2017 Archived Content
This track presents advances in the clinic and encouraging preclinical experiences, and examines modes of action and means of decreasing T regulators and suppressors while enhancing T effector activity. It features innovative target combinations such
as dual checkpoint inhibitors, combinations with B cell targets, agonists, and ADC bispecifics, and covers oncology, autoimmunity and multiple disease pathways.
Final Agenda
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Recommended Short Course*
SC6: Engineering of Bispecific Antibodies
*Separate registration required
WEDNESDAY 15 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA
08:35 Bispecific T-cell Engagers (BiTE) in Hematology and Beyond
Matthias Klinger, Ph.D., Principal Scientist, BiTE Technology, Amgen Research (Munich) GmbH
Following the approval of blinatumomab in relapsed/refractory ALL multiple BiTE candidates have or are about to enter the clinic in various indications. This presentation will give an update on Amgen’s BiTE pipeline at the discovery, translational,
and early clinical stage of development.
09:05 Tumor-Specific Carbohydrate Antigens as Preferable Targets for Novel Bispecific Antibody Constructs
Patrik Kehler, Associate Director, Immuno-Oncology, Preclinical & Immunological Research, Glycotope GmbH
Carbohydrates on the surface of cancer cells represent preferable targets for bispecifics due to their unique tumor-specificity with lack or inaccessibility on normal tissues and broad indication coverage. Multiple constructs were generated to demonstrate
the feasibility of carbohydrates as valuable targets for different bispecific approaches such as T cell recruitment. A comprehensive screening program was performed to identify the most preferable construct combining highest tumor specificity, anti-tumor
functionality and adequate safety.
09:35 Mechanistic Projection of First-in-Human Dose for Bispecific Immunomodulatory P-Cadherin LP-DART
Xiaoying Chen, Ph.D., Senior Manager, Early Oncology Development & Clinical Research, Pfizer, Inc.
An immunomodulatory bispecific molecule (P-cadherin LP-DART) was developed as a potential antitumor treatment. Because of its immune agonistic properties, a minimal anticipated biological effect level (MABEL) approach was applied to project the first-in-human
(FIH) dose. Particularly, a mechanistic PK/PD-driven approach, which accounts for the bispecific target binding, was explored to understand the exposure-response relationship and to project the MABEL dose. The current approach could potentially
be implemented for other bispecifics.
10:05 Development and Application of MOA-based Reporter Bioassays for Immunotherapy Drug Development
Jey Cheng, Senior Research Scientist, Research & Development, Promega Corporation
Having a functional bioassay that is MOA-based, accurate, precise, robust and reproducible is critical for the development of antibody-based biologics. We have developed reporter bioassays that meet these criteria for a broad range of antibody
modalities including Fc effector function, immune checkpoint modulation, bispecific antibody engagement, cytokine modulation, and others. Here we will present the latest technology advancements and demonstrate how these bioassays can be used
for a broad range of applications.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 KEYNOTE PRESENTATION: A Novel FAP-Targeted 4-1BB Agonist and Its Combination with T Cell Bispecific Antibodies
Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy
Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
Immune co-stimulation via 4-1BB agonism is an important element of next generation CAR-T cell therapy. The clinical development of first generation 4-1BB agonistic antibodies has been hampered by hepatic toxicity. Here we describe a novel FAP-targeted
4-1BB agonist for combination with T cell bispecific antibodies which may represent an off-the-shelf alternative to CAR-T cell therapies.
11:45 Multi-Functional Designed Ankyrin Repeat Protein Drugs: MP0250 and Beyond
H. Kaspar Binz, Ph.D., Vice President & Co-Founder, Molecular Partners
The use of the robust designed ankyrin repeat protein technology enables the nimble testing and establishment of drugs acting on multiple disease pathways. MP uses the platform to establish a portfolio of innovative drugs for the treatment of
cancer. The latest clinical data including MP0250 along with novel drug concepts will be presented.
12:15 ATOR-1015, a Bispecific Immunomodulatory Antibody Targeting OX40 and CTLA-4
Christina Furebring, Ph.D., Senior Vice President, R&D, Alligator Bioscience
Alligator Bioscience has developed a bispecific antibody targeting OX40 and CTLA-4 for immunotherapy of cancer. The mode of action of ATOR-1015 includes depletion/suppression of regulatory T cells as well as activation of effector T cells. The
design and the pharmacodynamics properties, as well as the biochemical properties and manufacturability, will be presented. ATOR-1015 is currently in pre-clinical development for clinical trials.
12:45 Carbohydrate Targeted Cancer Immunotherapy Using a Recombinant Malaria Protein
Mie Anemone Nordmaj, M.Sc., PhD Student, Immunology and Microbiology, Medical Parasitology,
University of Copenhagen
A unique malaria protein, VAR2CSA, binds to a distinct type of chondroitin sulfate found exclusively on a broad repertoire of cancer cells and in the cancer associated extracellular matrix. Here we describe the construction of an “armed”
rVAR2 molecule, capable of simultaneous recognition of cancer cells via rVAR2 and cytotoxic T-lymphocytes via anti-CD3. In vitro and in vivo efficacy showed significant anti-tumor effects, demonstrating the feasibility of using rVAR2 as
a component in a bispecific antibody.
13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:45 Session Break
14:00 Chairperson’s Remarks
Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals
14:05 Development of Anti-FcRH5/CD3 T Cell Dependent Bispecific (TDB) Antibody for the Treatment of Multiple Myeloma
Teemu Junttila, Ph.D., Senior Scientist, Genentech, Inc.
We have developed a novel T-cell dependent bispecific (TDB) antibody, anti-FcRH5/CD3 TDB, targeting the B cell lineage marker FcRH5 for multiple myeloma. This demonstrated cytotoxicity against human plasma cells and patient derived myeloma,
and induced immunosuppressive feedback signaling, including PD1 up-regulation, which can be overcome by PD-L1 antibodies. Data demonstrate the potential for anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD1/PDL1 signaling
in the treatment of multiple myeloma and other B-cell malignancies.
14:35 CD20 TCB (RG6026), a Novel “2:1” T Cell Bispecific Antibody for the Treatment of B Cell Malignancies
Sara Colombetti, Ph.D., Head, Oncology Discovery, Pharmacology, Roche Innovation Center, Zurich
The talk will focus on preclinical data of CD20 TCB, a novel differentiated CD20-targeting T cell bispecific antibody on the “2:1” IgG format that consistently demonstrated superior potency compared to other CD20 TCBs with a conventional
“1:1” IgG format. This translated into superior efficacy in vitro, ex vivo and in vivo, which could not be matched by increasing
doses of the “1:1” TCBs.
15:05 Therapeutically Targeting B Cells in Autoimmune Disease and Cancer Using a CD47xCD19 biAb Approach
Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA
Novimmune is developing a biAb approach to safely yet effectively treat B cell malignancies by targeting CD19 and CD47 with one molecule. CD47 restrains antibody dependent phagocytosis and CD19 covers a broad spectrum of the B cell lineages.
Thus, in addition to cancer, we are exploring the utility to use the biAb in autoimmunity, as the efficacy of B cell depletion in these patients positively correlates with clinical outcomes.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 Simultaneous Blockade of Multiple Immune Checkpoints with Bispecific Antibodies
David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc.
Combinations of checkpoint-blocking antibodies are more efficacious then single inhibitors, but also generate greater immune-related adverse events. We reasoned that a single bispecific antibody could achieve dual blockade to selectively target
tumor-reactive lymphocytes, possibly improving safety and efficacy. We have generated multiple dual-checkpoint inhibitors such as XmAb20717 (PD1 x CTLA4) that display compelling in vitro and in vivo activity relative to combinations of monospecific antibodies, suggesting that checkpoint bispecifics may have clinical advantages for the treatment of human malignancies.
16:45 FS118: An Anti-LAG-3/PD-L1 Bispecific Antibody Which Modulates T Cell Activity and Inhibits Tumour Growth
Mihriban Tuna, Ph.D., Vice President, Drug Discovery, F-star
A bispecific antibody (mAb2) which binds murine LAG-3 and PD-L1 simultaneously with high affinity was engineered and characterised. The anti-LAG-3/PD-L1 mAb2 inhibits LAG-3 binding to MHCII and PDL1 binding to PD-1 and CD80, resulting
in T cell activation in vitro. This translates into in vivo efficacy, where the mAb2 significantly decreased tumour burden in the MC38 colon carcinoma tumour model. Thus,
the preclinical data supports developing an anti-human LAG-3/PD-L1 mAb2 for the treatment of cancer.
17:15 Problem-Solving Breakout Discussions (View All Breakout Discussions)
Stimulation of Agonistic Pathways for Antibody-based Cancer Immunotherapy
Moderator: Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
- Choice of agonistic targets
- Approaches for stimulation of agonists
- Application for combination therapy
Humanized Mouse Models for Preclinical Assessment
Moderator: Sara Colombetti, Ph.D., Head, Oncology Discovery, Pharmacology, Roche Innovation Center, Zurich
- Choosing the right model: advantages and limitations of current models
- Value of humanized mice to analyze the efficacy of bispecific antibodies
- Designing an appropriate safety model
- Lessons learned from the clinic applicable to future preclinical models
- How to select the best humanized mouse model for specific immunotherapeutic applications
18:15 Networking Reception in the Exhibit Hall with Poster Viewing
19:15 End of Day
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THURSDAY 16 NOVEMBER
08:00 Registration and Morning Coffee
08:30 Chairperson’s Remarks
David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc.
08:35 Bispecific Antibodies and Antibody-Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs
Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals
There is a need for HER2-directed ADCs effective in patients expressing low/moderate levels of HER2. Cross-linking HER2 to constitutively internalizing PRLR, using a HER2xPRLR bispecific ADC, dramatically enhances lysosomal degradation of
HER2. Accordingly, bispecific ADC improve upon T-DM1 efficacy in cells expressing intermediate levels of HER2. These results demonstrate that coupling a tumor-specific ADC target to a rapidly internalizing protein may be a useful approach
to enhance efficacy of ADCs.
09:05 Advances with Bispecifics and Multi-Specifics in the Clinic – Lessons Learned
Tariq Ghayur, Ph.D., Distinguished Research Fellow, Foundational Immunology, Immunology Discovery,
AbbVie
Several bispecific DVD-Ig molecules have now been tested in preclinical models and in clinic. The emerging data show that these molecules behave like monoclonal antibodies and that the DVD-Ig format per se is not immunogenic. However,
target biology may play an important role anti-drug antibody response (ADA, immunogenicity). Lessons learned from these studies will be discussed.
09:35 Preclinical Development of MCLA-158, a Bispecific Antibody Targeting Lgr5 and EGFR
Berina Eppink, Ph.D., Project Manager, Merus NV
Biclonics is a robust and validated platform for the development of human full length IgG bispecific antibodies. MCLA-158 is a Biclonics that binds the wnt target gene Lgr5 and the growth factor receptor EGFR. MCLA-158 demonstrates superior
activity in both in vitro and in vivo tumor organoid based assays regardless of KRAS status and was shown to be well tolerated in non-human primates. These preclinical
data suggest MCLA-158 could benefit patients with metastatic CRC.
10:05 Design and Evaluation of Next-Generation Biologics for Cancer Immunotherapy
Maria Wendt, Ph.D., Head of Science Biologics, Genedata
Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific constructs can provide significant advantages for use in cancer immunotherapy.
However, as highly engineered molecules they pose new design, engineering, cloning, expression, purification, and analytics challenges. Genedata Biologics enables the automated design, screening, production, and testing of large panels
of these candidate therapeutic molecules and includes built-in tools for developability and manufacturability assessments.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 The Biology of IgG Hexamerization – Translating Basic Science to Antibody Therapeutics
Rob N. de Jong, Ph.D., Associate Director, CMC Research & Protein Chemistry, Genmab BV
In this presentation, we will present our understanding of the requirements of IgG hexamer formation at the submolecular level; functional aspects of antigen- and Fc-dependent IgG hexamer formation, the development of the Hexabody technology;
and progress towards clinical translation of Hexabody-based therapeutics.
11:45 Tetravalent Bispecific Antibodies with Unique CD16A-Binding Properties to Treat Non-Solid and Solid Tumors
Michael Tesar, Ph.D., Head, R&D, Affimed GmbH
Affimed has developed a unique NK-cell engager platform which delivers novel antibodies that not only activate innate immunity, but have also shown evidence of facilitating cross-talk with T-cell effectors. New data will be presented including
description of the technology, mode of action and potential combination strategies.
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:00 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 End of Advancing Bispecifics and Combination Therapy to the Clinic
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