7:50 am Check In & Light Breakfast
8:50 am Chair’s Opening Remarks
Successfully Targeting Extra-Hepatic Tissues with Novel RNAi Therapeutic Payloads to Expand the RNAi Treatment Paradigm
9:00 am Targeting Tumor-Associated Immune Cells with RNAi-Lipid Conjugates
Synopsis
- Refractory malignant solid tumors create an immunosuppressive TME which renders them resistant to standard-of-care immune checkpoint inhibitors
- How RNAi agents can silence CD274 (PD-L1) in tumor-associated immune cells, which mediate immune suppression in the TME
- Silencing Cd274 in antigen presenting cells remodeled the TME, increased cytotoxic T-cell infiltration and mediated single agent activity in immunotherapy resistant preclinical tumors. Human active PDL1 RNAi is in currently in Phase 1 clinical trials for immunotherapy-refractory cancers (NCT06504368)
NEW DATA
9:30 am Novel siRNA Platform for Cellular-Driven Tissue Repair & Regeneration
Synopsis
- Fidgetin-like 2 in cell migration
- Fidgetin-like 2 as a target for tissue repair
- Localized siRNA delivery for the treatment of traumatic injury
UNPUBLISHED DATA
10:00 am Receptor Mediated Targeted Delivery to Proximal Tubules in Kidney
Synopsis
- Complexity of the kidney as a tissue and the challenges of targeting kidney
- Our work with ligands for specific targeting in kidney cell types
- Insights into receptor biology and uptake of conjugated oligos
10:30 am Morning Break & Speed Networking
Synopsis
This is your opportunity to get face to face with some of the biggest names in RNAi therapeutics to connect and establish meaningful industry relationships.
Reaching Previously Undruggable Tissues through Identification of Tissue-Specific Cell Receptors to Expand the Therapeutic Potential of RNAi
11:30 am Applying Hydrophobically Conjugated siRNAs to the Treatment of Muscular Diseases
Synopsis
- A combinatorial treatment strategy for reducing heterotopic bone in a mouse model of Fibrodysplasia Ossificans Progressiva (FOP)
- Identification of a SNP-targeting siRNA against the mutant ACVR1 receptor implicated in FOP
- Systemic delivery of hydrophobic siRNAs to the muscle
UNPUBLISHED DATA
12:00 pm A Novel Platform to Discover Targeting Proteins for siRNA Delivery into Immune Cells
Synopsis
- Development of new protein libraries with expanded diversity to select ideal targeting proteins for extra-hepatic siRNA delivery
- Targeting proteins from new libraries using transferrin receptor specific binders that enabled siRNA delivery and gene knockdown in skeletal muscle
- In vitro and in vivo validation of novel immune cell specific -siRNA conjugates
NEW DATA
12:30 pm Delivery of siRNA to the Placenta for the Treatment of Preeclampsia
Synopsis
- Identification of sFLT1, a potential therapeutic target for the treatment of preeclampsia
- Optimization of conjugates for placental uptake
- Developing chemical technology for the silencing of placental sFLT1
1:00 pm Lunch & Networking
Integrating Novel Chemical Modifications to Enhance the Stability, Potency & Delivery of RNAi Therapies for Improved Therapeutic Intervention
2:00 pm Living in the World of RNA Therapeutics made possible by Novel Chemical Modifications
Synopsis
• Talk Details To Be Confirmed
2:30 pm Amide-Modified RNA: Using Protein Backbone to Improve Specificity of siRNAs
Synopsis
- Amides are excellent mimics of phosphate linkages in RNA and are well tolerated in the guide strand of siRNAs
- Amide modification at the 5’-end (position 1) of the passenger strand suppresses its undesired off-target activity
- Amide modification in the seed region of the guide strand suppresses undesired microRNA-like off-target activity
UNPUBLISHED DATA
3:00 pm Development of Novel Chemical Modification Strategies for miRNA and siRNA Based Cancer Therapeutics
Synopsis
- Novel chemical modifications to enhance stability of miRNA and siRNA
- How specific chemical modifications can reduce and eliminate the requirement of delivery vehicle for delivering RNAi therapies
- How to improve therapeutic efficacy using innovative chemical modifications
NEW DATA
3:30 pm Round Table Discussion: How Can We Design Better RNAi Payloads? Enhancing Stability & Maximizing Precision Targeting of RNAi Therapies through Chemical Modifications
Synopsis
- How can alternative siRNA structures alter therapeutic delivery, efficacy and stability
- How to employ nucleoside modifications to ligands to influence therapeutic stability
- What innovative biochemical strategies are providing scope to improve RNAi therapies
4:00 pm Afternoon Break & Poster Session
Synopsis
This is your opportunity to share your ground-breaking data and innovative delivery strategies with your fellow RNAi experts.
Employing AI & Computational Modelling to Design Tolerable RNAi Therapies to Target Specific Tissues for Improved Patient Health Outcome
4:30 pm Using Generative AI to Design Novel Synthetic RNAi Molecules
Synopsis
- How AI can support rational drug design
- Reviewing legacy Tallas AI models and approaches
- Projections for AI in drug discovery
NEW DATA
5:00 pm Deep Learning-based Design of Cell-targeting Ligands Enables Cellspecific, Functional siRNA Delivery in Multiple Extra-hepatic Tissues
Synopsis
- Receptor-mediated endocytosis drives cell tropism across RNA modalities
- Deep learning-based design of ligands targeting endocytosing receptors enables rapid in vivo testing of receptors for their capacity to mediate functional siRNA delivery
- This platform – Connexa – has led to the discovery of multiple receptors capable of mediating in vivo functional siRNA delivery in extrahepatic tissues
UNPUBLISHED DATA
5:30 pm AI Design of Targeted Ligands for Extra-hepatic siRNA Delivery
Synopsis
- How AI and other computational tools can help design peptides for tissue specific delivery of siRNA
- How peptide based delivery systems can allow better access to extra-hepatic tissues such as Kidney and CNS
- Preclinical data to support the use of these novel delivery systems