Investor Appetite for Expanding the Nucleic Acid Therapeutics Tool Box

The last few days saw two more eye-catching examples of investors daring to dream big by committing significant early-stage capital to building new Nucleic Acid Therapeutics platforms. 

First, start-up mRNA Therapeutics company Moderna Therapeutics took advantage of the hype it was able to create in the wake of a deal earlier this year with AstraZeneca which involved $240M in upfront monies alone to raise another chunky $110M in a private round.  This brings the total raised by Moderna to over $400M in the last 2 years or so.  Then on Monday of Thanksgiving week, a consortium of VCscommitted up to $43M to start up Editas Medicine, a company built around genome editing harnessing the recently identified CRISPR adaptive immune system in bacteria.

Counting in IPOs and private rounds by nucleic acid therapeutics companies (e.g. Bluebird Bio in gene therapy, Prosensa in exon skipping), well over half a billion raised by RNAi Therapeutics companies in 2013, partnership monies earned by ISIS etc, we are talking here probably about approx. $1.5B raised by the industry so far this year.  And what is best about this in my opinion is that these fund raisings were not intended to help with commercializing a newly approved product or running a large phase III trial for a late-stage clinical candidate- no, they were mainly the result of broader interests in the platforms.

What a departure from the post-2008 world of biotech and oligonucleotide therapeutics when pipelines were commonly regarded as a financial liability and the platform concept was the ultimate biotech heresy belonging to the 2000 genomics bubble era.

If you like to see the glass half empty and secretly hope that the world is coming to an end soon (e.g. in the form of a stock market collapse), good luck to you!   While I expect some volatility as the industry moves towards bringing meaningful drugs onto the market and cash flow positivity (just witness the recent Prosensa and Sarepta stumbles) , looking at the nucleic acid therapeutics pipelines and a healthcare environment friendly towards targeted therapies that are the sweet spot of nucleic acid therapeutics, it is hard to come up with scenarios in which this nucleic acid therapeutics revolution can still be halted.  Moreover, the strong cash balances of some companies mean a virtuous cycle of value creation for companies like Arrowhead Research which are capital constraint, not technology constraint, and should also allow them and their investors to weather short-term volatility.

Having said that, the time for some healthy pruning will ultimately come, likely in the wake of the next major upheaval in the normal economic cycle, and I expect some investors to throw in the towel even before some of these technologies have had the time to prove themselves.  You think that making delivery work for RNAi Therapeutics strained some investor patience, then what about getting a protein, RNA, and DNA into the nuclei of target cells all at the right amount and time for the correction of single-gene disorders as appears to be the first therapeutic frontier of Editas?

   

But until then, the fact that investors dare to dream of medical breakthroughs again means that the future of biotechnology which lives off such bold concepts remains bright.   Nucleic acid therapeutics will play a critical part in that future.

Marina Biotech as a bet on the oligonucleotide therapeutics tool box

As the economy improves and interest rates remain low, I expect money continue to move into the higher risk end of the market.  In terms of the stock market this generally means that while the 'safe' companies were the first to recover following the collapse of the housing bubble, the more innovative and 'risky' groups such as social media and biotech followed with even larger returns.

Thinking of the oligonucleotide therapeutics space, the ultimate high-risk play that has yet to respond to the improved market conditions is Marina Bio.  In hindsight, the two main reasons for Marina Bio's spectacular share price erosion were (1) that it promulgated the idea of an oligonucleotide therapeutics supermarket concept when nobody wanted to hear of it, and (2) that it did so after it had lost its credibility in the markets after many broken promises (largely under previous leadership) and then tried to re-define itself by the year.

Most would consider it dead now, but with a number of licenses to companies like Novartis, Monsanto, and Tekmira, two products in the clinic that utilize its SMARTICLE delivery technology (one for a microRNA Rx mimic by Mirna Therapeutics, one for an DNAi Therapeutic by ProNAi) and an in-house clinical candidate for an orphan indication (transkingdom RNAi for FAP cancer) in a suspended (for financial reasons) phase I study that one ought to be able to revive, it should have more inherent value than the $3-4M current market cap suggests.   In addition, it retains access to usiRNAi triggers and high-affinity antisense chemistry for RNaseH gene knockdown and steric blocking applications that I see on par with the technologies by ISIS Pharmaceuticals, Santaris, and Regulus.

As appetite for all things oligonucleotide therapeutics grows, this could be an interesting play.