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Cambridge Healthtech Institute 第8回

Bispecific Antibody Therapeutics
( 二重特異性抗体療法 )

Engineering Multi-Specificity

2019年1月17日~18日

 

二重特異性抗体療法をテーマにしたこのカンファレンスプログラムでは、2つ以上の分子標的と同時に結合することでより効果的な治療を可能にする多特異性抗体の開発にまつわる課題が議論されます。次世代の抗体フォーマットは、画期的な技術や組み換えの手法を採用することにより、がんをはじめとする疾病の克服に向けた取り組みのなかで高い有効性を示します。

Final Agenda

1月17日(木)

7:45 am Registration and Morning Coffee

T細胞と結合した二重特異性抗体

8:10 Organizer’s Welcome Remarks

Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute

8:15 Chairperson’s Opening Remarks

James Ernst, PhD, Senior Scientist, Protein Chemistry, Genentech, Inc.


KEYNOTE PRESENTATION

8:20 T Cell Therapeutics in Hematological Malignancies and Solid Tumors

Tara Arvedson, PhD, Director, Oncology Research, Amgen, Inc.

T cell therapeutics have demonstrated a clinical benefit in hematological malignancies and there is early evidence of activity in solid tumors. Analysis of data derived from T cell therapeutics in hematological malignancies will increase the chances of success for similar therapeutics in solid tumors. This presentation will describe key findings from recent trials of T cell therapeutics in hematological malignancies and will relate these findings to approaches for treating solid tumors.

9:00 Expanding Bispecific Antibody Technology to Enable Multiple Avenues of T Cell Activation

Matthew Bernett, PhD, Associate Director, Protein Engineering, Xencor, Inc.

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 PD1 x CTLA4 and CTLA4 x LAG3 bispecific antibodies, as well as a PD1 x ICOS bispecific antibody that combines checkpoint blockade and costimulation into a single molecule. Finally, we have utilized our heterodimeric Fc domain to create a novel long-acting IL15/IL15Rα-Fc for immunotherapy.

9:30 An Integrated Approach to Managing Immunogenicity Risk and Optimum Protein Design

Fry_JeremyJeremy Fry, Director, Sales, ProImmune, Ltd.

Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages. ProImmune offers mutational activity mapping for optimal protein design, DC-T/T cell proliferation assays for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation, HLA-peptide binding assays to characterize individual epitopes and undiluted whole blood cytokine storm assays.

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

T細胞と結合した二重特異性抗体 (続き)

11:00 A Novel Multi-Specific Antibody Targeting PD-L1-Overexpressing Cancers that Stimulates Antigen-Committed CD8+ T Cells through Concomitant Engagement the Costimulatory Receptor 4-1BB

Sebastian Meyer, PhD, COO, Numab Innovation AG

Targeting PD-L1 and 4-1BB with a multi-specific antibody format holds the promise of increased potency while improving safety. 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 close 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.

11:30 Leveraging Anti-Tumor Immunity through Bispecific DART Molecules

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

Boosting host immune responses through antibody-based blockade of checkpoint pathways has provided unprecedented response rates in select cancer types. Bispecific antibody targeting provides opportunity to optimize and expand benefit. Examples of such strategies utilizing the DART®/TRIDENT™ platforms will be presented, including simultaneous targeting of multiple checkpoints, redirected T-cell killing of tumor cells and tumor-anchored immune co-stimulation. Topics covered will span structural design, preclinical development and clinical proof-of-concept.

12:00 pm Session Break

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing

腫瘍とHER2を標的化するためのバイパラトピック抗体

2:15 Chairperson’s Remarks

G. Jonah Rainey, PhD, CEO, Oriole Biotech, Inc.

2:20 Redefinition of RTK Tumor Targeting: How to Design Truly Potent Anti-HER2/3 Bispecific and Biparatopic Agents

Rastislav Tamaskovic, PhD, Head, TC Facility, Biochemistry, University of Zurich

Due to adaptiveness of oncogenic networks, tumors readily develop resistance against targeted therapies. Recently, we developed a new class of bispecific and biparatopic anti-HER2/3 targeting agents to overcome the adaptive resistance. These targeting vehicles achieve their superior tumoricidal activity by trapping tumor-driving receptor tyrosine kinases in inactive conformations and/or supramolecular assemblies. Analogously, we built a new platform for tumor RTK fingerprinting to identify prospective therapeutic leads and combination therapies.

2:50 ZW25/ZW49, Development of a HER2-Targeted Biparatopic Antibody and Biparatopic Antibody-Drug Conjugate

David Poon, PhD, Executive Director, External R&D and Alliances, Zymeworks, Inc.

ZW25 is a bispecific antibody directed against two distinct epitopes (biparatopic) on HER2 that has been successfully engineered using the Azymetric™ IgG1 antibody scaffold. ZW25 is well tolerated and has demonstrated promising single-agent anti-tumor activity in heavily pretreated HER2-expressing breast, gastric, and other cancers. Preclinical development of ZW49, a biparatopic antibody-drug conjugate based on the unique design of ZW25 and armed with our proprietary ZymeLink™ cytotoxic payload, will also be discussed.

3:20 Sponsored Presentation (Opportunity Available)

3:35 Networking Refreshment Break

二重特異性抗体によるがん治療

4:00 SMITE Bispecifics: A Novel Combination Strategy to Combat Cancer

Ashok D. Bandaranayake, PhD, Director, Bioprocess Development and Automation, Protein Therapeutics Program, Fred Hutchinson Cancer Research Center

We propose a new way of gaining a high level of specificity for cancer by employing two bispecific molecules simultaneously. Importantly, each of these molecules is designed to have little or no activity on their own, so that healthy tissue bearing either one of the targets is not affected. However, when both targets are expressed (in cancer) the two bispecific molecules act in synergy, stimulating and co-stimulating T cells for maximum efficacy.

4:30 ATOR-1015, a Bispecific CTLA-4 x OX40 Antibody, Induces Anti-Tumor Effects through Tumor-Directed Immune Activation

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB

ATOR-1015, a next-generation CTLA-4 antibody designed to deplete Tregs and activate effector T cells. ATOR-1015 is tumor-directed, which is expected to result in a favorable benefit/risk profile. A clinical Phase I trial is planned to start in H2 of 2018.

5:00 Activating the Immune System with Bispecific Antibodies

Mihriban Tuna, DPhil, Vice President, Drug Discovery, F-star Biotechnology, Ltd.

Cancer proliferates through numerous evasion strategies and re-engaging the immune system is key in the control of tumor growth. In recent years, checkpoint immunotherapies and their combinations have rapidly progressed from being a promising therapeutic opportunity to a robust clinical reality. In this presentation, we will discuss how checkpoint-binding bispecific antibodies have the potential to go beyond combinations by reversing down-regulation of the immune system and promoting tumor elimination.

5:30 Close of Day

1月18日(金)

8:00 am Registration

8:00 BuzZ Sessions with Continental Breakfast

Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies and strategies, challenges, and future trends.


Moderator: Moderator: Rakesh Dixit, PhD, DABT, Vice President, Medimmune-AstraZeneca

 

多価抗体の開発

9:00 Chairperson’s Remarks

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB

9:05 Fully Human, Heavy-Chain Antibodies Facilitate Rapid Development of Multi-Specific Antibodies

Wim van Schooten, PhD, CSO, TeneoBio, Inc.

TeneoBio’s discovery platform utilizes VH domains of fully human heavy chain antibodies (UniAbs) to develop bi-, tri-, and tetravalent antibodies. Binding domains of UniAbs are stable structures that can be easily put together into multi-specific antibodies. Clinical trials of TeneoBio’s first trivalent antibody will be initiated in 2018.

9:35 Format and Isotype Selection for Optimal Bispecific Activity

G. Jonah Rainey, PhD, CEO, Oriole Biotech, Inc.

Bispecific antibodies are versatile molecules that allow diverse and potent mechanisms of action. As we move from the first-approved bispecifics that retarget killing of T cells to tumor cells, strategies that take into account the ability to interact with non-adaptive immune and non-immune components need to be exploited to achieve optimal efficacy and safety. Design considerations including valency, effector function, and half-life will be discussed.

10:05 A Toolbox for the Generation, Purification, and Customized Functional Adaptation of Bispecific ADCs

Harald Kolmar, PhD, Professor, Applied Biochemistry, Technical University Darmstadt

A platform was developed for the facile generation of common light chain antibodies using yeast display. pH-dependent binding can be introduced by common light chain engineering. Bispecific ADCs are generated using SEED technology followed by enzyme-mediated coupling of a polymer-drug conjugate with high payload (DextraMab). We also established a route for the purification of bispecifics via affinity chromatography using tailor-made anti-idiotype binders.

10:35 Networking Coffee Break

二重特異性抗体による疾病の克服

11:00 Development of Bispecific Antibodies at Novartis

John W. Blankenship, PhD, Senior Investigator, Antibody Discovery, Novartis Institutes for BioMedical Research, Inc.

11:30 A Bispecific Antibody Mimetic of FGF21 for the Metabolic Disease and NASH

James Ernst, PhD, Senior Scientist, Protein Chemistry, Genentech, Inc.

Activation of the FGF21 pathway has been shown to improve multiple features of metabolic disease in animals. Here we describe a novel bispecific antibody that mimics the function and metabolic effects of FGF21. Treatment with this antibody improves glycemic and lipid profiles in mouse disease models and reduces body weight in mice and non-human primates. These effects mimic the activity of FGF21 on both mice and non-human primates, suggesting that antibody-mediated activation of FGF21 pathway would be an effective treatment for type 2 diabetes.

12:00 pm Conference Wrap-Up

Rakesh Dixit, PhD, DABT, Vice President, Medimmune-AstraZeneca

12:30 Close of Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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