RNAi Therapeutics Companies

There are a few dozen companies now, small and large alike, that have started developing drugs based on RNAi. While most of them are in the pre-clinical stages, in 2004 Acuity Pharmaceuticals (soon to be known as Opko) was the first to start phase I trials for age-related macular degeneration (AMD). Since then 5 more programs have entered the clinic: 2 additional ones for AMD (Sirna Therapeutics, acquired by Merck in 2006 for the handsome sum of $1.1 billion; and Quark Biotech), and one each in RSV (Alnylam Pharmaceuticals), diabetic macular edema (Acuity), and acute kidney injury (Quark Biotech).

Due to reasons discussed in the previous post, almost all of these programs are Direct RNAi programs, i.e. the siRNA is administered close to the diseased site. All except for Acuity's program are also with siRNAs that have been chemically modified (to enhance stability etc), and it remains to be seen whether Acuity's strategy to plunge into the clinic first was a wise one. Sirna Therapeutics soon followed suit, but I think took the right decision to invest time to carefully think about how to position their potential product in the more and more crowded AMD market. Sirna Therapeutics was also the first public company based on RNAi. Formerly known as Ribozyme Pharmaceuticals, they leveraged their experience with RNAs to build an operation that had all the tools to to build a decent IP portfolio and quickly enter the clinic. This IP portfolio is mostly based on chemistry and targeting many genes one by one such that it could claim exclusivity for targeting those genes with RNAi. It remains to be seen, however, how this brute force approach will hold up in the patent courts. Also, ISIS pharmaceuticals may contest some of their chemistry claims. However, the strategy has paid off extremely well at least for those that engineered it with Merck's takeover of the company last year for about 50x the price it had been valued before it committed to RNAi. SR Pharma, known as of today as "Silence Therapeutics", of the UK, looks as if it was seting itself up for a similar sale with an almost 8-fold price appreciation since last year.

The brightest star in the sky of RNAi Therapeutics by far, however, is Alnylam Pharmaceuticals. This is the company whose scientific founders were seminal in the development of RNAi and microRNAs, particularly in humans. Consequently, the company sits on an unparalled exclusive IP portfolio that gives them freedom to operate and pursue highly lucrative deals with Big Pharma and Biotech. These deals should help it through the development phase and have brought in already well over $100M. All this is managed by a seasoned team, led by CEO John Maraganore, that has considerable experience in developing succesful biotech companies (many of them hail from Biogen). It is also the company mentioned by the Karolinska Institute in their explanation for the 2006 Nobel Prize Award to Fire and Mello, as having demonstrated the therapeutic potential of RNAi through ground-breaking studies. These studies represent important de-risking events that continue to attract academic and indrustrial collaborators and important investments, including the RNAi Therapeutics field as a whole.

Other notable companies involved in RNAi Therapeutics include Benitec, a pure-play Australian company that uses DNA-based RNAi vectors to tackle a range of viral diseases, Nastech Pharmaceuticals (not a pure-play; focuses on siRNA delivery and Dicer-substrate technology), and large pharmaceuticals such as Merck, Novartis, GSK, and Pfizer, and probably many more knocking on the doors of Alnylam and co.