CHI’s Second Annual Bispecific Case Studies & Clinical Relevance conference will bring together clinicians, regulators, and industry experts in the field to discuss and exchange ideas on promising bispecific candidates. We will showcase all crucial topics from understanding the biology behind different bispecific constructs to mitigating challenges in advancing novel platforms to the clinic. A companion diagnostic aspect for bispecific platforms will be examined for meaningful therapeutic selection based on patient identification, stratification, and the early assessment of treatment efficacies. An extension of bispecific applications in other diseases besides oncology will also be discussed.

Final Agenda

WEDNESDAY, AUGUST 21

1:00 pm Registration

CLINICAL PROGRESS FOR BISPECIFICS AND COMBINATIONS

1:35 Chairperson’s Opening Remarks

Rakesh Dixit, PhD, DABT Vice President, AstraZeneca Biopharmaceuticals

1:40 FEATURED PRESENTATION: Introduction and Overview of Bispecific Antibodies in the Clinic: Learnings from Success and Failures

Rakesh-DixitRakesh Dixit, PhD, DABT Vice President, AstraZeneca Biopharmaceuticals

This talk will provide an introduction and overview of leading bispecific antibodies along with other combinations that are currently in the clinic, including the learnings from successes and failures of bispecific antibodies.

2:10 M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGF-β in Advanced Solid Tumors

Julius_StraussJulius Strauss, MD, Assistant Research Physician, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, NIH

M7824 is a bifunctional fusion protein targeting PD-L1 and TGF-β. In Phase I/II trials, M7824 has shown evidence of clinical efficacy in a variety of tumor types, including NSCLC, gastric ca, biliary tract ca and HPV associated malignancies.

2:40 ZW49 – A Novel Bispecific Antibody-Drug Conjugate (ADC) Targeting HER2-Expressing Cancers

Babcook_JohnJohn Babcook, PhD, Senior Vice President, Discovery Research, Zymeworks

ZW49 is a bispecific anti-HER2 ADC currently being evaluated in a Phase I clinical trial. In preclinical studies, ZW49 demonstrated complete tumor regressions in a panel of high and low HER2-expressing patient-derived xenografts, and promising efficacy in a model of breast cancer brain metastases at exposures tolerated in non-human primates. These results compared favorably when benchmarked against approved and leading HER2 ADCs in clinical development.

3:10 Sponsored Presentation (Opportunity Available)

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing

4:05 Leveraging Host Anti-Tumor Immunity through Bispecific DART® Molecule

Paul_MoorePaul A. Moore, PhD, Vice President, Cell Biology & Immunology, MacroGenics, Inc.

This presentation will review MacroGenics clinical experience with redirected T-cell killing bispecific DART molecules, and approaches to maximize therapeutic responses through combination with checkpoint inhibitors and/or immune co-stimulators.

4:35 ABL001 (NOV1501): A Novel Bispecific Antibody Targeting VEGF & DLL4 for the Treatment of Solid Tumors

Sang_Hoon_LeeSang Hoon Lee, PhD, CEO, ABL Bio

To date, all approved antiangiogenic drugs primarily inhibit the VEGF/VEGFR pathway. Delta-like ligand 4 (DLL4) has been identified as a potential drug target in VEGF-independent angiogenesis. A dual blockade of both VEGF and DLL4 could be a promising strategy to overcome anti-VEGF therapy resistance. ABL001 (NOV1501) has been developed as a bispecific antibody to bind and inhibit both DLL4 and VEGF, thereby significantly suppressing tumor angiogenesis. I will report the most recent data for this ongoing Phase 1a study. Phase 1b/2a study is planned in combination of ABL001 with chemotherapy or anti-PD-1 antibody.

5:05 Problem Solving Roundtable Discussions

6:05 End of Day

THURSDAY, AUGUST 22

8:00 am Morning Coffee

UNDERSTANDING THE BIOLOGY FOR ENHANCED SAFETY AND EFFICACY

8:30 Chairperson’s Remarks

Dimasi_NazzarenoNazzareno Dimasi, PhD, Associate Director, R&D, AstraZeneca Biopharmaceuticals


8:35 KEYNOTE PRESENTATION: Bioassay Development for Bispecific Antibody from an FDA Standpoint

Wen_Jin_WuWen Jin Wu, MD, PhD, Senior Investigator, Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA CDER

Bispecific antibodies are the agents targeting two antigens, such as two receptors expressed on either the same or the different cells, two ligands, or one ligand and one receptor, and have the unique potential to mediate multiple biological effects and may kill the tumor cells more efficiently compared to monoclonal antibodies. Bispecific antibodies Investigational New Drug (IND) submissions have grown enormously in recent years. Therefore, to improve product manufacturing and testing to help ensure availability of high-quality bispecific antibodies during clinical study, it is essential to develop cell-based bioassay(s) that can characterize biological activity, demonstrate mechanism of action, detect structural changes, and function as a quality control release assay. The regulatory issues and the pitfalls in bioassays will be discussed.

9:05 Lessons Learned from the Bis4Ab Platform: From a Bispecific Engineering Concept to Clinical Investigation.

Dimasi_NazzarenoNazzareno Dimasi, PhD, Associate Director, R&D, AstraZeneca Biopharmaceuticals

Over the past several years, we have generated several bispecific bivalent antibody formats. Amongst those formats, Bis4Ab is the most advanced format we have in clinical investigation. In this presentation, the Bis4Ab engineering design and development are presented. As an example of Bis4Ab, lessons learned during the preclinical and clinical investigation of MEDI3902, which is being investigated in Phase II trials as immunoprophylactic against Pseudomonas aeruginosa in mechanistic ventilated subjects are presented.

9:35 Design Meets Biology – Engineering a PD-1/CTLA-4 Bispecific Antibody to Improve Both Safety and Efficacy

Yariv_MazorYariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, AstraZeneca Biopharmaceuticals

MEDI5752 is a monovalent bispecific IgG1 antibody (DuetMab), targeting the two clinically validated receptors; PD-1 and CTLA-4. The bispecific antibody introduces novel MOAs that may provide an improved therapeutic index when compared to the two monotherapies and mAb combinations. MEDI5752 is currently being clinically evaluated for safety and efficacy.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Manipulation of Cell Surface Antigen Dynamics by Bispecific Antibody

Bin Liu, PhD, Professor, Anesthesia, University of California, San Francisco

Cell-type specific intracellular payload delivery is desired for antibody-based targeted therapy development. However, tumor-specific internalizing antigens are rare to find, and even rarer for those that are expressed at uniformly high levels. At the heart of the issue is if the dynamic behavior of a given cell surface antigen can be manipulated against its natural propensity and if so what are the key parameters involved. We constructed a bispecific antibody with one arm binding to a rapidly internalizing antigen and a second arm binding to non-internalizing antigen, and found that the overall internalization property of the bispecific is profoundly impacted by a few factors and is quite plastic, capable of converting in either direction. Thus upon bispecific targeting, internalization or non-internalization is no longer an antigen-intrinsic property and can be readily manipulated to achieve a desired therapeutic outcome. Examples of potential applications are discussed.

11:20 Developing “Fit-for-Purpose” Bi- and Multi-Specific Biologics to Achieve Desired Functional Outcomes

Ghayur_TariqTariq Ghayur, PhD, Distinguished Research Fellow, Immunology Discovery, AbbVie

To achieve desired therapeutic outcomes multiple features need to be considered in a therapeutic modality, for example: (i) valency and geometry of target binding domains; (ii) glycosylation profile and (iii) PK. In this talk we will describe our efforts to engineer such functional properties in bi- & multi-specific biologics.

11:50 Sponsored Presentation (Opportunity Available)

12:20 pm Enjoy Lunch on Your Own

CASE STUDY OF BISPECIFIC

1:50 Chairperson’s Remarks

Paul_MoorePaul A. Moore, PhD, Vice President, Cell Biology & Immunology, MacroGenics, Inc.


1:55 A B-body™ Bispecific OX40 Agonist Antibody that Exhibits Superior Activity without Secondary Crosslinking

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

OX40 is a costimulatory molecule found on T cells belonging to the tumor necrosis factor receptor superfamily (TNFR). TNFR superfamily members require high-order receptor clustering in order to achieve full activity. Traditional monoclonal antibodies require secondary cross-linking to achieve this high-order receptor clustering. We have developed a biparatopic antibody to OX40 that in the absence of cross-linking meets or exceeds the level of activation of a traditional monoclonal cross-linked antibody and exhibits potent in vivo efficacy in a mouse model.

2:25 ND021 Trispecific Anti-PDL1/4-1BB/hAS

David Urech, PhD, CEO, CSO, Numab Therapeutics AG

IMMUNOGENICITY AND CLINICAL PHARMACOLOGY CONSIDERATIONS

3:55 Chairperson’s Remarks

Paul_MoorePaul A. Moore, PhD, Vice President, Cell Biology & Immunology, MacroGenics, Inc.


4:00 FEATURED PRESENTATION: Clinical Pharmacology Considerations of Bispecific Antibodies

Ji_PingPing Ji, PhD, Pharmacologist, OCP, FDA

Bispecific antibodies as therapeutic agents are characterized by the ability to bind two different targets, either cell-surface receptors or soluble ligands, on the same or different cell(s). Their PK/PD properties, including their immunogenic potential, are closely related to their structural features such as molecular weight and physicochemical properties and binding affinity to the antigen. This presentation will describe the clinical pharmacology properties of bispecific antibodies and their clinical development strategy. The challenges of bioanalytical assay of bispecific antibodies will also be presented.

4:30 Immunogenicity Assessment of Bispecific Antibody Therapeutics in Clinical Studies

Peng_KateKate Peng, PhD, Group Leader/Senior Scientist, BioAnalytical Sciences, Genentech

Bispecific mAbs (bsmAbs) are a novel class of mAbs that aim to improve drug efficacy by simultaneously working on two targets. This is a relatively new approach with limited experiences in clinical development. This presentation discusses our strategy for assessing the anti-drug antibody (ADA) responses to the bsmAb and summarizes the characterization results as well as the clinical impact of ADAs on drug exposure and safety.

5:00 End of Bispecific Antibody Pipeline Congress

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