A vast number of mainstream and emerging biotechs are now engaged in the discovery and development of cell and gene therapies, but significant advances in analytical and process technologies are required to support preclinical and clinical development, quality control strategies and progression through the regulatory steps needed to reach the market. The PEGS Cell and Gene Therapy Analytics conference offers an all case study format in which leading scientists will share their experiences with new tools, lessons and learnings – and what works and doesn’t work to move efficiently in this explosive new field of pharmaceutical science.

Final Agenda

Day 1 | Day 2

THURSDAY, MAY 7

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

CHARACTERIZATION ASSAYS

1:40 Chairperson’s Opening Remarks

Richard Rustandi, PhD, Principal Scientist, Merck

1:50 Assay Development for Emerging Single-Cell Platforms

Eric Alonzo, PhD, Senior Scientist, bluebird bio

Clinical-grade CAR T cell drug products contain a heterogenous mixture of phenotypically and functionally distinct cells. Such heterogeneity necessitates innovative and comprehensive strategies to characterize CAR T cell therapy investigational drug products. Here, we present how high-dimensional single-cell analytics in CAR T manufacturing and beyond can be used to resolve drug product complexity and identify potentially key clinical correlates.

2:20 Characterization of Gene Therapies by Charge Detection Mass Spectrometry

Martin Jarrold, PhD, Professor, Chemistry, Indiana University

Conventional mass spectrometry is usually limited to masses less than a Megadalton because of heterogeneity. Charge detection mass spectrometry (CDMS) can overcome this limitation and extend accurate mass measurements into the Gigadalton regime. Recent technical advances have dramatically improved the sensitivity of CDMS. Applications of CDMS to the analysis of complex biopharmaceuticals, including gene therapy products and vaccines, will be presented.

2:50 KEYNOTE PRESENTATION: T Cell-Intrinsic and -Extrinsic Mechanisms Response to CAR T Cell Therapy

Jan Joseph (Jos) Melenhorst, PhD, Adjunct Associate Professor, Pathology & Laboratory Medicine, University of Pennsylvania

This past decade has witnessed the transformation of cancer therapy via chimeric antigen receptor (CAR)-redirected lymphocytes. Translational sciences have shed light on the mechanistic basis of response and resistance, which are translated into the next-generation CAR therapies. I will summarize some of these principles and how those inform next-generation CAR T cell therapies for liquid and solid tumors.

3:20 Presentation to be Announced

3:50 Networking Refreshment Break

INCREASING ANALYTICAL DEPTH AND THROUGHPUT

4:20 Simple and Deep Analytical Tools for Process Characterization of Oncolytic Virus

Richard Rustandi, PhD, Principal Scientist, Vaccine Analytical Research Development, Merck

Oncolytic virotherapy is a new emerging modality where competent virus replication kills cancer cells and induces immune response. Development of oncolytic virus is relatively complex and requires a different analytical toolbox compared to traditional vaccine. During early stage process development, we have implemented simple and efficient analytical methods to understand the product. These methods are used to monitor at least six different quality attributes of the oncolytic virus product.

4:50 Understanding the Effect of Post-Translational Modifications of AAV Capsid Proteins and Their Impact on AAV Infectivity

Lin Liu, PhD, Principal Scientist, Biologics Development, Sanofi

Viral capsid proteins play an important role in cellular targeting and trafficking as part of the viral infection cycle, and thus changes in the viral capsid protein sequence or post-translational modifications (PTMs) might impact viral targeting and infectivity. We evaluated the role of AAV capsid protein PTMs on AAV transduction potential by generating AAV2 and AAV5 capsid mutants and performing a stress study.

5:20 End of Day

5:15 Registration for Dinner Short Courses

5:45-8:15 pm Recommended Dinner Short Course*

SC15: Introduction to Gene Therapy Products Manufacturing and Analytics

*Separate registration required.

Day 1 | Day 2

FRIDAY, MAY 8

8:00 am Registration and Morning Coffee

POTENCY ASSAYS

8:30 Chairperson’s Remarks

Eric Alonzo, PhD, Senior Scientist, bluebird bio

8:35 Overcoming the Limits and Variability of Cell and Gene Therapy Potency Assays

Zhenhong Li, PhD, Senior DIrector, Analytics, Regenxbio, Inc.

The development and validation of robust potency assays continues to be a significant challenge in the preclinical development of cell and gene therapies. This presentation outlines potential strategies for overcoming the limit and variability issues for these important studies.

9:05 High-Throughput Potency Methods Applied to Formulation Development of Live Viral Vaccines

Prashant Kumar, PhD, Senior Scientist, Vaccine Analytics, University of Kansas

We evaluated quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR) as an alternative to traditional Fluorescent Focus Assay (FFA) for measuring live virus in vitro potency. A high correlation between the two assays, no interference of pharmaceutical excipients, and the advantages of RT-qPCR assay (improved speed, throughput, and ease), together demonstrate the advantages of the RT-qPCR assay over FFA to more rapidly monitor and compare live virus vaccine stability in different formulations.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Networking Coffee Break

PRODUCT QUALITY ATTRIBUTES

10:35 Analytical Methods for Quality Assessment of Cell-Based Medicinal Products

Wim Jiskoot, PhD, Professor, Drug Delivery Technology, Leiden University, The Netherlands

My presentation will start with a brief introduction into quality attributes of cell-based medicinal products, including an overview of routine (QC) methods used to characterize such products. Next, I will discuss the potential applicability of image-based techniques to assess the viability and purity of cells, which I will illustrate with results obtained in my lab.

11:05 Challenges and Hope for the Chemical and Biological Characterization of AAV-Based Gene Therapy Products

Dong Xu, PhD, Senior Scientist, Biogen

Two case studies are included in this presentation to assess Critical Quality Attributes (CQA) for AAV-based gene therapy products; one focuses on the physical and chemical aspects for the capsid vector, while the other quantitatively measures the intracellular activity of target gene. They represent the current methods of choice and are applicable to platform analytical assay development for similar therapeutic programs.

11:35 U.S. Regulatory Update for Cell and Gene Therapy

Jean Stanton, Director, CAR-T Site Liaison, Janssen

In the last few years, the FDA has approved several oncolytic and gene therapy products. In 2018, the FDA issued, for public comment, six draft guidance documents intended to serve as part of a modern, comprehensive framework for how CBER will help advance the field of gene therapy. This presentation will provide an overview of three of those draft guidance documents, highlighting the impact on analytical development.

12:05 pm Observations and Insights from Cell and Gene Therapy Regulatory Interactions

William Motel, PhD, Associate Director, Regulatory Affairs, IQVIA

As advanced cell and gene therapeutics are more thoroughly investigated for a wide variety of indications, the FDA has had a number of years to begin to refine the regulatory requirements to develop and bring to market cellular therapies. This presentation will provide up-to-date observations and insights coming from recent interactions with the regulators on the development of advanced therapeutics across various phases of investigation.

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Networking Refreshment Break

ANALYTICAL CHALLENGES IN ADVANCING CELL AND GENE THERAPIES

1:35 Chairperson’s Remarks

Dong Xu, PhD, Senior Scientist, Biogen

1:40 Evaluating a Control Strategy for an Autologous Cell Therapy for Risk to Patients

Ken Riker, Director, Product Quality, Celgene

An integrated control strategy was developed for a late-phase CAR T cell therapy product based on our current understanding of the product quality attributes, the manufacturing process, and analytical capability. Based on this comprehensive assessment, the overall risk of drug product to patient safety and product efficacy was determined to be low, demonstrating that the combined operational and testing controls are suitable to ensure product quality from the proposed commercial process.

2:10 Machine Learning for the Rapid Classification of Flow Imaging to Characterize Cell Therapies

Amber Fradkin, PhD, Director, Particle Characterization Core Facility, KBI Biopharma

We used a very common analytical method to characterize subvisible particles in biologics (Micro-Flow Imaging) and applied the technique to cell therapy products. We have developed customized machine learning algorithms specific to cell therapy MFI data for rapid classification of images to establish particle profiles. The method has overwhelming potential to monitor cell particle size distributions, cell debris, cell agglomerates, as well as extrinsic material from batch to batch.

2:40 Deep Analysis to Support Early Stage Product and Process Characterization and Improved Release Assays

Alden Ladd, Scientist, Cellular Process Development, bluebird bio

Typical release assays for CAR T products have been shown to not be predictive of clinical outcomes. Characterization activities should integrate single-cell analytics and sensitive functional assays to define surrogate biomarkers of potency that can be used in release assays, process understanding, process improvement, and patient selection. As product complexity increases, new surrogate potency assays will need to be developed to address the multifaceted modes of action of these complex products.

3:10 Development and Qualification of a Cell Counting Assay for Dose Determination

Michele Perry, Lead Microbiology Associate, Analytical Development, Synlogic

Live bacterial products (LBP) are novel therapeutics with the potential to treat unmet needs in rare genetic diseases, such as phenylketonuria. Viability is a critical aspect of LBPs and traditionally determined through colony-forming unit methods. Another approach to determining viability is automated cell counting. When the methods were compared, the cell counting results were more indicative of in vivo activity of the LBPs and is now used to determine dose.

3:40 End of Conference

Day 1 | Day 2

* The program is subject to change without notice, due to unforeseen reason.