Breakfast Roundtable Discussions

TABLE 1: Adoption and Implementation of Innovative Technologies Used in Discovery and Delivery

Marvin Caruthers, PhD, Distinguished Professor, University of Colorado

TABLE 2: Considerations When Developing Splice Modulating Therapies

Moderator: Annemieke Aartsma-Rus, PhD, Professor of Translational Genetics, Leiden University Medical Center

• Developing splice modulating therapies for small patient numbers
• Selecting model systems and controls for pre-clinical exon skipping tests
• Deciding when to move from pre-clinical to clinical studies
• Involve patients in therapy development and trial design

TABLE 3: Oligonucleotide Drug Discovery: From the Drawing Board to the Clinic

Moderator: Troels Koch, PhD, CTO, SVP Science & Technology, IneXos Therapeutics

Drug discovery is an exceptionally complex undertaking. What is of paramount importance is that the initial steps in the process are conducted as well-informed and qualified as possible. We will discuss drug discovery fundamentals and try to identify how an “ideal” program would look like. Discussion points:
• Delivery - target – modality triangulation: Where to begin, any preference?
• In vitro and in vivo assays: Toxicity and potency validation – Establish the right controls and secure high degree of translation
• How to make the best selection of target and indication to favor oligonucleotide therapeutics in relation to competing modalities?
• Advancing in silico discovery: Going beyond sequence based bioinformatics with structure based quantum mechanical modelling?

TABLE 4: Examining the Safety and Toxicity of Nucleic Acid Therapeutics

Moderator: Steven Kates, PhD, VP, Regulatory Affairs, Dicerna Pharmaceuticals

• What tox studies are needed and when?
• How to assess your impurities (analytical methods)
• Discussing mutagenicity
• Examining ADA assays

TABLE 5: Adoption and Implementation of Innovative Technologies Used in CMC And Manufacturing

Moderator: Roumen Radinov, PhD, Director Process Chemistry, Alnylam Pharmaceuticals

• The solid phase oligonucleotide synthesis based on sequential coupling of phosphoramidite monomers is a well-established industrial manufacturing process
• Currently performed routinely on kilo scale mainly due to limitations of the current synthesis and purification processes
• Novel approaches will need to be designed and developed to support high-volume oligonucleotide drugs in the near future
• Participants are invited to share their insights and experience in the development of alternative synthesis and purification technologies with potential for the cost-effective ton scale manufacture of oligonucleotides

TABLE 6: CMC Regulatory Hurdles in Rare Disease

Moderator: Kimberly Tyndall, Principle, CMC Tyndall Consultant

• How to successfully proceed
• Never a marketed product N=1
• Overcoming CMC hurdles
• Why