Main Conference – Day 1Wednesday, 18 March 2026 - CET (Central European Time, GMT+01:00)

• The transformative potential of RNA-based therapies will be explored, focusing on their applications in treating both rare genetic disorders and chronic diseases.
• Experts will discuss the innovative approaches RNA therapeutics offer for targeted treatment, emphasising their ability to address unmet medical needs and improve patient outcomes.
• Scientific, regulatory, and commercial challenges in developing RNA therapies will be examined, alongside breakthroughs that are shaping the future of medicine.

• Review the latest advancements in RNA platforms as of 2025, showcasing key innovations and breakthroughs.
• Clinical milestones achieved with RNA-based therapeutics will be highlighted, offering insights into their impact on medicine.
• The session will provide an overview of the evolving RNA technology landscape and future opportunities in the field.

Chemically synthesized RNA oligonucleotides (oligos) have the potential of a powerful, multifaceted approach against cancer by acting as immune stimulators, RNA interference agents, and vaccines, as well as drug carriers. This presentation will first detail the simple chemical structure of RNA oligos that can be used for cancer vaccination. We will then introduce and discuss a new type of chemotherapeutic anticancer RNA oligo currently under development.

• Dysregulated mRNA processing has been identified as a new and druggable molecular hallmark of aging. Age-related changes in splicing factor expression disrupt physiological homeostasis, leading to loss of transcriptomic resilience, cellular senescence, and chronic diseases

• An antisense oligonucleotide approach has been developed to restore splicing regulator expression specifically in senescent cells. This method leverages endogenous autoregulation to achieve physiologically regulated expression of target genes within their normal homeostasis.

• Enabling pharmacokinetic (PK) properties and proof of principle for transcriptomic reprogramming of senescence have been demonstrated in an aged mouse model via an inhalation route.

• Initial applications of this technology target Idiopathic Pulmonary Fibrosis (IPF), a sentinel disease driven by senescence. Results show the ablation of harmful senescent properties in diseased cells and precision-cut lung slices (PCLS) from IPF patients, along with significant reductions in markers of inflammation and fibrosis

.• The approach has shown efficacy in senescent primary human cells across multiple cell lineages, suggesting potential applications for the treatment of various age-related diseases beyond respiratory conditions.

Cardiovascular disease is the leading cause of death worldwide; heart failure carries high mortality, and substantial health-economic burden. Cardiac infarcts can lead to loss of heart function and heart failure. Cardiomyocytes have limited regenerative capacity and current therapies only improve residual function and are not curative.

• Small non-coding microRNAs delivered as synthetic mimics in cardiomyocyte specific lipid nanoparticles can reactivate cardiomyocyte proliferation in the adult heart. Preclinical studies in mice and pigs demonstrate increased cardiomyocyte division, reduced infarct size, and improved function after myocardial infarction.
• The miRNA–LNP approach provides potent, transient, and repeatable effects with efficient myocardial delivery; Compared with AAV, protein and cell therapies, miRNA–LNPs offer better control of dose and optimal duration.
• miRNA-based regenerative therapy represents a promising, scalable strategy for curative treatment against heart failure, warranting further clinical development and safety evaluation.

• The development of transient cyclic structures in oligonucleotides enhances their drug-like properties by optimizing spatial configurations that bring the 3'- and 5'-ends into proximity.
• These cyclic oligonucleotide structures exhibit reduced protein binding and diminished interactions with pattern recognition receptors due to the inaccessibility of the 5’-end, improving their therapeutic profile.
• Transient cyclic oligonucleotides enable broad applications in RNA therapeutics, including RNaseH-mediated knockdown, splicing modulation, siRNA delivery, and gRNA-based mechanisms.

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

Partial hybridization of oligonucleotide therapeutics (ONT) to cellular RNA/DNA can drive unwanted off-target effects. Current design algorithms fall short of predicting these effects transcriptome-wide, so extensive experimental validation is required. To close this gap, we need robust, scalable, transcriptomics-based workflows that streamline ONT selectivity assessment. This is critical given the potentially long duration of action of ONT in the clinic.

This talk will address:

• Relevant models: What defines a biologically and clinically meaningful system for off-target assessment?
• Automation and scale: How can high-throughput transcriptomics and lab automation accelerate ONT safety profiling?
• Modality-specific risks: What unique off-target challenges arise across ONT classes and how should strategies adapt?

• Developing self-assembling siRNA therapeutics designed for effective and targeted delivery via inhalation to treat respiratory diseases.
• Optimizing siRNA formulations to ensure stability, efficient pulmonary uptake, and minimal off-target effects.
• Demonstrating safety and therapeutic efficacy through advanced preclinical models of respiratory disease

• Addressing the barriers to effective transport of nucleic acid therapeutics, such as stability, cellular uptake, and tissue specificity.
• Exploring lipid nanoparticles, polymer-based carriers, and conjugate systems for precise and efficient delivery.
• Highlighting preclinical and clinical advancements in delivery technologies for nucleic acid-based therapies.
• Discussing emerging approaches, such as extracellular vesicles and targeted delivery systems, to enhance therapeutic outcomes.