Cambridge Healthtech Institute’s Inaugural

Bispecific Antibodies for Cancer Immunotherapy

Engineering Next-Generation Biotherapeutics in Immuno-Oncology

August 28-29, 2018

Engaging multiple receptors with bispecific biologics offers the potential to improve upon single-agent checkpoint blockade and promises to be the next generation of immunotherapy. Cambridge Healthtech Institute’s Inaugural Bispecific Antibodies for Cancer Immunotherapy meeting will showcase preclinical, translational and clinical studies on using bispecific antibodies for dual blockade of checkpoint targets, T-cell-redirecting bispecific biologics, overcoming T-cell exhaustion, as well as strategies to improve efficacy and reduce toxicity, and engineer the next generation of bi- and multi-specific biologics.


Final Agenda

TUESDAY, AUGUST 28

12:00 pm Registration

EMERGING BISPECIFIC BIOTHERAPEUTICS IN IMMUNO-ONCOLOGY

1:25 Chairperson’s Opening Remarks

Matthias Klinger, PhD, Principal Scientist, BiTE Immunology, Amgen Research GmbH


1:30 FEATURED PRESENTATION: The Immune Force Awakens with Novel Bispecific Biotherapeutics: Challenges and Opportunities

Dixit_RakeshRakesh Dixit, PhD, DABT, Vice President, R&D; Global Head, Biologics Safety Assessment, MedImmune

This presentation will cover: 1) MOA-based smart strategies in making decisions about bispecific vs. combination mixtures; 2) novel bispecific strategies in maximizing the potential of combination biologics/targets through a single molecule; 3) smart engineering approaches to optimize valency, potency, avidity and half-life of bispecific IgG like mAbs; 4) minimize toxicity resulting from the simultaneous hit of two targets or redirected effector cells; 5) on and off-target toxicities and PK-PD resulting from the modulation of two targets should be carefully evaluated very early in drug development.

2:00 BiTE® Antibody Constructs beyond Blinatumomab: Overview of Amgen’s Early-Stage BiTE® Pipeline

Klinger_MatthiasMatthias Klinger, PhD, Principal Scientist, BiTE Immunology, Amgen Research GmbH

In the US, the bispecific T-cell engager (BiTE®) antibody construct blinatumomab has been approved for the treatment of relapsed or refractory B-precursor acute lymphoblastic leukemia and more recently, also in the respective minimal residual disease setting. This talk will focus on Amgen’s subsequent BiTE® pipeline in various hematologic malignancies like acute myeloid leukemia and multiple myeloma but also in solid tumor indications.

2:30 Advances with Bispecifics and Multi-Specifics in the Clinic – Lessons Learned

Ghayur_TariqTariq Ghayur, PhD, Senior Research Fellow, AbbVie

Of the many bi-/multi-specific biologics formats reported to date, some have progressed to clinical and late preclinical stages. Two areas of focus are now: 1) developing approaches to identify/select targets and/or target pairs with "novel" biology that absolutely requires bi-/multi-specific format; i.e., the specific biology cannot be achieved with monoclonal antibody combinations, and 2) to select the right format to achieve desired outcomes.   

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing


4:15 PLENARY KEYNOTE SESSION

4:20 CAR-T Therapy for B Cell Malignancies

Jennifer Brogdon, PhD, Director, Exploratory Immuno-Oncology, Novartis

 

Catherine Young4:55 Walking on the Moon: Reflections on the Work of the Cancer Moonshot and the Future of the Biden Cancer Initiative

Catharine Young, PhD, Senior Director, Science Policy, Biden Cancer Initiative

 

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

*Separate registration required.

6:30 End of Day

6:30-9:00 pm Dinner Short Course

SC1: Bioinformatics for Immuno-Oncology and Translational Research

6:30-9:00 pm Dinner Short Course

SC2: Next-Generation Immunotherapies: Part 1

WEDNESDAY, AUGUST 29

7:30 am Morning Coffee

T CELL AND TUMOR REDIRECTING BISPECIFIC ANTIBODIES

8:25 Chairperson’s Remarks

Bonnie Hammer, PhD, Vice President, Biologics Development, Invenra

8:30 A Novel Multi-Specific Antibody Targeting PD-L1 Overexpressing Cancers That Redirects and Stimulates Antigen-Committed CD8+ T Cells through Concomitant Engagement of a T Cell Costimulatory Receptor

David Urech, PhD, Co-CEO and CSO, R&D, Numab Therapeutics AG

9:00 Selective Blockage of the Innate Immune Checkpoint Receptor CD47 on Mesothelin (MSLN) Positive Solid Tumor Cells via Dual-Targeting Bispecific Antibodies

Stefano Majocchi, PhD, Research Scientist, Research Department, Novimmune SA

Up-regulation of CD47 is an immune evasion mechanism used by different cancers to evade immune surveillance through the delivery of a universal “don’t eat me” signal to phagocytes. In order to avoid poor pharmacological properties and potential hematological toxicities linked to the indiscriminate blockage of ubiquitously expressed CD47, we developed a bispecific antibody (NI-1801) capable of selectively inhibiting CD47 on mesothelin-positive tumor cells. Due to the specificity of a targeting approach, NI-1801 retains potent anti-cancer efficacy both in vitro and in vivo while showing favorable pharmacological and toxicology profiles.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Using B-BodyTM Bispecific Antibodies to Modulate Anti-Tumor Immune Responses

Hammer_BonnieBonnie Hammer, PhD, Vice President, Biologics Development, Invenra

Bispecific antibodies have distinct advantages over monospecific antibodies by enabling more specific targeting and novel mechanisms of action. We have used our B-Body™ bispecific antibody platform to create antibodies allowing for redirected T cell killing, SNIPER™ antibodies that specifically target subsets of cells for elimination, and antibodies with enhanced agonist activity. Using these antibodies, we show the advantages of being able to screen for functional activity in order to select for a desired response.

11:15 PM-CD3: A Novel Highly Tumor-Specific T Cell Engaging Bispecific for the Treatment of Solid Tumors

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

Carbohydrates on the surface of cancer cells represent preferable targets for bispecifics due to their unique tumor-specificity with lack or inaccessibility on normal tissues and broad indication coverage. In a platform approach, we designed and screened several T cell engaging bispecific constructs recognizing the highly tumor-specific carbohydrate/protein antigen TA-MUC1 and CD3 that differed in binding valencies and affinities towards both antigens, serum half-life, molecule size, and Fc-functionality and produced them in our human expression platform GlycoExpress®.

11:45 Bispecific Antibodies for Immunotherapy and Radioimmunotherapy

Cheung_Nai-KongNai-Kong Cheung, MD, PhD, Enid A. Haupt Endowed Chair in Pediatric Oncology, Memorial Sloan Kettering Cancer Center

Conventional IgG monoclonal antibodies (mAbs) rely on Fc-dependent mechanisms with insufficient potency because of poor therapeutic index and limited effector cell traffic. Bispecific antibodies (BsAb) have the potential to turn circulating polyclonal T cells into tumor-infiltrating cytotoxic T cells without MHC-restriction to overcome the immunosuppressive tumor microenvironment. BsAb can also be exploited to deliver massive doses of beta or alpha radiation in multistep targeting with vastly improved therapeutic indices.

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

12:45 Session Break

BISPECIFIC ANTIBODIES FOR COMBINATION THERAPY

1:40 Chairperson’s Remarks

John Desjarlais, PhD, Senior Vice President, Research, CSO, Xencor


1:45 FEATURED PRESENTATION: Bispecific Technology for Multiple Avenues of T Cell Activation

Desjarlai_JohnJohn Desjarlais, PhD, Senior Vice President, Research, CSO, Xencor

Xencor has applied its XmAb bispecific technology platform to create multiple novel modalities for T cell derepression and activation. These include dual checkpoint inhibitors such as a PD1 x CTLA4 bispecific antibody, and a CTLA4 x LAG3 bispecific antibody that combines productively with anti-PD1 for triple checkpoint blockade. We have also discovered a highly active PD1 x ICOS bispecific antibody that productively combines checkpoint blockade and costimulation into a single molecule. Finally, we have utilized our heterodimeric Fc domain to create a novel long-acting IL15/IL15Ra-Fc format for immunotherapy.

2:15 FEATURED PRESENTATION: Mechanisms of Action for the Application of BiTE Antibodies in Immunotherapy Combinations

Tara Arvedson, PhD, Director, Oncology Research, Amgen

2:45 Tumor Localized Activation of Costimulatory Pathways

Manuela Duerr, PhD, Project Leader, Immuno-Oncology, Pieris Pharmaceuticals GmbH

This presentation will cover: 1) role of costimulatory pathways in T cell biology; 2) rationale for tumor localized activation of costimulatory receptors; 3) case study: in vitro and in vivo characterization of the HER2/4-1BB bispecific molecule PRS-343.

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Combination Strategies to Augment Activity of CD3 Bispecific Antibodies

Junttila_TeemuTeemu Junttila, PhD, Senior Scientist, Genentech

CD3 bispecific antibodies induce rapid activation of T cells leading to degranulation of cytolytic vesicles and apoptosis of target expressing cancer cells. T cell activation results also in feedback inhibition. PD1 up regulation has been described with multiple molecules and shown to inhibit activity of CD3 bispecific antibodies. The role of other co-inhibitory molecules is less clear. Our goal is to systematically characterize induction and functional role of key co-inhibitory and co-stimulatory molecules upon treatment with CD3 bispecific antibodies to identify optimal combination strategies.

4:30 Coordinate Engagement of T-Cell Regulatory Pathways Using Bispecific DART® Molecules

Wigginton_JonJon Wigginton, MD, Senior Vice President, Clinical Development & CMO, MacroGenics

Informed by successes achieved using immunotherapeutic approaches including checkpoint inhibitors and CAR T cells, tremendous attention has now focused on further harnessing the inherent power of the immune system to treat cancer using various combination regimens. A diverse range of pathways provide positive and negative signals to regulate the overall function of T cells. To simultaneously target these pathways, antibody combinations have been tested and demonstrated encouraging clinical activity in patients treated with Anti-PD-1 antibodies in combination with antibodies targeting CTLA-4 or LAG-3.

5:00 Orthomab, a Tetravalent Dual-Specific T Cell Costimulator that Elicits Antitumor Immunity

Adler_AdamAdam J. Adler, PhD, Professor, Immunology, University of Connecticut

Combination immunotherapies can more effectively control tumors compared to monotherapies, but also have greater potential to elicit adverse events. We developed OrthomAb, a novel combinatorial single-drug biologic comprised of mAb agonists to the TNFR family costimulatory receptors CD134 and CD137 covalently-linked into a heterodimer, that potentiates T cell effector functions and in vivo tumor control. Importantly, OrthomAb’s tetravalent structure should enable the minimization of adverse events while preserving therapeutic efficacy.

5:30 Dinner Short Course Registration*

*Separate registration required.

5:30 Close of Bispecific Antibodies for Cancer Immunotherapy

6:00-9:00 pm Dinner Short Course

SC3: Next-Generation Immunotherapies: Part 2

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