Day 1 – Wednesday 4th September 2024Wednesday, 4 September 2024 - PT (Pacific Time, GMT-08:00)

• 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

• An overview of NCTM’s mRNA production process, from pDNA production to bulk freezing
• A list of QC assays and CQA ranges for the NCTM mRNA platform process
• A summary of the manufacturing-scale, hands-on training course for mRNA production, created in collaboration with industry partners

• Advancing a lncRNA tailored drug development platform to discover potential therapeutic targets in the dark genome
• Update on early clinical candidate, HTX-001, for treatment of nonobstructive hypertrophic cardiomyopathy

• An ASO RNA Medicine Platform Technology Targets Pathological RNAs in All Tissues (Except the Brain) Without Delivery Vehicles/Formulation through Subcutaneous or Inhalation Delivery in Saline
• Therapeutic Targeting of a Pathological MicroRNA Effectively Treats Post-Myocardial Infarction Heart Failure, Aging-Related Sarcopenia, and Duchenne Muscular Dystrophy, with POC Efficacy and Safety Data in Mice, Pigs, and NHPs
• POC Animal Data Support Expansion Potential to Pathological mRNAs and Structural Ultra-Conserved Viral RNAs

• Delivery issues have limited anticancer applications for nucleic acid-based drugs
• A tumor-targeted tissue-penetrating approach to enable effective solid tumor delivery

• Introduction of RiboX proprietary plug-and-play circular RNA and LNP platform

• Introduction of RiboX frontrunner projects- RXRG001 and RXRG002

• Identification of novel CNS targets
• Development of RNA therapeutics capable of driving renewal of the microglial niche

• Ionizable lipids are known to present varying degrees of immunotoxicity. Understanding the role of key cellular mediators such as the NLRP3 inflammasome in this context will be key to developing the next generation of safe, well tolerated non-viral delivery systems
• We developed a series of bio-degradable lipids that are rationally engineered to elicit specific immune responses
• Applications of these lipids to create precision mRNA therapeutics and vaccines will be presented

• 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

• Elixirgen Therapeutics is a clinical-stage RNA therapeutics company with multiple RNA platform technologies developed fully in-house.
• The Bobcat mRNA platform overcomes the carrying capacity limitations of other therapeutic approaches, and has been used to develop EXG-7001, an mRNA therapeutic delivering the first full-length dystrophin for Duchenne muscular dystrophy with functional in vivo proof of concept data.
• c-srRNA is a self-replicating RNA platform featuring temperature control to reduce off-target effects and improve efficacy

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

• Investigate the potential of self-amplifying mRNA to create effective immunotherapies for solid tumors
• Evaluate the safety, tolerability, and efficacy of saRNAs in the clinic

• Eclipsebio provides design, characterization, and optimization solutions for RNA-based and RNA-targeting medicines
• The eMERGE platform provides comprehensive characterization of therapeutic potency, safety, and purity for drug development success
• Double-stranded RNA (dsRNA) by-products decrease therapeutic stability and translation. eSENSE dsRNA identifies the sequences and structures that promote dsRNA formation

• Engineering cells ex vivo and in vivo using UltraSlice™ gene editing RNA for precision targeted insertion of durably expressed transgenes into defined genomic loci
• Unlocking the potential of next-generation engineered cell therapies including allogeneic and iPS cell-derived CAR-T for solid tumors and autoimmune diseases
• Enabling in vivo CAR-T and CAR-Macrophage using novel high-fidelity RNA chemistries and the ToRNAdo™ single-component fusogenic lipid delivery platform

• Integrative design through centralized, consistent and robust data is key to solving multi-factorial and inter-dependent structure/activity relationships.
• Efficiency of every programmable component is critical to performance of new eRNA therapies.
• Potential for In situ generated CAR-T cells for AID and novel multiple-mechanism cardio-metabolic therapies are exemplified .

• Pioneering the next generation of genetic medicines with our Gene Writing™ platform, designed to introduce a broad range of edits to the genome from inserting whole genes or exons to introducing single nucleotide changes
• Developing RNA Gene Writers that use target-primed reverse transcription (TPRT) as a mechanism to edit the genome with all-RNA compositions
• Advancing a proprietary non-viral delivery platform leveraging lipid nanoparticles (LNP) to deliver Gene Writers to the liver, hematopoietic stem cells, T cells and beyond

This workshop is aimed at boosting your comprehension of the pivotal processes in RNA therapeutics.

It will begin with an overview of mRNA Synthesis and Purification, Oligonucleotide Manufacturing, and Lipid Nanoparticle (LNP) Delivery. Moving on to a lively panel discussion with Thermo Fisher's subject matter experts as they delve into RNA therapeutics development. This interactive session will offer valuable insights into tackling the challenges with development and discuss solutions to these challenges.

This workshop is an ideal opportunity to chat with experts, engage in meaningful discussions, and enhance your knowledge in the field of RNA therapeutics.

Don't miss out on this chance to stay ahead in this dynamic and rapidly evolving field.

• Dry powder material thanks to disruptive, unique technology formulating and drying the most fragile RNA/LNP composition
• mRNA activity preserved or even increased in dry powder form, proven in-vitro and in-vivo
• Substantially lower costs, new treatments enabled, and particle engineering possible for inhalable RNAs

• Expanded use of conventional mRNA vaccines has been limited by unacceptable side effects at doses required for protection
• First generation srRNA showed some improvements in bioactivity, but were correspondingly more toxic narrowing their utility
• Here, we show next generation srRNA have major bioactivity improvements clinically, showing capacity to confer protection at very low doses without corresponding increase in toxicity

• panCAR combines a novel, synthetic, circular coding RNA platform (oRNA) and immunotropic lipid nanoparticles (LNP) to drive CAR expression on surface of multiple immune effector cells after i.v. administration, eliminating the need for external manufacturing
• LNPs deliver oRNA payloads to immune effector subsets including T cells, NK cells and macrophages in vivo, potentially increasing efficacy and broadening application beyond hematologic malignancies
• oRNA-enabled panCAR therapies promise a transient, re-dosable and scalable immune cell therapy without requiring immunodepletion

• Using ImmunoPrism, an ML-based predictive immune modelling platform, to refine predictive biomarkers for immuno-oncology patient response to treatment
• An update on clinical validation studies focussing on HNSCC (Head and Neck Squamous Cell Carcinoma), NSCLC (Non-Small-Cell Lung Cancer), CRC (colorectal cancer) and UCC (urothelial cancer)

• Advancing a new standardized approach to RNA therapeutic analytics using high-resolution LC-MS/MS

• Extracellular RNAs in Liquid biopsy reflect disease status
• PHGDH extracellular RNA from blood plasma predicts the clinical diagnosis of Alzheimer’s disease
• Eight patient cohorts corroborate the increased PHGDH expression in Alzheimer’s disease

· ARIZ-047, our preclinical novel siRNA formulated in a calcium-phosphate drug delivery system with a tumor targeting ligand, targets a histone methyltransferase that is one of the early changes in cancerization of the cell.

· Our siRNA-conjugate delivery platform solves the siRNA delivery issue beyond liver cells with specificity for cancer cells, including lung cancer.

• RNA modalities have incredible potential across numerous therapeutic areas. Following the success of mRNA vaccine formats, including linear modified mRNA and self-amplifying mRNA, therapeutic explorations in mRNA-enabled gene transfer, editing and writing are providing exciting possibilities for therapies of the future.
• Many opportunities exist for optimizing technologies for RNA medicines. These include optimal liver LNPs, extrahepatic targeting technologies to challenging tissues and difficult-to-target body compartments, nanoparticle delivery with lowest possible immune stimulation and flexible redosing options. In addition, cost and stability improvements are needed, to enable global reach of revolutionary products for as many patients as possible.
• Axelyf is a new biotech company focused on lipids as therapeutics in inflammation and auto-immunity and as delivery systems for RNA cargos. A brief company summary will be shared.

• Defining RNA architecture - the relationship between structure, function and the endogenous cellular context

• Discovering functional RNA binding small molecules, using in-cell chemi-transcriptomics

• Using machine learning to explore chemical space, defining the rules that govern functional RNA - small molecule interactions

• Dual Peripheral CB1R inhibition that reduces appetite and increases energy expenditure.
• Targeted gene silencing that activates fat-burning thermogenesis and improves metabolic function