PGD


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

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Recommended Pre-Conference Short Course*

SC1: Fluorescent Proteins in Protein Engineering

*Separate registration required


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_ElledgeStephen 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.


ADVANCES IN LIBRARY DESIGN

9:10 Preferential Germline Usage and VH/VL Pairing Observed in Human Antibodies Selected by mRNA Display

Lei_ChenLei 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_ChristDaniel 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


New Uses of Phage Display

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_KellyKimberly 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_MaoChuanbin 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_ConleyNick 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: Combining the Advantages of Panning and Cell
Sorting in One Technology

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 a 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.

APTA IT1:20 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_LawDeborah 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_CarterPaul 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

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TUESDAY, APRIL 26

8:00 am Morning Coffee


Phenotypic Screening

8:25 Chairperson’s Remarks

Andrew M. Bradbury, M.D., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory

8:30 Eukaryotic Virus and Cell Display for the Optimization of Antibodies

Mark_FederspielMark J. Federspiel, Ph.D., Associate Professor, Molecular Medicine, Mayo Clinic

The availability of a robust, eukaryotic display technology comparable to phage display would improve the discovery and optimization of high affinity antibodies to important therapeutic targets by overcoming the protein translation limitations of microorganisms as well as more seamlessly transition into a large-scale mammalian expression system for clinical production. We will demonstrate that a eukaryotic retrovirus, Avian Leukosis Virus (ALV), offers such a robust, eukaryotic version of bacteriophage display.

9:00 Phenotypic Screening for Novel Antibody Targets in the Tumor Microenvironment

PodcastRalph_MinterRalph 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.

9:30 Generation of Antibodies Targeting Intracellular Oncogenic Mutations Presented by Common HLA Complexes

Andrew_SkoraAndrew 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.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Awards


NEW APPLICATIONS AND TECHNOLOGIES FOR PHAGE AND YEAST DISPLAY

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_LiuDavid 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_KolmarHarald 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_Van_DeventerJames 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


PH DEPENDENT BINDING OF ANTIBODIES

2:00 Chairperson’s Remarks

David Lowe, Ph.D., Director, R&D, 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_GraslundTorbjorn 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 The Creation of Potent Peptidic Inhibitors of Trypsin-Like Serine Proteases

Peter_AndreasenPeter A. Andreasen, Ph.D., Professor, Molecular Biology and Genetics, Aarhus University

From phage-displayed peptide libraries, we isolated 10 – 12 amino acids long inhibitors of urokinase-type plasminogen activator, with Ki values around 0.5 mM. Through a maturation process involving additional library screenings, structure-based rational design, and the use of unnatural amino acids, we created highly specific urokinase inhibitors with Ki values down to 0.2 nM and retargeted the peptides from urokinase inhibitors to highly specific, high affinity inhibitors of plasma kallikrein.

3:05 Presentation to be Announced

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing


Antibodies against Ion Channels and Difficult Targets

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_ShustaEric 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_StockbridgeRandy 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*



RECOMMENDED DINNER SHORT COURSE*

SC10: Analyzing and Rationalizing Protein-Protein Interactions

*Separate registration required



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