Cambridge Healthtech Institute’s 3rd Annual

Bispecific Antibodies for Cancer Immunotherapy

Engineering Next-Generation Biotherapeutics in Immuno-Oncology

October 6, 2020

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 Third Annual Bispecific Antibodies for Cancer Immunotherapy meeting will showcase preclinical, translational, and clinical studies on using bispecific antibodies for dual blockade of checkpoint targets, T cell-redirecting bispecific biologics, and overcoming T cell exhaustion, as well as strategies to improve efficacy and reduce toxicity, and to engineer the next generation of bi- and multi-specific biologics.

Tuesday, October 6



Top Ten Challenges to the Development of Bispecific Biologics and ADCs

Rakesh Dixit, PhD, President & CEO, Bionavigen

Bispecific antibodies incorporating various anticancer modalities, including drug conjugates, enhanced CD3- and TCR-based BiTEs are revolutionizing the war on deadly solid and heme cancers. However, challenges remain in development of bispecific biologics. The presentation will discuss the top ten challenges, including challenges to selection of target pairs and effector function, efficacy of safety of CD3-based biologic, case studies of novel bispecific platforms of PD-1:CTLA4 bispecific and Her2-biparatopic, and bispecific ADCs. Additionally, manufacturing, clinical and regulatory challenges will be discussed.

9:20 am BiTE Immuno-Oncology Therapies to Treat Solid Tumors
Elizabeth Pham, PhD, Scientist, Oncology Research, Amgen, Inc.

Dr. Pham will discuss characteristics of tumor targets that may impact the successful development of BiTE® molecules for solid tumor indications and explore potential strategies to enhance activity.

9:40 am COBRA – A Novel Class of Conditionally Active, T Cell Engaging Bispecifics for the Treatment of Solid Tumors
Robert DuBridge, PhD, Executive Vice President, Research & CTO, Maverick Therapeutics

T cell-engaging bispecific antibodies have demonstrated highly potent cytotoxicity against cancer cells. This potency can engender off-tumor, ontarget toxicity problems when targeting solid tumors in humans. To address this, Maverick Therapeutics has developed a novel recombinant bispecific platform called COBRA™ (Conditional Bispecific Redirected Activation), which includes two active tumor targeting domains, a half-life extension domain and inactive T cell engaging domains, that become fully active within the tumor microenvironment in a protease dependent manner. This presentation will discuss the development of these molecules and demonstrate their efficacy against human tumor cells in vitro and in vivo.

Kristina Kremer, Product Manager Cell Separation, Cell Separation, Miltenyi Biotec

Density-gradient centrifugation is time-consuming, labor-intensive, and results vary depending on the user. Skip this process with our portfolio for isolation of primary cells directly from blood products for drug discovery assays. Join us to learn how we make your cell isolations faster and easier while improving reproducibility and user safety.

10:20 am Session Break - View Our Virtual Exhibit Hall


10:40 am Multi-Specific MATCH Antibodies Enable Novel Therapeutic Strategies by Targeting Synergistic Immunomodulatory Functions to the Tumor Microenvironment
Alexandre Simonin, PhD, Director, mAb Discovery, Numab Therapeutics AG

Numab’s MATCH platform was exploited for the generation of a monovalent trispecific 4-1BB/PD-L1/HSA MATCH3 molecule (NM21-1480) that agonizes 4-1BB on anti-cancer T cells, conditionally upon binding to and blockade of PD-L1 on tumor cells. NM21-1480 shows superior efficacy over conventional CPI therapies and avoids dose-limiting toxicities of systemic 4-1BB agonism. Further, tetra-specific MATCH4 molecules are exploited to improve on safety and efficacy of conventional bispecific strategies.

11:00 am Triclonics Engagers: Multi-Specific Common Light Chain Antibodies Discovered by Unbiased Functional Screening
Cecile Geuijen, PhD, Vice President Oncology Cell Biology, Merus NV

Triclonics™ Engagers are multivalent molecules with three Fab arms that bind up to three different targets and designed to have long half-life, stability and low immunogenicity. The presentation will highlight: 1) the novel features and therapeutic opportunities of the Triclonics platform, 2) the characteristics of a large, diverse CD3 Fab panel discovered using the MeMo® mouse, common light-chain transgenic technology, 3) functional screening of thousands of Triclonics Engagers in T cell assays.

11:20 am Modulating the Immune System with Multi-Specific Antibodies
Suhasini Iyer, PhD, CDO, 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.

11:40 am Session Break – View Our Virtual Exhibit Hall
Joe Jiang, Product Manager, ACROBiosystems

Bispecific antibodies are promising immunotherapeutic agents for cancer therapy. A variety of CD3 proteins from different species and with various tags can accelerate the development of anti-CD3 bsAbs.

12:10 pm Session Break – View Our Virtual Exhibit Hall


12:30 pm Enhancing Efficacy and Safety of 4-1BB Agonism with PRS343, a Tumor-Targeted Bispecific
Shane A. Olwill, PhD, Senior Vice President, Head of Translational Science, Pieris Pharmaceuticals GmbH
12:50 pm

Kinetics of in vitro Tumor Killing, Cytokine Profiling, and T Cell Phenotyping of Immune Cell Engager Combination Therapies

Josefa dela Cruz-Chuh, Senior Scientific Researcher, Biochemical and Cellular Pharmacology (BCP), Genentech

T cell-dependent bispecifics (TDB) induce T cell-mediated killing of tumor targets by engaging both tumor antigen and CD3 on T cells resulting in formation of a synthetic immunological synapse and subsequent T-cell degranulation. T cell redirecting molecules have proven efficacious in hematological malignancies, but still emerging in solid tumors. Recruiting synthetic co-stimulatory receptor signaling (signal 2) with T cell receptor activation (signal 1) has the potential to improve TDB dependent anti-tumor activity. In the present study, we studied mechanism of action of co-stimulatory receptor bispecific in combination with TDBs utilizing an in vitro image-based T cell-dependent cellular cytotoxicity (TDCC) kinetic assay that incorporated cytokine kinetic profiling and T cell marker phenotyping. Combining co-stimulatory receptor bispecifics and TDBs improved T cell functionality and target cell killing compared to TDB alone.


Thibaut Janss, PhD, Senior Scientist, Immuno-Oncology, ImmunXperts, a Nexelis group company

To develop better therapies, primary immune cell assays are used to characterize the effects immuno-oncology candidates have on the different players of the TME.

Through a number of case studies covering exhausted T cell and macrophage assays, the design and potential applications of these in vitro experiments is discussed.

1:30 pm Session Break - View Our Virtual Exhibit Hall
2:05 pm A Bispecific SNIPER Antibody Demonstrating Preclinical Efficacy Through the Selective Elimination of Tumor Tregs
Bonnie J. Hammer, PhD, Vice President, Research & Development, Invenra

A bispecific SNIPERTM antibody that selectively eliminates intratumoral regulatory T-cells (Treg) while not inducing systemic Treg depletion will be described. As the Treg targeted SNIPER™ did not change the levels of Tregs in the periphery, this SNIPER™ may be an effective way to relieve the immunosuppressive microenvironment in tumors leading to stronger anti-tumor efficacy while decreasing the systemic autoimmune toxicities associated with other therapies.

2:25 pm

Priming Neoantigen Specific T Cells with a Novel Bispecific Antibody

Laura von Schantz, PhD, Director, Antibody Engineering, Alligator Bioscience AB

ATOR-4224 is a tumor-directed CD40 x EpCAM bispecific antibody designed to improve cross-presentation of tumor neoantigens and boost the priming of neoantigen specific T-cells. We demonstrate that mode of action is dependent on high expression of EpCAM on tumor derived extracellular vesicles and tumor cells, and that dual targeting of CD40 and EpCAM mediates a superior anti-tumor effect and decreased unwanted systemic immune activation compared to monoclonal CD40 antibody control.


Advances in Bispecific Antibodies

Panel Moderator:
Rakesh Dixit, PhD, President & CEO, Bionavigen
Robert DuBridge, PhD, Executive Vice President, Research & CTO, Maverick Therapeutics
Cecile Geuijen, PhD, Vice President Oncology Cell Biology, Merus NV
Teng Peng, Technical Application Manager, ACROBiosystems
Laura von Schantz, PhD, Director, Antibody Engineering, Alligator Bioscience AB
3:15 pm Session Break – View Our Virtual Exhibit Hall
3:35 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join your colleagues and fellow delegates for a focused, informal discussion moderated by a member of our speaking faculty.  A small group format allows participants to meet potential collaborators, share examples from their own work and discuss ideas with peers.

Engineering of Bispecific and Multi-Specific Antibodies

Robert DuBridge, PhD, Executive Vice President, Research & CTO, Maverick Therapeutics
4:05 pm Close of Bispecific Antibodies for Cancer Immunotherapy Conference

preliminary Agendas Available