5th mRNA Process Development & CMC Summit

• Moving beyond single-CDMO reliance by building flexible partnership models, including balancing primary and backup manufacturers without overextending budget or timelines. Driving early alignment with CDMOs on process characterization, PPQ strategy, batch sizing, and scale-up assumptions to minimize revalidation risk and accelerate pivotal readiness
• Strengthening supply chain resilience, including strategies for critical raw materials such as lipids and key components
• Establishing effective governance models to enable faster decision-making and seamless execution across partners

• Reduce early development risk with early, structured CDMO engagement and shorten timelines for mRNA, neoantigen and personalized cancer vaccine programs in cell & gene therapy pipelines
• Aligning process development and CMC expectations between biopharma and CDMOs to avoid scale-up failures and enable smoother translation from preclinical to commercial supply
• Defining effective partnership models for complex modalities, including tech transfer best practices, capacity planning, and managing variability in patient-specific manufacturing workflows

Key questions include:

• How do you structure CDMO partnerships to balance speed, flexibility, and risk without overcomplicating your manufacturing network?
• What are the biggest misalignments between biopharma and CDMOs during scale-up – and how can they be avoided early?
• At what point should companies start designing for commercial-scale manufacturing, and how does that shape CDMO and supply chain decisions?

• Examining how differences in input components influence yield, consistency, and impurity profiles across mRNA manufacturing workflows
• Establishing control strategies to ensure consistency without restricting flexibility- defining specifications, sourcing approaches, and risk-based frameworks that maintain quality while supporting process optimization and platform development
• Embedding raw material considerations into next-generation platform design – ensuring approaches are adaptable across emerging modalities while enabling faster development timelines, improved robustness, and reduced cost of goods

• Investigating intrinsic yield loss mechanisms in linear DNA UF/DF that are not universally resolved by operational optimization alone
• Demonstrating plasmid-specific limitations of UF/DF through mechanistic analysis of flow-induced elongation and protein–DNA interactions
• Redesigning downstream processes by decoupling protein removal and buffer exchange, introducing HIC to improve robustness while enabling further optimization

• Overcoming Structural and Purification Bottlenecks: Explores how addressing the structural complexity of circular RNA (circRNA) allows for tunable purification strategies that simultaneously maximize yield, selectively remove small linear impurities, and consistently achieve ∼95% purity at milligram scales and greater for in vivo applications
• Correlating Purity and Sequence with Expression Dynamics: Highlights critical insights into how circRNA expression levels are tied directly to RNA purity, how translation duration is inversely correlated with immunostimulation, and how expression efficiency remains highly construct-specific based on primary sequence elements
• Advancing Analytics for Next-Gen Therapeutics: Demonstrates the application of stateof-the-art analytical approaches to rigorously confirm circularization and structural integrity, ultimately supporting the scalable, robust production of stable, next-generation RNA therapeutics

• How are emerging mRNA modalities in CGT changing the biggest process development and CMC challenges teams need to solve today?
• Where are current analytical and control strategies falling short when applied across diverse mRNA-enabled CGT applications – and how should they evolve?
• What does a truly scalable and flexible CMC framework look like when supporting multiple mRNA-driven CGT modalities with differing requirements?

• Exploring key CMC and process development considerations for delivering RNAbased gene editing systems across in vivo (e.g. LNP) and ex vivo manufacturing workflows
• Addressing challenges in achieving consistent editing efficiency while maintaining product quality, potency, and safety across different delivery modalities and target tissues
• Discussing how platform-based development strategies can support scalability, tech transfer, and clinical translation of next-generation genetic medicines

• Exploring how enzyme-free purification strategies can overcome key manufacturing bottlenecks in circular RNA development while improving scalability, recovery, and product purity
• Discussing the commercial and CMC implications of reducing purification complexity, lowering cost-per-dose, and minimizing supply chain dependency across clinical to commercial manufacturing
• Sharing early regulatory, process development, and scale-up considerations from advancing circular RNA therapeutics toward first-in-human studies

• Persistent virus reservoirs associated with dysfunctional anti-viral T cell responses is a root cause of Long COVID, a debilitating disease affecting >400 million people globally
• We have developed an mRNA-based immunotherapeutic targeting protective T cell antigens of SARS-CoV-2
• Treatment of Long COVID in mice resulted in reversal of T cell dysfunction, clearance of virus reservoirs, and amelioration of cognitive and behavioural deficits

• Exploring key considerations in RNA-LNP process development to improve reproducibility, product quality, and manufacturing robustness across development stages
• Sharing approaches to balancing formulation, process parameters, and analytical insight to reduce variability and support efficient scale-up
• Discussing how integrated CMC strategies can de-risk tech transfer, strengthen process understanding, and accelerate progression from early development to clinical and commercial manufacturing