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

NONSENSE

Down is up. Up is down.
Black is white. White is black

I had a colleague a few years back who was ex Navy. She served on the flight deck of an aircraft carrier.  Her job was to talk pilots down for landings, making sure they landed right side up.  Because they often became disoriented on the sorties, sometimes they didn't know which way was up. And which way was down. So she had to tell them, she was their voice of reason, to tell them which way was up. And which way was down.

One pilot, the one she thought about all these years, didn't listen.  He trusted his feelings, his emotions, which after a high velocity combat mission had disoriented him.  He was flying upside down. She told him to flip over, and pull up. He didn't, thinking up was down. And down was up.  He was the only one she lost.

So, here we are. Down is up. Up is down.
Great news, we fall by 8%.   Market tanks, we're up.

Nonsense.

Sense?

• AP26113, Breakthrough therapy status (one of only eight such cases in 2014). 
• Pona gets thumbs up from PRAC, kills damn near every mutant, has 5 plus untapped indications - including GIST. 
• Expansion in Europe is in the works, partnership in Japan is a matter of time. 
• And there's Denner.
• And Blackrock
• And Fidelity.
• And, best of all, good science. That most of all. 

Nonsense. Sense. Up. Down.

You decide, but trust facts.  And be careful. There are dangerous people out there and they are disorienting, always confident, and occasionally eloquent .  They'll have you  believing that white is black. That down is up. They will convince you that sense, that facts and science and logical conclusions, are nonsense. And ultimately,  if you listen long enough, they will fool you into believing that precious things, those you hold dear, are worthless.

TC

Impact of 2014 FDA "Breakthrough Status" on Market Capitalization, 30 and 60 days out

 FDA "Breakthrough Status" appears to have no consistent impact on market cap in the short term (30-60 days). 

Yah, and where did you come up with that?  

FDA web site lists drugs receiving breakthrough status, so check the list yourself, wise guy. FDA Breakthrough Status Approvals in 2014.  Now, if you have the time and energy, look at each of the firms, and track the share price/market cap the day before the status was granted, and then at 30 and 60 days out.  (And, for heaven's sake, yes, I get that it has not been  60 days yet for Glaxo and Merck, and the graph below should be interpreted accordingly).  Anyway, do the math yourself, but what I get (below) does not indicate any clear trend/pattern.  Yes, one little bio (Pharmacycics) and one BP (Gilead) got a near 20% bump, but the other five...not so much. So no consistent pattern. 

So What?

1. 30/60 days is  too early to see any change.  The real impact of "Breakthrough Status" is in the long run, and this because: a) you're likely to go to market earlier, and therefore generate revenues earlier and for a longer period (more years on patent); and b) you might skip a trial or two (which could save you $100-250m, depending on the indication and a thousand other things).

2. Stop your damn whining. The people complaining that Ariad "only" got an 11% bump after the FDA breakthrough blessing are a bunch of damn whiners that haven't done their homework.  There's no reason to think that this FDA designation should be a game changer in the short run. 

coming VERY soon: So What is Breakthrough Status Worth for a Pharma?

Evidence from 2014: How does getting an FDA "Breakthrough Therapy" impact market capitalization 30 and 60 days out?

Stay tuned for a summary of what this has meant for other pharmas in 2014.

To be continued.

TC

Dangerous people, and the poison over at ihub

Bulletin Boards can be dangerous places. But you knew that, right?

Sure.  How about a BB which by some (pompous) accounts is where the serious, science based discussions on biotech stocks happen - like iHub? Well, even there, and in spite of the over eager, finger-on-delete board monitors, some pretty dangerous folks are lurking. Here are my top two.

Biotech Researcher, aka BR, enemy no. 1.
He has been posting for eternity, before the continents separated, and used to be a long.  Or so the legend goes. This longevity has given him a certain credibility which, for many, makes him trustworthy. And, well, that Dr. Strangelove photo is kinda charming, no?   Not so much. Trust is the first thing a scam artist will try to get from you...before he picks your pocket.

He has also mastered, in a chimp-like sort of way, the vocabulary of biotech. This helps with trust. But at the end of the day, and the beginning and the middle, he's pumping for Ariad's demise...cheer leading on every dip - down we go!!  Who knows why. Short position? Recruited by a hedge fund to sow doubt? Just an asshole?  It doesn't matter.  His posts are full of vitriol,  systematically manipulate fear, sow doubt, and are without merit.  He's dangerous, and he will gleefully mislead you to make foolish investment decisions.

2DaMoon, aka 2da.
This one is a different story. He bet big before the flash crash, lost even bigger, and is bitter bitter bitter. BITTER! He's angry with Harvey B, wants the board to resign, and his diatribes roll from his clakety old keyboard in a frothy, rabid stream of consciousness.  There's rage, intense rage, and much of it with good reason.  He trusted Ariad with his life savings (so the legend goes), and they betrayed his trust. But now he needs to get a clue, and a life.  His iHub poison have killed that board.

So, long or short, be safe.  There are dangerous people out there, and they are prowling for prey in the most unlikely places.  And there are also powerful voices, to which we should, your's truly included, who deserve more respect and attention.

GLTA.

TC

The God Molecule? Ariad Registers New Patent

On September 25th, "Patentscope" published information on an Ariad application (filed in March of this year) for  a new molecule which functions as a choline kinase inhibitor. Patent The over expression of Choline Kinase has been associated with at least five types of cancers, which are summarized below.  We look forward to hearing more from Ariad about this new molecule, and its potential for treating many, many patients battling a variety of cancers.   

Stay tuned. 

Source for Choline Kinase data

Entity	Breast carcinoma
Oncogenesis	Normal and tumoral tissues from patients with breast carcinomas were analysed for ChoKα activity and expression. ChoKα activity was increased in 38.5% of tumoral tissues, whereas ChoKα over-expression determined by WB analysis was found in 17% of the 53 samples analysed (Ramirez de Molina et al, 2002).
Entity	Ovarian carcinoma
Oncogenesis	Choline Kinase activity in human epithelial ovarian carcinoma cells (EOC) was 12- to 24-fold higher when compared with normal or immortalized ovary epithelial cells (EONT) (Iorio et al, 2005).
Entity	Lung cancer
Oncogenesis	ChoKα mRNA levels were increased in lung tumour cell lines in comparison with human primary bronchial epithelial cells (BEC). This increase was higher in small-cell lung cancer (SCLC) than in non-small-cell lung cancer (NSCLC). Moreover, protein levels and ChoK enzymatic activity were also increased in tumour cells (Ramirez de Molina et al, 2007). When analysing tissues from patients with NSCLC, ChoKα over-expression was also observed with an incidence of 50%. Furthermore, patients with NSCLC with ChoKα over-expression had worse disease free and overall survival than those patients with normal levels of the enzyme (Ramirez de Molina et al, 2007).
Entity	Colorectal cancer
Oncogenesis	Both ChoKα activity and PCho levels were increased in colon cancer and adenocarcinoma tissues when compared with normal tissue. PCho levels in colon cancers were about 1.5 times higher than in normal colon tissue, whereas ChoK activity was 3.7 times higher in tumoral tissues with respect to normal ones (Nakagami et al, 1999).
Entity	Prostate cancer
Oncogenesis	Increased ChoKα was found in 48% tumoral prostate tissues when compared with their normal counterparts (Ramirez de Molina et al, 2002).

Japan

When?

Novartis ready to crash and burn, Pona trials wrapping up, and...all that healthy fish our brethren in the Rising Sun eat keeps vascular AEs to a minimum.

So, be a short. Make my day.

TC

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.