Cambridge Healthtech Institute’s 4th Annual

Gene Therapy CMC and Analytics

Improving the Analysis, Control, and Quality of Gene Therapies

14 - 15 March 2023 ALL TIMES CET

Cambridge Healthtech Institute’s Gene Therapy CMC and Analytics meeting uncovers the practical challenges facing the analysis, characterisation, and quality of viral vector-based gene therapies for clinical and commercial supply, with dedicated sessions on CMC strategy, analytical development and qualification, product-related impurities and their link to quality, bioassays, comparability, stability, formulation, and the emergence of non-viral gene therapies.

Tuesday, 14 March

Registration and Morning Coffee (Garden Room)07:00

ROOM LOCATION: Fallin 9

CMC AND TECHNICAL DEVELOPMENT STRATEGIES

08:25

Chairperson's Remarks

Christine Le Bec, PhD, Head, CMC Gene Therapy, Sensorion

08:30

Viral Safety: The Need for a Wholistic Approach

Christopher Bravery, PhD, Consulting Regulatory Scientist, Advanced Biologicals Ltd.

Because there are limited options to apply viral reduction or elimination steps in the manufacture of viral vectors, viral control becomes more important. As a consequence, viral testing likely needs to be more comprehensive. Multiple orthogonal methods increase the chances of detection and examples of viral contamination events will be presented.

09:00 FEATURED PRESENTATION:

Analytical Comparison of AAV Manufactured by Triple-Plasmid Transfection/HEK293 and Double-Baculovirus Infection/SF9 Processes

Jorge F. Haller, PhD, Director, Process & Analytical Development, Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company

Comparability between triple-plasmid transfection/HEK293 adherent and double-baculovirus infection/Sf9 suspension manufacturing processes was evaluated for AAV9 with the same transgene. Both processes yield viral capsid proteins with identical mass, comparable safety, strength, and biological activity. Differences in the impurity profiles, which are inherent to the processes, were observed. Overall, the double-baculovirus infection/Sf9 process was able to upscale AAV production and deliver a comparable AAV product to the triple-plasmid transfection/HEK293 adherent process.

09:30 KEYNOTE PRESENTATION

Challenges and Opportunities in Gene Therapy Technical Development

Markus Haindl, PhD, Global Head, Gene Therapy Technical Development, Roche Diagnostics GmbH

While gene therapies are offering unique and unprecedented treatment options for patients, these versatile toolboxes are coming with high complexity on a molecular level, which finally poses significant challenges to provide access to such therapies on a global scale. Gene therapies are currently where monoclonal antibodies were 25 years ago and we need a shift of our development paradigms and transformative innovation for reliable supply, more sustainable cost of manufacturing as well as enhanced molecular understanding of these next-generation therapeutics.

Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (Verdi/Vivaldi)10:00

IMPROVING PRODUCT QUALITY THROUGH IN-DEPTH CHARACTERISATION

10:45

Novel Approaches to Analyse AAVs and Lentiviruses Using BLI and Flow Virometry

Felix F. Fuchsberger, PhD, Scientist, Takeda

Advances in analytical approaches have the potential to gather novel information about gene therapy vectors and characterize the same better. Here, I will be talking about the application of biolayer interferometry (BLI) to characterize adeno-associated virus (AAV) to antibody binding. Additionally, I will be talking about flow virometry which is emerging due to more sensitive instruments for the analysis of larger vectors like lentiviruses.

11:15

AAV Genome Integrity: Going Deep with Nanopore Sequencing and Multiplex Digital PCR 

Peter Andorfer, PhD, Development Scientist, Gene Therapy, Takeda

In gene therapy a better understanding of the AAV content, in terms of transgene integrity and unwanted DNA contaminations, is fundamental to achieve the best possible therapy outcome and reduce the risk of side effects. Nanopore long read sequencing and multiplex digital PCR are two state-of-the-art technologies, which enable a detailed analysis of the DNA cargo and can help to improve the production process towards better gene therapy products.

11:45

Characterization of Dual AAV Vector Otoferlin

Christine Le Bec, PhD, Head, CMC Gene Therapy, Sensorion

Sensorion is a biotech company dedicated to the development of therapies for genetic forms of hearing loss. Two novel gene therapy programs include deafness due to Otoferlin deficiency as well as Usher Syndrome type 1. Since the Otoferlin gene is large and exceeds the AAV packaging capacity, two AAV vectors have been developed. The product characterization of the dual vectors will be presented.

12:15 Quantifying AAV Empty/Full Ratios with Mass Photometry 

Perla Vega Dominguez, Dr, Technical Sales Specialist, Sales, Refeyn

Quantifying empty/full ratios of capsids in AAV preparations is a bottleneck for characterizing rAAVs. Mass photometry is a novel, fast, and easy method to determine these ratios, as it measures the masses of AAVs in solution with minimal sample preparation. Refeyn’s mass photometer for AAVs characterization, the SamuxMP, differentiates between empty, partially filled and full capsids; being serotype agnostic, and in line with gold-standard techniques such as TEM and AUC.

12:30 Sensitivity, Scalability & Speed: The Value of NGS for Identity Testing of Plasmids & Viral Vectors

Pascale Buerdeley, PhD, Chief Scientific Officer, PathoQuest

PathoQuest offers GMP level identity testing / genetic characterisation for viral vectors and manufacturing plasmids by Next Generation Sequencing (NGS). This presentation will provide an overview of  some of the advantages PathoQuest’s NGS approach offers over Sanger sequencing and other classical methods like restriction analysis or PCR and why the additional data provided by NGS can provide important information to you.

Networking Lunch12:45

IMPROVING PRODUCT AND PROCESS CHARACTERISATION

13:45

Chairperson's Remarks

Christopher Bravery, PhD, Consulting Regulatory Scientist, Advanced Biologicals Ltd.

13:50

CMC Strategies for Gene Therapies

Christiane Niederlaender, PhD, Vice President, Technical CMC, Parexel

Viral vectors are becoming an established part of the armamentarium to address rare diseases, cancer and other indications. While platform approaches for some of the most commonly used vectors seem close, many CMC challenges remain. These include the continued need to demonstrate viral vector safety to regulatory agencies at CMC level, while at the same time substantial questions about safety and quality indicating attributes remain. The presentation will highlight common CMC regulatory concerns and strategies to address them.

14:20

New Chromatographic Approaches for Genome and Capsid Characterization in AAVs

Elena Dominguez Vega, PhD, Assistant Professor, Center for Proteomics and Metabolomics, Leiden University Medical Center

AAV quality assessment requires monitoring several attributes from the protein capsid and genome. While several analytical technologies have been established, still there are limitations in regard to their accuracy, sensitivity, sample consumption, and user-friendliness. We have developed new chromatographic approaches for the assessment of protein capsid and genome integrity as well as empty/full ratio. We will also show that multidimensional approaches offer additional possibilities for automation and reduced sample consumption.

14:50 Aura+: High-Throughput, Low-Volume Product Stability and Purity Analysis for Gene and Cell Therapies

Paul Dyer, PhD, Field Application Scientist, Halo Labs

Aura+ is the latest instrument designed specifically to detect, count, and characterize subvisible aggregates and extrinsic materials for product quality measurements in both gene and cell therapy applications. Specifically, Aura+ has the capability to detect SYBR® Gold staining, used to detect the presence of DNA in AAV and LVV aggregates, elucidating the role of leaky capsids in SVP formation resulting in reduced transduction efficiency and adverse patient responses. 

Refreshment Break in the Exhibit Hall with Poster Viewing (Verdi/Vivaldi)15:20

LINKING ANALYTICS TO PROCESS DEVELOPMENT

15:40 KEYNOTE PRESENTATION:

Expanding AAV Manufacturability Toolbox for Early-Phase Programs and beyond

Ayda S. Mayer, PhD, Executive Director, Vector Core, REGENXBIO, Inc.

The presentation will summarize the efforts of REGENXBIO’s Vector Core team to produce pre-clinical AAV material for pipeline programs and platform development. Implementation of high-throughput production and manufacturability assessments through evaluation of process titers and product quality, combined with continuous efforts to improve production processes through multiple work-streams, including cell line development, plasmid optimization, and early phase process development, have led to improvements in overall AAV yields exceeding 40-fold.

16:10

Addressing Challenges for Production and Analysis of AAV Vectors

Helen Young, PhD, Manager, Synthetic & Mammalian Upstream, CPI

Developing high-yielding, scalable, and commercially viable processes for AAV manufacture, with associated analytical methods for assessing the CQAs, presents challenges. Here, we present work being performed at CPI to address some of the upstream challenges, including development of an intensified N-1 seed train step to reduce inoculum requirements. Further, we discuss some of the approaches we have been working on for full and empty capsid determination, including mass photometry.

16:40 Gyrolab – An Automated & Integrated Solution for Better Bioprocess Characterization & Quality Control Testing

Ana Valero, PhD, Next Generation Analytics Consultant, Research and Development, VIVEbiotech

VIVEbiotech, a CDMO specialized in lentiviral vectors manufacture, is involved in the development of innovative CGT products and QC services to guaranty the success of projects from early development through manufacturing in preclinical, clinical and commercial stages to quality testing and product release. Utilization of robust and automated platforms for immunoassay analysis is a critical need to generate high quality data. The use of Gyrolab technology within VIVEbiotech will be presented.

Breakout Discussions17:10

Breakout Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. For in-person events, the facilitator will lead from the front of the room while attendees remain seated. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussion page on the conference website for a complete listing of topics and descriptions.

BREAKOUT DISCUSSION:

IN-PERSON ONLY: Ensuring Product Quality through Analytics

Tony Bou Kheir, PhD, Head, Analytical Development and QC, Purespring Therapeutics

  • Linking analytics to quality
  • Capsid capture and analysis
  • Emerging analytical methods

Welcome Reception in the Exhibit Hall with Poster Viewing (Verdi/Vivaldi)17:40

Close of Day18:45

Wednesday, 15 March

Registration and Morning Coffee (Garden Room)08:00

ROOM LOCATION: Fallin 9

ADVANCING PROCESS DEVELOPMENT, OUTSOURCING AND CARGO DELIVERY

08:25

Chairperson's Remarks

Hemant Kumar, PhD, Chief Manufacturing and Technology Officer, Genprex, Inc.

08:30

Managing Headwinds Due to CDMO’s M&A Activities and Its Impact on Gene Therapy Companies and Innovation

Hemant Kumar, PhD, Chief Manufacturing and Technology Officer, Genprex, Inc.

Dramatic increase in mergers and acquisitions within the global CDMO market has raised concerns about delays in bringing the disruptive innovative gene therapy target development and delays in clinical trials. This has encouraged CDMOs to provide integrated services to advance drug development but has become a financial burden on the clinical stage companies, e.g., higher cost for services, licensing fees, and ad delays in timelines for IND/BLA submissions.

09:00

Advancing Process Development for Gene Therapies

Florian Leseigneur, Head, Process Development, Dinaqor

Alignment of upstream and downstream processes and analytical methods from preclinical to GMP manufacturing reduces time to market and de-risks drug development. The use of standardized assays for the characterization of preclinical vectors provides critical insights on potency, identity, and purity, and strengths the value of PoC and IND-enabling studies performed with those vectors.

09:30

Expanding AAV Cargo Delivery Capacity

Ana Sofia Coroadinha, PhD, Lab Head, Health & Pharma Division, Animal Cell Technology Unit Cell Line Development and Molecular Biotechnology Lab, IBET

Adeno-associated virus (AAV) vectors are one of the most versatile gene therapy platforms. However, AAV vectors have a small packaging capacity impairing delivery of therapeutic genes over 3.5 kb in size. This limits their use in the treatment of innumerous genetic diseases. Herein dual AAV co-delivery strategies are discussed, namely the use of protein trans-splicing systems, to deliver larger genes.

Coffee Break10:00

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi/Vivaldi)10:30

ROOM LOCATION: Rossini 1 + 2

PLENARY SESSION: EMERGING MODALITIES, PLATFORMS, AND TECHNOLOGIES – FROM mRNA TO PROTEINS

11:15

Chairperson's Opening Remarks

Margit Holzer, PhD, Owner, Ulysse Consult

11:20 PLENARY PRESENTATION:

Overcoming CMC and Supply Chain Challenges for mRNA Technologies

Gregory Troiano, Chief Manufacturing Officer, mRNA Center of Excellence, sanofi

Thanks to the rapid development of mRNA vaccines for COVID-19, the industry now has the momentum and resources to overcome many of the early CMC challenges and realize its enormous potential. This presentation will discuss the strategies in place to overcome CMC and supply chain challenges for mRNA technologies already and future innovations primed to take it to the next level.

11:50 PLENARY PRESENTATION:

Affinity Proteins for Biotechnological and Medical Purposes

Sophia Hober, PhD, Professor, School of Biotechnology, KTH Royal Institute of Technology

Affinity proteins are crucial for life, for building structures, performing reactions, and for signaling purposes. In life sciences and medicine, affinity proteins are used to generate knowledge, but also for diagnostic and therapeutic purposes. This talk will cover how antibodies and small affinity molecules can be used to map the human proteome, develop diagnostic tools for in vivo visualization as well as efficiently purify therapeutics based on antibodies.

Transition to Sessions12:20

ROOM LOCATION: Fallin 9

12:30 Challenges of Building an AAV Platform in 2023

Quentin Bazot, PhD, Viral Vector Manufacturing & Process Development Specialist, ABL

AAV has emerged as leading vector for gene delivery for treating various diseases due to its safety profile and efficient transduction of various target tissues. With the shift beyond ultrarare indications and the use of engineered synthetic AAV capsids, there is a need for new, scalable and easy-to-implement AAV platform processes compatible with different AAV serotypes. This presentation will discuss challenges of starting the development of such a platform in 2023.

Networking Lunch (Sponsor Opportunity Available)13:00

Close of Gene Therapy CMC and Analytics Conference14:00