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The Engineering Antibodies program continues its quest to present the latest antibodies to watch. The conference will discuss novel platforms to engineer new molecules and emerging formats, such as conditionally-activated antibodies with masking strategies, single domain antibodies for in vivo targeting of intracellular proteins, bi- and multi-specific antibodies for treatment of SARS-CoV-2 as well as novel antibodies against challenging targets.Join us to hear from established biopharm veterans and rishing biotech stars as they share their latest programs and progress updates.

Sunday, 13 November

Recommended Short Course*14:00

SC5: Machine Learning Tools for Protein Engineering
*Separate registration required. See short courses page for details.

Tuesday, 15 November

Registration and Morning Coffee (Garden Room)07:30

ROOM LOCATION: Zafir

SINGLE DOMAIN ANTIBODIES

08:25

Chairperson's Opening Remarks

Lars Linden, PhD, Vice President, Head, Biologics Research, Bayer HealthCare AG

08:30

Engineering Options to Exploit the Novel Epitope Targeting of soloMER Biologics

Caroline J. Barelle, PhD, CEO & Founder, Elasmogen Ltd.

Our single domain technology consistently demonstrates novel epitope targeting compared with VHHs and mAbs. We have explored multiple engineered constructs to exploit this plus other advantages of our platform to develop novel autoimmune and cancer products. I will discuss technology platforms, advantages, and exploitation of these through engineering in addition to sharing our in vivo disease model data on both inflammatory and oncology indications as we progress towards the clinic.

09:00

AAV and mRNA Delivery of VHH Intrabodies for in vivo Targeting of Intracellular Proteins

Erwin De Genst, PhD, Senior Research Scientist, AstraZeneca

Intrabodies have significant biotherapeutic potential. However, challenges remain regarding development and delivery. Using a synthetic VHH phage display library and modified RNA, we developed VHH intrabodies that target the aberrant interactions between two intracellular calcium handling proteins in heart failure. We delivered these VHH intrabodies in vivo and expressed them specifically in the heart using Adeno-Associated Viral (AAV) transduction, resulting in improved cardiac function in a murine heart failure model.

09:30

Development of Brain Shuttles Based on TfR1-Specific VNAR Antibodies – Translation to Primates

Pawel Stocki, PhD, Vice President, Research, Ossianix, Inc.

Poor brain delivery is a major hurdle in the development of biological therapeutics for neurologic diseases because of poor Blood-Brain Barrier (BBB) penetration. Numerous brain shuttles based on single-domain VNAR antibodies were developed by Ossianix. These include TXP1, which was demonstrated to penetrate the brain with high efficiency when injected at a low therapeutic dose in non-human primates with an over 30-fold increase in comparison to the control.

10:00 Structure-Based Charge Calculations for Predicting Properties and Profiling Antibody Therapeutics

Nels Thorsteinson, PhD, Director of Biologics, Chemical Computing Group

We present a method for modeling antibodies and performing pH-dependent conformational sampling, which can enhance property calculations. Structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the FDA.

 

Session Break and Transition into Plenary Keynote10:30

ROOM LOCATION: Zafir

PLENARY KEYNOTE SESSION

10:40

Plenary Keynote Introduction

Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London

E. Sally Ward, PhD, Director, Translational Immunology; Professor, Molecular Immunology, Centre for Cancer Immunology, University of Southampton

10:45 KEYNOTE PRESENTATION:

Evolution of Antibody Technologies

Jane K. Osbourn, PhD, CSO, Alchemab Therapeutics Ltd.

It is nearly fifty years since the discovery of monoclonal antibodies, the first drug approval coming soon after in 1986. From this early success, approval rates took time to ramp up and significant efforts were focused on building a range of technologies to deal with the technical challenges of antibody-drug discovery. This talk will discuss how antibody technologies have evolved and consider where future innovation may lie.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)11:30

12:10

Chairperson's Remarks

Lars Linden, PhD, Vice President, Head, Biologics Research, Bayer HealthCare AG

12:15 KEYNOTE PRESENTATION:

Development of New Stimuli-Sensitive Antibodies

Benjami Oller-Salvia, PhD, Assistant Professor, "La Caixa" Junior Leader Fellow, Bioengineering, Protein and Peptide Targeted Nanotherapeutics Program, Ramon Llull University

Conditionally-activated antibodies enable decreased side effects resulting from off-site target engagement. Reversibly masking the antibody can maximize antigen binding in the tumor and minimize it in healthy tissues. In this talk, we will present efficient masking strategies we have recently developed that enable antibody activation with tumor-specific proteases.

12:45 Long Read Sequencing for Protein & Antibody Engineering

Caroline Obert, PhD, Staff Study Manager, Synthetic Long Read Applications, Element Biosciences

Our ability to efficiently engineer antibodies and proteins has been limited to a large extent by our ability to only read partial segments of protein coding sequences using short read sequencing technology. Here, we describe how highly accurate synthetic long read sequencing technology is integrated into and facilitates the design-build-test cycle in antibody and protein engineering. 

Session Break13:15

13:20 Using Physics-Based Molecular Modeling and Deep Learning Approaches to Understand and Design Therapeutic Nanobodies

Anne Goupil - Lamy, PhD, Science Council Fellow at BIOVIA, BIOVIA, Dassault Systèmes

Understanding how nanobodies interact with their target antigens at the atomic level is essential for successful engineering of better binders. The prerequisite is to have an accurate 3D model of the nanobody, especially in the CDR regions. We used comparative modelling approaches, as well as Machine Learning algorithms, to predict 3D structures of several nanobodies that target Glutamate receptors.

13:50 Implementing MOA-Reflective Cytotoxicity Assays using Ready-to-Use KILR Target Cells from Screening to Lot Release

Andrew Green, Senior Business Development Manager, Sales Department, Eurofins DiscoverX

Evaluation of Fc effector mechanisms of therapeutic antibodies is an important regulatory requirement. Eurofins DiscoverX’s MOA-reflective KILR cytotoxicity assays enable precise quantitation of multiple effector-mediated MOA’s including ADCP & ADCC applications. These dye-free, radioactivity-free assays measure direct target cell killing. Here we share phase-appropriate data for several KILR bioassay models demonstrating these assays are fit-for-purpose for screening, characterization, & relative potency applications in lot-release testing.

Session Break14:20

EMERGING FORMATS AND CHALLENGING TARGETS

14:30

Chairperson's Remarks

Caroline J. Barelle, PhD, CEO & Founder, Elasmogen Ltd.

14:35

KnotBodies – Next-Generation Antibody Therapeutics for Modulating Intractable Targets

Aneesh Karatt-Vellatt, PhD, CSO, Maxion Therapeutics

Cysteine-rich miniproteins (knottins) have potential as therapeutic modulators of ion channels but suffer from manufacturing difficulties, short half-lives, and poor specificity. To overcome these challenges, Maxion has developed a novel antibody fusion format (KnotBodyÒ), wherein the antibody gains ion channel modulating capability of the knottin and the knottin enjoys the extended half-life, engineerability, and manufacturability of the antibody. This presentation illustrates the generation of KnotBody inhibitors of multiple ion channels and their optimisation using phage and mammalian display.

15:05

GPCR Active State Conformations Enhancing Therapeutic Agonistic Antibody Discovery

Toon Laeremans, PhD, Co-Founder & Head, Discovery Biologics, Confo Therapeutics

ConfoBodies stabilize a desired conformational state of a GPCR and enable conformation-directed drug screening and structure-guided elaboration. We will show the unique potential of ConfoBody stabilized GPCR conformations to facilitate de novo discovery of therapeutic antibodies exhibiting full agonist pharmacology to human GPCRs.

15:35 Accelerating Lead Molecule Discovery against Difficult Targets

Jonathan Didier, PhD, Senior Field Applications Scientist, Berkeley Lights, Inc.

The Berkeley Lights’ Opto Plasma B Discovery (OPBD) 4.0 workflow enables recovery of 1000s of hits by screening up to 100,000 plasma cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally characterized antibodies in one week. By maximizing the diversity of antibodies through direct functional profiling of plasma cells, the OPBD 4.0 workflow allows users to tackle even the most challenging targets.

Refreshment Break in the Hall with Poster Viewing (Verdi and Vivaldi 1&2)16:05

17:00

Engineering ISB 2001, A First-In-Class Trispecific BCMA and CD38 T Cell Engager Based on the BEAT Technology

Carole Estoppey, PhD, Head of Structure-Guided Antibody Engineering, Ichnos Sciences Biotherapeutics SA

Ichnos’ BEAT platform (Bispecific Engagement by Antibodies based on the TCR) facilitates design of multispecific antibodies using efficient heavy chain heterodimerization and a common light chain. ISB 2001, a trispecific BCMA, CD38, and CD3-targeted T cell engager, was designed to enable high potency with low risk of on-target off-tumor toxicity and antigen sink effects. We will present the rational design of ISB 2001, exploring affinity of the three binding arms, avidity induction, as well as varying epitopes and architectures. ISB 2001 IND-enabling studies are ongoing, and a first-in-human study is expected to start in 2023.

17:30

Ensovibep, a Clinical Stage DARPin Therapeutic for SARS-CoV-2

Marcel Walser, Senior Director, Research, Molecular Partners AG

Ensovibep is a multi-specific 5-domain DARPin therapeutic under development. Three domains cooperatively bind and block the SARS-CoV-2 spike protein receptor-binding domain; two domains bind HSA. In vitro pan-variant (incl. BA.2, BA.2) neutralisation activity has been demonstrated. Ph-1 and Ph-2a studies show favourable safety and viral load reduction (VLR). Ph-2b data from the EMPATHY randomised controlled trial show significant VLR and decreases in hospitalisation and death in ensovibep treated subjects.

18:00

An Advanced Anticalin Platform to Locally Treat Respiratory Diseases

Hitto Kaufmann, PhD, CSO & Senior Vice President, Pieris Pharmaceuticals GmbH

Anticalins represent a class of small and stable therapeutic proteins that can be efficiently delivered to the lung and thus open new opportunities to treat various respiratory diseases locally. Accumulating preclinical and clinical data in asthma and idiopathic fibrosis suggest that these novel therapeutic interventions could help address unmet medical needs. The platform has further evolved with new bi-paratopic formats and tailor-suited developability assessments.

18:30

Antibodies from Resilient Individuals: Progress towards the Clinic

Ralph Minter, PhD, Vice President, Research, Alchemab Therapeutics

At Alchemab, we are harnessing the power of the immune system to counter complex diseases. Using a combination of next-generation sequencing, serum proteomics, and computational discovery we pinpoint antibodies associated with improved outcomes. Selected antibodies are characterized by their biological function and the targets which they bind. Many patient cohorts have been analyzed, across Neurodegeneration and Oncology, and antibodies to novel targets are progressing toward the clinic.

19:00

Direct Tie2 Agonists Promote Vascular Stability for the Intravitreal Treatment of Diabetic Macular Edema

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

Inhibition of Ang2, resulting in Tie2 activation, is a clinically validated approach for the treatment of diabetic macular edema. Here we describe the discovery and optimization of a hexavalent direct Tie2 agonist and its physiological impacts in both mice and cynomolgus monkeys. We show the molecule resolves vascular leak in response to multiple inflammatory stimuli, including stimuli not addressable by approved agents, and that it has exposure and stability consistent with infrequent intravitreal administration.

Close of Engineering Antibodies Conference19:30