Engineering Bispecific Antibodies banner

Numerous inventive platforms and engineering approaches have created the next-generation of bispecific antibodies with improved functionality, selectivity, and specificity. Many of these are advancing to the clinic and challenges in targeting and safety have been overcome. Explore one of the most exciting areas in biologics and discover what the newest platforms and engineering approaches are that promise an increasingly diverse array of successful constructs that can achieve unprecedented efficacy.

Sunday, 13 November

Recommended Short Course*14:00

SC1: Developability of Bispecific Antibodies            
*Separate registration required. See short courses page for details.

Wednesday, 16 November

Registration and Morning Coffee (Garden Room)07:30

ROOM LOCATION: Rossini 1+2



Chairperson's Remarks

Stefan Zielonka, PhD, Director, Protein Engineering & Antibody Technologies Discovery Technologies, Global Research and Development, Merck KGaA


KEYNOTE PRESENTATION: Ten Years in the Making – Therapeutic Applications of CrossMab Technology

Christian Klein, PhD, Head, Oncology Programs and Department Head, Cancer Immunotherapy Discovery, Roche Innovation Center Zurich, Roche Pharma Research & Early Development, pRED

With more than 20 CrossMab-based antibodies entering clinical trials and the recent FDA approval of faricimab (VABYSMO) CrossMab technology has evolved during the past decade into one of the most mature, versatile, and broadly applied technologies for the generation of BsAbs. An overview of CrossMab technology and its therapeutic applications will be provided.


Trispecific Antibodies Produced from mAb2 Pairs by Controlled Fab-Arm Exchange

Gordana Wozniak-Knopp, PhD, Senior Scientist, Molecular Biology, University of Natural Resources and Life Sciences Vienna

Bispecific antibodies and antibody fragments are one of the most rapidly progressing classes of antibody-based therapeutics. Their differentiating functionalities could profit from a third antigen specificity. We have employed symmetrical bispecific parental antibodies of mAb2 format, which features a novel antigen-binding site in the CH3 domains, and engineered them by controlled Fab-arm exchange into biologically active trispecific well-expressing molecules with good biophysical characteristics.

09:30 Mastering Immunogenicity in Biologics Development

Jeremy Fry, PhD, Director, ProImmune Ltd.

Mitigating immunogenicity risk is a crucial step in drug development. In this talk I will use a series of case studies to demonstrate ProImmune’s expertise with adaptive and innate immunogenicity and epitope identification, covering the range of solutions ProImmune provides. These include DC-T/T cell proliferation assays for lead selection/optimization, MAPPS assays for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)10:00


Trispecific Antibodies – Taking the Concept of Multi-Targeting One Step Further

Ercole Rao, PhD, Group Leader Biologics Research, Engineered Protein Therapeutics, Sanofi Germany GmbH

Despite the success of bispecific antibodies in the past decade, antibody engineers try to add even more functionality to the ever-growing multi-specific antibody toolbox. Novel tri-specific antibodies, like a triparatopic anti-HIV antibody or a trispecific CD3xCD28xCD38 T cell engager have been developed and are currently evaluated in clinical studies. However, the molecular complexity of such molecules may pose significant challenges to their developability. Therefore, Sanofi has developed a high-throughput engineering platform that allows combinatorial screening of up to 10.000 molecules directly in the desired multi-specific format, addressing multi-parametric design.


Prodrug-Activating Chain Exchange (PACE) Converts Targeted Prodrug Derivatives to Functional Bi- or Multi-Specific Antibodies

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

Antibody-domain exchange reactions can be applied to generate hybrid antibodies under physiological conditions, thereby enabling prodrug functionalities. T cell bispecific antibodies (TCBs) can be assembled on target cells from two inactive prodrugs. Prodrug-Activating Chain Exchange (PACE) can thereby conditionally activate therapeutics at the target site. Examples will be provided that demonstrate potential applications of PACE as a new approach in conditional immunotherapy.


Design and Characterization of a Trispecific Antibody Discovery Platform

Nesrine Chakroun, PhD, Senior Scientist, Merus NV

Triple-targeting formats hold great therapeutic promise but translation of concepts into active molecules is challenging both in obtaining differentiated functional activity, as well as meeting stringent developability criteria. We discuss the discovery and characterization of the components and final candidates of a trispecific antibody format referred to as Triclonics that permits high-throughput in-format repertoire screening to result in active molecules that harness the developability characteristics of regular human monoclonal antibodies.

12:15 Discovery of Diverse Antibody Panels Using AlivaMab® Mouse: The Foundation for Successful Antibody Therapeutics

Jane Seagal, PhD, VP of Antibody Discovery, AlivaMab Discovery Services

More challenging targets, more challenging design goals, and complexly engineered advanced therapeutic modalities require panels of highly diverse antibodies as the foundation for success. AlivaMab Discovery Services’ fit-for-purpose strategies and technologies efficiently deliver panels of highly diverse antibodies with inherent characteristics required for successful biologic drug discovery and development. These antibody panels are application-ready for both standard antibody formats and as substrate for advanced therapeutic modalities.

Session Break12:45

12:50 bYlok® Technology: A Novel Solution for Improved Production of Bispecific Therapeutics

Peter O'Callaghan, Head of Expression System Sciences, Biologics and Licensing, Lonza

Bispecific antibodies offer numerous advantages as therapeutic modalities over existing monoclonal antibodies, including more precise targeting and increased efficacy. However, their production can present challenges that significantly affect the cost of goods, such as how to achieve highly efficient inter-chain dimerization of both the heavy chains and heavy-light chain pairings. In this presentation we will described bYlok®, a new technology that promotes correct heavy-light chain dimerization with high efficiency


13:20 Potent Anti-Tumoral eEfficacy with a First-in-Class Antibody Drug Conjugate

Cecilia Drakskog, Head of Preclinical Program, Genagon Therapeutics AB

Clptm1 is a conserved TM protein whose natural role is to limit forward trafficking of receptors to the cell surface. In cancer, Clptm1 is dysregulated and accumulates on the cell surface, making it a promising novel target for tumor therapy. GEN202 is a tubulin-inhibitor conjugated ADC targeting Clptm1 with a rapid internalization rate and a potent anti-tumoral efficacy in over 10 murine tumor models (up 90% TGI). 

Dessert Break in the Exhibit Hall & Last Chance for Poster Viewing (Verdi and Vivaldi 1&2)13:50

Breakout Discussions14:45

Breakout Discussions are informal, moderated, small-group discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. For in-person events, the facilitator will lead while sitting with delegates around a table. For virtual attendees, the format will be in an online networking platform. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. 


Latest in the Development of Bispecific Antibodies and What’s Next on the Horizon (IN-PERSON ONLY)

Christian Klein, PhD, Head, Oncology Programs and Department Head, Cancer Immunotherapy Discovery, Roche Innovation Center Zurich, Roche Pharma Research & Early Development, pRED



Chairperson's Remarks

Christian Klein, PhD, Head, Oncology Programs and Department Head, Cancer Immunotherapy Discovery, Roche Innovation Center Zurich, Roche Pharma Research & Early Development, pRED


Immunomodulatory Trifunctional Antibody-Fusion Proteins for Cancer Therapy

Dafne Müller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart

We develop trifunctional antibody-fusion proteins composed of a tumor-directed antibody moiety and two different immunomodulatory molecules – common gamma chain receptor cytokines/ costimulatory ligands of the TNF-superfamily. Aiming for improved localization and efficacy at the tumor site, the design focus on targeted presentation and combined mode of action. Molecular properties will be discussed.


A Novel 2-in-1 Dual Antagonistic Antibody Targeting PD1/VEGFR2

Orla Cunningham, PhD, CSO, Ultrahuman Eight Ltd.

The number of combinatorial approaches in the clinic has increased exponentially with PD1/VEGF targeting combos being the most represented. While this combo has shown efficacy, dose-limiting tox is a concern. We have engineered a standard antibody targeting both PD1 & VEGFR2 to maximize potency while minimizing the significant peripheral tox associated with VEGF pathway targeting. Co-crystal structures describe a unique interaction mechanism for this 2-in-1 mAb and co-culture IO model systems suggest potential synergy in dual pathway targeting.

16:30 Comparing Potential Bispecific Formats of Trastuzumab and a Humanized OKT3

Donmienne Leung, PhD, Head, Protein Engineering, Absolute Antibody

Not every antibody can be combined to produce well-behaved multi-specifics.  The valency and geometry of each design can determine the production, target engagement and ultimately the requisite biological functions.  In this case study, we selected two established antibody therapeutics, trastuzumab and a humanized OKT3 to produce 20 different bispecific formats to compare the feasibility of each format.




Chairperson's Remarks

Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt


TrYbe: A Multi-Specific, Fc-Free, Therapeutic Antibody Format

Sam P. Heywood, PhD, Director, Antibody Therapeutics, Discovery Science, UCB Pharma

TrYbe is a multi-specific, Fc-free, therapeutic antibody format. The design consideration for this new fragment-based therapeutic format will be discussed, both in terms of the functional biology and the molecular properties. Data from multiple programs will be shared that exemplify a range of functional activities; demonstrate some beneficial properties of target engagement with respect to immune complex formation; show consistent in vivo PK from albumin binding; efficient and high yielding production at manufacturing scale; and long shelf-life stability.


Human Bispecific Antibodies against Infectious Diseases

Luca Varani, PhD, Group Leader, Institute for Research in Biomedicine

We developed CoV-X2, a fully human, IgG-like bispecific antibody rationally engineered to bind simultaneously to two sites on the SARS-CoV-2 Spike (Nature, 2021); it potently neutralizes all variants of concern, protects from the virus both prophylactically and therapeutically and prevents formation of viral escape mutants in vivo. Bispecifics against Zika (Cell 2017) and Prion also had synergistic properties beyond those of the parental monoclonals. Simultaneous targeting of non-overlapping epitopes by IgG-like bispecific antibodies is feasible and effective against infectious diseases, combining the advantages of antibody cocktails with those of single-molecule approaches.


Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis

Costantino Pitzalis, MD, PhD, FRCP, Professor, Rheumatology Versus Arthritis; Director Versus Arthritis Experimental Arthritis Treatment Centre; Deputy Director, William Harvey Research Institute; Head of Centre for Experimental Medicine & Rheumatology, Barts and The London School of Medicine & Dentistry, Queen Mary University of London

Biologic drugs, especially anti-TNF, are considered as the gold standard therapy in rheumatoid arthritis. However, non-uniform efficacy, incidence of infections, and high costs are major concerns. Novel tissue-specific agents may overcome the current limitations of systemic administration, providing improved potency, and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, via the synovial-specific single-chain variable fragment (scFv)-A7 antibody, and TNFa neutralization, via the scFv-anti-TNFa of adalimumab, with the binding/blocking capacity comparable to adalimumab immune globulin G (IgG). Tissue-targeting capacity of the BsAb was confirmed on the human arthritic synovium in vitro and in a synovium xenograft Severe combined immune deficient (SCID) mouse model. Peak graft accumulation occurred at 48 h after injection with sustained levels over adalimumab-IgG for 7 days and increased therapeutic effect, efficiently decreasing tissue cellularity, and markers of inflammation with higher potency compared to the standard treatment. This study provides the first description of a BsAb capable of drug delivery, specifically to the disease tissue, and strong evidence of improved therapeutic effect on the human arthritic synovium, with applications to other existing biologics.

Close of Summit18:30