It seems that Dan Loeb's hedge fund bought 2.1 million shares this past quarter:

Third Point 13F

I would also note that of all actual cases worldwide, a far greater portion of the US cases will be identified and treated.

To the extent that public health services in non-US areas improve, I would expect those figures to grow relative to the US figures.

Regarding macro environment, NFLX and AAPL missed everything and are down sharply AH. Ideally, this would be a great chance to show that ARIA isn't a high-beta tail on the NASDAAPL dog....

Someone just dipped into the kitty to pick up 400+ calls 2014 JAN 25 at about $2.40.

Any of you folks dropping $100k today?

[EDIT: Corrected exp date 2012 --> 2014.]

This is total BS.

What does an ARIA investor have to do to get an entry point these days, HUH?!?

(I know -- what a luxury problem, right?)

Not a mod, but I suspect it wasn't sufficiently Ariad-specific.

They'll delete my response too -- try not to take it personally, since active moderation is the difference between this and a Yahoo-like free-for-all.

(That's not a value judgement -- if free-for-all is your thing, then Yahoo is made for you!)

Cheers!

I don't think we have to worry about the legislators supplying correctives to our selfishness of liberty -- the NSA has an archive of everything we've ever written on this board and everywhere else, along with a trillion other tweets, phone calls, and emails.

Just sayin'.

[Mods: delete as needed.]

Following up on multiple mutations, slide 15 that shows the list of 20 non-T315I mutations has the following note at the bottom:

I think this is clearly an attempt to explain that certain patients have more than one mutation and that this causes some mis-match in the data set (e.g., total mutations > total patients), although their phrasing is a bit elliptical. I read this as:


Comments? Thoughts? Reflections?

IIRC, HB's statement that there is no known mutation that resists Pona means that there is no mutation that, alone, survives.

If you recall, they said that there are 50+ mutations that confer resistance to imatinib and 7 that resist 2nd-line drugs. (slide 9) They also said that there are 20 non-T315I mutations in the Pona test population. (slide 15)

They didn't say anything about combination mutations. Mathematically, 50c2=1227 possible pairs, so there are more than that in the imatinib resistance sample. It would be alot of testing to ensure that no combination (including 3 or more) of mutations is Pona-resistant.

I don't think people thought that's what they said.

Also, it's a great argument for 1st-line use.

Agree on the complexity issue -- there is a reason (aside from barriers to competition) that there is a separate bar exam for patent lawyers.

Also, I suspect that at best a discovery process would qualify as what they call a business process patent. But keep in mind that although business process patents have been around a while (think Amazon's "One Click") there is no Sup. Ct. decision that a business process qualifies as patentable.

That, and patents run out (think Green Mountain Coffee) whereas trade secrets can last a long, long time (think Coca Cola) -- they are as good as your NDA. Between those two, I know which I'd pick.

I think BTH was offering a snarky reminder to the M&A-fixated of the series of comments speculating on a NVS/ARIA deal when ARIA announced its CH-based Euro-HQ.

That's the beauty of limited liability -- you're -200% return investments are relatively rare. If they're not, you should review your broker's fee schedule!


LOL -- yes, ARIA's almost as good as a company that has Chinese factory workers stamp out 10-cent plastic shoes. I agree -- I'll stick with Clackson.

You say that like ARIA won't be worth $50B when the deal closes. What a pessimist!

OK, so $340/share might be a bit over the top, but that's what they said about AAPL in 2002. 1 iPod, 1 iTunes, 1 iPhone later, not so crazy....

The Rida CRL news release is out:

Rida CRL news release

WHITEHOUSE STATION, N.J., Jun 05, 2012 (BUSINESS WIRE) -- Merck MRK +0.11% , known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has issued a complete response letter regarding the New Drug Application (NDA) for ridaforolimus. Ridaforolimus is an investigational oral mTOR inhibitor under development for maintenance therapy for patients with metastatic soft tissue or bone sarcoma who have stable disease or better after four or more cycles of chemotherapy.

The complete response letter states that FDA cannot approve the application in its present form, and that additional clinical trial(s) would need to be conducted to further assess safety and efficacy. Merck also is in ongoing discussions with health authorities in Europe and other countries as part of their application procedures for ridaforolimus for the treatment of metastatic soft-tissue or bone sarcomas in patients who had a favorable response to chemotherapy. Additionally, Merck is studying ridaforolimus in combination with other mechanisms in several tumor types.

"Merck remains confident in the potential of ridaforolimus," said Eric Rubin, M.D., vice president, Clinical Research Oncology, Merck. "We will continue to work closely with the FDA to define potential paths forward for this investigational therapy."

Sarcomas are a group of cancers of connective tissue of the body for which there are currently limited treatment options. Sarcomas can arise anywhere in the body and are divided into two main groups -- bone tumors and soft-tissue sarcomas.

Ridaforolimus is an investigational small-molecule inhibitor of the protein mTOR, a protein that acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins, such as PI3K, AKT and PTEN, known to be important to malignancy.

As part of an exclusive license agreement with ARIAD Pharmaceuticals, Inc ARIA +3.65% , Merck is responsible for the development and worldwide commercialization of ridaforolimus in oncology.

OK -- but if you're planning to hold through the full set of '113 data, you might consider post-approval Pona SAEs to be important.

Granted, not often. But see: Darvon/Darvocet; Neutro Spec; Bextra; Tequin -- there are likely others, but that was just a quick Google search.

No -- and I think that's Dew's point.

Pona's approvability is likely baked in, and evidence that would suggest otherwise would be new and unwelcome information that would change valuations sharply.

But given that there are lots of folks around who have seen promising drugs explode in late-stage studies, I don't think that reminding us that there is still risk in these outcomes is a bad idea.

We all want to believe that we've reached the promised land on Pona -- me more than anyone -- but until you're out of the desert and have the milk and honey in hand, you're still just wandering.

GLTA!

Interesting -- I guess the prevailing wisdom that Rida would see its most effective use as part of a combination therapy is, after all, being pursued.

It would be interesting to know some of the science that (I hope) is behind this new 3-drug cocktail.

Are those ratings the extent to which HB focuses on these factors? I'd take issue with the sand-bagged compensation score, then!

I kid! I kid!

But honestly, I don't think these are the reasons that longs have hope. I would suggest that HB's significant stake in the company (a cursory review of Form 4s suggests that it rose on net, despite the flurry of sales) is a better bet.

GLTA -- especially longs!

New 628-week high, as well -- but who's counting?

Careless, yes. Shocking? Well, perhaps I'm cynical, but the truth is that sell-side analysis is just not that great.

Real buy-side analysis is thorough, expensive, actionable and closely guarded.

As for Illverson, I agree that his value, while perhaps non-pecuniary in nature, is positive.

And Cramer's short-attention-span-theatre is basically the distracting shill for the HFT algos and market makers who pick the pockets of over-active traders.

As far as smart people making poor decisions, perhaps "Stupid is as stupid does."

I did hear HB state that all warrants were exercised (no surprise, as they were priced at $1.69, IIRC -- a nice 10-bagger for those in on the PIPE) so that there would be no line item for warrant-related effects in future filings.

I think that she'll take this out soon. It's been in there for three years, so I suspect folks just forgot about it.

The theory would be that Pona will eat Tasigna sales regardless of who owns it -- the question is whether NVS wants to own that cash flow.

NVS won't get the money from the Tas sales that are killed off by Pona either way, so that should be irrelevant to a rational decision maker.

Now if NVS thinks that they can somehow market Tas better and minimize the losses, that does go into the calculation of how much they would be willing to pay for Pona/ARIA, and it may reduce their offer below a competitor's -- that is a real possibility.

Dude -- look at his avatar. Now tell me you take Ill seriously.

Gotta keep it light, unless you're talking science, right?

<admittedly OT>
Nothing's impossible, but I would tend to disagree. DPRK worries less about what the world thinks of it and more about that the world thinks of it. It's like dealing with Bart Simpson -- the pleasure they derive from attention so out-weighs the discomfort of sanctions (for the decision-making rulers, that is) that punishment of any sort can actually be counterproductive.

As far as a parking lot for 2d Inf. Div., that would actually be complicated on both tactical and strategic levels. Tactically, it would be like a knife fight in a phone booth -- we would win, but it would not be pretty.

IMO, nothing will change until China feels that having DPRK as a buffer state is more of a liability than an asset -- and then the situation will resolve quickly. Not necessarily cleanly or peacefully, but quickly. The risk I see is that China may simply try to annex the DPRK, much like the USSR went into Afghanistan with an orchestrated invite.
</OT>

Actually, I'm rather reassured. DPRK is a crazy zoo that put a lot of effort into this launch (including, I'm sure, prison camp sentences for failure) and all they got was a 1-minute fizz-and-pop. I think this says more about their inability to create mischief than anything else.

The market sell-offs in the AM are linked to Europe. I see much more weakness in US trading when Euro markets are open, then recovery after the Euro close. Not saying one or the other is the better price discovery mechanism -- just that we may see buying in the PM.

With all the insider selling (tax-related at least in part, but selling none the less) I'm not surprised to see some weakness. I've been expecting this for some time and my own half-baked theory is that it is partly due to funds having achieved their desired positions, akin to what we saw after the run-up driven by Fidelity's 14.9% stake.

I did note that it was a single-site trial.

Is the upshot of this that the trial could form the basis for future research but is not part of an over-all Ariad-spearheaded plan to move for 1st-line status?

Not so sure what to make of it, although the market took to it in the last 15 minutes.

TIA

Thanks for posting -- very interesting!

I'm a bit surprised that the study is only a single arm of 50 patients.

I have to assume that to get true front-line status, they would do a follow-on study that would be larger and double-blind, no?

Agreed -- thank you for your diplomatic reporting. Much appreciated.

IHMO, we should keep in mind that the graveyard is littered with drugs that showed enormous promise in Ph2, only to act like a sugar pill once the Ph3, double-blind, independently-assessed data is opened.

So was it the trial design? I suspect that it may be -- not in the good way ("It works, but we got an unlucky control group") but rather in the bad way ("Once we really look at this, its hard to see the Rida benefit in sarcoma.")

I only say this because -- despite what HB said about the OS trend favoring Rida -- the real OS trend didn't add much support.

I'm not saying that Rida isn't an active compound, but rather that (as others have pointed out) it may be more useful in combination.

Hey -- don't feed the trolls!

I agree with pretty much everything you said -- with one caveat:

The single Rida-related topic that I think Harvey could be faulted for is the discussion of the trend in overall survival.

I think that the OS metric was held out as both showing a favorable trend and the substance that would validate the barely-technical trial result.

Neither of those things came to pass, and frankly, at some point, HB knew it. And that was before today.

If we are going to hold his feet to the fire, it would be for something along the lines of failing to correct his prior statements, rather than simply not talking about Rida any longer.

Ouch -- then I can understand being incensed.

However, I suspect that Rida may have more than just this one chance to squeeze a run in. Endometrial data was positive and combination studies have promise.

Right, but how many outs are there?

From Bloomberg/Businessweek:



Link

I have a hard time believing that it can be the norm to have a panelist tell you that it was "crazy" to include the quality-of-life data slide in the consideration, and that it was not even an "apple-to-oranges" comparison and more like "apples-to-pizza" comparison.

Pretty grim.

Look, these guys are not all criminals. Some are just idiots.

I talked to a broker about a fixed income quote. He told me it was "not investment grade". I told him it was rated BBB, and asked whether he knew what "investment grade" meant. No answer.

Anyone who think that there are 15 rating agencies, or that they matter, isn't someone to listen to. No doubt, he meant that ARIA was "rated at the bottom" by 15 equity research desks, but semantics and lexicon matter. They're the first sign that someone doesn't really understand what s/he is talking about.

It's always interesting to hear what someone like that recommends instead. If one is the short-selling or put-buying type, it's a good place to start some DD!

I knew it was something related to relaxing the walls of the circulatory system -- which is why it...um...does what it does.

That'll teach me to rely on Wikipedia for info on their original Phase I trial....

I can't wait to hear the answer, but it's a bit like saying that "Pfizer didn't discover Viagra, because their primary endpoint was angina."

I'd be more willing to accept the formulation that "Statistically, Columbus' voyage was a failure because his primary endpoint was India."

I agree. The post-discounting value is not a huge portion of the price -- but, IMHO, if you're going to list it as part of the value, you need a down-side risk factor as well.

It doesn't need to be big, but really, it should be there. JMHO.

Which is really why sell-side analysis is free and plentiful -- and why buy-side analysis is expensive and rare.

Cheers!

Honestly, what I don't understand is how you can have a $2 value assigned to '113 and not have a down-side risk factor for '113.

If I were paying for that report, I'd be troubled by that.