7:50 am Check In & Light Breakfast
8:50 am Chair’s Opening Remarks
Safeguarding Purity & Quality of Interfering RNA During Large Scale Manufacturing to Enable Sustainable Production of RNAi Therapies
9:00 am Centyrin-siRNA Conjugates: CMC development path to Clinic
Synopsis
- Platform manufacturing considerations for Centyrin-siRNA conjugates
- CMC development challenges for protein-oligonucleotide conjugates
- Analytical control strategy considerations and product stability
NEW DATA
9:30 am Innovation in therapeutic-oligonucleotide manufacturing to sustainably meet future demand
Synopsis
- Pursuing a zero-waste strategy that meets Sustainable Development Goals (SDG) in oligonucleotide manufacturing
- Designing and building the future plant: achieving BREEAM certification
- Case study: purification resin substitution
9:40 am Roundtable Discussion: Streamlining CMC & Maintaining Purity During Scale Up of RNAi Payloads & Delivery Systems to Streamline RNAi Therapeutic Production & Maximize Clinical Success
Synopsis
- Employing analytical methods to measure toxicity and purity of manufactured RNA
- Increasing efficiency during manufacturing and scale up
- How different delivery platforms require differing CMC considerations
10:10 am Morning Break & Networking
RNAi Therapies in the Clinic: Clinical Data on Innovative Delivery Strategies & Lessons on Maximizing Success of Early-Stage RNAi Assets & Platforms
11:00 am Clinical Experience with a First-in-Class ASO Against miR-10b for the Treatment of Metastatic Cancer
Synopsis
- In early discovery efforts, miRNA-10b was identified as a master regulator of the viability of metastatic tumor cells and we developed a therapeutic strategy based on miR-10b inhibition
- The specific inhibition of miR-10b was achieved using ASOs delivered to metastatic sites by TransCode’s proprietary delivery system (termed TTX-MC138).
- On the path to clinical development of TTX-MC138, we received FDA authorization for a now completed Phase 0 and an ongoing Phase 1 clinical trial in patients with advanced metastatic cancer
NEW DATA
11:30 am Enhanced Delivery Oligonucleotide (EDO) – A Novel Peptide Delivery Platform for Superior Oligonucleotide Delivery
Synopsis
- EDOs are designed to enhance delivery of oligonucleotide therapeutics to muscle and other target tissues
- EDOs show higher uptake to muscle nuclei and corresponds with increased pharmacological activity in multiple preclinical models
- EDO platform has enabled initiation of 2 clinical programs, including a Phase 2 (CONNECT1-EDO51) study to investigate the effects of PGN-EDO51 in people with DMD amendable to exon 51 skipping and a Phase 1 (FREEDOM-DM1) study to investigate the effects of PGN-EDODM1 in people with DM1
NEW DATA
12:00 pm Interactive Session: Attracting Investment & Securing Preclinical Funding for Early-Stage RNAi Therapeutic Candidates & Platforms
Synopsis
- How to build a successful network and establish a functioning start up to attract investment
- How to successfully gain funding for preclinical candidates and platform based companies
- What are the hurdles and pitfalls to starting an RNAi therapeutics company and what are the timelines and levels of investment required
12:45 pm Lunch & Networking
Advancing Cutting-Edge RNAi Therapeutic Delivery Systems to with Increased Selectivity & Durability to Enable Targeting of Hard-To-Drug Tissues
1:45 pm Unlocking the Full Potential of RNAi with LEADTM (Ligand and Enhancer Assisted Delivery)
Synopsis
- Ligand-mediated conjugate is often insufficient for extrahepatic delivery. Adding an enhancer addresses delivery inefficiencies including PK, receptor binding, internalization, or intracellular trafficking
- Sanegene’s innovative Ligand and Enhancer Assisted Delivery (LEAD™) technology has demonstrated robust siRNA delivery and potent gene knockdown across multiple extrahepatic tissues and cells, including muscle, adipose, macrophages, CNS/PNS, and ocular
- Leveraging LEAD™ technology to develop treatments for obesity and metabolic disorders by targeting the liver, muscle, and adipose tissues. LEAD™ technology demonstrates robust gene knockdown, weight loss, and improved body composition in combination with GLP-1RA or siRNA monotherapy
NEW DATA
2:15 pm Engineering Antibody Oligonucleotide Conjugates (AOCs): Preclinical, Clinical Progress and Lessons Learned
Synopsis
- Discussing antibody oligonucleotide conjugates and exploring how AOCs can help solve oligo delivery challenges
- Developing cellular and animal models with relevant disease readouts to demonstrate target engagement;
- AOC development candidate selection and clinical progress
2:45 pm A Ligand-targeted Calcium-phosphate Drug Delivery System for Cancer
Synopsis
- Alternatives to traditional RNAi delivery approaches are needed for cancer targets
- ARIZ’s 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 earliest changes in cancerization of the cell
- Proof of concept with our ligand targeted calcium-phosphate siRNA-conjugate delivery platform broadly solves delivery issues beyond liver cells with specificity for cancer cells.
3:15 pm Afternoon Break & Networking
Overcoming Toxicity & Safeguarding Tissue Specificity with Innovative, Precise Delivery Platforms to Develop Tolerable, Efficacious RNAi Therapies
3:45 pm Improving Targeted Endosomal Escape through Sapreme’s Endosomal Escape Enhancer Platform for More Potent & Durable Therapeutics
Synopsis
- Showcasing developable and conjugatable compounds to improve delivery of different RNA payloads through improved endosomal escape
- Showcasing preclinical proof of concept for enhancing endosomal escape through this unique enhancer platform for more potent therapeutics
- Examples how to conjugate this enhancer platform to targeting ligands for extra hepatic delivery
NEW DATA
4:45 pm Targeted Extra-Hepatic Delivery of Custom Oligonucleotide-Peptide Conjugates for Enhanced Tumor Bioavailability, Efficacy, & Safety in a Breast Cancer Model
Synopsis
- How to design antisense oligonucleotide shortmers with custom RNA amidites for optimal efficacy and reduced off-target effects
- How to enhance tumor uptake and minimize liver accumulation of oligonucleotides via peptide ligand conjugation
- How to design tissue-specific peptide ligands for RNAi therapeutics using AI/ML-driven approach
UNPUBLISHED DATA