Original Agenda
We are actively working with our speakers to confirm their availability for the virtual event. Initial response from our speakers has been very positive, and we are optimistic we will have the new programs ready to share here soon.

Engineering Bispecific Antibodies track banner

Bispecific antibody engineering has led to numerous inventive platforms and constructs that promise to overcome current limitations and give rise to a range of molecules now advancing to clinical development. This vibrant community will share recent results, progress, and ideas about how to engineer the next generation of molecules. Join this premier event in Europe to learn about one of the hottest areas in biologics today.

Thursday, 12 November

13:00 Registration
13:15 Dessert Break in the Exhibit Hall with Poster Viewing

DEFINING CLINICAL CHALLENGES AND ENGINEERING SOLUTIONS: THERAPEUTIC PLATFORMS

14:00

Chairperson's Opening Remarks

Daniel S. Chen, MD, PhD, CMO, IGM Biosciences
14:05 Clinical Challenges and Engineering Solutions in Cancer Immunotherapy: What Do We Need Now?
Daniel S. Chen, MD, PhD, CMO, IGM Biosciences

Cancer immunotherapy has resulted in long-term durable benefit for some patients with otherwise terminal cancer. But why are we struggling to deliver a similar benefit to the majority of cancer patients? Advances in biology and technology offer opportunities for the future, but what are the challenges that they should be focused on now? Presentation of clinical and biomarker data and scientific framework, challenges and engineered approaches will be discussed.

14:35 KEYNOTE PRESENTATION:

TriTACs – A Next Generation of T Cell-Engaging Antibody Constructs for Solid Tumor Therapy

Patrick Baeuerle, PhD, Managing Director, MPM Capital LLC

This presentation aims to demonstrate the promise and challenges of T cell-engaging therapeutics, and to highlight the approach taken by Harpoon Therapeutics. By the use of single-domain antibodies, of serum albumin binding, and by an unusual design, we created the TriTAC (for ‘trispecific T cell-activating constructs’) platform. With its extended serum half-life, small size, and very high potency of redirected cancer cell lysis, TriTACs promise to overcome limitations of other platforms.

15:50 Networking Refreshment Break

FORMAT ARCHITECTURE: CHOOSING THE RIGHT EPITOPE-AFFINITY COMBINATION

15:55

Chairperson's Remarks

Stefan Zielonka, PhD, Associate Director, Protein Engineering & Antibody Technologies, Merck KGaA
Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt
16:00 Harnessing Innate Immunity in Cancer Therapy
Éric Vivier, PhD, CSO, Innate Pharma

New therapies that promote antitumor immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy. Given the crucial role of innate immune responses in immunity, harnessing these responses opens up new possibilities for long-lasting, multilayered tumor control. We will present innovative anti-tumor therapies based on the manipulation of the innate immune system.

16:30

Bispecific Antibodies – Next-Generation Molecules & Applications

Ulrich Brinkmann, PhD, Expert Scientist, Pharma Research & Early Development, Roche Innovation Center Zurich

The presentation will provide an overview and examples of our bsAb molecules, including examples of novel exploratory approaches. Important aspect that will be covered include also high-throughput technologies to identify optimal binder-format combinations to elicit desired bsAb functionalities, and examples that demonstrate its relevance. 

17:00 End of Day
17:00 Dinner Short Course Registration
17:30 Recommended Dinner Short Course*
SC6: Engineering of Bispecific Antibodies and Multi-Specific Non-Antibody Scaffolds

*Separate registration required. See short course page for details.

Friday, 13 November

08:00 Registration and Morning Coffee

FORMAT ARCHITECTURE: CHOOSING THE RIGHT EPITOPE-AFFINITY COMBINATION

08:30

Chairperson's Remarks

Stefan Zielonka, PhD, Associate Director, Protein Engineering & Antibody Technologies, Merck KGaA
Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt
08:35 Anti-Idiotypic Bispecific Antibody Derivatives for Personalized Medicine
Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt

We report an approach for a personalized cancer therapy by generating patient-specific binders against the B-cell receptor of lymphomas. To this end, we established a platform for rapid yeast surface display identification of shark-derived vNAR antibody domains from semisynthetic libraries specifically targeting lymphoma cells. Several formats of vNAR bispecifics and ADCs were evaluated aimed at widening the therapeutic window for B-cell lymphoma therapy.

09:05

Developing a Plethora of Innate Cell Engagers for New Cancer Treatments on the ROCK® Platform    

Arndt Schottelius, MD, PhD, CSO, Affimed GmbH

Many cancer therapies don’t involve the innate immune system. Affimed’s ROCK platform is designed to develop innate cell engagers (ICEs) for various indications. All ICEs bear a CD16A-binding paratope, which triggers tumor cell killing through activating NK cells and macrophages.The modular ROCK platform allows to customize ICEs with respect to tumor target, affinity, pharmacokinetics, and the plethora of molecules in our pipeline has demonstrated rapid and predictable engineering capabilities.

09:35 Talk Title to be Announced
Annelise Vuidepot, PhD, Vice President & Head, Oncology Pipeline & Research, Immunocore
10:05 Networking Coffee Break
10:35 Targeting Bispecific Biologics to Disease Tissues
Lorenzo Benatuil, PhD, Senior Principal Research Scientist & Head, Biologics, AbbVie

Bispecific biologics such as dual variable domain immunoglobulins (DVD-Igs) offer new opportunities for innovative tissue/disease targeted therapies and have permitted the exploration of tissue specific and disease tissue specific targeting of biologics. 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.

11:05

Formation of Multivalent and Multispecific Antibodies for Therapeutical Therapy

Oliver Seifert, PhD, Senior Scientist, Institute of Cell Biology and Immunology, University of Stuttgart

Multispecific antibodies find increasing interest for therapeutic applications. With our newly designed antibody platform technologies we are able to generate Ig-like molecules of varying valency, specificity, geometry, flexibility, and size. Data will be presented demonstrating the effects of these parameters on the efficacy of bispecific T cell engagers.

Claudia Wagner, Director, Immunology, Immatics Biotechnologies

T cell receptor (TCR)-mediated immunotherapy holds great promise for the treatment of cancer. A prerequisite for successful therapy is the availability of highly tumor-specific targets in combination with potent and safe TCRs. At Immatics, the TCR platform XCEPTOR™ and the target discovery XPRESIDENT® work in concert to deliver suitable TCR candidates for clinical applications. We will provide data for the process of selection of TCR candidates, as well as exemplary data from our clinical ACTengine® trials.

12:05 Problem Solving Breakout Discussions with Light Snack*

*Topics to be announced.

ADVANCING T CELL BISPECIFIC ANTIBODIES

13:00

Chairperson's Remarks

Christian Klein, PhD, Cancer Immunotherapy Discovery, Roche Pharma Research & Early Development, Roche Innovation Center Zurich
13:05 Tumor-Conditional Anti-CTLA4 Uncouples Antitumor Efficacy from Immunotherapy-Related Toxicity
Feng Dong, PhD, Principal Research Scientist II, Foundational Immunology, AbbVie Cambridge Research Center

While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. We developed an anti-CTLA4 DVD-Ig possessing an outer tumor-specific antigen-binding domain engineered to shield the inner anti-CTLA4-binding domain until the outer domain was cleaved by MT-SP1 present in the tumor microenvironment. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities.

13:35 On-Target Restoration of a Split T Cell Engaging Antibody for Precision Immunotherapy
Gernot Stuhler, MD, Senior Physician & Group Leader, Hematology & Oncology & Medical Clinic II, University Hospital Wuerzburg

Hemibodies are complementary fragments of a split T cell engaging device. A pair of hemibodies gain T cell recruiting properties after simultaneous binding to a target cell, consequential reassembly of the two fragments and reconstitution of a CD3 binding unit. Thus, ultra-high precision tumor cell targeting is accomplished by addressing a combination of antigens that signify cancer using a technique that closely resembles the well-known two-hybrid system.

14:05 Mechanistic Basis of Bispecific Antibodies Targeting Immune Receptors
Wei Xu, MD, PhD, Vice President, New Drug Biology & Translational Medicine, Innovent Biologics Co. Ltd.

Cancer immunotherapy, such as PD1/PD-L1 inhibitors, have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies affect anti-tumor immunity, especially in exisiting immunity in the tumor microenvironment. I will discuss how to harness the power of immunity using bispecific antibodies that could create new biology.

14:35 Dissecting the IgG-[L]-scFv Format: How BsAb Design Impacts Function
Brian Santich, PhD, Research Fellow, Pediatrics, Memorial Sloan Kettering Cancer Center

T-cell bispecific antibodies (BsAbs) couple T-lymphocytes against tumor cells, inducing their destruction. We have recently identified 3 features of the IgG-[L]-scFv BsAb format which impacted their function: i) spatial configuration (cis-configuration), ii) interdomain spacing (one Ig-domain) and iii) valency (two cis-modules). When combined these parameters enhanced cytotoxicity, cytokine release and anti-tumor responses. These findings highlight the importance of BsAb design and provide guidelines for improving BsAb function.

15:05

Revision of RTK Tumor Targeting: Turning Receptors on and off with Bi-Paratopic 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 DARPin and IgG chimeric agents 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 built a novel platform for tumor RTK fingerprinting aimed at identification of prospective therapeutic leads or truly synergistic combination therapies.

15:35 Close of Summit