Monday, November 7, 2011

RNAi Therapeutics Investors Hoping for a Merry Christmas

I’ve just come back from working at the Starbucks across my street which strongly reminded me that Christmas was just around the corner. Christmas this year in RNAi Therapeutics is synonymous with data releases by Alnylam from its transthyretin amyloidosis (ALN-TTR01; data presentation November 20-22 in Japan) and hypercholesterolemia (ALN-PCS02; release of top-line results by year-end) phase I clinical trials. These have the potential to demonstrate, for the first time, direct and physiologically meaningful target gene knockdown following systemic RNAi delivery, and thereby have the potential to turn around still negative RNAi Therapeutics sentiments and depressed valuations.

Some of the anticipation can already be felt in the form of appreciating share prices of Alnylam and Silence Therapeutics, together with Tekmira the companies most directly exposed to the current RNAi Therapeutics dataflow, and the financial analyst-investment community which have turned noticeably bullish on Alnylam. Only Tekmira, the inventor of SNALP technology that powers ALN-TTR01, ALN-PCS02 and 5 other candidates in or close to clinical development, has not participated in the rally by failing to find investors willing to defend its stock after taking on well-connected Alnylam.

In assessing the data, a primary focus will be on whether dose escalation was able to proceedeup to the highest planned doses (1.0mg/kg for ALN-TTR01 and 0.25mg/kg for ALN-PCS02) and whether, despite the small number of patients at the high dose levels, there are clear signs for target gene knockdown. 50% target gene knockdown in both cases would be reasonable goals, and probably also necessary ones to have the desired impact. In the case of ALN-PCS02 there should also be at least a 30% reduction in ‘bad’ LDL-cholesterol, the intended pharmacologic outcome of a PCSK9-targeting agent. In terms of safety, the absence of grade 3 adverse events or worse would be highly welcome, of course, as we would be the absence of consistent and clinically meaningful innate immune activations.


Santaris’ anti-miR122 HCV Drug Continues to Impress

MicroRNA Therapeutics seems to have found its poster child already with Santaris’ miR122 LNA antagonist for the treatment of HCV. In an oral presentation at The Liver Meeting which is just wrapping up in San Francisco, the company reported robust dose-dependent anti-HCV activity in a phase IIa study, with close to a 3-log mean reduction of HCV RNA from baseline and viral load below detection in 4 of 9 patients at the highest dose of miravirsen (7mg/kg). The corresponding abstract marking a milestone in microRNA Therapeutics by reporting first clinical activity of an microRNA Therapeutic was released in early October (click here for commentary). There is no doubt that this drug candidate works as expected/hoped for, and unless the future of HCV treatment is in all-oral combos, anti-miR122 with its uniquely differentiated mechanism of action looks like a valuable addition to the fast-moving field of HCV care.

20 comments:

tettrazini said...

"MicroRNA Therapeutics seems to have found its poster child already with Santaris’ miR122 LNA antagonist for the treatment of HCV"

Poster child with a paternity law suit.

Anonymous said...

I thought with your qualifications you could get a better job than working at Starbucks!

Anonymous said...

HaHaHaHa!!! That's exactly what I thought when I read it too. I nearly choked on my cornflakes. Not that there's anything wrong with working at Starbucks. So many Phd's working there now, I hear it has become a job requirement.

Anonymous said...

When Benitec's fortunes go tearing straight past Alny in
the not so distant future, now that the ddRNAi patents are all secured in the U.S, Europe and Asia, we'll gladly have Dirk on board the management team. Coffee, Aussie dollar remuneration & Qantas flights thrown in as a bonus.

Anonymous said...

I just went to work at the Starbucks next door on my paper, with a cup of latte I like most. This does not mean that I am working to make a living at the starbuck. Do I mean to let you know I am a staff working for the starbuck? Come on, guys, even if you are working at the starbuck with 2 phds, it does not mean that there is anything to be irrespectful for a guy to make a living at the starbuck or a way of life that he/she enjoys? Respect others for others to respect you.

Anonymous said...

Yea, Dirk is actually pretty crafty with words than we give him credit for. Puts us in the holiday mood and gave him a sense that many out there still cares on what he writes.

Anonymous said...

Benitec will be bankrupt in less than 18 months. Its all talk talk talk with those guys, they have yet to deliver anything of value.Just take a look @ there share price, you guys need to wake up and smell the coffee.

Anonymous said...

Right. Just looked up Benitec stock information (0 and 0 trade). I guess they are surviving on licensing income? Dangerous. Wonder what is their burn rate, might be sooner than 18 months without a major financing deal. With limited financing, they probably could not do much product development either. Catch-22.

Anonymous said...

0 & 0 trade cause aus stock exchanged was closed. It opens during US night time.. Collab struck last week with a London group for orphan disease (MD) - they are particularly impressed with Benitec's IP. Benitec mtg with Chinese group this week re: taking a chronic pain therapeutic into clinic.

Anonymous said...

If you are actually prepared to look outside the box for a second, and look at what Benitec have got, instead of just writing them off, you may be very surprised. ShRNA has much greater efficiency, without the delivery problems. Sure, Benitec live from year to year with whatever funding they can get, but all RNAi companies save Alnylam are the same. Benitec have very loyal shareholders that will make sure they are still around in 18 months. Excellent animal studies using expressed RNAi are coming out thick and fast, so in effect, Benitec have thousands of scientists proving up their technology at no cost to them every day. The Chinese love ddRNAi and Benitec are there as we speak with all their 'talk, talk, talk' looking to shore up a deal involving some of that $300 billion they have to spend on biotech. To say they are yet to produce anything of value is a bit rich when siRNA has had billions invested and has little to show for it. To date, shRNA has proven to lasts 4 years and counting in an animal model, still expressing the target gene and still no toxic side effects. How long is it for siRNA?

Anonymous said...

Good that Benitec has loyal followings. 16 M market cap is certainly not that far off from Silence's 26.7 M, perhaps one clinical trial can be started to show where the money is to the rest of the world. We still have not seen or heard anything yet. I don't know if Benitec have that much of exclusivity on ddRNAi. To say there is no delivery problem may be a bit naive. Anything hanging around animal for four years will certainly scare many regulatory agencies, I bet even Chinese government will have issue with. Tons of animal data without entering into clinical trial smells like trouble. Hope Benitec has more to show than just a few loyal followers. As a public company they should follow Arrowhead's suit, be open so investors can have more confidence.

Anonymous said...

I don't really see why ddRNAi should be subject to greater regulatory hurdles than vaccines. They both stimulate the body's immune system to recognise foreign agents, destroy them, and prevent future invaders for life. They just do it in different ways. The fact that Benitec's pain therapeutic will be used on end stage cancer patients only, at least initially, should make regulators happy, even in China. Sounds just like the stringent regulation required for any other drug in clinical trials to me. I'm not sure why the mere mention of Benitec on this blog creates such scoff when it is clearly giving siRNA a run for its money. Or perhaps that is the reason. Benitec will be in clinical trials next year, while the rest of them will still be trying to develop an effective delivery system.

Anonymous said...

What has been missed as Benitec don't run such a big pr as Alny is ddrnai is already into the clinic. Gradalis are now recruiting for their PII clinical trial against melanoma using shRNA in a vaccine. That if commercialized in US is via a licence from Benitec. Expressed RNAi is via nucleus which is Benitec's Graham patent. Benitec mnmgt very busy at present - pr and sp not their priority

Anonymous said...

Also the Rossi/City of Hope trial achieved proof of concept w ddRNAi in haemopoetic stem cell transplantation into humans with HIV with persistence for over 2 years and no safety issues. No therapeutic effect but it was designed as proof of concept/safety only.

Anonymous said...

And Calimmune starting their ddRNAi HIV trial next year. Them boys going for the cure on Berlin patient proof of concept.

Rossi in aus next week with Benitec's chief investigators group meeting. If he likes ddrnai so do I.

Anonymous said...

Benitec believers, honestly how much can a
Chinese university afford. They will come back with nothing but an. Mou.

Anonymous said...

The money would be coming from the Chinese gov. Read this carefully.
http://www.nature.com/nbt/journal/v29/n9/full/nbt0911-779b.html

Dirk Haussecker said...

Thanks for the article. As you know, the change is already happening all around us. It won't stop at RNAi Therapeutics, and indeed has not. The knowledge-based economy is also moving more and more to the East and this should also benefit Western RNAi companies with innovative technologies to sell, especially with the paralysis elsewhere.

Anonymous said...

It's interesting to take note: look up recent rnai research on PubMed and have a look at the origin of the papers, I would say fully 50% are from China in recent times.

Anonymous said...

Rossi said today, of the CoH HIV work, one patient now with modified gene cell markers for 3years, with 6 fold increase in the number of
modified stem cells. He's described the result as spectacular and opens the door for a cure.

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