• Current mRNA vaccine characterization methods currently use testing methods require large capital investment, a considerable workforce, can be slow and cumbersome and do not always analyze the native molecule.

• Explore rapid comprehensive Technologies based CQA testing pipeline extending from the plasmid precursors to the drug substance and drug product (mRNA) can complement state of the art techniques by providing an orthogonal analysis while addressing these bottlenecks, such as

• direct RNA sequencing chemistry enables sequencing RNA transcripts without the requirement of first converting to DNA, nor the need for PCR amplification

• specific basecallers for transcripts containing RNA modifications, including N1-methyl-pseudouridine, which is relevant to mRNA vaccine production

• World’s first continuous RNA manufacturing system
• Construct agnostic process for high quality DS
• No scale up required due to a radical redesign of the process
• Simplified, integrated, automated workflow in a single system enabling ug to kg production

• Explore Moderna’s clinical programs currently in development to create mRNA vaccines for wide range of indications outside of infectious diseases
• Reviewing the commercial activities of vaccine candidates in clinical development

• R&D to GMP Supply at WACKER BIOTECH
• Proprietary pDNA technologies
• State-of-the-art mRNA manufacturing and LNP formulation

• RNA interference has emerged as a potent tool for gene regulation, holding substantial therapeutic promise. Small interfering RNAs (siRNAs) represent a rising class of molecules for drug development, allowing the selective modulation of target genes. Effective bioinformatics tools are vital for the strategic selection and optimization of siRNAs, ensuring their therapeutic efficacy and safety.

• This presentation will be focused on the critical role of bioinformatics tools in developing siRNA-based treatments, addressing multiple challenges that go beyond predictions of target sites and off-target effects.

• We'll explore how bioinformatics is streamlining research and actively shaping the future of siRNA therapies in precision medicine.

• The miND® NGS pipeline enables absolute quantitation of small RNAs such as microRNAs and siRNAs in liquid biopsies, cells, and tissues
• Circulating microRNAs are sensitive and specific biomarkers of drug induced organ injury including the liver, pancreas, and central nervous system
• The SMARTer whole transcriptome workflow provides deep insight into the circulating transcriptome in liquid biopsies including extracellular vesicles

• Simplified assays for transcriptome-wide ribosomal profiling

• RNA structure probing of in vitro transcribed mRNA

• SHAPE databases profiling RNA structure in human cell lines and normal tissues

• Scalable, multiplex technology for mapping RNA binding protein binding sites

• Direct, quantitative profiling of miRNA targets
  
  

• Widespread use of RNA-based innovative therapeutics remains a significant challenge, mainly due to the lack of effective delivery systems beyond the liver, which can overcome the body’s natural barriers, and/or maintain a sustained expression of the payload.
• AGS develops MEVs, as a new kind of safe, targeted, and highly versatile delivery system for innovative therapeutics and vaccines.
• MEVs are extremely versatile in terms of receivable payloads: mRNA, siRNA, dsRNA, miRNA, lncRNA, peptides, proteins, ASO, plasmids, DNA fragments, small chemical molecules.
• MEVs can be effectively administered by different routes. They deliver active biologics through oral, intranasal, respiratory, intravenous, intramuscular, and topical administration.
• By topical administration (drop instillation) on the surface of the eyes, MEVs deliver their payload to the choroid-retina cells, supporting the expression of mRNA specifically in those tissues. This is a huge differentiation from all existing or in development treatments for back-of-the-eye diseases, which relay in all cases on invasive and low patient-compliance intraocular injections.

The successful clinical translation of LNP-RNA therapies has paved the way for a medical revolution. To advance the delivery of RNA payloads to immune cells with improved therapeutic index (ex vivo and in vivo), NanoVation Therapeutics has developed LNP platform technologies offering a clear path to the clinic

• OligoPhore and SemaPhore are peptide-based nanoparticle platforms for extrahepatic delivery of RNA
• These platforms deliver RNA specifically to inflamed or cancerous tissues though a combination of passive targeting and receptor mediated tissue-retention
• The peptide component of the platform promotes a very efficient endosomal escape increasing the availability of RNA inside the target cell
• OligoPhore and SemaPhore are well tolerated in animal models

• Sixfold is overcoming the RNA delivery challenge by systematically screening a large and diverse conjugate space.
• The unique Mergo® system uses modified RNA tags that allow rapid in vivo evaluation of novel modifications that alter biodistribution and cell uptake, and mimic how RNA is naturally shuttled between cells.
• Sixfold will further present how highly curated in vivo data is powering their ML/AI algorithms for more effective conjugate selections

• Discussion around the challenges associated with CNS gene therapy delivery
• Introduction to a revolutionary micro-robotic CNS precision drug delivery platform
• Overview of our pre-clinical gene therapy and large animal safety data

• In depth review on how more mRNA vaccines (against infectious diseases and cancer) are currently in clinical development and are expected to be approved in the coming years.

• In addition, mRNA-based therapies using non-immunogenic formulations of mRNA are being developed.

• Thus, the potential of synthetic mRNA in medicine is just starting to be unraveled and this versatile biomolecule is expected to be the active pharmaceutical ingredient in many future prophylactic and therapeutic drugs.

• Current ‘1st generation’ systems for the formulation of nucleic acids into nanoparticles have limitations. Fluid dynamic effects are the main driver for fast and reliable mixing.

• Designing a ‘2nd generation’ mixing device based on computational fluid dynamics can solve many of the limitations.

• The fast, reliable, and scalable mixing device FDmiX will be presented at the conference, together with initial data

• Putting RNA biology at the center of a therapeutic intervention

• Use the succession of modalities, starting with oligonucleotides as the frontrunner potentially been followed by other modalities such as gene therapy

• Address key enabling factors such as delivery to the brain

• IV-formulated, BDDSTM-encapsulated RNAi targeting
• In-vivo validation across species, including NHP
• RNAscope update

• Using RNA activation to restore normal function to cells.
• How to predict clinical response with small activation RNAs
• New concepts for brain delivery

We are in an age of mRNA lipid nanoparticle (mRNA-LNP) technology, expanding beyond infectious disease vaccines to new modalities and applications, nucleic acid therapeutics can be designed and formulated to silence, express, and edit specific genes, providing a flexible and powerful approach to preventing and treating diseases.

The complexity and diversity of mRNA-LNP approaches leads to different challenges for research and manufacturing. Together, Precision NanoSystems and Cytiva, offer strategies to de-risk and accelerate the development of promising RNA-LNP drug candidates for clinical evaluation and successful commercialization.

• Access to Proven mRNA-LNP Expertise with pre-optimized formulations and methods, leveraging well-characterized lipids to expedite lead candidate selection and lock in potent formulations
• Complement Critical Quality Attributes with robust analytics and scalable bioassays to accelerate regulatory submission and de-risk program development
• Utilize Scalable mRNA-LNP Technologies to fast-track clinical evaluation
• Leverage end-to-end mRNA-LNP workflows from research to GMP manufacturing and partner with experts to strategically roadmap clinical development milestones including data and document packages to enable regulatory submissions

Precision NanoSystems is a global leader in nanoparticle technologies and solutions with the goal of empowering our clients to develop genomic medicines, including mRNA vaccines and therapeutics that define the future of medicine. We have developed a Genomic Medicine Toolbox for the end-to-end development of RNA-lipid nanoparticles (RNA-LNP). This toolbox comprises an RNA drug substance platform, a nanoparticle delivery platform, and a microfluidics-based nanoparticle manufacturing platform. In this presentation, we provide examples of how these platform technologies are enabling research scientists to rapidly discover new RNA-LNP based vaccines, gene therapies and cell therapies. Furthermore, we will show how PNI’s Biopharma Services Team can de-risk and accelerate the development of promising RNA-LNP drug candidates for clinical evaluation and successful commercialization.

• End-to-end concept: from cell bank to DNA template to bulk mRNA
• GMP conform characterization and QC testing of mRNA
• Full-scale case study data from GMP batches

• Showcasing the powerful capabilities of our Sunny Suite platforms = ensuring consistent high-throughput formulation screening through process optimization and pre-clinical scale-up.

• Illustrating significant acceleration in LNP formulation screening—performing up to 96 experiments in under 6 hours.

• Highlighting the seamless transition to process optimization—adjusting flow rates and ratios—and the effortless scale-up to continuous flow on a single instrument.

• Advanced ionizable lipids
• Versatility in cargo encapsulation
• Targeted delivery of RNA therapeutics
• Tailoring lipid nanoparticles for specific applications

• Chronic liver disease stands alone among major health challenges of our time as mortality rates continue to climb.
• To tackle this major challenge, Ochre Bio have built one the fastest and most comprehensive ‘big data’ liver R&D pipelines.
• By generating comprehensive deep phenotyping datasets, we identify novel targets, develop RNAi therapies, and assess their efficacy in human models that better reflect human physiological and clinical conditions.

Developing a new RNA therapy from scratch, be it an ASO, an RNA-targeting small molecule or an mRNA vaccine, is a multi-faceted endeavor, requiring several areas of expertise and several layers of experimental assays to tease out the best candidates. In recent years, many institutions are building upon their knowledge foundations and putting conscious effort into upscaling or 'platformizing' their R&D. This is done with the ambition to actively use the data they generate, in many cases in conjunction with historical data (after appropriate reformatting), to learn the rules of how to develop better candidates.

• In the age of data-centricity, what questions are researchers hoping to query from their data?
• How would you need to collect and format your data in order to make such queries?
• Can your data be as much an asset as your drug candidates?

• Regulated mRNA processing is achieved by the combinatorial action of splicing factors; proteins which activate or inhibit splice site choice.
• Splicing factor expression declines during ageing as a consequence of constitutive and unresolved cellular signalling, with is a provocation towards cellular senescence.
• We have generated a portfolio of small molecule modulators of splicing factor expression able to ameliorate multiple features of senescence in human primary skin cells.
• Dysregulation of mRNA splicing represents a new (and druggable) driver of cellular ageing, which can be targeted to treat the causes, rather than the consequences, of cellular ageing.

• Switch’s triple-stranded, next-generation RNAi technology, CASi, demonstrates efficient self-delivery and uptake, potency andduration of effect, and cell selectivity
• Switch Therapeutics is developing these biomarker-gated, innovative genetic medicines to transform the treatment of central nervous system diseases

There are major challenges in circular RNA-based drug development. This presentation will discuss:

• The first challenge is circularization efficiency, which is a critical factor in determining purity and yield for producing circular RNA drugs on an industrial scale.
• The second challenge is to engineer circular RNAs to express more protein than mRNA genetically.
• Levatio Therapeutics has established a Circular RNA platform technology that drives high circularization efficiency and expression of therapeutic proteins.

• Ultra-short oligos can up- and down-regulate inflammatory responses induced by RNAs

• Highly targeted effects on TLR7/8 receptors (and potential for others)

• Broad applicability for co-packaging with RNA therapeutics & vaccines, and as standalone autoimmune drugs