Wednesday, December 31, 2014

Tekmira Enters 2015 a Different Company

Today is the last official day for Chief Technology Officer Ian MacLachlan at Tekmira.   While scientifically a great loss to Tekmira, the change marks the end of Tekmira as a technology development company and the official beginning as a commercially focused clinical product development company.  From the clinical pipeline, it is TKM-HBV, Tekmira’s gene silencing candidate for the finite treatment of HBV infection, which stands out as the most important, if not existential asset to be watched in 2015.

After generation 1, 2, 3, and now even 4 SNALP LNP, and 10, 100, 1000x fold improvements in the potency and therapeutic window, the time has come to stop telling us that ‘next time will be better’ after yet another immunostimulatory setback.  In both cases (TKM-ApoB, TKM-EBOLAold), I was willing to take the bait as the company and Dr MacLachlan explained the basis for their continued confidence with scientific authority.  For TKM-EBOLA, the plausible explanation for the immunostimulation seen in the healthy volunteer study was particle heterogeneity following resuspension of the lyophilized liposomes (note: a lyophilized formulation was used in that case because Ebola may have to be used in areas with unreliable cold chains; other SNALP LNP products are provided as 'wet' formulations).

However, with the recent initiation of phase I studies of generations 3 and 4 formulation of TKM-HBV and the departure of Dr MacLachlan, the company seems comfortable with taking their last two shots at proving that SNALP LNPs can enable potent gene knockdown in the absence of transient immune suppression at comfortable safety margins and with profiles that are competitive with the emerging conjugate platforms in RNAi and RNaseH antisense.

Although a bit under the radar for the moment, the new studies with non-lyophilized 3rd generation TKM-Ebola Guinea should be informative as to whether the lyophilization hypothesis holds water.  As these studies should likely be of shorter duration than the TKM-HBV phase I studies, the safety results from those studies should be a harbinger for the safety for at least TKM-HBVgen3, if not TKM-HBVgen4.  

The changes at the company will be welcome by some investors which might have grown tired of holding shares in a lab experiment.  On the other hand, they dampen my outlook for other liposomal delivery opportunities not only in RNAi for oncology (see today's ho-hum update on TKM-PLK1), but also in the sizzling hot fields of mRNA and CRISPR Therapeutics.

So good luck Ian and thanks for leaving the company in good order. Yours is also a great loss to the field of RNAi Therapeutics.  Hope you will come back to Nucleic Acid Therapeutics with renewed motivation.

Hello 2015

Lastly, a Happy New Year to all my readers.  2015 should be a year that will be marked by clinical RNA Therapeutics data of ever higher quality which will make it crystal clear that RNA Therapeutics has become the 3rd major drug discovery engine of the pharmaceutical industry. 

First up: Regulus end of January/February 4mg/kg RG-101 in HCV.


Anonymous said...

Dirk, I'm not really following. You said Ian is a loss for tkmr but investors are probably happy he has left. Have they lined up a replacement, sorry not really following the company as much as before.

Anonymous said...

Dirk just can't bring himself to recognize the fact: BLT/BTEBY first out of the blocks with data. Not RGLS.

Anonymous said...

RA Capital's Mr. Kolchinsky can't bring himself to recognize the fact either despite being a major shareholder in BLT even after a significant selldown.

Apparently, because of the lack of data from BLT the company is not worth mentioning in his xconomy piece. But without the data it is sufficient to put in millions of dollars of, I would assume to be, other peoples money.

Mr. Kolchinsky can't have it both ways. One doesn't get to have one's cake and eat it too.

The BLT HCV program is a factor for consideration in his game theorized future marketplace for HCV as much as RGLS' RG-101 is. Or it isn't. Because neither have sufficient data and both are trying to achieve the same thing.

Both companies have RA Capital on the registry.

So what is his motivation for recommending RGLS but not BLT? Especially after this invite.

"While these arguments stand on their own merits and represent my views, if I, as a professional investor, held such views without owning stock in these companies, readers should question my sincerity."

Mr. Kolchinsky can definitely consider the sincerity of his recommendations questioned.

Anonymous said...

Amateur hour is underway again!

Anonymous said...

Dirk, what implications would this have on RNAi cos?

Bristol-Myers, valued at $81 billion, could receive a potential bid from Pfizer valuing each Bristol-Myer share at $72, a premium of 23% to the company’s closing price of $58.89 Thursday – a day before rumors started circulating in the market about a potential acquisition.

Dirk Haussecker said...

More Big Pharma dead wood out of the way, freeing up space for innovative biotechs.

Anonymous said...

"because of the lack of data from BLT the company is not worth mentioning in his xconomy piece. But without the data it is sufficient to put in millions of dollars of, I would assume to be, other peoples money."

Moral hazard or totally duplicitous.

Not a good look either way.

If I were a BLT holder I'd be sweating. Cold.

Anonymous said...

Peter Kolchinsky has explained his reasons for not mentioning his large investment in BLT. He has explained that the stocks he discussed have efficacy data. BLT will not have efficacy data until mid year at this rate. Read the comments section.

As for BLT being amateur hour.... I think the names of the eminent scientists on BLTs scientific board and the other names behind the likes of Calimmune and Gradalis et al tell a very different story.

Anonymous said...

Previous post confirms Kolchinsky's position is one of moral hazard.

Anonymous said...

RA Capital has no cash exposure to BLT. They have a no cost free ride equity position due to the huge spike in price that allowed them to sell down to retrieve monies outlayed.

Therefore, no moral hazard exists.

Some will say its smart trading. More like insider trading. Mr Kolchinsky must've had data with which to take the position in the first place. Or else it really is a case of moral hazard. That he sold down his position on the back of an engineered price spike means he has traded on information not known to the market. That information being data from BLT's TT-034 program. Be it good or bad.

It is not sufficient to say it was an opportune trade because of the price spike if the price spike was due to washed trading. It is still trading on privileged information.

Thence, the claim of no data being the reason why he did not discuss or rate BLT in his xconomy article is bogus since he has already traded, perhaps inside traded, on this data.

A reader of the xconomy piece will be fully justified to question the sincerity of his words. An investor in BLT will quite rightly feel anxious about what is in store. And a regulator will be within his or her jurisdiction to inquire as to the legality of Mr Kolchinsky's trading in BLT.

William Joletti said...

RA Capital remain a substantial holder of Benitec.

They have not traded their shares, did not sell into the spike and could not have had inside data as there is none.

Get a life and stop your lies.

Anonymous said...

William Joletti said...

OK, yeah so he's gone from 12% to 11% on one tiny sale which was @ a ten percent gain.

Probably a single distressed holder. Your argument holds no water.

I'd like to thank you Dirk for allowing this discussion on a TKMR thread. I suppose it had to be this way... You hardly ever mention the use of ddRNAi. It's as if you don't want want to recognise it at all. Maybe this is because you can trade Benitec Gradalis or Calimmune but I thought this was a blog about RNAi therapeutics not just your short term trading blog.

Anonymous said...

Does anyone know if he is still selling?

I notice the price is still going down, could the two be related?

Anonymous said...

Who sold out to RA Capital when they went from 7% to 12%? Hope it wasn't CSIRO deserting the ship.

The implications for ddRNAi must be huge after JNJ signs up with ISIS for their antisense tech.

It leaves the lingering question, where is PFE? Or MRK and BMY for that matter.

William Joletti said...

RA deal was done in two tranches and the CSIRO have never sold one share. They have been diluted though.

Anonymous said...

Please provide the link showing that to be the fact.

William Joletti said...

Just check the annual reports and allow for the consolidation, you will see. They have been diluted from circa 10% to 2%. A quick perusal of the announcements on the Benitec website will provide the answer to your question on the two tranches of the RA deal. The second part required shareholder approval.


Anonymous said...

(That CSIRO haven't sold down)

He cannot.

They've only been diluted down to a level where they don't have to disclose selling or not despite having a stand still clause??

Nothing to worry about then if you hold BLT.

William Joletti said...

As I said, read the annual report..... Go to the last few pages and actually talk fact not fiction.

Dirk, good on you mate. Keep accumulating quietly.

Anonymous said...

Todays announcement from tinpot RNAi developer, Benitec, indicates that after fifteen years of existence they have now matured to become biology's equivalent of the Higgs-Boson hub cap chasers.

It only took them a hundred years to be proven correct.

Can expect to see some road kill on the way, i.e. shareholders.

Anonymous said...

What bollocks. There's a growing number of Benitec shareholders who are now free ride, still long, and the Company has only just started in the clinic.

Dirk, not sure why a green light to next TT-034 cohort, as well as independent papers indicating the timely identification of two more hard to treat cancer targets should evoke such negative sentiment from you. To be orderly, at least an acknowledgment of one of their now functional labs would be due first before jumping to other criticisms.

Anonymous said...

Just look at the difference between RGLS and BLT today.

RGLS heading for a market cap of nigh on a billion. BLT $100m.

Do Australians know how to spell shellacking? If they don't, they should at least know when to give up.

Anonymous said...

BLT must be one of the last presentors at JPM. Today at 4.30PM.

Them and their Australian buddy PYC both at the same time.

Can imagine how much interest will be shown when everyone is pretty much in pack up mode.

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