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

The manufacture of high-quality, GMP grade DNA is a major bottleneck in the production of mRNA and viral vectors for use in gene therapy and vaccines.

• Evaluate a scalable, fully enzymatic synthesis process for the production of linear DNA constructs via our Trueprime™ amplification technology
• Compare the synthesis of in vitro transcribed (IVT) mRNA using opDNA™ versus linearised plasmid DNA across a panel of constructs ranging from 1.5kb to 9kb
• See how the technology can overcome the difficulties associated with complex polyA tails for mRNA constructs, which are inherently difficult to synthesise via bacterial propagation systems

• Reviewing factors in manufacturing site design for sustainable and rapid production of both mRNA vaccines and therapeutics
• Exploring the needs of mRNA vaccine and therapeutic manufacturing processes to be fully continuous, and exploring the latest solutions

• 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

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

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

• 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

Manuel is a biologist and serial entrepreneur with more than 30 years of experience in the biotech sector. Manuel was a postdoc and visiting researcher across leading institutes in Germany, France, and The Netherlands. He was the Founder and CEO of Nautilus Biotech (France and USA), a pioneering biotech company focused on directed evolution of proteins for long-lasting and oral variants (such as long-lasting interferon-alpha and oral human growth hormone). Nautilus Biotech filed INDs with FDA, and secured licensing deals with Aventis Pasteur, Serono, Wyeth Pharma and Hanall Pharmaceuticals. Since 2020, he’s co-founder and CEO of AGS Therapeutics.

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

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

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 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

• Current delivery systems for the encapsulation of Nucleic Acids have strengths and weaknesses

• New technologies for the encapsulation in development can potentially overcome limitations of currently available standard mixing technologies

• Results of comparative studies will be presented at the conference

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.

• 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

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

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