Denner's Game

For the sake of argument,  let's consider this is Denner's game.

1. Denner understands that Ariad's products and pipeline are significantly undervalued by the Market.

2. Denner concludes that Big Pharma understands Ariad's  true value and would be willing to pay much more than post crash valuation.

3. Denner buys lots of shares, with the hope of flipping them to BigPharma in 24 months (his term on board)

4. Denner signs on to Ariad board knowing HB will be impediment no 1, but has to help turn around the ship and work with Harvey for a while to make the company credible. Thus he cuts deals and partnerships and probably helped with 113 application for Breakthrough Therapy Designation (BTD) - which is granted.

5. While turning around the ship, Denner courts big pharma partners,  and assures that other institutional investors are aligned with his game plan. Tute's holdings increase to 71%.

6. While all this is going on, Denner has been in discussions with Harv about buy out, but gets no traction.  Harvey refuses both the buy out, and the possibility of stepping down.

And now it gets interesting....

7. Knowing that further discussions with Harv are futile,  he now openly declares war.  This declaration is the CNBC "leak" (as we say in Washington).

8. Having publicly declared war with Harv, there is no going back. We are now officially in the end game. Clock is ticking.

9. Note: he could only move to end game position if agreements with BigPharma and other tutes are in place.

10. Why publicly declare war?? Simple.

A. Telegraph tutes to hold positions (note low volume recently, in spite of drama).

B. Position his conclusion as only logical one for Ariad and investors (can't continue with disgraced CEO).

C. Ramp up the pressure,  because that is precisely what activist investors do to achieve their objectives.

11. When Harv is forced out in, say, 30 to 90 days,  sell the company to Big Pharma, per prior negotiations,  and move the hell on...with a much stronger brand for Sarissa, and another notch in Denner's belt.

Game Over.

GLTA

TC

EARTHQUAKE TODAY???

The tectonic plates have moved, the earth has trembled, and the inevitable is underway...and soon the markets will open!

Denner has publicly declared war on Harvey. On CNBC, no less.  If he doesn't move Harv out through "an agreement with the company,” he’s waging  a proxy war.  Which he will win. 

Harvey is shaken.  Visibly so.  During his last interview, he forgot the name of 113 (the journalist reminded him it was Brigatinib), and he became incoherent when queried about his relationship with Denner.  END GAME.

So what now?

Sale.  Possibly a fire sale. Denner has 27% of Sarissa’s holdings in Ariad, nothing to show, and its been over a year.  $100m plus on the line. Bad. Bad. And Bad again.  After investing so big, tying up so much capital – dead money – for so long, it’s time to move on.   And that means selling Ariad to the highest bidder. Pronto!

Low end, $15pps.   

Disgraceful, below the pre-flash crash price, and the old school Ariad crew will be outraged (and out of pocket).  Denner, however, can declare a 100% plus profit, move on to the next battle, and be done with all this yucky drama with Berger and his aspirations to be President For Life. That’s the worst case, and it happens in 60 days.

High end, $35 pps.  

This happens if the God Molecule woos big pharma,  Brigatinib is on the verge of FDA approval, and there’s good news on Pona dosing trials on the way.  60 days, 90 max, and it's over. OVER!

Either way, shorts are toast and the (new) longs’ patience will soon be rewarded.

Good luck to all.

TC

Who's Your Daddy?

Who to believe?

In one corner, we have....

• Otsuka
• Denner
• Blackrock
• Fidelity
• Other Tutes
• The FDA (giving AP26113 BTD)
• commercial agents throughout Europe, Eastern Europe, Asia (see above) and of course Australia
• Docs and patients who went to bat after the debacle
• Science (just peruse prior abstracts from publications about Pona, 113 etc....multiple indications, impact, efficacy...and, yes, learning how to manage the risk/benefit trade off).
• A logical plan about the strategy for growing the company, and a conservative scenario of $400m revenues in 3 years.

And in the other corner, we have...

• Daily bashers (shorts in long's clothing?)
• daily market fluctuations
• bitter investors that didn't sell when we were at 20+ (not that I can blame that, it's just them emotion clouds one's judgement). 

So, who's your daddy?

GLTA

TC

BOOM!

God molecule going to clinic, partnership on AP26113.  Read all about it!

Press release

A P 26113 Approval In February...or more likely July?

Looks like approval might come earlier than we thought. 

Here is a recent  article which estimated time from BTD to approval at four months.  

BTD approval speed

However, I did the math, using data published on the FDA web site (FDA) as well as press released from individual Pharma companies re BTD announcements.  I found that the average days to market was 235, or roughly 8.8 months.   That would suggest an AP26113 approval date somewhere around July (my estimate in a prior post was August, so not much as changed).   However, as I noted previously, the approval can be as fast as 55 days (Amgen's Blincyto), or as long as 498 days (Merck's Keytruda)  

Hang in there everyone. 

TC

God Molecule Coming Wednesday: update

What would happen? 

First of all, this could happen. The molecule has been nominated, which was an internal corporate event. Investor relations (Kendra) has also been clear that they would share the profile of the molecule at an appropriate public event.  So go figure.

• God Molecule nominated. Check.
• Biggest healthcare conference of the year is happening next week. Check. 

There isn't a better time to unveil The God Molecule.  And when they do, and if it is good,  it will be an extremely interesting day. Big Institutional investors will want in.  Shorts will be trapped at the exit. And the outcome could conceivably be a 100% plus increase in share price.  

UPDATE:  I wrote to Kendra at investor Relations and asked her to confirm if the internal nomination for the new molecule happened.  Her reply was that "She encourages that [we] listen to the webcast at the JP Morgan conference for a full update." 

This is not a good time to sell.

Good luck to all.

TC

AP26113 Approval could come at any time based on existing data

Short Version of the Story: Ceritinib received FDA Approval based Phase One Trail data that was that was inferior to AP26113 Phase I/II data. As such, FDA approval for AP26113 could come at any moment, and the FDA might not wait for results from the Alta Phase II trial (for which recruitment is now underway).


Long Version of Story...

First of all, things can move quickly.  Let's take the Ceritinib, which received FDA Approval based on PHASE ONE trail data.  Here's the language about that data.

In April 2014, the next-generation ALK inhibitor ceritinib received an accelerated approval as a treatment for patients with ALK-positive NSCLC following progression on crizotinib. This approval was based on phase I data from the ASCEND-1 trial showing an overall response rate (ORR) of 58.5%. The early median duration of response was near 7.5 months - See more at: http://www.onclive.com/peer-exchange/nsclc-needs/Next-Generation-ALK-Inhibitors-in-NSCLC#sthash.g9PjxxjH.dpuf   Source 

Now, let's compare that to the AP26113 Phase I/II Trial Data Results (and note it's phase I/II, not just phase I):

The objective response rate (The objective response rate (ORR) in 72 evaluable patients with ALK-positive NSCLC was 72%. The median duration of response was 49 weeks. The median progression-free survival (PFS) was 56 weeks. In the 65 evaluable patients treated with prior crizotinib, the ORR was 69% with a median PFS of 47.3 weeks.  In 7 evaluable patients with treatment-naïve ALK-positive NSCLC, AP26113 demonstrated 2 complete and 5 partial responses, for an ORR of 100%. In patients with untreated or progressing brain metastases (n = 14), 71% of patients had evidence of radiographic disease improvement. - See more at link     

Now, you do the math.   AP26113 has better clinical data than a drug that the FDA recently approved based on Phase I Clinical Data.

The punch line is that AP26113 Approval could come at any time. 

   

2015

Away we go...

Japan deal done.  Check. 

AP26113 gets FDA Breakthrough therapy Designation.  Check

Financing in place for at least next nine months.  Check. 

Billionaires going long on Ariad. Check.

God Molecule coming any day now.  Check

2015 is going to be fun.  I can't wait.

Merry Christmas everyone. 

TC

please send this letter to Kendra Adams at IR

Kendra.Adams@ariad.com

Dear Ms. Adams,

The year is now coming to a close, and  many are wondering if Dr. Berger will be honoring his commitment to announce the new molecule in 2014.  Could you kindly advise if Ariad will be respecting this comittment to shareholders?

Best regards,  and thank you.

[Your Name]

ASH Flash 3: Strong Evidence of Superior Efficacy and Durability of Response with Ponatinib vs. Bosutinib

From American Society for Hematology conference:

Paper No: 3154
Benefit-Risk of Ponatinib Vs. Bosutinib in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients Who Failed Two Prior Tyrosine Kinase Inhibitors (TKIs): An Indirect Comparison
Moshe Yair Levy, MD, Baylor University Med Center

CONCLUSIONS:  Our indirect comparison using a variety of surrogate measures provides strong evidence of superior efficacy and durability of response with ponatinib vs. bosutinib in 3L CP-CML patients; the higher proportion of ponatinib patients continuing on therapy and the longer duration of therapy also suggest patients experience better overall response and tolerability outcomes with ponatinib vs. bosutinib.  Based on the surrogate measures of patient benefit- risk examined in this analysis, ponatinib appears to provide a net overall benefit vs. bosutinib in 3L CP-CML patients.:  

ASH Flash 2: Initial Data Show Responses are Maintained After Dose Reduction

From the American Society of Hematology:

3135 Long-Term Follow-up of Ponatinib Efficacy and Safety in the Phase 2 PACE Trial

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: 

Conclusions: Ponatinib continues to exhibit deep and durable responses in heavily pretreated pts with longer follow-up, particularly CP-CML. A dose reduction strategy was implemented in response to the observation of ATEs.  Initial data show responses are maintained after dose reduction; longer follow-up is needed to understand impact on safety.  A dose-ranging trial of ponatinib in refractory CML to evaluate benefit/risk is being planned.

ASH Flash 1: Ponatinib Doses as low as 10 mg were still associated with disease control overall.

From the American Society of Hematology:

3153 High-Resolution Analysis of the Relationship Between Dose and Molecular Response in CP-CML Patients Treated with Ponatinib or Imatinib

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II

Conclusions:

BARD enables a detailed exploration of dose-response relationships in CP-CML.  In newly diagnosed patients, ponatinibdoses as low as 15 mg induced more rapid decreases in BCR-ABL levels than 400 mg imatinib.  Consistent with the possibility that sequential treatment with TKIs increases the degree of BCR-ABL independence, the magnitude of BCR-ABL decreases induced by ponatinib in heavily pretreated patients was reduced compared with newly diagnosed patients. Nonetheless, ponatinib doses as low as 10 mg were still associated with disease control overall.  These analyses will help inform the design of future studies aimed at optimizing the benefit/risk of ponatinib treatment for patients with CML.

The God Molecule Countdown: T-31

Is the God Molecule (i.e. next Ariad molecule) a "Third Generation" TKI?

A strong medical need still exists for better tolerated therapy to treat NSCLC patients harboring EGFR mutations. Here we report the discovery and development of a potent third generation, irreversible mutant-selective EGFR TKI that is expected to improve/maintain efficacy on oncogenic EGFR mutant patients while demonstrating reduced side effects. EGF816 potently inhibits both activating (L858R and Ex19Del) and T790M resistant mutations in various cellular assays; it is selective against a large panel of kinases in both Ambit and BaF3 profiling, and more importantly is selective against WT EGFR. EGF816 is efficacious in mutant EGFR-driven xenograft models, is well tolerated in IND-enabling toxicology studies, and is entering phase 1 trials.

The God Molecule Countdown: T-32

Will it be KRAS related?

If so, that would be profound and we would quickly be to 30.

KRAS

More to follow. Watch this space

TC

God Molecule Countdown: Day T-34

Here we go.  Reason 1 to love the God Molecule - This one from Jesspro on iHub.

Ariad's probable advantage with the New molecule is that, during clinical trials, its performance will likely be compared to placebos as there - this because there are no current treatments for "unmet medical needs,"  which is how Ariad has described the purpose of this new molecule.   As a result, even a modest advantage in the trials over placebos maybe considered successful.  Furthermore, once P1 and P2 have been completed, and if they are successful, accelerated approval could follow. Unlike 113 and pona(CML), which had to  compete with existing therapies,  the Nmole development may not be as expensive and could advance more quickly. 


 Note: The following is from Kendra at Ariad IR regarding the God Molecule

Kendra Adams <Kendra.Adams@ariad.com>	Sep 30
to me

We have communicated that we expect to nominate our next development candidate by year-end.

Regards,

Kendra

Countdown to GOD MOLECUE - SHORTS BEWARE!!

COMING SOON.

The GOD MOLECULE, Ariad's new "Best in Class" product is due out before the end of the year.  I have written to Kendra Adams, Director of Investor Relations, and she has CONFIRMED that there will be an announcement before the end of the year. CONFIRMED.

This means...as of December first, we have 30 days until the GOD MOLECULE is unveiled.  And when it is....expect a significant increase in PPS, or perhaps a buy out.  My prediction is that, when this happens, we'll be at at least 10.  

more to follow....on what it is, what the market will look like, and what this will mean for Ariad.

TICK.  TOCK. TICK. TOCK

TC

What Dr. Strangelove is Afraid to Tell You About AP26113

This one, Dr. Strangelove, is for you.

1. AP26113 is an amazing molecule by all accounts, and has tremendous life saving potential. 

2. It is one of only 58 molecules (57, but let's not get into that here) that has been promising enough for the FDA to elevate to Breakthrough Therapy status (many applications have been rejected). 

3. Not only is this reason for hope on the part of cancer patients and their families is potentially game changing for Ariad and it's investors (and count me in). Revenue in YEAR ONE of approval could be on the order of 350m, this based on CURRENT crizotinib sales...and that is for just one indication. 

4. There is now evidence to suggest additional indications for AP26113, thus the potential for multiples of crizotinib revenues. 

5. Given the FDA's rules for approval under breakthrough therapy Designation, and the experience with other molecules previously given BTD, approval could actually happen as early as JANUARY OF 2015. 

6. And here's my favorite...only a madman would initiate a short position against this equity, and I am confident that those currently stuck holding such positions are frantically looking for an exit ramp (which may explain some of the irrational posts we have seen cropping up on various boards lately). 

Kind regards to all, 

TC

When will AP26113 get FDA Approval?

AP26113 Will probably get FDA approval sometime around August of 2015.    This guesstimate is based on the mean number of days that 14 drugs which have received  FDA Breakthrough Therapy Designation (BTD) have taken to receive FDA approval.

That said, given the history of drugs that have previously received  BTD,  AP26113 could conceivably be approved  as early as January 2015.  This guesstimate is based on the fastest movement from BTD to FDA approval, which was 82 days (Eltrombopag: BTD on 2/3/2014; FDA approval on 26-Apr-14).

On the other hand, it might be as late as March, 2016.  This is based on the slowest movement (531 days) fromBTD to FDA approval (Ibrutinib: BTD 2/12/2013 FDA Approval 7/28/2014)

Breakthrough Therapy Designation Table          (Source for table)

So, now the disclaimers...

1. Double check my math (it's late, I'm tired, and...seriously, help me out here).

2. There were 58 drugs approved (one list says 68, but I'm only counting 58), and of these...14 have have been approved: I have NOT counted the days that unapproved drugs have been waiting for approval, so someone might want to calculate new intervals given these "not yet approved" drugs. I have treated FDA Approved and "NOT APPROVED" as apples and oranges because, well, see point 1 above.

3. Yes, I get that every drug is different and the path for one drug's approval need not predict the path of another. As such, who the heck knows when AP26113 will get approved....I'm just giving a RANGE of possible approval dates IF it gets approved.

4. And, yes, it may never be approved. There's no guarantee whatsoever the "BTD" leads, without fail, to FDA Approval.

Looking forward to your comments and quibbles.

Trading Cyclist.

Hark, The Angels Sing

or not.

The end is in sight. We're up and away and the fours and fives and soon the sixes will be gone for ever and ever because, well, the angels sing.  And sing and sing and sing.

And sing they do, the boards are all aglow with Christmas cheer.

And not only that, 2Da  and BR are on the run. (Thank GOD!). So, hark the angels sing - we're up, we're out of the woods!  And I should feel absolutely just fine about putting way, way waayyyyy too many eggs in my pretty new Ariad basket.  As only a fool could weight down a single financial container.

Yup. We're up. And we're confident. And we're giddy with our prospects and the hint, lo, the promise of a happy ending before too long. Or soon even.

But, amidst all that that singing and rejoicing I paused and, heaven and angels forbid (and forgive me) took a minute to look at the PPS over the last six months or so.  And we've been here before. At least four times. Who knows what happens next. Or when.

Be safe.

TC

Harvey Forever?

Forget about it.

Forget about the question. It's a red herring.  Harvey stays until he goes, and there ain't nonthin' you, little retail investor (just like me) can do about it. 

And then, who cares. The science, being what it is, will outlast/overpower HB. It's that good.

And then....seriously.   Harvey built the company from scratch, it's his life opus, our little retail rants, our frustration don't mean a thing to this man. He's rich, fantastically rich.  He's successful - wince if you must, but think about the life saving products he has produced with Ariad. That doesn't change b/c YOU lost money and are pissed off. 113 works, pona works, rida back from the dead in a combo/tag team version, and the God Molecule (nM), or so we hope, is on the way.  And I didn't even say GIST (GIST!) or lung cancer.  Deal with it.

And, then...most of the board is in his pocket. 

A Denner led Coup?  Maybe, but to what end?   Let's say there's a coup and that Ariad is ripped from Harvey's control...he's pushed out of the car moving at high speed, rolls down the street, and 2da and BR and the rest of the Harvey Hater's have a good laugh...and feel, well, vindicated.  So what?

Maybe you get a buy out. Ok, I'll give you that. We get 12 or 15 or 18 if we're super lucky. Great. I'm up in multiples, and have no complaints.  Then again, what if the buy out is at half or a third of a long term value.  Seriously.   We hit 24 previously with only one partially exploited drug in the system.  Now we have two, with multiple kick-ass indications, and a third BIC mystery molecule (we think) to be delivered in the next 75 days.

What's all that worth in, say, two or three years?  40? 50? 60?   Pick a number, but it will be multiples of whatever we get if Harv is thrown out of the car and we sell out cheap. In a panic.

I've got time. I'm working, paying the bills, and am happy to sit tight and see how all this plays out. And, ultimately, as far as Harvey goes, neither he nor the board members nor the tutes give a rat's ass what you and me think.  However frequently and angrily we post - we just don't mater.

So just enjoy the ride. Or get out of the car.  And in the meantime, forget about Harvey. He's driving.

TC