Main Conference – Day 1 - CET (Central European Time, GMT+01:00)
- Exploring how RNA-based therapies can be customised to address the unique challenges of rare genetic disorders and the broader demands of widespread conditions
- Discussing the trade-offs between developing highly targeted RNA treatments for rare diseases and scalable solutions for broad-spectrum conditions with larger patient populations
- Examining the scientific, regulatory, and commercial hurdles in advancing RNA therapeutics, including delivery technologies, manufacturing complexities, and market access
- Highlighting cutting-edge breakthroughs in RNA technology and delivery systems that are driving progress across rare and broad-spectrum applications, shaping the next generation of precision medicine
- Marie Wikstrom-Lindholm - CSO, Silence Therapeutics
- Nathaniel Wang, PhD - CEO, Replicate Bioscience
- Karina Thorn - Vice President, Head of Nucleic Acid Research, Novo Nordisk
- Renee Williams - CBO, Signify Bio
- Rapidly growing therapeutic oligonucleotide demand for indications with large patient populations require innovative manufacturing solutions. Answering the call for a more scalable and sustainable process, Codexis introduced the ECO Synthesis® Manufacturing Platform — a fully aqueous, enzymatic high yielding production approach for safe, quality, and efficacious siRNA. In this presentation, we will demonstrate the scalability of ECO Synthesis while illustrating the ability to transition from research to manufacturing scale and cGMP production, highlighting its potential to exceed productivity of traditional SPOS.
- Robust in-process control (IPC) testing is critical to achieving consistent product quality and purity in oligonucleotide manufacturing. Conventional solid-phase oligonucleotide synthesis (SPOS) presents IPC testing limitations due to the closed reaction environment and resin-bound intermediates. This platform, ECO Synthesis, enables early detection of process performance and/or deviations, and the opportunity for closed loop adjustment of reaction parameters in the future, resulting in high standards of API product quality, ensuring patient safety.
- David Entwistle - Sr Director, Program & Pipeline Management, Pharma Manufacturing, Codexis
- Synthetic, enzymatically produced DNA is shaping the future of mRNA manufacture: rapid, scalable GMP-grade production capable of handling complex sequences and long poly A tails without the bacterial contaminants.
- Explore opDNA®, an application-specific IVT template open at the 3’ end, facilitating direct use in the IVT reaction without enzymatic linearization. As a linear template without bacterial backbone sequences, equivalent mRNA yields are achieved with less DNA mass.
- Homologous recombination of polyA tails in bacterial hosts is a major limitation of plasmid DNA. 4basebio’s enzymatic platform can handle long polyA tails (>180 bp) encoded directly into the template, while our novel polyA analytics ensure homogeneity in every construct.
- Clinically validated and regulatory-ready, opDNA® supports efficient, flexible, and compliant manufacturing. This approach can support clinical programs at every scale, from large-scale production to small-batch and scale-out demands of personalized immunotherapies.
- Emily Young - Director of Scientific Applications, 4Basebio
• A novel RNA splicing modulation platform that selectively activates pseudo-exons to precisely control gene and protein expression at the source of disease.
• Targeted oligonucleotides function as an innovative molecular switch, displacing repressive RNA-binding proteins to enable pseudo-exon inclusion during splicing, deliberately altering mRNA and downstream protein production.
• Powered by a proprietary map spanning over 90% of spliced protein-coding genes with pseudo-exons, the platform unlocks a vast therapeutic targeting space with broad applicability across many conditions.
- Poul Sørensen - CEO, Inverna therapeutics
Data will be presented validating two Argonaute dual targeting siRNAs (bis-siRNAs), respectively addressing residual risk/unmet need for ASCVD, including heart attacks and stroke, and fatty liver diseases (MASLD/MASH). We will present compelling and comprehensive results from in vitro and large in vivo studies, including extensive biochemical, gene expression and metabolomics assays demonstrating the extraordinary efficacy and safety of these agents. Together a strong case will be made for pursuing clinical development of these agents with the aim of launching first in man studies in the next 12-18 months.
- Michael Khan - CEO, ARGONAUTE RNA LIMITED
Linear synthesis by continuous-flow SPOS is the current state-of-the-art technology to manufacture oligonucleotide APIs. A very promising alternative, especially to manufacture large quantities, is the enzymatic ligation of short oligonucleotide fragments. This approach offers several advantages compared to the conventional strategy like higher yields and reduced purification burdens. Bachem will present a case study focusing on a therapeutically relevant siRNA sequence and benchmark different technologies used to manufacture siRNA fragments. We will discuss a holistic view of the manufacturing process and review control strategies for residual enzyme
- Sabine Fenner - Director Oligo R&D, bachem
Manufacturing success of RNA therapeutics depends on precise control of quality of raw materials, in vitro transcription (IVT) reaction conditions and purification strategies that apply across constructs. The presentation will outline a conceptual framework for mRNA and saRNA production that integrates rapid at-line analytics to monitor IVT kinetics, enabling data-driven endpoint selection and feed strategies that raise yield and batch-to-batch consistency. A Quality by Design approach maps critical IVT factors—NTP/Mg2+ ratio, polymerase selection, temperature and time, template design, and capping strategy—to critical quality attributes (CQAs) and cost, defining a robust design space that optimizes productivity without compromising quality.
Downstream processing requires scalable, high recovery purification tools and techniques that effectively remove double-stranded RNA, RNA fragments, residual reaction components (NTPs, T7), to reduce immunogenicity and increase cellular potency for both mRNA and saRNA. Affinity, multimodal and reverse-phase chromatography each offer technical advantages and practical challenges that have to be understood and managed in manufacturing environments.
Universal requirements (integrity, dsRNA burden, residuals) and format-specific needs (capping for mRNA; long-transcript handling and hydrolytic potential of saRNA) demand decision frameworks for selecting appropriate IVT strategies and purification approaches. The ultimate goal is a manufacturing approach that scales efficiently and accelerates onboarding of new RNA constructs—translating bench-top control into reliable, multi-product production platform.
- Rok Sekirnik - Head Process Development mRNA/pDNA, Sartorius BIA Separations
- Addressing scalability challenges with a continuous manufacturing platform: the same equipment and recipe from pre-clinical to commercial and from individualized medicines to epidemic vaccines.
- Accelerating mRNA Therapeutics Development Through Mechanistic Process Modeling: focus on a mechanistic IVT performance model that predicts reaction kinetics and the two key CQAs that are directly linked to mRNA functionality: capping efficiency and intactness.
- Cost reduction without compromising quality: cases studies of mRNA and saRNA will be presented with CQA data, targeted capacities and costs.
- Christophe Bonneville, PhD - CEO & Co-Founder, Dillico
RNA nanotherapeutics have risen to prominence following recent clinical successes, yet their broader potential remains constrained by liver biased biodistribution, a restricted cell tropism, and inadequate cell delivery due to poor endosomal escape. To gain a deeper understanding of the many complex in-vivo mechanisms and to identify the optimal drug characteristics needed to navigate these processes, we must devise a robust platform of assays and models capable of evaluating each relevant property of the drug. Establishing such a comprehensive and predictive preclinical cascade is essential to support the rational design and optimisation of next-generation RNA delivery vehicles, ultimately accelerating the future success of RNA therapeutics. To address this, five UK partner organisations have established the Intracellular Drug Delivery Centre (IDDC), creating a centre of excellence for lipid nanoparticle (LNP) innovation. The centre integrates high-throughput screening of novel lipid chemistries and formulation with mechanistic assessment of key formulations in cell models and small mammals. Our data from thousands of LNP formulations reveals the complexity of their structure-activity relationships, allowing us to map specific biological functions to distinct LNP components. Furthermore, we find that exceptions to the internalisation rupture-expression model highlight as yet unappreciated biological intricacies that control LNP functionality in target cells. Altogether, this work has advanced the rational design of next-generation RNA nanotherapeutics and revealed principles to guide the design of future LNPs.
- Aadarash Zia - Senior Scientist - Drug Delivery, Medicines Discovery Catapult
Current industry bottlenecks: Why narrow signal peptide testing limits process performance today and how the secretory pathway remains a manufacturing ‘black box’
Common challenges and solutions in signal peptide selection for improving manufacturability
Latest technological and computational advances, moving from testing dozens of signal peptides to high-throughput screening of thousands
Case examples on how choice of signal peptide impacts protein expression
- Tero-Pekka Alastalo - CEO & Founder, Avenue Biosciences