Bispecific antibodies have taken center stage in protein engineering for their versatile and effective targeting properties. The scope and breadth of work being done is impressive and the Eighth Annual Engineering Bispecific Antibodies meeting will focus
on progress in oncology as well as emerging areas such as hemophilia, ophthalmology, infectious disease, and inflammation. The latest developments in manufacturing, purification, stability, enhanced targeting, modulating immune response, expression,
characterization, humanization and clearance will be featured.
Scientific Advisory Board
Mahiuddin Ahmed, Ph.D., Assistant Attending, Immunotherapies, Department of Pediatrics, Memorial Sloan Kettering Cancer Center
Christian Klein, Ph.D., Head, Oncology Programs, Department Head Cancer Immunotherapy Discovery, Pharma Research and Early Development (pRED), Roche Glycart AG
Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics
G. Jonah Rainey, Ph.D., Executive Director, Head of Antibody Research, MabVax Therapeutics Holdings, Inc.
Eric Smith, Ph.D., Associate Director, Bispecifics, Regeneron Pharmaceuticals
Final Agenda
Recommended Short Courses*
SC3: Genomics in the Service of Cancer Immunotherapy - Detailed Agenda
SC11: Adoptive Therapy with CAR T Cells - Detailed Agenda
*Separate registration required
THURSDAY, MAY 4
12:00 pm Registration
12:35 Luncheon in the Exhibit Hall with Poster Viewing
1:40 Chairperson’s Remarks
Christian Klein, Ph.D., Discovery Oncology oDTA, Pharma Research and Early Development (pRED), Roche Glycart AG
1:50 KEYNOTE PRESENTATION: Engineering Bispecific Antibodies for Cancer Immunotherapy
Nai-Kong V. Cheung, M.D., Ph.D., Enid A. Haupt Endowed Chair, Pediatric Oncology, Memorial Sloan Kettering Cancer
Center
Conventional IgG monoclonal antibodies (mAbs) utilize Fc-dependent mechanisms which are constrained by low killing potency, poor cell trafficking, and the absence of memory. Bispecific (or multi-specific) antibody (BsAb) constructs can drive polyclonal
T cells into solid tumors to enhance the anti-tumor response despite the immunosuppressive tumor microenvironment. These antibodies bypass the need for prior immunization, as well as the need for tumor HLA and costimulatory molecules. For payload
delivery, bsAb can also be exploited in multistep targeting to vastly improve the therapeutic ratio.
2:20 Novel Approaches in the Use of Bispecific Antibodies for Cancer Immunotherapy
Christian Klein, Ph.D., Head, Oncology Programs; Department Head, Cancer Immunotherapy Discovery, Pharma Research
and Early Development (pRED), Roche Glycart AG
Cancer immunotherapy has emerged as key modality to achieve long term response in cancer therapy. A number of antibody-based cancer immunotherapies has been approved recently and/or is currently being investigated in clinical trials. This presentation
will give an overview over the design and the in vitro and in vivo pharmacological properties of T cell bispecific antibodies and novel strategies introduced to enhance their activity.
2:50 Development of T Cell Redirecting Fully Human Bispecific Antibodies
Eric Smith, Ph.D., Associate Director, Bispecifics, Regeneron Pharmaceuticals
This presentation will describe Regeneron’s bispecific antibody platform as well as the development of REGN1979, a fully human CD20xCD3 bispecific antibody. Characterization of the in vitro and in vivo properties of this bispecific will be discussed, along with findings from preclinical and phase 1 clinical studies. In addition, development of new T cell redirecting bispecifics for solid tumor indications will be discussed.
3:20 Design and Evaluation of Next-Generation Biologics for Cancer Immunotherapy
Maria Wendt, Ph.D., Head of Science, Biologics, Genedata
Bi- and multi-specifics, alternative scaffolds, ADCs, TCRs, CARs can provide significant advantages over traditional mAb molecules. However, as highly engineered molecules they pose new design, cloning, expression, purification, and analytics challenges.
Our workflow platform employed by top biopharma companies enables the automation, engineering, production, and testing of large panels of these candidate therapeutic molecules. We demonstrate the platform’s high-throughput capability when
handling novel molecule-specific designs and its built-in tools for developability and manufacturability assessments.
3:50 Refreshment Break
4:20 Enhanced Affinity TCR-Based Cancer Immunotherapy: Development of Novel Targets
Adriana Gambardella, Ph.D., Senior Scientist, Autoimmune Group, Immunocore Ltd.
Immune Mobilising Monoclonal TCRs against Cancer (ImmTACTM) molecules are bispecific reagents comprising a monoclonal TCR (binding a unique tumour-associated peptide) and an anti-CD3 scFv domain (recruiting and activating T cells). ImmTAC molecules
are extremely efficient and specific in recognising and enabling target cell killing. Target selection and affinity engineering of TCRs are critical steps in the development of potent ImmTAC molecules through a robust process involving in-depth
molecular and cellular analyses.
4:50 PANEL DISCUSSION
5:20 Registration for Dinner Short Courses
Recommended Dinner Short Course*
SC18 Clinical Prospects for Cancer Immunotherapy
*Separate registration required
FRIDAY, MAY 5
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Eric Smith, Ph.D., Associate Director, Bispecifics, Regeneron Pharmaceuticals
8:35 The “Evil Hitch-Hiker” Effect: Bispecific Antibodies to Target Viruses in Endosomes
Kartik Chandran, Ph.D., Professor, Microbiology and Immunology, Harold and Muriel Block Faculty Scholar
in Virology, Albert Einstein College of Medicine
Conventional antiviral immunotherapies cannot access the exquisitely sensitive “cryptic” viral epitopes that are unmasked in endosomes during cellular invasion. To target these epitopes in Ebola virus, we developed bispecific antibodies
that coopt virus particles themselves for endosomal delivery. Blockade of the endosomal virus-receptor interaction by these antibodies afforded broad antiviral efficacy in vivo. This approach should be widely
applicable to the development of antiviral immunotherapeutics.
9:05 Preclinical Development of HIVenv x CD3 Bispecific DART® Molecules for Elimination of Latent HIV Reservoirs
Annie Lam, Ph.D., Scientist II, Antibody Engineering, MacroGenics, Inc.
The principal barrier to HIV cure is a remarkably stable reservoir of latently infected cells. To eliminate this reservoir, we generated and tested several HIVenv x CD3 bispecific DART® molecules capable of redirecting T cells against latently-infected
cells. In this talk, we will discuss considerations that guide our molecular design and present data that support further development of HIVenv x CD3 DART® molecules towards clinical applications.
9:35 IGM2323: Bispecific CD20 x CD3 IgM with Enhanced Potency and Safety
Bruce Keyt, Ph.D., CSO, IGM Biosciences
IGM Biosciences has constructed a unique bispecific CD20xCD3 IgM. The IgM pentamer binds CD20 and a modified J-chain displays a scFv binding CD3e domain. IGM-2323 binds CD20 antigen more potently (1000x) with greater CDC (100x) compared to IgG. TDCC
is effective on CD20 low B cells with reduced cytokine release profile. In vivo studies show low doses (3 ug/mouse) yield complete B-cell killing. These data indicate broad application for potent asymmetric bispecific IgM formats.
10:05 Coffee Break
10:30 Chairperson’s Remarks
G. Jonah Rainey, Ph.D., Executive Director, Head of Antibody Research, MabVax Therapeutics Holdings, Inc.
10:35 Bi-and Multi-Specific Biologics for Cancer Immunotherapy: Selecting Target Combinations and Designing Biologics to Modulate Anti-Tumor T Cell Functions
Tariq Ghayur, Ph.D., Distinguished Research Fellow, Biologics, AbbVie Bioresearch Center, Inc.
The technological challenges of making bi-/multi-specific biologics are mostly solved and several formats are now in clinical development. The key challenge now is identify the right target combinations and designing the right bi-/multi-specific molecule(s)
to achieve the desired outcomes. In this presentation we will describe novel approaches we have developed to identify target combinations and novel bi-/multi-specific formats to reveal novel biology and/or address key biological questions.
11:05 Tuning Bispecific Antibodies for Efficacy and Safety
Stephen J. Demarest, Ph.D., Senior Research Advisor, Protein and Antibody Engineering, Lilly Biotechnology
Center
Bispecific antibodies provide more than the ability to deliver two drugs in one molecular package. They can be used to fine tune receptor binding, more precisely target specific cell types, and provide novel receptor/cellular engagements unattainable
with antibody combinations. This presentation will focus on new advances in bispecific technology and novel therapeutic modalities realized through fine-tuning of bispecific antibody binding to cell surface receptors.
11:35 Overcoming Obstacles to CAR T Cell Therapy in Solid Tumors
Sujith K Joseph, Ph.D., Staff Scientist, Department of Pediatrics Center for Cell and Gene Therapy Baylor College of Medicine
Our bispecific CAR technology, which includes a second binding domain on the CAR T cell that can lead to either an inhibitory or amplifying signal, can increase specificity of our CAR T cells for cancer cells versus normal cells. For example,
a CAR T cell can be engineered such that it would be triggered in the presence of one target protein, but if a second protein is present it would be inhibited. Alternatively, it could also be engineered such that two target proteins would
be required for maximal activation. These approaches may increase the specificity of the CAR for tumor relative to normal tissue.
12:05 pm Engineering Anti-PDL1 Antibody Based Bifunctional Fusion Protein and Bispecific Antibody for Enhanced Antitumor Activity
Zhenping Zhu, M.D., Ph.D., CSO and President, R&D, 3SBio, Inc.
This talk will cover the rationale for dual target engagement, describe the design and engineering the molecules and present in vitro and in vivo proof-of-concept studies.
12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:05 Refreshment Break
1:35 Chairperson’s Remarks
Nai-Kong V. Cheung, M.D., Ph.D., Enid A. Haupt Endowed Chair, Pediatric Oncology, Memorial Sloan Kettering Cancer Center
1:40 Efficient Payload Delivery by a Bispecific Antibody-Drug Conjugate Targeting HER2 and CD63
Bart De Goeij, Scientist, Antibody Science, GenMab A.V.
To improve efficacy of antibody-drug conjugates (ADCs), we have designed a bispecific ADC, in which one binding domain would provide tumor specificity (anti-HER2), whereas the other binding domain would facilitate targeting to the lysosomal
compartment (anti-CD63). The resulting bsHER2xCD63his-ADC demonstrated strong binding, internalization and lysosomal accumulation in HER2-positive tumor cells as well as potent cytotoxicity against HER2-positive tumors, which was not observed
with monovalent HER2- and CD63-specific ADCs.
2:10 Increased T Cell Infiltration into Tumor Microenvironment to Overcome Checkpoint Blockade Resistance
Yang-Xin Fu, M.D., Ph.D., Mary Nell and Ralph B. Rogers Professorship in Immunology, University of Texas, Southwestern Medical Center
Targeting tumors with tumor necrosis factor superfamily member LIGHT activates lymphotoxin beta receptor signaling, leading to the production of chemokines that recruit massive numbers of T cells. Furthermore, targeting non-T cell-inflamed
tumor tissues by antibody-guided LIGHT creates a T cell-inflamed microenvironment and overcomes tumor resistance to checkpoint blockade. Our data indicates that targeting LIGHT might be a potent strategy to increase the responses to checkpoint
blockades and other immunotherapies in non-T cell-inflamed tumors.
2:40 Beyond TfR: Identification of Novel Targets to Facilitate Uptake of Therapeutic Antibodies into the Brain
James A. Ernst, Ph.D., Senior Scientist, gRED, Protein Chemistry and Neuroscience, Research and Early Development,
Genentech, Inc.
Therapeutic antibodies have shown tremendous success in the treatment of human disease. However several physiological compartments, including the central nervous system (CNS), allow for limited penetration of large molecules. Improved transport
into these compartments could extend the opportunities for therapeutic antibodies in neuro-degeneration, improving both safety and efficacy. This presentation will focus on the selection of novel targets in the vasculature to facilitate
receptor-mediated transcytosis into the brain.
3:10 Balancing Selectivity and Efficacy of Bispecific EGFR x c-MET Antibodies and Antibody-Drug Conjugates
Carolin Sellmann, Ph.D., Postdoctoral Researcher, Protein Engineering and Antibody Technologies, Merck KGaA (Darmstadt, Germany)
Therapies targeting the tumor-associated antigen epidermal growth factor receptor (EGFR) often suffer from toxicities due to basal EGFR expression in normal tissue. Furthermore, EGFR-directed inhibitors might struggle with limited efficacy
because of c-MET mediated resistance mechanisms. Hence, we aim to construct bispecific EGFR x c-MET antibodies employing affinity-optimized binding moieties to balance selectivity and anti-tumor efficacy and to evaluate their potential
for an innovative antibody-drug conjugate approach.
3:40 End of Conference