Ariad patents molecule for treatment of Parkinson Disease

March 2014 Patent re use of ponatinib for PD


[0064] In pharmacokinetic experiments in rodents, We have
found that the potent multi-kinase inhibitor, ponatinib, can
actually accumulate in brain to levels betWeen tWo- and three
foldhigher than inblood. This Was an unexpectedly fortuitous
?nding. The very favorable accumulation of ponatinib in
brain combined With its signi?cant inhibitory potency against
kinases such as Abl, permits delivery of pharmacologically
relevant concentrations of drug to the brain, e.g., at levels
effective to inhibit the phosphorylation of parkin in brain
Which has been associated With the development of PD. This
noW makes compounds of Formula I such as ponatinib very 
attractive agents for treating PD.


[0065] As discussed herein, this disclosure provides a 
method for treating PD by administering to a patient in need 
thereof an effective amount of a compound of Formula I such 
as ponatinib or a pharmaceutically acceptable salt thereof. 

Therapy
[0068] Therapy according to the invention may be provided
at home, the doctor’s of?ce, a clinic, a hospital’s outpatient
department, or a hospital. Treatment generally begins at a
hospital so that the doctor can observe the therapy’s effects
closely and make any adjustments that are needed. The dura
tion of the therapy depends on the age and condition of the
patient, the stage of the patient’s Parkinson’s disease, and
hoW the patient responds to the treatment. Additionally, a
person having a greater risk of developing Parkinson’s dis
ease (e.g., a person Who is genetically predisposed) may 
receive ponatinib therapy to inhibit or delay symptoms of the 
disease.

etc., as illustrated beloW.
[0174] For example, White opaque capsules Were prepared 
containing nominally 2 mg of ponatinib free base, provided as
the hydrochloride salt, With no excipients. White opaque cap
sules Were also prepared containing 5 mg, 15 mg, or 20 mg of
ponatinib free base, provided as the hydrochloride salt, mixed
With conventional excipients.

Applicant’s oWn WO 2007/075869, Which is hereby
incorporated herein by reference for all purposes, discloses
certain compounds that inhibit inter alia Abl. One notable Abl
inhibitor is ponatinib, Which is currently the subject of a
clinical trial to determine the e?icacy of ponatinib in patients
With chronic myeloid leukemia (CML) in chronic phase (CP),


Korean Patent Info

Open Letter to Ariad Investor Relations about the next molecule, aka "The God Molecule"

Investors: IF YOU AGREE with this open letter, PLEASE SEND Kendra Adams of Ariad Investors Relations (Kendra.adams@ariad.com) a message 

Dear Ms. Adams,

For quite some time now, Dr. Berger and others in Ariad management have been talking about the imminent announcement of a  Best in Class" new molecule for an "unmet medical need." Yet, in spite of multiple promises for nearly a year, we've heard absolutely nothing. Not a word, not a peep, not a clue.  And in the meantime, the share price of Ariad continues to plummet leaving many if not most small investors under water.  

So the question that all small  investors are asking, and the one I believe we deserve an answer to without further delay, is when will the "Mystery Molecule" be revealed?

With kind regards,

Trading Cyclist

New patent for our old friend pona?

Ariad applied for a patent in 2013, and was awarded same on July 15th 2014.   What follows here, after a brief commentary, are excerpts from the full patent record which can be found at  US Patent no. 8,778,942.   My layman's take away from this patent award is that ponatinib (Iclusig)  is better than we think, and is a  a potential replacement for Gleevec  - up to 10X more powerful, and with applications for a wide variety of cancers (including lung and pancreatic cancer).   Read the patent and draw your own conclusions.    

-------------------------------------------------
5. Uses, Formulations, Administration 

Pharmaceutical Uses; Indications 

This invention provides compounds having biological properties which make them of interest for treating or ameliorating diseases in which kinases may be involved, symptoms of such disease, or the effect of other physiological events mediated by kinases. For instance, a number of compounds of this invention have been shown to inhibit tyrosine kinase activity of Src and abl, among other tyrosine kinases which are believed to mediate the growth, development and/or metastasis of cancer. A number of compounds of the invention have also been found to possess potent in vitro activity against cancer cell lines, including among others K-562 leukemia cells. Observed potencies have been as much as 10-fold more powerful than Gleevec in conventional antiproliferation assays with K562 cells. 

Such compounds are thus of interest for the treatment of cancers, including both primary and metastatic cancers, including solid tumors as well as lymphomas and leukemias (including CML, AML and ALL), and including cancers which are resistant to other therapies, including other therapies involving the administration of kinase inhibitors such as Gleevec, Tarceva or Iressa. 

Such cancers include, among others, cancers of the breast, cervix, colon and rectum, lung, ovaries, pancreas, prostate, head and neck, gastrointestinal stroma, as well as diseases such as melanoma, multiple myeloma, non-Hodgkin's lymphoma, melanoma, gastric cancers and leukemias (e.g., myeloid, lymphocytic, myelocytic and lymphoblastic leukemias) including cases which are resistant to one or more other therapies, including among others, Gleevec, Tarceva or Iressa. 

Resistance to various anticancer agents can arise from one or more mutations in a mediator or effector of the cancer (e.g., mutation in a kinase such as Src or Abl) which correlate with alteration in the protein's drug binding properties, phosphate binding properties, protein binding properties, autoregulation or other characteristics. For example, in the case of BCR-Abl, the kinase associated with chronic myeloid leukemia, resistance to Gleevec has been mapped to a variety of BCR/Abl mutations which are linked to a variety of functional consequences, including among others, steric hindrance of drug occupancy at the kinase's active site, alteration in deformability of the phosphate binding P loop, effects on the conformation of the activationloop surrounding the active site, and others. See e.g. Shah et al, 2002, Cancer Cell 2, 117-125 and Azam et al, 2003, Cell 112, 831-843 and references cited therein for representative examples of such mutations in Bcr/Abl which correlate with drug resistance.   

Again, we contemplate that compounds of this invention, both as monotherapies and in combination therapies, will be useful against leukemias and other cancers, including those which are resistant in whole or part to other anticancer agents, specifically including Gleevec and other kinase inhibitors, and specifically including leukemias involving one or more mutations in BCR/Abl, within or outside the kinase domain, including but not limited to those noted in any of the foregoing publications. See in particular Azam et al. and references cited therein for examples of such mutations in BCR/Abl, including, among others, mutations in the drug binding cleft, the phosphate binding P loop, the activation loop, the conserved VAVK of the kinase beta-3 sheet, the catalytic alpha-1 helix of the small N lobe, the long alpha-3 helix within the large C lobe, and the region within the C lobe downstream of the activation loop.

Cliff Notes Guide to Ariad Message boards: intro for new investors

New to ARIA? Cruising the bulletin boards?   Here's everything you need to know to stay sane, and not take any of it too seriously...

Yahoo: 75% adolescent potty humor, 15% pumping and bashing, and 10% absolute gems of investing insight (thank you Bart H. , SullyinFL and MikiesBack). Problem is you have to wade through (or try to block) all the potty humor and pumping and bashing, and that gets incredibly tiring.  That said, in spite of the grotesque potty humor, there's something unmistakably honest about this place, which is why I keep going back. At the end of the day, we're just gamblers, however clever we think we are or how many degrees we might have. All that's quite clear on Yahoo.

StockTwits: Good folks, nobody gets emotional, or pathological... There is a  fair amount of pumping and bashing (which you'll find anywhere), but also genuine camaraderie whatever your viewpoint might be.  People share good intel, links, and it's a fun place to spend some time.  Down side is that posts are limited to 140 characters...which, as you'll see in a minute, might actually be an upside.  I'm migrating back there, as it's a good, comfortable, smart place to respectfully trade ideas about your investment.

iHub: Just, absolutely...amazing. And infuriating. The site is dominated by two bashers (former longs), sir 2da and Dr. BiotechResearcher (aka, BR) who, like the worst broken record on the planet, play their mournful, pompous laments about the stupidity of Ariad management (in particular its MD CEO) and the futility of investing in Ariad  again and again and again. And again.  I don't know who these guys are in real life, but I imagine them to be prune like, bitter old white guys whose lives (and investments) have not turned out as they hoped.  They are bitter, that much is clear...and they need to move on.  That said, there are also some extremely intelligent, insightful and well researched posts (thank you Jesspro, STOCKSEEK and Amplekind) that are must reads for any new investor.  I'd just recommend that you put the bitter old white guys on "ignore" from the get go -  you'll have a much better experience.

Good luck to all.

TC

Open Letter to Adam Feuerstein and Jim Carmer re Ariad

Dear Mr. Feuerstein and Mr. Cramer,

On July 24th, the peer review journal Cancer Cell published an article by Lee et al. entitled Drug Resistance via Feedback Activation of Stat3 in Ocogene-Addicted Cancer Cells.   One of the important findings from this paper (see below) is that ponatinib, aka Iclusig, invented and manufactured by Ariad, is highly effective, in in vitro studies, at reducing or nearly eliminating the development of resistant cancer cell colonies when used in combination with first line cancer drugs to treat non-small cell lung cancer, and specifically erlontinib (Tarceva) which is manufactured by Roche.

Which brings me to my question for you:

Given the demonstrated potential of Iclusig to improve first line therapies for lung cancer (and by implication a wide variety of other cancers), as well as early results with AP26113, what is the basis and/or justification for  taking a  "short" position with ARIA stock?  Put  differently, given the known evidence about the science of Ariad's products, would a patient "long" position with ARIA be a more rational posture, one that is consistent with the rapidly evolving field of  oncology?

With kind regards, and please find more detailed comments on the recent Cancer Cell article below.

TC

New article in Cancer Cell journal re applications of Ponatinib (Iclusig)

Short Version: There is new evidence of the dramatic potential (from in vitro studies) to use Iclusig in combination with other drugs to treat a wide variety of cancers, in particular lung cancer. This has important implications for the future of Ariad, and it leads me to believe this is not a $6.0 stock in the long run - it is large multiples of that.

Long Version: An article was published in Cancer Cell, a peer review oncology journal, about the biological pathways the lead to the development of resistance to drugs which target cancers, in particular erlontinib (Tarveca) which is used to treat advanced stage non-small cell lung cancer (NSCLC). To find the article (and you will have to pay $31.50 to get it), google "Cancer Cell, Drug Resistance via Feedback Activation of Stat3." This article is written for biochemists, which I am not. However, what I surmise is the following.

1. Existing treatments to non-small cell lung cancer, and a variety of other cancers (including colon cancer), are invariably compromised by the emergence of treatment resistant strains of cancer cells.

2. Substantial progress has been made recently to understand the cellular mechanics of the development of resistance strains, in particular the role of Stat3 activation.

3. The article just released, which includes 62 references to Iclusig (ponatinib) highlights the important role that Iclusig (ponatinib) may potentially play in reducing reducing/minimizing treatment resistance (in particular to Traveca, which is relevant for non-small cell lung cancer).

4. The authors summarize the significance of their conclusions by noting that "Pathway targeted drug therapies can effectively promote tumor regression in some patients. However, responses are typically limited in both magnitude and duration, prompting the need for combination treatments to promote longer term clinical benefits...suggesting a co-treatment strategy...may be broadly effective.

Waiting is boring, and gambling is fun.

 

Seriously, why on earth would you not hold ARIA securely and wait for movement north? We’re way better off than we were back in October when we were at 23 because…. let me get this over with in a quick run on sentence in a tiny font, and then  get to the point. 

We understanding the Iclusig dosing protocol better, and can mitigate AEs, the the powerful/positive effect of Iclusg is now better understood – and have been validated; the Lords at the FDA have twice blessed the pearl; patient/doc community has demonstrated that they will march on Washington if need be to keep Iclusig (because it saves lives); and then there's the impressive new data Iclusig’s impact Iclusig's impact on GIST; Major league investors are stepping up to the plate and getting behind Ariad (hint hint…), and then there's 113 and the soon to be unveiled SUPER MOLECULE! (red cape and all).

So there's that.

Now, really, what’s the downside of hanging on?   There are several.

1. You’re a short, and your life is flashing before your eyes (ok, but shorts aren't hanging on, they are just making noise).
2. Waiting is a drag. You’re impatient, and you want your money, MO MONEY, now now now! Waiting two months or six months or (God help us) A YEAR is just, well, BORING!!!
3. You have a better idea, a better stock to hang on to.  But please tell us what it is!
   
            ...and best of all!!!
4. Gambling, perversely, is fun.  (But you should get help for that.)
    

If there's a better excuse, let me know?

TC

What Happens Post ASCO?

2daMoon, or just Kinda-Flat?

Given the news and the drama and the hundreds of posts, a sensible long, or short (if there is such a thing) might well ask - what now?   Having read many/most of the feedback, the original abstracts published two weeks ago as well as the recent "press releases," I'd wager there are two competing camps. 

Camp 1: 2daMoon

Given the sheer awesomeness of the results and the good data, the positive vibe and the Longs' hug fest around the campfire...it simply MUST be that we're about to launch this rocket 2daMoon - either on our own power, or with an impending buy out.  Events foreshadowing the buyout include, but ain't limited to...The Activist Investor signing up; FDA turn around; encouraging early results from AP26113; GIST data; an imminent "reveal" of the new SUPER MOLECULE! (it will have a red cape), BlackRock bypassing the poison pill...and so on.  So, how up? Double? Triple? In a day a month or a year? Or faster and more and... OMG  you're a millionaire TOMORROW up?  I would love me some of that, absolutely.

or...

Camp 2: Just Kinda-Flat

This is the sour-puss, sky will always fall, "Ariad-is-boring-I-want-my-MONEY-NOW, AF, Cramer....I'm so over this and have far better ideas" school of thought.  As a rah-rah long, I don't like these guys, this camp.  At all. But here's the thing....it's hard to blame them. First, FDA gives the 2nd thumbs up, and no gap filled.  Last month or so, we're down 30% on mostly good or non-news (might be more or less, I try not to think about what this has done to my portfolio).  But, and here's the worst part, all the GRRRRRREAT, Tony-the-Tiger-esque news from this weekend's press releases is.....old. OLD OLD OLD OLD.  

Quibble if you want, but the "new" results were darn near identical to the abstracts that came out mid month... which I posted 12,000 times on this very blog.  To no avail. The stock didn't budge on the good news, and it rarely does.  Finally, the real hard-core short/pessimist/sour-puss gang would tell you that the only thing that drives a spike is a good, juicy British BO rumor. (And God could we use one of THOSE now).    Like I said, I don't like this crowd...mostly because they're a threat and I don't want to be working at The Golden Arches in my retirement.  

So, what the hell?

Sadly, I think my foes, my  nemeses, are more right than wrong.  Mostly for the wrong reasons.  Sure, we might get a bump, and maybe there's a buy out lurking there someplace (only Alex knows for sure), but the punch line is that while speculation is good fun, ultimately it's the monetization of this science that will give us a solid and irreversible push up...maybe even to 50 in a few years.   But that, Dear Ariad Investor, will not be happening tomorrow morning before the market opens. 

Good Luck to All. 

TC

Conclusions from Ariad related ASCO Conference Abstracts

The purpose of this post is to provide access to conclusions from Ariad related abstracts for upcoming presentations at the ASCO conference in Chicago. Breaking with previous tradition for this blog, there will be no editorial comments or analyses by the author or any other party.     

Abstract 1:

Title:    Economic burden of tyrosine kinase inhibitor (TKI) treatment failure in patients with chronic myeloid leukemia (CML).

Conclusions:  Although TKI failures have lower pharmacy burden, their overall economic burden is higher, primarily due to increased inpatient days. These findings suggest that minimizing TKI failure through more efficacious treatment may decrease the overall health care burden and costs of managing CML.

Abstract  2:

Title: A phase 2 study of ponatinib in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after failure of tyrosine kinase inhibitor (TKI) therapy: Initial report       .

Conclusions:  Initial analysis of this ongoing trial suggests that ponatinib has activity in pts with advanced GIST after failure of prior TKI therapy. .

Abstract  3:

Title: Longer-term follow up of a phase 1 study of ponatinib in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias       .

Conclusions: Substantial and durable responses were observed with ponatinib in heavily pretreated CP-CML pts. Vascular occlusive events were observed. Risk and benefit considerations should be evaluated when utilizing ponatinib in this pt population.

Abstract  4:

Title: Clinical impact of dose modification and dose intensity on response to ponatinib (PON) in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias .

Conclusions:  Pts on PON] who undergo dose modification may still respond to treatment and dose modification may be an effective management tool. Careful consideration of the potential benefits and risks of PON should guide treatment decisions.

Abstract  5:

Title:    Ponatinib (PON) in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation: Longer-term follow up of the PACE trial.

Conclusions:   PON has substantial clinical activity in heavily pretreated pts with Ph+ leukemias. PON is an important treatment option for pts in whom the need and benefit outweigh the risk.

Abstract  6:

Title: EPIC: A phase III trial of ponatinib (PON) versus imatinib (IM) in patients (pts) with newly diagnosed CP-CML.

Conclusions:  While PON demonstrated early activity in frontline CP-CML, EPIC was terminated as its objectives could not be met with PON dose reductions implemented mid-trial due to safety observations in PACE. Further investigation of PON safety is warranted. PON remains an important treatment option for pretreated CML and Ph+ ALL pts in whom the need and benefit outweigh the risk.

Abstract  7:

Title: Updated efficacy and safety of the ALK inhibitor AP26113 in patients (pts) with advanced malignancies, including ALK+ non-small cell lung cancer (NSCLC).

Conclusions: AP26113 has promising anti-tumor activity in pts with crizotinib-resistant ALK+ NSCLC, including pts with brain metastases. A randomized Ph2 trial evaluating 90 mg QD vs. 90mg QD escalating to 180mg QD in crizotinib-resistant ALK+ NSCLC will begin shortly.   .


Abstract  8:

Title: Phase II study of combination of hyperCVAD with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL).

Conclusions:  Combination of hyperCVAD + ponatinib is highly effective in pts with Ph+ ALL. Due to the vascular events observed, some pts switched to alternative TKI; in the remaining, ponatinib dose was modified to 30 mg daily during consolidation with subsequent reduction to 15 mg in pts in CMR

Disclosures: I am a “long” ARIA investor. I was not paid by any party to write this blog, and have no affiliation with Ariad Pharmaceuticals. 

Games

Having fun?

Ok, this is FUN!   CEO keeps reminding us all of commitment to "increasing shareholder value," Sir Alex the Activist Investor signs up, FDA gives thumbs up (twice!), Pona looks ready to conquer the world (GIST, four other indications), AP26113 replicates the Lazarus Effect, the "mystery molecule" is about to be unveiled ("Best in Class!") and...now.. BlackRock gets the nod to buy a gazillion shares. And still...

Down we go.

We're sinking to pre-FDA re-approval, falling faster than companies with no FDA approved drugs and no rock-star pipeline, and we can't even blame Adam at this point. (He's giggling senseless, rocking back and forth in the dark as a digital display of ARIA's PPS sinks below the dreaded 666.) 

And yet...

Just yesterday, and for nearly a few years, we were at 23. Almost four times where we are now, sans bells and whistles and the CEO mantra and Alex and (your's truly) working out that the market value for GIST is (get this) $500,000,000 annually. 

Games. Just Games. 

In time, all will be revealed. The curtain will be drawn, Japan comes on line, ASCO abstracts are broadcast from the hilltops to the tune of Julie Andrews singing The Hills Are Alive....And the only question then, I'd wager, is are you still holding your ARIA shares? 

Good Luck to All.   And on with The Games.

TC

Are you CRAZY?

Like me?

It doesn't make sense, what I'm doing.  Which is crazy.   I don't gamble, or text while driving, or behave in reckless ways or indulge too much in anything and have no substance abuse issues. And I have an advanced degree, a solid career, and have exercised good judgement (mostly) throughout my life. 

And yet. 

I should and do know better. Don't put all your eggs in one basket, diversify risk, don't gamble with money but invest. I know all that, like you, fellow Ariad investor. 

And yet. 

And yet, truth be told, my portfolio is lopsided. I have way too much Ariad, 65-75% in this single stock, which I know is completely crazy and breaks every rule about rationale investing and responsible behavior and, honestly, it feels dark. Like a secret or a flaw or weakness or some Greek tragedy in the making. 

And yet.

I don't think I'm crazy. I've done my homework, understand the pipeline, have estimated the value of future indications of Iclusig (one of them, anyway), have looked at Ariad 10 year trends read all of their SEC filings (seriously) studied the bios of their entire executive team and tried to educate myself on oncology and the epidemiology of cancer and...you name it. I've don'e my due diligence, extreme due diligence, and I can't for the life of me conclude that there's an end game other than 20. Or higher. In spite of AF and the other naysayers that, in my humble opinion, have not done their DD, I can't see any other outcome than up. Way up. 

So, I'm comfortable being crazy and breaking rules and taking the risk of putting nearly all my chips on one stock.  But help me out here. Do you have a compelling reason that I, that you, should do otherwise given everything we know about Ariad?

Or are you as crazy as me?

TC

OMG! ADAM IS CLUELESS

Tell me, tell me please Adam!!!!

• Why in God's name do you not mention AP26113?
• For what reason do you withhold information about the five additional indications of Iclusig, including GIST?
• Can you do any, any math at all? And if you can, can you check my numbers (see previous posts from this blog) which estimate the annual GIST market for Iclusig at half a billion dollars a year?
• Have you seriously never heard anything about the "mystery molecule" or the computation drug development platform?

. 

TC

You seriously need to FORGET about tomorrow's earnings report.

Please, just forget about it. 

The earnings report tomorrow does not, will not, can not matter. And if you don't understand that, you really should not be investing in Ariad.  And I mean INVESTING.  Not day trading, or speculating, or trying to make a quick buck.

Investing.

Investing is about the future of a company.  It's about catalytic events, the latent and powerful potential of a company and its ideas and its future value. So ask yourself, are you an investor?

If you're an investor, you'll know all about the multiple indications for Iclusig - including the half billion dollar a year market for the GIST indication.

If you're an Ariad INVESTOR, you'll know about AP26113, the mystery molecule, and the raw, powerful potential of the computational platform for drug development. You'll know about Japan and Australia and expansion in the European market (once pricing schedules and other issues are sorted out).

If you're truly an Ariad investor, you will understand the raw, tremendous potential ready to explode in new life changing, paradigm changing products that will flood vast global markets.

And, dear friend, if you know about all that, you won't give a damn about tomorrow's earning report. 

Ariad is a long game. So just forget about tomorrow. However it turns out.

TC

Revised Estimate for GLOBAL Market of Iclusig for GIST indication $500m - $1.5b

I have revised the model per suggestions from comment received on first version, but note the following:

1. I need source for GLOBAL incidence of GIST (only have US estimate, per previous post).

2. Need a clinician to advise how long a patient would likely be on Iclusig to treat GIST (this has implications for number of patients on treatment in a given year)

		Low Estimate	High estimate
Global Annual Incidence of GIST		7,500	10,000
No. Cases Treated with Iclusig		25%	40%
Cumulative Years' Incidence being treated per year		2	3
Total Case treated with Iclusig per year		3,750	12,000
Annual cost of treatment	125,000
Annual GIST related Iclusig Revenue		$468,750,000	$1,500,000,000

The Unforseen Catalyst: Pona as Orphan Drug for GIST.

This one wasn't on the radar.  Until now. 

If/when Ariad gets approval to market Ponatinib for GIST, it means that it's the drug of choice - first line for this indication.  Note that we already have FDA DESIGNATION of orphan status of Ponatinib for the GIST indication.  What we don't have yet is approval to market for this indication.  And if that happens,  we have huge and unanticipated catalyst.  Here's why.

1. Orphan status gets you a monopoly protection for the indications for 7 years, per FDA guidelines.

2. Per above,  we shoot to first line as its clearly the drug of choice (only one drug gets orphan status per indication).

3.  Additional revenues of up to $1.5 billion. The model to calculate the potential revenue range follows below. Suggestions to improve the model and assumptions are more than welcome, so please do weigh in.

Here are the assumptions.

1. Annual INCIDENCE of GIST (new cases) estimated at 3,300 to 6,000 in the US.   This estimate is from the National Cancer Institute.   See: National Cancer Institute GIST Incidence Estimate
2. Use endpoints of NCI incidence for annual new cases, multiply by percent of cases treated with Iclusig: LOW estimate = 50%, HIGH estimate = 100%
3. Estimate number of years a patient is on treatment: LOW = 1.5  years, HIGH = 2 years.  Note: This is probably the weakest link in the model, as I don't have data on how long patients would need to be on treatment.
4. 
   
   
   

   		Low Estimate	High estimate
   Global Annual Incidence of GIST		3,300	6,000
   No. Cases Treated with Iclusig		50%	100%
   Culmulative Years' Incidence being treated per year		1.5	2
   Total Case treated with Iclusig per year		2,475	12,000
   Annual cost of treatment	$125,000
   Annual GIST related Iclusig Revenue		$309m	$ 1.5b

   
   
   I welcome your suggestions on how to improve these estimates.

Market value of AP26113 and additional indications of Iclusig

Where are we going?

I have yet to see an analysis of the potential market value of AP26123 and the additional indications for Iclusig.  Ultimately, this is what will drive future PPS and/or acquisition price. But why don't the pundits comment on this?

I am going to take a stab at this analysis, which will take some time. If you have data or suggestions that will help, please post them here.

Stay tuned?

Whiplash!

Ok, that wasn't fun.  From yesterday's low of -12% to today's closing at +6%, a lot of us are still recovering from whiplash.  So now what? 

ARIA-AHAAA!

First, I'm renaming this stock, Dr. Berger. Your company shall forevermore be referred to as Ariad VOLATILE Pharmaceuticals, and ARIA will be replaced by AVP.

Second, WOW!  Do I have the stomach for this kind of roller coaster? Do you, Ariad Investor?

And Third, are you a trader or an investor? If the former, well, good luck. I admire your fearless, thrill seeking spirit. Really.  But if you're the latter, if you're really an investor AND  you believe in Denner and Cole and 113 and the Mystery Molecule and the five new potential indications for Iclusig, then there's a question you need to ask yourself.

Are you strong enough to hang on and ride this beast to the mountain top?

FRODO! TELL ME IT IS SO!!

This one will be short, b/c Frodo said it best...

Frodo's Take on the ARIA Rollercoaster...

Ok, something serious after I finish my beer...

TC

Why Ariad Investors should cheer, not fear, the Biotech Bubble deflation

Ok, it looks like the sky is falling for the biotech sector.  At least that’s how it feels, especially when you look at the Biotech indexes like NBI which have fallen well over 20% in the last few months.   On the other hand,  this same index was UP over 65% in the previous ten months.    

The zig zag has led a lot of pundits to conclude that maybe the sky isn't falling, but what we have here is a timely deflation of a bubble.   And honestly, wouldn't you rather have a prophylactic deflation of a bubble than a full-on implosion or pop?    You most certainly would, I’d wager, because the implosion/pop scenario could rattle capital markets and complicate biotech related acquisitions.

Which is where Ariad comes in.

While this Biotech bubble deflation is hard to watch, and has certainly put a damper on ARIA PPS, the thing to remember  here is that ARIA’s chart over the last year is really an “inverse bubble.”   ARIA suffered a major deflation after the FDA induced flash crash, from which we've achieved (on a good day) a 50% recovery.    We’re filling a gap here, folks, that is still ARIA’s story.

So, if you are an ARIA shareholder feeling sick about the recent PPS decline, take heart.   The current deflation of the biotech bubble  is not the ARIA narrative.    The Aria  story is about getting back to where we were after a completely unnecessary flash crash.  It is a story in which future catalytic events are on the horizon  -  AP26113, new indications for Iclusig including colon cancer & combination therapy, and of course the (soon to be released?) mystery molecule.

So why cheer on the biotech bubble deflation?   Do so because it’s not the ARIA narrative, and it’s giving us all a chance to go buy shares of Ariad at an even steeper discount.

Happy shopping. 

British Medical Journal Documents Successful Use of Iclusig in Combination Therapy

And still more on the value of Iclusig...in addition to colon cancer treatment and five other indications under evaluation. 

Headline: Haematological complete remission by ponatinib and bortezomib in a patient with relapsed, Ph+ pre-B acute lymphoblastic leukaemia

Punchline:  Our experience with a single patient suggests the feasibility of combined targeted therapy with ponatinib and bortezomib. This novel treatment approach achieved clinical remission with a manageable toxicity profile. 

Please note: all credit for the due diligence goes to Kipster210, he found this the day it was published (yesterday) and posted on Ihub.  Thank you Kipster!  The full abstract, as published yesterday in the British Medical Journal (BMJ) follows below.   

BMJ Case Reports 2014; doi:10.1136/bcr-2014-203894 

CASE REPORT 

Haematological complete remission by ponatinib and bortezomib in a patient with relapsed, Ph+ pre-B acute lymphoblastic leukaemia 

Sara Robinson1, Yair Levy2, Christopher Maisel1, Alex W Tong2 

+ Author Affiliations 

1Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas, USA 

2Innovative Clinical Trials Center, Baylor Sammons Cancer Center, Dallas, Texas, USA 

Correspondence to - Dr Yair Levy, Moshe.Levy@baylorhealth.edu 

Accepted 17 March 2014 

Published 12 April 2014 

Summary 

A 74-year-old man was previously diagnosed with BCR-ABL1-positive pre-B cell acute lymphoblastic leukaemia (pre-B ALL) based on bone marrow cytology, flow cytometry, cytogenetics and fluorescent in situ hybridisation findings. Following a highly complicated hospital course, the patient achieved cytogenetic remission by consolidated chemotherapy and the tyrosine kinase inhibitor dasatinib. He subsequently presented with relapsed pre-B ALL after 3 years in remission. In consideration of his challenging clinical history, he was started on concurrent ponatinib (45 mg daily) and bortezomib (1.3 mg/m2 intravenous weekly). The major molecular response was achieved (<0.0893% BCR-ABL1 transcripts) after 3 months. Bone marrow now demonstrates a BCR-ABL1-negative, complete cytogenetic response. The patient continues to do well with mild thrombocytopenia and improved anaemia on bortezomib and 30 mg daily ponatinib. Our experience with a single patient suggests the feasibility of combined targeted therapy with ponatinib and bortezomib. This novel treatment approach achieved clinical remission with a manageable toxicity profile.  

Ariad Hires Hugh Cole, Shire Pharmaceuticals M&A Guy. Any guesses why??

Ok, clever Ariad investor, you read Cole's bio on the Ariad web site. Very good. But did you check his FORMER employer's web site to see what Cole was up to at Shire, M&A wise, during his seven year tenure? Fourteen (yup, 14) acquisitions and/or major partnerships during his reign. But don't believe me, count 'em yourself.

http://www.shire.com/shireplc/en/business/shire-partnerships-and-acquisitions

So, why did Ariad hire M&A guru Hugh Cole about 30 days after Activist Investor Denner signs on?  

You tell me.