Cambridge Healthtech Instituteの第4回年次会議
Gene Therapy CMC and Analytics
2023年3月14 - 15日、CET（中部欧州標準時）
Registration and Morning Coffee07:00
CMC AND TECHNICAL DEVELOPMENT STRATEGIES
Challenges and Opportunities in Gene Therapy Technical Development
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.
Analytical Comparison of AAV Manufactured by Triple-Plasmid Transfection/HEK293 and Double-Baculovirus Infection/SF9 Processes
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.
Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing10:00
IMPROVING PRODUCT QUALITY THROUGH IN-DEPTH CHARACTERISATION
Novel Approaches to Analyse AAVs and Lentiviruses Using BLI and Flow Virometry
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.
AAV Genome Integrity: Going Deep with Nanopore Sequencing and Multiplex Digital PCR
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.
Characterization of Dual AAV Vector Otoferlin
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.
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.
Presentation to be Announced12:30
Networking Lunch (Sponsor Opportunity Available)12:45
IMPROVING PRODUCT AND PROCESS CHARACTERISATION
Viral Safety: The Need for a Wholistic Approach
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.
New Chromatographic Approaches for Payload and Capsid Characterization in AAVs
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.
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 Viewing15:20
LINKING ANALYTICS TO PROCESS DEVELOPMENT
Expanding AAV Manufacturability Toolbox for Early-Phase Programs and beyond
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.
Addressing Challenges for Production and Analysis of AAV Vectors
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.
Interactive 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.
Welcome Reception in the Exhibit Hall with Poster Viewing17:40
Close of Day18:45
Registration and Morning Coffee08:00
ADVANCING PROCESS DEVELOPMENT, OUTSOURCING AND CARGO DELIVERY
Managing Headwinds Due to CDMO’s M&A Activities and Its Impact on Gene Therapy Companies and Innovation
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.
Advancing Process Development for Gene Therapies
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.
Expanding AAV Cargo Delivery Capacity
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 Break in the Exhibit Hall with Poster Viewing10:30
PLENARY SESSION: EMERGING MODALITIES, PLATFORMS, AND TECHNOLOGIES - FROM mRNA TO PROTEINS
基調講演：新興のモダリティ、プラットフォーム、技術 - mRNAからタンパク質へ
Overcoming CMC and Supply Chain Challenges for mRNA Technologies
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.
Affinity Proteins for Biotechnological and Medical Purposes
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
Sponsored Presentation (Sponsor Opportunity Available)12:30
Networking Lunch (Sponsor Opportunity Available)13:00
Close of Gene Therapy CMC and Analytics Conference14:00