’ unique bioanalytical challenges
Mauricio Maia, Ph.D., Scientist, Genentech, USA 16.50
Case study: Development of an ELISA based analytical platform for determination of recombinant hepatitis B virus X (HBx) protein refolding yields The Hepatitis B Virus X (HBx) protein has been well associated with the initiation and development of hepatocellular carcinoma (HCC) and is an ideal representative of the bioprocessing challenges associated with producing novel protein molecules. The current study focuses on the development of a novel ELISA platform to quantitate HBx refolding yields. HBx refolding yields were measured by determining the amount of HBx bound to immobilized GST–p53 on a GSH- functionalized maleimide surface. Refolding yields were distinguished from soluble yields, which were determined by measuring total HBx protein bound to a maleimide surface under reducing conditions. This platform is amenable to scaleup studies for HBx bio-production Anindya Basu, Research Associate, Nanyang Technological University, Singapore 17.30
Closing remarks from the Chair. End of Day 1 09.00 Opening remarks from the Chair
Michael G. Tovey Ph.D., INSERM Director of Research, Laboratory of Biotechnology & Applied Pharmacology, ENS-Cachan, France | Regulatory Expectations and Risk Assessment for Immunogenicity |
09.10
KEYNOTE: Review of the FDA Draft Guidance on Immunogenicity Dr Jack Ragheb, Chief Medical Research Officer, Laboratory of Immunology, Food & Drug Administration, USA 09.50
Overcoming challenges in immunogenicity assessment of biosimilars in preclinical through clinical development This presentation will discuss the evaluation of robust regulatory approaches for successful and cost-effective immunogenicity assessment of biosimilars. You will gain an overview of successful design of immunogenicity testing strategies to ensure effective comparability exercise in addition to overcoming challenges around development of anti-drug and anti-HCP immunoassays for biosimilars. Dr. Arumugam Muruganandam PhD., MBA, Chief Scientific Manager, Head Preclinical and Bioanalytical, Biocon Research Limited, India 10.30
Round-table discussions: Risk assessment of immunogenicity needed for the approval of biopharmaceutical and biosimilar products In this interactive session, participants will have the opportunity to share and discuss their challenges and experiences. Topics of discussion will include: - Strategies for implementing a tiered approach to risk analysis
- Tools and data to assess the risk of immunogenicity prior to clinical studies
- Assessing the impact of immunogenicity: PK/PD correlations
11.10
Morning refreshments and networking | Immunogenicity Considerations in Biosimilars Development |
11.40
Immunogenicity assessment: Improved analytical methods for the successful development of biosimilars Successful development of biosimilars is dependent upon the establishment of validated and standardized assays that allow direct comparisons of the immunogenicity of biosimilars and innovator products. Improved analytical methods based on normalized dual luciferase reporter gene assays have been developed that for the first time allow direct comparisons of the potency and relative immunogenicity of biosimilars and innovator products in fully validated and standardized assays. Case studies will be presented where these methods have been used to compare the relative immunogenicity of interferon beta products and TNF-alpha antagonists of different molecular structure. Michael G. Tovey Ph.D., INSERM Director of Research, Laboratory of Biotechnology & Applied Pharmacology, ENS-Cachan, France. 12.20
Spotlight Presentation This session will be hosted by a leading company who operates in the field of immunogenicity and will offer the opportunity to learn about the latest development and technical advancements in the industry. For details about speaking in this session or other sponsorship opportunities at this conference please contact Yvonne Leong, Tel: +65 6508 2489 begin_of_the_skype_highlighting +65 6508 2489 end_of_the_skype_highlighting, Email: Yvonne.Leong@ibcasia.com.sg 12.40
Lunch 13.40
CASE STUDY: Immunopathogenesis of hand, foot and mouth disease: cross-reactive and Th2-prone immunity Hand, foot and mouth disease (HFMD) is a common sickness among children. Multiple enterovirus species are causative pathogens of the disease. We used immunonformatics tools to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. We then validated the epitope predictions via ELISpot assays and flowcytometry analysis of intracellular staining. We found two dominant CD4+ T cell epitopes located in the EV71 capsid regions. The most dominant eiptope is highly conserved among enterovirus species, including HFMD-related coxsakieviruses as well as echoviruses and polioviruses. We further found that higher levels of Th2 response to the dominant epitope negatively correlated with the slower recovery of HFMD patients. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection, thus limiting HFMD severity. Qibin Leng, Ph.D., Principal Investigator, Professor, Institut Pasteur of Shanghai, Chinese Academy of Sciences, China | Immunogenicity Prediction |
14.20
Prediction of immunogenicity Tools to predict the immunogenic potential of therapeutic proteins or peptides have been used for at least half a decade with the aim to reduce the immunogenicity of drugs in clinics. However, these tools are still considered to be at an infancy state with regards to general acceptance. Although data derived from in silico, in vitro and in vivo models get more and more access to investigational new drug applications and other documents submitted to health authorities, there is still room for optimization. This is mainly due to the following reasons: (i) the need to apply these tools in combination rather than in isolation; (ii) the time it takes to link prediction data with clinical immunogenicity data, (iii) the need to understand the causal link between clinical immunogenicity data and the immunosafety profile of a drug. Case studies will be discussed to provide insight into the complexity of this topic. Harald Kropshofer, PhD, Senior Personalized Healthcare Leader, F.Hoffmann-La Roche Ltd., Switzerland | Assessing & Minimizing Impact of Immunogenicity on the Patient |
15.00
CASE STUDY: Monitoring patients for the presence of anti-drug antibodies in routine medical practice Monitoring patients for the development of anti-drug antibodies (ADA), and their impact on clinical outcome is an important part of drug safety evaluation and is essential for the more effective and rational use of biopharmaceuticals. Quantification of neutralizing ADAs requires the use of cell-based assays that reflect the mode of action of the product. Results will be presented on monitoring patient with Crohn’s disease for the presence of neutralizing ADAs against TNF-alpha antagonists using engineered cells that express a normalized reporter-gene under the control of a drug-responsive promoter. Michael G. Tovey Ph.D., INSERM Director of Research, Laboratory of Biotechnology & Applied Pharmacology, ENS-Cachan, France 15.40
Afternoon refreshments and networking 16.10
Drug eruption revisited A drug eruption is an adverse drug reaction in the skin. Genetic associations between HLA haplotype and drug eruption have been reported. Recently, the immune response in Drug Reaction with Eosinophilia and Systemic Symptom (DRESS), previously thought to be directed against drug components, was shown to be also mediated by herpes-virus specific cytotoxic CD8+ T lymphocyte. We believe that it is essential to understand the immune mechanisms by which some drugs induce hypersensitivity in order to target these pathways to limit drug side effects. Our results suggest a new role for drugs in the pathogenesis of drug eruption. Sebastien Calbo, Research Scientist, Group Leader, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 16.50
Re-engineering biologics for reduced immunogenicity Recombinant therapeutic proteins inherently carry the risk of inducing immunogenicity. While significant effort has been invested in prediction and assessment of immunogenicity, much less has been done with respect to de-immunization of biologics. Approaches ranging from synthetic modifications such as synthetic modifications to glycoengineering are being developed and starting to show promising results in pre-clinical models of immunogenicity. However, much effort remains to be done in validating existing de-immunization technologies and development of novel and innovative approaches for eliminating immunogenicity. Fred J. Aswad, J.D., Ph.D., Senior Staff Scientist, Bayer HealthCare, USA 17.30
Closing remarks from the Chair. End of conference
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