Engineering Bispecifics banner

- 双特异性抗体工程 -

Exciting progress is being made in engineering for more targeted bispecific therapeutics that have optimal stability and half-life, and proven functionality. Balancing the affinity of the two arms of the bispecific, especially for CD3 targeting products, is seen as a common challenge and efforts are clearly underway to overcome this for enhanced targeting and minimal toxicity. Engineering Bispecifics will present novel approaches to optimize the product and address the challenges.

Final Agenda

THURSDAY 15 NOVEMBER

13:00 Registration

13:15 Dessert Break in the Exhibit Hall with Poster Viewing

FOCUS ON T-CELL ENGAGERS

14:00 Chairperson’s Opening Remarks

Thomas Van Blarcom, PhD, Associate Research Fellow, Protein Engineering, Pfizer, Inc.


14:05 KEYNOTE PRESENTATION: Novel T Cell Engagers for Targeted Recruitment of Effector Cells to Tumors

Yoram Reiter, PhD, Head, Molecular Immunology, Technion-Israel Institute of Technology

We have developed a new class of recombinant chimerical molecule that serve as T cell engagers to re-direct potent immune effector functions to specifically kill tumor cells. These T cell engagers are based on the genetic fusion of antibody fragments, specific for tumor cell surface antigens to monomeric HLA molecules that carry immunodominant peptides that can recall potent effector T cells. The molecular feature of these molecules/approaches and their in vitro and in vivo activities will be described.

14:35 Engineering of a T-Cell Dependent Bispecific to Broaden the Therapeutic Index for Solid Tumors

Christoph Spiess, PhD, Senior Scientist, Antibody Engineering, Genentech, Inc.

I will present the engineering of the bispecific to achieve selective binding to tumor cells and provide data demonstrating improved tumour infiltration in vitro and in vivo and preclinical safety.

15:05 Presentation to be Announced

15:35 Networking Refreshment Break

16:00 Creating a Novel T-Cell Engaging Bispecific Antibody Platform: Fine Tuning Anti-Tumor Activity with Sequence-Based Discovery and Machine Learning

Nathan Trinklein, PhD, Vice President, Teneobio

Using a multiple myeloma tumor cell line along with primary human PBMCs, we demonstrate a spectrum of in vitro tumor cell killing activity with varied levels of cytokine release using our bispecific molecules with diverse CD3 binding activities. In summary, we have created a T-cell engaging bispecific antibody platform with tuned T-cell agonism that can be used to optimize the therapeutic index for a variety of tumor antigens.

16:30 Developing Humabody VH Therapeutics for Immuno-Oncology

James Legg, PhD, Vice President, R&D, Crescendo Biologics

This presentation describes our approach to developing immune-oncology therapeutics, in particular Humabody VH products, small highly adaptable multi-functional proteins which can be developed into differentiated therapeutics with excellent characteristics for tumour targeting. It includes the development of a Biparatopic PD-1 inhibitor showing efficacy in a Pembrolizumab insensitive in vivo model, a Bispecific PD-1, LAG3 inhibitor and a targeted IO approach in which T-cell co-stimulation is focused away from the periphery and into the tumour microenvironment.

17:00 End of Day

17:00 Dinner Short Course Registration*

17:3020:30 Dinner Short Courses



Recommended Short Courses*

SC8: Selection, Screening and Engineering for Affinity Reagents

Julia Neugebauer, PhD, Director, MorphoSys AG

Birgit Dreier, PhD, Senior Scientist and Group Leader HT-BSF, Plückthun Lab, University of Zurich

Biologics such as recombinant antibodies and alternative binding scaffolds are routinely used in a wide variety of applications from basic research to clinical indications. This success has led to the development of a vast number of different selection, screening and engineering technologies for these molecules. This short course will give a comprehensive overview on different display technologies as well as screening approaches for the selection of specific binders. In addition, it will discuss engineering strategies including affinity maturation and how to implement these strategies. Classical antibodies and antibody fragments as well as alternative binding scaffolds such as DARPins will be covered.

SC10: Engineering of Bispecific Antibodies

Nicolas Fischer, PhD, Head, Research, Novimmune SA

Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J

By attending this interactive workshop, you will learn about the various approaches used for the engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different technologies will be compared, and examples for applications of bispecific antibodies in drug development will be presented with a focus on candidates that are currently being evaluated in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific antibodies will be discussed.

*Separate registration required.

FRIDAY 16 NOVEMBER

08:00 Registration and Morning Coffee

FC ENGINEERING FOR ENHANCED PRODUCT PROPERTIES AND FOR BRAIN DELIVERY

08:30 Chairperson’s Remarks

Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research and Early Development, Roche

08:35 Glyco-Optimization of Antibodies Targeting Immune Checkpoint Molecules: Case Studies of an Agonist and an Antagonist

Christoph Goletz, PhD, Associate Director, Preclinical Pharmacology & Cancer Immunology, Glycotope GmbH

Glyco-engineering is an established strategy to improve tumor antigen-targeting antibodies, e.g. anti-CD20, anti-EGFR, regarding their ADCC activity. In two case studies of an agonistic anti-CD40 and an antagonistic anti-PD-L1 antibody, we show that glyco-optimization can also be applied to enhance activity of antibodies targeting immune checkpoint molecules.

09:05 Development of a Novel Fc Heterodimerization Technology

Fabian Richter, PhD, Post-Doc, Biomedical Engineering, Cell Biology and Immunology, University of Stuttgart

The innovative heterodimerization technology “Fc1k” (Fc-one-kappa) was created and used for the generation of monovalent as well as polyvalent and multi-specific antibody-like molecules. We demonstrated the applicability in a monovalent Fv-Fc1k format, used for cytokine receptor blockade and in a bispecific scFv2-Fc1k molecule, simultaneously targeting two antigens. This novel platform technique provides for covalent heterodimerization of immunoglobulin domains, based on fully human and naturally occurring sequences.

09:35 Identification of a PD-L1 Binding Fcab: A Potent Inhibitor of Immunosuppressive Signals

Jose Munoz Olaya, PhD, Principal Scientist, Drug Discovery, F-star

Checkpoint inhibitors have been very popular and successful targets in the field of immuno-oncology. Here we describe the isolation of an Fcab, an antibody Fc domain modified to bind to a target, specific to PD-L1. The Fcab exhibits high affinity to human PD-L1 that translates into strong potency in cell-based functional assays. An anti-murine surrogate molecule, with similar potency, also exhibits activity in an MC38 syngeneic tumour model. This activity is improved when the Fcab is paired with Fabs targeting other immune checkpoint regulators.

10:05 Networking Coffee Break

10:35 Antibody Transport Vehicle (ATV): A Novel Brain Delivery Platform

Mark S. 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 β-secretase 1 (BACE1) in brain which was robustly inhibited by ATV:BACE1 leading to a sustained reduction in amyloid beta levels.

11:05 Turning Affibody Molecules into Efficient Peptide Binders by Dimerization

John Lofblom, PhD, Associate Professor, Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology

Affibody molecules are small three-helical affinity proteins. Generating binders for the amyloid beta peptide yielded a variant with 20-pM affinity, and with a unique 2:1 stoichiometry mode of binding as well as structural rearrangements in both the affibody domains and the amyloid beta peptide that is sequestered in a tunnel-like cavity. Engineered binders for other peptides show similar structural rearrangements and mode of binding, indicating that the new dimeric scaffold is well suited for such molecular recognitions.

11:35 Industrializing IO Therapeutic Discovery Platforms: Multispecifics, Engineered TCRs and CARs

Maria Wendt, PhD, Head, Science Biologics, Genedata

Novel classes of bio-molecules are currently evaluated for their use in cancer immunotherapy. Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific constructs promise significant advantages. However, these highly engineered molecules pose new challenges in design, engineering, cloning, expression, purification, and analytics. We present an infrastructure that addresses these challenges and enables the industrialization of these various novel therapeutic platforms.

12:05 Problem-Solving Breakout Discussions with a Light Snack

TECHNOLOGIES FOR DISCOVERY AND SCREENING, CMC, TARGETING, POTENCY AND LOW RISK OF TOX

13:00 Chairperson’s Remarks

Mark S. Dennis, PhD, Fellow, Denali Therapeutics

13:05 Case Studies on How Digital and Automated Solutions Transform the Discovery and Development of Next-Generation Antibodies

Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research and Early Development, Roche

We systematically introduced automated and digital solutions along our antibody discovery and development chain. A number of examples will be highlighted that demonstrate how automation and data science speed up 1) developability predictions to enable fast selection of clinical leads, 2) automation during functional characterization, and 3) machine learning during cell line selection and bioprocess modeling. As a consequence, output during the antibody discovery and development phase increases substantially.

13:35 Engineering, Efficacy and Functional Evaluation of a First In Class IgE Antibody for Cancer Therapy

Sophia N. Karagiannis, BA, MS, PhD, Reader, Translational Cancer Immunology, St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King's College London

Fc region engineering to enhance antibody effector functions could be an important determinant of clinical efficacy. Engineering anti-tumour antibodies with IgE class Fc regions may harness known properties of IgE that mediate immune clearance of parasites. Anti-tumour IgE potentiated monocyte/macrophage recruitment and re-education against tumours. A first-in-class antibody has reached clinical testing in patients with solid tumours and may offer opportunities to extend the current IgG-only class of monoclonal antibodies.

14:05 Redefinition of ErbB2/3 Tumor Targeting: How to Design Truly Potent Bispecific and Biparatopic Agents

Rastislav Tamaskovic, PhD, Head, TC Facility, Senior Scientist, Biochemistry, University of Zurich

Due to adaptiveness of oncogenic networks, tumors readily develop resistance against targeted therapies. Recently, we have described major compensatory routes, which become activated in therapy of ErbB2-positive cancer - and developed a new class of bispecific and biparatopic anti-ErbB2/3 targeting agents endowed with capabilities to overcome the adaptive resistance. Analogously, we build a new platform for tumor RTK fingerprinting aimed at identification of prospective therapeutic leads and truly synergistic combination therapies.

14:35 Productive Common Light Chain Libraries Yield Diverse Panels of High Affinity Bispecific Antibodies

Javier Chaparro-Riggers, PhD, Senior Director, Protein Engineering, Pfizer, Inc.

Here we describe the design of a synthetic human antibody library based on common light chains to generate antibodies with biochemical and biophysical properties that are indistinguishable to traditional therapeutic monoclonal antibodies. We used this library to generate diverse panels of well-behaved, high affinity antibodies toward a variety of epitopes across multiple antigens including mouse 4-1BB in order to investigate the therapeutic potential of biparatopic bispecific antibodies.

15:05 DuoBody Technology: A Versatile Platform for Bispecific Antibody Discovery and Development

Rick Hibbert, MBA, PhD, Assistant Director, Protein Production and Chemistry, Genmab B.V.

The DuoBody® platform represents a versatile, elegant and robust technology for generating bispecific antibodies. The post-production process is based on controlled Fab-arm exchange and yields bispecific antibodies that retain the molecular structure and quality attributes of therapeutic IgGs. The process is robust, high-throughput compatible and shows linear scalability from bench to manufacturing scale. This presentation will highlight recent insights in the preclinical and CMC development of DuoBody products.

15:35 End of Summit

* 活动内容有可能不事先告知作更动及调整。

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