Conference Day One

8:00 am
Registration & Morning Networking Coffee

9:05 am Chair’s Opening Remarks

Exploring Novel Technologies & Approaches for Targeted & Effective siRNA Delivery

9:15 am Developing the Next Generation of siRNA Chemical Scaffolds for Extrahepatic Delivery

  • Julia Alterman Assistant Professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School

Synopsis

  • Conjugation strategies for tissue and cell type enhanced delivery of oligonucleotides
  • Novel architectures and branching provide unique accumulation and delivery profiles
  • siRNA backbone and sugar modification enhance potency, specificity, and duration of effect

9:45 am Panel Discussion – Delivery Carriers for Efficient siRNA Therapies

  • Tamar Grossman Global Head of RNA & Targeted Therapeutics, The Janssen Pharmaceutical Companies of Johnson & Johnson
  • Robert Shaffer Founder & COO, Vrata Therapeutics
  • Ioanna Mylonaki Head of Preclinical R&D, Sixfold Bioscience
  • Iris Grossman Chief Strategy Officer, Eleven Therapeutics

Synopsis

With the development of new carrier technologies for delivery of siRNA therapeutics, there is a greater need to understand better formulation and mechanistic strategies to enhance efficacy and reduce toxicity. From design to development, we will delve deeper into techniques beyond GalNac for effective siRNA therapeutic delivery

  • How to design novel carriers to reduce toxicity and improve extra-hepatic targetin
  • How to make an effective carrier for RNAi molecules to minimize off-target effects
  • What is the future of RNAi carriers 2.0 to improve safety and mode of delivery?

10:30 am
Morning Break & Stuctured Networking

11:30 am Lipid Conjugation for siRNA Extrahepatic Delivery

Synopsis

  • Exploring lipid conjugation for enhancing siRNA delivery beyond liver
  • Discussing the impact of lipid structure on siRNA distribution and efficacy
  • Outlining lipid conjugates for muscle siRNA delivery

12:00 pm Emerging Strategies to Target Extrahepatic Tissues with RNAi-Based Therapeutics

Synopsis

  • Overview of RNAi delivery problem/challenges
  • Overview of antibody-based approaches to overcome those challenges, pros over CPPs
  • Rationale and progress to date for using 3E10 antibody to deliver RNAi

12:30 pm
Networking Lunch

Track A

Track B

Developing Next Generation of RNAi Drugs with Better Stability and Efficacy

1:30 pm Unexpected Benefits of Replacing Phosphorothioates with Achiral Phosphordithioates for siRNA End Stabilization

Synopsis

  • Phosphordithioates (PS2s) were investigated as they could simplify oligonucleotide purification by replacing the undefined stereo centres introduced in phosphorothioate (PS) couplings
  • A single PS2 provides a similar strand stability as two PS
  • In vivo, PS2 linkages appears to introduce a longer duration of action than PS-containing siRNA with the same sequence

2:00 pm Creating a New Class of Receptor-Targeting Genetic Medicine

Synopsis

  • Centyrins are alternative scaffold proteins with properties ideal for targeted oligonucleotide delivery
  • Centyrins enable RNA delivery at a particular cellular “address”
  • Centyrins, targeting CD71 receptor, result in robust and selective gene knockdown in skeletal muscles

Unlocking Disease Specific Applications of siRNABased Therapeutics

1:30 pm siRNA Therapeutics to Treat Oncology Indications

Synopsis

  • Delivery of siRNAs that can treat oncology indications
  • Discuss the benefit of delivering 2 siRNA
  • Demonstrate the efficacy in vitro and in vivo of novel constructs

2:00 pm Novel siRNA-Based Therapies for Cancer

Synopsis

  • Development and proof-of-concept studies validating the potential of siRNA for tumor targeting
  • Application of a novel RNAi-based checkpoint inhibitor for the treatment of pancreatic cancer
  • Potential of RNAi-based cancer therapy: A longer-term look at the future of RNAi for the treatment of cancer

2:30 pm
Afternoon Networking Break

Track A

Track B

Scaling The Challenges of Chemistry, Analytical Development & CMC for the Clinical Success of siRNA-Based Therapeutics

3:30 pm CMC Considerations for siRNA Drug Substance Manufacturing

  • Jeske Smink Head of Drug Substance, Silence Therapeutics

Synopsis

  • Quality considerations for conjugates and linkers
  • Challenges of solid-phase synthesis of siRNA’s
  • Impurity profiling of siRNA drug substance

4:00 pm Challenges & Process Innovations in Early to Late-Stage Clinical Trials of siRNA Drug Substance Process Development & Manufacturing

Synopsis

  • Selection of raw materials for single and double strand siRNA for phase wise development
  • To present and discuss new trends and innovations in siRNA drug substance manufacturing
  • Conjugation chemistry and techniques

4:30 pm Analytical Approaches for Pharmacokinetics of siRNA & its Application in Ocular Studies

  • Ying Yu Associate Director, AbbVie

Synopsis

  • Analytical approaches for Pharmacokinetics of siRNA
  • High sensitivity and specificity RT-qPCR method for siRNA detection
  •  Application of RT-qPCR method for siRNA detection in rat eyes
  • Correlation between PK /PD of siRNA in rat eyes

5:00 pm Chair’s Closing Remarks

Advancing Disease Specific Applications of siRNA-Based Therapeutics for the Liver & Beyond

3:30 pm siRNA-Based Prevention of Cardiovascular Disease – Digital Presentation

  • Ulf Landmesser Medical Director , Charite - Universitatsmedizin Berlin

Synopsis

  • Cardiovascular disease remains the most frequent cause of death in developed countries. The main underlying disease is atherosclerotic cardiovascular disease
  • In recent years causal genes for development and progression of atherosclerosis could be identified
  • These genes are now targeted using siRNA-based therapeutics to prevent and treat atherosclerotic cardiovascular diseases

4:00 pm DegradaBALL-siRNA Complex (LEM-S401) for Effective Local Administration to Treat Skin Fibrosis

  • Dal-Hee Min CTO & Co-Founder & Professor, Seoul National University, Lemonex Inc.

Synopsis

  • New concept of DDS, DegradaBALL, was employed for siRNA therapeutics against skin fibrosis (LEM-S401)
  • Local injection of LEM-S401 showed highly effective and sustainable knockdown efficiency at the injection site
  • Local injection of the DegradaBALL-RNA complex would be well-suited for extrahepatic delivery by minimizing liver accumulation

4:30 pm MCJ siRNA: A Novel Metabolic Regulator for Treating Acute & Chronic Liver Diseases

Synopsis

  • Identified MCJ/DNAJC15, a novel negative regulator of mitochondrial metabolism, which is highly expressed in liver, kidney and heart
  • Knockdown is effective in treating acute and chronic liver diseases, including acute drug-induced injury, NAFLD/NASH, cholestatic liver disease and liver fibrosis
  • Designed novel siRNA drug candidates and appropriate delivery technologies to target liver, and also kidney and heart as additional disease indications

5:00 pm Chair’s Closing Remarks