CELL AND GENE THERAPY INSIGHTS

Spotlights 2024

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Induced pluripotent stem cells (iPSCs)

What progress in addressing the preclinical-clinical translation bottleneck for induced pluripotent stem cell-derived therapeutics?
- Learning from trailblazers in the field
- To what extent have safety risks associated with iPSCs been successfully addressed?
Overcoming the complexity in iPSC banking
- What do we really know about stability and variability of iPSCs?
- At what stages are/aren’t GMP workfows needed in iPSC master cell bank creation?
- Platform opportunities and market evolution in the iPSC cell line development space
  - What will be key specific cell lines as demand outstrips supply?
  - In-house development versus outsourcing
- What are the main priorities and needs for standardization in the iPSC field?
Automation and avoiding contamination in iPSC cell selection and harvesting
Multiplex iPSC editing approaches—latest advances and lingering concerns
Looking to the future
- Personalized iPSC-derived therapies (e.g., iPSC-derived oocytes)
- Should exosomes manufacture stick to standard producer cell lines or seek to harness iPSCs instead?

Non-clinical/translational tools & technologies

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Non-clinical/translational tools & technologies

Guest Editor:

Shon Green, Director, Clinical Translation at Adicet Bio

What does the ‘umbrella IND’ mean for cell and gene therapy preclinical development? How much can you leverage from one advanced therapy product or platform to another?
What is the future of preclinical in vivo testing requirements?
- Are regulators coming round to less animal testing in practice (e.g., non-human primates)? If so, in what specific circumstances?
- How and when will the use of organoids and other in vitro models become more standardized and mainstream in preclinical R&D?
- What is the current state-of-the-art in modelling that can help to explain the difficulties in translating preclinical into clinical success for AAV-driven gene therapy?
- How can we leverage the ever-increasing body of advanced therapy clinical data to facilitate clinical translation?
- How far can one push the envelope in terms of a reduced preclinical package?
Which process and analytical innovations are can streamline the transition to early-phase clinical manufacturing and beyond?
Assessing the application of AI in non-clinical R&D—where are advances in automated bioinformatics translating into R&D insights for the cell and gene therapy field?
How are next-generation sequencing, multiomics, and single cell analysis technologies being employed to rewrite the script for advanced therapy drug discovery?

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Vector processing and materials

Guest Editor:

Chia Chu, Director, AAV Process Development at Intellia Therapeutics

Guest Editor:

Francesca Vitelli, VP, Cell Therapy and AAV Process Development at Intellia Therapeutics

The battle to boost yields in viral vector manufacturing: where have improvements been made recently to boost yields in viral vector manufacturing?
- Producer/packaging cell lines vs transient transfection vs helper viruses: how are they comparing and evolving in relative terms?
- What cell lines are available beyond HEK293 and how they are performing?
- Vector purification
Driving down Cost of Goods for viral vector production to reach viable price points for rare and non-rare disease gene therapies
- What does a viral vector platform actually look like, and what are the difficulties in building one?
  - Who is winning the race to find the optimal ‘quick to clinic’ vector manufacturing platform process?
  - What lessons can we take from the biopharma world?
  - Where in vector processing is further innovation required?
- Reducing batch-to-batch variability
- What are the pros and cons of harnessing synthetic raw and starting materials for gene therapy manufacture?
- Comparing and contrasting perfusion equipment options for suspension-based production of viral vectors
- How to capitalize on the application of design of experiments (DoE) and digital twin approaches in vector process development?

Cell therapy upstream processing & materials

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Cell therapy upstream processing & materials

Guest Editor:

Isabelle Riviere, , Vice President, Head of Oncology Cell Therapy Technologies and Product Engine at Takeda

Ensuring manufacturability: how to assemble all the pieces required for a viable cell therapy process?
Cell sourcing
- Enabling sourcing of allogeneic donor-derived cellular starting material
  - Optimal approaches to donor identification and characterization
  - Overcoming regulatory guidance and divergence barriers
Autologous cell collection
- How to establish clear patient inclusion/exclusion criteria pre-commercialization?
- The importance of defining the number of target cells required to manufacture a therapeutic dose
- How to enable large-scale autologous cell collection in the decentralized outpatient setting?
- Apheresis material characterization
- Standardization initiatives
- Harmonization of harvest—what are the overall requirements?
Cell therapy upstream processing
- Exploring recent technological innovations (e.g., automated solutions) and initiatives driving:
  - Shorter manufacturing timeframes
  - Reduced Cost of Goods
  - Enhancing process control (eg. development of non-destructive sensors)
  - Improvements in flexibility and interoperability
  - Distributed (e.g., hospital-based) manufacture
- Transduction/transfection and expansion of allogeneic cell therapies
- Can adaptable engineering platforms for organoid production transform the regenerative medicine field?

Viral & non-viral vector platform evolution

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Viral & non-viral vector platform evolution

Guest Editor:

Zhenghong Gao, Director, Non-Viral Delivery at AskBio

Viral delivery
- How will we move the needle to allow sustainable success in both rare and non-rare disease settings?
- Is the rare disease gene therapy model failing? How to address this?
- How effectively is the AAV field addressing lingering immunogenicity and vector integration issues?
- Profiling recent advances in viral vector engineering (lentiviral and AAV)
Non-viral delivery
- Nanoparticles: overcoming targeting limitations beyond the liver
  - The pros and cons of LNPs in advanced therapy applications
- How is the toolkit of non-viral alternatives for ex vivo immune cell engineering evolving/improving? mRNA
  - Where is it being applied currently in the therapeutic setting? What are the key gaps mRNA can fill?
  - How safe is mRNA proving to be in therapeutic application? How durable (and how viable is redosing)? How targeted?
  - What benefits can next-generation technologies deliver?
- Extracellular vesicles/exosomes
  - What are the likely next steps in their application?
    - What lessons can we learn from viral vector development to resolve targeting issues?
  - Extracellular vesicles versus synthetic particles: will they converge? What can one field learn from the other?
- Emerging alternatives to plasmids (e.g., dbDNA)—what can they offer the cell and gene therapy space?
- What is the state-of-the-art in long oligos?

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Gene therapy CMC & analytics

Guest Editor:

Stuart Beattie, Associate Director, Gene Therapy Global Regulatory CMC Clinical Lead at Biogen

How best to leverage the expanding analytical toolkit for viral vector characterization and QC?
- Maximizing the benefits of high-performance liquid chromatography (HPLC) and liquid chromatography/ mass spectrometry (LC/MS)
- Harnessing the cutting edge in capsid characterization tools
- Characterizing aggregation
Addressing ongoing CMC challenges and associated regulatory evolution:
- Dissecting key recent guidances—implementation and points to consider for the field
- Where is further guidance and standardization most needed?
  - How many assays do you require for your potency assay matrix?
  - What does a phase-appropriate potency assay actually look like?
  - What if none of the your potency assays fail to correlate with a positive clinical outcome?
- What are the keys to successfully integrating QA into viral vector manufacture?
- Comparability—how to find the optimal balance in early development (costs vs quality)?
- How will the empty-full-partially full capsid analysis picture continue to develop?
Exploring key areas of need for (affordable) analytical innovation and its application
- Priorities for future lentiviral vector-specific analytical technology innovation
- How is the LNP QC/analytics field evolving?
- Rapid/real-time process analytical technologies
- Key directions for derisking vector manufacture through analytical technology
  - How can we make assays more agnostic/standard across different vectors/capsids?
  - What impact are instruments capable of multiple in-process assays having on cost and efficiency?
  - How will we continue to move towards automating data analysis and enhancing predictive abilities?

Innovation in cellular immunotherapy: how to reach more patients?

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Innovation in cellular immunotherapy: how to reach more patients?

Guest Editor:

Nina Bauer, Chief Business Officer at SmartCella

Where and when will we see real progress in solid tumors? What is the latest clinical data telling us?
- CAR-T (allogeneic and autologous approaches)
- NK cell therapy
- Macrophages
What are the most promising approaches towards addressing issues of safety and durability of response in hematological malignancies?
The rise of in vivo cellular immunotherapy—barriers to success and potential solutions
- How will mRNA continue to influence the cellular immunotherapy field?
Applying cutting-edge enabling technologies to overcome challenges presented by solid tumors and the TME
- Driving advances in our understanding of functional biology in solid tumors in order to address key knowledge gaps
- Exploring the practical application of big data analytics and AI/ML—what new insights are they providing?
- Profiling the next wave of R&D tools—what specific capabilities will they deliver?
Analyzing the impact of recent regulatory guidance evolution in the field, and likely next steps in this regard
How and where to continue expanding the reach of cellular immunotherapies beyond oncology?
- How will regulators react to an increasing number of applications in autoimmune/infectious disease therapeutic areas?
As more and more patients are treated, how are supply chain/logistics models and tools evolving?

Scale-up/scale-out of cell & gene therapy manufacturing

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Scale-up/scale-out of cell & gene therapy manufacturing

Cell therapy downstream processing
- Exploring recent technological innovations and initiatives driving shorter manufacturing timeframes, reduced Cost of Goods, improvements in flexibility and interoperability, and distributed manufacture
- Optimizing cell therapy fill-finish: what are the key innovation gaps?
How are developers interpreting and responding to recent regulatory guidance regarding potency assays?
- Can we identify any best practices, particularly in terms of potency assay matrix development?
- What are the preclinical ‘must-do’s’ to prepare for potency assay success?
- How can we advance to improved, standardized analytical toolkit to allow developers to implement potency assay matrixes that correlate with clinical outcomes?
Comparability: what exactly do we need to show, and how to prepare from an early stage?
- Finding the optimal balance between product development and speed to patient post-IND
- What knowledge can we leverage from cell therapy products that have already been through the clinic in terms of how best to approach process changes?
What does phase-appropriate analytical control of cell therapy manufacture look like?
Are novel cell therapy analytical tools and technologies delivering the required degree of repeatability and precision?
How can we move further towards the automation of data analysis in cell therapy manufacture?
How are regulatory CMC compliance strategies and analytical toolkit innovation evolving to address the ever-increasing complexity of engineered cell therapy products?
- What do/don’t we understand about the associated risk?
- How and where specifically can off-the-shelf therapy developers leverage the fund of autologous cell therapy-derived CMC knowledge to help advance the allogeneic cell therapy field?
Dissecting critical areas of international regulatory divergence impacting cell therapy CMC and QC

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Gene editing

Tackling remaining safety concerns as the era of commercial genome editing-based therapeutics arrives
- On- and off-target editing analysis—which tools/models should we use?
- What is the current state-of-the-art in the area of multiplex editing analysis?
Analysis of the pros and cons of genome editing and gene writing platforms as next-generation approaches enter the clinic
- To what extent is promising preclinical data being borne out in humans?
- What are the key opportunities to utilize CRISPR knockout and how to capitalize?
Gene editing delivery: the benefits and challenges in applying viral and non-viral platforms
What improvements can recent innovations in the enzymes area deliver?
- What are the pros and cons of next-generation Cas technologies in application?
Predicting future developments in gene editing and its application
- What can we expect in the way of further regulatory guidance for the field? What are some of the key areas of convergence/divergence to look out for?
- Assessing the epigenome editing opportunity: what is possible currently in the realm of epigenetic modulation, and what might the future hold in the context of both combinatorial and synergistic therapeutic approaches?

Cell therapy downstream processing & analytics

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Cell therapy downstream processing & analytics

Cell therapy downstream processing
- Exploring recent technological innovations and initiatives driving shorter manufacturing timeframes, reduced Cost of Goods, improvements in flexibility and interoperability, and distributed manufacture
- Optimizing cell therapy fill-finish: what are the key innovation gaps?
How are developers interpreting and responding to recent regulatory guidance regarding potency assays?
- Can we identify any best practices, particularly in terms of potency assay matrix development?
- What are the preclinical ‘must-do’s’ to prepare for potency assay success?
- How can we advance to improved, standardized analytical toolkit to allow developers to implement potency assay matrixes that correlate with clinical outcomes?
Comparability: what exactly do we need to show, and how to prepare from an early stage?
- Finding the optimal balance between product development and speed to patient post-IND
- What knowledge can we leverage from cell therapy products that have already been through the clinic in terms of how best to approach process changes?
What does phase-appropriate analytical control of cell therapy manufacture look like?
Are novel cell therapy analytical tools and technologies delivering the required degree of repeatability and precision?
How can we move further towards the automation of data analysis in cell therapy manufacture?
How are regulatory CMC compliance strategies and analytical toolkit innovation evolving to address the ever-increasing complexity of engineered cell therapy products?
- What do/don’t we understand about the associated risk?
- How and where specifically can off-the-shelf therapy developers leverage the fund of autologous cell therapy-derived CMC knowledge to help advance the allogeneic cell therapy field?
Dissecting critical areas of international regulatory divergence impacting cell therapy CMC and QC

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Review of 2024/previewing 2025

Examining the major advances and setbacks, stories and trends from the past 12 months—what will be likely repercussions for the cell and gene therapy field moving forward?
Profiling key enabling technology innovation trends and advances for the year(s) to come