Cambridge Healthtech Institute’s 9th Annual
Bispecific Antibody Therapeutics
Combination Therapy & Engineering Multi-Specificity
January 23-24, 2020
Part of the Antibody Therapeutics pipeline
CHI’s Bispecific Antibody Therapeutics conference explores the challenges of engineering multi-specificity to achieve more effective therapies that bind to at least two targets simultaneously. The conference examines how these molecules are used
to fight a wide array of diseases, as well as in combination therapy for enhanced effects in the fight against cancer. Along with increased efficacy, Bispecific Antibody Therapeutics can also optimize expenses by reducing the cost of development and
clinical trials. Case studies highlight novel engineering approaches and platform constructs that improve safety, stability, enhanced targeting, and manufacturability.
Final Agenda
THURSDAY, JANUARY 23
7:45 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:10 Organizer’s Welcome Remarks
Mary Ruberry, MA, Senior Conference Director, Cambridge Healthtech Institute
8:15 Chairperson’s Opening Remarks
Steffen Goletz, PhD, Professor and Deputy Head, Biotechnology and Biomedicine, and Vice Director, Institute of Bioengineering, Technical University of Denmark
KEYNOTE PRESENTATION
8:20 The Landscape of Multi-Specific Antibodies
Partha S. Chowdhury, Senior Director, Biologics Research, Sanofi Genzyme
Etiology and progression of diseases usually involves an intricate interplay of a number of molecular entities. Targeting and modulating activities of two or more of these molecules or homing an effector component, such as a cell to the disease site
or bridging two components in the pathologic site, serves an important therapeutic mechanism of action (MOA). This talk will be a synopsis of the different designs and their associated biological MOA.
FEATURED PRESENTATION
9:00 Bispecific Antibodies: Combinatorial and Activatable Functionalities
Ulrich Brinkmann, PhD, Expert Scientist and Scientific Director, Roche Pharma Research & Early Development, Roche Innovation Center Munich
9:30 Dealing with the Combinatorial Complexity of Protein Engineering: Bi- and Multi-specifics, TCRs and CAR Ts
Sebastian Kolinko, PhD, Scientific Consultant, Biologics, Genedata
We present a new technology platform to fully automate both molecular design, as well as the integrated assessment of potency, efficacy, and developability profiling of large panels of bispecific candidates. We will present use cases showing how the
platform allows for the systematic cloning, expression, purification, and characterization of complex multi-specific, CAR T and TCR modalities, with a focus on immuno-oncology applications.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 Maximizing Therapeutic Potential of Bispecific Antibodies and Cytokines by Affinity and Avidity Engineering
David E. Szymkowski, PhD, Vice President, Cell Biology, Xencor, Inc.
New immunotherapeutic modalities, such as T cell-engaging, tumor-targeted bispecific antibodies, T cell-activating cytokines, and checkpoint blockers are rapidly changing the cancer treatment paradigm. However, an unintended consequence of these biologics’
high potency is a suboptimal therapeutic index due to immune-related adverse events (irAEs). I will discuss case studies showing that next-generation immunotherapeutics can be engineered by affinity- and avidity-tuning to improve efficacy while
reducing irAEs, thereby increasing their therapeutic index.
11:30 Benchmarking T Cell-Redirecting Therapies for Cancer: Comparing CD3-Bispecifics and CAR T Cells
Thomas Craig Meagher, PhD, Senior Research Scientist, Regeneron Pharmaceuticals, Inc.
The two leading platforms for redirecting a patient’s T cells to recognize tumors, CD3-binding bispecific molecules and chimeric antigen receptor (CAR) T cells, both show clinical activity. We have developed pre-clinical in vitro and in vivo models to mechanistically compare these two technologies and will discuss our findings, as well as the clinical implications.
12:00 pm Development of "Imbalanced" CD3-bispecific Antibody with Balanced Safety, Efficacy and Developability
Yue Liu, CEO, Ab Studio, Inc.
Applying computer aided antibody design (CAAD), we were able to develop novel IgG like CD3-BsAbs with “imbalanced” binding to cancer and T cell and balanced safety, efficacy and developability in vitro and in vivo. One case study, a CD20/CD3
“imbalanced” BsAb (ABS BsAb), served as a proof of concept.
12:15 Sponsored Presentation (Opportunity Available)
12:30 Session Break
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
2:15 Chairperson’s Remarks
Thomas Craig Meagher, PhD, Senior Research Scientist, Regeneron Pharmaceuticals, Inc.
2:20 Advancing a Novel T Cell-Engaging Bispecific Antibody that Induces Lysis of Small Cell Lung Cancer Cells in vitro and Shows Potent T Cell-Redirected Anti-Tumor Activity in Vivo
Justin Scheer, PhD, Director, Antibody Engineering,
Boehringer Ingelheim
2:50 Novel Insights into T Cell-Redirected Killing of Tumor Cells
Stephen Demarest, PhD, Senior Research
Fellow, Lilly Biotechnology Center, Eli Lilly and Company
Using computational modeling and protein engineering, we generated novel agents to redirect T cells to fight cancer. We created a novel platform for robust production of these novel agents and demonstrate interesting novel geometrical constraints
for redirected lysis.
3:20 Networking Refreshment Break (Sapphire West & Aqua West Foyer)
3:45 Engineered Multi-Specific Antibodies for Targeted Inhibition of Cancer Metastasis
Jamie B. Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University
Metastasis is responsible for 90% of all cancer-related deaths, yet current anti-cancer therapies are designed to inhibit growth of the primary tumor and fail to address or sometimes even exacerbate metastasis. We leverage our recent discovery
of a biochemical pathway that drives tumor cell migration to engineer multi-specific antibodies that potently block metastasis. This new approach presents an exciting opportunity for targeted therapeutic design that synergizes with
current anti-cancer therapies.
4:15 Modulating the Immune System with Multi-Specific Antibodies in Cancer
Nathan Trinklein, PhD, Chief Technology Officer, TeneoBio, Inc.
Using a unique sequence-based discovery approach, we have created a large collection of fully human antibodies targeting a variety of tumor antigens and activating receptors on immune cells. Using machine learning tools, we rapidly establish
sequence-activity relationships and identify key residues and variable region positions in the antibody repertoire with desired agonist behavior. Our lead program, TNB383B (BCMAxCD3) is currently in phase 1 clinical studies. In summary,
we have created a platform for tunable immune activation at the site of the tumor that works with a variety of tumor antigens.
4:45 Revision of RTK Tumor Targeting: How to Design Truly Potent Bispecific and Biparatopic Agents
Rastislav Tamaskovic, PhD, Head, TCL Tumor Targeting, Biochemistry, University of Zurich
Due to adaptiveness of oncogenic networks, tumors driven by hyperactivated RTK receptors readily develop resistance against targeted therapies. We developed multivalent chimeric vehicles devoid of toxic payloads, which achieve their tumoricidal
activity by trapping tumor-driving receptor tyrosine kinases in inactive conformations and/or supramolecular assemblies. Using analogous construction scheme, we build a new platform for tumor RTK fingerprinting aimed at identification
of prospective therapeutic leads or truly synergistic combination therapies.
5:15 Close of Day
FRIDAY, JANUARY 24
8:00 am Registration (Sapphire West Foyer)
8:00 BuzZ Sessions with Continental Breakfast
Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the
stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies
and strategies, challenges, and future trends.
Click here for more details
9:00 Chairperson’s Remarks
David E. Szymkowski, PhD, Vice President, Cell Biology, Xencor, Inc.
9:05 Utility of the ADAPTIR Platform to Build Stable, Bispecific Proteins with Novel Mechanisms of Action
David Bienvenue, PhD, Senior Director, Protein Sciences, Aptevo Therapeutics
The ADAPTIR™ bispecific platform offers key advantages due to its flexible and modular nature. Preclinically, potent biological activity has been demonstrated with ADAPTIR bispecifics designed to engage the immune system
via several different mechanisms while retaining antibody-like manufacturing characteristics. An update on advanced preclinical and clinical bispecific candidates will be covered. The presentation will include a discussion
of developability criteria to consider during the selection and development of bispecific antibodies.
9:35 CB213: A Second-Generation Checkpoint Inhibitor Optimally Configured for Therapeutic Efficacy
James Legg, PhD, Senior Vice President, Research, Crescendo Biologics, Ltd.
Crescendo has a proprietary transgenic mouse platform for generation of fully human VH domains (Humabody VH). The talk will describe the identification and characterisation of CB213, a tetravalent, trispecific therapeutic delivering
dual checkpoint blockade through dual inhibition of PD-1 and Lag3.
10:05 Targeted and Conditional Biologics
Wendy Ritacco, MSc, Senior Scientist III, Global Biologics, AbbVie
Targeted and locally activated biologics, such as the bi-specific conditional dual variable domain immunoglobulins (cDVD-Igs), offer new opportunities for engineering efficacy while sparing systemic side effects. We will describe
preclinical examples of tissue targeting in normal and disease in vivo models as part of a new generation of locally acting “regio-specific” biologics therapies.
10:35 Networking Coffee Break (Sapphire West & Aqua West Foyer)
11:00 Development of NM21-1480, a Trispecific Anti-PD-L1x4-1BBxhSA Antibody Fragment
Timothy Egan, PhD, Vice President, Business Development, Numab Therapeutics AG
NM21-1480 is a molecule that potently blocks PD-L1/PD-1 signaling and elicits T cell activation through its costimulatory domain solely in the proximity of cells that overexpress PD-L1. Preclinical data show efficacy on tumor
growth in combination with an enhanced intratumoral CD8+ T cell activation when compared to the combination of the PD-L1 and 4-1BB modalities. Next to NM21-1480, Numab advances several immune-modulatory products targeting
specific tumor antigens based on its proprietary antibody fragment technology.
11:30 Engineering Multi-Specific Antibodies Leveraging Patients’ Active B Cell Responses
Shaun Lippow, PhD, Director, Protein Engineering, Atreca, Inc.
Atreca discovers novel cancer-specific targets and native human antibodies to those targets, through examination of the active B cell responses of cancer patients. Antibodies that specifically bind non-autologous human tumor
are advanced through our drug discovery pipeline, including standard IgG formats and next-generation multi-specifics. I will discuss our selection of multi-specific formats for cell engagement and the engineering of potent
anti-tumor molecules.
12:00 pm Conference Wrap-Up
Steffen Goletz, PhD, Professor and Deputy Head, Biotechnology and Biomedicine, and Vice Director, Institute of Bioengineering, Technical University of Denmark
12:30 Close of Conference