2019 Archived Content

Breakout Discussions

Commonwealth Hall

MONDAY, APRIL 8
2:20 - 3:20 PM

Display of Antibodies

TABLE 1: Phage-Display of Recombinant Affinity Reagents

Moderator: Brian K. Kay, PhD, Professor, Department of Biological Sciences, University of Illinois, Chicago

Two-site capable affinity reagents are challenging to discover
Pair discovery can be built into phage-display through MegaSTAR
Millions of pair-wise combinations can be created and easily screened
MegaSTAR yields 5-15 pairs per target
Bispecific reagents have affinities < 22 nM

TABLE 2: Cyclic Peptides – Going from Hits to Leads and to the Clinic

Moderator: Gregory A. Weiss, PhD, Professor, Chemistry, Molecular Biology & Biochemistry, University of California, Irvine

Several methods available for identifying cyclic peptide hits
The path from hit to lead is less clear
We will discuss strategies for converting cyclic peptide hits into leads

TABLE 3: Phage Display for Biomarker Discovery

Moderator: Lobelia Samavati, MD, Associate Professor of Medicine, Department of Medicine, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine

T7 phage display as novel nexus for biomarker discovery of inflammatory diseases
Biomarkers as expression of disease pathogenesis
Biomarkers for the development of targeted therapy

TABLE 4: Getting from NGS Data to Testable Clones in in vitro Antibody Discovery?

Moderator: Fortunato Ferrara, PhD, Vice President, Specifica, Inc.

Importance of NGS to isolate lead candidate after in vitro selections
Will NGS completely replace high throughput screenings?
Novel and future NGS platforms and their use in guiding recombinant antibody discovery

Antibodies for Cancer Therapy

TABLE 5: Engaging Innate and Adaptive Immunity

Moderator: Paul M. Sondel, MD, PhD, Reed and Carolee Walker Professor of Pediatrics, Human Oncology, and Genetics, and Director of Research, UW Division of Pediatric Hematology, Oncology and BMT, UW Carbone Cancer Center and American Family Children’s Hospital, University of Wisconsin

Tumor reactive mAbs can have activity against small amounts of solid tumor in vivo, likely via innate immunity
Induction of Innate Immunity can help trigger subsequent adaptive immunity
This may enable an existing tumor to function as an in situ vaccine

TABLE 6: Clinical Development, Early Phase Studies, Immunotherapy Combinations, and Engineering Cancer Immunotherapy

Moderator: Daniel Chen, MD, PhD, CMO, IGM Biosciences

We face specific challenges in developing next generation cancer immunotherapy
Improved immunotherapy must start by reversing specific immune escape mechanisms – or bypass them
Engineered cancer immunotherapy may target biologic modification more specifically – improving efficacy and safety, or bypass endogenous immune biology
Rational combinations for cancer immunotherapy are likely necessary to obtain optimal outcomes and durable responses
Assessing contribution of parts and optimal dose/schedule in cancer immunotherapy Phase I studies require attention to specific study design features

TABLE 7: Anti-B Cell Maturation Antigen Chimeric Antigen Receptor T Cell therapy for Multiple Myeloma

Moderator: Dexiu Bu, MD, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institute for Biomedical Research

How to best target the low level of Antigen
The stemness of Antigen: Escape mechanisms after treatment
Therapeutic modality: Cell therapy vs therapeutic Abs (ADC, or bispecific)

TABLE 8: The Emerging Profile of Immunotherapy in Acute Leukemia

Moderator: Naval G. Daver, MD, Associate Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center

Immune therapy toxicity management in AML/MDS
Biomarkers for response to immune therapy in leukemia

Improving Immunotherapy Efficacy and Safety

TABLE 9: Improving Immunotherapy Efficacy

Moderators: Baochun Zhang, MD, PhD, Assistant Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School

Prabuddha K. Kundu, PhD, Co-Founder & Managing Director, Premas Biotech Pvt Ltd

Current efforts to improve efficacy
New targets, modalities
Novel CAR target antigens in hematologic and solid tumors

TABLE 10: Commercial Manufacturing of Gene-Modified Cell Therapies: The Challenges Ahead

Moderator: Michael D. Jacobson, PhD, Managing Partner, Cambridge Biostrategy Associates

What are the most important problems that need to be solved over the next 3-5 years for this industry to thrive?
What key innovations would you like to see that you believe would be transformative?
How low do COGS need to go, and how (and when) will we get there?
How automated and integrated will cell therapy manufacturing become over the next 5-10 years? What parts of the workflow are most ripe for integration, and which are not?

Difficult to Express Proteins

TABLE 11: Challenges of Producing Integral Membrane Proteins

Moderator: Nicola Burgess-Brown, PhD, Principal Investigator, Biotechnology, Structural Genomics Consortium, University of Oxford

Construct design: preferred tags, proteases, how many constructs to screen?
Challenges of expressing integral membrane proteins: which expression host?
Problems of scale of production for structural biology: resource and cost issues.
Strategies to improve purification and stability of membrane proteins: detergents, lipids, affinity reagents, liposomes, nanodiscs, SMALPs.

TABLE 12: Why are we Stuck with HEK and CHO? What New Eukaryotic Expression Systems are Ready to Use? Are We Making the ‘Right’ Proteins?

Moderator: James Love, PhD, COO, Institute for Protein Innovation

Engineering cell lines or find new cell lines with enhanced properties?
Opportunities for purification from natural sources?
What proteins can’t be made?

TABLE 13: Next Generation of Biotherapeutics: Challenges to Express Complex Format Proteins (Host vs. Titer vs. Product Quality)

Moderator: Shahram Misaghi, PhD, Senior Scientist, Early Stage Cell Culture, Genentech, Inc.

Therapeutic molecules are becoming increasingly more complex (no longer just antibodies).
Many of these molecules are highly potent (especially the ones that elicit immune cells), requiring lower dosage but very consistent product quality.
Are we, as an industry, prepared to express these increasingly more complex molecules?
Are we, as an industry, focusing enough on product quality besides productivity?
What innovations (engineering, media, hosts, etc.) should we focus on to address these issues?
Have new large-scale manufacturing approaches being adequately developed and tested to consistently manufacture these complex molecules?

Characterization of Biotherapeutics

TABLE 14: Characterization Issues for Cell Therapy Products

Moderator: Kuldip Sra, PhD, Senior Director, CRISPR Therapeutics

Lot release of cell therapy products
Stability program for cell therapy products
Raw material testing strategy

TABLE 15: Impact of HPLC-MAM-MS Workflows to the Analytical Drug Development Process

Moderator: Jennifer F. Nemeth, PhD, SCPM, Director, Biophysics, Structural Characterization, Biologics Discovery Sciences, Janssen Research & Development

What assays are being replaced by HPLC-MAM-MS Workflows?
What assays have people tried to replace and have run into difficulties?
Is the vendor software meeting compliance needs for GLP / GMP environments?
What could vendors be doing better to help our industry execute MAM workflows?

TABLE 16: Development Issues for CAR-Ts

Moderator: Zhimei Du, PhD, Director, Bioprocess, Merck & Company, Inc

What are major COGs during CAR-T cell therapy and how to reduce it?
How to improve process consistency during CAR-T cell therapy?
How to apply the experience of biologics development to CAR-T cell therapy?
Scale up vs scale-out

TABLE 17: Best Practices for Assessment of Critical Quality Attributes (CQAs) for Antibody-Drug Conjugates

Moderator: Lisa Zhou, Senior Scientist, Protein Analytics, AbbVie

Application of platform vs. product-specific attribute knowledge in CQA assessments for ADCs
CQAs assessment and determination of specifications, early stage and late stage strategies
Analytical methods used for the release vs. characterization
CQAs and process characterization

Immunogenicity Case Studies and Clinical Management

TABLE 18: Immunogenicity Risk Assessments for Complex Biotherapeutics

Moderator: Joleen White, PhD, Director and Head, NBE DMPK Project Support, EMD Serono Research & Development Institute Inc.

How Immunogenicity Assessments differ (or not) for complex multi-domain biotherapeutics versus traditional mAbs or therapeutic proteins
Immunogenicity Risk Assessments during clinical development

TABLE 19: How Can We Translate, Integrate and Implement ADA Testing in Clinical Routine in the Most Efficient Way?

Moderator: Anna Fogdell-Hahn, PhD, Associate Professor, Clinical Neuroscience, Clinical Neuroimmunology, Center for Molecular Medicine (CMM)

Can we transfer ADA methods from industry to clinical routine (challenges versus benefits)?
What type of data is missing to convince clinicians to integrate ADA testing in treatment decisions?
What would be the consequences of routine testing for ADA in the clinic for the pharma industry, health care, patients, clinicians and society?

Fusion Protein Therapeutics

TABLE 20: Novel Formats and Platforms for Fusion Proteins

Moderator: Dario Neri, PhD, Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich)

Fusions based on full IgG vs. antibody fragments
Monovalence vs. multivalence
Tissue penetration and half-life
Activity-on-demand

TABLE 21: Fusion Proteins as Immunotherapy Agents

Moderator: Oliver Hill, PhD, Vice President, Molecular Biology/Protein Engineering, Apogenix AG

Evaluation of immunotherapeutic formats - Fusion proteins, Antibodies, Antibody-fragment based fusion proteins and Multiformats:

Is there superiority of a specific format regarding agonistic versus antagonistic signaling approaches?
Are there target-structure based preferences for certain formats?

Performance of multidomain fusion proteins to locally override an immune checkpoint:

Are there enabling formats?
Which targets to address (ECM, immune cell, tumor cell)?
What are useful therapeutic combinations?

Emerging Indications for Therapeutic Antibodies

TABLE 22: Preclinical Development Strategies for Antibody Therapeutic Candidates

Moderator: An Song, PhD, Senior Vice President, Development Sciences, Immune-Onc Therapeutics, Inc.

Pros and cons of technologies for generating antibody therapeutic candidates
What antibody affinities do you usually target and when would you do affinity maturation?
Assessment and design of Fc effector functions for IND?
Pros and cons of using single clone material for IND-enabling studies or pooled clone material
Approaches to pilot studies prior to GLP and IND-enabling studies

TABLE 23: Emerging Technologies for Antibody Discovery and Engineering

Moderator: Juan Carlos Almagro, PhD, Founder and Director, GlobalBio, Inc.

Human content and immunogenicity
Diverse phage display libraries, advantages and limitations
Engineering novel properties in the antibodies, for instance, pH-dependent binding
Novel transgenic platforms for antibody discovery, for instance, transgenic chickens

TABLE 24: Alternate Conjugation Strategies

Moderator: Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, Biochemical Pharmacology, Queen Mary University, United Kingdom

Synthetic scaffolds in oncology
Biological scaffold in oncology: vesicles shaded scaffolds and liposomes
Biological scaffold in auto-immune diseases
What can we learn for future combined treatment development?

WEDNESDAY, APRIL 10
4:45 - 5:45 PM

Engineering Antibodies

TABLE 25: Biochemical Analysis of Complex Antigens and Antibody-Antigen Interactions

Moderator: Kathryn Hastie, PhD, Staff Scientist, Immunology and Microbiology, The Scripps Research Institute

How to assess the mass and oligomeric state of complex proteins (particularly glycoproteins) using light scattering – necessary information for down-stream analyses
Epitope binning using Octet
Kinetics and affinity using Octet
Kinetics, affinity and stoichiometry analysis using light scattering

TABLE 26: The Application of Machine Learning in Antibody Discovery

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

Difference between machine learning and deep learning
Concepts of machine/deep learning in drug discovery
How can machine/deep learning be used for antibody therapeutics?
What are major challenges for implementing machine/deep learning strategies?

Advancing Bispecific Antibodies and Combination Therapy to the Clinic

TABLE 27: Bispecific Antibodies: The Road Less Traveled and the Road Up Ahead

Moderator: James L. Gulley, MD, PhD, FACP, Chief, Genitourinary Malignancies Branch, Head, Immunotherapy Group, GMB Director, Medical Oncology Service, Center for Cancer Research, NCI, NIH

Cancer immunotherapy approaches and opportunities in solid tumors
Why combination approaches in immunotherapy are the next big thing
Why bispecific proteins are an important rational approach to combination immunotherapy

Concentrating immune activity within tumor
Drug development strategies

Examples of bispecifics (M7824, NHS-IL12, N-809)

TABLE 28: Developability of Bispecific Antibodies

Moderator: Nimish Gera, PhD, Director, Research and Development, Mythic Therapeutics

Format selection for biological problem at hand
Developability of different formats IgG-like, appended IgG and non-Fc formats
What are the most important developability features and ways to assess them?

TABLE 29: Bringing Novel Bispecific Antibodies to the Clinic: Challenges and Solutions

Moderator: Charlotte Russell, MD, PhD, CMO, Alligator Bioscience AB

Translating non-clinical data to the human setting
Limited availability of non-clinical data due to lack of relevant models
Justification of first-in-human starting dose and escalation
Design of studies with combinations, e.g. Standard of care + novel compound and/or novel + novel compound
Selection of patients for first-in-human trials

TABLE 30: Building Better T Cell- and NK Cell-Engaging Bispecifics

Moderator: Gundo Diedrich, PhD, Director, Antibody Engineering, MacroGenics

Targets on T and NK cells that induce stimulation/co-stimulation
Can T cell stimulation be uncoupled from cytokine release?
T cell- vs. NK cell-engagers: What are their advantages and disadvantages?
What can we learn from CAR T cell designs

CAR-Ts, TCRs and TILs

TABLE 32: Advances in Allogenic Cell-Based Therapies

Moderator: Barbra Sasu, PhD, CSO, Allogene

Limitations and Novel approaches for CAR-T therapy Differences between autologous and allogeneic cell therapy
Generation of a renewable source for large scale manufacturing of cellular therapeutics
Challenges of cell therapy for solid tumors
Combinations for cell therapy

TABLE 33: Present and Future of Genetically Engineered T Cells in Oncology

Moderators: Adrian Bot, MD, PhD., Vice President, Translational Sciences, Kite, a Gilead Company

Current results and limitations of CAR-T therapy
Innovative receptor designs
Desired features of T cells: potency and controllability
Manufacturing optimizations to scale out, diminish cost, and fully utilize this platform technology
Beyond blood cancers and beyond cancer: what is next?

Optimizing Protein Expression

TABLE 34: The Future of Cell Line Development: Random Integration, Targeted Integration or Both? Pros and Cons

Moderator: Ulrich Goepfert, PhD, Principal Scientist, Cell Line & Molecular Development, Roche Innovation Center Munich

DNA cloning efforts
Quality of stable pools
Diversity of clones
Production stability
Timelines

TABLE 35: Transient Cell Lines for CHO and Stable Pools

Moderator: Samuel Ellis, Vice President, Thomson Instrument Company

Which cell lines are best to work with
Which cell lines are best for scaling up for commercial use
Pros/Cons of different cell lines

TABLE 36: Strategic Outsourcing in Cutting-Edge Biologics Development

Moderator: Ian Wilkinson, PhD, CSO, Absolute Antibody, Ltd.

What drives developers to outsource? Is this the future or a fad; will development gradually be brought back in-house? What might drive that?
What processes can be readily outsourced? Is there anything that should never be outsourced?
What measures could CDMOs and CROs take to make themselves more useful for biologics developers?

Biophysical and Structural Analysis

TABLE 37: Multi-Attribute Method for Product Quality Attribute Understanding in Biotherapeutics

Moderator: Kristin Boggio, PhD, Senior Scientist, Protein Mass Spectrometry, Pfizer

What does MAM mean to you?
Attributes to be monitored
Correlation between MAM and early release methods
Automation
Technical and practical limitations of implementing MAM

TABLE 38: What are the Applications and Limitations of the Assays Used for Measuring Higher Order Structures?

Moderator: Jihong Wang, PhD, Principal Scientist, AstraZeneca

What kind of data should be included or not to be included in regulatory filings?
What assays needed to be included in comparability?
How HDX MS and NMR are used during protein drug development?
What’s new and high throughput assays can be used to evaluation higher order structures?

TABLE 39: The Role of Denaturing and Native-MS in Pharma: From mAbs to Membrane Proteins and Beyond

Moderator: Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen

Native-MS in pharma: is it established or still niche?
Required improvements for native-MS to become main-stream in pharma
LC-MS and native-MS in membrane protein analysis: what role does it have?
Specific MS improvements which would highly benefit pharmaceutical research
Which deconvolution algorithm is optimal for use in biopharma?

Immunogenicity Assessment and Regulatory Approval of Biologics

TABLE 40: Solutions for a Drug-Tolerant Neutralizing Antibody Assays

Moderator: Zhandong Don Zhong, PhD, Associate Director, Specialty Bioanalytics, Teva Pharmaceuticals

A risk-based approach to developing a drug tolerant neutralizing antibody (NAb) assays
The implication of the NAb positive controls
Pros and cons of various methods for improving detection of NAb

TABLE 41: Acid Dissociation for ADA Assays: Is it as Useful as Assumed?

Moderator: Eric Wakshull, PhD, Principal Scientist/Group Leader, Bioanalytical Sciences, Genentech

Acid dissociation is used to increase drug tolerance, and is often insisted upon by regulators
Acid dissociation has the potential to alter a sample in an unknown way
Does using acid dissociation methods bring added value to clinical immunogenicity assessment?

Engineering Antibody-Drug Conjugates

TABLE 42: Solid Tumor Resistance Mechanisms to Antibody-Drug Conjugate Therapeutics and Strategies to Overcome Them

Moderator: Anton Neschadim, PhD, MBA, CEO, ImmunoBiochem Corporation

Target-based resistance mechanisms: target heterogeneity; target loss and selective pressures acting against target; poor tumor penetration.
Payload-based and multifactorial resistance mechanisms: drug transporters and payload efflux; altered ADC trafficking and processing; mutations in cytotoxic drug target.
Lessons from the clinic, and congruence between clinical data and preclinical models.
Strategies to overcome resistance and their translation: novel targets; improved linkers and payloads; dual-payload design; small-molecule drug conjugates; bystander effects; bispecific and biparatopic ADCs, enzymatically- or environment-activated ADCs; combination therapies.

TABLE 43: Designing Optimum ADCs- Linkers and Conjugation Technologies

Moderator: James Baker, PhD, Associate Professor, Chemistry, University College London

Site-selective methods vs stochastic conjugation, the importance of controlling the attachment chemistry.
Serum stable linkers, with/without controlled cleavability. Leading approaches and new opportunities.
Strategic linker design, to offer the opportunity to increase the DAR/reduce hydrophobicity.

TABLE 44: Novel Payloads and New Platforms for ADCs

Moderator: Hans-Georg Lerchen, PhD, Chief Scientist, R&D Pharmaceuticals, Bayer AG

Experience and lessons learned from current effector chemistries utilized in ADCs in clinical trials
Is there a particular need for novel payload classes?
What are the criteria transforming toxophore moieties into payloads successfully employed in ADCs?
What are the desired profiles of payloads for treatment of solid tumors and hematological malignancies, resp.?

Oncolytic Virtual Therapy

CANCELLED - Please join Table 46 or other tables of interest

~~TABLE 45: Strategies to Maximize Potential of Oncolytic Viruses~~

~~Moderator:~~

~~What makes a better oncolytic virus? A more potent oncolytic backbone? Greater inducer of anti-tumor immunity?~~
~~Oncolytic virus engineering strategies~~
~~Rational combination therapy approaches~~

TABLE 46: Combining Virotherapy with Immunotherapy: Challenges and Opportunities

Moderator: Smita Nair, PhD, Professor, Surgery, Neurosurgery and Pathology, Duke University School of Medicine

Understanding the biological mechanism of oncolytic virus efficacy
Developing biomarkers (1) of response to therapy, (2) of prediction to allow patient selection, (3) of acquired adaptive immune resistance following therapy
Prioritizing rational combinations based on (1) the biological mechanism of oncolytic virus therapy, and (2) pre-clinical studies testing
Designing hypothesis-driven early phase clinical trials to test combinations with emphasis on (1) patient selection, (2) novel trial design, (3) biomarker validation, (4) clearly defined outcomes

Analytical Support for Drug Product Development

TABLE 47: Development Issues for High Concentration Monoclonal Antibody Drug Products

Moderator: Chaitanya Sudrik, PhD, Postdoctoral Associate, Molecular Engineering, Massachusetts Institute of Technology

Novel excipients for viscosity reduction in liquid high concentration formulations
Novel drug formats like antibody particle suspensions: opportunities and challenges
Drug delivery device solutions like on-body injectors.: opportunities and challenges
Fill-finish and other manufacturing challenges with high concentration mAb formulations

TABLE 48: Definition of Clinically-Reliable Specifications

Moderator: Gerald Gellermann, PhD, Senior Fellow, Novartis, Switzerland

What is a clinically-reliable specification?
How is it defined in ICHQ6 and what are the consequences?
Do we need to test every variant at its maximal level in clinical trials to back-up specifications anticipating future process variability e.g. during process/capacity improvements?
What is a clinical reliable specification for a non-critical product variant?

TABLE 49: 3D Assays, a Paradigm Shift: Shortening Development to and Through Clinics

Moderator: Prabuddha Kundu, Co-Founder and Managing Director, Premas Biotech