Attending the Oligonucleotide Therapeutics
Society meeting last week in Boston, I could sense a new bullishness around RNAi Therapeutics like I haven’t
in a long time.
Big Pharma: Tipping
the Scales in Favor of RNAi Therapeutics
Over the last year, we have been witness to the clinical successes of
Tekmira’s SNALP delivery that literally saved the sector. After nightmarish years, these results had investors enjoy the doubling and tripling of the share prices of companies
like Alnylam, Tekmira, and even non-SNALP players such as Silence Therapeutics.
For the next leg of expanding investments in RNAi
Therapeutics, a renewed, publicly visible commitment by Big Pharma would be important. With Genzyme taking a license to Alnylam’s
transthyretin amyloidosis program, a first step in that direction has been just made. On the platform side, it is worth noting that the two most significant Big Pharma players in RNAi Therapeutics, Merck and
Novartis, were also represented at the conference. One can only hope that the current RNAi
Therapeutics clinical and scientific tailwind will give their internal
champions the ammunition to push the technology into the clinic in the next 2-3
years and therefore escape the Sword of Damocles that surely must have been felt dangling
above them.
Unfortunately, if these two companies, like so many others
it seems, big and small, insist on using ‘their’ own delivery technologies, chances
for that will be much reduced. With all
due respect, but the presentation on RNAi delivery by Merck was just a review
of the most advanced systemic delivery technologies, SNALP (Tekmira), DPCs
(Arrowhead Research), and GalNAcs (Alnylam) exemplified by Merck’s homebrew
versions. Somebody needs to show me the
math behind it- I just don’t get it. The
only explanation for me is pride and the resistance against collaborating after
having invested internally so much.
A re-commitment towards RNAi Therapeutics should also be at
the expense of ‘naked’ RNaseH antisense.
Although in his keynote speech, Alnylam’s CEO made a point of congratulating ISIS CEO Stan
Crooke (sitting in the first row) on the recent mipomersen Advisory Panel, there was considerable talk during the conference about antisense-related toxicity, also as regards the high-affinity
versions. And even Stan Crooke could not
help but admit that the RNAi Therapeutics results have ‘exceeded [his] expectations’. However, since ISIS
claims ownership over RNAi Therapeutics, as it does indeed over most of oligonucleotide therapeutics anyway, his pain should be limited if indeed he believes what he is saying [note: Dr. Crooke in discussing the safety of mipomersen went as far as saying that there has been no imbalance in its safety profile compared to placebo, and when there was an imbalance, it was in favor of mipomersen...for a starkly different view, see here].
A Breath of Fresh Air
in Delivery
A conference highlight were the new results from Arrowhead Research on their new DPC delivery, a conjugate approach. Potent gene knockdowns in the liver with an
apparently reassuring safety profile in non-human primates using subcutaneous
delivery is certainly deserving of some serious attention. Having had systemic delivery of synthetic
RNAi triggers almost for themselves for the last few years, Tekmira seems to be
finally getting some company- although in terms of validation, SNALP is still years ahead and more de-risked. Such
increased diversity of approaches should also be good for attracting general interest to the sector as it
would be viewed as more vibrant and with more disease opportunities.
5 Reasons to be Bullish on RNAi Therapeutics
1)
Clinical results show that RNAi Therapeutics in
Man can be made to work (Tekmira’s SNALP delivery);
2)
RNAi Therapeutics ideally suited to address
orphan disease, the hottest category in drug development;
3)
RNAi Therapeutics has taken the lead over RNaseH
antisense for gene knockdown;
4)
Big Pharma coming back to RNAi Therapeutics;
A Side Note on the
Conference
