Wednesday, March 5, 2014

With Success, Pure-Play RNAi Therapeutics No More

As RNAi Therapeutics are charging forward towards first marketing approvals, it is time to consider how this will change the face of some of the pure-play companies involved.  Alnylam is set to become the dominant player in TTR amyloidosis, Arrowhead Research and Tekmira are vying to become just that in Hepatitis B, and Tekmira is increasingly isolating their biodefense division involving the formation of a filovirus alliance with non-RNAi modalities (prophylactic and therapeutic vaccines) as revealed yesterday.

Under normal circumstances, getting drugs approved that revolutionize the treatment of particular diseases provides great incentives to protect the resultant franchises.  Witness BiogenIdec .  BiogenIdec started out as a molecular biology pioneer and serendipitously established itself as the major player in multiple sclerosis, and is now considering all therapeutic modalities, including RNA Therapeutics, to build on that strength and further expand into neurology.  

Although it breaks my scientific heart, I do not expect that to be any different for RNAi Therapeutics companies.  HBV is a great example since an immune de-repressing RNAi Therapeutic alone is unlikely to facilitate the 100% cure rates now seen with combinatorial HCV treatments.  Instead, the addition of a direct immune-activating agent such as a TLR agonist should enhance cure rates and shorten treatment durations.  For an acute fatal infection such as Ebola, you also do not want to limit yourself to one treatment, but recruit multiple mechanisms to save an infected person, or start vaccinating populations around areas of viral outbreaks.

To extract maximal value from such disease indications, it is often best to combine the various options under one roof.  It may be partly this fear of moving away from your roots that is responsible for ISIS Pharmaceuticals giving up marketing rights early on for a few cents on the dollar worth (SMN, myotonic dystrophy, TTR).

Having said that, just like BiogenIdec with recombinant proteins and monoclonal antibodies, most of these RNAi Therapeutics companies will continue to focus their internal R&D efforts on RNAi Therapeutics.  In special cases such as Ebola and other biodefense opportunities, a spin-out may create most shareholder value without damaging the platform technology value of the parent company.


Nothing of what I just said is revolutionary.  It is, however, worth keeping in mind as the first major RNA(i) Therapeutics wave will make landfall in 2-3 years. 

6 comments:

Anonymous said...

The valuation gap between TKMR and ARWR and, in particular, DRNA seems quite strange. Is TKMRs tech really that inferior despite long history and considerable experience (and clinical/pre-clinical proof) and, in addition, the possibility of significant Ebola revenue in the next 2years...

Dirk Haussecker said...

No it's not, or course. TKMR mgmt needs to realize that in a game where cost of capital is crucial, they should not just cater to (potential) pharmaceutical collaborators, but also to the capital markets. They are a bit behind the curve here for sure. Still, I invest in the comfort of their scientific strength.

Anonymous said...

It seems that Alnylam can use its C5 drug to help activate anti viral immune system to work in synergy with the HBV drugs being developed by Tekmira and Arrowhead.

Anonymous said...

Is Benitec really going to be OK like everyone says it will be? That means Dirk is the one who has it all wrong. In which case, what are you going to do once you've been hung out to dry and the keyboard taken off of you?

Anonymous said...

What a petty and out of place comment. Why don't you wait for the science to prove itself before you say something. I doubt you'll show here to apologize and take your medicine if things don't go your way. So take the cheap shot and go home or say something on topic instead.

Anonymous said...

Agreed. What a nonsense post. And I'm a Benitec investor.

In any case Dirk's main gripe is the lack of their own lab, not with ddRNAi or their pipeline.

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.