Day One

• How to optimize screening approaches to rapidly evaluate large libraries of LNP compositions and identify candidates with enhanced extrahepatic tropism?
• What screening approaches are most effective for selecting and testing targeting moieties to ensure high specificity, manufacturability, and reproducible performance after LNP conjugation?
• How can AI/ML and predictive models be integrated into experimental screening workflows to improve lipid and ligand selection?

• We develop a new high-throughput screening strategy that can screen LNP libraries and accurately predict delivery in vivo directly from tissue sequencing
• Our strategy can screen LNPs in organs that traditional screening methods are impractical, such as the heart, kidneys, and brain
• We use our strategy to screen a new class of lipids to identify LNPs with extrahepatic tropisms and low reactogenicity

This session is your opportunity to get face-to-face with many of the brightest minds working on extrahepatic delivery, and establish meaningful business and scientific relationships to pursue for the rest of the conference

• Introduce a SHARP platform that enables efficient nucleic acid delivery without multicomponent formulation complexity
• Demonstrate programmable organ tropism achieved through molecular-level control of amphiphilic structure, enabling selective delivery to organs such as liver, lung, spleen, and the lymphatic system etc
• Highlight the translational potential and future directions of this platform for organ-selective nucleic acid therapeutics across diverse disease indications

• Will discuss how helper phospholipid identity is a tunable parameter that can enhance LNP functionality. Beyond structural stabilization, helper lipid selection can dictate LNP behavior with fusogenic phospholipids
• Phospholipid composition is a mechanistic handle for SORT targeting to deliver outside of the liver. Various strategies will be discussed to help facilitate extrahepatic delivery
• Phospholipids are essential components across a full spectrum of modern vaccine platforms, including liposomal adjuvant systems, cationic emulsions, and lipoplexes

• Redefining the LNP Core (The “Active Fusion Core”): Introducing the Hyper-15™ Active Fusion LNP. Liver Detargeting & Safety: The technology reduces reliance on toxic cationic lipids. This not only improves the safety profile but effectively allows the payload to bypass the liver, addressing a key challenge in the current therapeutic landscape.
• Bypassing the “Acidification Trap”: While standard LNPs lose >98% of cargo to endosomal degradation, Hyper-15™ completely bypasses the endocytic pathway. By forcing active, instantaneous fusion at the plasma membrane surface, we demonstrate the ability to achieve 100% cytosolic bioavailability of genetic payloads without requiring pH-dependent acidification or receptor upregulation
• Unlocking “Endocytically Quiet” Tissue: Presenting breakthrough efficacy data in Human Skeletal Muscle Myotubes and Adipocytes. We show how this mechanical fusion mechanism successfully transfects mature, non-dividing tissues that are impenetrable to standard LNPs, overcoming the industry’s longest-standing delivery bottleneck in metabolic and neuromuscular disease

• Overview of Stylus’ in vivo gene editing system and therapeutic potential
• Key insights on optimizing process conditions to enhance mRNA and DNA LNP formulation quality and consistency
• Advances in lipid formulation design that improve extrahepatic biodistribution and drive efficient T-cell delivery in vivo

• LNPs conjugated with targeting ligands are emerging as the preferred system for delivery of RNA therapeutics to specific cell types
• Quantifying ligand concentrations in LNPs is notoriously difficult and time consuming with current analytical methods
• Scatter free absorbance (SFA) offers a new rapid, precise and reagent-free method to directly quantify targeting ligand concentrations via UV detection 
• This talk will introduce SFA and demonstrate it's capability to characterise ligand and RNA concentrations simultaneously in targeted LNPs

• What are the remaining barriers for achieving efficient, organ-specific delivery to difficult targets?
• Which design strategies and technologies are most promising for enabling precise extrahepatic targeting while minimizing liver accumulation?
• What unmet therapeutic needs could next-generation extrahepatic LNPs address to expand the RNA, gene editing, and cell therapy landscape?

• Mirai’s modular targeted particle design enables rapid development of immune and blood cell targeted LNPs 
• Base LNP development vi ML-based in vivo active learning dramatically reduces liver uptake 
• Modular addition of targeting moieties to our base LNPs supports targeting of many hematopoietic cell types
• T cell targeted LNPs have been rapidly advanced to NHP studies with CAR cargo showing B cell depletion and high tolerability

• Defining the design space: composition and component variations and their impacts in LNP delivery
• Defining the funnel: Formulation and in vitro considerations
• Automation assistance: Increasing throughput while maintaining particle and data quality

As extrahepatic targeting for LNP-mediated therapeutics continue to progress from strength to strength, it is more important than ever to collaborate and learn with your peers. Join this dedicated session to share your latest data and have the first look on what your peers are working on!

• Nanoparticle design: Principles & practice
• Case study: Unlocking the payload – LNPs for next-generation immune cell engineering

• RNA-based therapy that controls the cGAS-STING pathway in vivo
• cGAS-STING pathway activation in T-cells to create an intracellular factory of apoptosis-inducing signals
• Delivery of mRNA to activated T-cells mediated by targeting moieties on LNPs