
第15回年次会議「二重特異性と併用療法の臨床的進歩」
二重特異性抗体や多重特異性抗体のプラットフォームと技術開発の進歩により、新しい構築物や臨床候補が大量に生まれ、臨床における安全性と有効性が検証されています。臨床・前臨床データのレビューは、2023年11月15日にリスボン(ポルトガル)で開催されるPEGS Europe Summitの第15回年次会議「二重特異性と併用療法の臨床的進歩:新規かつ相乗的な組み合わせ」で特集される予定です。FDAの承認を得て上市されている、二重特異性抗体医薬のレパートリーを増やすために、候補のトランスレーショナルアプローチと最適化について、業界リーダーらが議論する予定です。
Scientific Advisory Board:
Nicolas Fischer, PhD, CEO, Light Chain Bioscience
Pieter Fokko van Loo, PhD, Senior Director, Oncology - Immunology, Merus NV
Jeanette H.W. Leusen, PhD, Professor, Translational Immunology, Utrecht University
Paul WH Parren, PhD, Executive Vice President and Head, Research and Development, LAVA Therapeutics; Professor,
Molecular Immunology, Leiden University Medical Center
David E. Szymkowski, PhD, Vice President, Preclinical Operations, Xencor, Inc.
Recommended Short Course*
Monday, 13 November, 14:00 - 17:00
SC2: Developability of Bispecific Antibodies: Formats and Applications
*Separate registration required. See short courses page for details. All short courses take place in-person only.
11月15日(水)
Registration Open and Morning Coffee07:30
TRANSLATIONAL APPROACHES TO OPTIMIZING DOSING
投薬の最適化に対するトランスレーショナルアプローチ
Bispecific Antibodies: Preclinical and Translational Strategies to Support Clinical Dose Setting
Esther C.W. Breij, PhD, Vice President, Head of Translational Research, Genmab BV
The presentation will review preclinical and translational strategies to help identify the optimal dose in the clinical setting. Examples of preclinical pharmacodynamic studies for CD3 bispecifics and immune agonist bispecific antibodies will be provided, as well as clinical biomarker data to monitor pharmacodynamic activity in the clinic.
KEYNOTE PRESENTATION: T Cell Redirecting Antibodies for the Treatment of Hematological Malignancies
Ulrike Philippar, PhD, Senior Director & Head, Oncology & Discovery Hematological Malignancies, Janssen Pharmaceutica NV
Within the past decade, therapies that activate T cells and redirect them to cancer cells have changed the landscape of treatment of hematological malignancies. Key factors for a successful T cell-redirecting therapeutic include selective target expression on the tumor cells, with minimal to no expression in other tissues, and a potent molecule, e.g.; a bispecific antibody, that can eliminate malignant cells to achieve long-term benefit.
Session Break to Transition into Plenary Keynote10:00
PLENARY KEYNOTE SESSION
基調講演(プレナリーセッション)
Benchmarking the Impact of AI Biologics Discovery and Optimisation for Pharma
Rebecca Croasdale-Wood, PhD, Director, Augmented Biologics Discovery & Design, Biologics Engineering, Oncology, AstraZeneca
The biologics landscape is rapidly changing with the number of AI-enabled biologics in pre-clinical and clinical stages estimated to be 50-60 (1). This change is driven by the increase in enterprise software solutions to capture and store data, augmented discovery workflows, improvements in machine learning technology, and advances in computing power. Augmented biologics discovery has the potential to revolutionize biologics discovery, yet information of how in silico technologies perform, versus traditional discovery platforms is scarce. At PEGS Europe, we will present current in silico biologics design and optimisation technologies, with a focus on our internal efforts to benchmark the impact of combining novel in silico technologies with our existing biologics discovery platforms.
Coffee Break in the Exhibit Hall with Poster Viewing11:00
T CELL ENGAGERS
T細胞エンゲージャー(TCE)
ISB 2001: A First-in-Class Trispecific BCMA and CD38 T Cell Engager Designed to Overcome Mechanisms of Escape from Treatments for Multiple Myeloma by Targeting Two Antigens
Mario Perro, PhD, Vice President, Head of Oncology Research Department, Ichnos Sciences
ISB 2001, trispecific molecule based on the BEAT platform. ISB 2001 targets CD3 on T cells and co-targets BCMA and CD38 on Multiple Myeloma (MM) cells. Binding arms on ISB 2001 were derived from a synthetic phage display library using a common light chain. ISB 2001 exhibited higher killing potency (EC50) than all tested BCMA specific T cell engagers (TCE). In vivo tests with ISB 2001 show IgG-like half-life and efficient tumour eradication. Based on the specific dual targeting of MM cells, significant benefit is anticipated for relapsed/refractory patients, who may experience tumor escape through target downregulation mechanisms.
Bispecific Antibody Mediated, PD-L1-Dependant, CD28 Co-Stimulation
Sara Majocchi, PhD, Discovery Program Leader, Light Chain Bioscience - Novimmune SA
By associating a blocking anti-PD-L1 antibody arm with an agonist anti-CD28 antibody arm, we generated a PD-L1xCD28 bsAb (NI-3201) inducing CD28 signaling upon PD-L1 blockade on PD-L1+ tumor and immune cells (e.g., antigen-presenting cells). Data from the preclinical development of NI-3201 will be presented, with a focus on in vitro and in vivo de-risking activities.
Session Break13:15

Phil Leighton, PhD, Senior Director, Molecular Biology, OmniAb
We have developed an engineered chicken that produces VHH antibodies with human variable regions. In these birds, the human VH contains framework mutations to provide stability and a truncated light chain that facilitates immunoglobulin secretion in the absence of the VL domain. Productive B-cell development is observed, and when immunized with various targets, antigen-specific VHH offered a diverse repertoire of sequences, broad epitope coverage, and binding affinities reaching single-digit nM.
Session Break14:20
HARNESSING NEUTROPHILS USING BISPECIFICS
二重特異性を使用した好中球の利用
Bispecific IgA to Activate Neutrophils to Kill Cancer
Jeanette H.W. Leusen, PhD, Professor, Translational Immunology, Utrecht University
All current therapeutic monoclonal antibodies are based on IgG. For the past 25 years, we have been working on IgA as a different isotype to treat cancer, since it activates neutrophils very efficiently, even the suppressive type of neutrophils in the TME. At the moment, we are developing a bispecific antibody based on IgA, that also blocks CD47 as a myeloid checkpoint inhibitor molecule.

Lei Shi, PhD, Senior Vice President, Biointron Biological
Biointron has established an industry-leading 2-week antibody production service, supported by a powerful high-throughput expression platform. Armed with this high-efficiency platform, our FC-MES affinity maturation system is able to provide non-biased antibody optimization and affinity maturation in less than 2 months. Our VHH and Single B cell-based discovery projects are also benefited and expedited by this unique capability.
Refreshment Break in the Exhibit Hall with Poster Viewing16:05
CO-STIMULATORY BISPECIFICS
共刺激の二重特異性
Tumor-Targeted CD28 Bispecific Antibodies Preferentially Enhance T Cell Costimulation and Activation in the Tumor Microenvironment
David E. Szymkowski, PhD, Vice President Preclinical Operations, Xencor, Inc.
T cell costimulation via CD28 signaling (Signal 2) enhances anti-tumor activity. However, solid tumors often lack CD28 ligands. We hypothesized that tumor-associated-antigen x CD28 bispecifics could focus a strong Signal 2 in the tumor microenvironment. We assessed antigens including CEACAM5, mesothelin, STEAP-1, and Trop-2. Such bispecifics enhanced T cell degranulation, cytokine secretion, and tumor-cell cytotoxicity only when coupled with TCR engagement (Signal 1). To promote a favorable therapeutic index, we also tuned bispecific formats and affinities to preferentially target cancer cells with high antigen expression. Costimulatory bispecifics against these four tumor antigens show promising activity and warrant further development for solid tumors.
CB307: A Novel T Cell Costimulatory Humabody VH Therapeutic for PSMA-Positive Tumours
Colette Johnston, PhD, Vice President, Discovery, Crescendo Biologics Ltd.
CB307 is a novel trispecific Humabody therapeutic targeting CD137, prostate specific membrane antigen (PSMA) and human serum albumin (HSA), enabling tumour-specific T cell activation, with minimal systemic activation. It is generated by formatting fully human VH domains from the Crescendo Mouse. CB307 mediates CD137 reporter cell signaling in PSMA dependent manner and enhances human T cells activity in co-culture assay. The first human clinical study (NCT04839991) is ongoing.
Tumor-Targeted Costimulation via CD28 Bispecific Antibodies: Turning Immunotherapy “Cold” Tumors “Hot"
Dimitris Skokos, PhD, Senior Director, Cancer Immunology, Regeneron Pharmaceuticals
Monoclonal antibodies that block the programmed cell death 1 (PD-1) checkpoint have revolutionized cancer immunotherapy. We have recently described a class of costimulatory bispecifics that crosslink a tumor specific antigen to CD28 (e.g. PSMAxCD28, REGN5678), synergize with the broader anti-PD-1 approach, and endow responsiveness against tumors that otherwise do not respond to anti-PD-1 alone: such as, metastatic castration-resistant prostate cancer (mCRPC). By combining these costimulatory bispecifics as off-the-shelf drugs, with Libtayo (aPD-1), we have the opportunity to create novel therapeutic synergies to address some of the most difficult-to-treat cancers.
Two Targets, Two Signals: A Combinatorial Concept for Cancer Therapy with Bispecific Antibodies Directed to CD3 and CD28
Martin Pflugler, PhD, CEO, TWYCE GmbH
Success of bispecific antibodies (bsAbs) in solid tumors is still limited due to (i) lack of accessibility of the tumor site for immune effector cells, (ii) lack of sufficiently tumor-specific target antigens and (iii) lack of costimulatory “signal 2” that enables thorough and long-lasting T cell activation. Using our proprietary antibody platform, we overcome these limitations by a combination of functionally interrelated bsAbs that target two different antigens on tumor cells, and notably also the tumor vasculature, and stimulate CD3 and CD28 on T cells.
Close of Advancing Bispecific Antibodies and Combination Therapy to the Clinic Conference19:00
* 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。
Conference Programs


- Antibody-Based Therapies
治療用抗体 - Emerging Targets & Approaches
新興の標的と治療アプローチ - Membrane Protein Targets
膜タンパク質の標的

- Safety & Efficacy of Bispecifics
二重特異性抗体の安全性と有効性 - Advancing Bispecifics
二重特異性の進歩 - Engineering Bispecifics
二重特異性の工学


- Optimisation & Developability
最適化と開発可能性 - Analytical Characterisation
アナリティクス特性評価 - Protein Stability & Formulation
タンパク質の安定性と製剤


