Wednesday, September 26, 2012

Alnylam’s Imminent PCSK9 Partnership Deal

A lot of the business development and corporate communications strategy that the 17 VPs at Alnylam come up with these days is, you guessed correctly, directed at building investor confidence so that it may survive the Trade Secret case with Tekmira.  So also the planted interview by John Maraganore a few weeks ago in which he suggested that a PCSK9 deal (ALN-PCS) may be imminent.

Needless to say, without having resolved the important questions about ownership and control over SNALP delivery, chances for a real deal are pretty slim.  Instead, expect a VSP-type deal with minimal upfront, and where the press release will state that development efforts will be focused on the subcutaneous GalNAc conjugates at the expense of (Tekmira’s) SNALP delivery.  

It would, of course, be extremely convenient to announce such a deal just in time for trial, as Alnylam will be able to look the jurors in the eye and state that TTR, PCS, and hemophilia are all now employing a non-Tekmira technology.   A minimal upfront would have the further advantage of depriving cash-strapped Tekmira financial ammunition for the litigation.

Of course, no IND has been filed for any of these yet and, most importantly, clinical validation has not been established leaving a big question mark behind the value (and safety) of GalNAc-conjugates.  I’m wondering what type of messaging the 4-person PR team will come up with to explain, after things have calmed down, that they are still favoring the SNALP-delivered versions.

Note: To put (the estimated) 17 VPs and 4 PR employees in context, Alnylam had 115 employees after the latest lay-offs earlier this year.


Anonymous said...

You should disclose your financial interests in this kind of posts.

Dirk Haussecker said...

Maybe the analysts showing their support of Alnylam should do so. I've been pretty open with my long position in Tekmira. In any case, this is just speculation, but sometimes my reading between the lines (e.g. in the PR messaging) has proved me right.

Giles said...

On a bigger picture Dirk do you see the general RNAi and MiRnai space beginning to really pick up?Will it last?I do think on a personal note you should reduce yuor tekmira/Alnylam diatribes.The blog has lost alot of its quality since you seemed to get into a personal vendetta.Theres a world of exciting RNAi out there and all you seem to go on about is Tekmira.Its a small canadian comapny thye may or may not particpate in the wave and they will rely on people wnating immuno-suppressed delievery.

Dirk Haussecker said...

6 of the industry's 8 clinical, systemically delivered programs have been based on Tekmira's technology, and while there is transient immune suppression now, the scientific development has not stopped. Why do you think that e.g. Silence Therapeutics stock went up?

These are facts. When new data presents, I will also pay attention to other technologies (e.g. more information at AtuPLEX and endothelial cell targeting), but right now, this is where the music is. It is also about the bigger question of how small and large companies can co-exist in this industry.

Anonymous said...

"Its a small canadian comapny"

better it be a small US company,
& lest it be a small Australian company???

nothing like objectivity to pick your best stocks

Anonymous said...

"6 of the industry's 8 clinical, systemically delivered programs have been based on Tekmira's technology"

Is not this statement a little exaggerated? If one considers that ddrnai is more akin to gene therapy and there have been/are ~3000 clinical trials for gene therapy and most of these use a viral vector for delivery (as can ddRNAi) then the importance of Tekmira is somewhat diminished.

I am not saying it is not important but, as other comments say, it is not the only RNAi game in town.

Anonymous said...

"this is where the music is"

I guess it depends on what music you're listening to. Gradalis' patients are listening to 'alive and kicking' thanks to the bi-shRNA FANG vaccine. Sorry Dirk, but your bias seems to be preventing you from looking at things clearly. It's results that matter at the end of the day and if shRNA rather than siRNA continues kicking the goals, Tekmira is dust.

Dirk Haussecker said...

Did you read the Gradalis clinical trial paper? Changing the CRO and then getting the desired knockdown results? Nothing in there instills confidence that they are conducting a scientifically rigorous development program.

Anonymous said...

Wow Dirk, big kick in the teeth to the research organisation that have conducted more than 300 FDA clinical trials and the company with the most phase II clinical trails using RNAi in the world. It's probably not worth burning too many bridges in this job market.

Anonymous said...

"Nothing in there instills confidence that they are conducting a scientifically rigorous development program."

Now that the FDA has complete control over clinical trials and increased reporting is going to be policed, won't it be up to the FDA to determine what is "scientifically rigorous"? So far, I have not heard that they are questioning the Gradalis approach.

Anonymous said...

I believe in time all these RNAI companies will have their day in the sun. No one company will dominate as each delivery technology will find some space where it is best suited for a particular indication that was previously undruggable. With so many targets don't you think these companies will try to avoid areas where there is direct competition? They will try to find theor own niche where others are not playing.

Anonymous said...

Is GalNAc the delivery system developed by Roche and transferred to Arrowhead Research? I understand that Alnylam signed a deal with Arrowhead for rights to some delivery technology.

Dirk Haussecker said...

No, while some of Arrowhead's delivery technology involves targeting the same receptor, Alnylam's version has not been a collaboration with Arrowhead's as far as I understand.

Anonymous said...

I certainly agree " in time all these RNAI companies will have their day in the sun". Tekmira's delivery system is not the only game in town. Highly publicized scientific data (somewhat hastely, in my opinion) from well known studies (by Dirk's standard) such as high expression liver toxicity, off-target effects, etc. all turn out to be managable. On the other hand, those studies pushed the industry back for many years. We now know those highly publicized issues are not as sound as it appeared, all RNAi companies will have their day in sun.

Anonymous said...

Merck's drug Tredaptive for raising HDL, like its Pfizer and Roche predecessors, has raised safety issues and been suspended in Europe. However, Reuters reports that Merck CEO Ken Frazier said the U.S. drugmaker would continue to press ahead with clinical research on HDL raising, even though the scientific case so far remained inconclusive.

Does this mean that Merck are going to confirm a clinical trial of their AAV8 LCAT treatment that they announced at last years ASGCT along with their AAV8-shPCSK9 treatment for lowering LDL?

Seems like a real possibility as the Reuters report referred to Merck's on-going research in this area.

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