Part 1 will focus on the discovery workflow, and explore best practices for identifying and using new and legacy technologies to discover novel and functional drug candidates in an environment where speed and efficiency is now a mandate. The meeting will consider new approaches to the essential steps in the discovery process and how to make these more efficient by selectively and intelligently integrating the many new tools now available on the market. A key focus of the agenda will be a discussion of methods used to discover well-performing candidates and leads as early as possible – and to accomplish this goal at the lowest possible cost needed to achieve a high-quality outcome.

Final Agenda

Wednesday, September 26

7:00 am Registration Open and Morning Coffee (Foyer)

Optimizing The Discovery Workflow
Republic A

8:00 Welcome Remarks

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

8:05 Chairperson’s Opening Remarks

Avinash Gill, PhD, Senior Scientific Manager, Genentech

8:10 High Throughput Generation of Challenging Antigens

Medha Tomlinson, PhD, Principal Research Scientist, AbbVie

Generation of proprietary therapeutics in disease requires recombinant protein antigen or a cell-based immunogen. Target antigens are challenging to produce since they have to maintain secondary and tertiary structures to maintain functionality. Here we describe the design and production of a challenging antigen and strategies we have set up to increase throughput to support our discovery workflow.

8:40 Meeting the Needs of Antibody Discovery and Engineering Campaigns with Automated Workflows

Avinash Gill, PhD, Senior Scientific Manager, Genentech

An increasing need for high-throughput (HTP) processes to rapidly produce large numbers of antibodies has accompanied the rising scale and complexity of antibody discovery and engineering. Automated HTP workflows have been put in place to combine highly productive small-scale mammalian expression and purification platforms for generating antibodies and other therapeutic formats. The availability of purified material has enabled unambiguous identification of “hits” in biological and functional screening assays.

9:10 Luncheon Presentatio: Optimizing Therapeutic Antibody Discovery with OmniAb

Bill Harriman, PhD, MBA, Vice President, Antibody Discovery Services, Ligand

Shelley Izquierdo, PhD, Director, Antibody Discovery, Ligand

The OmniAb® portfolio of transgenics leverages 3 species to generate the OmniMouse®, OmniRat® and OmniChicken™ antibody discovery platforms, enhancing the diversity of immunological responses to therapeutically relevant targets and potentially uncovering novel epitopes for improved biological activity.  Due to precise transgene design and effective in vivo affinity maturation, typical programs yield large cohorts of developable antibody candidates. Next generation transgenic animals and recent case studies will be discussed.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:25 Applying Fully Automated Antibody Discovery Workflows for Finding the Needle in the Haystack

Stefan Zahn, PhD, Principal Scientist, Antibody Technology, Novo Nordisk AS, Denmark

The discovery of therapeutic antibodies depends on finding the right antibody with proper functionality, affinity and developability within a highly diverse B-cell repertoire. In vivo antibody platforms have proven to efficiently deliver on these parameters. We will present a highly automated antibody discovery workflow based on traditional hybridoma technology and discuss emerging technologies for deeper mining of the B-cell repertoire providing eventually greater and faster success.

10:55 Enhancing Antibody Discovery Methods and Maximizing Throughput in the Absence of Automation

Colby Souders, PhD, Chief Technology Officer, Abveris Antibody

The way in which therapeutic antibodies are discovered has rapidly progressed in the past decade. New methods allow us to find potent human clinical candidates at an accelerated pace; however, proprietary technology and fully automated platforms are not available for every campaign to facilitate discovery efforts. Here we address ways of finding the optimal drug candidate by exploring multiple discovery techniques and integrating the most current technology available to every researcher, such as single B-cell sorting and next-generation sequencing.

11:25 INTERACTIVE PANEL AND AUDIENCE DISCUSSION: Best Practices for Improving the Discovery Workflow

Avinash Gill, PhD, Senior Scientific Manager, Genentech (Moderator)

Colby Souders, PhD, Chief Technology Officer, Abveris Antibody

Medha Tomlinson, PhD, Principal Research Scientist, AbbVie Bioresearch Center

Stefan Zahn, PhD, Principal Scientist, Antibody Technology, Novo Nordisk AS, Denmark

12:25 pm Session Break

12:35 Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

Screening And Selection
Republic A

1:50 Chairperson’s Remarks

Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc.

1:55 Best Practices for Evolving in House Screening Libraries and Discovery Platforms

Andrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer Ingelheim

The choices that we make early in the discovery process have a profound impact on the quality of the antibodies that are advanced into development and the subsequent speed to the clinic. Here we will discuss how to approach and iterate during the early screening stages to ensure successful identification of therapeutic candidates.

2:25 How Can NGS Support Library Production, Selection and Screening?

Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc.

The use of next-generation sequencing (NGS) as a routine tool during antibody library generation, selection and screening provides deep understanding of all aspects of in vitro antibody generation. NGS analysis of the PCR products generated by primers used to create a naive antibody library from lymphocytes, for example, revealed that primers are far more promiscuous than anticipated and amplify many other V genes, even when the primers have been designed to be V gene or family specific. This talk will discuss other insights gained from the routine use of NGS in antibody library production and selection.

2:55 Leveraging Computational Modeling Methods to De-Risk the Development of Biologics

Hubert Li, PhD, Senior Scientist, Schrödinger

Computational approaches applied upstream can play vital complementary roles in reducing failure rates, development delays, and the cost of advancing biologic drug candidates. We present in silico methods for detecting protein liabilities early in the discovery phase and describe how to integrate these approaches to screen and mitigate common issues like instability and aggregation propensity. These approaches are designed to guide experimentalists in making triage decisions by identifying classes of hits for continued exploration.

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced (Grand Ballroom)

4:05 PANEL DISCUSSION: Best Practices for Phenotypic and Functional Antibody Screening

Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc. (Moderator)

Andrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer Ingelheim

Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich, Switzerland

5:05 Interactive Breakout Discussion Groups

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.

Room: Back Bay A

Table 20: How Can NGS Support Library Production, Selection and Screening?

Moderator: Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc.

• Different NGS platforms
• NGS traps
• NGS in estimating library diversity
• NGS in screening analysis

Table 21: Tools for Enhancing Antibody Discovery

Moderator: Colby Souders, PhD, Chief Technology Officer, Abveris Antibody

• Design and production of quality antigens and reagents required for discovery
• Integration of next-generation sequencing in the discovery and engineering platform
• Naïve discovery: library, hybridoma or B cell sorting?
• Transitioning from low-throughput to high-throughput to full automation

Table 22: Synthetic Single-Domain Antibody Libraries and the Future of Antibody Discovery

Moderator: Conor McMahon, PhD, Postdoctoral Fellow, Biological Chemistry and Molecular

Pharmacology, Harvard Medical School

• Library design and discovery of binders
• What makes a synthetic antibody library good?
• Measuring library quality: Can we learn something from structural biologists?
• Phage and yeast…is that the best we can do?
• Pushing the limit: Interfacing with computer scientists to design ‘smart’ libraries
• Will synthetic libraries ever be as good as animal derived?

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing (Grand Ballroom)

7:10 Close of Day

Thursday, September 27

7:30 am Registration Open and Morning Coffee (Foyer)

Implementing Emerging Discovery Technologies
Republic A

8:00 Chairperson’s Remarks

Jane Seagal, PhD, Senior Scientist, Biologics Generation Group, AbbVie Bioresearch Center

8:05 High-Throughput Antibody Engineering in Mammalian Cells by CRISPR/Cas9-Mediated Homology-Directed Mutagenesis

Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich, Switzerland

Homology-directed mutagenesis (HDM) extends the concept of CRISPR/Cas9-mediated homology-directed repair to generate site-directed mutagenesis libraries in mammalian cells. Following cleavage by the Cas9 protein, single-stranded oligonucleotides containing degenerate codons serve as the repair template, providing integration of sequence diversity into the genome. We used HDM to generate libraries in the antibody CDRH3 and combined this with a mammalian surface display platform for high-throughput screening.

8:35 Developments in Computational-Based Methods for Antibody Design

Andrew Wollacott, PhD, Principal Scientist, Visterra, Inc.

Over the last decade, there have been notable developments in computational protein design methods, high throughput protein characterization, and availability of antibody repertoire data. The convergence of these methods has led to significant advances in structure-guided design and antibody engineering. Here we provide an overview of recent developments and applications in the field of protein design and offer our perspective on best practices for applying these tools for antibody discovery.

9:05 Reports from Wednesday Evening Breakout Discussions

9:35 Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:20 Engineering Cells at the Protein Level with Intracellular Antibodies

Andrea Marschall, PhD, Postdoctoral Researcher, Biochemistry, Brandeis University

Intracellular antibodies (intrabodies) can knock down functions by acting at the protein level and allow gradual quantitative tuning of membrane-receptors. We demonstrated gradual reductions of vascular adhesion molecule 1 (VCAM1) in vitro. In the world’s first transgenic intrabody mouse that we generated, ablation of VCAM1 by an intracellular antibody resulted in aberrant localization of B cells in adult animals. Intrabody mice were viable although genetic knockouts of VCAM1 are lethal.

10:50 Best Practices for Evaluation and Implementing New Technology Platforms

Shiv Krishnan, PhD, Head, Business Development & Licensing, Technology Platforms, Sanofi

Access to cutting edge technologies is critical for sustaining innovation and productivity in drug discovery. The advent of high throughput technologies powered by miniaturization and computation has increased access to a large variety of molecular modalities. With the large variety of options in the marketplace, the objective selection of the right technologies is a major challenge. This presentation covers strategies and methodologies used for identifying, evaluating and implementing technologies for drug discovery and development.

11:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

11:50 Conference Registration Open (Foyer)

12:20 pm Plenary Keynote Program (Constitution Ballroom)

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

2:45 Close of Conference