Day 2 – Thursday 5th September 2024Thursday, 5 September 2024 - PT (Pacific Time, GMT-08:00)

• Screening for identification of lead formulation candidates
• Thermostability of various dosage form presentations
• Next generation vaccines using alternative routes of administration

• PEP-NPs constitute an unique RNA Therapeutic platform that leverages novel peptide technology that is able to systemically target and deliver RNA therapeutic in vivo
• PEP-NPs are highly selective for diseased tissues and have been rationally designed to overcome hepatic accumulations and interact specifically with targeted organ-specific proteins and receptors including lung, tumors, muscle, spleen and brain
• Systemic administrations of PEP-Nanoparticles mediated effective mRNA delivery in the tumor and have been successfully used to rescue Tumor Suppressor functions or for gene editing of Oncogene mutations as potential therapeutic approach in lung cancer, breast cancer, pancreatic cancer and osteosarcoma

• The landscape of mRNA medicines is evolving, marked by an expanding pipeline of drugs, a diverse range of targeted prophylactic and therapeutic indications, and advancements in drug design and delivery
• Innovative technologies and solutions are imperative to address key challenges in mRNA manufacturing, safety, and efficacy
• Primrose Bio develops and supplies advanced RNA polymerases, the key enzyme used in mRNA manufacturing by in vitro transcription (IVT). The company’s panel of RNA Polymerases (Prima RNApols) enhances mRNA quality and lowers costs by improving target capped mRNA yield and reducing the amount of expensive IVT reagent input, while greatly reducing double-stranded RNA (dsRNA) impurities, to address manufacturing needs across a wide range of therapeutic and vaccine applications, capping chemistries, and other mRNA manufacturing and product requirements

• Obtaining high-quality mRNA is a highly desired starting point for therapeutic applications
• Strategies to achieve this are discussed with example data
• Data shows that plasmid, coding sequence, and process optimization are important aspects to be considered

• Creating transformative genetic medicines for diseases of the liver, CNS, and beyond

• OPERA (Oligonucleotide Promoted Editing of RNA) platform is a differentiated approach to identifying highly potent RNA editing therapeutics

• KRRO-110 is potentially a best-in-class therapeutic for the treatment of Alpha-1 Antitrypsin Deficiency (AATD)

• The RNAfix platform has broad therapeutic application to correct missense mutations, modulate protein expression, or modify protein-protein interactions
• Using diffusion models trained on billions of proprietary experimental data points, the RNAfix platform can generate specific and efficient ADAR-recruiting gRNAs for any adenosine transcriptome-wide
• In pharmacology models, RNAfix achieved >90% target editing in the mouse and non-human primate brain, demonstrating unparalleled efficiency and robust translatability across species

• RADAR leverages simple, elegant “logic” gates to enable timely, target, and controlled expression of a genetic payload at the level of translation
• RADAR senses cellular signatures encoded in the cell’s transcriptome
• RADAR is a safe, scalable, and highly modular technology allowing for precise genetic manipulation of a broad variety of cell types and states, unlocking in vivo programmability for several key indications

• Splice Editors increase trans-splicing efficiency by leveraging CRISPR-Cas systems
• Splice Editor-enabled multi-kilobase edits unlock several key indications and pathogenic variants
• Splice Editing is a promising new modality for RNA editing

• Overview of Arcturus Therapeutic’s LUNAR Delivery Platform and our Therapeutics/Vaccine Pipeline
• The global commercialization partnership our Covid-19 Vaccine, Kostaive®, (World’s first Self Amplifying mRNA Vaccine )
• Establishing a joint venture CDMO for mRNA Vaccines and Therapeutics

• Discuss how microfluidic characteristics such as swappable closed wetted paths and at-line analytical sensors enable rapid manufacturing of personalized cancer vaccines
• Learn how microfluidic manufacturing was used to develop effective HPV-driven tumor therapies

• Accelerating discovery of saRNA for vaccine and therapeutic applications
• Discussing pre-clinical results for a saRNA vaccine program
• Differentiating saRNA discovery and design for a therapeutic application from a vaccine approach

• Exploring RBP (RNA binding protein) biology and its regulatory function in post-transcriptional processing of RNA
• Modulating gene expression by drugging RBPs to restore pathogenic mutations associated with neurodegeneration and cancer

• Building an integrative RNA-targeting small molecule discovery platform that integrates large-scale genomics, advanced screening, and state-of-the-art med chemistry to identify and develop drug-like small molecule regulators of RNA target expression.
• Discussing lead program as a case study to demonstrate our discovery process. By targeting the RNA of an oncogenic transcription factor, we are able to show stellar anti-tumor in vitro and in vivo efficacy and robust PK-PD relationship, unlocking the therapeutic potential of this previously undruggable target.

• Accurately modelling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation and the formulation of tailored therapeutics
• Introducing BigRNA, an advanced RNA foundation model trained on over one trillion signals from genome-matched datasets to predict tissue-specific RNA expression, splicing, microRNA sites, and RNA binding protein specificity from DNA sequence
• Single BigRNA model outperforms state-of-the-art models across a diverse range of tasks and extends to a wide range of R&D applications, specifically in the prediction, identification, and design of RNA-targeting therapeutic opportunities

• Exploring a tRNA biology platform that utilizes ML and high-throughput automated in vitro assays to design and test tRNA molecules with optimized sequences and chemical modifications
• Developing tRNA therapeutics that identify and correct nonsense mutations (also called premature termination codons) to restore protein production

• Leveraging engineered tRNAs to overcome genetic disease
• Using ‘PTCX’ to design tRNAs that recognize and suppress non-sense mutations via insertion of required amino acid
• Insight into new secondary tRNA platform, ‘SWTX’, enabling labelling of disease causing proteins for degradation

• Pioneering novel tRNA therapeutics that increase protein to cure genetic diseases
• Lead Suppressor tRNA platform targets diseases caused by nonsense mutations – Tevard’s therapeutic focus is in genetic epilepsies, cardiology, and muscular dystrophies

The RNA Leaders CXO Forum provides a unique, powerful and valuable space for the candid sharing of ideas and experience between executives of ~20 RNA Biotech private companies. This forum will include 2-3 case studies discussing the right approach to engage and partner with pharma assessing the key factors why pulling together a biotech valuation, from an investor, pharma and biotech perspective. It will also include a general discussion focused on brainstorming solutions to the collective challenges of CEO/CSO/CBOs in the sector.