Phage and yeast display drive the design and engineering improvements of biologics which has fueled an expanding market. An array of constructs is now possible with the activity and properties to address novel targets and improve pharmacology of existing
molecules. The leaders in display technologies will disclose the latest trends and results in technologies and approaches for creating the next generation of drug candidates. This track is the cornerstone of the PEGS Summit and drew record attendance
last year.
Scientific Advisory Board
Andrew M. Bradbury, M.D., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory
Jennifer Cochran, Ph.D., Hitachi America Associate Professor, Bioengineering and Chemical Engineering, Stanford University
David Lowe, Ph.D., Director, R&D, Antibody Discovery and Protein Engineering, MedImmune Ltd
Aaron K. Sato, Ph.D., Vice President of Research, Sutro Biopharma
Gregory A. Weiss, Ph.D., Professor, Chemistry, Molecular Biology & Biochemistry, University of California, Irvine
K. Dane Wittrup, Ph.D., J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
MONDAY, APRIL 25
7:00 am Registration and Morning Coffee
KEYNOTE SESSION
8:30 Chairperson’s Remarks
Aaron K. Sato, Ph.D., Vice President, Research, Sutro Biopharma
8:40 KEYNOTE PRESENTATION: Serological Profiling of Antibody Targets Using a Synthetic Human Proteome
Stephen J. Elledge, Ph.D., Gregor Mendel Professor, Genetics, Harvard Medical School; Division of Genetics,
Brigham and Women’s Hospital; Investigator, Howard Hughes Medical Institute
I will present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses.
We will show why the VirScan is a powerful approach for studying interactions between the virome and the immune system.
9:10 Preferential Germline Usage and VH/VL Pairing Observed in Human Antibodies Selected by mRNA Display
Lei Chen, Ph.D., Senior Scientist, Global Biologics, Abbvie, Inc.
We report here the development of an mRNA display technology and an accompanying HCDR3 size spectratyping monitor for human antibody discovery. We will show how we have identified trends and determined the productivity of each germline subgroup in the
libraries that could serve as the knowledge base for constructing fully synthetic, next generation antibody libraries.
9:40 Fully Human Antibody Single Domains that Rival the Stability and Cleft Recognition of Camelid Antibodies
Daniel Christ, Ph.D., Associate Professor and Head, Antibody Therapeutics, Garvan Institute of Medical Research
Here we report the engineering and characterization of phage display libraries of stable human VH domains. Unlike ‘camelized’ human domains, the domains do not rely on potentially immunogenic framework mutations and maintain the structure
of the VH/VL interface. Structure determination in complex with antigen revealed an extended VH binding interface, with CDR3 deeply penetrating into the active site cleft, highly reminiscent to what has been observed for camelid domains. Taken together,
our results demonstrate that fully human VH domains can be constructed that are not only stable and well-expressed, but also rival the cleft binding properties of camelid antibodies.
10:10 Coffee Break
Chairperson’s Remarks
Aaron K. Sato, Ph.D., Vice President, Research, Sutro Biopharma
10:50 Matrix Guided Selection of Selective and Specific Affinity Ligands
Kimberly Kelly, Ph.D., Associate Professor, Biomedical Engineering, Robert M. Berne Cardiovascular Research Center,
University of Virginia
Numerous applications such as targeted drug delivery and molecular imaging require the generation of high affinity targeted ligands. I will highlight a strategy that uses phage display as a starting point that utilizes quantitative and in silico methodologies
as a means of rapidly generating high affinity targeted ligands for use in therapy and imaging. The discussion will be centered on pancreatic cancer as an example of the power of phage display derived peptide ligands.
11:20 Phage as a Surrogate for Counting miRNA Molecules in a Petri Dish
Chuanbin Mao, Ph.D., George Lynn Cross Research Professor, Chemistry & Biochemistry; Member, Peggy and Charles
Stephenson Cancer Center, University of Oklahoma
T7 phage is used as a surrogate to establish a one-to-one correspondence between the macroscopic plaques and the target miRNAs. Target miRNAs crosslink a magnetic microparticle and one-to-one complexes of fluorescent phage and gold nanoparticles to
form a sandwich complex. The phage is then released from the sandwich complex and developed into one fluorescent plaque in a Petri dish. Counting the plaques enables the multiplexed quantification of attomolar miRNAs.
11:50 Curing the Modern Dairy with Precision Microbiome Engineering
Nick Conley, Ph.D., CEO, EpiBiome
Bovine mastitis is an inflammation of the udder tissue, usually caused by bacterial infection, that results in annual losses of $35 billion and $2 billion to the global and US dairy industries, respectively. It is the #1 reason to treat a cow with
small-molecule antibiotics. EpiBiome, an eleven-person, venture-backed precision microbiome engineering company based in South San Francisco, is using phage therapy as a replacement for small-molecule antibiotics to kill the bacteria that cause
bovine mastitis.
12:20 pm Cancer Biotherapeutics - Affimers: A Novel Scaffold
for Biotherapeutics
Amrik Basran, Ph.D., CSO, Therapeutics, Avacta Life Sciences
Affimers are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the protease inhibitor Stefin A, large diverse libraries have been created by engineering in peptide loops into the scaffold backbone. Using
phage display, we have identified competitive binders to a ranage of targets, including the immune check point, PD-L1. We have shown that the scaffold is amenable to being engineered with a range of half-life extension technologies, giving
“IgG like” PK.
12:50 Luncheon Presentation I: Antibody Library Display on a
Mammalian Virus: Application to Both Soluble and Complex Membrane Antigens
Ernest S. Smith, Ph.D., Senior Vice President, Research & CSO, Vaccinex, Inc.
We have developed an antibody discovery platform that enables efficient mammalian cell based expression of a library of human antibodies in full length IgG format on the surface of a mammalian virus. Upon infection of mammalian cells the antibody
is not only incorporated into newly produced virus, it is also displayed on the surface of the host cell. This technology allows us to combine the advantages of virus panning and cell sorting into one technology.
1:20 Luncheon Presentation
II: Improved Identification of Peptide and Antibody Ligands from Display Experiments by Analysis of Deep Sequencing Data
Michael Blank, Ph.D., Co-Founder & CSO, Research & Development, AptaIT GmbH
AptaIT’s bioinformatic approach allows the exploitation of NGS data at very high resolution and therewith improves the identification of peptide and antibody ligands from display experiments. Besides quality control and optimization of libraries,
early identification of rare but high quality ligands otherwise lost in the screening experiment as well as advanced screening strategies for difficult targets become possible. The wealth of comparative sequence data from the screening experiment
is furthermore useful for subsequent lead optimization.
1:50 Session Break
2:20 Problem-Solving Breakout Discussions
The Unusual and Controversial Architecture of Dual-Topology Membrane Proteins
Randy B. Stockbridge, Ph.D., Assistant Professor, Biophysics and Molecular, Cell, and Developmental Biology, University of Michigan
- How do we experimentally validate predictions of dual topology?
- How does the cell maintain dual topology?
- What can these tell us about structural motifs in other membrane transport proteins?
Pancreatic Cancer as an Example of the Power of Phage Display Derived Peptide Ligands
Kimberly Kelly, Ph.D., Associate Professor, Biomedical Engineering, Robert M. Berne Cardiovascular Research Center, University of Virginia
- Phage display to identify novel biomarkers of disease
- Development of phage display derived peptides for non-invasive in vivo imaging – from bench to bedside
- Using phage display derived peptides for targeted drug delivery – increasing the efficacy to toxicity ratio
Bringing Expanded Chemical Functionality into Display Technologies
James A. Van Deventer, Ph.D., Assistant Professor, Chemical and Biological Engineering, Tufts University
- Introducing chemical functionality into display technologies with noncanonical amino acids
- Other approaches to introducing additional chemical functionality into display technologies
- Compatibility between display technologies and chemical reactions of interest
- Therapeutically relevant examples
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
PLENARY KEYNOTE SESSION
4:00 Chairperson’s Remarks
4:10 The Promise of Cancer Immunotherapy: An Overview of Recent Advances and Jounce’s Approach to Delivering the Right Therapy to the Right Patient
Deborah Law, D. Phil., CSO Jounce Therapeutics, Inc.
As immunotherapies become an increasingly important component of cancer treatment the challenge will be to identify ways to provide the best therapy(s) to the individual. This presentation will provide an overview of current cancer immunotherapies
as well as highlight some of the challenges ahead including selection of optimal combinations, moving outside of T cell-directed approaches, and will highlight how Jounce Therapeutics is using its Translational Science Platform as an approach
to develop and deliver the right therapy to the right patient.
4:50 Antibody as Drugs: Then, Now and Tomorrow
Paul J. Carter, Ph.D., Senior Director and Staff Scientist, Antibody Engineering, Genentech
Antibodies have grown into a clinically and commercially important drug class with more than >45 antibodies marketed for imaging or therapy in the USA and/or Europe and with ~$63 billion in worldwide sales in 2013. This presentation
will highlight progress in developing antibody drugs and consider opportunities for future innovation.
5:30 Welcome Reception in the Exhibit Hall with Poster Viewing
6:45 End of Day
TUESDAY, APRIL 26
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Andrew M. Bradbury, M.D., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory
8:30 Phenotypic Screening for Novel Antibody Targets in the Tumor Microenvironment
Ralph
R. Minter, Ph.D., Fellow, Antibody Discovery and Protein Engineering, MedImmune Ltd.
The biopharmaceutical industry would benefit from better tools to discover and validate new antibody targets. Phenotypic antibody screening, which combines target-agnostic phage display with the early functional screening of antibodies, is an
effective approach to target discovery and validation. Case studies will be presented to show that phenotypic screening has been successful in finding novel targets in the tumor microenvironment.
9:00 Generation of Antibodies Targeting Intracellular Oncogenic Mutations Presented by Common HLA Complexes
Andrew D. Skora, Ph.D., Postdoctoral Fellow, Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins
Kimmel Cancer Center
Genetics alterations of the KRAS oncogene are present in nearly all incidents of pancreatic cancer and half of colorectal cancer cases. We have devised a method to identify single chain variable fragments (scFvs) that target KRAS mutant epitopes
present in the context of HLA-A2 on the cell surface. We demonstrate that scFvs identified through our technique can be successfully converted to full-length antibodies.
9:30 Poster Presentation: Bispecific Antibodies Targeting the Intracellular Virus-Receptor Interaction Protect Against Ebola Virus in Vivo
Anna Z. Wec, Ph.D. Candidate, Dept. of Microbiology & Immunology, Albert Einstein College of Medicine
10:00 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Awards
10:45 Chairperson’s Remarks
Jennifer Cochran, Ph.D., Hitachi America Associate Professor, Bioengineering and Chemical Engineering, Stanford University
10:50 KEYNOTE PRESENTATION:
Phage-Assisted Continuous Evolution (PACE) of Proteins with Therapeutic and Industrial Potential
David R. Liu, Ph.D., Professor, Chemistry & Chemical Biology, Harvard University
Phage-assisted continuous evolution (PACE) enables proteins to evolve continuously in the laboratory. In this lecture I will describe the development and application of PACE to rapidly evolve a wide variety of proteins, several of which have
potential to serve as novel therapeutic agents. In addition, I will describe a new effort that uses PACE to provide a solution to a major problem facing worldwide agricultural productivity: the rise of insects resistant to a widely used
biological insecticide.
11:20 Shark-Derived Antibodies for Applications in Biotechnology and Medicine
Harald Kolmar, Ph.D., Professor & Head, Biochemistry, Technical University of Darmstadt
Due to their high affinity and specificity, physicochemical stability, small size and low-cost of production, single domain antibodies from sharks have evolved as promising target-binding scaffolds. We established a generic method for the isolation
of shark-derived binding domains (sharkbodies) by yeast surface display obviating animal immunization. Tailor-made pH-selective as well as bispecific vNAR domains were generated for various applications in downstream processing and medicine.
11:50 Enhancing the Versatility of Yeast Display with Noncanonical Amino Acids
James A. Van Deventer, Ph.D., Assistant Professor, Chemical and Biological Engineering, Tufts
University
The introduction of noncanonical amino acids into proteins offers attractive opportunities for engineering new classes of reagents, diagnostics, and therapeutics. We present here a noncanonical amino acid-compatible yeast display platform that
enables the construction, evaluation, and screening of bioconjugates on the yeast surface.
12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Ralph R. Minter, Ph.D., Fellow, Antibody Discovery and Protein Engineering, MedImmune Ltd.
2:05 Engineered Affibody Molecules Binding to the Neonatal Fc Receptor (FcRn) for Use in Medical Applications
Torbjorn Gräslund, Ph.D., Staff, Division of Protein Technology, School of Biotechnology, KTH
Royal Institute of Technology and Affibody
The pH-dependent interaction of IgG (Fc) and serum albumin with FcRn results in extended serum circulation half-lives of these ligands and recombinant fusions including them. The talk will focus on alternative and much smaller affinity proteins
(affibody molecules), capable of selectively interacting with FcRn in a pH-dependent manner. Examples of their potential use in different medical applications will be presented, including in vivo half-life extension and depletion of serum
IgG.
2:35 Protein Engineering with a Focus on the Tumor Microenvironment: Anti-EGFR ADC and PEG-ADA2
Christopher D. Thanos, Ph.D., Senior Director, Biotherapeutics Discovery, Halozyme
3:05 Combining the Benefits of Immunized Libraries, in vitro Selections and Computational Design for Antibody Discovery
Vera Molkenthin, Ph.D., Chief Scientist, AbCheck
Rabbits are known to produce high affinity and diverse antibodies even against difficult targets. A library-based method allows the humanization of the complete VH/VL sequence repertoire of an immunized rabbit in one batch and offers a new
approach to antibody discovery. The libraries are computationally designed for optimal developability properties, excluding T-cell epitopes and biochemical liabilities. Special strategies allow the selection of antibodies with slow dissociation
rates, species cross reactivity and high thermal stabilities.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
Chairperson’s Remarks
K. Dane Wittrup, Ph.D., J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
4:25 Identifying Antibodies Recognizing Plasma Membrane Targets
Eric V. Shusta, Ph.D., Howard Curler Distinguished Professor, Chemical and Biological Engineering, University
of Wisconsin-Madison
Plasma membrane proteins represent key targets for many therapeutic applications. We have developed several different enabling platforms for the identification and engineering of antibodies against such targets. Here we will describe our recent
efforts using phage and yeast display to increase the in vivo relevance of selected antibodies and to target specific molecular machinery present at the plasma membrane, such as that involved in endocytosis.
4:55 Ion Channel Topology Probed with Fibronectin-Domain Monobody Inhibitors
Randy B. Stockbridge, Ph.D., Assistant Professor, Biophysics and Molecular, Cell, and Developmental
Biology, University of Michigan
The Fluc family of fluoride channels has an unusual and controversial architecture, with the subunits of the dimer arrayed in an antiparallel orientation. We established that topology using monobody inhibitors, based on a human fibronectic
III domain scaffold, and selected using combinatorial phage- and yeast display libraries. In electrophysiological recordings, these monobodies block fluoride currents arising from single channels, allowing observation of single-molecule
binding kinetics of the monobody applied sequentially to both sides of the membrane.
5:25 End of Phage and Yeast Display of Antibodies
5:30 Registration for Dinner Short Courses*