Cambridge Healthtech Institute’s Inaugural

Intelligent Antibody Discovery

Next Generation Technologies to Improve the Speed and Focus of Biotherapeutic Discovery

January 17 - 18, 2022 ALL TIMES PST

Peptalk’s inaugural Intelligent Antibody Discovery conference offers delegates a unique opportunity to explore the contributions of new science and technologies to discovery and early-stage biopharmaceutical development. The meeting examines the evolution of display methods and the role of tailored library design and how repertoire screening platforms are now being applied to new targets and capabilities. These new directions will be illustrated with case examples of rapid Covid-19 R&D projects and their use with challenging target classes.

Sunday, January 16

4:00 pm Conference Registration Open (Sapphire West Foyer)

Monday, January 17

7:00 am Registration and Morning Coffee (Sapphire West Foyer)


Session Room: Sapphire P

9:00 am Organizer's Welcome Remarks

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 am

Chairperson's Remarks

Gregory C. Ippolito, PhD, Research Associate Professor, Molecular Biosciences, University of Texas at Austin
9:10 am

Precision Functional Screening for Intelligent Antibody Discovery Against Public Health Targets

Brandon DeKosky, PhD, Phillip and Susan Ragon Career Development Professor of Chemical Engineering, MIT Core Member, The Ragon Institute of MGH, MIT, and Harvard

Recent work has revealed critical vulnerable antibody targets that interrupt malaria and HIV-1 transmission. We performed efficient antibody engineering by screening all possible single amino acid substitutions throughout the antibody variable region, enabling exquisite anti-malarial protective potency. Using the same strategy, we engineered the most broadly-neutralizing antibody reported against the HIV-1 fusion peptide. This presentation will share these unpublished molecular studies and outline effective strategies for precision drug discovery.

9:40 am

High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity

Ivelin Georgiev, PhD, Associate Professor, Pathology, Microbiology, and Immunology, Vanderbilt University Vaccine Center

LIBRA-seq (LInking B-cell Receptor to Antigen specificity through sequencing) enables high-throughput antibody discovery through simultaneous screening of B cells against a theoretically unlimited number of antigens at a time. Using LIBRA-seq, we have identified antibodies with unique phenotypic properties against a number of pathogens, including HIV-1, hepatitis C, and coronavirus. Overall, the LIBRA-seq technology offers unmatched capabilities for high-throughput discovery of novel antibody therapeutics and for assessment of vaccine efficacy.

10:10 am

In Vitro Screening Tools for the Selection of Membrane-Permeable Peptides

Iriny Ekladious, PhD, Associate Principal Scientist, Sterile & Specialty Products, Merck

Peptides are a highly promising class of therapeutics; however, their full potential has not yet been realized due to their poor cell permeability and limited oral bioavailability. mRNA-display is a powerful high-throughput in vitro screening technology in which peptide drug candidates are screened against a target of interest. The work described herein demonstrates the utility of in vitro approaches that interrogate peptide permeability, with the goal of integrating these tools into mRNA display. The integration of these approaches into mRNA-display has the potential to facilitate the development of peptides that exhibit activity against their target as well as membrane permeability.

10:40 am Networking Coffee Break (Sapphire West Foyer)


11:00 am

Accelerating Antibody Discovery with in silico Repertoire Screening and Rational Design

Bryan Wu, PhD, NGS Lead, GlaxoSmithKline Biopharm Discovery, United Kingdom

Antibody repertoire sequencing has enabled us to access unprecedented amounts of antibody sequences. Here we will demonstrate our approach to comprehensive screening of antibody repertoires and in silico development of potent antibody leads.

11:30 am

Plasma IgG Proteomics for the Discovery of Pan-Coronavirus Antibodies Induced by SARS-CoV-2 Infection or Vaccination

Gregory C. Ippolito, PhD, Research Associate Professor, Molecular Biosciences, University of Texas at Austin

The most clinically advanced COVID-19 vaccines use the full SARS-CoV-2 spike (S1 + S2) as immunogen. Molecular proteomics of plasma IgG (Ig-Seq) indicates that S2-targeting antibodies typically comprise the most abundant antibody lineages in circulation and that S2-targeting antibodies arise predominantly from pre-existing cross-ß-coronavirus lineages. These Ig-Seq observations, and others, are being harnessed in the development of a new pan-ß-coronavirus vaccine based on S2-only antigens.

Roza Bidshahri, PhD, Senior Research Scientist and BD Liaison, AbCellera

GPCRs and ion channels are highly sought-after drug targets, but only two antibody drugs targeting them have been approved. AbCellera tackles the biggest challenges limiting antibody discovery for transmembrane proteins: producing antigens, driving antibody responses, and finding hits. Optimized immunization strategies, single-cell screening, and hyper-scale data science leads to hundreds of hits, and by integrating Tetrahymena — a natural membrane protein factory — we’re driving powerful solutions to unlock these targets.

12:30 pm Session Break
Jonathan Hurtado, PhD, Post-doctoral fellow, The Scripps Research Institute
1:10 pm Session Break


1:50 pm

Deep Learning Approaches for Neoantigen Prediction

Kai Liu, PhD, Principal AI Scientist, Head, Medical Language Processing, Early Clinical Development, Genentech, Inc.

This neoantigen recognition mechanism is one of the pillars of the immunological surveillance of tumor cells for cancer therapies. By leveraging the enriched immunopeptidomics dataset, we developed deep learning based models to characterize the peptide-MHC interaction and predict the antigen presentation and immunogenicity. The ranking of the neoantigens from patients could pave the way for the development of personalized cancer immunology therapies.

2:20 pm

Epitope-Specific Antibody Design via Deep Learning-Based Structural Modeling

Possu Huang, PhD, Assistant Professor, Bioengineering, Stanford University

Epitope-specific binders can potentially be created by computational protein design strategies. By leveraging the unique properties of neural networks, we developed a generative model for immunoglobulin structures, with which diverse structures can be modeled with unprecedented speed. A design pipeline incorporating this neural network model can achieve flexible backbone protein-protein interface design. We will discuss this novel protein docking/design strategy and its potential application in creating epitope-specific novel immunoglobulin binders.

2:50 pm Find Your Table and Meet the BuzZ Sessions Moderator
3:00 pm BuzZ Sessions with Refreshments (Sapphire Foyer)

PepTalk BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic. Continue to check the event website for detailed discussion topics and moderators.

BuzZ Table 1: In Silico Antibody Design

Possu Huang, PhD, Assistant Professor, Bioengineering, Stanford University
  • Algorithmic challenges related to modeling antibodies and predicting antibody properties
  • Designed diversity versus natural immune combinatorial repertoire
  • Experimentalists' wishlist for computational methods ​
  • Challenging targets for which computation tools (may) offer solutions

BuzZ Table 2: Antigens, Antibody Engineering and Specificity

John Williams, PhD, Professor of Molecular Medicine and Co-Director, Drug Discovery and Structural Biology Core, Beckman Research Institute at City of Hope
  • Are there unique antigens for oncology?
  • How do we find them?
  • How can we identify multiple antigens to improve specificity?
  • How do we build them?​


4:00 pm

Blood-Brain Barrier Delivery in Non-Human Primates by Single Domain VNAR Antibodies to TfR1

Pawel Stocki, PhD, Director, Research, Ossianix, Inc., United Kingdom

Poor brain delivery is a major hurdle in the development of biological therapeutics for neurologic diseases because of poor Blood-Brain Barrier penetration. Numerous BBB shuttles based on single-domain VNAR antibodies were developed by Ossianix. These include TXP1 which was demonstrated to penetrate the brain with high efficiency when inject at low therapeutic dose in non-human primates with an over 30-fold increase in comparison to the control.

4:30 pm

Merging Antibody and Small Molecule Drug Discovery: CLAMPs to Study and Drug Dynamic Proteins

James T. Koerber, PhD, Principal Scientist, Antibody Engineering, Genentech, Inc.

We will describe Conformation Locking Antibodies for Molecular Probe discovery (CLAMPs) to distinguish and induce rare protein conformational states. We discover novel KRAS CLAMPs that recognize and induce a rare KRAS conformation. These CLAMPs enable new biology insights through visualization of inhibitor-bound KRAS in cells and tumors, a high-throughput screen to discover small molecule ligands, and structure-based characterization to provide a new framework for drug discovery against dynamic proteins.


Merging MOA, Structural Information & Single Cell Screening to Identify Potent mABs as Potential Therapeutic Candidates

John Williams, PhD, Professor of Molecular Medicine and Co-Director, Drug Discovery and Structural Biology Core, Beckman Research Institute at City of Hope

Beyond their unique specificity and high affinity, mAbs are imbued with additional functionality including ADCC/ADCP/CDC where the position of the epitope within the antigen has emerged as a critical determinant driving these activities.  Herein, we provide examples where we leverage such information to create unique reagents and combine these reagents with single cell screening efforts to identify multiple hits that differentiate healthy and disease cells and elicit potent immune activity.

Andrew Bradbury, PhD, CSO, Specifica

The Specifica Generation 3 Library Platform is based on highly developable clinical scaffolds, into which natural CDRs purged of sequence liabilities have been embedded. The platform uses phage+yeast display to directly yield highly diverse (100-1000 clusters differing by Levenshtein distance 30-40), high affinity (20% subnanomolar), extremely developable (>80% lack biophysical liabilities), drug-like antibodies, which in a recent Covid campaign were as potent as antibodies from immune sources.

6:00 pm Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:30 pm Close of Day

Tuesday, January 18

8:30 am Registration and Morning Coffee (Sapphire West Foyer)


Session Room: Sapphire P

9:00 am

Chairperson’s Remarks

Vu L. Truong, PhD, CEO & CSO, Aridis Pharmaceuticals, Inc.
9:05 am

Rapid Discovery of Infectious Disease Targets

Vu L. Truong, PhD, CEO & CSO, Aridis Pharmaceuticals, Inc.

The COVID-19 pandemic has provided an unprecedented incentive for researchers to devise strategies for rapid target discovery and development of therapeutics and vaccines. The net effect has been breathtaking speed of discovery and product creation that may forever change how infectious diseases targets are identified and therapies developed. This presentation will provide an overview of discovery and product development platform approaches that could set the tone for the future development of infectious disease therapies. Case studies will be presented on viral and bacterial targets.

9:35 am

Discovery and Development of SARS-CoV-2 Neutralizing Antibody LY-CoV555

Bryan E. Jones, PhD, Research Fellow, BioTechnology Discovery Research, Eli Lilly & Co.

Near the start of the pandemic in 2020 caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), AbCellera and Eli Lilly & Co. partnered to discover and develop antibodies capable of neutralizing infection by SARS-CoV-2. From this partnership, Ly-CoV555, also known as bamlanivimab, was rapidly identified from a blood sample of one of the first convalescent patients located in the US. Bamlanivimab became the first SARS-CoV-2 targeted antibody to enter US clinical trials, and receive Emergency Use Authorization, just three months after discovery. The rapid discovery and progression of bamlanivimab into clinical evaluation will be described.

10:05 am Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 am

Rapid Generation of Potent SARS-CoV-2 Nanobodies by Autonomous Hypermutation in Yeast

Alon Wellner, PhD, Postdoctoral Researcher, Biomedical Engineering, University of California, Irvine

In my talk, I will describe Autonomous Hypermutation yEast surfAce Display (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. By encoding antibody fragments on an error-prone orthogonal DNA replication system, surface-displayed antibody repertoires continuously mutate through simple cycles of yeast culturing and enrichment for antigen binding to produce high-affinity clones in as little as 2 weeks. AHEAD was applied to generate a diverse set of potent nanobodies that target different epitopes on the surface of the SARS-CoV-2 S glycoprotein, a GPCR, and other targets, offering a template for streamlined antibody generation at large.

11:30 am

From Grass to Greener Grass – The Construction of a Biomanufacturing Facility on Budget and in Record Time

Maria J. Aubrey, Vice President, Biologics Manufacturing Center Project, National Research Council Canada

The NRC was mandated by the Government of Canada to establish the new Biologics Manufacturing Centre in Montréal to help support Canada’s biomanufacturing vaccine production capacity and pandemic readiness in response to the COVID-19 pandemic and in the future. A team of industry professionals and subject matter experts was assembled to design and build a facility within one year that would normally take 2 to 3 years in normal circumstances.

Volker Lang, Managing Director, AbCheck s.r.o.

Specific requirements have to be met for the discovery of antibodies with challenging Target Product Profiles (TPPs). AbCheck has developed a technology to efficiently meet these requirements;  e.g., functional antibodies or antibodies against targets with high homology. Our novel, tailored microfluidics technology is based on high throughput functional sorting of immune plasma cell repertoires at single cell level.

12:30 pm Session Break
Piotr van Rijssel, Application Scientist, ENPICOM

The integration of high-throughput sequencing data in antibody screening accelerates and improves the discovery of novel therapeutic antibodies. However, getting from millions of sequences to a diverse set of developable antibodies with the right therapeutic properties can be incredibly challenging, time-consuming, and requires significant software and computational resources. In this session, we will discuss how you can predict exposed liability for thousands of antibodies to accelerate and de-risk your candidate selection.

1:10 pm Close of Intelligent Antibody Discovery