Advancing Bispecifics and Combination Therapy to the Clinic banner

The track on Advancing Bispecifics and Combination Therapy to the Clinic features case studies for haematological and solid tumours, bispecific-like products and biotherapeutics in combination. Presenters explain the rationale for the choice of combination, the background to the mode of action and how the products perform, as well as PK profile, PK/PD relationships, safety/toxicology studies, getting the right potency: side effect balance, translational studies, and risk assessment. Where appropriate, investigators present clinical trial design, demonstration of safety, issues that have arisen and have been resolved, proof of concept, dose escalation studies, and interaction with clinicians.

Final Agenda


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

Auditorium VI

08:30 Chairperson’s Remarks

Marina Bacac, PhD, Head, Cancer Immunotherapy, Roche Innovation Center Zurich

08:35 Multi-Specific Antibody Technology Engaging NK Cells in Oncology

Gauthier_LaurentLaurent Gauthier, PhD, Senior Director, Research and Development, Innate Pharma

We report the design and generation of new multi-specific antibodies which selectively recruit NK cells against tumour targets (NKCE). NCKEs bind to NKp46 on NK cells and can potentially co-engage other activating receptors like CD16 to induce tumor target killing. NKCEs show good developability profile, anti-tumour activity in in vitro and in vivo preclinical models and provide new therapeutic options for cancer treatment.

09:05 ATOR-1015, a Next-Generation, Bispecific CTLA-4 x OX40 Targeting Antibody for Tumor Directed Immunotherapy of Cancer

Furebring_TinaChristina Furebring, PhD, Senior Vice President, Research, Alligator Bioscience AB

ATOR-1015 is a next-generation CTLA-4 x OX40 bispecific immune activating antibody developed for tumor-directed immunotherapy. ATOR-1015 binds both targets simultaneously, promoting cell-cell interactions expected to enhance the immuno-stimulating effect of the compound. The mode of action of ATOR-1015 is a combination of regulatory T-cell (Treg) depletion and effector T-cell activation. ATOR-1015 is currently in preclinical development and clinical trials will start in the second half of 2018.

09:35 Development of an Agonist Redirected Checkpoint, SIRPa-Fc-CD40L, for Cancer Immunotherapy

George Fromm, PhD, VP, R&D, Shattuck Labs

We will present the generation of a novel, two-sided human fusion protein incorporating the extra cellular domains of SIRPα and CD40L, SL-172154. SL-172154 binds both CD47 and CD40 with high affinity, activates CD40 signaling in the absence of Fc receptor cross-linking, outperforms CD47 and CD40 antibodies in multiple tumor models and was safe in non-human primates. SL-172154 will enter the clinic in 2019 in multiple indications.

10:05 Development and Application of MOA-Based Reporter Bioassays for Immunotherapy Drug Development

Mei Cong, Director, Custom Assay Services, Promega Corporation

Having a functional bioassay that is MOA-based, accurate, precise, robust and reproducible is critical for the development of antibody-based biologics. We have developed reporter bioassays that meet these criteria for a broad range of antibody modalities including Fc effector function, immune checkpoint modulation, bispecific antibody engagement, cytokine modulation, and others. Here we will present the latest technology advancements and demonstrate how these bioassays can be used for a broad range of applications.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

Auditorium VI

11:15 KEYNOTE PRESENTATION: Development of Effective Combination Therapies for Immuno-Oncology

de_Haan_LolkeLolke de Haan, PhD, Senior Director R&D, Global Immuno-Oncology Safety Lead, Biologics Safety Assessment, Medimmune Ltd 

This presentation will cover: the rationale for combination therapies in immunotherapy; the challenges of selecting the combination drugs that would give synergism; translational and precision medicine approaches in combination immune-oncology, and safety considerations in development of the combination drugs.

11:45 Development of Novel Fully Human Bispecific Antibodies for Oncology

Smith_EricEric Smith, PhD, Director, Bispecific Antibodies, Regeneron, Inc.

This presentation will describe Regeneron’s bispecific platform and present preclinical data on T-cell redirecting bispecifics being developed for solid and liquid tumor indications. In addition, a brief update on the status of REGN1979, Regeneron’s CD20xCD3 bispecific in Phase I clinical trials, will be presented.

12:15 CD20 TCB (RG6026), a Novel “2:1” T-Cell Bispecific Antibody for the Treatment of B-Cell Malignancies

Bacac_marinaMarina Bacac, PhD, Head, Cancer Immunotherapy, Roche Innovation Center Zurich

We give an overview of preclinical data of CD20-TCB, a novel CD20-targeting T-cell bispecific antibody on the “2:1” IgG format that consistently demonstrated superior potency compared to other CD20-TCBs with conventional “1:1” IgG format. In addition, we present a novel approach enabling safer administration of such potent drug consisting of a single administration of obinutuzumab (Gazyva pre-treatment, Gpt) prior to the first infusion of CD20-TCB.

12:45 Affimer Therapeutics: A Novel Human Scaffold for the Generation of Bi-Specific Molecules

Amrik Basran, PhD, CSO, Avacta

Affimer therapeutics are based on the human protein Stefin A, a small (12kDa) intracellular protease inhibitor. We have built large (1x1010) phage display libraries and generated highly selective Affimer binders to range of therapeutically relevant targets such as PD-L1 and LAG-3. We have shown that the Affimer scaffold can be formatted as in-line fusions, to the Fc domain or a full antibody to create bispecific molecules are able to engage both target antigens.

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

14:15 Session Break

14:30 Chairperson’s Remarks

Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron

14:35 Targeting B-Cell Malignancies with a CD3 Bispecific Antibody - Preclinical Evaluation of DuoBody-CD3xCD20

Hiemstra_IdaIda Hiemstra, PhD, Lead Scientist, Translational Research, Genmab B.V.

An overview will be presented of preclinical data identifying DuoBody-CD3xCD20 as the most potent B-cell-targeting CD3 bispecific antibody in an in vitro functional screen covering a comprehensive panel of B cell targets. DuoBody-CD3xCD20 induced potent T cell activation and cytotoxic activity in the presence of malignant B-cells in vitro and in vivo. The capacity of DuoBody-CD3xCD20 to deplete B cells from blood and lymphoid organs, after intravenous or subcutaneous administration, was assessed in cynomolgus monkeys as part of the non-clinical safety studies. A clinical study evaluating the DuoBody-CD3xCD20 is currently enrolling.

15:05 APVO436: A CD3 Engager with Low Cytokine Release Profile Targeting CD123 for AML

McMahan_CatherineCatherine J. McMahan, PhD, Senior Director, Pharmacology and Cell Sciences Research and Non-Clinical Development, Aptevo Therapeutics

APVO436 is a CD123 x CD3 bispecific ADAPTIR antibody designed to treat AML. It contains an Fc region for extended half-life and has bivalent binding to both the tumor target and CD3. APVO436 was optimized for manufacturability, specificity and low levels of cytokine release compared to other bispecific formats. APVO436 induces robust proliferation of T-cells and tumor target lysis in vitro and in vivo xenograft models.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

Auditorium VI

16:15 Engineering Bispecific Cytokine-Fc Fusions to Create Safer and More Effective Immuno-Oncology Therapies

Szymkowski_DavidDavid Szymkowski, PhD, Vice President, Cell Biology, Xencor

Immunostimulatory cytokines such as IL-2 and IL-15, while extremely potent, suffer from poor tolerability and rapid clearance, limiting their potential as cancer treatments. Using our clinically-validated bispecific Fc domain, we generated a heterodimeric IL15/IL15Rα-Fc with reduced potency and longer half-life. IL15/IL15Rα-Fc demonstrates improved exposure and stimulates multiple effector-cell responses in mice and monkeys. Such cytokine-Fc biologics may possess better tolerability and improved efficacy with less-frequent dosing than recombinant cytokines.

16:45 Immunostimulatory Properties of a Novel IL-15-Based Tumor-Targeted Immunocytokine

Anika Jäkel, PhD, Director, Preclinical Pharmacology & Cancer Immunology, Glycotope GmbH

Interleukin-15 (IL-15), a potent stimulator of NK and CD8 T-cells, is considered to be one of the most encouraging immunotherapeutics for cancer treatment. We created novel IL-15-based immunocytokines with different potencies and Fc effector functions binding to a tumor-specific carbohydrate antigen to potentiate tumor targeting. By applying a comprehensive screening approach considering PK, PD and cytokine profile, we seek to identify a promising lead candidate suitable for mono or combinatorial therapy of solid tumors.

17:15 Development of Novel Interleukin-2 Variants for Immunotherapy of Cancer and Autoimmune Diseases

Moessner_EkkehardEkkehard Moessner, PhD, Head, Protein Engineering, Large Molecules Research, Roche Innovation Center Zurich

The development of interleukin-2 muteins throughout the preclinical development will be described, for two different approaches. In one approach the IL-2 will be used for cancer immunotherapy, and in the other, the IL-2 is engineered for applications in autoimmune diseases.

17:45 Networking Reception in the Exhibit Hall with Poster Viewing (Pavilion 1)

18:45 Problem-Solving Breakout Discussions (Foyer E&F)

Development of Effective Combination Therapies for Immuno-Oncology

Moderator: Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron, Inc.

  • What makes for a good combination therapy?
  • Strategies for conducting preclinical studies with combinations and how to translate the results to humans
  • Determination of optimal dosing regimens and schedules for combination therapies
  • Measures to ensure safety
  • How to examine combination approaches that are not well tolerated
  • Addressing potential long term safety concerns

Overcoming the Challenges of CD3 Bispecifics

Moderator: Catherine J McMahan, PhD, Senior Director, Pharmacology and Cell Sciences Research and Non-Clinical Development, Aptevo Therapeutics

  • Sharing of experiences regarding cytokine release and toxicity and means of overcoming this
  • Benefits of Fc engineering
  • Selection procedures to use
  • Measures to enhance potency and specificity
  • Means of enhancing manufacturing
  • Preclinical models to use

19:45 End of Day


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

Auditorium VI

08:30 Chairperson’s Remarks

David Szymkowski, PhD, Vice President, Cell Biology, Xencor

08:35 Update on BiTE® Antibody Constructs Currently in Clinical Development

Nägele_VirginieVirginie Nägele, PhD, Senior Scientist, BiTE Technology, Amgen Research (Munich) GmbH

The BiTE® technology is a clinically explored approach targeting malignant cells by T-cells with blinatumomab being the first bispecific T-cell engager (BiTE) approved for the treatment of patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) in the US. More recently, blinatumomab has also received accelerated approval for the treatment of B-ALL minimal residual disease. This presentation will give an update on the current clinical development of BiTE antibody constructs at Amgen focusing on hematologic malignancies like acute myeloid leukemia and multiple myeloma, and on solid tumor indications.

09:05 DVD-Ig Platform: Clinical Lessons and Future Directions

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

Several DVD-Ig molecules have been tested in preclinical models and in clinic for autoimmune and oncology indications. Emerging data suggests that the DVD-Ig format per se is not immunogenic. However, target biology may play an important role in anti-drug antibody response (ADA, immunogenicity). Lessons learned from these studies may be broadly applicable and will be discussed.

09:35 Development of a Potent Anti-Cancer Bispecific Antibody Targeting VEGF and DLL4

Weon-Kyoo_YouWeon-Kyoo You, PhD, Head, R&D, Vice President, ABL Bio, Inc.

Simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways is known to lead potent inhibition of tumor progression. In this presentation, we will talk about ABL Bio’s bispecific antibody platforms and development processes of the most advanced asset, a bispecific antibody targeting VEGF and DLL4 (ABL001) which is currently ongoing a Phase I clinical study. We will cover an overview of preclinical data as well as interim clinical data of ABL001.

10:05 SMAB: a Novel Bispecific Antibody Platform for Therapeutic Development

Janice Jin, Head, Project Management Center, Project Management Department, GenScript

Urgent demands for new therapeutic strategies, such as novel modalities are raised during explosive growth of therapeutic antibody drugs. In this presentation, we will introduce GenScript proprietary SMAB bispecific antibody platform which minimizes the immunogenicity and manufacture concerns of current bispecific antibody platforms while enabling bi-valent and multi-valent therapeutics.

10:20 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

Auditorium VI

11:15 Agonist Bispecific Antibodies Delivering the Next Immuno-Oncology Breakthrough

Tuna_MihribanMihriban Tuna, PhD, Senior Vice President, Drug Discovery, F-star

Targeting T cells via TNFRSF costimulatory pathways has the potential to strongly activate the immune system due to broad expression across multiple immune cells. However, FcgR-mediated crosslinking is often required for optimal activity, limiting clinical efficiency, due to low affinity of Fc:FcgR interactions and ADCC-mediated T cell depletion. We will present novel bispecific programmes that do not rely on FcgR binding, but instead crosslink their two targets, resulting in a potent and controlled T cell activation.

11:45 Tumor-Localized T-Cell Co-Stimulation Using Antibody-Anticalin Fusion Proteins: From Flexible Design to Proof-of-Concept and Beyond

Marina Pavlidou, PhD, Project Leader, Discovery, Pieris Pharmaceuticals GmbH

We describe the generation of bispecific molecules by fusing T-cell targeting Anticalin proteins to tumor targeting antibodies. We show superior potency of the bispecific over the combination of building blocks and the combination of benchmark molecules. The activity of the bispecific is dependent on the expression of the tumor target showing the potential of providing a tumor localized activation of the immune system with high efficacy and reduced peripheral toxicity.

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

13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

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

17:00 Dinner Short Course Registration* (Foyer C)

17:3020:30 Dinner Short Courses

Recommended Short Course*

SC10: Engineering of Bispecific Antibodies - View Detailed Agenda

Nicolas Fischer, PhD, Head, Research, Novimmune SA

Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J

By attending this interactive workshop, you will learn about the various approaches used for the engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different technologies will be compared, and examples for applications of bispecific antibodies in drug development will be presented with a focus on candidates that are currently being evaluated in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific antibodies will be discussed.

*Separate registration required.