Tuesday, April 7, 2015

Time is running out for Benitec

Benitec announced today that almost 1 ½ years after filing an IND for its DNA-directed RNAi HCV candidate, it has now obtained liver biopsy data from first 3 of the 4 patients dosed so far.  Needless to say, the analysis was a resounding success confirming that the right AAV vector coding for the shRNAs against HCV was administered to the trial subjects.

Given that no details were provided on the methods, I assume that the evidence is based on PCR analysis which pretty much picks up almost any activity.

TT-034 also shined on safety with ‘no treatment-related serious adverse effects (SAEs) in any of the four patients dosed’.

To wit, the motivation behind the gene therapy ddRNAi HCV trial is to provide a one-shot cure from HCV infection.  The company, however, said that ‘the amount of shRNA produced will not result in reduction of hepatitis C viral load’.  

So while this statement almost makes it sound like they did not look for antiviral efficacy, but that there might well have been, we can safely assume that they did (standard blood test to look for HCV; plus RNA analysis from biopsies) and failed to see such.  

It is also curious that no results from PCR-based target mRNA cleavage assays were disclosed which, while still PCR, requires a certain amount of RNAi robustness to detect with confidence and would have been used to further tout trial success. 

At this point, Benitec has almost completed the first 2 of 5 planned dose cohorts.  According to my notes, the top dose is about 25x higher than dose group 2.  To get from no change in viral titer to undetectable while increasing dose by 25x seems quite optimistic to me.  And even if this highly unlikely scenario materialized, at this pace, it will be sometime in 2023-4 when it would even be considered for approval.

So please, Benitec, if you cannot see a knockdown at the next higher dose cohort, give it a rest.   



31 comments:

Anonymous said...

So the assumption is that if there is a viral knockdown in the next cohort you are going to pay the premium and BUY BUY BUY?

Dirk Haussecker said...

Which reminds me of getting fooled by the CEO of RXi Pharmaceuticals when they proclaimed knockdown without giving numbers. Turned out something like 15% knockdown (i.e. 85% remaining) and I'm not sure how they could even measure that. It lost me money.

Anonymous said...

What the hell are RA Capital in on BLT for?

Koch in sky must've had the wool pulled over his eyes.

Anonymous said...

A blogger on SA pumps BLT regularly. After the GALE debacle anyone or any company associated with that site deserves close scrutiny.

Can't understand why he doesn't come here and debate the issue of BLT and it's attributes.

Anonymous said...

Dirk/Dick, You are making us mad.
BLT will rock very soon you will see, end of this year it will be $100/S.

Anonymous said...

I'm not really sure what it is that you expect Dirk. This is still technically in phase I, so why would anyone be expecting to hear about efficacy? Why not wait until cohort III (the beginning of Phase IIa) is at least dosed until you start suggesting that the TT-034 doesn't work. Everyone is frustrated that the dosing is taking forever, however this is hardly surprising and certainly not any different to any other gene therapy study. Current market darling Bluebird took even longer to get their first 4 subjects dosed in the early phases. However as they were not then a publicly listed company, they were spared the ridicule.

Anonymous said...

Dirk's comments are a really good indication that Benitec will succeed, especially when compared to what he has said about ISIS.

This is what he said about ISIS on May 23 2014.

"I have been following ISIS Pharmaceuticals for a dozen years now and have heard Stan Crook, its CEO, promise his shareholders in as many years that profitability was just around the corner. Over the last 4 years, he’s also been promising that KYNAMRO will be highly profitable, and indeed just at the R&D day yesterday, he said that KYNAMRO would make ISIS profitable or at least will be profitable for ISIS under the Genzyme agreement.

The reality has been that none of that has materialized and sales of KYNAMRO, which essentially is a placebo with serious safety issues, must be so enormous that ISIS has not had to break out its sales one year following its launch (my sense is that it’s been growing exponentially from 1 patient to 2, 4, and now perhaps 8 subjects with familial hypercholesterolemia).

In fact, his delusion (he would probably call it his optimism) was on full display at the 2012 OTS meeting when he gave a keynote speech during which he celebrated himself for the first approval of a systemically administered oligonucleotide (KYNAMRO) which he said ‘had no side effects’. "

Less than six months later Dirk says, "In the case of ISIS Pharmaceuticals, however, I can foresee that, due to the currently wider choice of modalities and tissues amenable to single-strand antisense technology (incl. single-strand RNAi), full maturity could result in the world’s largest company by market capitalization."

So in less than six months Dirk has gone from saying ISIS never achieves anything to them becoming the world's largest company. At this rate we should see Benitec getting glowing praise before the end of the year.

Anonymous said...

Dick - you're a dirkhead.

Anonymous said...

While your sentiment is understood, it serves no purpose to call him names. I would rather he was engaged in an actual debate and there is little to be gained in debating with people who resort to name calling.

Anonymous said...

everyone is entitle to change his mind, however, usually Dirk is right about what is going to happen, taking just the Kynmaro example is very low and stupid in my opinion....
someone is involved with Benitec I am afraid....

Anonymous said...

Drick,

RXII NEWS - http://immuno-oncologynews.com/2015/04/07/rxi-pharmaceuticals-and-mirimmune-llc-ink-exclusive-sd-rxrna-cancer-immunotherapy-technology-licensing-agreement/

Stop bashing that one too!

Anonymous said...

Dirk,

For a frog in a bucket, the world is just one bucket big...

Anonymous said...

You were down on Novogen a while back. You missed that spike then and now look at them again today.

Anonymous said...

"everyone is entitle to change his mind, however, usually Dirk is right about what is going to happen, taking just the Kynmaro example is very low and stupid in my opinion....
someone is involved with Benitec I am afraid...."

And how are those people feeling right now who invested in Arrowhead back in Sep/Oct last year when Dirk was spruiking their technology?

Anonymous said...

Dirk comments are a parody of sorts on trading.

First, he says ISIS will be the next Apple while continually beating up ALNY.

His position on ARWR has changed so many times I don't even know what it is.

On the next breath he says the leadership of RNAi is about to change but doesn't say how or by who. Yet still maintains his view ISIS is the bomb and will never sell.

Instead he says he sold out of his RGLS position. The JV baby of ISIS and ALNY which a gambler would have to back as the most likely candidate to replace those leaders he said are about to be replaced.

Hope someone else can figure this trading out. Makes no sense to me. I wonder if it's even genuine. But it's not like I read his blog for investment advice.

ENORMOOUS JOHNSON said...

Dirk is a confused transgender reject
ISIS - world's most valuable stock ?
ALNY a fraud ?
RGLS a ???
Face it folks Dirk is a paid shill
Carnival Huckster
He is now naked
He is totally exposed
and he has a small pecker

Anonymous said...

That's the problem with those who have a sense of self importance and entitlement.

They always think they are so much better than everyone else they can talk down to them as if they are idiots for they are the great unwashed.

As the great Abraham Lincoln once said, ...you can't fool all of the people all of the time.

PfizerSloth said...

The Merck with Moderna photo says it all.

Who is going to get into the flea ridden bed of ALNY to develop RGLS technology?

Seems to me there is still a large piece of the jig-saw puzzle missing.

Anonymous said...

Yes. We are allowed to talk about Merck. The contract however, stipulates we are not allowed to talk about the other one. Isn't that right Dirk?

Newsurfer said...

Anonymous said, "And how are those people feeling right now who invested in Arrowhead back in Sep/Oct last year when Dirk was spruiking their technology?"

By any reasonable analysis, Dirk deserves high marks for his calls on ARWR (and many other RNAi stocks). Your cherry picking of the Sep/Oct 2014 time frame is either the result of ignorance of the larger picture or a deliberate effort to cast obfuscating aspersions.

Long time readers of Dirk's Blog know the enormous value he provides. Less knowledgeable readers would do well to go back and read his posts. If they do, they will see that his blog is fact based and remarkably prescient.

Anonymous said...

Dirk, The first tt034 cohort was 1 percent of cohort 5 dose. You know the "magic" of tt034 is the continued production of SHRNA in the cells cytoplasm. Dose does not need a high multiple because it will continue to be produced in the cell. I think that is what many people are missing about ddrnai

Anonymous said...

Roche doing deals with 4D for viral vector delivery of gene therapy?

That Benitec mob must be on to something good if Roche are following their lead.

Cohort four will get the response and the knockers will eat crow. More improvements to come from doggybone and 4D for ddRNAi. Some people just don't get it.

Anonymous said...

Twenty years of just a little bit more and then it will all be right. Twenty years work to get a total of four patients dosed with no viral knockdown. Say what you like about them but don't say they are not dogged and determined. But its as if someone else has to come in and tell them what the situation really is.

That the probability of the next thing making it a success are remote. That there are better alternatives out there. And that they are really just leading everyone up the garden path. Patients included.

FDA authority needs to be imposed so PF and his shareholders can wake up and smell the coffee.

Anonymous said...

Just to put things into some perspective I'll make a little comparison. Genetix Pharmaceuticals (renamed Bluebird Bio) raised $12m in 2003 to fund their PI/II for sickle cell and thalassemia major. The first patients were enrolled in 2015 and 2014 respectively. Benitec first dosed 3 patients in 2007 for HIV and only re-acquired the HCV program in Oct 2012 and have now dosed 5 patients. I guess that PF has already smelled the coffee and is busy brewing a blend of his own. Actually, if you look at the history of the two companies, they both have faced very similar hurdles that were/ are slowly being lowered. I'm betting that Benitec will follow a similar path of success in the near future.

Anonymous said...

When comparing, it is best to compare like with like. In that case, we are better to compare BLT's NASDAQ listing ambitions with those of ACL: it got pulled the day of expected listing.

Anonymous said...

Dirk:
Will #Moderna's spin-outs each develop their own delivery from scratch? How does 'de-centralization' make sense in light of 'delivery'?

No. Would expect the structure to like a pearl necklace. Each pearl demonstrating its own beauty while being tied to a greater whole by a invisible thread. As long as proper structures and channels exist for the invisible thread to link them all up.

Benitec beginning to look like the Emperor with his robes. Declaring they will IPO in the US but withholding details while the science slowly grinds to a halt as they reach the point where they have to increase dose to pursue efficacy.

TKMR too looking a bit ragged on the back of ARWR news today. I remember when the experienced munter said he was getting his sons in to the stock at about cap. raise time. That was enough to make sure I never even thought about going in to TKMR.

ARWR all the way it looks.

Anonymous said...

let me help . . . we are using a shotgun (tt034) that is clearly targeted on a large dartboard. HCV is only present in a few of the sections (cells) on the board (liver). cohort 1 is a 1 percent dose. when "shot" from the gun, it will hit 1 percent of the whole target. the virus may not be in any of the cells "hit" by the first shot. now, when we get to cohort 5, using a 100 percent dose, the shot will obliterate the dart board. In other words, all liver cells containing the virus will be "hit".

Anonymous said...

OBLITERATE HCV in one shot. I have nothing to compare.

GENE genie said...

If the HEP C program works , excellent , but Benitec is a platform company with its technology being used by a number of other player. The Tacere Hep C program as a first of kind gene therapy dosing was deliberately conservative , hence can be increased on further review . Please be patient new cures are a difficult path to follow.

Anonymous said...

A difficult path it is. But please, be patient you say, you must be kidding. A publicly listed company for between fifteen and twenty years. Tens of millions of dollars. An equal amount of wealth destruction while personnel are grotesquely and hypocritically enriched. The best and the brightest brains working tirelessly for those years and all you can say is be patient!

Get lost is all I can say to that.

Anonymous said...

What is this company?!!

In the beginning it was a HIV cure all. Then it was in to different things including hair loss. Only to end up as the Holy Grail for HCV when they bought back their own program from Tacere. Now that seems to be superceded by the same stunt for HBV!

They are buying back their own JV program from the Chinese outfit Bionomics!

This isn't as mad as it first sounds because BLT is now an American owned company with RA Capital fronting it as a key shareholder and proxy for Citigroup interests. Bionomics is a Chinese company calling the shots on a now American company. Like, since when does that happen? Like never. Thus, Kolchinsky just bought what is rightfully his back.

But wait! Isn't TKMR the HBV go to company? The world leader in HBV supposedly. What are they going to say about this move?

Could it be TKMR who buys out BLT? Or maybe their is a higher supra body about to be established and TKMR will only take the BLT HBV rights.

Want to know more? Stay tuned to the same crazy Bat channel for more.

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