Advancing Bispecifics and Combination Therapy to the Clinic banner

Bi- and multi-specific antibodies and combination therapy are the way forward and five molecules have already been FDA approved and are on the market. Investigators working on novel approaches for activating the immune response and targeting otherwise intractable targets will share recent development and promising results. Learn strategies for ensuring the safety of new molecules while maximizing efficacy for a range of indications.

Sunday, 13 November

Recommended Short Course*14:00

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

Tuesday, 15 November

Registration and Morning Coffee (Garden Room)07:30

ROOM LOCATION: Rossini 1+2



Chairperson's Remarks

Jeanette H.W. Leusen, PhD, Associate Professor, Translational Immunology, Utrecht University


Implementing "Activity-on-Demand" Strategies with Bispecifics and Antibody-Cytokine Fusion Proteins

Dario Neri, PhD, CEO and CSO, Philogen

Bifunctional antibody therapeutics (e.g., bispecific antibodies, antibody-cytokine fusions) can be potently active for the therapy of cancer and other types of diseases, but their use may be associated with certain side effects. In this lecture, I will present experimental strategies for achieving "activity-on-demand", helping spare normal tissues from undesired toxicity. Protein engineering opportunities for "activity-on-demand", mode of administration, and opportunities enabled by combination therapy will be discussed.


Manipulating the Innate-Adaptive Immune Interface with CD27 Stimulation for Effective Anti-Cancer Therapy

Sean H. Lim, MBChB PhD, Associate Professor & Honorary Consultant in Haematological Oncology, Centre for Cancer Immunology, University of Southampton

The translation of immunostimulatory antibodies into clinically effective therapies lags behind that of checkpoint inhibitors and direct targeting monoclonal antibodies. This talk will focus on the reasons for this, and how might immunostimulatory antibodies be developed into more effective anti-cancer drugs, using the TNFRSF CD27, as an example.


Activating and Killing by PMN-MDSC with Tumor-Targeted IgA Antibodies

Jeanette H.W. Leusen, PhD, Associate Professor, Translational Immunology, Utrecht University

At present, all antibody therapeutics are based on IgG antibodies. However, IgA has great potential to stimulate neutrophils to kill tumor cells. We have investigated whether IgA can also be used to activate the myeloid-derived suppressor cells (MDSC) to kill cancer cells. MDSC are a major problem in the TME, because they suppress a plethora of immune cells, and thereby impede immunotherapeutic approaches. Both in vivo and human data will be presented.

10:00Meet and Greet

Session Break and Transition into Plenary Keynote10:30




Plenary Keynote Introduction

Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London

E. Sally Ward, PhD, Director, Translational Immunology; Professor, Molecular Immunology, Centre for Cancer Immunology, University of Southampton


Evolution of Antibody Technologies

Jane K. Osbourn, PhD, CSO, Alchemab Therapeutics Ltd.

It is nearly fifty years since the discovery of monoclonal antibodies, the first drug approval coming soon after in 1986. From this early success, approval rates took time to ramp up and significant efforts were focused on building a range of technologies to deal with the technical challenges of antibody-drug discovery. This talk will discuss how antibody technologies have evolved and consider where future innovation may lie.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)11:30


Bispecific Antibodies Increase the Therapeutic Window of CD40 Agonists through Selective Dendritic Cell Targeting

Rony Dahan, PhD, Principal Investigator, Immunology, Weizmann Institute of Science

I’ll describe our approach of cell-selective bispecific agonistic antibodies as a drug platform to bypass the dose-limiting toxicities of agonistic antibodies used for cancer immunotherapy. We designed bispecific antibodies that target CD40 activation preferentially to dendritic cells, the cells leading to antitumor activity but not toxicity by these agonists. These bispecific reagents demonstrate a superior safety profile compared to their parental CD40 monospecific antibody while triggering potent antitumor activity.

12:45 CMC Strategy to take Bispecifics from DNA to IND in 13 Months

Stuart Jamieson, Director, Global Technical & CMC, Downstream Development, Lonza

Lonza has applied 35 years’ of CMC experience in Biologics development to deliver a 13 month end-to-end DNA to IND strategy for bispecific molecules. Case studies highlighting key approaches and technologies for vector, process, analytical and formulation development, which enable acceleration of bispecific antibody pre-clinical development, will be presented.

Session Break13:15

13:20 Building Next-Gen Biologics Leveraging Industry-Leading Technology Platforms with Nona Biosciences

Frank Grosveld, PhD, CSO, Harbour BioMed Rotterdam, Harbour BioMed

Nona Biosciences is a newly established independent subsidiary company of Harbour BioMed.  Nona is committed to providing a total solution to therapeutic antibody discovery, engineering, and development for academics, biotech startups and biopharma giants from Idea to IND. The core platform is our proprietary transgenic Harbour Mice® H2L2 and HCAb fully human antibody technologies that have been well validated by 50 industry and academic partners with over 200 projects.

13:50 Innovative Bispecific Therapeutic Antibody Discovery with the Relite™️ Fully Human Common Light Chain Antibody Platform

W. Frank An, PhD, Senior Director of Antibody Therapeutics, Biocytogen Pharmaceuticals (Beijing) co. ltd

Bispecific antibodies are increasingly employed as a versatile, off-the-shelf approach in therapeutic antibody discovery. Biocytogen, a clinical-stage biotech company, features the world-leading transgenic RenLite™️ mice that produce high-quality fully human common light chain antibodies that greatly expedite bispecific antibody construction. This presentation introduces Biocytogen’s bispecific antibody discovery platform, highlighting recent innovative applications including bispecific checkpoint inhibitors and bispecific antibody drug conjugates (ADCs).

Session Break14:20



Chairperson's Remarks

Pieter Fokko van Loo, PhD, Senior Director, Oncology – Immunology, Merus NV


Antibody Engineering Towards HIV Cure

Marit van Gils, PhD, Associate Professor, Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Centers

Since the discovery of HIV-1 as the causative agent for AIDS, no vaccines or therapeutics for a total cure are available to date. Recently, there is a growing interest in potentiating the effector functions of antibodies to improve the use of antibodies as therapeutics and possibly leading to HIV-1 cure. We use four approaches of antibody engineering towards this goal; 1) bi and trispecific antibodies, 2) Fc-modifications to increase antibody effector functions, 3) antibody-drug conjugation and 4) engager antibodies. Improving antibody therapeutics using these strategies has the potential to complete the ultimate goal of curing HIV infection.


Trispecific T Cell Engagers for Solid Cancers

Pieter Fokko van Loo, PhD, Senior Director, Oncology – Immunology, Merus NV

The wide expression of tumor-associated antigens (TAA) on solid tumors as well as on normal tissue limits the therapeutic window of T cell engagers for solid tumors. Solid tumor selectivity can be created by targeting two tumor targets (TAA1xTAA2) simultaneously that are only co-expressed on solid tumors and not on normal tissue. This paper discusses pre-clinical data of TAA1xTAA2xCD3 Triclonics that selectively eradicate TAA1xTAA2 double expressing cells while sparing TAA1/TAA2 single expressing cells, thereby providing a rational for the development of trispecific T cell engagers for solid tumors.

15:35 A Platform for Tuning Therapeutic Efficacy of T-Cell-Engaging Bispecific Antibodies

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

T-cell activation requires appropriate strength of stimulation and costimulation. Blocking coinhibitory pathways prevents T-cell exhaustion and escape. Here, we present diverse panels of lead-quality antibodies ready for reformatting into advanced modalities for the development of finely tuned multi-drug approaches against a variety of tumor targets. We demonstrate that in bispecific contexts these antibodies are biologically active and have favorable biophysical properties.

Refreshment Break in the Hall with Poster Viewing (Verdi and Vivaldi 1&2)16:05


Phase I Study of AMG 509, a STEAP1 x CD3 T Cell-Recruiting XmAb 2+1 Immune Therapy, in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Daniel C. Danila, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is overexpressed on prostate cancer cells with low or no expression on normal tissue. AMG 509 is a bispecific XmAb 2+1 T cell engager that simultaneously binds to STEAP1 on tumor cells and the CD3 complex on T cells resulting in T cell-mediated lysis of STEAP1-expressing cells. AMG 509 demonstrated significant antitumor activity in preclinical prostate cancer models. Preliminary safety data warrant further studying.



Chairperson's Remarks

Nicolas Fischer, PhD, CEO, Light Chain Bioscience


Costimulatory CD28 Bispecific Antibodies for Tumor-Targeted T Cell Activation

Sara Majocchi, PhD, Discovery Program Leader, Light Chain Bioscience – Novimmune SA

Tumor-targeted CD28 bispecific antibodies (bsAbs) are designed to co-stimulate T cells specifically within the tumor microenvironment. By bridging T cells to malignant cells expressing a selected tumor-associated antigen (TAA), CD28 bsAbs deliver Signal 2 to T cells, unleashing their full cytotoxic potential. Using our κλ body antibody platform, CD28 bsAbs targeting multiple TAAs were designed for tumor-specific activation of the immune system. The resulting TAA-CD28 κλ bodies enhance the antitumor response induced by CD3-retargeting bsAbs via stimulation of T cell proliferation and activation, increased cytokine secretion and cytotoxicity.


CD19-Targeted Affinity-Reduced CD28-Bispecific Antibody Enhances and Prolongs Anti-Tumor Activity of Glofitamab

Johannes Sam, PhD, Principal Scientist & Group Leader, Roche Innovation Center Zurich

A new CD19-CD28 bispecific antibody for the combination with Glofitamab (CD20-TCB) will be introduced. Costimulation via CD19-CD28 enhances Glofitamab-induced T cell activation and deepens and prolongs the anti-tumor efficacy. The IND-enabling preclinical data package will be summarized.


Harnessing T Cell Costimulation in Solid Tumors with Targeted CD28 Bispecific Antibodies

David E. Szymkowski, PhD, Vice President Preclinical Operations, Xencor, Inc.

T cells in the tumor microenvironment require both TCR/MHC (“Signal 1”) and costimulatory receptor (“Signal 2”) engagement to achieve complete activation. Solid tumors often lack expression of CD28 ligands, so we hypothesized that alternative activation of CD28-mediated Signal 2 could be beneficial in the TME. We designed tumor-associated-antigen (TAA) x CD28 bispecifics that conditionally costimulate T cells only in the presence of both target antigen and Signal 1. By providing a tumor-targeted Signal 2, this novel class of T cell engagers has the potential to enhance clinical responses to both anti-PD(L)1 antibodies and classical TAA x CD3 T cell engagers.



SIRPa-Fc-CD40L Engagement with CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade to Bridge Innate and Adaptive Immunity

George J. Fromm Jr., PhD, Vice President, R&D, Shattuck Labs, Inc.

CD47/SIRPa blockade enhances macrophage-mediated phagocytosis of tumor cells that are dying or have been tagged with an ADCP-competent antibody, however, this event does not enhance anti-tumor immunity in the absence of antigen presentation to CD8+ T cells. SIRPa-Fc-CD40L (SL-172154) links these two mechanisms via a type I interferon response and has shown profound activity in both mouse and non-human primate studies.

Close of Advancing Bispecific Antibodies Conference19:30