Cambridge Healthtech Institute's 4th Annual

Gene Therapy Analytics & Manufacturing

CMC Strategies, Tools, Process Development, and Scale-Up Considerations for Gene Therapies

January 17 - 18, 2023 ALL TIMES PST

The rapid boom in gene therapy medicines must be met with the fast development of robust, scalable, and well-characterized processes and products. Cambridge Healthtech Institute’s 4th Annual Gene Therapy Analytics & Manufacturing conference will bring together leading scientists from the biopharmaceutical industry, academia, and government to discuss unpublished, in-depth case studies, new technologies, assay on CMC strategies, characterization, critical quality attributes, analytical toolbox, process development and scale-up, role of CDMOs in manufacturing of gene-based therapies. This conference is part of the Cell & Gene Therapy Pipeline that also features the 4th Annual Cell Therapy Analytics & Manufacturing conference and a training seminar on Introduction to CMC for Biotech, Cell & Gene Therapy Products.

Tuesday, January 17

Registration (Indigo Foyer)12:45 pm

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)1:00 pm

Organizer's Welcome Remarks1:30 pm

ROOM LOCATION: Aqua Salon E

IMPORTANT CONSIDERATION FOR DEVELOPMENT OF NOVEL BIOTHERAPEUTICS

1:35 pm

Chairperson's Opening Remarks

Susumu Uchiyama, PhD, Professor, Biotechnology, Osaka University

1:40 pm KEYNOTE PRESENTATION:

Optimizing Drug Product Presentation and Manufacturing Processes for Gene Therapy Products

Sandeep Yadav, PhD, Senior Director, Drug Product Formulation & Fill/Finish, Sangamo Therapeutics

Biotechnology companies are extensively leveraging adeno-associated viruses (AAVs) to deliver therapeutic DNA for genomic medicine applications. The field however is still in early stages of gaining experience with stability, analytics, drug substance (DS) and drug product (DP) manufacturing processes. Some of the notable challenges are extremely low titers, limited manufacturing lots to develop process knowledge, and complex analytical methodologies required to characterize AAV systems. Collectively, these challenges lead to higher cost of goods (COGs) while catering to the rare/orphan disease space. This talk focuses on developing and optimizing DP formulation/presentations and manufacturing strategies to support patient safety, healthcare provider convenience, and reducing COGs to enable patient accessibility.

2:20 pm

Latest Developments in Particulate Impurity Characterization Technologies for Biologics

Bruce A. Kerwin, PhD, Principal, Kerwin Biopharma Consulting LLC

Within the talk novel approaches for the characterization of particulate impurities in biologics will be presented, and compared to state-of-the-art technologies for submicron and subvisible particle analysis. Besides new analytical technologies, the integration of machine learning for data analysis will be presented.

ROOM LOCATION: Aqua Salon F

2:50 pm Strategies to Propel Your Viral Vector Therapy from Lab to Clinic

Hung Nguyen, PhD, Global Program Design, Manager, FUJIFILM Diosynth Biotechnologies

Gene Therapies continue to offer promising avenues as curative therapies for unmet patient needs; however, developers of these life-changing therapies often face various challenges on their journey to the clinic, including compressed timelines and high costs. FUJIFILM Diosynth Biotechnologies provides a flexible AAV development and manufacturing platform that can help our partners navigate these challenges by streamlining the critical path from pre-clinical and clinical development through commercialization.

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)3:20 pm

ANALYTICAL TOOLS AND CMC STRATEGIES FOR GENE THERAPIES

4:00 pm

Analytical Assessment of AAV-Based Gene Therapy: Best Practices and Lessons Learned

Jerome Jacques, PhD, Principal Scientist, United States Pharmacopeia

Gene therapies offer tremendous promise to address human disease, but their complexity and diversity present unique challenges to those seeking to standardize materials and methods. Establishing relevant and applicable standards that apply to gene therapy development is essential in maintaining safe and effective therapeutics. Alignment on best practices can also provide clarity and consistency for developers of these therapeutics, especially as gene therapies progress into the late stages of development. Setting standards is especially important in the gene therapy space, where changes to manufacturing processes are frequent, and the development is in orphan indications, limiting the possibilities for comparison with other manufacturing processes. Therefore, the USP is working with stakeholders to respond to the needs in the field by developing both documentary and physical reference standards to help harmonize and standardize methods and practices. This presentation will summarize existing documentary standards that apply to gene therapies and provide an update on new standards under development to the support quality of raw materials like plasmid DNA and the manufacturing and testing of AAV-based gene therapies. Development of reference standards to support analytical testing of critical quality attributes will also be discussed.

4:30 pm

Analytics for AAV-Based Gene Therapy Products

Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics

Demonstrating Analytical Comparability in Gene Therapy:


1. Challenges of demonstration analytical comparability
2. Best practices for analytical comparability
3. Case study in gene therapy
5:00 pm

Biophysical Characterizations of AAV Vectors with Small Volume

Susumu Uchiyama, PhD, Professor, Biotechnology, Osaka University

Biophysical characterizations of AAV vectors are necessary for understanding the quality of purified AAV vectors. I will introduce characterization methods that can be performed with small amount of AAV vectors and will contribute to the improvement of the manufacturing process.

Close of Day5:30 pm

Wednesday, January 18

Registration and Morning Coffee (Indigo and Aqua Foyer)8:30 am

ROOM LOCATION: Aqua Salon CDE

9:00 am

Organizer's Remarks

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

9:10 am Plenary Fireside Chat:

Supporting and Driving Biotech: Past, Present, and Future

PANEL MODERATOR:

Julie Ames, Vice President, Corporate Communications, Biocom California

Innovation can refer to something new, such as an invention, or the development and introduction of new practices. The end result is often a new product, but it can also be a new practice, procedure, or way of thinking. Change and challenges are often what inspire innovation and propel us forward into new ways of thinking and doing. This Fireside Chat convenes long-term supporters of PepTalk: The Protein Science and Production Week who will be exploring the following:

  • Innovations and technology development in the last 5 years ​
  • Takeaways from the post-pandemic world – what lessons did we learn?
  • Collaborations and strategic partnerships – advice to early-stage/small companies ​
  • Is there a trend toward diversification of scientists’ roles, skill sets and responsibilities? Why?
  • What is an unexpected market trend you are seeing?
  • What excites you/what keeps you working in this industry?
PANELISTS:

Amy K. Butler, PhD, President, Biosciences, Thermo Fisher Scientific

Taegen Clary, Vice President, Marketing, Unchained Labs

Jonathan Haigh, PhD, MBA, Vice President, Process Development, Fujifilm Diosynth Biotechnologies

Craig R. Monell, PhD, Senior Vice President, Business Operations, BioLegend (a PerkinElmer company)

Coffee Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)10:15 am

ROOM LOCATION: Aqua Salon F

ANALYTICAL TOOLS AND CMC STRATEGIES FOR GENE THERAPIES, CONT.

11:00 am

Chairperson's Remarks

Jerome Jacques, PhD, Principal Scientist, United States Pharmacopeia

11:05 am

AAV Characterization with Multiwavelength Analytical Ultracentrifugation

Amy Henrickson, Research Associate, Biochemistry, University of Lethbridge

Multi-wavelength analytical ultracentrifugation offers two highly precise and orthogonal characterization methods in one experiment to identify the ratio of any loading state of AAVs, ranging between empty capsids to overfilled capsids. Furthermore, our method can detect contaminants such as protein aggregates and free nucleic acids. The method can be performed in sedimentation velocity mode, providing ultimate resolution and contaminant identification through an extended molar mass dynamic range, while obtaining highly accurate molar ratios for protein and DNA, present in each analyte. The second method is an analytical buoyant density equilibrium (ABDE) experiment, which offers higher throughput and sensitivity, and much lower sample requirements. For both methods, multi-wavelength decomposition of the hydrodynamic dimension additionally provides an orthogonal characterization dimension, further improving the resolution of this approach. In this talk, I will present examples, and discuss the experimental approaches used to characterize viral vectors and their nucleic acid cargo load by multi-wavelength analytical ultracentrifugation.

11:35 am

Mass Spectrometry Applications in Cell & Gene Therapy

Jill Bradley-Graham, PhD, Scientist, BioAnalytics Characterization, Sanofi Genzyme

We are performing extensive MS method development to characterize critical quality attributes in gene and cell therapy products, not only proteins but lipids and oligonucleotides as well. Utilizing new MS technologies for protein analysis, we are gaining a better understanding of post-translational modifications on gene and cell therapy products as well as investigating critical structure/function relationships.

12:05 pm Improving titer and impurity analysis for gene therapy products on the Gyrolab® platform

Emily Menesale, Scientist II, Ultragenyx

Many types of analytical assays are needed in the support of gene therapy product development. Immunoassays are one such platform that are used to measure attributes such as capsid titer and impurity levels. Typical ELISAs are hands-on and time-consuming. We describe the development of automated immunoassays on the Gyrolab® platform. These assays not only increase efficiency, but also produce high quality data needed to support process development and product release. 

12:20 pm

Selected Poster Presentation: Technology Foresight for the Identification of New Targets, Opportunities, and Partnerships for Vaccines and Biotherapeutics in Plant-Based Platforms

Diana Freire, FIOTEC

Plant-based technologies are an emerging field, with few registered products or in the market. Therefore, we aim to present the results of technology foresight (TF) obtained about the current scenario and trends for vaccines and biotherapeutics in molecular pharming. In general, we demonstrated that transient expression system can be the best choice for many targets. Also, the current scenario shows an increase in infectious disease vaccines compared to 2019. Therefore, the systematic TF can help to organization’s decision-making for target selection and project prioritization.

Session Break and Transition to Luncheon Presentation12:35 pm

12:45 pm LUNCHEON PRESENTATION:Scalable, High Titer Production of AAV in the Gibco CTS AAV Production System

Jon Zmuda, R&D Director, Cell Biology, Thermo Fisher Scientific

We present data on the Gibco™ CTS™ AAV-MAX Production System, a suspension based AAV production system that allows for scalable, high titer AAV production using a clonal 293F-derived cell line and chemically defined reagents.  The AAV-MAX system delivers titers of ≥5x1010 viral genomes per mL (vg/mL) across multiple serotypes, with excellent scalability from multi-well plates to stirred tank bioreactors, making it an ideal platform for clinical and commercial production of AAV.

Session Break1:45 pm

PROCESS CHARACTERIZATION

2:00 pm

Chairperson's Remarks

Vikas Bhat, PhD, Associate Director, Process Development, BioMarin Pharmaceutical, Inc.

2:05 pm

Orthogonal Analytics to Monitor Quality Attributes of AAV Capsids to Support Efficient Process Development

Vikas Bhat, PhD, Associate Director, Process Development, BioMarin Pharmaceutical, Inc.

Process development for adeno-associated virus (AAV) manufacturing faces unique challenges given the complex nature of the molecule. Biomarin employs multiple biochemical and biophysical techniques to overcome these challenges in order to optimize process development efforts with the ultimate goal of innovating in the field of AAV production for the benefit of our patients.

2:35 pm

Process Design and Characterization to Enable Production of AAV-Based Gene Therapy for Clinical Use

Benson Gikanga, Associate Director, Cell & Gene Therapy Formulation, Sangamo Therapeutics

Many challenges faced by CGT products impact the strategy taken to design, characterize, and validate manufacturing processes. Specifically, the complexity of these modalities coupled with scarcity of material for use in knowledge building studies makes it hard to reduce studies needed for launch. Current regulatory requirements such as justifying scale-down models and/or surrogates used pose additional challenges. This presentation will explore such challenges and approaches used in CGT process validation. A few case studies will be presented.

PROCESS, SCALE-UP, AND MANUFACTURING CONSIDERATIONS

3:05 pm

High-Throughput Chromatography Studies to Risks in Gene Therapy Clinical Manufacturing

Matthew Petroff, PhD, High-Throughput Process Development Lead, Spark Therapeutics, Inc.

Challenges of AAV downstream processing – including high levels of product variants and complex characterization – are exacerbated by pressures for early implementation of process innovations. We show high-throughput case studies for early assessment of platform fit, process optimization, and process sensitivity. Together these generate optimization and risk assessments early in development, reducing risks of process changes in large-scale manufacturing.

PepTalk Plaza: Speed Networking

IN-PERSON ONLY:

Speed Networking

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

Bring yourself, your phone, or your business cards (if you still have them) and be prepared to share and summarize the key elements of your research in a minute. PepTalk will provide a location, timer, and fellow attendees to facilitate the introductions.

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)3:35 pm

4:15 pm

Cytosolic miRNA-Inducible Nuclear Translocation of CRISPR Protein for Disease-Specific Genome Modification

JiMin Lee, PhD, Assistant Professor, KAIST

Inspired by the intrinsic nature of microRNA-mediated mRNA cleavage, we developed a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate translocation of proteins. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs. Using the endogenous mRNA decay mechanism, our platform is able to remodel a cell's natural biology to allow the entry of precise drugs into the nucleus, devoid of non-specific translocation. This strategy is promising for applications in which the reaction must be controlled via intracellular stimuli and modulates Cas9 proteins to ensure safe genome modification in diseased conditions.

4:45 pm

HPC-Powered AI/ML BioCAD Platform for Viral Bioengineering

Stefan N. Lukianov, PhD, CEO, Technology, Salve Therapeutics, Inc.

We are building a high-performance computing-powered bioengineering platform to mine, design, model, and test novel viral biologics. Better viral delivery methods will expand the available biologic tool kit to produce better medicines for intractable and incurable diseases. A new software platform specifically tailored to mine, design, model, and test the human virome (and others) for new therapeutic modalities will enable exploration of this therapeutic space in a safe, rapid, and cost-effective manner.

5:15 pm PANEL DISCUSSION:

Overcoming Process and Analytics Challenges for Gene Therapies

PANEL MODERATOR:

Vikas Bhat, PhD, Associate Director, Process Development, BioMarin Pharmaceutical, Inc.

PANELISTS:

Matthew Petroff, PhD, High-Throughput Process Development Lead, Spark Therapeutics, Inc.

Stefan N. Lukianov, PhD, CEO, Technology, Salve Therapeutics, Inc.

JiMin Lee, PhD, Assistant Professor, KAIST

Networking Reception in the Exhibit Hall with Poster Viewing (Indigo Ballroom)5:45 pm

WOMEN IN SCIENCE MEET UP AT PEPTALK PLAZA

6:50 pm

Women in Science Meet Up at PepTalk Plaza

Christa Cortesio, PhD, Senior Scientist and Group Lead, Protein Science, Protein Biochemistry & Analytics Core, Kite Pharma

Michelle R. Gaylord, MS, Principal Scientist, Protein Expression Lead, Velia, Inc.

The Women in Science Meet Up at the PepTalk is a networking and inspiring event tailored for female attendees. We invite the entire scientific community to discuss these barriers, as we believe that all voices are necessary and welcome. Please join fellow scientists and discuss your personal and professional journey.​

  • What do you struggle with most as a woman in science?
  • What are you proudest of?
  • As we return to a post-pandemic work-life environment, have there been any challenges or improvements that have impacted you?
  • Do you feel that we as a society have made good progress towards equal treatment of women and men in the workplace?
  • What can each of us do to improve things further?​

Close of Gene Therapy Analytics & Manufacturing7:00 pm