IBC Life Sciences
The leading provider of scientific, technological and business information
Main menu
My IBC
Next Generation Protein Therapeutics Summit
CSS
CSS - agenda
conference titles
|
Event Information
Document Title
Immunogenicity of Biologics Agenda
Immunogenicity of Biologics
Main Conference: Monday | Main Conference: Tuesday
1:45
Chairperson's Remarks
Michel Awwad, Ph.D., Director, Pharmacokinetics, Dynamics and Metabolism (PDM), Pfizer
Michel Awwad, Ph.D., Director, Pharmacokinetics, Dynamics and Metabolism (PDM), Pfizer
Nonclinical and Clinical Immunogenicity Assessment and Assays
2:00
Immunogenicity of Aggregates: Myths and Facts
Based on animal experimentation, recent publications and commentaries are suggesting that aggregates are the predominant causes of immunogenicity in patients. Teasing out the cause(s) of immunogenicity in a clinical setting has proved to be a diificult task. It is critical that historic and immunological data of therapeutic proteins in the clinical setting be discussed in an effort to determine what needs to be done to identify the offending elements.
Michel Awwad, Ph.D., Director, Pharmacokinetics, Dynamics and Metabolism (PDM), Pfizer
Based on animal experimentation, recent publications and commentaries are suggesting that aggregates are the predominant causes of immunogenicity in patients. Teasing out the cause(s) of immunogenicity in a clinical setting has proved to be a diificult task. It is critical that historic and immunological data of therapeutic proteins in the clinical setting be discussed in an effort to determine what needs to be done to identify the offending elements.
Michel Awwad, Ph.D., Director, Pharmacokinetics, Dynamics and Metabolism (PDM), Pfizer
2:25
Generation of Anti-idiotype Antibodies as Reagents for the Development of Immunogenicity Assays
The pre-clinical and clinical development of therapeutic antibodies requires assays that measure the potential immune response to the candidate drug. Anti-idiotype antibodies with high affinity and specificity for the candidate drug are ideal reagents for the development of such assays. We describe methods for generating anti-idiotype antibodies using either phage display or hybridoma technology. This has been combined with high-throughput screening utilizing parallel HTRF assays to identify anti-idiotype antibodies with the required specificity and function
Claire Dobson, Ph.D., Associate Director, Display Technology, Medimmune, United Kingdom
The pre-clinical and clinical development of therapeutic antibodies requires assays that measure the potential immune response to the candidate drug. Anti-idiotype antibodies with high affinity and specificity for the candidate drug are ideal reagents for the development of such assays. We describe methods for generating anti-idiotype antibodies using either phage display or hybridoma technology. This has been combined with high-throughput screening utilizing parallel HTRF assays to identify anti-idiotype antibodies with the required specificity and function
Claire Dobson, Ph.D., Associate Director, Display Technology, Medimmune, United Kingdom
2:50
Immunogenicity Assessment in Nonclinical/Clinical Programs: Antibodies and Novel Scaffolds
Monoclonal antibodies (mAbs) are an important and successful class of biotherapeutics, and there is ongoing effort to engineer mAbs to improve efficacy, PK, and/or to reduce safety risks. Immunogenicity strategies for mAbs and their derivatives to support nonclinical and clinical programs will be discussed and case studies of different type of molecules will be presented.
An Song, Ph.D., Associate Director/Senior Scientist, Genentech
Monoclonal antibodies (mAbs) are an important and successful class of biotherapeutics, and there is ongoing effort to engineer mAbs to improve efficacy, PK, and/or to reduce safety risks. Immunogenicity strategies for mAbs and their derivatives to support nonclinical and clinical programs will be discussed and case studies of different type of molecules will be presented.
An Song, Ph.D., Associate Director/Senior Scientist, Genentech
3:15
Generation of Therapeutic Antibodies against Inflammatory Disease and Cancer Targets with a Low Risk of Clinical Immunogenicity
Data from clinical studies show that one of the major problems associated with the use of therapeutic antibodies is the development of an anti-therapeutic antibody response. Such responses have been observed in studies with anti-TNF and integrin antibodies for rheumatoid arthritis and inflammatory bowel disease, as well as with anti-A33, anti-PSMA and anti-CEA-CPG2 conjugates for various cancers. Data will be presented that provides evidence linking the presence of T cell epitopes in the sequences of therapeutic antibodies with immunogenicity observed in patients as well as how antibodies can be engineered to avoid T cell epitopes
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
Data from clinical studies show that one of the major problems associated with the use of therapeutic antibodies is the development of an anti-therapeutic antibody response. Such responses have been observed in studies with anti-TNF and integrin antibodies for rheumatoid arthritis and inflammatory bowel disease, as well as with anti-A33, anti-PSMA and anti-CEA-CPG2 conjugates for various cancers. Data will be presented that provides evidence linking the presence of T cell epitopes in the sequences of therapeutic antibodies with immunogenicity observed in patients as well as how antibodies can be engineered to avoid T cell epitopes
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
3:40
Q&A Panel Discussion with Afternoon Speakers
4:00
Networking Refreshment Break
Featured Presentation
4:30
Subvisible Aggregates and their Impact on Immunogenicity
It is well established that large protein aggregates are produced during the pharmaceutical manufacturing of therapeutic protein products and can enhance immunogenicity. In turn, the patients' immune response can compromise the efficacy and safety of the therapeutic protein. This talk will focus on 0.2-10 µm subvisible protein aggregates, how they may interact with the immune system, the potential impact these particles may have on a product's safety and efficacy profile, the factors affecting this risk, and recent efforts to evaluate and control the associated risk.
Jack Ragheb, M.D., Ph.D., Principal Investigator and Senior Regulatory Research Officer, Laboratory of Immunology, CDER, US FDA
It is well established that large protein aggregates are produced during the pharmaceutical manufacturing of therapeutic protein products and can enhance immunogenicity. In turn, the patients' immune response can compromise the efficacy and safety of the therapeutic protein. This talk will focus on 0.2-10 µm subvisible protein aggregates, how they may interact with the immune system, the potential impact these particles may have on a product's safety and efficacy profile, the factors affecting this risk, and recent efforts to evaluate and control the associated risk.
Jack Ragheb, M.D., Ph.D., Principal Investigator and Senior Regulatory Research Officer, Laboratory of Immunology, CDER, US FDA
Panel Discussion
5:00
Managing Immunogenicity of Therapeutic Proteins
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
Jack Ragheb, M.D., Ph.D., Principal Investigator and Senior Regulatory Research Officer, Laboratory of Immunology, CDER, US FDA
- Regulatory expectations and lessons learned
- Development and validation of immunogenicity assays
- Predicting and engineering reduced immunogenicity
- Strategies for antibodies and alternative scaffolds
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
Jack Ragheb, M.D., Ph.D., Principal Investigator and Senior Regulatory Research Officer, Laboratory of Immunology, CDER, US FDA
5:30
Close of Day One
Main Conference: Monday | Main Conference: Tuesday
7:45
Morning Coffee
8:00
Chairperson's Remarks
H. Kaspar Binz, Ph.D., Vice President Technology and Co-Founder, Molecular Partners, Switzerland
H. Kaspar Binz, Ph.D., Vice President Technology and Co-Founder, Molecular Partners, Switzerland
Engineering Bispecific and Multifunctional Proteins
Keynote Presentation
8:15
Antibody Combinations and Bispecific Antibodies Potently Neutralize Botulinum NeurotoxinsWe have generated human monoclonal antibodies that neutralize botulinum neurotoxins. When individual mAbs are combined, the potency of neutralization increases dramatically. Strategies to capture this potency in a single antibody based molecule will be described.
James D. Marks, M.D., Ph.D., Professor, Department of Anesthesia and Pharmaceutical Chemistry, Member, Comprehensive Cancer Center, University of California, San Francisco
8:45
mAb2: Novel Bispecific Antibodies that are Minimally Changed from IgG
We have developed two novel antibody formats: Fcab, in which antigen-binding sites are introduced into a human Fc fragment and mAb2, in which additional binding sites are engineered into the Fc of an intact antibody. Fcabs allow small therapeutic antibody fragments to be isolated that retain all normal antibody functionalities (antigen binding, effector functions and long half life) while mAb2 represents an elegant way to create bispecific antibodies.
Max Woisetschlager, Ph.D., Director of Target Biology, f-star, Austria
We have developed two novel antibody formats: Fcab, in which antigen-binding sites are introduced into a human Fc fragment and mAb2, in which additional binding sites are engineered into the Fc of an intact antibody. Fcabs allow small therapeutic antibody fragments to be isolated that retain all normal antibody functionalities (antigen binding, effector functions and long half life) while mAb2 represents an elegant way to create bispecific antibodies.
Max Woisetschlager, Ph.D., Director of Target Biology, f-star, Austria
9:10
Bispecific Antibodies: Delivering Combination Therapy in a Single Agent
Abstract not available at time of print.
Scott M. Glaser, Ph.D., Director, Antibody Therapeutics, Biogen Idec, Inc.
Abstract not available at time of print.
Scott M. Glaser, Ph.D., Director, Antibody Therapeutics, Biogen Idec, Inc.
9:35
Surrobodies with Functional Tails
Surrobodies™ are a unique type of antigen-binding protein based on the pre-B cell receptor (pre-BCR). Unlike canonical antibodies, the pre-BCR subunit is a trimer composed of an antibody heavy chain paired with a two subunit surrogate light chain (SLC). The heterodimeric surrogate light chain provides unique opportunities for protein engineering, namely the functional derivatization of their non-immunoglobulin-like tails. Through recent work with both of these novel tails we have recombinantly fused fully active cytokines to generate bifunctional Surrobodies, and similarly fused single chain Fv antibodies to form bispecific Surrobodies. Insights into the utility and combinatorial derivatization of this protein platform will be discussed.
Ramesh Bhatt, Ph.D., Vice President of Research, Sea Lane Biotechnologies
Surrobodies™ are a unique type of antigen-binding protein based on the pre-B cell receptor (pre-BCR). Unlike canonical antibodies, the pre-BCR subunit is a trimer composed of an antibody heavy chain paired with a two subunit surrogate light chain (SLC). The heterodimeric surrogate light chain provides unique opportunities for protein engineering, namely the functional derivatization of their non-immunoglobulin-like tails. Through recent work with both of these novel tails we have recombinantly fused fully active cytokines to generate bifunctional Surrobodies, and similarly fused single chain Fv antibodies to form bispecific Surrobodies. Insights into the utility and combinatorial derivatization of this protein platform will be discussed.
Ramesh Bhatt, Ph.D., Vice President of Research, Sea Lane Biotechnologies
10:00
Networking Refreshment Break and Poster/Exhibit Viewing
Keynote Presentation
10:30
Chemically Programmed Immunity: Antibodies and VaccinesRecently, we invented a new class of immunotherapeutics, Chemically Programmed Antibodies or CovX-bodies, now advancing in numerous clinical trials. This presentation will focus on fundamentals of cpAb technology, its applications, and its ongoing elaboration. Advancing this approach to vaccinology, we show that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccinology in cancer and infectious disease.
Carlos F. Barbas III, Ph.D., Kellogg Professor and Chair, The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute
Emerging Preclinical and Clinical Results
11:00
Advancing DARPins to the Clinic
DARPins are a high-affinity, low-immunogenicity-potential protein drugs that combine the advantages of antibodies and small molecule drugs. The favorable properties of DARPins enable the fast generation of a variety of drug candidates for different indications. MP0112, a best-in-class therapeutic program for the treatment of ocular neovascularization diseases will be presented along with other examples for therapeutic applications where DARPins are superior to monoclonal antibodies.
H. Kaspar Binz, Ph.D., Vice President, Technology and Co-Founder, Molecular Partners, Switzerland
DARPins are a high-affinity, low-immunogenicity-potential protein drugs that combine the advantages of antibodies and small molecule drugs. The favorable properties of DARPins enable the fast generation of a variety of drug candidates for different indications. MP0112, a best-in-class therapeutic program for the treatment of ocular neovascularization diseases will be presented along with other examples for therapeutic applications where DARPins are superior to monoclonal antibodies.
H. Kaspar Binz, Ph.D., Vice President, Technology and Co-Founder, Molecular Partners, Switzerland
11:25
Anticalins, A Unique Class of Targeted Protein Therapeutics
Anticalins are modified versions of human lipocalins. Pieris' lead project PRS-050 (VEGF antagonist) is now entering human studies. Unique features of this drug class such as the ability to bind therapeutically relevant hapten targets will be presented, along with their broad formulation and formatting flexibility.
Kristian Jensen, Ph.D., Chief Operating Officer, Pieris AG, Germany
Anticalins are modified versions of human lipocalins. Pieris' lead project PRS-050 (VEGF antagonist) is now entering human studies. Unique features of this drug class such as the ability to bind therapeutically relevant hapten targets will be presented, along with their broad formulation and formatting flexibility.
Kristian Jensen, Ph.D., Chief Operating Officer, Pieris AG, Germany
Featured Presentation
11:50
Monoclonal Antibodies, Next Generation Antibodies, and Antibody Alternatives: An FDA Perspective
The clinical success of therapeutic monoclonal antibodies in the 1990's spurred an increase in the number of these products in the development pipeline. Currently there are over 200 monoclonal antibodies in clinical development including 2nd generation products and novel antibody constructs. The FDA perspective on the regulation of these products, including quality considerations for different routes of administration and how to communicate with the appropriate review divisions will be discussed.
Ruth Cordoba-Rodriguez, Ph.D., Product Quality Reviewer, Division of Monoclonal Antibodies, Office of Biotechnology Products, CDER, US FDA
The clinical success of therapeutic monoclonal antibodies in the 1990's spurred an increase in the number of these products in the development pipeline. Currently there are over 200 monoclonal antibodies in clinical development including 2nd generation products and novel antibody constructs. The FDA perspective on the regulation of these products, including quality considerations for different routes of administration and how to communicate with the appropriate review divisions will be discussed.
Ruth Cordoba-Rodriguez, Ph.D., Product Quality Reviewer, Division of Monoclonal Antibodies, Office of Biotechnology Products, CDER, US FDA
12:10
Luncheon Discussion & Debate Sessions
(Lunch will be provided)
(Lunch will be provided)
-
Novel scaffolds and scaffold engineering
Discussion Leader: Andreas Plückthun, Ph.D., Professor of Biochemistry, University of Zurich, Switzerland -
Selection and library design
Discussion Leader: Jonathan Davis, Ph.D., Principal Scientist, Protein Design, Adnexus, a Bristol-Myers Squibb Company -
Strategies for plasma half-life extension of biopharmaceuticals
Discussion Leader: Arne Skerra, Ph.D., CEO, XL-protein GmbH, Germany -
De-immunization strategies
Discussion Leader: TBA -
What are the differentiators of next generation biologics in the marketplace?
Discussion Leader: Kristian Jensen, Ph.D., Chief Operating Officer, Pieris AG, Germany -
Blocking multimeric targets with bivalent IgGs; Does immune complex formation pose a safety risk?
Discussion Leader: Volker Schellenberger, Ph.D., Vice President, Drug Discovery, Amunix, Inc. -
Regulatory issues associated with next generation protein therapeutics
Discussion Leaders:
Jack Ragheb, M.D., Ph.D., Principal Investigator and Senior Regulatory Research Officer, Laboratory of Immunology, CDER, US FDA Ruth Cordoba-Rodriguez, Ph.D., Product Quality Reviewer, Division of Monoclonal Antibodies, Office of Biotechnology Products, CDER, US FDA -
Modulating the intracellular undruggable target space
Discussion Leader: Hanjo Hennemann, Ph.D., Executive Director and Head of R&D, Nexigen GmbH, Germany
1:15
Dessert and Exhibit/Poster Viewing
1:45
Chairperson's Remarks
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
Matthew Baker, Ph.D., Chief Scientific Officer, Antitope, United Kingdom
Featured Presentation
2:00
Analysis and Prediction of HLA Class II Restricted Responses
Our group has been involved in the measurement of helper CD4 T cell reactivity in human populations, restricted by HLA class II, in a variety of experimental systems. In some instances responses are beneficial, like in the case of reactivities observed following vaccination or involved in resolution of microbial infections. In other instances the reactivity is undesired, like in the case of drug reactions and allergies. From these analyses overall, certain general features associated with helper CD4 responses in humans can be discerned. This information is relevant in the context of the different methodologies available to predict T cell reactivity, and potential modification to increase or reduce immunogenicity.
Alessandro Sette, Ph.D., Head and Member, Center for Infectious Diseases, Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology
Our group has been involved in the measurement of helper CD4 T cell reactivity in human populations, restricted by HLA class II, in a variety of experimental systems. In some instances responses are beneficial, like in the case of reactivities observed following vaccination or involved in resolution of microbial infections. In other instances the reactivity is undesired, like in the case of drug reactions and allergies. From these analyses overall, certain general features associated with helper CD4 responses in humans can be discerned. This information is relevant in the context of the different methodologies available to predict T cell reactivity, and potential modification to increase or reduce immunogenicity.
Alessandro Sette, Ph.D., Head and Member, Center for Infectious Diseases, Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology
Protein Design and Engineering to Minimize Immunogenicity
2:30
Deimmunization Strategy for Adnectins, Human Fibronectin Based Targeted Biologics
Immunogenicity assessment with in silico tools and in vitro T cell based assays opens the possibility to change the human immune response to therapeutic proteins by protein engineering. Here we will discuss the strategy for minimizing the immunogenic potential of Adnectins in the discovery stage.
Nick Marsh, Ph.D., Director of Pharmacology, Adnexus, a Bristol-Myers Squibb R&D Company
Immunogenicity assessment with in silico tools and in vitro T cell based assays opens the possibility to change the human immune response to therapeutic proteins by protein engineering. Here we will discuss the strategy for minimizing the immunogenic potential of Adnectins in the discovery stage.
Nick Marsh, Ph.D., Director of Pharmacology, Adnexus, a Bristol-Myers Squibb R&D Company
3:00
Deimmunizing Humanized and Fully Human Antibodies
We studied human CD4+ T cell responses in antibody V regions. Early attempts to deimmunize adalimumab were unsuccessful, demonstrating the limits of current methods. We selected functional, deimmunized variants only after the development and application of a comprehensive mutational analysis tool. Deimmunization of antibodies in general will be discussed.
Fiona A. Harding, Ph.D., Associate Director, New Technologies, Facet Biotech
We studied human CD4+ T cell responses in antibody V regions. Early attempts to deimmunize adalimumab were unsuccessful, demonstrating the limits of current methods. We selected functional, deimmunized variants only after the development and application of a comprehensive mutational analysis tool. Deimmunization of antibodies in general will be discussed.
Fiona A. Harding, Ph.D., Associate Director, New Technologies, Facet Biotech
3:30
Networking Refreshment Break and Exhibit/Poster Viewing
4:00
Activation of Natural Regulatory T cells by IgG Fc-derived Peptide "Tregitopes"
We have confirmed that co-administration of T regulatory epitopes (Tregitopes) with a range of proteins in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. We have also demonstrated that Tregitopes are not immunogenic in vivo even emulsified with IFA or CFA. In this presentation, we will review the evidence that consideration of regulatory T cell induction represents a new paradigm for the suppression of immune response to protein therapeutics (like Factor VIII and novel scaffolds), as well as for treatment of autoimmune diseases.
Anne S. De Groot, M.D., Adjunct Associate Professor of Medicine, Brown University; Founder, CEO and CSO, EpiVax, Inc.
We have confirmed that co-administration of T regulatory epitopes (Tregitopes) with a range of proteins in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. We have also demonstrated that Tregitopes are not immunogenic in vivo even emulsified with IFA or CFA. In this presentation, we will review the evidence that consideration of regulatory T cell induction represents a new paradigm for the suppression of immune response to protein therapeutics (like Factor VIII and novel scaffolds), as well as for treatment of autoimmune diseases.
Anne S. De Groot, M.D., Adjunct Associate Professor of Medicine, Brown University; Founder, CEO and CSO, EpiVax, Inc.
Immunogenicity and Alternative Scaffolds
4:30
Assessment of Clinical Immunogenicity for an Adnectin, a Novel Targeted Biologic Evaluated from a PK and PD Perspective
Adnectins are a novel, proprietary class of targeted biologics that are derived from human fibronectin, which is a well-characterized, highly-expressed plasma protein. This presentation will demonstrate the low risk immunogenicity profile of Adnectins, based on the minimal clinical relevance of the immune response in patients treated with CT-322, a VEGFR-2 inhibiting Adnectin.
Jochem Gokemeijer, Principal Scientist, Pharmacology, Adnexus, a Bristol-Myers Squibb R&D Company
Adnectins are a novel, proprietary class of targeted biologics that are derived from human fibronectin, which is a well-characterized, highly-expressed plasma protein. This presentation will demonstrate the low risk immunogenicity profile of Adnectins, based on the minimal clinical relevance of the immune response in patients treated with CT-322, a VEGFR-2 inhibiting Adnectin.
Jochem Gokemeijer, Principal Scientist, Pharmacology, Adnexus, a Bristol-Myers Squibb R&D Company
5:00
Monitoring Potential Immunogenicity: Experience with the First Nanobody® in Clinical Development
Currently 4 llama-derived Nanobodies are in clinical development. The first was the Ablynx anti-vWF Nanobody (ALX-0081). In Phase 1 trials completed to date over 80 subjects/patients have been exposed to ALX-0081 with no immunogenicity detected. Data will be presented on assessment of immunogenic potential of ALX-0081 from bench to bedside.
Debbie Law, Ph.D., Chief Scientific Officer, Ablynx, Belgium
Currently 4 llama-derived Nanobodies are in clinical development. The first was the Ablynx anti-vWF Nanobody (ALX-0081). In Phase 1 trials completed to date over 80 subjects/patients have been exposed to ALX-0081 with no immunogenicity detected. Data will be presented on assessment of immunogenic potential of ALX-0081 from bench to bedside.
Debbie Law, Ph.D., Chief Scientific Officer, Ablynx, Belgium
5:30
Close of Day Two
Bottom menu
Copyright IBC Life Sciences, a part of Informa Life Sciences Group. | Phone: 800.390.4078 | Email: reg@ibcusa.com