Discovery on Target’s Antibody Forum offers R&D research scientists the opportunity to participate in a unique meeting format that encourages discussion and the exchange of best practices on the application of new science and technology for
the discovery and development of novel biotherapeutics. The meeting will feature short presentations, panel discussions, facilitated roundtables and an audience layout that allows a sharing of ideas and experiences. Part 2 picks up
at the transition from Discovery into Development, examining the screening approaches used for candidate selection, engineering problem solving and approaches for challenging molecules and new modalities.
Final Agenda
Wednesday, September 18
11:20 am Conference Registration Open (America Foyer)
12:20 pm Event Chairperson’s Opening Remarks
An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute
12:30 Plenary Keynote Introduction
Anjan Chakrabarti, Vice President, Discovery Chemistry, Syngene International Ltd
12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells
David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University
1:20 PROTACs: Past, Present, and Future
Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University
2:00 Close of Plenary Keynote Program
2:00 Dessert Break in the Exhibit Hall with Poster Viewing (America Ballroom)
2:45 Organizer's Welcome Remarks
2:50 Chairperson’s Opening Remarks
Noah Pefaur, Senior Scientist, AbbVie
2:55 Deep Mutagenesis for Integrative Structure Determination, Binding Site Characterization, and Conformational Engineering of Dynamic Membrane Proteins
Erik Procko, PhD, Assistant Professor, Biochemistry, University of Illinois at Urbana-Champaign
When the directed evolution of mutant libraries is tracked with deep sequencing, the phenotypes of thousands of sequence variants can be determined simultaneously. This method, known as deep mutagenesis, has been applied in cell culture to dynamic membrane
proteins with roles in mental health and immunity, including GPCRs, transporters, an MHC chaperone, and viral immunogens. The mutational landscapes help define ligand-binding sites, inform mechanism, assist engineering, and constrain computational
modeling.
3:25 Monoclonality Does Not Mean Monospecificity – Paratope Refinement to Mitigate Antibody Polyspecificity
Jonny Finlay, PhD, CSO,
Ultrahuman, United Kingdom
Antibodies are well known to become ‘polyreactive’ (randomly sticky) via excess charge or hydrophobicity. We have a much poorer understanding of what causes off-target reactivity to disparate, but selective, targets (polyspecificity). There
is also a paucity of understanding in how this drives antibody toxicity. This will show that polyspecificity is an underappreciated phenomenon in therapeutic antibody development, but that these unwanted properties can be fully ameliorated by paratope
refinement.
View Speaker Interview
3:55 Rapid Assembly of Diverse Gene Variant Libraries Using Semiconductor Technologies
Irene Song, Scientific Advisor, GenScript USA Inc.
Optimization of therapeutics requires the use of high quality mutant libraries. Traditional methods for library construction suffer from limited control over codons, resulting in poor variant representation. Our advanced oligo synthesis platform allows
for precise control over codon usage, creating a diverse and fully represented mutant library, improving screening efficiency.
4:10 Use of Mammalian Virus Display to Select Antibodies Specific for Complex Membrane Antigens
Ernest Smith, PhD, Senior Vice President & CSO, Vaccinex
We have developed a technology to enable direct incorporation of multipass membrane proteins into the membrane of a mammalian virus. Antigen expressing virus is easily purified for antibody selection. This method does not require any detergents or refolding
and produces properly folded protein that is necessary for antibody selection.
4:25 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Emerging Technologies to Evaluate Developability and Manufacturability
Aaron Beach, Investigator,
Novartis Biologics Center, Novartis Institute for BioMedical Research, Inc.
The diversity and increasing complexity of new protein formats requires a change from former platform approaches often applied for antibodies. The Novartis developability assessment combines information about expression, aggregation propensity, process
fit, stability, solubility, physicochemical properties, in vivo fitness and immunogenicity of potential candidates. This integrated approach prior to lead selection provides a thorough, yet resource efficient approach.
The presentation will provide an overview about the concept and provide selected case studies.
5:30 Utilization of Throughput-Based Platforms to Identify Optimal Bispecifics
Noah Pefaur, Senior Scientist,
AbbVie
Following entry of the DVD-Ig format into the clinic it has become a preferred format for bispecifics at AbbVie. As with any engineered biologic identification of potent molecules with favorable drug like properties frequently requires engineering and
screening to identify optimal lead candidates. Here, we present a throughput-based strategy to increase project probability of success, reduce time spent on lead optimization, and increase the quality of identified leads.
6:00 UPDATE: Speaker has cancelled; delegates may attend parallel talks in the other meeting rooms. Creating a New Paradigm for Biotherapeutics: Attributes More Potent than Potency
Vishal Toprani,
PhD, Scientist, Pharmaceutical Development, Alexion Pharmaceuticals, Inc.
The field of biotherapeutics is rapidly advancing into novel molecular formats from traditional antibody-based products. This shift to novel protein modalities will require addressing new types of liabilities and implementing modern technologies to evaluate
the risk/benefit profiles of these molecules. This presentation will focus on using DOE approaches and automated high throughput biophysical tools, in combination with automated sample preparation to identify attributes that may overrun the potency
selection, predominant in protein engineering.
6:30 Dinner Short Course Registration (America Foyer)
Click here for details on short courses offered.
9:30 Close of Day
Thursday, September 19
7:00 am Registration Open (America Foyer)
Essex Ballroom
7:30 Interactive Breakfast Breakout Discussion Groups - View All Breakouts
Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future
collaborations around a focused topic.
Structure-Based Antibody Discovery and Design
Moderator: Christopher Corbeil, PhD, Research Officer, Human Health Therapeutics, National Research Council Canada
- De novo design of antibodies: Useful and feasible?
- Computational predictions in real-life projects: Better integration needed?
- Using computational tools to access difficult-to-target proteins
- Structure-based antigen design
Opportunities in Antibody Discovery for Membrane Proteins
Moderator: Christyne Kane, PhD, Senior Scientist, Biologics Generation, AbbVie Bioresearch Center
- In vivo vs. in vitro Approaches: The pros and cons
- Antibody Databases: Requirements for the ideal database
- IHC Tool Antibodies: Best practices for generation
Characterization of Antibodies Against Membrane Proteins
Moderator: Joseph Rucker, PhD, Vice President, Research and Development, Integral Molecular, Inc.
- Affinity and Kinetics: Useful approaches for characterizing antibody binding
- Epitopes: Different techniques for epitope mapping; binning versus mapping; why do epitopes matter?
- Cell Function: Integrating functional assays into antibody discovery and development
Additional Breakouts to be Announced
8:30 Transition to Sessions
8:40 Chairperson’s Remarks
Colby Souders, PhD, CTO, Abveris
8:45 Engineering Patient-Derived Anti-HIV Broadly Neutralizing Antibodies for Therapeutic Development
Nathan Thomsen, PhD, Senior Research Scientist, Gilead Sciences
Advances in discovery technology have led to the isolation of HIV broadly neutralizing antibodies (bNAbs) with exceptional breadth. These bNAbs hold promise for the treatment or cure of HIV, with many in clinical trials. Evolving alongside the virus within
a single individual, HIV bNAbs diverge significantly from the human germline repertoire and present unique engineering challenges. Strategies to identify and mitigate development challenges in HIV bNAbs will be discussed.
9:15 Identification, Characterization & Engineering of Antibodies Directed against Complex Target Molecules
Christian Kunz, PhD, Director, Discovery Alliances & Technologies, MorphoSys AG, Germany
Methods generating highly specific antibodies against classical target molecules, as e.g. receptor tyrosine kinases or cytokines, are routinely established. Antibody compounds inhibiting these classical target classes are widely used in clinical development
and as approved therapeutics. Innovative selection strategies have to be applied to broaden target space and bring new target classes, as GPCRs or HLA/Peptide complexes, into clinical development.
9:45 KEYNOTE PRESENTATION: Chemical and Physical Determinants of Drug-Like Monoclonal Antibodies
Peter M. Tessier, PhD, Professor, Pharmaceutical Sciences and Chemical Engineering, University of Michigan
Therapeutic antibodies display variable and difficult-to-predict levels of non-specific and self- interactions that lead to various drug development challenges, including abnormally high viscosity and fast antibody clearance. We are developing bioinformatics
methods for predicting the overall specificity of antibodies in terms of their relative risk for displaying high levels of non-specific and self-interactions. We will report novel types of chemical descriptors that are strong predictors of antibody
specificity.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced (America Ballroom)
10:55 Development Stage Problem Solving
Moderator: Colby Souders, PhD, CTO, Abveris
Panelists: Georg Fertig, PhD, Head, Screening & Functional Assays, Roche Pharmaceuticals, Germany
Peter M. Tessier, PhD, Professor, Pharmaceutical Sciences and Chemical Engineering, University of Michigan
Nathan Thomsen, PhD, Senior Research Scientist, Gilead Sciences
Discovery and Development stage scientists are under pressure to improve the quality of lead selections, avoid later stage liabilities and advance programs more rapidly to the clinic. Join our panel and your colleagues to hear about tools and technologies
being used to achieve these goals and share ideas on how to respond to challenges at this critical point in the pipeline. The panel will include discussion by the panelists and provide the opportunity for participants to guide the discussion by offering
perspectives and pose questions.
11:55 Overnight Target Engineering
Katie Lyons, Senior Scientist, Research & Development, SGI-DNA Inc.
Advancements in DNA synthesis and modification have yielded powerful new techniques for target engineering. As these techniques become more specialized, engineering becomes more resource-intensive. Here, we discuss a fully-automated workflow
for protein engineering using SGI-DNA’s BioXp™. The instrument generates Libraries, Clones, and Tiles from sequence information in an overnight run.
12:10 pm Just a Specific Target is Not Good Enough to Achieve Desired Effect; The Case of Vedolizumab (Entyvio®)
Pierre Eftekhari, PhD, Founder and CEO, Inoviem Scientific
Vedolizumab an antibody against ITGB7 is used for treatment of IBD. Molecular analysis of 31 IBD outpatients, in a prospective clinical study treated with Vedolizumab, showed that the efficient treatment could only be reached when ITGB7 interacts
directly with 4 other proteins forming a signaling complex. In the absence of these proteins despite the presence of ITGB7 no therapeutic effect was observed. A therapeutic target is therefore defined as the presence of primary target within its
corresponding signaling complex.
12:25 Session Break
12:35 Luncheon Presentation: Lead Optimization of Biologics Using Physics-Based Computational Methods
Eliud Oloo, PhD, Senior Principal Scientist, Schrödinger
In this presentation, we will describe how calculated properties derived from 3D structural analyses and simulation through physics-based methods are applied to not only optimize binding affinity and selectivity but also identify and mitigate potential
liabilities in the development of biologics. Using such computational strategies to direct experimental focus can result in reductions in cost and timelines.
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Remarks
Benjamin Smith, PhD, Scientist, Biologics Drug Discovery, CNS Delivery, Biogen
2:10 Strategies, Considerations and Challenges in Engineering Antibody-Drug Conjugates
Chen-Ni Chin, PhD, Director, Antibody Discovery, Mersana Therapeutics
Antibody-drug conjugates (ADCs) are a growing class of biopharmaceuticals designed to harness the targeting specificity of a mAb by linking it to highly potent drugs for delivery. In this talk we will discuss what it means to make an ADC through engineering
the antibody as well as applying novel linker and payload technologies for the optimal pharmacological profile. Case studies will be presented.
2:40 Bispecific Antibodies – A Platform Approach for Generation and Screening in Final Format
Georg Fertig, PhD,
Head, Screening & Functional Assays, Roche Pharmaceuticals, Germany
The generation of bi-functional bispecific antibodies requires the combination of two monospecific binders, which bind to the right epitope of the respective target in the right format. High-throughput generation and screening of such antibodies will
be discussed in the context of an effective and robust technology platform, an automated production of bsAb binder-format combination matrices and the format, which defines the function.
3:10 Protein Engineering for Enhanced and Sustained CNS Exposure of Neuro-Therapeutic Antibodies
Benjamin Smith, PhD, Scientist, Biologics Drug Discovery, CNS Delivery, Biogen
The single domain antibody FC5 engages receptor-mediated transcytosis and is a promising BBB carrier. Here the humanization and stability engineering of FC5 and design of FC5 bispecifics with antibodies against neurodegenerative disease targets will
be described. Enhanced BBB penetration of the bispecifics in an in vitro BBB model as well as CNS pharmacokinetics in rats and monkeys dosed at therapeutically relevant doses by systemic injections will be shown.
3:40 Screening Tools for Early Prediction of Development and Clinical Success
Colby Souders, PhD, CTO, Abveris
As industry-wide advancements in antibody drug discovery continue to push toward larger panels of candidates for early-stage characterization, more efficient identification of lead molecules through enhanced screening resolution is required. Integrating
tools and methods into the overall characterization workflow enables reliable, high throughput selection of lead candidates more effectively than alternative traditional techniques. Comparisons across platforms, including traditional ELISA,
flow cytometry, Octet and in vivo studies will be presented that provide enhanced prediction of downstream development and clinical success.
4:10 Close of Conference
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