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EVENT DATES
Dec 2018
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Venue

Manchester Grand Hyatt Hotel 1 Market Place San Diego , California 92101
Tel: (619) 232-1234
Website
Google Map

Antibody Engineering & Antibody Therapeutics

Attendees

-

Exhibitors

57

Register

$499 - $2,599

Overview

Exhibitor Prospectus and Kit

Agenda

Dec 9   

9:00am - 1:00pm 240 mins

Info

Full Day Pre-Conference Training Course: Introduction to Antibody Engineering

Introduction to Antibody Engineering (Morning Session)

David Bramhill, PhD - Consultant, Bramhill Biological Consulting, LLC

This is a full-day training course that runs from 9am-5pm

Today’s wealth of knowledge of protein structures will be reviewed along with the genetics of diversity generation of antibodies, to give insights into the best strategies for improving protein function. There is particular emphasis on the choice of a functional assay to monitor effectively the changes in a desired property, and the use of functional enrichment steps where a library approach is employed. Not only is amino acid sequence amenable to engineering, but glycan structures and other modifications may also be engineered. The course will focus on the engineering and enhancement of antibodies and antibody-like scaffolds. Examples will include work on antibody fragment affinity improvement by 100-fold to low pM affinity. Also the engineering of bispecific antibodies by diverse approaches and the adaptation to generate Chimeric Antibody Receptor (CAR) constructs will be discussed. Expression platforms for producing antibodies for testing and for manufacture will also be covered. A background in biochemistry and molecular biology is useful, as the course is designed to progress rapidly from simple to advanced concepts.

Course Agenda

Functions amenable to engineering: affinity, specificity, stability, solubility, immunogenicity

The measure of success: functional assays

Engineering by design

Engineering by random mutation

Designed libraries

Display technologies

Improving manufacturing by protein engineering methods

Glycosylation engineering – function and homogeneity

Other protein modifications

Immunogenicity engineering

Bispecific antibodies

Antibody-drug conjugates (ADCs)

CAR-T strategies

Expression of antibodies and fragments for discovery and testing

Manufacturing platforms for antibodies and fragments

Pre-Conference Workshops

1:00pm - 1:15pm 15 mins

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Workshop Co-Moderators Remarks

Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica

Sai Reddy, PhD - Assistant Professor, Department of Biosystems Science & Engineering, ETH Zurich

1:00pm - 1:15pm 15 mins

Info

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Workshop Co-Moderators' Remarks

Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute

James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer , Panorama Research, Inc.

This workshop will provide an introduction to the immune system with emphasis on how the immune system works and how this knowledge underpins successful immuno-engineering to facilitate development of therapeutic antibodies. Many of the following concepts will be explored: The adaptive immune system, how foreign antigens mount an immune response, how the immune response is regulated and how this can be manipulated, T cell development, the T cell receptor and T-cell subsets.   B cell development, the B cell receptor, immunoglobulin genes and use of transgenic mice for antibody drug discovery.  Antibody anatomy:  the importance of Fv structure for antigen binding and how Fc regions exert effector functions by interaction with complement and with cells expressing activating/inhibitory Fcγ receptors. Immunomodulatory antibodies, checkpoint inhibitors and bispecific T-cell engagers.  Engineered T cells, T cell receptors and CAR-T.  Numerous examples to illustrate these concepts will be provided by expert speakers and interactive discussions and Q&A will be encouraged during the workshop. A summary of the workshop will be posted on the Antibody Society website as part of the Antibody Society Educational programme.

 

1:00pm - 5:00pm 240 mins

Info

Full Day Pre-Conference Training Course: Introduction to Antibody Engineering

Introduction to Antibody Engineering (Afternoon Session)

David Bramhill, PhD - Consultant, Bramhill Biological Consulting, LLC

This is a full-day training course that runs from 9am-5pm

Today’s wealth of knowledge of protein structures will be reviewed along with the genetics of diversity generation of antibodies, to give insights into the best strategies for improving protein function. There is particular emphasis on the choice of a functional assay to monitor effectively the changes in a desired property, and the use of functional enrichment steps where a library approach is employed. Not only is amino acid sequence amenable to engineering, but glycan structures and other modifications may also be engineered. The course will focus on the engineering and enhancement of antibodies and antibody-like scaffolds. Examples will include work on antibody fragment affinity improvement by 100-fold to low pM affinity. Also the engineering of bispecific antibodies by diverse approaches and the adaptation to generate Chimeric Antibody Receptor (CAR) constructs will be discussed. Expression platforms for producing antibodies for testing and for manufacture will also be covered. A background in biochemistry and molecular biology is useful, as the course is designed to progress rapidly from simple to advanced concepts.

Course Agenda

Functions amenable to engineering: affinity, specificity, stability, solubility, immunogenicity

The measure of success: functional assays

Engineering by design

Engineering by random mutation

Designed libraries

Display technologies

Improving manufacturing by protein engineering methods

Glycosylation engineering – function and homogeneity

Other protein modifications

Immunogenicity engineering

Bispecific antibodies

Antibody-drug conjugates (ADCs)

CAR-T strategies

Expression of antibodies and fragments for discovery and testing

Manufacturing platforms for antibodies and fragments

1:15pm - 1:45pm 30 mins

Info

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Ultra-deep Sequencing of the Baseline Human Antibody Repertoire

Bryan Briney, PhD - Assistant Professor, The Scripps Research Institute

In principle, humans can make an antibody response to any non-self-antigen molecule. We have examined the circulating B cell populations of ten healthy human subjects and present the largest single collection of human adaptive immune receptor sequences described to date, comprising almost 3 billion nearly full-length antibody heavy chain sequences. This repertoire-scale dataset reveals a surprising degree of repertoire uniqueness, a subpopulation of public antibody clonotypes, and exceptional repertoire diversity.

1:15pm - 2:00pm 45 mins

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Overview of the Adaptive Immune Response with A Focus on T cells

Jamie Scott, MD, PhD - Professor and Canada Research Chair , Simon Fraser University

1:45pm - 2:15pm 30 mins

Info

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Antibody Discovery and Engineering by Analyzing Repertoire Sequence Space

Sai Reddy, PhD - Assistant Professor, Department of Biosystems Science & Engineering, ETH Zurich

In this presentation I will describe how we are analyzing antibody repertoires by identifying convergent antigen-specific molecular patterns. Molecular convergence is specifically identified by bioinformatic recoding of high-throughput sequencing data of antibody repertoires into constituent biochemical sequence space. By combining this approach with a statistical learning framework, we can accurately predict antigen exposure and antigen specificity based on antibody sequences alone.

2:00pm - 2:30pm 30 mins

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

T cells, Development, TCR and CAR-T

Jamie Scott, MD, PhD - Professor and Canada Research Chair , Simon Fraser University

Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute

2:15pm - 2:45pm 30 mins

Info

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Finding the Needle in the Haystack: Combining Next Generation Sequencing (NGS) and Immunoinformatics to Characterize and Screen Antibody Libraries

Hans de Haard, PhD - Chief Scientific Officer, Argenx

The use of NGS techniques to understand the full richness and diversity of antibody libraries is on the verge of becoming a standard method in the selection of novel antibody leads. As typical selection processes of antibody leads are restricted by the biology of the expression system used, antibody discovery teams will most often focus on the most abundantly expressed clones and miss out on a significant part of the library diversity. Rarely expressed clones will often not be picked up or will vanish during subsequent panning rounds. This presentation will focus on the use of immunoinformatics in conjunction with NGS data to characterize both the abundant and rare antibody leads with the desired attributes from an antibody library, hence giving the scientist insight in the full library diversity, breath and potential library biases. Applying immunoinformatics in combination with NGS allows to screen and cluster millions of antibody clones by V-, J- and germline-gene use, homologs, CDR distribution, canonical structure and the like. The first case study discusses the extraction of representatively expressed sequences from NGS data using Antibody-Extractor Suite. The second case study will focus on library drift over time and over different panning rounds, leading to a shorter selection process and understanding the pre- and post-panning status of a library. A final case study starts from an initial antibody lead, subsequently annotating the NGS data to extract more desirable functional antibodies based on a specific signature and their framework and CDR motifs.

2:30pm - 3:00pm 30 mins

Info

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

The B Cell Response

Larry Green, PhD - CEO, Ablexis & AlivaMab Discovery Services

This talk provides an overview of the orchestrated events occurring in a B cell, starting at the immunoglobulin loci and continuing through activities of the resulting immunoglobulin polypeptides, that yield primary and secondary high-affinity antibody responses.  This knowledge can be exploited for engineering transgenic animals as platforms for therapeutic antibody discovery.

2:45pm - 3:15pm 30 mins

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Networking Refreshment Break

3:00pm - 3:30pm 30 mins

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Networking Refreshment Break

3:15pm - 3:50pm 35 mins

Info

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Optimization of Antibody Discovery from Mouse Repertoires Using Microfluidics, Deep Sequencing, and Yeast Display

David Johnson, PhD, MBA - Founder and CEO, GigaGen, Inc.

Most antibodies on the market were discovered in mouse repertoires using hybridomas, but hybridomas are slow and inefficient. Previously we have reported a method for ultra-fast discovery of rare antibodies from mouse repertoires, with native heavy and light chain pairing intact. In this talk we will discuss how we are applying our technologies to optimize mouse immunization protocols, in order to produce high-affinity antibodies against immuno-oncology targets. Our methods provide the most detailed insight into the response of mice to adjuvant, immunogen format, and administration regimens. We also discuss efforts to generate antibodies against novel epitopes and against antigen targets embedded in cell lysates.

3:30pm - 4:00pm 30 mins

Info

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Antibody Anatomy: The Importance of Antibody Structure

Robyn Stanfield, PhD - Institute Investigator, The Scripps Research Institute

With about 3000 antibody-related structures currently in the PDB there is a wealth of structural information available to help guide antibody engineering and design projects.  In this introduction to antibody structure we will review the basics of antibody structure as well as highlight some of the novel and interesting ways antibodies have evolved to target antigen.

3:50pm - 4:25pm 35 mins

Info

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

Applying Antibody NGS Analysis to Naive Antibody Library Construction

Andre Teixeira, PhD - Scientist, Specifica, Inc.

An extensive set of informatics analysis tools has been developed for the analysis and construction of naive antibody repertoires and libraries. These allow library diversity, both naive and after selection, to be measured and analyzed. Examples of the use of these tools in the construction of naive antibody libraries will be presented.

4:00pm - 4:30pm 30 mins

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Antibody Interactions with Other Components of the Immune System

Paul Parren, PhD - Professor, Leiden University and EVP and Head of R&D, Lava Therapeutics

4:25pm - 5:00pm 35 mins

Workshop A: Next-generation Sequencing for Antibody Library Analysis and Monoclonal Discovery and Engineering

NGS with Proteomics for Antibody Repertoire Analysis and Discovery

Yariv Wine, PhD - Principal Investigator, Systems Immunology and Immunotechnology, Tel Aviv University

4:30pm - 5:00pm 30 mins

Info

Workshop B: Immuno-engineering: Bridging the Immune System and Antibody Therapeutics

Recent Progress with Immunomodulatory Antibodies

James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer , Panorama Research, Inc.

Antibodies provide a unique platform to modulate various functions of both the innate and acquired immune systems. Progress with development of  T cell engager antibodies, checkpoint inhibitors and immune stimulatory antibodies will be described.  Representative pre-clinical models and human clinical studies will be reviewed to illustrate therapeutic concepts and provide a roadmap for future clinical applications. 

5:00pm - 5:05pm 5 mins

Close of Pre-Conference Sessions

Dec 10   

7:15am - 8:15am 60 mins

Registration and Coffee

8:15am - 8:25am 10 mins

Keynote Presentations

Chairperson's Opening Remarks

Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute

8:25am - 9:10am 45 mins

Keynote Presentations

Keynote Presentation TBA

9:10am - 9:15am 5 mins

Keynote Presentations

Keynote Questions

9:15am - 10:00am 45 mins

Info

Keynote Presentations

Towards Next Generation de novo Designed Protein Therapeutics

David Baker, PhD - Professor of Biochemistry, University of Washington

This presentation will describe recent advances in de novo protein design, and the application of these advances to new therapeutic and vaccine modalities.

10:00am - 10:05am 5 mins

Keynote Presentations

Keynote Questions

10:05am - 10:35am 30 mins

Networking Refreshment Break

10:35am - 11:20am 45 mins

Info

Keynote Presentations

TCR Sequencing: Transforming the Diagnosis and Care of Cutaneous T cell Lymphomas

Rachael Clark, MD, PhD - Shing-Yiu Yip and Cecilia M. Hepp Associate Professor of Dermatology, Harvard Medical School

Cutaneous T cell lymphomas are a heterogeneous collection of non-Hodgkin’s lymphomas that arise from T cells tropic for the skin. High throughput TCR sequencing (HTS) is transforming the care of patients with these cancers.  HTS provides rapid and accurate diagnoses, allows direct measurement of malignant T cells in skin before and after therapeutic interventions and discriminates patients with indolent lymphomas from those that will develop progressive, often lethal disease.

11:20am - 11:25am 5 mins

Keynote Presentations

Keynote Questions

11:25am - 12:10pm 45 mins

Info

Keynote Presentations

Benralizumab, A Monoclonal Antibody Engineered for Enhanced NK-cell Mediated Eosinophil Depletion

Bahija Jallal, PhD - President and Executive Vice President, Medimmune and AstraZeneca

Eosinophilia in patients with asthma correlates with increased exacerbation susceptibility. Benralizumab is a humanized, monoclonal antibody that targets the IL-5 receptor alpha antigen on eosinophils. Afucosylation of benralizumab enhances antibody-dependent cell-mediated cytotoxicity activity resulting in potent and rapid depletion of eosinophils. Benralizumab has demonstrated clinical efficacy in two pivotal Phase III trials, resulting in reductions of asthma exacerbations.

12:10pm - 12:15pm 5 mins

Keynote Presentations

Keynote Questions

12:15pm - 1:15pm 60 mins

Info

Scientific Luncheon Briefing 1

Accelerate Your Antibody Discovery with High throughput Array SPR

Yasmina Abdiche, PhD - Chief Scientific Officer, Carterra

Carterra’s new LSA platform enables high throughput antibody characterization, including kinetics, affinity, epitope binning, mapping, and quantitation with minimal sample consumption. We will demonstrate capture kinetics and epitope binning studies on a 384-antibody array, providing key parameters to make informed decisions quickly and confidently to streamline library-to-leads

12:15pm - 1:15pm 60 mins

Info

Scientific Luncheon Briefing 2

Ligand Scientific Briefing

 

12:15pm - 1:15pm 60 mins

Info

Scientific Luncheon Briefing 3

SGI-DNA Scientific Briefing

 

12:15pm - 1:15pm 60 mins

Info

Scientific Luncheon Briefing 4

Positioning for Success in Discovery and Development with AlivaMab Mouse and AlivaMab Discovery Services

Larry Green, PhD - CEO, Ablexis & AlivaMab Discovery Services

Transgenic mice have delivered more than twice as many approved antibody drugs as in vitro display technologies.  Ablexis’ AlivaMab Mouse is the only transgenic animal designed for the efficient discovery and development of therapeutic antibodies.  The team at AlivaMab Discovery Services, with its deep expertise, provides solutions to the challenges of outsourcing the successful discovery of the next generation of human therapeutic antibodies.

 

1:15pm - 1:45pm 30 mins

Info

Scientific Briefing 1

Build Better Antibodies with Machine Learning and SynBio

Claes Gustafsson, Ph.D. - Chief Commercial Officer and Co-Founder, ATUM

ATUM has built and deployed a unique pipeline for the efficient design and manufacturing of antibody genes, proteins and cell lines enabling fast and accurate engineering of optimized antibody molecules. Several independent case studies will be presented.

 

1:15pm - 1:45pm 30 mins

Info

Scientific Briefing 2

Speeding Discovery and Development with High-Throughput, High-Precision Characterization of Clonal Populations

Troy Lionberger, PhD - Senior Manager, Technology Development, Berkeley Lights

Characterizing thousands of single cells or clones rapidly is critical for success in drug discovery and development. Applying light and semiconductor technology in a nanofluidic chip, the Beacon platform isolates single cells, cultures, assays, and exports clones of interest in an automated process. What use to take weeks to months now just takes days.

 

1:15pm - 1:45pm 30 mins

Info

Scientific Briefing 3

Validation of the Alexandria™ Fully Synthetic Human Fab Library

Guy Hermans, Ph.D. - Chief Scientific Officer, Isogenica

We have previously discussed the design and synthesis of Alexandria™, Isogenica's fully synthetic human Fab library. Here, we will provide an update on the validation of this library, both in its fully diversified and common light chain formats, using example antigen selection campaigns.

 

1:15pm - 1:45pm 30 mins

Info

Scientific Briefing 4

WSGR Scientific Briefing

 

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 1

An Integrated Approach to Managing Immunogenicity Risk and Optimum Protein Design

Emilee Knowlton, Ph.D. - Immunology Sales Specialist, ProImmune Inc.

Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages.  ProImmune offers mutational activity mapping for optimal protein design, DC-T/T cell proliferation assays for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.

 

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 2

High Throughput Antibody Characterization Workshop by ForteBio

 

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 3

Mabplex Scientific Briefing

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 4

The Systems Immunology Revolution: How Computational Design Has Enabled Thousands of Clinic-ready Antibodies in Weeks

Jacob Glanville, PhD - Chief Science Officer, Distributed Bio, Inc.

 

2:25pm - 2:30pm 5 mins

Track 1: Novel Methods to Interrogate Receptors As Targets

Chairperson's Remarks

Andreas Plückthun, PhD - Professor and Director, University of Zurich

2:25pm - 2:30pm 5 mins

Track 2: Immunogenicity

Co-Chairs’ Remarks

Paul Carter, PhD - Senior Director and Staff Scientist , Antibody Engineering, Genentech, Inc.

Valerie Quarmby - Staff Scientist and Director, BioAnalytical Sciences, Genentech, A member of the Roche Group, USA

2:30pm - 3:00pm 30 mins

Track 1: Novel Methods to Interrogate Receptors As Targets

Clinically Important Receptors and Techniques for Interrogating Them

Ira Mellman, PhD - VP, Cancer Immunology, Genentech

2:30pm - 3:00pm 30 mins

Info

Track 2: Immunogenicity

Immunogenicity in Biotherapeutic Development

Valerie Quarmby - Staff Scientist and Director, BioAnalytical Sciences, Genentech, A member of the Roche Group, USA

Every biotherapeutic has the potential to elicit unwanted immune responses in treated patients. These may compromise safety or efficacy; if there is a profound impact on the drug’s risk/benefit profile, immunogenicity can even cause termination of drug development. This talk will review immunogenicity and discuss approaches to risk mitigation.

3:00pm - 3:30pm 30 mins

Info

Track 1: Novel Methods to Interrogate Receptors As Targets

More Than Blocking Ligands: Designing Therapeutic Proteins to Surface Receptors

Andreas Plückthun, PhD - Professor and Director, University of Zurich

Therapeutic proteins can be designed that uncouple surface receptors from signaling, and crosslink them in inactive forms and induce their internalization and even degradation. Design strategies to achieve such activities will be discussed for several surface receptors of great importance in a variety of tumors. Several novel analysis methods have been developed to untangle the mode of action of these therapeutic proteins on the cell surface.

3:00pm - 3:30pm 30 mins

Info

Track 2: Immunogenicity

Post Hoc Assessment of the Immunogenicity of Bioengineered Factor VIIa Demonstrates the Use of Preclinical Tools

Kasper Lamberth, PhD - Principal Scientist, Screening & Bioassay Technology, Novo Nordisk A/S

The development of a bioengineered recombinant Factor VIIa (rFVIIa) analog was discontinued after phase 3 trials due to development of ADAs. The FVIIa analog has three mutations compared to the unmodified parent molecule rFVIIa. By using computational and experimental methods we demonstrate that the observed ADAs could have been elicited by neo-epitopes in the engineered-protein

3:30pm - 4:00pm 30 mins

Info

Track 1: Novel Methods to Interrogate Receptors As Targets

Decoding Ligand Receptor Interactions

Bernd Wollscheid, PhD - Professor, Chemical & Systems Biology, Institute of Molecular Systems Biology and Department of Health Sciences and Technology (D-HEST), ETH Zurich

Cellular responses depend on the interactions of extracellular ligands, such as nutrients, growth factors, or drugs, with specific cell-surface receptors. The sensitivity of these interactions to non-physiological conditions makes them challenging to study using in vitro assays. HATRIC-based Ligand Receptor Capture technology (HATRIC-LRC) enables antibody target validation within the native nanoscale organization of the surfaceome.

3:30pm - 4:00pm 30 mins

Track 2: Immunogenicity

A Mechanistic Model of the Immune System to Predict Biotherapeutic Immunogenicity

Xiaoying Chen - Principal Scientist, Pfizer

4:00pm - 4:45pm 45 mins

Networking Refreshment Break and Opening of Exhibit Hall

4:45pm - 5:15pm 30 mins

Info

Track 1: Novel Methods to Interrogate Receptors As Targets

Pathology from the Molecular Scale on Up

Garry Nolan, PhD - Richard and Carlota A. Harris Professor, Stanford School of Medicine

High parameter single cell analysis has driven deep understanding of immune processes.  Using a next-generation single-cell “mass cytometry” platform we quantify surface and cytokine or drug responsive indices of kinase target with 45 or more parameter analyses (e.g. 45 antibodies, viability, nucleic acid content, and relative cell size).  Similarly, we have developed two advanced technologies termed MIBI and CODEX that enable deep phenotyping of solid tissue in both fresh frozen and FFPE formats (50 – 100 markers). Collectively, the systems allow for subcellular analysis from the 70nm resolution scale to whole tissue in 3D. I will present evidence of deep internal order in immune functionality demonstrating that differentiation and immune activities have evolved with a definable “shape”.  Further, specific cellular neighborhoods of immune cells are now definable with unique abilities to affect cellular phenotypes—and these neighborhoods alter in various cancer disease states.   In addition to cancer, these shapes and neighborhoods are altered during immune action and “imprinted” during, and after, pathogen attack, traumatic injury, or auto-immune disease.  Hierarchies of functionally defined trans-cellular modules are observed that can be used for mechanistic and clinical insights in cancer and immune therapies.

4:45pm - 5:15pm 30 mins

Track 2: Immunogenicity

Approaches to Immune Response Mitigation - Use of Systemic and Targeted Approaches to Immune Suppression

Amy Rosenberg, MD - Director, Division of Biotechnology Review and Research III, CDER, US FDA

5:15pm - 5:45pm 30 mins

Info

Track 1: Novel Methods to Interrogate Receptors As Targets

Emerging Approaches to Modulate Receptor Function in Stem Cells

Rami Hannoush, PhD - Principal Scientist & Group Leader, Genentech

The Frizzled (FZD) 7 receptor (FZD7) is enriched in LGR5+ intestinal stem cells and plays a critical role in their self-renewal. This presentation will highlight our group’s peptide drug discovery approaches for targeting specific FZD isoforms, providing new structural insights into the molecular arrangement of members of the FZD receptor family and their mode of regulation. The peptides discovered modulate stem cell function in intestinal organoids and can be utilized as probes to further study the role of individual FZD receptors in cancer stem cell biology.

5:15pm - 5:45pm 30 mins

Info

Track 2: Immunogenicity

Emicizumab Case Study: A Risk Mitigation Practice of Immunogenicity and Its Clinical Relevance

Shuichi Chiba, PhD - Department Manager, Safety Assessment, Chugai Pharmaceutical Co. Ltd.

A case of de-immunization practice during the molecular designing process of an engineered bispecific antibody, emicizumab, will be presented. Although the lead molecule shows low immunogenic potential in in silico analysis, our in vitro assay suggested the higher possibility of immunogenicity. The final candidate has been selected after several trials of in vitro assay and shows low immunogenicity in the clinical trials

5:45pm - 6:15pm 30 mins

Info

Track 1: Novel Methods to Interrogate Receptors As Targets

xPloration™: A Platform Enabling High-throughput Functional Screening of Antibody Libraries

Jennifer Cochran, Ph.D. - Professor and Department Chair of Bioengineering, Stanford University

We present a novel platform for rapid antibody discovery based on cell binding and functional activity readouts. Our microcapillary array technology, which is essentially a 1-20 million well microtiter plate, allows us to screen antibody libraries, displayed on or secreted by yeast and mammalian cells, using a wide variety of assay formats.  Additionally, our human inspired synthetic antibody library is enabling the rapid isolation of antibodies against a number of clinically-relevant targets.

5:45pm - 6:15pm 30 mins

Info

Track 2: Immunogenicity

Secukinumab Demonstrates Significantly Lower In vitro Immunogenicity Potential Compared to Ixekizumab and Other Therapeutic Antibodies

Frank Kolbinger, PhD - Executive Director, Novartis Pharma AG

Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate to severe plaque psoriasis (PsO) demonstrating a rapid onset of action and sustained responses with a favorable safety profile. Biotherapeutics, including monoclonal antibodies (mAbs), can be immunogenic, potentially generating anti-drug antibodies (ADAs) that can cause hypersensitivity and/or compromise efficacy. Clinically, secukinumab has been shown to have a low rate of ADAs in a pooled analysis of Phase 3 trials. Using in vitro techniques, we wanted to understand the potential reasons for this low clinical immunogenicity incidence rate. We therefore analyzed peptides presented by antigen-presenting cells and T cell precursor frequencies for 4 different mAbs: secukinumab, ixekizumab, adalimumab and ustekinumab and observed that secukinumab demonstrated a low in vitro immunogenicity potential compared with other therapeutic antibodies used to treat PsO patients. Results from these in vitro studies will be presented along with a more detailed evaluation of the T-cell peptide specificities of antibody-reactive T-cell clones.

6:15pm - 7:15pm 60 mins

Info

Opening Night Reception with Exhibits and Poster Viewing

Dec 11   

7:30am - 8:00am 30 mins

Scientific Breakfast Briefing #1

Advances in Automated Microfluidic Capillary Electrophoresis for IgG Analysis, from Screening through QC, using PerkinElmer’s IntelliChip™ Assays

James White, PhD - Senior Application Scientist, PerkinElmer

7:30am - 8:00am 30 mins

Info

Scientific Breakfast Briefing #2

Harbour Mice Generated Fully Human Heavy Chain Only Antibodies (HCAbs) for Mono- and Bi-specific Antibody Therapeutics

Minmin Qin, PhD - Senior Vice President and Head of CMC, Harbour BioMed

HCAbs are efficiently generated from transgenic Harbour Mice where mouse VH loci were replaced with selected human VH genes, concurrent with the CH1 gene deletion. These HCAbs resemble camelid HCAbs in size and solubility, but have added advantages due to their human origin. HBM4003, a CTLA4 antagonist, will be reported to showcase Harbour's HCAb versatility as monospecific therapeutics. Furthermore, their use as natural building blocks for bispecific antibodies will be discussed.

8:10am - 8:15am 5 mins

Track 1: Novel Indications for Therapeutic Antibodies

Chairman's Remarks

James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer , Panorama Research, Inc.

8:10am - 8:15am 5 mins

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Co-Chairs' Remarks

Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute

Janine Schuurman, Ph.D. - Vice President, Research, Genmab

8:15am - 8:45am 30 mins

Track 1: Novel Indications for Therapeutic Antibodies

ab initio Antibody Design for Novel Targets

Monica Berrondo, PhD - CEO, Macromoltek

8:15am - 8:45am 30 mins

Info

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Targeting GD2 on Diffuse Intrinsic Pontine Glioma (DIPG): A Tumor Driven Target

Robbie Majzner, MD - Instructor, Pediatrics - Hematology & Oncology, Stanford

Diffuse Intrinsic Pontine Glioma (DIPG) is a universally fatal high-grade glioma of the brainstem that occurs in children. We have identified GD2 as overexpressed on DIPG and other gliomas bearing the H3K27M mutation. GD2 CAR T cells demonstrate potent activity against xenograft models of DIPG. Despite low level expression of GD2 on brain tissues, we did not observe on target, off tumor toxicity. We did observe toxicity in some models that appears to be due to the precarious neuroanatomical location of these tumors.

8:45am - 9:15am 30 mins

Info

Track 1: Novel Indications for Therapeutic Antibodies

IL1RAP as a Therapeutic Target

Goran Forsberg, PhD - Chief Executive Officer, Cantargia AB

IL1RAP is a coreceptor for several cytokine receptors, such as the IL-1, IL-33 and IL-36 receptors, and is essential for signalling through these receptors. IL-1, IL-33 and IL-36 all mediate pro-inflammatory signalling and blocking of these signalling pathways with antibodies against IL1RAP have potential in autoimmune, inflammatory as well as in malignant diseases. An antibody against IL1RAP is currently in clinical development in oncology.

8:45am - 9:15am 30 mins

Info

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Glypicans as CAR T-Cell Therapy Targets in Cancer

Mitchell Ho, PhD - Senior Investigator, Laboratory of Molecular Biology, NIH NCI

CAR T-cell therapy has emerged as an attractive component in the cancer treatment landscape. However, for most cancers we know little about what tumor antigens can be safely and effectively targeted. We previously studied mesothelin as a target for many cancers. In recent years, we have investigated cell surface glypicans including GPC3 and GPC2 as potential targets for treating liver cancer, childhood cancers (e.g. neuroblastoma) and other cancers.

9:15am - 9:45am 30 mins

Info

Track 1: Novel Indications for Therapeutic Antibodies

Discovery of GDF15 Receptor (GFRAL/RET) and Its Novel Biological Pathway that Controls Body Weight and Its Clinical Applications

David Shen, PhD - SVP, Biologics Research and CMC, NGM Biopharmaceuticals

We have identified GDF15 as a potent hormone for potentially treating diabetes and weight loss. GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses. In the course of pursuing its molecular mechanism, we have undertaken extensive biochemical, cell-based, and functional screenings, culminating in the discovery of GFRAL/RET as the cognate receptor for GDF15. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. Furthermore, we have co-crystalized GDF15 with its cognate receptor GFRAL to gain insight of detailed molecular interactions. We have then identified an array of antagonistic antibodies, including competitive, non-competitive and allosteric modulators. Co-crystal structures of antibodies with GFRAL further defined the nature of interactions of these modulators with GDF15 receptor; and this led us to have successfully generated antibodies intended for preventing weight loss in cancer cachexia. Presently GDF15 for treating diabetes and weight loss is in development by Merck through licensing, and antibody for GFRAL is in phase 1 clinical study by NGM.

9:15am - 9:45am 30 mins

Info

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Correlating Function of Anti-ROR1 CARs with Binder Origin and Characteristics

Alex Kinna, PhD - Research Scientist, Autolus

ROR1 is a potential therapeutic target in both haematological and solid tumour immunotherapy. CARs with binding domains isolated from either immunised animals or a human phage display library were compared. We demonstrate that binder origin and biophysical properties influence the functional performance of CARs.

9:45am - 10:30am 45 mins

Info

Networking Refreshment Break, Exhibit and Poster Viewing

10:30am - 11:00am 30 mins

Info

Track 1: Novel Indications for Therapeutic Antibodies

Integrin Alpha11beta1, A Potential Anti-fibrosis Target on Fibroblasts

Donald Gullberg, PhD - Professor, Department of Biomedicine, University of Bergen

Integrin a11b1 is a receptor for fibrillar collagens with a central role in cell adhesion, collagen reorganization and tissue homeostasis. Work with animal models have revealed its role in tooth eruption and wound healing. More recent work has suggested its involvement in heart and skin fibrosis. It is suggested that novel a11b1- based tools (including monoclonal antibodies and transgenic mice), will be central to elucidating molecular mechanisms of tissue fibrosis.

10:30am - 11:00am 30 mins

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Late Breaking Presentation

11:00am - 11:30am 30 mins

Info

Track 1: Novel Indications for Therapeutic Antibodies

Collagen Fibrillogenesis Inhibitory Antibody

Andrzej Fertala, PhD - Biomet Professor of Orthopaedic Research, Thomas Jefferson University

Fibrosis is a serious complication of injuries to tissues and organs. The formation of collagen-rich deposits is the ultimate problem that affects functions of fibrotic tissues. This presentation identifies collagen fibrillogenesis as an anti-fibrotic target. The antibody-based inhibition of collagen fibril formation demonstrates efficacy in relevant models of fibrosis

11:00am - 11:30am 30 mins

Info

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Adoptive T-cell Therapies against Novel Intracellular Targets

Harpreet Singh, PhD - Managing Director, CSO and Co-Founder, Immatics Biotechnologies GmbH

CAR-T cell therapies to membrane antigens have been highly successful in hematological but not in solid tumors. Addressing intracellular pMHC targets only possible through T-cell receptor (TCR)-based approaches is thought to be a key element to successful treatment of solid cancers. Using the XPRESIDENT platform to discover and validate novel targets and TCRs, we will be reporting on clinical trials using endogenous and gene-engineered T cells in various solid cancers conducted at MD Anderson Cancer Center.

11:30am - 12:00pm 30 mins

Info

Track 1: Novel Indications for Therapeutic Antibodies

A Novel Therapeutic Antibody for Inflammatory and Fibrotic Diseases Targeting LRP6, A Master Regulator of Tissue Repair

Andrew Mendelsohn, Ph.D. - Director, Molecular Biology, Panorama Research, Inc.

We are developing a therapeutic antibody for Inflammation and fibrosis targeting LRP6, a master regulator of tissue repair. LRP6 is a key co-receptor for canonical Wnt signaling that plays role in orchestrating wound healing and tissue repair.  Because the LRP6 receptor has a large extracellular region with two separate ligand binding domains, successfully targeting LRP6 signaling requires novel antibody engineering.

11:30am - 12:00pm 30 mins

Info

Track 2: CAR-T/T-cell Recruitment in Solid Tumors

Oncolytic Vaccines Encoding T cell Engagers: Tumor-targeted Delivery and Anti-tumor Synergy

Christine Engeland, MD, PhD - Physician-Scientist, NCT/DKFZ

Challenges in current cancer immunotherapy include increasing response rates and decreasing toxicity. We have developed tumor-selective oncolytic vectors for delivery of immunomodulators to avoid systemic exposure and mitigate toxicity. Furthermore, vector-mediated oncolysis serves as an in situ tumor vaccine, inducing synergistic anti-tumor immune responses. This talk highlights the versatility of our vector system and avenues for clinical translation.

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 1

NGS is Accelerating Therapeutic Antibody Discovery - What Lies Beyond? Predicting the Successful Biologic Drugs of the Future

Jannick Bendtsen, PhD - Vice President of Technology Services, Geneious Biologics

NGS is accelerating the field of therapeutic antibody research. Scientists face a growing need for software that enables them to efficiently and accurately analyze their rapidly expanding data sets. Automating the screening, annotation and analysis of antibody sequences will free research scientists to spend less time managing data and more time focused on science - but what lies beyond as innovators start applying pattern recognition technologies to their data?

 

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 2

Ligand Scientific Briefings

 

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 3

Abzena Scientific Briefing

 

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 4

Soteria®: Revolutionizing Oral Delivery of Antibodies

Vipul Yadav, PhD - Director of Product Development, Intract Pharma Ltd

Oral delivery of biologics is still considered as the ‘holy grail’, however, very few products have reached the market. Intract has invented the Soteria® technology that involves targeted delivery of biologics to the colon - which utilises the clinically validated Phloral® coating - and protects the biologic from degradation in the colon where it can exert its therapeutic effect.

 

12:30pm - 1:45pm 75 mins

Networking Luncheon, Exhibit and Poster Viewing

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 1

Affinity Maturation of An Anti-Cathepsin S Antibody Using a Rational Library Design Approach

Richard Buick, PhD - Chief Technical Officer, Fusion Antibodies plc

A case study will be shown for the affinity maturation of an anti-Cathepsin S antibody by rational library design followed by molecular docking of variants in a step-wise combinatorial fashion.

 

1:45pm - 2:15pm 30 mins

Scientific Briefing 2

Scientific Briefing TBA

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 3

MaxCyte Scientific Briefings

 

1:45pm - 2:15pm 30 mins

Info

Scientific Briefing 4

Use of Mammalian Virus Display to Select Antibodies Specific for Complex Membrane Antigens

Ernest Smith, PhD - Chief Scientific Officer, Vaccinex, Inc.

We have developed a technology to enable direct incorporation of multipass membrane proteins such as GPCRs and ion channels into the membrane of a mammalian virus. Antigen expressing virus can be readily purified and used for antibody selection. This method is rapid, does not require any detergents or refolding and produces properly folded protein that is necessary for antibody selection.

 

2:25pm - 2:30pm 5 mins

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Co-Chair's Remarks

Anne Messer, PhD - Principal Investigator, Neural Stem Cell Institute

James Huston, PhD - Chairman, The Antibody Society , Huston BioConsulting, LLC

2:25pm - 2:30pm 5 mins

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Chairwoman's Remarks

Janine Schuurman, Ph.D. - Vice President, Research, Genmab

Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute

2:30pm - 3:00pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Antibody Transport Vehicle (ATV): A Novel Brain Delivery Platform

Mark Dennis, PhD - Fellow, Denali Therapeutics

The Antibody Transport Vehicle (ATV) enables the delivery of large molecule therapeutics to the brain for the treatment of neurological diseases. The ATV platform contains an engineered Fc domain that binds the transferrin receptor and utilizes receptor-mediated transcytosis to cross the BBB. Transport in nonhuman primates was assessed by the inhibition of beta-secretase 1 (BACE1) in brain which was robustly inhibited by ATV:BACE1 leading to a sustained reduction in amyloid beta levels.

2:30pm - 3:00pm 30 mins

Info

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Using VHH Antibody Fragments to Target the Tumor Microenvironment

Stephanie Dougan, PhD - Principal Investigator, Dana-Farber Cancer Institute

Although cytokines modulate immune responses, systemic administration necessitates high doses. With the use of cytokines fused to alpaca antibody fragments (VHHs) specific for PD-L1, systemic delivery of low doses led to intratumoral localization, allowing for therapeutic effects in pancreatic cancer models. Many tumors and tumor-infiltrating myeloid cells express PD-L1, rendering them potentially susceptible to this form of targeted immunotherapy.

3:00pm - 3:30pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Structural and Functional Analyses and Humanization of an Anti-pyroglutamate-3 Abeta Antibody for Immunotherapy of Alzheimer’s Disease

Thore Hettmann, PhD - Project Management, Probiodrug AG

N-terminally truncated and post-translationally modified Abeta peptides, pGlu-Abeta, are emerging targets for therapeutic approaches against Alzheimer’s Disease (AD). In contrast to common anti-Abeta therapies, these antibodies are tailored approaches to clear highly neuro/synaptotoxic forms of soluble and aggregated Abeta, which are directly implicated with cognitive decline in AD patients. Here, we present the structural and functional analyses of pGlu-Abeta antibodies. The structural basis of target binding specificity, the humanization, de-immunization and effector function modifications of the lead therapeutic antibody, PBD-C06, will be presented.

3:00pm - 3:30pm 30 mins

Info

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Antibody Fragment Drug Conjugates (FDCs): Tailored Therapies for Solid Tumors

Mahendra Deonarain, PhD - Chief Executive and Science Officer, Antikor Biopharma Ltd

Antikor has harnessed the tumor penetration and rapid clearance properties of single-chain Fvs to make them more effective and tolerated alternatives to ADCs. We will present data on our antibody discovery capabilities that can lead to a potentially new class of therapeutics of high-payload carrying FDCs for gastric cancer and beyond.

3:30pm - 4:00pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Targeting of Nonlipidated, Aggregated ApoE with Antibodies for Alzheimer’s Disease Therapy

Nga Bien-Ly, PhD - Scientist, Denali Therapeutics

The strongest genetic factor for late-onset Alzheimer’s disease is the apolipoprotein E4 (apoE4) allele with overwhelming evidence pointing to its pathogenic role in amyloid β (Aβ) aggregation and clearance. To test whether anti-human apoE antibodies decrease Aβ pathology in APOE4KIxAPPPS1-21 mice, we administered centrally and peripherally apoE antibodies that preferentially bind nonlipidated, aggregated apoE. We observed decreased amyloid accumulation that was dependent on Fcgamma receptor binding, demonstrating the therapeutic potential of targeting microglia to aggregated apoE species in Aβ plaques.

3:30pm - 4:00pm 30 mins

Info

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Preclinical Validation of a Site-specifically Conjugated, ROR1-specific Anthracycline-ADC with Potent Immune-stimulatory Functions

Roger Beerli, PhD - Chief Scientific Officer, NBE-Therapeutics Ltd.

We present a novel ADC based on site-specific conjugation of a derivative of the anthracycline PNU-159682 using the transpeptidase Sortase A. The use of a non-cleavable peptide linker provides exquisite stability, whereas the anthracycline payload endows the ADC with superior potency combined with attractive immune-oncology properties intrinsic to this class of payloads. Validating data obtained in numerous PDX models, as well as in immunocompetent syngeneic models, will be presented.

4:00pm - 4:45pm 45 mins

Info

Networking Refreshment Break, Exhibit and Poster Viewing

 

4:45pm - 5:15pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Gene Therapy Delivery of Neuro-immunotherapeutics

Anne Messer, PhD - Principal Investigator, Neural Stem Cell Institute

Recent advances in gene therapy for neurological diseases include several clinical trials of gene replacements, and further engineering of viral vectors capsids to allow targeted and/or systemic delivery. This approach is especially powerful for antibody fragments that have been engineered to function intracellularly as intrabodies, and it is also being applied more broadly for several neurodegenerative diseases.

4:45pm - 5:15pm 30 mins

Info

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Immunotherapy with CD3 Bispecific Antibody in Immuno Competent Mouse Models

Thorbald Van Hall, PhD - Associate Professor, Leiden University Medical Center

Immunotherapy of cancer with CD3-targeting bispecific antibodies (CD3 bsAb) is a very promising strategy, also for solid malignancies. Xenograft mouse models often fail to fully recapitulate the natural tumor microenvironment, and therefore we investigated the immunological consequences of CD3 bsAb therapy in fully immune-competent mouse tumor models.

5:15pm - 5:45pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Targeted Degradation of Neurodegenerative Proteins with Bifunctional Intrabodies

David Butler, PhD - Principal Investigator, Neural Stem Cell Institute

Currently, there are no treatments available that stop or slow the progression of Huntington’s Disease, Parkinson’s Disease, and tauopathies. To solve this problem, our lab developed bifunctional intrabodies that targeted mutant huntingtin protein and α-synuclein to the proteasome for degradation via a PEST degron fusion. I am currently utilizing induced pluripotent stem cell (iPSC) disease modeling to validate candidate intrabodies for treatment of neurodegenerative disorders.

5:15pm - 5:45pm 30 mins

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Data and Learnings from JTX-2011 and Other Earlier Stage Projects

Deborah Law - Chief Scientific Officer, Jounce Therapeutics

5:45pm - 6:15pm 30 mins

Info

Track 1:Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

Mechanisms of Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies

Einar Sigurdsson, PhD - Professor, Department of Neuroscience and Physiology, NYU School of Medicine

Active or passive tau immunotherapies have advanced to eight clinical trials, although the mechanisms involved are not well defined. Some tau antibodies appear to work primarily extracellularly whereas others can also clear/neutralize tau intracellularly. Since most pathological tau is within neurons, such broadly acting antibodies are likely to be more efficacious than those that only work extracellularly. In addition, humanization can dramatically change antibody properties and thereby may affect their biodistribution and efficacy. Hence, those derivatives need to be re-examined thoroughly prior to clinical trials. These therapeutic studies have also led to the development of antibody fragments as imaging probes, which are more specific than the β-sheet dyes that are being tested in humans, and may then allow tailoring the immunotherapy to the most prominent pathological tau epitopes in each subject.

5:45pm - 6:15pm 30 mins

Track 2: Meeting Challenges for Antibody Therapies in the Tumor Microenvironment

Presentation Title TBA

John Desjarlais - SVP and Chief Scientific Officer, Xencor, Inc.

6:15pm - 7:15pm 60 mins

Info

Networking Reception, Exhibit and Poster Viewing

Dec 12   

7:30am - 8:00am 30 mins

Info

Scientific Breakfast Briefing #1

AbTHENEUM Technology Delivers Antibody Metadata: Native Sequence Pairs Correlated with Binding Activity against Your Targeted Region of Antigen

Chun-Nan Chen, PhD - Chief Scientific Officer, Single Cell Technology, Inc.

The best chance to find a low frequency hit is to capture a broad diversity of the immune response. Single Cell Technology uses affinity-maturated B cells on a platform that collects metadata per cell: binding activity against multiple screening molecules is correlated with native VH and VL sequence pairs. Case studies from antibody campaigns will be presented.

 

7:30am - 8:00am 30 mins

Info

Scientific Breakfast Briefing #2

Combining High-Throughput Single-Cell Screening with Ig-Seq: Deep Screening and Functional Annotation Of Human Antibody Repertoires

Sherie Duncan, PhD - Manager Programs and Partnerships, AbCellera

The application of high-throughput sequencing to antibody repertoires (Ig-Seq) enables comprehensive analysis of natural immune responses. A key challenge to realizing its potential for vaccine development, antibody discovery, and diagnostics is connecting sequence diversity with functional data. We present the combination of Ig-Seq with AbCellera’s microfluidic single-cell screening technology to enable deep profiling and functional annotation of human immune responses to viral pathogens.

 

8:10am - 8:15am 5 mins

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Co-Chairs Remarks

Jamie Scott, MD, PhD - Professor and Canada Research Chair , Simon Fraser University

Eline (Nina) Luning Prak, MD, PhD - Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School

8:10am - 8:15am 5 mins

Track 2: Vaccines and Antibodies in Infectious Disease

Co-Chair's Remarks

Paul Parren, PhD - Professor, Leiden University and EVP and Head of R&D, Lava Therapeutics

Dennis Burton, PhD - Professor and Chairman, Department of Immunology & Microbiology, The Scripps Research Institute

8:15am - 8:45am 30 mins

Info

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Defining and Tracking Large B Cell Clones in Humans

Eline (Nina) Luning Prak, MD, PhD - Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School

Clonal expansion is a fundamental property of adaptive immunity.  Monitoring immune responses as well as evaluating and monitoring patients for lymphoproliferative disorders all require robust methods for defining clone size and tracking clones across different samples. To perform these studies, we have developed a series of experimental and analytical methods.  Evaluations of B cells will be described that highlight some of these methods revealing how clones can be studied to define tissue-based B cell networks, B-cell subsets and clonal evolution of malignant B cells.    

8:15am - 8:45am 30 mins

Info

Track 2: Vaccines and Antibodies in Infectious Disease

Imaging Complement by Phase-plate Cryo-electron Tomography from Initiation to Pore Formation

Thom Sharp, PhD - Assistant Professor, Leiden University Medical Center

We have used cryo-electron tomography to image the build-up of complement complexes on liposomal membrane surfaces, from activation by antibody complexes to stepwise formation of terminal pathway components. We recently determined the structure of hexameric and pentameric IgM-C1 initiation complexes, where we observed complete density for the C1r2s2 proteases bound to C1q, as well as C1s interacting with C4b, providing novel insights into C4 cleavage and subsequent C4b2a-C3 convertase formation.

8:45am - 9:15am 30 mins

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Speaker TBA

8:45am - 9:15am 30 mins

Info

Track 2: Vaccines and Antibodies in Infectious Disease

Complement Activation Alone Drives Efficacy of a Novel Anti-gonococcal Monoclonal Antibody

Sanjay Ram, Ph.D - Professor of Medicine, University of Massachusetts Medical School

The human IgG1 Fc of a chimeric monoclonal antibody (mAb) directed against gonococcal lipooligosaccharide was engineered to enhance Fc:Fc interactions and hexamerisation following surface-target binding, thereby increasing complement activation (HexaBody® technology). This modified mAb showed significantly greater bactericidal activity in vitro and efficacy in mice compared with ‘Fc-unmodified’ chimeric 2C7. Efficacy of the mAb in a mouse model of gonococcal colonization required terminal complement pathway activation.

9:15am - 9:45am 30 mins

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Exploring How Pre-immune B-cell Receptor Repertoires Are Shaped

Duane Wesemann, MD, PhD - Assistant Professor in Medicine, Harvard Medical School, Brigham and Women's Hospital

9:15am - 9:45am 30 mins

Info

Track 2: Vaccines and Antibodies in Infectious Disease

Engineered Antibodies against Plasmodium falciparum Transmission for Elimination of Malaria

Robert Sauerwein, MD, PhD - Professor, Faculty of Medical Sciences, Radboud UMC

Malaria transmission in the population starts with mosquitoes’ blood-feeding on humans infected with Plasmodium parasites. In the mosquito midgut, sexual forms egress from the red blood cells and males fertilize female parasites. Pfs48/45 and Pfs230 are essential proteins in this process. Transmission blocking antibodies are critical for eradication of malaria. We developed (engineered) monoclonal antibodies with strong potency to block fertilization. The newly generated antibodies provide new leads for the development of passive immunization strategies against Plasmodium transmission.

9:45am - 10:30am 45 mins

Networking Refreshment Break in Poster & Exhibit Hall

10:30am - 11:00am 30 mins

Info

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Antibody Repertoire Responses to Infection and Vaccination

Scott Boyd, MD, PhD - Assistant Professor, Stanford University Medical Center

Almost all successful vaccines rely on antibody production and the formation of B cell memory, but the diversity of individual humoral responses has posed challenges in human immunological research. By combining single-cell analysis of antibody specificities and high-throughput sequencing of B cell receptor repertoires, we have identified common features of the antibody responses of human subjects to vaccinations and infections, including convergent antibody species with highly similar sequences.

10:30am - 11:00am 30 mins

Info

Track 2: Vaccines and Antibodies in Infectious Disease

Antibody Recognition of P. falciparum Circumsporozoite Protein and Implications for Malaria Vaccine Design

Ian Wilson, D.Phil - Hansen Professor of Structural Biology, The Scripps Research Institute

RTS,S is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats. We have determined structures of antibodies from a human RTS,S trial that recognize the NANP repeats and inhibit parasite development in the liver. Such structural insights may aid in design of a next-generation malaria vaccine

11:00am - 11:30am 30 mins

Info

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

B Cell Repertoire Selection in Early Multiple Sclerosis

Nancy Monson, PhD - Associate Professor, UT Southwestern

Patients at high risk to develop Multiple Sclerosis display an expansion of plasmablasts and an antibody gene signature that is distinct. The data supporting these observations will be presented in this talk along with implications for diagnosis and therapy of Multiple Sclerosis.

11:00am - 11:30am 30 mins

Track 2: Vaccines and Antibodies in Infectious Disease

Malaria Prevention by Passive Administration of a Monoclonal Antibody to a Unique Junctional Epitope on the P. falciparum Circumsporozoite Protein

Robert Seder, MD - Chief, Cellular Immunology Section, Vaccine Research Center, NIAID, NIH

11:30am - 12:00pm 30 mins

Info

Track 1: Clonal Expansion of Lymphocytes in Immune Repertoires

Anti-tumor Immune Repertoires

Daniel Emerling, PhD - Senior Vice President, Research, Atreca, Inc

Adaptive immunity to tumors not only relies on T cells, but also involves immunoglobulins. We sequenced immunoglobulin repertoires from over 100 cancer patients and used sequence and clonal lineage analyses to select specific antibodies for recombinant expression and characterization. Screened antibodies bound non-autologous human tumor tissues at high rates, consistent with recognition of public tumor antigens. Some antibodies caused tumor regression in mouse cancer models. Clonal lineages in immune responses to cancer can be a repository of anti-tumor receptors.

11:30am - 12:00pm 30 mins

Info

Track 2: Vaccines and Antibodies in Infectious Disease

Rapid Identification of Broad and Potent “Super-antibodies” to Speed Pandemic Responses

Laura Walker, Ph.D - Associate Director, Adimab, LLC.

A new generation of broad and highly potent "super-antibodies" offer promise for the prophylaxis and therapy of a wide range of infections. In this talk, I will provide an overview of Adimab's B cell isolation platform and describe how we have used this technology for the isolation of super-antibodies to multiple emerging viral pathogens.

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 1

Computational Approaches for Optimizing the Developability of Biotherapeutics

Nels Thorsteinson - Scientific Services Manager, Biologics, Chemical Computing Group

mAb candidates identified from high-throughput screening or binding affinity optimization often present liabilities for developability, such as aggregation-prone regions or poor solution behavior. In this work, we optimized an integrin α11 binding mAb for developability using homology modeling and rational design where reducing hydrophobic surface patches improved HIC behavior. A retrospective data analysis demonstrates that 3D descriptors and multi-parameter models can screen candidates and enrich libraries with favorable developability properties for a range of biotherapeutics.

 

12:00pm - 12:30pm 30 mins

Info

Scientific Briefing 2

A Computational Framework for Predicting Protein Liabilities & Improvement of Antibody Developability

Johannes Maier, PhD - Principal Scientist, Schrodinger

We are presenting a novel method for predicting aggregation hotspots on proteins/peptides termed "AggScore". This method is entirely structure-based and is agnostic to the presence of natural amino acids or training to amyoloidic aggregation. In addition, we introduce a machine-learning engine to address protein liabilities termed BioQSPR and showcase its versatility and applicability in retrospective and prospective examples

 

12:00pm - 12:30pm 30 mins

Scientific Briefing 3

TBA

12:30pm - 2:10pm 100 mins

Networking Luncheon, Last Chance for Exhibit and Poster Viewing

2:10pm - 2:15pm 5 mins

Track 1: Microbiome

Co-Chair's Remarks

Bertrand Routy, MD, PhD - Assistant Professor, CRCHUM, University of Montreal Research Center

Paul Parren, PhD - Professor, Leiden University and EVP and Head of R&D, Lava Therapeutics

2:10pm - 2:15pm 5 mins

Track 2: Libraries, Display, Selection and Screening

Chairperson's Remarks

Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica

2:15pm - 2:45pm 30 mins

Info

Track 1: Microbiome

Taking the Microbiome and Antibody Therapies to Market: Like Peanut Butter and Jelly or More Like Oil and Water?

Keith Batchelder, MD - CEO and Founder, Genomic Healthcare Strategies

 

Traditional Pharma therapies and Companion Diagnostics still have fraught economic relationships. Will Microbiome and Antibodies be better/worse/different?

What might the FDA have to say?

Who will control the IP?

What might distribution channels look like?

What can be done to make the path to market better?

2:15pm - 2:45pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

The Impact of Next Generation Sequencing on Antibody Library Generation and Selection

Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica

Deep integration of next generation sequencing into aspects of antibody library generation and selection provides insights into antibody library diversity and overlap between different antibody libraries, as well as the diversity of specific selected repertoires, issues that will be addressed in this talk.

2:45pm - 3:15pm 30 mins

Info

Track 1: Microbiome

Exploiting the Interactions between the Microbiota and Immune Checkpoint Inhibitors in Anticancer Therapies

Bertrand Routy, MD, PhD - Assistant Professor, CRCHUM, University of Montreal Research Center

Despite their unprecedented results in various cancers, predictors of clinical benefit and strategies to safely enhance immune checkpoint inhibitors (ICB) efficacy are urgently needed. Preclinical studies have highlighted that immune-based therapies rely upon the composition of the gut microbiota to exert their bioactivity. Recently, we and others have demonstrated that the gut microbiota composition could predict response to ICB for patients with NSCLC and melanoma. The discovery of immunogenic bacteria capable to predict and increase clinical benefit of ICB will help for the development of novel biomarker tools and a future therapeutic concept, whereby treatment of cancer can be improved by the modulation of gut microbiota.

2:45pm - 3:15pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

Novel Techniques for Fab Library Generation and Antibody Hit Discovery Using Yeast Surface Display

Stefan Zielonka, PhD - Associate Director, Merck KGaA/EMD Serono

A novel one-step approach for easy and rapid construction of large yeast surface display antibody libraries will be presented. This Golden Gate Cloning-derived method allows for simultaneous introduction of heavy- and light chain diversities into one display plasmid leading to a significant streamlining of library generation. This technique seems to be valid to adequately sample antibody diversities. Additionally, a new fluorescence reporter read-out for antibody display will be presented.

3:15pm - 3:45pm 30 mins

Info

Track 1: Microbiome

Discovery and Development of Microbiome-derived Molecules as Novel Therapeutics in Cancer and Chronic Inflammatory Diseases

Lorenzo Tibaldi, PhD - Project Leader - Drug Discovery, Enterome Bioscience

Enterome dedicates its activities to the development of innovative therapeutic approaches (drugs and biomarkers) to support a personalized medicine for microbiome-related diseases. Based on its metagenomics screening platforms, Enterome identifies microbiome-derived molecules acting as specific and unspecific immunomodulators. In addition to several candidates currently tested at the preclinical stage, Enterome is pursuing the early clinical development of a molecule in Crohn disease and of an innovative immunotherapy in glioblastoma.

3:15pm - 3:45pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

Interpreting Antibody Function on a Repertoire Scale

Brandon DeKosky, Ph.D. - Assistant Professor of Chemical Engineering and Pharmaceutical Chemistry, The University of Kansas

Recently developed technologies in paired heavy:light sequencing, native antibody library display, and computational analysis of NGS datasets have opened up new possibilities for discovering and annotating antibody performance on a repertoire scale. We will discuss the application of these technologies to understand immune function and to identify new antibody molecules with desired functional properties.

3:45pm - 4:15pm 30 mins

Networking Refreshment Break

4:15pm - 4:45pm 30 mins

Info

Track 1: Microbiome

Generation and Development of a Rationally Designed Consortia of Human Derived Commensals for Cancer Immunotherapy

Bruce Roberts, PhD - Chief Scientific Officer, Vedanta Biosciences

Vedanta has created a rationally-designed consortia of human gut derived commensals capable of inducing CD8 T cells and enhancing anti-cancer immunity in conjunction with checkpoint inhibitors. The consortia called VE800 can be produced via cGMP manufacturing and administered orally on a repeated basis and thus constitutes an attractive agent for targeted modification of the microbiome of cancer patients to enhance anti-cancer immunity.  

4:15pm - 4:45pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

Synthetic Antibody Repertoire Design and Generation in Mammalian Cells Using CRISPR-Cas9-mediated homology-directed Mutagenesis

Sai Reddy, PhD - Assistant Professor, Department of Biosystems Science & Engineering, ETH Zurich

We have recently established a technique known as homology-directed mutagenesis (HDM), which is able to generate mutagenesis libraries directly in mammalian cells using CRISPR-Cas9. In HDM, we introduce genetic diversity into target proteins (e.g., antibodies) by using single stranded oligonucleotides (ssODNs), which serve as DNA donor templates following Cas9-induced DNA cleavage. HDM enables several of the most essential methods of antibody engineering to be performed in directly in mammalian cells expressing full-length IgG. This includes generation and screening of synthetic libraries for antibody discovery and affinity maturation

4:45pm - 5:15pm 30 mins

Info

Track 1: Microbiome

Mucosal B Cell Responses to the Microbiota

Steven Erickson - Senior Graduate Student, University of Chicago

 

The vast majority of mammalian antibody-secreting cells reside in the intestinal lamina propria and produce immunoglobulin A (IgA). However, the antigenic targets and function of IgA remain poorly understood. Our laboratory uses genetic, microbiological, and monoclonal antibody approaches to explore the origins and function of the mucosal IgA response.

4:45pm - 5:15pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

Library-scale Reformatting of Enriched Phage-display Pools to IgG for High-throughput Functional Screening

Michael Kierny, PhD - Scientist 1, Antibody Discovery & Protein Engineering, Medimmune

Phage-display selections using combinatorial libraries yield single chain fragment variable (scFv) binders that require individual conversion to IgG for functional assessment. In a method termed Screening in Product Format (SiPF), this process is streamlined by reformatting the selected library in emulsions to maintain the original VH-VL pairing and enable functional screening directly in IgG format. Examples will compare the performance and efficiency of traditional methods to SiPF.

5:15pm - 5:45pm 30 mins

Info

Track 1: Microbiome

IgA As An Anchor for Symbiotic Mucosal Bacteria

Gregory Donaldson, PhD - Postdoctoral Associate, The Rockefeller University

 

In the gut, IgA is important for neutralizing enteric pathogens and viruses, but it also targets commensal bacteria. In mouse models allowing a reductionist study of intestinal colonization, the common human commensal Bacteroides fragilis modifies its surface architecture to attract IgA for its own benefit.

5:15pm - 5:45pm 30 mins

Info

Track 2: Libraries, Display, Selection and Screening

Bispecific Target Discovery by High Throughput Functional Screening of Hundreds of Combinations of Different Target Pairs

Helene Finney, PhD - Director, Functional Screening, UCB

To exploit the true potential to access novel biology with bispecific antibodies we have developed technology to facilitate unbiased target pair identification and validation through grid screening in functional human cell assays large numbers of bispecific antibodies. Combination of our antibody discovery capabilities, a novel bispecific screening format and high throughput flow cytometry or imaging enables us to screen thousands of bispecific antibodies to hundreds of antigen combinations and identify new target pairs for a defined patient phenotype. The technology and a specific example application from patient phenotyping to new target pair discovery will be described.

5:45pm - 6:30pm 45 mins

Info

Special Session of the Antibody Society

Antibodies to Watch in 2019

Janice Reichert, Ph.D. - Executive Director, The Antibody Society Managing Director, Reichert Biotechnology Consulting LLC

Dec 13   

8:25am - 8:30am 5 mins

Track 1: Antibody Developability

Chairperson's Remarks

Karl Dane Wittrup, Ph.D. - C.P. Dubbs Professor, Massachusetts Institute of Technology

8:25am - 8:30am 5 mins

Track 2: Preclinical and Clinical Antibodies in Development

Co-Chairs' Remarks

Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio

Matthew Robinson, PhD - VP, Research & Development, Immunome, Inc.

8:30am - 9:00am 30 mins

Info

Track 1: Antibody Developability

Establishing Early Developability Screens to Enable Human PK Prediction

Laura Lin, PhD - Executive Director, BioMedicine Design, Pfizer Inc.

The presentation will showcase our strategies of applying early stage developability assessment to enable the selection of clinical candidates. In particular, I will focus on efforts to establish in vitro assays that are predictive of human clearance and PK, and will be sharing several examples highlighting the impact of such assessment on lead selection and optimization.

8:30am - 9:00am 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

Preclinical Studies of Targeted Radionuclide Therapy and Radiosensitization Strategies for Cancer Therapy

Marika Nestor, PhD - Associate Professor & Head of Research Group, Uppsala University

Targeted radionuclide therapies, including the use of radiolabeled monoclonal antibodies, are gaining importance as anti-cancer treatments. In recent years, new opportunities to utilize molecularly targeted therapies to increase the therapeutic effects of radiotherapy have emerged. Here, we combine the concepts and explore the use of antibodies and peptides for targeted radionuclide therapy and radiosensitization strategies.

9:00am - 9:30am 30 mins

Info

Track 1: Antibody Developability

Physicochemical Determinants of Drug-like Monoclonal Antibodies

Peter Tessier, PhD - Albert M. Mattocks Professor of Pharmaceutical Science, University of Michigan

The success of therapeutic drugs is dependent not only on their functional activities but also on their physicochemical properties (e.g., solubility, stability and specificity). We are developing methods for identifying drug-like monoclonal antibodies based on their chemical compositions and biophysical properties. These methods are expected to improve antibody drug development by more reliably identifying antibody candidates with drug-like properties and increased likelihood of success in the clinic.

9:00am - 9:30am 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

IgG Engineering to Mediate the Delivery of Enzymes into the Cytosol of Specific Cells

Bradley Pentelute, PhD - Professor, Chemistry, Massachusetts Institute of Technology

Immunoglobulin G (IgG) is currently an important class of therapeutics. Due to its wide application and favorable in vivo properties, there is significant interest in using IgG as a drug carrier. Here we report a bioconjugation method to chemically modify antibodies with the non-toxic 83 kDa protective antigen from anthrax toxin. We found that when protective antigen was conjugated to Trastuzumab or Cetuximab the resulting variant mediated efficient delivery of large enzymes into the cell cytosol in a receptor dependent manner. Further, we showed the antibody-delivered effector protein was able to overcome antibody resistance in multiple cancer cell lines.

9:30am - 10:00am 30 mins

Info

Track 1: Antibody Developability

Biochemical Developability of the Clinical Antibody Landscape

Yingda Xu, PhD - Director, Adimab

Isomerization and deamidation of therapeutic leads can often delay development timelines and provide challenge and risks for downstream process.  Sequence based prediction to scan for NG and DG can often lead to false positive results.  Here we report the chemical liability analysis of ~140 clinical stage antibodies, under forced degradation conditions.

9:30am - 10:00am 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

Cancer Therapy Revisited

H.Kaspar Binz, Ph.D. - Vice President and Co-Founder, Molecular Partners AG

The DARPin® platform is key in generating novel cancer therapeutics by overcoming classical limitations in oncology. The presentation highlights how we overcome dose-limiting toxicity of immuno-modulating drugs by generating locally restricted immune cell activators, including FAP/4-1BB candidate MP0310. Likewise, we use VEGF/HGF escape pathway blocking in clinical phase II candidate MP0250 to re-sensitize cancer patients to previously failed anti-tumoral therapy.

10:00am - 10:30am 30 mins

Networking Refreshment Break

10:30am - 11:00am 30 mins

Info

Track 1: Antibody Developability

Proteomics Identifies a CHO Host Cell Protein that May Impact Polysorbate Degradation

Kelvin Lee, PhD - Professor of Chemical & Biomolecular Engineering, University of Delaware

There is great interest in a better understanding of difficult to remove host cell proteins. We used proteomics approaches to identify different classes of difficult to remove CHO host cell proteins. One of the proteins that was identified may play a role in polysorbate degradation. We evaluated cell line development strategies to mitigate the expression of this protein and any resulting impact on polysorbate degradation.

10:30am - 11:00am 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

Development of a Novel Therapeutic Antibody Drug Conjugate for the Treatment of Autoimmune Disease

Michael McPherson, Ph.D. - Principal Research Scientist, In Vitro Technologies and iADCs, Global Biologics

We have developed a plasma stable antibody drug conjugate (ADC) that has steroid molecules linked to an anti-TNF a mAb.  This ADC is targeted to TNF-a expressing inflammatory cells and internalized to cellular lysosomes. We demonstrate that anti-TNF-steroid ADC treatment, after established disease, appears to heal the joints of previously arthritic mice when compared to a group of satellite animals sacrificed 7 days after disease onset.  The tarsal joints from these mice were evaluated using micro computed tomography and by histologic evaluation.  Restoration of normal joint architecture was seen in at least 40% of mice with TNF-steroid ADC treatment that was not seen with either an isotype control ADC or with the anti-TNF mAb alone.  These promising results suggest that a steroid targeted to cells involved in joint destruction via TNF binding has the potential to achieve not only lasting remission but also repair of the arthritic joints in RA patients, while sparing patients from steroid induced side effects.

11:00am - 11:30am 30 mins

Info

Track 1: Antibody Developability

Improving Biotherapeutic Development Through Structured Data Utilization

Randal Ketchem, PhD - Vice President of Molecular Design, Just Biotherapeutics

Biotherapeutic development is slow and expensive. Large scale, curated data collection across the therapeutic development pipeline enables predictive modeling and automated decision making, leading to faster development of improved biologics. We explore the challenges of biologics data capture and utilization toward improved biotherapeutic development.

11:00am - 11:30am 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

Design and Preclinical Development of An Anti-CD123 ADC, IMGN632, Which Exhibits Potent and Highly Selective Cytotoxicity to Leukemic Cells

Thomas Chittenden, PhD - Executive Director, Pipeline R&D, ImmunoGen


IMGN632 is a novel anti-CD123 ADC incorporating an indolinobenzodiazepine payload that alkylates, but does not cross-link DNA. Of multiple ADC designs evaluated, only IMGN632 demonstrated potent anti-leukemic activity at concentrations 100-fold below those that impact normal cells. The strategy to select an optimal antibody, payload and conjugation method will be discussed for IMGN632, which is currently in a phase I trial for CD123+ heme malignancies.

11:30am - 12:00pm 30 mins

Info

Track 1: Antibody Developability

Extensional Flow Induced mAb Aggregation

David Brockwell, PhD - Associate Professor, University of Leeds

Protein-based biopharmaceuticals are susceptible to unfolding, mis-folding and aggregation events induced by environmental perturbations that include hydrodynamic flow. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation and storage. To address this problem, we describe the development of a bench-top device to assess candidate manufacturability or process suitability for the manufacture of aggregation-prone biopharmaceuticals.

11:30am - 12:00pm 30 mins

Info

Track 2: Preclinical and Clinical Antibodies in Development

Preliminary Results of VISTA: A Phase 3 Study of Vicinium in Subjects with High Grade Non-Muscle Invasive Bladder Cancer (NMIBC)

Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio

Vicinium, an anti-EpCAM scFv/Pseudomonas Exotoxin A fusion protein, is in development for the local-regional treatment of EpCAM over expressing carcinomas. A registrational phase 3 study of Vicinium for the treatment of NMIBC recently completed enrollment and preliminary 3 month efficacy and safety data will be discussed.

12:00pm - 1:25pm 85 mins

Networking Luncheon

1:25pm - 1:30pm 5 mins

Track 1:Innovating Antibody Therapeutics

Chairman's Remarks

Paul Carter, PhD - Senior Director and Staff Scientist , Antibody Engineering, Genentech, Inc.

James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer , Panorama Research, Inc.

1:25pm - 1:30pm 5 mins

Track 2:Clinical Stories: Antibodies in Development

Chairman's Remarks

Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio

1:30pm - 2:00pm 30 mins

Info

Track 1:Innovating Antibody Therapeutics

The Next Generation of Programmable T cell Engaging Antibody Circuits

Werner Meier - Chief Scientific Officer and Acting CEO, Revitope Oncology

Revitope Oncology is developing the next generation of programmable antibody circuits aimed at minimizing toxicity while enabling effective immune-control of solid tumors. T cell Engaging Antibody Circuits (TEAC) are activatable T cell engaging modules that can be combined with any targeting moiety. TEAC consist of two stability-engineered modules with silent T cell engaging half-paratopes that are under the control of target-specific activation sites. The modules are targeted to the tumor through two modality-independent binding moieties. Thus, T cell engagement is subjected to a logic gate in which targeting and activation of TEACs are both required. These novel constructs are designed to expand the antigenic targeting space in immune oncology and constrain immune-activation to the cancer cell surface with the goal to widen the therapeutic index.

1:30pm - 2:00pm 30 mins

Info

Track 2:Clinical Stories: Antibodies in Development

Fortifying Mucus Membranes Using IgG Antibodies That Crosslink Pathogens to Mucins

Sam Lai, PhD - Associate Professor- Director, Pharmacoengineering Program, UNC Eshelman School of Pharmacy - University of North Carolina at Chapel Hill

I will describe our work in discovering and engineering of IgG antibodies that could effectively immobilize both viral and bacterial pathogens in native mucus secretions; the work has been recognized by a NSF CAREER Award and a Packard Fellowship. I will also discuss our recent efforts in extending this strategy for respiratory infections, STIs and contraception ex vivo and in vivo.

2:00pm - 2:30pm 30 mins

Info

Track 1:Innovating Antibody Therapeutics

Orientation-dependent Effector Function of Brain Shuttle Fusion Proteins

Jens Niewoehner, PhD - Senior Principal Scientist, Roche Pharmaceutical Research and Early Development

Transferrin receptor (TfR) has shown promise for transport of antibodies (mAbs) across the blood-brain barrier. However, safety liabilities have been reported associated with peripheral TfR binding and Fc effector function. Here, we present the Brain Shuttle-mAb (BS-mAb) technology and investigate the role of Fc effector function in vitro and in a novel FcgR-humanized mouse model. Strong immune reactions were observed for a conventional mAb against TfR with a native IgG1 Fc. Remarkably, no effector cell stimulation was observed for the BS-mAb construct, in spite of a native IgG1 Fc. Using various BS-mAb constructs we show that TfR binding through the C-terminal BS-module attenuates Fc-FcgR interactions, primarily due to steric hindrance. Nevertheless, BS-mAbs maintain effector function activity when bound to their brain target. Taken together, mAbs with full effector function can be transported in a “stealth mode” in the periphery and become activated in the brain when engaged to their target.

2:00pm - 2:30pm 30 mins

Track 2:Clinical Stories: Antibodies in Development

Checkpoint Studies

Jonathan Cheng, M.D - Executive Director, Oncology Clinical Research, Merck

2:30pm - 3:00pm 30 mins

Info

Track 1:Innovating Antibody Therapeutics

Structure of the 4-1BB/4-1BBL Complex and Distinct Binding and Functional Properties of Therapeutic Antibodies, Utomilumab and Urelumab

Christopher Kimberlin, PhD - Senior Scientist, Protein Engineering, Pfizer

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate distinct differences in activation by both antibodies. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.

2:30pm - 3:00pm 30 mins

Track 2:Clinical Stories: Antibodies in Development

Late Breaking Presentation

3:00pm - 3:30pm 30 mins

Info

Track 1:Innovating Antibody Therapeutics

Isolation of State-dependent Monoclonal Antibodies against the 12-transmembrane Domain Glucose Transporter 4 Using Virus-like Particles

Joseph Rucker, PhD - Vice President Research and Development, Integral Molecular

The insulin-responsive 12 transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational MAbs against complex and highly-conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking,or detect the conformational state of the protein. Here we report the isolation and characterization of novel conformational monoclonal antibodies (MAbs) that recognize the extracellular and intracellular domains of GLUT4, including MAbs that are specific for the inward-open and outward-open states of GLUT4. MAbs against GLUT4 were generated using virus-like particles (VLPs) to present this complex membrane protein in its native conformation, and using a divergent host species (chickens) for immunization to overcome immune tolerance. As a result, the isolated MAbs recognize conformational epitopes on native GLUT4 in cells, with apparent affinities as high as 1 pM and with specificity for GLUT4 across the human membrane proteome. Epitope mapping using shotgun mutagenesis alanine scanning across the 509 amino acids of GLUT4 identified the binding epitopes for MAbs specific for the states of GLUT4, as well as comprehensive identification of the residues that functionally control the GLUT4 inward-open and outward-open states. The MAbs identified here will be valuable molecular tools for monitoring GLUT4 structure, function, and trafficking, for differentiating GLUT4 conformational states, and for the development of novel therapeutics for the treatment of diabetes.

3:00pm - 3:30pm 30 mins

Track 2:Clinical Stories: Antibodies in Development

Targeting MDSC Derived Resistance to PD1 Based therapies: “In Like A Lion, Out Like a Lamb”

Anthony Tolcher, M.D. - CEO and Co-Founder, NEXT OncologyTM

3:30pm - 4:00pm 30 mins

Networking Refreshment Break

4:00pm - 4:25pm 25 mins

Info

Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018

Celebrating the Contributions of George P. Smith, Extraordinary Inventor, Mentor and Friend

Jamie Scott, MD, PhD - Professor and Canada Research Chair , Simon Fraser University

 

This presentation will review how Dr. Smith’s ideas for phage display, phage libraries and affinity selection developed, and will draw on some personal observations from my time in his lab.

4:25pm - 4:50pm 25 mins

Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018

Display Technology: Past, Present and Future

John McCafferty, PhD - CEO and Founder, IONTAS

4:50pm - 5:15pm 25 mins

Info

Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018

CLOSING KEYNOTE PRESENTATION: Exploiting the Diverse Functions of FcRn to Generate Therapeutics

Sally Ward, PhD - Professor, University of Southampton and Texas A&M University Health Science Center

 

The presentation will discuss how studies of FcRn, using a combination of antibody engineering, fluorescence microscopy

and mouse disease models, have been used to inform the design of therapeutics to modulate the dynamic behavior of

antibodies. In addition, a novel role for FcRn as a metabolic regulator will be discussed.

 

5:15pm - 5:20pm 5 mins

Close of Conference

Keynote Speakers

David Baker, PhD

Professor of Biochemistry at University of Washington

Towards Next Generation de novo Designed Protein Therapeutics

This presentation will describe recent advances in de novo protein design, and the application of these advances to new therapeutic and vaccine modalities.

Rachael Clark, MD, PhD

Shing-Yiu Yip and Cecilia M. Hepp Associate Professor of Dermatology at Harvard Medical School

TCR Sequencing: Transforming the Diagnosis and Care of Cutaneous T cell Lymphomas

Cutaneous T cell lymphomas are a heterogeneous collection of non-Hodgkin’s lymphomas that arise from T cells tropic for the skin. High throughput TCR sequencing (HTS) is transforming the care of patients with these cancers.  HTS provides rapid and accurate diagnoses, allows direct measurement of malignant T cells in skin before and after therapeutic interventions and discriminates patients with indolent lymphomas from those that will develop progressive, often lethal disease.

 

Bahija Jallal, PhD

President and Executive Vice President at Medimmune and AstraZeneca

Benralizumab, A Monoclonal Antibody Engineered for Enhanced NK-cell Mediated Eosinophil Depletion

Eosinophilia in patients with asthma correlates with increased exacerbation susceptibility. Benralizumab is a humanized, monoclonal antibody that targets the IL-5 receptor alpha antigen on eosinophils. Afucosylation of benralizumab enhances antibody-dependent cell-mediated cytotoxicity activity resulting in potent and rapid depletion of eosinophils. Benralizumab has demonstrated clinical efficacy in two pivotal Phase III trials, resulting in reductions of asthma exacerbations.

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