Bispecific antibodies are gaining widespread adoption thanks to a multi-pronged approach which has proven to be a powerful tool against intractable targets. Oncology is the best example where bispecific antibodies employ novel functionality for efficacy
that is vastly improved over existing approaches. This meeting will review preclinical and clinical data and investigate tools and strategies for advancing molecules to the clinic.
WEDNESDAY, MAY 6
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Remarks
Rakesh Dixit, Ph.D., DABT, Vice President, R & D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
8:10 KEYNOTE PRESENTATION
Clinical Progress in the Development of Immunotherapy for Advanced Cancer: Focus on Targeted Therapy Combinations
Jason J. Luke, M.D., FACP, Assistant Professor, Medicine, Hematology/Oncology, University of Chicago
Immunotherapy is a centerpiece of melanoma treatment and early results in lung, kidney and bladder cancers suggest robust activity. Prior to immune-checkpoint blocking antibodies, standard of care in most tumors included targeted and chemotherapies.
A clear imperative is to understand which treatments are rational partners for immunotherapy and which may be combined safely. Immunotherapy combinations completed and in development in multiple tumors will be discussed.
8:40 Improving Cancer Treatment through Combination Immunotherapy
Ashok K. Gupta, M.D., Ph.D., Vice President, Clinical Oncology, MedImmune
9:10 GBR1302-BEAT® Bispecific Antibody for the Treatment of HER2 Positive Cancers
Jonathan Back, Ph.D., Head, In Vivo Pharmacology, Biologics Research, Glenmark Pharmaceuticals
Glenmark Pharmaceutical’s BEAT® platform is a novel bispecific heavy chain hetero-dimerization platform based on a unique concept of bio-mimicry. We have produced a bispecific antibody, GBR1302, designed to effectively recruit cytotoxic T cells
against HER2 positive breast cancer cells. GBR1302 potently re-directs T cells to HER2 positive cancer cells demonstrating strong tumor cell lysis activity and possessing an excellent safety-efficacy margin.
9:40 Activating the Immune System with Bispecific Technologies
J
ustin M. Scheer, Ph.D., Senior Scientist, Protein Chemistry, Genentech
Bispecific antibody technologies are validated for their ability to selectively activate immune effector cells in the presence of a tumor cell target. This presentation will describe recent advances in targeting B-cells for hematological malignancies
using bispecific technologies. Further, we will explore conformational and geometrical considerations that may influence the design of more effective bispecifics.
10:10 A Bispecific Antibody Targeting CD40 and CTLA-4 Generates Anti-Tumor Effects and Tumor Immunity
Peter Ellmark, Ph.D., Principal Scientist, Alligator Bioscience AB
10:17 Development of Interleukin-2 'Superkines' for Cancer Immunotherapy
Rodrigo Vazquez-Lombardi, Ph.D. Candidate, Immunology Program, Garvan Institute of Medical Research
10:24 A Novel Antibody-Based Modular Platform for an Accelerated Development of Highly Efficient Bi- or Multispecific T Cell Retargeting Approaches
Dr. Armin Ehninger, Ph.D., Chief Scientific Officer, GEMoaB Monoclonals GmbH
10:31 Targeted Costimulation with Novel Single-Chain 4-1BBL or OX40L Antibody-Fusion Proteins Promotes Tumor Directed T Cell Activation
Sina Fellermeier, Institute of Cell Biology and Immunology, University of Stuttgart
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:25 Controlled Fab-Arm Exchange for the Generation of Stable Bispecific IgG1
Joost Neijssen, Ph.D., Senior Scientist, Antibody Science, Genmab B.V.
The DuoBody platform represents a novel and elegant post-production technology for the generation of stable bispecific antibodies. This platform is based on the easy-to-use method of controlled Fab-arm exchange and is used to generate bispecific antibodies
that retain the biochemical characteristics and quality attributes of regular IgGs. The process has shown to be robust and scalable from bench (μg-mg) to mini bioreactor (mg-g) and manufacturing (kg) production. The presentation will highlight
recent progress in terms of DuoBody discovery, proof-of-concepts, characterization and development.
11:55 PANEL DISCUSSION
Moderator: Rakesh Dixit, Ph.D., DABT, Vice President, R & D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
Panelists:
Jason J. Luke, M.D., FACP, Assistant Professor, Medicine, Hematology/Oncology, University of Chicago
Ashok K. Gupta, M.D., Ph.D., Vice President, Clinical Oncology, MedImmune
Jonathan Back, Ph.D., Head, In Vivo Pharmacology, Biologics Research, Glenmark Pharmaceuticals
Justin M. Scheer, Ph.D., Senior Scientist, Protein Chemistry, Genentech
12:25 pm Enjoy Lunch on Your Own
1:55 Session Break
2:10 Chairperson’s Remarks
Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics
2:15 Identification and Optimization of T Cell-redirecting Asymmetric Bispecific Fully IgG Antibody
Takahiro Ishiguro, Ph.D., Researcher, Discovery Research, Chugai Pharmaceutical Co., Ltd.
T cell engaging bispecific antibody currently tested in clinical trial is BiTE molecules which are different from most popular IgG antibodies. We have generated T cell engaging antibody which is asymmetric bispecific fully IgG antibody recognizing
CD3 and tumor specific antigen. Validated proprietary antibody engineering technologies were applied to enable large scale manufacturing of the bispecific antibody. Identification, optimization and pharmacology of this bispecific antibody will
be presented.
2:45 Re-Envisioning “Classical” Cancer Therapy through the Lens of the Immune System to Develop Optimal Combination Immune Therapies
Israel Lowy, M.D., Ph.D., Vice-President, Clinical Sciences; Head, Translational Science and of Oncology, Regeneron Pharmaceuticals,
Inc.
Regeneron is conducting new clinical trials with REGN1979, an anti-CD20xCD3 bispecific antibody, to treat CD20+ NHL or CLL, and REGN2810, an anti-PD-1 mAb for multiple tumor types. Each is being developed as an immunologic foundation for therapeutic
regimens capable of eliciting durable responses. Further augmentation of anti-tumor activity by combination with classical agents will not rely on standard of care dosing, but instead seek to optimize their immune enhancing effects.
3:15 IMCgp100 ImmTAC: A Bispecific TCR Anti-CD3 Fusion for the Treatment of Malignant Melanoma
Annelise
Vuidepot, Ph.D., Head, Protein Science, Immunocore Ltd.ImmTACs are soluble bispecific-TCR-antiCD3 fusions suitable for the treatment of several tumor types. Unlike antibodies, TCRs target MHC-bound peptide antigens derived from endogenously
processed proteins, providing a large pool of intracellular antigens from which to select appropriate target molecules. Our most advanced program, IMCgp100, is currently in a phase IIa clinical trial for the treatment of malignant melanoma.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
Trispecific & Tetraspecific Antibody Derivatives and Beyond
Georg H. Fey, Ph.D., Professor Emeritus, Biology, University of Erlangen-Nuremberg
- Does dual targeting equals dual toxicity?
- From dual-targeting to dual triggering
- Dual-targeting plus dual-triggering agents
Advancing Bispecific Antibodies or Combination Therapy to the Clinic
John Haurum, Ph.D., CEO, F-star
- How does the desired MOA influence the choice of format – combo vs bispecific?
- How to define the lead candidate components?
- Is synergy required or is additive activity sufficient to differentiate over SOC?
- What are the biggest manufacturing and developability challenges?
- Impact of PK and dose schedule considerations
Emerging Technologies
Justin M. Scheer, Ph.D., Senior Scientist, Protein Chemistry, Genentech
• Antibodies and proteins for redirecting T-cells vs. emerging cell-based therapies
• Opportunities and challenges with emerging technologies
• Accommodating new investments or opportunities scientifically and logistically
5:45 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
THURSDAY, MAY 7
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Steven Coats, Ph.D., Senior Director, R&D, MedImmune
8:35 Multifunctional ADCs Unleash the Limitations of Conventional ADCs
Zhenwei (David) Miao, Ph.D., CTO, Sorrento Therapeutics
Our multifunctional ADC platform is able to expand the scope of the conventional ADC format that is limited by one target and one class of payloads. In this presentation, we will talk about the design and conjugation process of multifunctional ADCs
from the regular IgG antibodies. The newest in vitro and in vivo results of multifunctional ADCs with improved potency and safety profiles will be discussed as well in the case studies.
9:05 Bi-Specific Redirected T Cell Killing Using Site Specific Incorporation of Tumor Cell Ligands
Marco Gymnopoulos, Ph.D., Group Leader and Project Leader, Ambrx, Inc.
Our novel bi-specific conjugate (anti CD3-Folate) utilizes Ambrx’s RECODE™ technology that site-specifically incorporates novel amino acids into proteins recombinantly expressed in E.coli. Folate is chemically linked to the anti CD3 Fab containing the unnatural amino acid. Ambrx’s bi-specific conjugate is developed for targeting epithelial ovarian cancer and consists of a Folate entity that binds to FOLR1 receptor on tumor cells and anti-human CD3ε Fab that binds to the CD3 receptor on T cells. The concurrent engagement of T cells and ovarian cancer cells by anti CD3-Folate leads to T-cell activation and subsequent target cell lysis.
9:35 Dual-Targeting Triplebodies for the Elimination of Leukemic Blasts and Leukemia Stem Cells
Georg H. Fey, Ph.D., Professor Emeritus, Biology, University of Erlangen-Nuremberg
Triplebodies carry 3 single-chain Fv (scFv) binding domains in a single polypetide chain. The 2 distal modules bind 2 different targets on the same cancer cell, the central one a trigger on a cytolytic effector (NK- or T-) cell. Triplebody
33-16-123 binds CD33 and CD123 on acute mye¬loid leukemia (AML) cells, and recruits NK cells through CD16 (Fc gamma RIII). This pair allows us to target both AML blasts and AML Leukemia Stem Cells (LSCs), the presumed culprits responsible
for Minimal Residual Disease (MRD) and frequently life-limiting relapses.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
11:05 Harnessing Effector and Regulatory Pathways for Immunotherapy with DARTs
Scott Koenig, M.D., Ph.D., President & CEO & Director, Macrogenics, Inc.
Monoclonal antibodies (mAbs) are a mainstay of therapy for treating or preventing malignancies, autoimmune disorders, and infectious diseases. Engineering modifications in the primary structure of certain domains of mAbs or combining them
with small molecules or toxins has enhanced their therapeutic potency in some cases and has led to recent regulatory approvals of the next-generation of biologicals. In this presentation, promising approaches to modulate physiological
mechanisms with Dual Affinity Re-Targeting molecules or DARTs will be discussed with illustrations of their utility to treat leukemias and solid tumors, autoimmune diseases, or viral infections with our clinical and preclinical candidates.
11:35 Development of a Novel HER2-Targeting ADC to Address Unmet Medical Needs
John Li, Ph.D., Senior Scientist, Biosuperiors, MedImmune
Only 20-25% of the breast cancer patients are eligible for currently approved anti-HER2 therapies. Not all eligible patients respond to the therapies; moreover the vast majority of patients who initially respond to the treatment will eventually
relapse. To date metastatic breast cancer remains an incurable disease. This presentation will discuss the development of a novel HER2-specific biparatopic antibody-drug conjugate and its potential in treating metastatic breast cancer
patients that are refractory to or ineligible for current HER2-targeted therapies.
12:05 pm Attend Concurrent Session
12:35 End of Conference
5:15 Registration for Dinner Short Courses