Day 1 – Wednesday 5th March 2025Wednesday, 5 March 2025 - CET (Central European Time, GMT+01:00)

• direct sequence mapping of mRNA using mass spectrometry
• analysis of poly(A) tail length and heterogeneity using mass spectrometry
• studying the effects of DNA template and mRNA manufacturing on poly(A) tail length and heterogeneity

• mRNA production is limited by availability of high quality, GMP grade DNA. Synthetic DNA produced enzymatically can address the draw backs associated with plasmid derived DNA templates.
• opDNA™ is a synthetic DNA template with a 3’ open end, which can feed directly into IVT processes without the need for linearisation. opDNA™ is devoid of a bacterial backbone and can be designed with long continuous poly-(A) tails encoded within the sequence.
• opDNA™ achieves significantly higher mRNA yields, comparable proinflammatory cytokine/chemokine responses, and equivalent gene expression as compared to plasmid derived templates.

• Discuss siRNA synthesis by assembly of multiple short, single-stranded RNA fragments into the desired double-stranded RNA duplex using ligation
• Compare various ligation approaches with a particular focus on substrate design. In combination with double-stranded RNA ligase engineering and protocol optimization, such integrated process development can increase target drug substance yield and reduce manufacturing costs
• Process performance will be demonstrated on the synthesis of a commercially approved siRNA asset

• Mercurna’s technology platform combining unique cell-targeting moieties with LNP-based delivery to deliver therapeutic mRNA with high specificity

• Active targeting strategies through optimized technology on targeted LNPs

• Examples on how Mercurna leverages its platform for development of targeted mRNA therapeutics to treat kidney diseases

• How to engineer vectors for circular-mRNA expression

• Enabling reduced dosing by enhancing payload expression level and potency

• Dual-function gene therapy vectors for a “remove-&-replace” strategy

• AGS specializes in developing extracellular vesicles from microalgae (MEVs) as a universal delivery system for therapeutics, vaccines, and gene therapies.
• MEVs have proven to be a performant, safe, and flexible delivery system for a variety of payloads (mRNAs, siRNAs, oligos, plasmids, peptides, and proteins). MEVs can be administered through multiple and non-invasive routes of administration (RoA) (topical, ocular, oral, respiratory, intranasal, intramuscular, and intravenous), to deliver treatments to hard-to-reach tissues. MEVs overcome well-known limitations associated with other existing delivery systems.
• MEV manufacturing is sustainable, straightforward (simple), cost-effective, safe, GMP-ready. MEV production is green (literally and environmentally), relying solely on light, fresh water, and minerals.

• Antisense oligonucleotides (ASOs) incorporating Bridged Nucleic Acids (BNAs), such as LNA, have demonstrated the potential to surpass conventional ASOs and siRNAs in efficacy, but their safety has remained a significant challenge.
• Liid's proprietary BROTHERS technology (BRO) addresses this issue by avoiding unwanted off-target interactions, such as with proteins and off-target genes, significantly expanding their therapeutic window.
• Liid has established a robust pipeline primarily targeting central nervous system (CNS) disorders.

• 96-well high-throughput LNP formulation device featuring automated lipid mixing and dialysis.
• First-in-class single-use LNP mixing system, eliminating the need for cleaning in GMP production.

• The patient population – how it impacts the business model
• An approval pathway when you cannot conduct a traditional clinical trial - creating the argument for regulators
• An industry solution vs. the “bench-to-bedside” approach

• Case study: Transfer of self-amplifying mRNA Covid-19 vaccine in Japan and pandemic readiness
• Good practices to ensure a successful technology transfer
• Key points to select a CDMO partner

As editing technologies push into the RNA space, we open a forum discussion bringing together RNA editing leaders to evaluate its current and future potential as a therapeutic tool.

• Reviewing existing and emerging RNA editing techniques, including CRISPR, ADAR, base-editing

• Discussing opportunities and challenges for targeted delivery of RNA editing machinery

• Exploring new and future disease targets that can be accessed with RNA editing technology

• Clinical progression of RNA editing technologies - sharing insights and lessons learned

• Navigating the pathway to regulatory success for RNA editing therapies

• How to build a cohesive strategy that includes sequence optimization, characterization, and potency studies
• Reducing development timelines
• 5' and 3' UTR optimization strategies
• Other aspects of comprehensive mRNA characterization
• Developing models to better understand the functional activity of mRNA products

Explore the methods for quantifying the relative amounts of different mRNA molecules within a product, ensuring that the desired proportions are achieved for optimal efficacy.

• The quality of lipids is critically important to the functionality of nucleic acid therapy.
• For new materials the rational design of a target molecule and the development of a robust and scalable manufacturing route are key.
• The routine GMP production of high-quality products requires an experienced cross-functional team and a unique set of competencies.

• Combining AI and NMR to search and discover new targets in miRNA

• Developing novel delivery technology to achieve increased internalisation at lower doses

• Developing novel therapies to activate endogenous cardiac muscle regeneration processes in diseased adult hearts by manipulating the activity of microRNAs

• Our current focus is Ischemic Heart Disease, but the therapy can be applied to many cardiac diseases where cardiac muscle regeneration is required. We are also developing a therapeutic for hypertrophic cardiomyopathy which is the leading cause of sudden cardiac death in young adults. We aim to initiate clinical testing in 2026 for our lead programs

• Exploring a discovery stage pipeline of LNP-delivered mRNA and saRNA vaccines targeting HPV, Monkeypox, HER2+ tumours and EBV+ tumours

• Spotlighting tumour specific delivery of saRNA

-Identification of novel dysregulated disease driving lncRNAs in oncology and neuroscience

-Development of small molecules disrupting the interaction between LncRNA and RNA binding protein.

Showcase your innovations to an audience of potential partners at RNA Leaders and tap into the expertise to drive your business forward. Available for early-stage biotechs with an active pipeline or delivery technology.

For more information please contact Martha Phillips martha@lsxleaders.com

As we uncover new capabilities of the dark genome, how does this translate to the world of RNA therapeutics?

• Diving into current ncRNA modalities and their potential for new targets

• Exploring recent clinical milestones of ncRNA therapeutics

• Reviewing how to minimize off-target effects and systemic toxicity

• Discussing how ncRNA can be used a biomarker for disease

• Phosphorodiamidate Morpholino Oligomers (PMOs) are synthesized from activated morpholino subunits via linear solid-phase synthesis. After the oligomer chain assembly, the crude drug substance is released from solid support. This crude material undergoes purification through Strong Anion Exchange (SAX) chromatography, and the purified drug substance is isolated by lyophilization following desalting with Tangential Flow Filtration (TFF)
• While the impurity classes and categories of PMOs are similar to those of typical Antisense Oligonucleotides (ASOs), PMOs have several unique impurities due to their distinct nature. These include impurities originating from starting materials, processes, and degradants
• This presentation will provide an overview of the PMO impurity profile, approaches for PMO impurity characterization and control strategy, and a detailed examination of several impurities specific to PMOs

• Cell-free RNAs (cfRNAs), stabilized by extracellular vesicles (EVs), lipoproteins, and RNA-binding proteins (RBPs), represent a new frontier in RNA therapeutics and biomarker research. These molecules are actively being investigated for their role in cell-to-cell communication, offering insights that could transform RNA-based treatment strategies
• Presenting recent findings that highlight the crucial role of RBPs in cfRNA biology and discuss their potential to develop next-generation RNA therapeutics, specifically for enhancing stability, specificity, and targeted uptake. I will also explore the use of cfRNAs as non-invasive biomarkers, enabling precise, real-time monitoring of therapeutic efficacy and facilitating the optimization of personalized treatment regimens
• By integrating discoveries on cfRNA into RNA therapeutic pipelines, we could pave the way for more effective and individualized treatment strategies, setting a new standard in RNA-based medicine and significantly improving patient outcomes

• In our earlier discovery efforts, miRNA-10b was identified as a master regulator of the viability of metastatic tumor cells

• This knowledge allowed us to develop a therapeutic (TTX-MC138) based on miR-10b inhibition that could cause complete and persistent regression of metastases in cancer models with no evidence of systemic toxicity

• For clinical development of TTX-MC138, we conducted critical, exploratory IND enabling studies in rats, dogs, and non-human primates resulting in FDA authorization (IND163800) for initiation of an ongoing microdosing Phase 0 clinical trial in patients with advanced metastatic cancer of multiple tissue origins to assist in the identification of susceptible tumor types (or patients), but also to support future clinical efforts by providing proof of concept and quantification of delivery to clinical metastases

As tRNA emerges as an untapped RNA modality, key leaders join to discuss their progress, and future opportunities that can be unlocked with tRNA.

• A deep dive into tRNA biology, and the mechanism of action of tRNA-based therapeutics

• Discussing current and future disease areas that can be targeted with tRNA therapeutics

• Bench to bedside – sharing thoughts on tRNA clinical progression