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

T CELL ENGAGING BISPECIFIC ANTIBODIES
Harbor I

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

Nguyen_CokeyCokey Nguyen, PhD, Senior Director, Oncology R&D, Pfizer


2:30 Recruiting, Expanding, and Activating T Cells with Bispecific Antibodies and Optimized Cytokines

Desjarlais_JohnJohn 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

Li_JingJing 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.

Moderator

Pamela Carroll, PhD

Senior Vice President, Immuno-Oncology, Genocea Biosciences

 

 

 

 

Panelists

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

BISPECIFIC ANTIBODIES FOR COMBINATION IMMUNOTHERAPY
Harbor I 

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

Schmidt_MichaelMichael 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

Goldstein_JoelJoel 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

Jure-Kunkel_MariaMaria 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

Simonin_AlexandreAlexandre 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.

Biocytogen 12:30 Luncheon Presentation: Accelerating Bispecific Antibody Candidate Discovery with Innovative Humanized Mouse Models

Lin_QingcongQingcong 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

ENGINEERING BISPECIFIC AND MULTI-SPECIFIC ANTIBODIES
Harbor I 

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

Dubridge_BobBob 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

Throsby_MarkMark 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

Van_Schooten_WimWim 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

Reinhardt_CarstenCarsten 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.

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