Wednesday, October 10, 2012

The Regulus IPO: A Reason to Invest in MicroRNA Therapeutics

Many of you will already have seen it: With little fanfare, Regulus Therapeutics (ticker: RGLS) is now a publicly traded company.  Rather than re-hashing the financials of the IPO and whether the first (depending on whether you count Rosetta Genomics in) public exit was good for the microRNA Therapeutics sector or not, I want to remind readers of one key selling point of the technology, one that I believe explains why Regulus has been so successful in  generating partnership revenues from the likes of Sanofi-Aventis, GSK, and AstraZeneca: microRNAs are a major class of genes and their products can only be targeted by oligonucleotide approaches.

Big Pharma companies are a conservative bunch and small molecules habits die hard.  While the industry has embraced monoclonal antibodies with all their benefits, but also warts, oligonucleotide therapeutics are still considered outcasts in the industry.  Maybe a therapeutic area group in Big Pharma will take a look at it when nothing else seems to work (hello respiratory disease groups).   While this could change given therapeutic (and vaccine) oligonucleotide candidates in TTR amyloidosis (Alnylam and ISIS/GSK), HBV (Dynavax), and hypercholesterolemia (mipomersen/ISIS) and the excitement around the exon-skipping drug candidates from Prosensa and Sarepta, the precise timing of a lasting turnaround in sentiment would probably depend on whether and when sales of any of these potential products really take off.  Money does not smell to Big Pharma either.  But until then, it's likely to continue being a roller-coaster ride.

Despite falling in the oligonucleotide therapeutics category and despite being younger and technically less validated, microRNA Therapeutics have an important marketing advantage over RNAi and RNaseH antisense.  Unlike RNAi and RNaseH which often have to hide in the ‘undruggable’ space, i.e. in addition to the desperate research groups they may be considered by Big Pharma if small molecules and monoclonal antibodies cannot address a biologically attractive target, microRNA Therapeutics do not stand in such direct competition.  Biologically too important to ignore and implicated in many diseases, oligonucleotides, at least for the foreseeable future, are what it takes to tap this critical group of genes.  

Because of that, I expect industry interest (= partnership $$$) in microRNA Therapeutics, and as a leading company in that area, in Regulus Therapeutics, to be less volatile than what has been the case for its two older siblings.  Having a strong balance sheet, should also help in that regard.  So welcome, Little Emperor, to the public markets.


Anonymous said...

So does the rise of microRNA therapeutics help Silence Therapeutics, Marina Biotech and Tekmira the most? Are lipid delivery systems ideal for microRNA mimics and inhibitors?

Dirk Haussecker said...

For the delivery of microRNA mimics, and some inhibitors, additional delivery technologies will be used, and yes, RNAi Co.s may capitalize on that. Of course, depends on cell type being targeted.

Jerry said...

I hope you would be willing to expound on your belief that oligonucleotide microRNA mimetics have a potential niche that is different (?broader) than the targets so far selected by the likes of ALNY and TKM.
"Despite falling in the oligonucleotide therapeutics category and despite being younger and technically less validated, microRNA Therapeutics have an important marketing advantage over RNAi and RNaseH antisense."
Could you describe in more detail what types of targets are more suitable for these microRNA mimics?

Jerry said...

Also, are there any theoretical reasons that some particular type of delivery methodology would be best suited for the Regulus pipeline? For instance, do you see any relative advantage for Tekmira, Alnylam, or Arrowhead in this regard----or does Regulus have its own angle on delivery?

Dirk Haussecker said...

The targets...totally depends on the specific disease, but: microRNAs are involved in many diseases (that makes them targets in the first place) AND they regulate biology in new ways (that raises possibility that microRNA Rx can provide new treatment approaches, esp. for some of the more complex diseases). Consequently, Big Pharma can ill afford to ignore them.

Regulus mostly does microRNA inhibition using single-stranded phosphorothioated oligonucleotides without much additional delivery. Delivery techs initially especially for the microRNA mimic approaches. One disadvantage of the Arrowhead DPC approach for microRNA mimic delivery is that they need to accommodate extensive stabilization chemistries. Especially with Tekmira's SNALPs, this is not required.

By Dirk Haussecker. All rights reserved.

Disclaimer: This blog is not intended for distribution to or use by any person or entity who is a citizen or resident of, or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would subject the author or any of his collaborators and contributors to any registration or licensing requirement within such jurisdiction. This blog expresses only my opinions, they may be flawed and are for entertainment purposes only. Opinions expressed are a direct result of information which may or may not be accurate, and I do not assume any responsibility for material errors or to provide updates should circumstances change. Opinions expressed in this blog may have been disseminated before to others. This blog should not be taken as investment, legal or tax advice. The investments referred to herein may not be suitable for you. Investments particularly in the field of RNAi Therapeutics and biotechnology carry a high risk of total loss. You, the reader must make your own investment decisions in consultation with your professional advisors in light of your specific circumstances. I reserve the right to buy, sell, or short any security including those that may or may not be discussed on my blog.