At the Fifth Annual Advancing Bispecific Antibodies and Combination Therapy to the Clinic conference, leaders will share insights and review encouraging clinical data. The proliferation of novel multi-specific antibody constructs and combination therapy
approaches has yielded exciting results, and this meeting will delve into solutions for improving the technology and selecting the best molecules for manufacturing and developability concerns.
Scientific Advisory Board
Steven Coats, Ph.D., Vice President, R&D, MedImmune
Rakesh Dixit, Ph.D., DABT, Vice President, R & D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics
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
WEDNESDAY, MAY 3
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
Rakesh Dixit, Ph.D., DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
8:40 Personalized Antibody-Mediated Immunotherapy Approaches
Kipp A. Weiskopf, M.D., Ph.D., Resident Physician, Medicine, Brigham and Women's Hospital
Insights into myeloid development have informed us of mechanisms of programmed cell removal. The CD47/SIRPα axis, a myeloid-specific immune checkpoint, limits macrophage removal of HSCs but can be exploited by hematologic and solid malignancies.
Therapeutics targeting CD47 represent a new strategy for treating cancer. Overall, an understanding of hematopoiesis and myeloid cell development has implications for regenerative medicine, hematopoietic cell transplantation, malignancy, and many
other diseases.
9:10 Bi-Specific T Cell Engagers and Chimeric Antigen Receptors: T Cells Strike Back
Matthew J. Frigault, M.D., Clinical Fellow in Medicine, Dana-Farber Cancer Institute
There have been significant advances in tumor directed immunotherapy. For the last two decades, monoclonal antibodies have been on the forefront of cancer therapeutics. Despite their success they’re unable to engage one of the most powerful subsets
of the host immune response – T cells. With the advent of bi-specific antibodies, as well as chimeric antigen receptors, we are now able to combine the targeting specificity of monoclonal antibodies with the cytotoxic effects of cellular therapy.
9:40 A Tale of Two SpecifiCITIES: The Balancing Act of Tumor-Targeting Selectivity and Therapeutic Index in Bispecific Antibodies
Yariv Mazor, Ph.D., Senior Scientist, Antibody Engineering, MedImmune
Dual targeting of antigen double-positive cancer cells over single-positive normal tissue is believed to enhance the therapeutic efficacy, restrict major escape mechanisms and increase tumor-targeting selectivity, leading to reduced systemic toxicity
and improved therapeutic index. However, the interplay of factors regulating target selectivity is not well understood and often overlooked when developing clinically relevant bispecific therapeutics. We show in vivo that dual targeting alone is not
sufficient to endow selective tumor-targeting, and report the pivotal roles played by the affinity of the individual arms, overall avidity and format valence.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 KEYNOTE PRESENTATION: Immunotherapy for Cancer: The Need for More Effective Combination Therapies
Ronald Herbst, Ph.D., Vice President and Head, Oncology Research, MedImmune
Combination therapies with anti-PD1/PD-L1 and anti-CTLA4 have already increased response rates in certain cancer indications, beyond checkpoint monotherapies. However, a significant subset of patients still fails to benefit from current immune therapies.
New, more effective combinations, beyond checkpoint blockade, are needed to further broaden and deepen the response of cancer patients to immunotherapy.
11:55 ERY974; First-in-Class T Cell–Redirecting Bispecific Antibody Targeting Glypican-3: A Highly Tumor-Selective Antigen
Mika Sakurai, Ph.D., Biologics Discovery Dept., Chugai Pharmaceutical Co., Ltd.
T cell–redirecting antibody (TRAB) may be a solution to recent problems facing cancer immunotherapy. ERY974 is a fully IgG-type TRAB that targets glypican-3 and exhibits highly potent anti-tumor efficacy. Chugai’s ART-Ig technology enables
large scale production of this asymmetric and bispecific antibody. Antibody optimization, non-clinical safety, pharmacology (including combination study with other immunotherapies or chemotherapies) and design of the Phase I study will be presented.
12:25
pm Predicting Marketed PD-1 Dosing and Optimal PD-1 x TIM-3 Dual Targeting Approaches in Immuno-Oncology
John Burke, Ph.D., Co-Founder, President, and CEO, Applied BioMath, LLC
We will look at an example of integrating systems modeling to predict optimal drug properties targeting PD-1 and TIM3 in I/O for bispecific biologics and fixed dose combinations. We assess risk by performing an in silico differentiation for a bispecific
vs. FDC and as part of model benchmarking we analyze why BMS and Merck anti-PD-1s therapeutic antibodies have similar dosing regimens when their affinities differ by two orders of magnitude.
12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:55 Session Break
2:10 Chairperson’s Remarks
Steven Coats, Ph.D., Vice President, R&D, MedImmune
2:15 Generation of BiKEs and TriKEs to Improve NK Cell-Mediated Targeting of Tumor Cells
Jeffrey S. Miller, M.D., Professor, Medicine, Division of Hematology, Oncology and Transplantation; Deputy Director,
Masonic Cancer Center, University of Minnesota
We have performed clinical trials using NK cell infusions. The major limitation is their lack of specificity and their inability to proliferate when targeted, which limits their clinical efficacy. IL-15 is a cytokine critical for NK cell development
and homeostasis. We have recently developed a class of molecules that combine antigen specificity and IL-15’s proliferative activity together into a novel class of multifunction molecules we call trispecific killer engagers (TriKEs).
2:45 The Two Faces of Interleukin-2: Engineering towards Induction of Immune Tolerance or towards Immune Activation
Ekkehard Moessner, Ph.D., Head, Protein Engineering, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
3:15 Enabling Technologies for Development and Optimization of Bi-Specific Antibodies for T-Cell Redirection
Jane Lamerdin, Ph.D., Director, Research & Development, DiscoverX Corporation
Bi-specific antibodies that redirect T-cells to kill cancer cells, like blinatumomab, represent an innovative approach to cancer immunotherapy. Novel physiologically-relevant approaches to test preclinical candidates are required. We present data
from blinatumomab across three novel platforms to evaluate target engagement, T-cell-specific killing, and safety and efficacy in primary human co-cultures.
3:30Advancing
the Discovery of Immunotherapeutics with Large Scale, Multiplexed Experiments on Cells and Proteins of Immune System
Thomas Duensing, CTO, IntelliCyt Corporation
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues
within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas
and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Hurdles in Moving BsAb from Preclinical Stage to the Clinic
Christian Klein, Ph.D., Head, Oncology Programs, Department Head Cancer Immunotherapy Discovery, Pharma Research and Early Development (pRED), Roche Glycart AG
- Experiences with BsAb: Challenges, benefits
- Selecting the suitable formats
- Over-coming production challenges
- Choosing the most promising targets
- Where BsAb are superior to combinations
5:45 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
THURSDAY, MAY 4
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Steven Coats, Ph.D., Vice President, R&D, MedImmune
8:35 Bispecific Antibody Efficacy and Safety: From Research to Clinic
G. Jonah Rainey, Ph.D., Executive Director, Head of Antibody Research, MabVax Therapeutics Holdings, Inc.
MedImmune now has multiple bispecific molecules that have progressed to clinical development. As these projects mature, there have been valuable lessons learned and perspectives gained. Preclinical data will be presented for multiple projects,
with clinical data demonstrating translatability to humans.
9:05 Nanobodies (Entering) in Clinical Phase: Update on their Immunogenicity
Sam Massa, Ph.D., PostDoc Scientist, VIB Center for Inflammation Research, VUB Cellular and Molecular Immunology laboratory, Vrije University Brussels (VUB)
Nanobodies, the variable domain of heavy-chain only antibodies naturally occurring in camelids, are the smallest antigen-binding antibody fragments, with exceptional characteristics. Several Nanobodies are (entering) in clinical phase, some of
which are discussed in this talk. Due to their sequences foreign to human, their immunogenicity is of special concern and analyzed in more detail. The latest data are presented here.
9:35 Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody/Anticalin Fusion Protein PRS-343
Manuela Duerr, Ph.D., Project Leader Immune-Oncology, Pieris Pharmaceuticals GmbH
Pieris used its proprietary Anticalin® platform to generate the 4-1BB-based bispecific PRS-343 (4-1BB/HER2). PRS-343 leads to efficient tumor target-dependent T-cell activation ex vivo. In a humanized mouse model, PRS-343 dose-dependently
inhibits tumor growth accompanied by high tumor infiltration with human lymphocytes (hCD45+). The positive preclinical data of PRS-343 suggest a promising efficacy and safety profile in humans and its excellent developability profile support
investigation of its anti-cancer activity in clinical trials.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
11:05 From the Bench to the Clinic: Developing Next-Generation ADAPTIR™ Molecules
Peter Pavlik, Ph.D., Principal Scientist, Molecular Biology & Protein Engineering, Aptevo Therapeutics
The ADAPTIR™ (modular protein technology) platform of bispecific protein therapeutics has unique properties compared to other bispecific antibody formats. A pipeline of ADAPTIR therapeutics is currently under development from early discovery
to clinical stage, targeting both solid and hematologic malignancies. Updates will be provided on advanced ADAPTIR therapeutics, including MOR209/ES414 and ES425.
11:35 Modulating Target Binding Affinity to Minimize Immune-Related Adverse Events
Justin M. Scheer, Ph.D., Director, Antibody Engineering, Boehringer Ingelheim Pharmaceuticals, Inc.
Unprecedented durable clinical response for tumor targeting can be achieved by immunotherapy. Bispecific antibodies can specifically activate T-cells and induce tumor cell killing in an MHC-independent manner. However, by unbalancing the immune
system, immunotherapies also generate dysimmune toxicities collectively termed as immune-related adverse events (IRAEs). In an attempt to minimize IRAEs and to raise the threshold for MTD (maximum tolerated dose), we’ve taken parallel
engineering approaches to modulate binding affinity to T-cells. These approaches are yielding variants with a broad range of binding affinities and are being profiled to understand how they maintain the balance of efficacy and safety.
12:05 pm Engineering Manufacturable IgG-like Bispecifics for Promoting Bone Mass Accrual and Fracture Repair
Guna Kannan, Ph.D., Director, Biologics-Antibody Engineering, Pharmaceutical Development
Santen Inc.
Significant progress has been made in the design and development of recombinant bispecific IgG-fusions, such as the IgG-single chain Fv, and fragment formats. However, success of full length IgG-like bispecific engineering and production without
additional process manipulation is limited. This talk will review IgG-like bispecific formats, describe a manufacturable IgG-like bispecific design, and demonstrate co-inhibition of two different targets leads to synergistic bone formation
in rodents and non-human primates.
12:35 End of Advancing Bispecific Antibodies and Combination Therapy to the Clinic