Cambridge Healthtech Institute’s 2nd Annual
Bispecific Antibodies for Cancer Immunotherapy
Engineering Next-Generation Biotherapeutics in Immuno-Oncology
August 6-7, 2019
Engaging multiple receptors with bispecific biologics offers the potential to improve upon single-agent checkpoint blockade and promises to be the next generation of immunotherapy. Cambridge Healthtech Institute’s Second Annual Bispecific Antibodies
for Cancer Immunotherapy conference will showcase preclinical, translational and clinical studies on using bispecific antibodies for dual blockade of checkpoint targets, T-cell-redirecting bispecific biologics, overcoming
T-cell exhaustion, as well as strategies to improve efficacy and reduce toxicity, and engineer the next generation of bi- and multi-specific biologics.
Final Agenda
TUESDAY, AUGUST 6
12:00 pm Registration
1:25 Chairperson’s Opening Remarks
Tara Arvedson, PhD, Director, Oncology Research, Amgen
1:30 KEYNOTE PRESENTATION: Bispecific T Cell Engaging Molecules: Mechanism of Action and Clinical Activity
Tara Arvedson, PhD, Director, Oncology Research, Amgen
Bispecific T cell engaging molecules have demonstrated clinical benefit in hematological malignancies and solid tumors. This presentation will provide an update on the latest clinical results along with recent work evaluating the mechanism of action of
T cell engager molecules.
2:00 T Cell Engaging Bispecific Antibodies
Cokey Nguyen, PhD, Senior Director, Oncology R&D, Pfizer
2:30 Recruiting, Expanding, and Activating T Cells with Bispecific Antibodies and Optimized Cytokines
John Desjarlais, PhD, Senior Vice President, Research, CSO, Xencor
Xencor has applied its XmAb bispecific technology platform to create multiple novel modalities for T cell derepression and activation. These include dual checkpoint inhibitors such as a PD1 x CTLA4 bispecific antibody, and a CTLA4 x LAG3 bispecific antibody
that combines productively with anti-PD1 for triple checkpoint blockade. We have also discovered a highly active PD1 x ICOS bispecific antibody that productively combines checkpoint blockade and costimulation into a single molecule. Finally, we have
utilized our heterodimeric Fc domain to create a novel long-acting IL15/IL15Ra-Fc format for immunotherapy.
3:00 WuXiBody™, an Innovative and Versatile Bispecific Antibody Format Opens a New Era for Therapeutic Antibody Development
Jing Li, Senior Vice President, Discovery, WuXi Biologics
Bispecific antibodies are a growing area of biotherapeutics but with many development challenges. Many of the new platforms have limitations in yield, purity, stability, solubility, half-life, and immunogenicity. Thus, a one-size-fits-all solution is
still desired. Aiming to solve those issues, WuXi Biologics has generated WuXiBody™, a flexible, proprietary bispecific antibody format that can reduce the development time by 6 -18 months and can decrease cost of goods by 90%.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
Harbor II & III
4:15 PLENARY KEYNOTE SESSION
PANEL DISCUSSION: Next-Generation Immunotherapies
CHI’s Immuno-Oncology Summit brings you the latest advances in immunotherapy every year. This panel of industry thought leaders will discuss the technology advances and implementation strategies for next-generation immunotherapies, including emerging
immunotherapy combinations, bispecific antibodies, oncolytic virotherapy, adoptive cell therapy, personalized vaccines and neoantigen targeted therapies, small molecules and ADCs, cytokines, and innate immunity targeted therapies.
Pamela Carroll, PhD
Senior Vice President, Immuno-Oncology, Genocea Biosciences
Rakesh Dixit
PhD, DABT, President & CEO, Bionavigen
Tara Arvedson, PhD
Director, Oncology Research, Amgen
Michael A. Curran, PhD
Associate Professor, MD Anderson Cancer Center; President, Immunogenesis, Inc.
Raymond Tesi, MD
CEO/CMO, INmune Bio
David Kirn, MD
Co-Founder & Executive Chairman, IGNITE Immunotherapy
5:30 Welcome Reception in the Exhibit Hall with Poster Viewing
WEDNESDAY, AUGUST 7
7:30 am Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
John Desjarlais, PhD, Senior Vice President, Research, CSO, Xencor
8:30 B7-H3 as a Target of Bispecific Antibody-Based Immunotherapy
Soldano Ferrone, MD, PhD, Professor in Residence, Surgical Oncology, Massachusetts General Hospital, Harvard Medical School
9:00 Novel NK-Cell Engager and Checkpoint Bispecifics Selected from Unbiased Screen of Common Light Chain-Based Multispecific Antibodies
Michael Schmidt, PhD, SVP & Head, Research, Compass Therapeutics
At Compass, we combine high-throughput antibody discovery with proprietary platforms for multispecific generation and screening to empirically determine optimal combinations for drugging immunological pathways. Here we describe how this approach led to
the generation of a novel class of NK-cell engagers targeting NKp30 and bispecific checkpoint blockers inhibiting PD-1 & PD-L1.
9:30 Development of a Novel Bispecific Immune Modulating Antibody Targeting PD-L1 and CD27
Joel
Goldstein, PhD, Senior Director, R&D, Celldex Therapeutics
CDX-527, a tetravalent human anti-CD27/PD-L1 IgG1 bsAb, was developed as a novel approach to immunotherapy of cancers. Combining CD27 costimulation with PD-1/PD-L1 blockade in a bsAb provided greater immune activating properties than combining the individual
mAbs due to enhanced CD27 activation by crosslinking through PD-L1 in addition to Fc receptors. A pilot study in cynomolgus macaques identified no PK, PD or safety issues. Development activities in preparation of a clinical trial with CDX-527 have
been initiated.
10:00 Model Aided Drug Invention: In Silico Differentiation in I/O and Predicting Optimal Drug Properties in OA
John Burke, PhD, Co-Founder, President and CEO, Applied BioMath, LLC
Model Aided Drug Invention is a mathematical modeling and engineering approach to translational medicine that quantitatively integrates knowledge about therapeutics with an understanding of its mechanism of action in the context of human disease mechanisms.
Two case studies will explore integrating mathematical modeling to predict optimal drug properties targeting PD-1 and TIM3 in immuno-oncology for bispecific biologics and fixed dose combinations and determining best in class properties for targeted
anabolic growth factor to arthritic joints.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:30 DuoBody-PD-L1x4-1BB Combines Checkpoint Blockade with Conditional 4-1BB Co-Stimulation to Promote Antigen-Specific T Cell Stimulation and Proliferation
Maria Jure-Kunkel, PhD, Head, Late Stage Oncology Translational Medicine, Genmab
DuoBody®-PD-L1x4-1BB (GEN1046) is a bispecific antibody that induces conditional activation of T cells through 4-1BB stimulation which is dependent on simultaneous binding to PD-L1. In addition, the PD-L1-specific arm of DuoBody-PD-L1x4-1BB functions
as a classical immune checkpoint inhibitor by blocking the PD-1/PD-L1 axis, also in the absence of 4-1BB binding. DuoBody-PD-L1x4-1BB is being jointly developed by Genmab and BioNTech for the treatment of solid tumors.
12:00 pm A Novel, Monovalent Multi-Specific Antibody-Based Molecule that Simultaneously Modulates PD-L1 and 4-1BB Exhibits Potent Anti-Tumoral Activity in vivo
Alexandre Simonin, PhD, Director, mAb Discovery, Numab Innovation AG
The combined immunomodulation of PD-L1/PD-1 and 4-1BB is considered a promising strategy for the treatment of multiple solid tumors, but such combination therapies have not yet translated into durable clinical success, because 4-1BB-agonistic antibodies
are either intolerable at effective doses or ineffective, despite tolerability. To eliminate this safety/efficacy tradeoff, we engineered a novel, monovalent Fc-less tri-specific molecule targeting PD-L1, 4-1BB and serum albumin allowing a conditional
4-1BB agonism upon drug-mediated formation of an immunological synapse between PD-L1+ cells and 4-1BB+ cells, restricting costimulation of 4-1BB+ cells to the tumor microenvironment. Efficacy of the molecule to costimulate T cells was demonstrated
in vitro as well as its ability to slow tumor growth and enhanced intratumoral CD8+ T cell activation in vivo.
12:30 Luncheon Presentation: Accelerating Bispecific Antibody Candidate Discovery with Innovative Humanized Mouse Models
Qingcong Lin, PhD, CEO, Biocytogen Boston Corp.
The talk will cover Biocytogen preclinical pharmacology services for your antibody discovery with focusing on bispecific antibody discovery, including in vivo efficacy and toxicity, using Biocytogen IO target humanized mouse models, B-NDG based
PBMC/CD34+ human immune reconstituted mouse models, and CD3e humanized models to evaluate efficacy of IO blockage antibody combination and bispecific antibodies. Case study includes hCD3e model for CD3-directed bispecific antibody, hPD1/hLAG3, hPD1/CTLA4
models for double IO blockage antibody screening.
1:00 Session Break
1:55 Chairperson’s Remarks
Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron Pharmaceuticals, Inc.
2:00 KEYNOTE PRESENTATION: Development of Novel Fully Human Bispecific Antibodies for Oncology
Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron Pharmaceuticals, Inc.
This presentation will describe Regeneron’s bispecific platform and present preclinical data on several new bispecifics being developed for solid and liquid tumor indications. In addition, status updates on Regeneron’s clinical stage bispecific
antibodies (REGN1979, REGN4018, and REGN5458) will be presented.
2:30 COBRAs – Development of a Potent, Conditionally Active Bispecific T Cell Engager Platform
Bob DuBridge,
PhD, Executive Vice President, Research & CTO, Maverick Therapeutics
T cell engaging bispecific antibodies have demonstrated potent cytotoxicity against cancer cells. This potency can engender off-tumor, on-target toxicity when targeting solid tumors. Maverick Therapeutics has developed a bispecific platform called COBRA™,
which includes two active tumor targeting domains and inactive T cell engaging domains, that become active within the tumor microenvironment. This presentation will demonstrate the efficacy of these molecules against human tumor cells in vitr
o and in vivo.
3:00 CD47 Bispecific Antibody Design
Junjian Liu, PhD, Vice President, Head of Drug Discovery and Preclinical Development, Innovent Biologics
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 MCLA-158 and MCLA-145: Unbiased Functional Screening Unlocks the Therapeutic Potential of Bispecific Antibodies
Mark Throsby,
PhD, Executive Vice President & CSO, Merus NV
The Merus Biclonics® technology leverages the natural human IgG1 format to enable high throughput functional screening for the discovery of bispecific antibodies with exceptional drug properties. Preclinical data from two clinical pipeline candidates,
MCLA-158 that potently targets tumor formation, and MCLA-145 that recruits and supercharges tumor-infiltrating lymphocytes (TILS), will be discussed to highlight the power of the approach.
4:45 Targeting T Cell Agonists to the Tumor Environment with Multi-Specific Human Heavy Chain Antibodies
Wim van Schooten, PhD, CSO, TeneoBio
Hetero-multivalent antibodies targeting agonists on T cells in conjunction with tumor-associated antigens may yield therapeutics with superior biological activities and safety profiles. Teneobio’s discovery platform utilizes VH domains of fully
human heavy chain antibodies (UniAbs) to develop bi-, tri-, or tetravalent antibodies. Data from different assay types show that multivalent UniAbs can be engineered to display superior tumor cell cytotoxicity through multiple mechanisms of action.
5:15 TCER Bispecific Molecules: TCR-Based T Cell Engaging Receptors for the Treatment of Cancer
Carsten Reinhardt, MD, PhD, Managing Director, CMO, Immatics Biotechnologies
T cell receptor (TCR)-based immunotherapy is emerging as a promising treatment modality for malignant diseases. Immatics’ XCEPTOR® platform generates TCRs highly specific for mass spectometry-validated tumor antigens. These TCRs are further
engineered as high-affinity binders into our proprietary bispecific TCER® scaffold comprising a T cell-engaging antibody for potent redirection and activation of T cells. Extensive optimization of the TCER® platform has resulted in highly
stable molecules with extended serum half-life.
5:45 Close of Bispecific Antibodies for Cancer Immunotherapy
5:45 Dinner Short Course Registration
6:30 Dinner Short Course: Development of Bioassays for Checkpoint Immunotherapy and Other Immuno-Oncology Leads*
*Separate registration required.