Interview with Keynote Presenter:
Arthur M. Krieg, M.D.
President and Chief Executive Officer, RaNA Therapeutics, Inc.

Thank you to Art Krieg, M.D. for taking the time to answer these questions. Dr. Krieg will be presenting a keynote on "Therapeutic Oligonucleotide Development: A Promising Outlook" on Monday, May 21, 2012 at TIDES in Las Vegas, NV.

Why have some of the major Big Pharmas changed their approaches to oligo research?

Some pharmas are responding to declining revenues by cutting R&D spending, especially on relatively early, relatively “unvalidated” platforms. Since only 2 oligo drugs have been approved, the platform is considered less validated than MAb, and so is far more likely to be cut from the budget for internal R&D. yes clearly the appetite for oligo drugs remains, and may even be whetted – witness Pfizer’s recent acquisition of Excaliard for their exciting antisense program to CTGF: positive human clinical data is advancing the field, and can provide investment returns for innovative programs. I believe that the decision by some pharma to drop internal oligo development, and to effectively outsource much of their early discovery, creates a great opportunity for biotechs to step in and create value.

What have been some of the most promising research results in the past few years?

In antisense applications the development of short gapmers using constrained sugars has provided a 5-10 fold improvement in potency over the 2nd generation designs. Splice alteration applications have made a huge leap forward with the positive in vivo data in boys with Duchenne muscular dystrophy, and this has also given the morpholino modification a higher profile, together with that chemistries outstanding safety characteristics. In RNAi we have seen strong in vivo data in humans that eliminates any doubt that this platform won’t be safe or effective in vivo. Finally, the microRNA (miR) applications for oligo drugs have advanced on multiple fronts, with Santaris’s positive human data in HCV with miR 122 antagomir, the Miragen collaboration with Servier to pursue exciting mouse data in the CV space, and the exciting data from Mirna showing that miR delivery is also a therapeutic option.

Why do you think the outlook is so positive for this field?

The diversity of therapeutic approaches that can be developed with oligo drugs is incredible! In addition to antisense and RNAi, human clinical trials have shown efficacy in oligo applications as aptamers, immune stimulators (CpG), splice alteration, and antagonizing miR.

What are you most looking forward to hearing from other TIDES speakers?

I find TIDES to be a great meeting for finding out how other companies are solving many of the practical challenges in oligo drug development, from CMC and regulatory issues to sharing exciting new preclinical findings. As important as finding out what’s working is learning from the inevitable mistakes and setbacks along the way, which otherwise can be difficult to access.