Cambridge Healthtech Instituteの第11回年次

Advancing Bispecific Antibodies and Combination Therapy to the Clinic
(臨床への二重特異性抗体と併用療法の進展)

キラーコンボの創出

2023年5月16〜17日 EDT(東部夏時間)

二重特異性抗体は、10年以上にわたってバイオロジクスの世界を席巻しており、現在、臨床への進出が非常に有望視されています。前臨床および臨床開発の結果は、これらの構造がin vivoでどのように作用するかを示しています。新たな構造は革新的なアプローチと共に大きな進展を見せ、ターゲットの精度を高めるために前進しています。PEGS Bostonサミットの第11回「臨床への二重特異性抗体と併用療法の進展」トラックでは、業界の主要研究者が集まり、新しい構造の安全性と有効性について戦略を立て、最新の臨床結果を検討し、腫瘍学を超えた領域への使用を拡大します。

Scientific Advisory Board
Frank Comer, PhD, Associate Principal Scientist, AstraZeneca
Eric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals, Inc.
Nathan D. Trinklein, PhD, Co-Founder and President, Rondo Therapeutics

5月14日(日)

- 5:00 pm Main Conference Registration1:00 pm

Recommended Pre-Conference Short Course2:00 pm

SC1: Antibody Drug Discovery: From Target to Lead

*Separate registration required. See short courses page for details.


5月16日(火)

Dessert Break in the Exhibit Hall with Poster Viewing1:40 pm

NON-T CELL ENGAGERS AND OTHER BISPECIFIC MECHANISMS
非T細胞エンゲージャーとその他の二重特異性のメカニズム

2:15 pm

Chairperson's Remarks

Nathan D. Trinklein, PhD, Co-Founder and President, Rondo Therapeutics

2:20 pm

Antibody-Lectin Bispecifics for Glyco-Immune Checkpoint Blockade

Jessica Carol Stark, PhD, American Cancer Society Postdoctoral Fellow, Stanford University

Tumors use sugars, or glycans, to evade the immune system. I will describe development of antibody-lectin bispecifics as a modular and programmable approach to target glycans for cancer immunotherapy.

2:50 pm

PROTABs for Targeted Degradation of Transmembrane Proteins

Nicholas Agard, PhD, Principal Scientist, Antibody Engineering, Genentech, Inc.

PROteolysis TArgeteing Bispecifcs (PROTABs) are antibodies that colocalize transmembrane E3 ubiquitin ligases with target receptors to induce their ubiquitination and degradation. We will describe the discovery of PROTABs targeting ligases overexpressed in colorectal cancer and their activities in vitro and in vivo. We further demonstrate applicability of PROTABs for multiple ligases and receptors and describe protein engineering rules for maximizing the efficiency of degradation.

3:20 pm Miniaturized quality assays to accelerate selection of clones producing a high percentage of bispecifics heterodimer

Aurora Fabrey-Wood, Ph.D, Product Manager, Cell Line Development, PhenomeX, Inc

Microfluidic chips can be used to sort and clone CHO cells, perform miniaturized assays, and recover top performers.  This automated process reduces the number of clones that must be expanded and characterized, while simultaneously increasing the likelihood of finding a cell line producing a high percentage of bispecific heterodimer. Here, I will present data demonstrating how miniaturized quality assays enable selection of top performing clones within five days of cloning.

Refreshment Break in the Exhibit Hall with Poster Viewing3:50 pm

4:30 pm

Surrogate Cytokine Agonists (SCAs): Unlocking Natural and Novel Cytokine Signals with Nanobody-Based Therapeutics

Sandro Vivona, PhD, Senior Director of Biochemistry and Biophysics, Synthekine, Inc.

At Synthekine, we have generated a series of functional synthetic cytokine agonists (SCAs) that mimic and modulate natural signals or create new ones. These molecules are expected to provide therapeutic immunomodulation while exhibiting antibody-like druggability. 

5:00 pm

PD1-IL2v: PD-1-Cis IL-2Rbg Agonism Yields Better T Cell Effectors from Stem-Like CD8+ T Cells

Pablo Umana, PhD, Head, Oncology Discovery, Roche

This talk will describe a new generation of PD1-cis-targeted IL-2R agonists resulting from the fusion of a high-affinity PD-1 antibody to an IL-2Rbg agonist. Such agonists maintain the advantages of IL-2Rbg-biased agonists for systemic immunotherapy, but in addition allow the expansion of a unique subset of less exhausted and more cytotoxic effector T cells when acting on antigen-experienced stem-like CD8+ T cells. These findings provide the basis for the development of a new generation of PD-1 cis-targeted IL-2R agonists with enhanced therapeutic potential for the treatment of cancer and chronic infections.

5:30 pm PANEL DISCUSSION:

Surface Proteomics for Target Discovery: Finding Target Combinations That Improve Tissue Specificity and Therapeutic Index

PANEL MODERATOR:

Jan E. Schnitzer, MD, Institute Director, Proteogenomics Research Institute for Systems Medicine

  • Why and how multi-targeting can help 
  • How best to find cell surface targets
  • How to combine and prioritize targets based on therapeutic goals
  • Examples of multi-targeting advances
PANELISTS:

Rakesh Dixit, PhD, President & CEO, Bionavigen

Close of Day6:00 pm

Dinner Short Course Registration6:00 pm

Recommended Dinner Short Course6:30 pm

SC6: Developability of Bispecific Antibodies

*Separate registration required. See short courses page for details.

5月17日(水)

Registration and Morning Coffee7:30 am

TRIGGERED BISPECIFICS
トリガーとなる二重特異性

8:25 am

Chairperson's Remarks

Frank Comer, PhD, Director, Tumor Targeted Delivery, Early Oncology R&D, AstraZeneca

8:30 am

KEYNOTE PRESENTATION: Triggered Bispecifics  

JoAnn A. Suzich, PhD, Head, Research, Immunocore LLC

Tissue-restricted immune modulators may provide better therapeutic approaches to autoimmune disease. We are developing bispecifics consisting of a high affinity targeting domain fused to a PD-1 agonist moiety to inhibit autoreactive T cells for the treatment of skin diseases such as vitiligo and atopic dermatitis. These molecules, once bound to target cells, activate the PD-1 pathway potently inhibiting inflammatory cytokine production and cytotoxic activity. In the absence of target cell binding, they are unable to inhibit T cells. These immune-modulating bispecifics have the potential to deliver skin-restricted T cell inhibition while avoiding systemic immunosuppression.

9:00 am

Design Meets Biology - Engineering Immune Engagers with Potentially Improved TI

Yariv Mazor, PhD, Senior Director, R&D, Biologics Engineering, AstraZeneca

T cell engagers are highly potent anti-cancer immunotherapeutic molecules. However, on-target, off-tumor toxicity and cytokine release syndrome (CRS) limit the broad application of these drug modalities. Through several case studies, we’ll showcase the development of next generation immune engagers that can better engage and modulate T cell reactivity with the aim to decouple tumor cell killing from systemic toxicity.

9:30 am PANEL DISCUSSION:

Overcoming Obstacles with Triggered Bispecifics

PANEL MODERATOR:

Frank Comer, PhD, Director, Tumor Targeted Delivery, Early Oncology R&D, AstraZeneca

PANELISTS:

Yariv Mazor, PhD, Senior Director, R&D, Biologics Engineering, AstraZeneca

JoAnn A. Suzich, PhD, Head, Research, Immunocore LLC

10:00 am Talk Title to be Announced

Weian Zhao, Professor, Aureka Biotechnologies

10:15 am Talk Title to be Announced

Speaker to be Announced

Coffee Break in the Exhibit Hall with Poster Viewing10:30 am

Transition to Plenary Keynote Session11:10 am

PLENARY KEYNOTE SESSION
プレナリーセッション・基調講演

11:20 am

Plenary Keynote Introduction

Maria Wendt, PhD, Head, Biologics Research US & Global Head, Digital Biologics Platform (ML/AI), Large Molecule Research, Sanofi

11:30 am

Advancing Innovative Biologics Modalities from Research to Clinical Application - Novel Platforms, Automation, and Computation

Rebecca A. Sendak, PhD, Head, Global Large Molecules Research Platform, Sanofi

Addressing disease biology in the clinic with protein therapeutics has become increasingly complex. Turning to innovative and novel scaffolds offers opportunities to tailor therapeutics not previously possible due to advances in host cell engineering and protein design approaches. Designing and developing these modalities requires a next-generation approach as we exploit increased potential design space and also growing data sources to leverage as we invent the next wave of therapeutics.

YOUNG SCIENTIST KEYNOTE
若き科学者の基調講演

12:15 pm

Engineering Prime Editor Proteins for Therapeutic Applications

Andrew V. Anzalone, MD, PhD, Director & Head, Prime Editing Platform, Scientific Co-Founder, Prime Medicine, Inc.

Precision gene editing technologies have the potential to address a wide range of genetic diseases. Prime Editing is a recently developed “search-and-replace” gene editing approach that can precisely perform a wide variety of DNA sequence edits at programmed target sites in human genomes without requiring double-strand DNA breaks or donor DNA templates. I will describe advances to prime editing technology that improve its efficiency, specificity, and capabilities for therapeutic applications.

Session Break1:00 pm

1:10 pm LUNCHEON PRESENTATION:Wrangling Diverse OmniAb Antibody Repertoires with OmniDeep

Bob Chen, PhD, Sr. Director, Systems Engineering, OmniAb, Inc.

We are presenting a showcase of discovering common light chain antibodies against a NK cell target. OmniDeep is a suite of in silico tools for antibody therapeutic discovery and optimization. Deep screening and high-throughput expression/characterization were used to seed information on top of NGS data sets. Our results demonstrate the power of this approach in corralling diverse OmniAb antibody repertoires and accelerating the development of effective therapeutics.

1:40 pm LUNCHEON PRESENTATION:Luncheon Presentation to be Announced

Speaker to be Announced

INTERACTIVE DISCUSSIONS
インタラクティブディスカッション

2:10 pmFind Your Table and Meet Your Moderator
2:15 pmInteractive Discussions

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.

INTERACTIVE DISCUSSION:

Therapeutic platforms for antibody-mediated protein degradation.

Nicholas Agard, PhD, Principal Scientist, Antibody Engineering, Genentech, Inc.

  • Review the multiple technologies have recently emerged to induce targeted degradation of cell surface or secreted proteins including LyTACs, PROTAbs/AbTACs, and KineTACs.
  • Discuss pros and cons of targeted degradation vs. inhibition, and where targeted degradation may be most applicable.
  • Compare different antibody-mediated degradation technologies and discuss where they may be optimally used.
  • Discuss what protein-engineering approaches might be applicable to enhance degradation efficiency.

CO-STIMULATION AND COMBINATIONS
共刺激と併用

3:00 pm

Chairperson's Remarks

Eric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals, Inc.

3:05 pm

Combining Signals 1, 2, and 3 for Optimal T Cell Activation against Tumors

John R. Desjarlais, PhD, CSO, Xencor, Inc.

Xencor is developing a growing pipeline of CD3 and CD28 T cell engagers, together with several potency-optimized cytokine-Fc fusions, including IL15, IL12, and IL18. We will discuss preclinical data exploring combination of these various agents with themselves and PD1 inhibition to promote optimal T cell activation in the tumor microenvironment.

3:35 pm

Targeted Therapies for the Enhancement of Anti-Tumor T Cell Responses

Eric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals, Inc.

This presentation will describe key pre-clinical data from Regeneron’s new clinical approaches to enhancing anti-tumor efficacy of T cells, focusing on the combination of costimulatory bispecific antibodies with checkpoint blockade and T cell redirecting bispecifics. In addition, data from new classes of T cell targeted enhancement strategies in pre-clinical development will be discussed.

4:05 pm Talk Title to be Announced

Speaker to be Announced

Ice Cream Break in the Exhibit Hall with Poster Viewing4:35 pm

5:10 pm

T Cell Activation via Co-Stimulatory CD28 Bispecific Antibodies

Nicolas Fischer, PhD, CEO, Light Chain Bioscience

Antibodies CD28 bispecific antibodies (bsAbs) were generated to co-stimulate T cells in the presence expressing a selected tumor-associated antigen (TAA) or by co-engaging PD-L1 on cancer cells or antigen-presenting cells. Using our κλ body antibody platform, CD28 bsAbs targeting multiple TAAs were designed for tumor-specific activation of the immune system. CD28-engaging κλ bodies enhance the antitumor response via stimulation of T cell proliferation and activation, increased cytokine secretion, and directed cytotoxicity. Desired characteristics of the anti-CD28 arm, approaches to drive selective co-engagement, and TAA-dependent co-stimulation versus immune checkpoint-dependent co-stimulation will be discussed.

5:40 pm

Partners-in-Crime: Co-Stimulation via 4-1BB or CD28 to Boost the Efficacy of T Cell Bispecifics

Christian Klein, PhD, Head, Oncology Programs and Department Head, Cancer Immunotherapy Discovery, Roche Innovation Center Zurich, Roche Pharma Research & Early Development, pRED

The presentation will cover an overview and update on preclinical properties of solid and heme tumor co-stimulators including FAP-4-1BBL, CD19-4-1BBL, and CD19-CD28 in active clinical development in combination with cibisatamab and glofitamab, respectively.

6:10 pm

Strength in Partnerships: Duobody CD40x41BB (GEN1042) Therapeutic for Advanced Solid Tumor Treatment

Homer Adams III, PhD, Associate Director, Genmab US, Inc.

Duobody GEN1042 is a conditional activator of co-stimulatory molecules 4-1BB and CD40 which has shown early promise in the treatment of advanced solid tumors. Preclinical data shows enhanced priming and anti-tumor activity inclusive of T cell proliferation and effector functions. Furthermore, monotherapy and combination data from our FIH, open-label, phase I/II trial (NCT04083599) reveal a manageable safety profile, clinical activity, and pharmacodynamics consistent with the mechanism of action.

Networking Reception in the Exhibit Hall with Poster Viewing6:40 pm

Close of Advancing Bispecific Antibodies and Combination Therapy to the Clinic Conference7:40 pm

* 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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Engineering
Oncology
Bispecific Antibodies
Immunotherpary
Expression
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Immunogenicity
Emerging Modalities