Antibody Forum – Part 2

 

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


PLENARY KEYNOTE PROGRAM
Click here for full abstracts.

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

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

Transitioning From Discovery To Development

2:45 Organizer's Welcome Remarks

2:50 Chairperson’s Opening Remarks

Noah Pefaur, PhD, 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.

3:55 Presentation to be Announced

 

Vaccinex 4:10 Presentation to be Announced

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, PhD, 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 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
Click here for details on short courses offered.

9:30 Close of Day

Thursday, September 19

7:00 am Registration Open

7:30 Interactive Breakfast Breakout Discussion Groups

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. Visit the conference website for discussion topics and moderators.

8:30 Transition to Sessions

Engineering Problem Solving

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

Panel Discussion

10:55 Development Stage Problem Solving

Moderator: Colby Souders, PhD, CTO, Abveris

Panelists: Georg Fertig, PhD, Head, Screening & Functional Assays, Roche Pharmaceuticals, Germany

Jonny Finlay, PhD, CSO, Ultrahuman, United Kingdom

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 Presentation to be Announced

12:10 pm Sponsored Presentation (Opportunity Available)

12:25 Session Break

Schrodinger 12:35 Luncheon Presentation to be Announced

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

Development Challenges Of New Modalities And Complex Biologics

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 Targeting the STn Glycan in Ovarian Cancer Using a Highly Specific Anti-STn Antibody Drug Conjugate

Jeff Behrens, PhD, CEO, Siamab Therapeutics

Sialyl-Tn (STn) is a tumor-associated carbohydrate antigen that is expressed in multiple solid tumors – ovarian, pancreatic, gastric, and others. STn is implicated in immune suppression, chemoresistance, and a cancer stem-cell phenotype. Carbohydrate antigens, including STn, pose unique challenges in antibody discovery; Siamab’s glycan array is a key tool used to overcome these challenges enabling the discovery of a panel of highly specific, high-affinity mAbs, currently formatted as an IND-ready ADC.

4:10 Close of Conference
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