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Cambridge Healthtech Institute’s 9th Annual

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

Combination Therapy & Engineering Multi-Specificity

1月23日~24日

Part of the Antibody Therapeutics pipeline

CHI’s Bispecific Antibody Therapeutics conference explores the challenges of engineering multi-specificity to achieve more effective therapies that bind to at least two targets simultaneously. The conference examines how these molecules are used to fight a wide array of diseases, as well as in combination therapy for enhanced effects in the fight against cancer. Along with increased efficacy, Bispecific Antibody Therapeutics can also optimize expenses by reducing the cost of development and clinical trials. Case studies highlight novel engineering approaches and platform constructs that improve safety, stability, enhanced targeting, and manufacturability.

Final Agenda

1月23日(木)

7:45 am Registration and Morning Coffee

多特異性抗体療法の効能の実現

8:10 Organizer’s Welcome Remarks

Mary Ruberry, MA, Senior Conference Director, Cambridge Healthtech Institute

8:15 Chairperson’s Opening Remarks

Steffen Goletz, PhD, Professor and Deputy Head, Biotechnology and Biomedicine, and Vice Director, Institute of Bioengineering, Technical University of Denmark

KEYNOTE PRESENTATION

8:20 The Landscape of Multi-Specific Antibodies

Partha S. Chowdhury, Senior Director, Biologics Research, Sanofi Genzyme

Etiology and progression of diseases usually involves an intricate interplay of a number of molecular entities. Targeting and modulating activities of two or more of these molecules or homing an effector component, such as a cell to the disease site or bridging two components in the pathologic site, serves an important therapeutic mechanism of action (MOA). This talk will be a synopsis of the different designs and their associated biological MOA.

FEATURED PRESENTATION

9:00 Bispecific Antibodies: Combinatorial and Activatable Functionalities

Brinkmann_UlrichUlrich Brinkmann, PhD, Expert Scientist and Scientific Director, Roche Pharma Research & Early Development, Roche Innovation Center Munich


9:30 Dealing with the Combinatorial Complexity of Protein Engineering: Bi- and Multi-specifics, TCRs and CAR Ts 

Kolinko_SebastianSebastian Kolinko, PhD, Scientific Consultant, Biologics, Genedata

We present a new technology platform to fully automate both molecular design, as well as the integrated assessment of potency, efficacy, and developability profiling of large panels of bispecific candidates. We will present use cases showing how the platform allows for the systematic cloning, expression, purification, and characterization of complex multi-specific, CAR T and TCR modalities, with a focus on immuno-oncology applications.

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

次世代の組み換え技術と設計

11:00 Maximizing Therapeutic Potential of Bispecific Antibodies and Cytokines by Affinity and Avidity Engineering

Szymkowski_DavidDavid E. Szymkowski, PhD, Vice President, Cell Biology, Xencor, Inc.

New immunotherapeutic modalities, such as T cell-engaging, tumor-targeted bispecific antibodies, T cell-activating cytokines, and checkpoint blockers are rapidly changing the cancer treatment paradigm. However, an unintended consequence of these biologics’ high potency is a suboptimal therapeutic index due to immune-related adverse events (irAEs). I will discuss case studies showing that next-generation immunotherapeutics can be engineered by affinity- and avidity-tuning to improve efficacy while reducing irAEs, thereby increasing their therapeutic index.

11:30 Benchmarking T Cell-Redirecting Therapies for Cancer: Comparing CD3-Bispecifics and CAR T Cells

DiLillo_DavidDavid J. DiLillo, PhD, Senior Staff Scientist, Immuno-Oncology, Regeneron Pharmaceuticals

The two leading platforms for redirecting a patient’s T cells to recognize tumors, CD3-binding bispecific molecules and chimeric antigen receptor (CAR) T cells, both show clinical activity. We have developed pre-clinical in vitro and in vivo models to mechanistically compare these two technologies and will discuss our findings, as well as the clinical implications.

12:00 pm Presentation to be Announced



12:15 Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

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

T細胞組換え二重特異性抗体

2:15 Chairperson’s Remarks

David J. DiLillo, PhD, Senior Staff Scientist, Immuno-Oncology, Regeneron Pharmaceuticals

2:20 Advancing a Novel T Cell-Engaging Bispecific Antibody that Induces Lysis of Small Cell Lung Cancer Cells in vitro and Shows Potent T Cell-Redirected Anti-Tumor Activity in Vivo

Scheer_JustinJustin Scheer, PhD, Director, Antibody Engineering, Boehringer Ingelheim


2:50 Novel Insights into T Cell-Redirected Killing of Tumor Cells

Demarest_StephenStephen Demarest, PhD, Senior Research Fellow, Lilly Biotechnology Center, Eli Lilly and Company

Using computational modeling and protein engineering, we generated novel agents to redirect T cells to fight cancer. We created a novel platform for robust production of these novel agents and demonstrate interesting novel geometrical constraints for redirected lysis.

3:20 Networking Refreshment Break

多特異性抗体によるがん治療

3:45 Engineered Multi-Specific Antibodies for Targeted Inhibition of Cancer Metastasis

Spangler_JamieJamie B. Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University

Metastasis is responsible for 90% of all cancer-related deaths, yet current anti-cancer therapies are designed to inhibit growth of the primary tumor and fail to address or sometimes even exacerbate metastasis. We leverage our recent discovery of a biochemical pathway that drives tumor cell migration to engineer multi-specific antibodies that potently block metastasis. This new approach presents an exciting opportunity for targeted therapeutic design that synergizes with current anti-cancer therapies.

4:15 Modulating the Immune System with Multi-Specific Antibodies in Cancer

Trinklein_NathanNathan Trinklein, PhD, Chief Technology Officer, TeneoBio, Inc.

Using a unique sequence-based discovery approach, we have created a large collection of fully human antibodies targeting a variety of tumor antigens and activating receptors on immune cells. Using machine learning tools, we rapidly establish sequence-activity relationships and identify key residues and variable region positions in the antibody repertoire with desired agonist behavior. Our lead program, TNB383B (BCMAxCD3) is currently in phase 1 clinical studies. In summary, we have created a platform for tunable immune activation at the site of the tumor that works with a variety of tumor antigens.

4:45 Revision of RTK Tumor Targeting: How to Design Truly Potent Bispecific and Biparatopic Agents

Tamaskovic_RastislavRastislav Tamaskovic, PhD, Head, TCL Tumor Targeting, Biochemistry, University of Zurich

Due to adaptiveness of oncogenic networks, tumors driven by hyperactivated RTK receptors readily develop resistance against targeted therapies. We developed multivalent chimeric vehicles devoid of toxic payloads, which achieve their tumoricidal activity by trapping tumor-driving receptor tyrosine kinases in inactive conformations and/or supramolecular assemblies. Using analogous construction scheme, we build a new platform for tumor RTK fingerprinting aimed at identification of prospective therapeutic leads or truly synergistic combination therapies.

 

5:15 Close of Day

1月24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.

Click here for more details

プラットフォーム技術

9:00 Chairperson’s Remarks

David E. Szymkowski, PhD, Vice President, Cell Biology, Xencor, Inc.

9:05 Utility of the ADAPTIR Platform to Build Stable, Bispecific Proteins with Novel Mechanisms of Action

Bienvenue_DavidDavid Bienvenue, PhD, Senior Director, Protein Sciences, Aptevo Therapeutics

The ADAPTIR™ bispecific platform offers key advantages due to its flexible and modular nature. Preclinically, potent biological activity has been demonstrated with ADAPTIR bispecifics designed to engage the immune system via several different mechanisms while retaining antibody-like manufacturing characteristics. An update on advanced preclinical and clinical bispecific candidates will be covered. The presentation will include a discussion of developability criteria to consider during the selection and development of bispecific antibodies.

9:35 CB213: A Second-Generation Checkpoint Inhibitor Optimally Configured for Therapeutic Efficacy

Legg_JamesJames Legg, PhD, Senior Vice President, Research, Crescendo Biologics, Ltd.

Crescendo has a proprietary transgenic mouse platform for generation of fully human VH domains (Humabody VH). The talk will describe the identification and characterisation of CB213, a tetravalent, trispecific therapeutic delivering dual checkpoint blockade through dual inhibition of PD-1 and Lag3.

10:05 Targeted and Conditional Biologics

Ritacco_WendyWendy Ritacco, MSc, Senior Scientist III, Global Biologics, AbbVie

Targeted and locally activated biologics, such as the bi-specific conditional dual variable domain immunoglobulins (cDVD-Igs), offer new opportunities for engineering efficacy while sparing systemic side effects. We will describe preclinical examples of tissue targeting in normal and disease in vivo models as part of a new generation of locally acting “regio-specific” biologics therapies.

10:35 Networking Coffee Break

多特異性抗体開発の画期的な成果

11:00 Development of NM21-1480, a Trispecific Anti-PD-L1x4-1BBxhSA Antibody Fragment

Meyer_SebastianSebastian Meyer, PhD, Chief Operating Officer, Numab Therapeutics AG

NM21-1480 is a molecule that potently blocks PD-L1/PD-1 signaling and elicits 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. Next to NM21-1480, Numab advances several immune-modulatory products targeting specific tumor antigens based on its proprietary antibody fragment technology.

11:30 Engineering Multi-Specific Antibodies Leveraging Patients’ Active B Cell Responses

Lippow_ShaunShaun Lippow, PhD, Director, Protein Engineering, Atreca, Inc.

Atreca discovers novel cancer-specific targets and native human antibodies to those targets, through examination of the active B cell responses of cancer patients. Antibodies that specifically bind non-autologous human tumor are advanced through our drug discovery pipeline, including standard IgG formats and next-generation multi-specifics. I will discuss our selection of multi-specific formats for cell engagement and the engineering of potent anti-tumor molecules.

12:00 pm Conference Wrap-Up

Goletz_SteffenSteffen Goletz, PhD, Professor and Deputy Head, Biotechnology and Biomedicine, and Vice Director, Institute of Bioengineering, Technical University of Denmark


12:30 Close of Conference

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