9:00 am Registration & Morning Coffee

9:25 am Chair’s Opening Remarks

Unveiling Pre-Clinical Data in Rodent Models & Novel Strategies for Bioanalysis to Advance into the Clinic

9:30 am Extrahepatic Delivery With OligoPhore & SemaPhore, Peptide-based Nanoparticles for siRNA & mRNA Therapeutics

Synopsis

  • Noncovalent polyplexes with any RNA that are highly stable in circulation and RNAase resistant
  • Extrahepatic delivery and efficacy for siRNA and mRNA polyplexes have been demonstrated in myriad disease models in vivo, including cancer, atherosclerosis, arthritis, metabolic syndrome, and bowel disease
  • Safety profiles after serial dosing in rodent models to date have been devoid of tissue and organ toxicity, complement activation, and immunological responses to polyplex components

10:00 am A Novel Strategy for Quantitative Analysis of Ligand-conjugated siRNA in Mouse Tissues and Plasma with UHPLC-MS/MS

Synopsis

  • Overview of siRNA and oligonucleotide bioanalysis platforms and challenges
  • A novel strategy to streamline quantitative analysis of Ligand-conjugated siRNA in mouse tissues and plasma by UHPLC-MS/MS
  • New strategy applications

10:30 am Morning Break & Scientific Poster Session

Evaluating Pre-Clinical Disease Models with Improved Selectivity & Translatability for Accelerated Development

11:30 am RNAi-based Modulation of Autoimmunity in the Skin

  • Qi Tang Postdoctoral Fellow, University of Massachusetts Medical School

Synopsis

  • Improving drug selectivity through RNAi approaches
  • Preclinical evaluation of therapeutic siRNAs in a skin disease model
  • Human skin explant as a valuable tool for the development of dermatological therapeutics

12:00 pm Using Whole Human Livers to Develop RNA Therapies, for Better Translation

12:30 pm Round Table: Tackling Toxicology Studies in Animal Models

Synopsis

  • How to show knockdown in rodent species?
  • What are the best models for determining safety and efficacy?
  • Optimizing the dosing strategy to reduce toxicity while achieving a therapeutic effect
  • How can adding a targeting ligand benefit improve efficacy?
  • What chemical modifications can be made to reduce toxicity?
  • How to tackle IND-enabling studies in preclinical pharmacology and toxicology models
  • What tools are available to successfully assess PKPD?
  • What PKPD properties are optimal for the desired effect?

1:15 pm Networking Lunch

Developing Robust Processes to Enable Large Scale Manufacturing to Scale Up for the Clinic

2:15 pm Round Table Discussion: Streamlining Process Development for Accelerated R&D

Synopsis

  • How to ensure the process is nailed down to achieve desired yield and purity levels?
  • What purity levels are optimal to advance through the clinic?
  • Is it a requirement to characterize impurities before moving to phase 2?

3:00 pm Strategies for Rapid Scale-up of Diverse asiRNA Duplexes

Synopsis

  • Our asiRNA portfolio is designed to treat ocular, dermatologic, alopecia and multiple liver diseases; diverse conjugation strategy poses unique chemistry-related challenges
  • Rapid product delivery is often required to meet tight timelines for first-in-human clinical studies while developing robust production processes. Significant issues were encountered during the synthesis of lipid and GalNAc-conjugated strands
  • Phase-appropriate strategies were implemented to address the challenges associated with each program

3:30 pm Lessons Learned in Developing & Scaling Novel Platforms

  • Richard Welch Vice President - Chemistry, Manufacturing & Controls, Sirnaomics

Synopsis

  • A high-level overview of the early phase clinical development of one of our core platforms, including not only the challenges to the early phase and transfer from concept to clinic but indications about the challenges to commercialization as well
  • As part of this review will explore how the use of platform technologies can streamline development and provide savings in time and resources; they must be approached with a full understanding of their limitations as well as their benefits. This applies not only to development but to production planning, scale-up, method development, and phase-appropriate validation
  • Outlining how recent changes in the global supply chain and global regulatory and legal frameworks continue to offer challenges in translating concepts to clinical material. Examples of challenges and possible solutions include alternate suppliers to backfill supply chain shortfalls, developing multiple lines of regulatory options to deal with the constantly changing global environment

4:00 pm Chair’s Closing Remarks

4:15 pm End of 4th Annual RNAi-Based Therapeutics Summit