advancing bispecifics and combination therapy to the clinic

Advancing Bispecific and Combination Therapy to the Clinic focuses on novel concepts and their developments. Presentations will include synergistic combinations together with their rationale and provide data showing improved performance, including potency, targeting, stability, half-life and reduced toxicity. Preclinical studies leading up to proof-of-concept and IND enabling studies will be included as well as developments up to phases 2 and 3 for the more advanced products.

Final Agenda


07:45 Registration (Foyer A) and Morning Coffee (Foyer D)

Auditorium VI

08:30 Chairperson’s Opening Remarks

Paul W.H.I. Parren, PhD, Executive Vice President, Head, R&D, Lava Therapeutics B.V.

08:35 Progress with Bispecific Vγ9Vδ2-T Cell Engagers

Parren_PaulPaul W.H.I. Parren, PhD, Executive Vice President, Head, R&D, Lava Therapeutics B.V.

Vγ9Vδ2-T cells constitute the largest γδ-T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. Our Vγ9Vδ2-T cell engager platform brings important advantages over existing (CD3-based) T cell engagers. Recent preclinical development data including potency, mechanism of action, activity with patient-derived tumor cells, and safety will be discussed.

09:05 Preclinical Combinations of T Cell Bispecifics Targeting Solid Tumors and Hematological Malignancies

Bacac_MarinaMarina Bacac, PhD, Head, Cancer Immunotherapy Department 2 (CIT-2), Roche Innovation Center Zurich

We give an overview of preclinical activity of CEA-TCB and CD20-TCB, two clinical stage T cell bispecific antibodies based on the “2:1” IgG format. In addition, we present combination strategies of these two TCBs with checkpoint inhibitors and novel targeted costimulatory molecules.

09:35 A Novel Mucin 16 Bispecific T Cell Engaging Antibody for the Treatment of Ovarian Cancer

Crawford_AlisonAlison Crawford, PhD, Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals, Inc.

REGN4018 binds both Mucin 16 (MUC16) and CD3. REGN4018 induced T cell killing of MUC16-expressing tumor cells in vitro in the presence of CA-125. REGN4018 potently inhibited tumor growth in a xenogeneic mouse model, as well as in immuno-competent mice genetically engineered to express human CD3 and human MUC16. Toxicology studies in cynomolgus monkeys revealed no overt toxicity, supporting clinical evaluation of REGN4018 in patients with advanced ovarian cancer.

Biocytogen 10:05 Renmab™ Mouse: A Leading Platform for Fully Human Antibody Generation 

Chaoshe Guo Vice President, Global Head of Business Development, Biocytogen

Biocytogen has recently developed RenMab Mouse, a fully human antibody mouse with its entire variable regions replaced by human Ig heavy chain and light chain. The RenMab™ model has also demonstrated a similar immune response to the wildtype strain as it carries the full human antibody repertoire. Combined with existing inventory of single, double or triple target humanized mouse models, Biocytogen is poised to provide an one-stop solution from target validation to IND application.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

11:15 KEYNOTE PRESENTATION: Bispecific Antibodies: Discovery, Development, and Next Generation

Tomoyuki Igawa, PhD, CEO, Head, Research, Global Biologics Leader, Chugai Pharmabody Research Pte. Ltd.Tomoyuki Igawa, PhD, CEO, Head, Research, Global Biologics Leader, Chugai Pharmabody Research Pte. Ltd.

Emicizumab, a humanized anti-FIXa/FX bispecific antibody for hemophilia A, is the first bispecific IgG antibody which was approved by the FDA. Now, many T cell-redirecting bispecific IgG antibodies are being developed. In my presentation, I will talk about the discovery and development of these bispecific IgG antibodies, and how novel antibody engineering can further improve the properties of these molecules.

11:45 Discovery and Optimization of a Novel T Cell Bispecific for the Treatment of Solid Tumors

Root_AdamAdam Root, MSc, Senior Principal Scientist, BioMedicine Design, Pfizer Inc.

PF-07062119 is a novel T cell bispecific that targets guanylin cyclase 2C (GUCY2C) and CD3. PF-07062119 was engineered to have optimal efficacy and developability properties and is currently being developed for the treatment of gastrointestinal cancers. PF-07062119 demonstrates potent in vivo efficacy in human CLX and PDX adoptive transfer models as well as in syngeneic tumor models in immuno-competent human CD3 transgenic mice. PF-07062119 shows combination benefits with checkpoint inhibitors and with chemo- and anti-VEGF-therapy. I will review the discovery and pre-clinical testing of this molecule.

12:15 Targeting Cancer with BiTE® Antibody Constructs

Kischel_RomanRoman Kischel, MD, Director, Research, Amgen Research (Munich) GmbH

The presentation will discuss the structure and mode of action of BiTE antibody constructs, provide an update on the development of the BiTE antibody platform, and showcase early clinical data for a novel BiTE antibody construct targeting myeloma.

12:45 The Journey to ‘the’ Antibody: Tailoring for Success

González-Pajuelo_Maria_PGDMaría González Pajuelo, CSO, FairJourney Biologics

To maximize the possibility to select “the” antibody, at FJB we have taken antibody discovery to an unprecedented level by creating a versatile toolbox that allows the selection by phage display of antibody fragments of different species from large naïve and immune repertoires. Ultimately, these fragments can be engineered and converted to mono- and bi-specific formats that are produced in CHO cells.

13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

14:15 Session Break

Auditorium VI

14:30 Chairperson’s Remarks

Adam Root, MSc, Senior Principal Scientist, BioMedicine Design, Pfizer Inc.

14:35 Developing Bi- & Multi-Specific Immune-Modulatory Biologics to Address Unmet Needs

Ghayur_TariqTariq Ghayur, PhD, Distinguished Research Fellow, AbbVie Bioresearch Center

This will examine the technical challenges of making bi-/multi-specific biologics that have been (or can be) solved, and address the key challenges, namely to design molecules that match the disease biology and meet clinical needs. We are developing methods and tool molecules to understand the biology of the various aspects of cancer, ranging from the immunity cycle to the design of therapeutic molecules. Examples of these efforts will be discussed.

15:05 Benefits of Chicken-Derived Antibodies for Combination Immunotherapy

Koefoed_KlausKlaus Koefoed, PhD, MSc, Director, Antibody Technology, Symphogen A/S

Development of novel antibodies and more powerful therapeutic combinations for immunotherapy is an intense area of focus. However, difficult and/or conserved targets, finding antibodies with unique functionality, and generating early PoC pose challenges to the development of novel antibody therapeutics. Symphogen’s approach to discovery and development of potent antibody combinations for cancer immunotherapy using different species, including chicken, will be presented. Examples from our clinical pipeline will be shown.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

16:15 DuoHexaBody-CD37, a Novel CD37-Targeting Bispecific Antibody with a Hexamerization-Enhancing Mutation, Demonstrating Superior Preclinical Activity Against Malignant B Cells in vitro, ex vivo, and in vivo

Esther Breij, PhD, Senior Director, Translational Research, Genmab B.V.

DuoHexaBody™-CD37 is a bispecific antibody with a hexamerization-enhancing mutation that targets two different epitopes on CD37. DuoHexaBody-CD37 was designed to induce highly potent cytotoxicity of B cells in a variety of B cell malignancies through enhanced complement-dependent cytotoxicity (CDC) and other Fc-mediated effector functions. Here we will present studies on the rational design, mechanism of action, and pre-clinical efficacy of DuoHexaBody-CD37.

16:45 Towards RNA-Based Cancer Immunotherapy: Advances in the Development of mRNA Encoded Therapeutic Antibodies

Ellinghaus_UrsulaUrsula Ellinghaus, PhD, Scientist, Bispecific Antibodies, BioNTech RNA Pharmaceuticals GmbH

BioNTechs RiboMAB® platform, based on in vitro-transcribed non-immunogenic mRNA encoding for a variety of antibodies, is circumventing the production challenges and manufacturing cost of protein-based monoclonal antibodies. Systemic administration of RiboMABs formulated in LNPs results in sustained antibody levels and elimination of advanced tumors in mice as efficient as the corresponding purified antibody. Given the feasibility and safety of RiboMABs, we created an exciting platform technology for cancer immunotherapy.

17:15 Anticalin Proteins and Their Application in Respiratory Disease

Rothe_ChristineChristine Rothe, PhD, Vice President, Discovery & Alliance Management, Pieris Pharmaceuticals GmbH

Anticalin® proteins are based on human lipocalins and can be formulated as inhalable biologics, allowing local delivery to the lung. This was demonstrated with AZD1402/PRS-060, an IL-4Ra antagonist that Pieris is developing in collaboration with AstraZeneca for the treatment of moderate-to-severe asthma. A first-in-human study has revealed a promising clinical profile. The ability to generate bi- and multi-specific Anticalin proteins offers the potential to address more than one target in a disease pathway and thus improve efficacy and/or broaden the patient population for a range of respiratory diseases.

17:45 Networking Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)

18:45 Problem-Solving Breakout Discussions

TABLE 14: Next Generation Bispecific T Cell Engagers

Moderators: Paul W.H.I. Parren, PhD, Executive Vice President, Head, R&D Lava Therapeutics B.V.
Adam Root, MSc, Senior Principal Scientist, BioMedicine Design, Pfizer Inc

  • Limitations and opportunities
  • Increasing the therapeutic window
  • Format optimization and Fc engineering
  • Preclinical models to use

TABLE 15: Development of Effective Combination Therapies for Immuno-Oncology

Moderators: Marina Bacac, PhD, Head, Cancer Immunotherapy Department 2 (CIT-2), Roche Innovation Center Zurich
Christian Klein, PhD, Head, Oncology Programs, Head, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development (pRED)Roche Innovation Center Zurich


  • Which are the most promising combination partners for CD3 bispecific antibodies beyond a-PD(L)1 antibodies?
  • Which could be the best combination strategies for inflamed/immunogenic and non inflamed/non immunogenic tumors?
  • What makes a good combination therapy and how to translate the results to humans?
  • What do we know about the optimal dosing regimens and schedules for combination therapies?
  • How do we assess the safety of combination therapies in pre-clinical models? Can this be accurately assessed at all?

19:45 End of Day


08:00 Registration (Foyer A) and Morning Coffee (Foyer D)

Auditorium VI

08:30 Chairperson’s Remarks

Tariq Ghayur, PhD, Distinguished Research Fellow, AbbVie Bioresearch Center

08:35 PD-1 x LAG-3 (MGD013) and PD-1 x CTLA-4 (MGD019): Two Clinical-Stage DART® Molecules Designed to Simultaneously Block Two Checkpoint Pathways

Berezhnoy-AlexeyAlexey Berezhnoy, PhD, Scientist, Cell Biology & Immunology, MacroGenics, Inc.

Tumor-infiltrating lymphocytes frequently co-express multiple immune checkpoint receptors, whose co-blockade provides additional benefits in immunotherapy. Here we applied a bispecific platform to increase stringency and specificity of immune checkpoint co-blockade. Two clinical-stage bispecific DART molecules, PD-1 x CTLA-4 (MGD019) and PD-1 x LAG-3 (MGD013), will be discussed in this presentation, including format selection, preclinical pharmacology, IND-enabling studies, and clinical trial design.

09:05 A Novel, Monovalent Tri-Specific Antibody-Based Molecule that Simultaneously Modulates PD-L1 and 4-1BB Exhibits Potent Anti-Tumoral Activity in vivo

Stefan Warmuth, PhD, Head, CMC, Therapeutic Program Lead, Numab Therapeutics AG

Targeting PD-L1 and 4-1BB with multi-specific antibodies holds the promise of increased potency, while improving the safety profile compared to combination therapy. Numab develops a molecule that potently blocks PD-L1/PD-1 signaling and elicits further T cell activation through its costimulatory domain solely in the proximity of cells that overexpress PD-L1. Preclinical data show efficacy on tumor growth in combination with an enhanced intratumoral CD8+ T cell activation when compared to the combination of the PD-L1 and 4-1BB modalities.

09:35 Development of a Novel Bi-Functional Fusion Protein Platform (Agonist Redirected Checkpoint or ARC) for Cancer Immunotherapy

Fromm_GeorgeGeorge Fromm, PhD, Vice President, Research & Development, Shattuck Labs, Inc.

The ARC platform was developed to solve the challenge of incorporating immune-checkpoint blocking functional domains and tumor necrosis factor (TNF) superfamily agonists (OX40, CD40, 4-1BB, etc.) into single therapeutics. This was achieved by engineering hexameric TNF ligands, which uniquely activate TNF receptors compared to mono- or di-valent antibody-based approaches. The ARC platform has provided a means to unlock this family of costimulatory molecules, which is currently being evaluated in a clinical study.

Promega 10:05 Next-Generation Reporter Technologies for Immunotherapy Discovery and Potency Testing

Jamison Grailer, Senior Research Scientist, Research & Development, Promega Corporation

Immunotherapy strategies, including immune checkpoint monoclonal antibodies (mAbs), bispecific molecules, and chimeric antigen receptor T (CAR T) cells, are promising new approaches for treating cancer, autoimmunity, and other diseases. A major challenge in immunotherapy drug development is access to quantitative and reproducible functional assays for screening (e.g. TCR screening), measurement of target cell-specific killing, and potency testing. Here we will present a variety of next-generation reporter technologies to address these needs in the context of mAb-mediated ADCC, bispecific molecules, and TCR-mediated cell therapies.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

Auditorium VI

11:15 Unbiased Functional Screening of Large Bispecific Antibody Panels to Unlock Novel Biology

Van_Loo_Peter_FokkoPieter Fokko van Loo, PhD, Director, Oncology-Immunology, Merus N.V.

The Biclonics® technology platform leverages the natural human IgG1 format; enabling high throughput functional screening to discover drug candidates with excellent anti-tumour properties. The discovery of two clinical stage pipeline candidates will be discussed that highlight the power of this functional screening approach: MCLA-117, a CLEC12AxCD3 T cell engaging antibody for acute myeloid leukemia and MCLA-145, CD137xPD-L1 bispecific antibody that recruits and supercharges tumor infiltrating lymphocytes.

11:45 An International Collaborative Study to Establish a 1st Reference Panel for Cytokine Release Assays

Vessillier_SandrineSandrine Vessillier, PhD, Principal Scientist, Head, Immunotoxicology Cellular Immunology, Biotherapeutics, National Institute for Biological Standards and Control, UK

Cytokine release assays (CRAs) are key for hazard ID of immunotherapeutics, such as cytokine release syndrome (CRS). To gain a better understanding of the comparability between different CRA formats, NIBSC recently produced a panel of lyophilised recombinant antibodies known to induce CRS of different intensities and three isotype-matched negative controls. The relative potency of these antibodies to stimulate cytokine release was evaluated in an international collaborative study.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

14:00 End of Advancing Bispecifics and Combination Therapy to the Clinic

17:00 Dinner Short Course Registration*

17:3020:30 Dinner Short Courses

Recommended Short Course*

SC10: Engineering of Bispecific Antibodies and Multi-Specific Non-Antibody Scaffolds - LEARN MORE

*Separate registration required.