Sunday, July 20, 2014

Fed-Induced Sell-Off Offers Attractive Values in RNA Therapeutics

For whatever reason, Janet Yellen does not like cheerful biotech investors and between her first policy speech as new chairwoman of the Fed in April and comments last week decrying biotech and social media stocks as inflated she caused two major sell-offs in RNA Therapeutics stocks.  As a result, industry bellwethers ISIS Pharmaceuticals and Alnylam are trading at less than half their 52-week highs, though better than ‘second-tier’ RNA Therapeutics companies such as Tekmira and Arrowhead Research which are trading down even more than that.

When the technology has matured to the point that it can bring significant value to patients, pipelines rapidly progress and expand, and with companies flush in cash by historical standards, this sell-off offers in my opinion great risk:rewards.  Here is a run-down of my five favorite plays.

1.       $ISIS. ISIS Pharmaceuticals is my current RNA Therapeutics core holding that I would not want to be out of.  With ligand-targeted technologies offering much lower tissue exposures and therefore much better safety margins, multiple mechanisms of actions and a pipeline that rivals any in the industry, this company is on track to become the most valuable in the industry- if not economy (subject to the vagaries of the healthcare policy directions). 

At a $3B market cap, no foreseeable financing needs, and a healthy newsflow (especially regarding partnerships), the downside should be relatively limited, and I will sleep tight even knowing that Yellen (who seems to confuse the Dow and large cap biotechs with the broad biotech industry) might open her mouth again to talk about something she obviously understands very little about.

Best long-term risk/reward.

2.       $TKMR. Tekmira is the most beaten-up stock of the bunch that gets credit for almost nothing.  This is mainly the result of the Ebola trial results which were a disappointment- little doubt about that.  However, translating these results from the unthankful ‘Haertetest’ to the rest of the pipeline is unwarranted.  This is because a highly most potent knockdown technology for the liver, should be able to carve out some market for itself.  And if the HBV product won’t require transient immune suppression and/or if its use is deemed acceptable in HBV with its expected finite treatment period, there is an enormous opportunity for which the favorable newsflow is only about to heat up with the presentation of the preclinical dataset..

It is the newsflow from new product candidates (esp. HBV)), clinical trial starts (liver cancer, HBV, alcohol dependency), clinical trial results (ALN-TTR02 OLE, TKM-PLK1 interim phase II with little to no expectations by the markets), and business development (mRNA), that makes TKMR an attractive buy at these severely depressed levels ($31 in April, now trading at $9).  And with the Ebola Haertetest on Clinical Hold, TKM-EBOLA does not scare me anymore as an investor.  It even offers a potential near-term catalyst should the Hold be lifted.

Best 6-12 month risk/reward (until release of phase IIa HBV knockdown results).

3.       $RGLS.  I’ve never liked Regulus much as a stock, mainly because of its anemic pipeline that its own management does not even seem to be excited about given that it now calls the potent GalNAc-targeted anti-miR122 product candidate for HCV merely a proof-of-concept for the company.  However, given that the HCV market emerges as one with a long-tail, not all is lost for this pan-genotypic, potentially one or two-shot treatment when used in conjunction with other HCV drugs. 

When HCV-competitor Achillion recently surged on the back of the Merck takeout of HCV play Idenix as it reminded investors of the long-tail nature of the market, Regulus was forgotten.  It may reach investors’ consciousness when they report phase I results possibly early next year.  Solid financials with more than $100M in cash and a reasonable $300M market cap given its prominent position in the microRNA Therapeutics industry.

Speculative buy with regard to single catalyst.

4.       $ARWR. All eyes are on the outcome of the ARC520 phase IIa study in HBV-infected patients which could be announced any day now.  My prediction is a ~80% HBsAg knockdown at the 2mg/kg dose.  My problem is that I have little idea about how the market will respond to that given that the trial is not designed to achieve the ultimate goal for this therapeutic candidate: a functional cure.

Most investors seem to expect an easy double (or more) from current levels, an notion that I do not want to necessarily reject for an 80% knockdown.  It all seems to depend on how the results will be framed by the analysts and how successful the dueling hedge funds are in painting the tape to their advantage. 

With more than 10% of the float short and given ARWR's historical trading pattern, great volatility is a given.

Highly speculative buy, so much so that options may actually be the best way to play it.

5.       $SRPT. No matter the negative market reception to the recent release of the 144-week study results, Sarepta and patients will get their accelerated approval for eteplirsen.  The debate has reached a point that the drug development clock for Duchenne Muscular Dystrophy cannot be set back another 5-10 years by rejecting the current class of candidates of which Sarepta’s looks to be the most promising- despite the highly anecdotal nature of the results.  This is because eteplirsen seems amazingly safe, so the potential harm from giving a potentially non-effective medicine is limited.  This is clearly not the case for Prosensa’s exon skipping drug candidate, and don’t even get me started about PTC Therapeutics …

Solid 12-month risk:reward juiced by the large short position (>30%).


Anonymous said...

What! No Benitec. Can't you recognize a steal when you see one? lol.

How about Silence?

Anonymous said...

Benitec may have opened a lab, but
now there must be another reason not to value them.

Anonymous said...

Have you got an address for service on that lab?

It's like BLT itself. Best kept secret on the stock market.

Anonymous said...

Any thoughts on what could happen to TKMR if ARWR HBV data isn't too impressive? Are both outcomes likely to be positive for TKMR since the delivery tech is different?

Latebloomer said...

ALT data for ARWR's 2A is an important wild card (not much downside b/c billed as bonus, but a lot of upside if some consistent positive results - across several patients - shows up). But I don't know if that data will be included with the topline results or not.

It would take a few more weeks (beyond the time when key HBsAg data would be ready), and they may wish to report sooner than later, and/or they may wish to isolate the HBsAg data in a report of its own, regardless of what the ALT data shows; perhaps - if there's something to talk about - coming out with ALT data 3 weeks or so later; or waiting to include it with the more formal fall presentations.

So there may (or may not) be TWO, rather than ONE, key reports from ARWR regarding Phase 2A.


Anonymous said...

Well Dirk, TT-034/AAV8 getting into the liver!

Get with the program old mate.

Anonymous said...

Alibaba IPO been delayed til end of summer from late August. Read it as markets to remain closed until then.
Might explain the need for two reports as per prior post.

Anonymous said...

Sorry. Should've said late July.

Anonymous said...

i think for arrowhead this phase 2 just as big of a de-risking event as phase 1 was. if arrowhead can prove they have a certain efficacy in humans the market knows they can increase dose to achieve necessary KD but what the market doesn't know yet is, if it even works on humans. just proving that will have considerable value, aren't there multiple phase 2b scheduled to get "cocktail" right? just my two cents. thanks dirk . big fan.

Anonymous said...

Alibaba IPO been delayed til end of summer from late August. Read it as markets to remain closed until then.

Alibaba got bumped outta the way by BBB (big blue n beautiful).

Why else would Dirk be making his recommendations. Gotta make himself look good, see.

As for the BLT sycophants, guess they can't see a cheap buyout until it smacks them in face.

Anonymous said...

You mentioned Sarepta and being the best of the three DMD candidates-do you not think Summit in the UK has an interesting candidate progressing well,very safe,some efficacy already but with delivery issues?

Anonymous said...

"Have you got an address for service on that lab?

It's like BLT itself. Best kept secret on the stock market. "

San Francisco. It's not a secret. Company has already announced it and was in Genome Web article.

"As for the BLT sycophants, guess they can't see a cheap buyout until it smacks them in face."

No adverse reaction in first systemic dose for ddRNAi, and shRNA turning up where it was designed to, via the magic of the DNA construct doing it's natural thing.

The sycophants are only saying Benitec's TT-034 trial, and ddRNAi as a whole, may be better than what the experts with the vested interests &/or good mates in competing companies don't want to let the market know.

As for your cheap buyout prediction, with benitec's IP if that was going to happen it would have happened when they were $15M market cap. But if you do have some reasoning behind your bold claim don't be afraid to share so we can follow along.

Anonymous said...

Dirk Is The Stupidest Guy

by investron • 3 minutes 58 seconds ago

I've ever known worth commenting on.

Usually stupid people are not worth a comment.

Here's the exception because so many appear to follow the pied piper.

Dirk keeps talking about KD percentage and implying that TKMR will do better.

Dork is apparently the only one who does not see the irony of ARWR's pumping 2mg/kg into people with no ill effects...

ARWR's Ph 1 passed with flying colors and Ph 2a is apparently concluding without getting halted.

This is now the only game in town for a long, long time!

. .

Lock Him Up And Throw Away The Key

by investron • 20 minutes ago

He's Baaaaacccckkkk!!!

by investron

Dear Leader is back to pumping TKMR hoping for preclincals to lift the stock.

Trouble is, I don't think preclinicals will cut it for TKMR anymore.

Not after a Ph 1 blow up.

The trouble with Dirk is the guy shifts like quick sand trapping all who follow.

How many times did he pump and sell out this stock, I'm losing count?

Just two weeks ago he was posting TKMR wasn't it anymore.

Now pumping to unload for a quick profit while again trying to minimize ARWR about to report on Ph 2.

TKMR should lock up his funds indefinitely.

Anonymous said...

In all seriousness Dirk, how come no Rxi?

Am looking at Tufulipo's post on IV where he provides the following link on masking agents for delivery. Though he has it under ARWR it is what Rxi does as well. If it is the billion dollar difference, why aren't you on it?

Anonymous said...

Perhaps Dirk could head to San Francisco and seek some tutelage from David Suhy. Seems he has a much broader understanding of the mechanism and application of RNAi. Benitec were right to turn down Dirks offer of employment years ago, such a one-eyed 'analyst' would go nowhere.

Anonymous said...

Anonymous @ I would like to invite you to write about Benitec on
If you intrested, Just send a comment

Terry Chrisomalis said...

Wanna see a write up on Benitec Biopharma check out my SA article then " Benitec: An Undiscovered Biotechnology With A Twist"

Also some nice reading on RXII as well

"Why I’m Still Long Rxi Pharmaceuticals After Recent Developments"

Anonymous said...

Dirk, you've done a great job of analysis over the years. First you were attacked by ISIS followers, now some of the competitor's followers are attacking you. To be attacked by such a wide range of people and interests, must mean you're doing something right.

Anonymous said...

The Art Krieg decision should color your SRPT view somewhat I imagine.

I don't know if it is a good thing or a bad thing.

Attacked by ISIS followers. What a crock. He was running them in to the ground then and now he is singing their praises. On other words, he was wrong and they were right. But he would've known that then and we can now see it as yet another attempt to influence the market through his blog.

I think the influence bit is well overrated by a over inflated sense of worth, an out of control ego and a huge desire to ingratiate himself with those he perceives to be higher up on the totem pole all in the pursuit of riches.

Anonymous said...

World Hepatitis Day on Monday. Would be a goodly day to say something if you have something worthwhile to say about hepatitis. No matter what the strain...or company.

Anonymous said...

Dirk, Any thoughts on the BCRX ebola drug and how it compares to TKMR's? Thanks.

Anonymous said...

Dirk, did you ever hear that story about the wife of Citi's boss or something being so loose lipped that they lost control of foundation ssRNAi IP and the deep genome sequencing software?

I don't know if it's true or urban myth. That's why I'm asking.

Probably a Ripleys.

Anonymous said...

FDA and Consumer Welfare | Robert Higgs

Published on Jul 23, 2014

Archived from the live broadcast, this Mises University lecture was presented at the Mises Institute in Auburn, Alabama, on 23 July 2014.

Anonymous said...

Stop Squabbling, Mom Tells Troubled Biotech: 'Just Get My Kid the Drug'

Imagine for a harrowing moment that your child has a debilitating, deadly disease for which there’s no cure. A biotech company has a drug that might arrest your child’s decline, maybe keep him out of a wheelchair, possibly add years or decades to his life. It would be tough—no, unbearable—to watch infighting at the company impede access to the medication.
“It’s heartbreaking,” Mindy Leffler told me by phone over the weekend. Her son Aidan, 11, has Duchenne muscular dystrophy (DMD), an inherited muscle-wasting disease that afflicts 1 in 3,500 boys born in the U.S. DMD robs its victims of the ability to walk in early adolescence. Pulmonary or other complications typically kill sufferers in their twenties.
Leffler was reacting to a regulatory filing and related news reports about the firing of a key executive at Sarepta Therapeutics (SRPT), a biotech company in Cambridge, Mass. Sarepta is seeking Food and Drug Administration approval for a DMD treatment that could keep Aidan on his feet and extend his life. On Thursday, Sarepta disclosed that it had fired its chief scientific officer, Arthur Krieg. The company didn’t explain the move.

Anonymous said...

Stop Squabbling ...

Same article continues ...

While Krieg was a senior figure at Sarepta, he wasn’t centrally involved in the eteplirsen program or dealings with the FDA, according to former colleagues. He focused on more basic research. Corporate reshuffling isn’t pleasant, but in the big scheme of things, it’s not as important as whether a life-extending drug gets to people who need it. Krieg’s departure may eliminate a source of distraction and allow the company to move beyond a period of infighting, one longtime Sarepta investor told me.

Anonymous said...

did you ever hear that story about the wife of Citi's boss or something being so loose lipped that they lost control of foundation ssRNAi IP and the deep genome sequencing software?

Totally true story I think. I know something happened on this website.

If you can believe the, sometimes too tall to be real, stories she posts under the name Capitalist and someone else called Enumerate was in the middle of it all.

It was years ago and probably all been deleted now.

Anonymous said...

Recent RXII movement validates the question posed below especially since you hold a patent in this area with Dr. Kay.

Suspect silence on this one.

In all seriousness Dirk, how come no Rxi?

maria said...

Want to sell your stuff online? Check this out!!!
Sell your stuff here

By Dirk Haussecker. All rights reserved.

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