"I would love to know why you think Dimebon and bapineuzumab had zero credibility. Dimebon had the Russian trials and bapi was the first drug to target amyloid"


Dimebon "Absolutely Zero Effect" . Samuel E. Gandy, MD, PhD, from Mount Sinai School of Medicine in New York City, who has also done some investigation with this drug, told Medscape Neurology that he was always skeptical of the meteoric rise of this agent.

"This was a drug with no plausible mechanism that emerged from an incomprehensible series of screens that then had a 'better than anything ever' effect in a Russian trial and then gave absolutely zero effect in a US replicate trial," Dr. Gandy said.

Dr. Gandy pointed to another situation now unfolding, relating to results reported last month with a compound called NOV-002 (Novelos) for lung cancer. Used in combination with chemotherapy, results of a phase 2 study conducted in Russia showed treatment with NOV-002 increased 1-year survival from 17% to 63%, representing an 80% improvement over the US standard of care of 35%. However, in top-line results reported February 24 from a pivotal phase 3 trial, which had been conducted under a Special Protocol Assessment and Fast Track designation by the Food and Drug Administration, the drug failed to improve overall survival in patients with advanced non–small cell lung cancer.

The company is now facing a class action suit claiming that Novelos violated section 10(B) of the Securities Exchange Act in connection with "alleged disclosures" related to the phase 3 trial of NOV-002.

"While formally one should consider differences in drug, in subjects, and in trial design and conduct, it is worth noting that this is the third or so trial within the last few years to be spectacular in Russia and totally ineffective in the US," Dr. Gandy added.

"I would not dismiss the possibility of execution irregularities in the Russian study, and forensic review of that study would go a long way toward reassuring already skeptical experts like myself."

At last summer's International Conference on Alzheimer's Disease, Dr. Gandy presented animal data showing that, despite the promising clinical results, latrepirdine actually increased levels of ß-amyloid in mouse brain tissue up to 2-fold, a confusing finding that fueled discussion at the time about what is really known about the role of ß-amyloid in the AD process. http://www.medscape.com/viewarticle/718401#1

Bapineuzumab
The company did not provide detailed results, saying they would be presented at a medical meeting in September. But one of the principal investigators in the study, Dr. Reisa Sperling, said in an interview that there was no sign of any effect.
“There was absolutely no evidence at all of a clinical benefit of treatment on either of the primary measures, one cognitive and one functional,” said Dr. Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston.

To be sure, most doctors and Wall Street analysts had been expecting the drug not to succeed, since an earlier phase 2 trial had not shown a statistically significant effect.
http://www.nytimes.com/2012/07/24/business/alzheimers-drug-fails-its-first-clinical-trial.html?_r=0

here is the whole article link http://www.nbcnews.com/health/aging/alzheimers-hits-women-hardest-report-finds-n56236

Quote:
"so any Fidelity purchases more recent than 12/31/13 wouldn’t yet be publicly disclosed."
Actually this is not true, because Fidelity and other public companies reports 13-G every months, in March that was 3/10, in February that was 2/14, in January that was 1/10, so everything they bought after 3/10 will be posted around April 14 . You can check all Fidelity and others companies 13-G here http://www.sec.gov/cgi-bin/browse-edgar?company=FMR+LLC&owner=exclude&action=getcompany

Today Bloomberg interview with Prana CEO: March 03 2014 -- 09:28:34am
Geoffrey Kempler, executive chairman and chief executive officer of Prana Biotechnologies, said he is optimistic about the results of the Imagine trial, testing lead candidate PBT2 in Alzheimer's disease due this month. In an interview with Bloomberg's Elizabeth Krutoholow, he said the agent may be useful early stages of the disease when it can combat the prevention of memory formation. He said the company's recent Phase II results in Huntington's disease provide additional support for the drug's mechanism.
Q: Are you on track to announce top-line results from the. Imagine study this quarter?
A: We are on track for a March target.
Q: Will you pursue a Phase IIb or registrational Phase II/III adaptive trial?
A: We have started to think about it, and it is something we will discuss with the regulators. We are a small ambitious company. The trials we have conducted are small in terms of patient numbers. The question is how many times do we need lightening to strike to prove our drug works? I am optimistic for several reasons. In an earlier trial we have shown a 13 percent reduction in beta-amyloid and we improved executive function scores. These results were published in the Lancet Neurology in 2008 and 2009. The data looked good, so we invested more money in the program. Everyone has been chasing beta amyloid and after several failures, the hypothesis was questioned. Still, the genetics point to beta-amyloid, Oligomers are toxic and their formation is a metal dependent event. If the metal is removed, they won't aggregate. This is where PBT2, our metal-protein attenuating compound comes in. In addition, metals in the brain are part of memory formation, so it is useful to remove them from oligomers and plaques and redistribute to neurons for improved function and increased synaptic transmission. We can best intervene early in the disease. In the Imagine study, our primary endpoint is a decrease in beta-amyloid as measured by PET imaging. We have an enriched population since PET scans were performed as part of our entry criteria. We hope we can catch people early in the disease.
Q: What is your sense of the regulatory view of a decrease in brain amyloid beta without an improvement in executive function? Why did you choose the imaging endpoint as your primary endpoint?
A: It is not reasonable to expect functional improvements in patients with very early disease because patients may not yet have functional problems to treat. The NEJM article published last year by the FDA says it may be possible to achieve early approval for a drug by demonstrating improvements in cognitive tests, and that companies may be able to look for functional improvements afterwards. More specifically to your question, in the NEJM article the authors said that a lot more work is needed because a decrease in brain amyloid alone, without some cognitive benefits, would be enough for approval.
Q: If you obtain a disease modifying claim, what is the market opportunity?
A: The disease modifying claim versus the symptomatic treatment has been debated for a long time. It is important to look at the sustainability of the benefit. There is a large number of patients. This is the Holy Grail. With an aging population, there would be massive demand. Safety must be established first. If there is a real and meaningful benefit, there are millions of people who could be treated.
Q: Let's talk about Reach2HD results. You saw improvements in cognitive function at the highest dose after 12 and 26 weeks. Why do you think there wasn't an effect on motor function, behavior or functional capacity???
A: This was a small Phase II study, not a Phase III trial. It was conducted to establish safety and tolerability. We met the primary endpoint, and had 95 percent of participants finish the study. We saw a statistically significant improvement in executive function as measured by the Trail Making Test Part B. We don't think this was a fluke since we saw that PBT2 also improved executive function Alzheimer's disease patients in an earlier trial. This is why we are so enthusiastic. This was a go/no-go trial and we think what we have seen in the real. Regarding other measures, it is too soon to say if PBT2 will/won't have an effect as these parameters are probably best addressed in a larger Phase III population.
Q: You spoke to the heterogenous patient population in this study. Will you look to better stratify patients in the Phase III trial
A: We might stratify different characteristics in the next trial. In Reach2HD, we saw a very small but positive signal in the TFC scale. We enrolled patients that were TFC (Total Functional Capacity) 6-13, which captures early-stage to midstage disease. The signal was seen in the early stage group, so it might be useful to focus more on this group in the next trial.
Q: What is your capital position? When will you look to raise additional capital/pursue partnerships?
A: We have about 20 million AUD and we will have a few million additional in tax credit at the end of March. We can raise additional capital any time after we see the Imagine results. There is a possibility of working with a pharmaceutical partner. We hired Dr. Peter Smith as our VP of business development. He will make us reaction ready when it comes to any partnerships. We are open to it.

Who is AF? The guy with Political science degree? I've never heard and read about AF in any medical journal or article …
but here is some info about Dr. George Zavoico from H.C. Wainwright : Dr. George Zavoico joined H.C. Wainwright & Co. in January 2014 to focus on healthcare research. He has more than 10 years of experience as a life sciences equity analyst writing research on publicly traded equities. His principal focus is on biotechnology, biopharmaceutical, specialty pharmaceutical, and molecular diagnostics companies. He received The Financial Times/Starmine Award two years in a row for being among the top-ranked earnings estimators in the biotechnology sector. Before joining HCW, Zavoico was managing director and senior equity analyst at MLV & Co., and helped establish the healthcare equity research platform there. Previously, Zavoico was an equity research analyst in the healthcare sector at Westport Capital Markets and Cantor Fitzgerald. Prior to working as an analyst, Zavoico established his own consulting company serving the biotech and pharmaceutical industries, providing competitive intelligence and marketing research, due diligence services and guidance in regulatory affairs. Zavoico began his career as a senior research scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals Inc. and T Cell Sciences Inc. (now Celldex Therapeutics Inc.). Zavoico has a bachelor's degree in biology from St. Lawrence University and a Ph.D. in physiology from the University of Virginia. He held post-doctoral fellowships at the University of Connecticut School of Medicine and Harvard Medical School/Brigham & Women's Hospital. He has published more than 30 papers in peer-reviewed journals and has coauthored four book chapters. http://www.thelifesciencesreport.com/pub/htdocs/expert.html?id=6760

PRAN, sorry to say that,but your HD knowledge is very low,actually Pbt2 has good chance to get approval in HD after Phase 3, take a look at ONLY approved drug in HD: Xenazine. The study was conducted on small population.

The primary efficacy endpoint was the Total Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28.

Total Chorea Scores for subjects in the drug group declined by an estimated 5.0 units during maintenance therapy (average of Week 9 and Week 12 scores versus baseline), compared to an estimated 1.5 units in the placebo group. The treatment effect of 3.5 units was statistically significant. At the Week 13 follow-up in Study 1 (1 week after discontinuation of the study medication), the Total Chorea Scores of subjects receiving Xenazine returned to baseline.

Xenazine-treated patients were more likely to have any given degree of improvement in chorea score. Thus, for example, about 7% of placebo patients had a 6-point or greater improvement compared to 50% of Xenazine-treated patients. The percentage of patients achieving reductions of at least 10, 6, and 3-points from baseline to Week 12.

In general, measures of functional capacity and cognition showed no difference between Xenazine and placebo. However, one functional measure (Part 4 of the UHDRS), a 25-item scale assessing the capacity for patients to perform certain activities of daily living, showed a decrement for patients treated with Xenazine compared to placebo, a difference that was nominally statistically significant. A 3-item cognitive battery specifically developed to assess cognitive function in patients with HD (Part 2 of the UHDRS) also showed a decrement for patients treated with Xenazine compared to placebo, but the difference was not statistically significant.

Xenazine include Box warning about possible Risk of Depression and Suicidality. In a 12-week, double-blind placebo-controlled study in patients with chorea associated with Huntington's disease, 10 of 54 patients (19%) treated with Xenazine were reported to have an adverse event of depression or worsening depression compared to none of the 30 placebo-treated patients. In two open-label studies (in one study, 29 patients received Xenazine for up to 48 weeks; in the second study, 75 patients received Xenazine for up to 80 weeks), the rate of depression/worsening depression was 35%.

In all of the HD chorea studies of Xenazine (n=187), one patient committed suicide, one attempted suicide, and six had suicidal ideation.
so FDA approved Xenazine and won't approve PBT2 because of what??? Why PBT2 is less safe than Xenazine? or less effective??? I'm not saying that Prana data is very impressive but its also not bad…

In the world of science your claim is worth nothing, I can say that I saw 5000 HD scientist who claim opposite, so show me just one link from HD scientific journal???

PRAN -masterlongevity Can you name just one HD or AD scientist ??? Can you name one other HD trial that showed P=.038 or better improvement in composite EF???Can you name one other HD trial that showed any improved cognition measurement in 26 weeks??? Can you point to another HD trial that found indications of reduced hippocampal atrophy over that period of time? ???

Link: http://dealbook.nytimes.com/2007/03/20/cramer-market-manipulator/?_php=true&_type=blogs&_r=0

MARCH 20, 2007, 9:22 AM
Jim Cramer’s Guide to Market Manipulation
By DEALBOOK

“Mad Money” host Jim Cramer has gained a huge following, and more than a few critics as well, with his explosive stock-picking patter. But in a revealing video interview with TheStreet.com, the financial Web site he cofounded, Mr. Cramer drops some bombshells that go well beyond his usual chair-throwing, ‘Booyah’-shouting routine. In the clip, which has drawn lots of commentary on YouTube, Mr. Cramer brags about his ability as a former hedge-fund manager to game the stock market and offers what amounts to a how-to to aspiring stock manipulators, The New York Post reported Tuesday.
In the December interview with the site’s “Wall Street Confidential” Webcast, Mr. Cramer describes at least two strategies, including a way of driving stock futures up or down that he explicitly said was legal. “A lot of times when I was short, I would create a level of activity beforehand that would drive the futures. … It’s a fun game,” he told TheStreet.com’s executive editor, Aaron Task.
But Mr. Cramer spends most of the interview describing a practice called “fomenting,” where a hedge fund manager essentially creates a false impression about a company in order to drive its stock one way or another — which he says is “blatantly illegal,” but adds that “the Securities and Exchange Commission doesn’t understand it.” While he claims this practice is widespread, he never says he has used it himself.
Here’s how fomenting works, according to Mr. Cramer: Say a hedge fund manager is holding a short position — a bet that a stock will decline — in Research in Motion, which has just announced blockbuster quarterly earnings results. An enterprising fund manager might call several brokerage houses and either feed them bad information or order a slew of short sales. Then he or she could call up a “bozo reporter” with a fake news tip about Resarch in Motion rival Palm.
The result, he says, is a perfect storm of bad news that temporarily lowers R.I.M.’s stock price, long enough for the manager to reap a tidy profit. He recommends a similar procedure with Apple (the video was filmed before the company introduced its iPhone at its annual Macworld convention in January).
“These are all the things that you should be doing on a day-to-day basis and if you’re not doing it, maybe you shouldn’t be in the game,” Mr. Cramer tells Mr. Task.
Mr. Cramer sums up his philosophy this way:
What’s important when you are in that hedge fund mode is to not do anything remotely truthful, because the truth is so against your view, that it’s important to create a new truth, to develop a fiction.

PRAN= source: Casey Extraordinary Technology Researched Group

PRAN; From a newsletter I'm subscribed to…

Classen is entitled to his opinion, but we're skeptical of his "analysis." Just in this short note above, Classen fundamentally mischaracterizes the mechanism of action regarding PBT2. He says that PBT2 is supposed to work, "as the company stated, dissolving beta amyloid plaques." But that's not what the drug does, nor what it is supposed to do.

For years scientists thought that beta-amyloid plaques were the primary cause of the damage to neurons seen in Alzheimer's disease. This is what's known as the "amyloid cascade hypothesis." And while it's been the dominant focus of Alzheimer's drug R&D for the past couple decades, drugs designed to induce or accelerate the removal of beta-amyloid plaques have failed to show a real benefit to patients in late stage clinical trials. (It's also worth noting that many people who have beta-amyloid plaques in their brains never show any sign of Alzheimer's or cognitive impairment.)

Prana is working under a different hypothesis. It, along with a growing number of scientists, now think that small beta-amyloid oligomers are the real culprits in Alzheimer's disease, because they have been found to float into synapses and short-circuit nerve cells important for memory. Consistent with these findings is the hypothesis by Prana scientists that it's the interaction between beta-amyloid and metals (such as zinc and copper) in the synapse that leads to the formation of small, toxic beta-amyloid oligomers which inhibit neurotransmission.

Prana's theory has been referred to as the "metal interaction theory", the "metal-protein complex theory," and the "metals dyshomeostasis hypothesis". The crux of the idea is that the toxicity observed in neurodegenerative diseases such as Alzheimer's is the result of excessive interaction of synaptic metals with beta-amyloid proteins in the brain.

PBT2 is designed to work upstream of the typical amyloid-cascade approach by preventing the interaction of synaptic zinc and copper with beta-amyloid in order to stop the beta-amyloid from becoming toxic and causing synaptic failure. According to Prana scientists, PBT2 is "able to achieve this by 'disarming' the beta-amyloid oligomers of synaptic metals, to achieve two beneficial outcomes: prevention of toxic metal-laden oligomer formation resulting in synaptic toxicity; and return of critical synaptic metals, otherwise bound to oligomers, to neurons, facilitating normal neurotransmission."

So the drug is not meant to "dissolve beta-amyloid plaques" at all. The targets are the oligomers, which are much smaller than the plaques that ultimately form from hundreds of thousands or millions of the oligomer fragments sticking together.

Barclays note Today: Ariad: Face Uphill Battle Based on Current and Future Commercial & Developmental Risks of Iclusig; Little Data to Support Potential Label Expansion Across Other Indications
Iclusig has limited potential in CML: We reiterate our position that due to its adverse event profile, restrictive label, and competitive environment, Iclusig will be largely reserved as a salvage therapy. Furthermore, while studies are underway using a lower dose of Iclusig in order to dampen the drug’s toxicity, we have yet to see if the efficacy is maintained. As a result, we believe Ariad face an uphill battle based on current and future commercial/developmental risks of Iclusig.
There could be upside in the potential label expansion across other indications, but little data to support this:
Iclusig is currently being tested across multiple cancer types including lung cancer, head-and-neck cancer and gastrointestinal stromal tumors (GIST); of note, Gleevec is the current standard of care for GIST. To-date there is limited data with Iclusig for the treatment of cancers other than CML and Philadelphia chromosome-positive ALL. We believe it is too early to speculate on the potential of Iclusig in other indications, especially with the lack of clinical data and known safety concerns. Furthermore, we also believe ‘113 is not particularly differentiated relative to other ALK inhibitors.

ARIAD Story is big Headline here!!!! http://www.buzzfeed.com/tabathaleggett/ridiculous-daily-mail-headlines

Daily Mail is tabloid http://uk.answers.yahoo.com/question/index?qid=20111007060552AALtuAx

writing failure PR its easier , I just think that Prana HD trial will succeed , like I wrote two months ago on Seeking Alpha blog about Cytrx Aldoxorubicin vs. Doxorubicin trial that Aldoxorubicin will succeed , many people didn't think so, but I just compare few trials( one succeed, two failed ) with Doxorubicin and figured out that Aldoxorubicin beat Doxorubicin,that was what happened…PS, If you just take here odds, you have 50%/50%, so better than lottery ticket…

if they can beat Xenazine(The only FDA approved drug in HD)-I belive PBT2 can do this, PRAN will be winner. The Xenazine study was conducted on small population.

The primary efficacy endpoint was the Total Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28.

Total Chorea Scores for subjects in the drug group declined by an estimated 5.0 units during maintenance therapy (average of Week 9 and Week 12 scores versus baseline), compared to an estimated 1.5 units in the placebo group. The treatment effect of 3.5 units was statistically significant. At the Week 13 follow-up in Study 1 (1 week after discontinuation of the study medication), the Total Chorea Scores of subjects receiving Xenazine returned to baseline.

Xenazine-treated patients were more likely to have any given degree of improvement in chorea score. Thus, for example, about 7% of placebo patients had a 6-point or greater improvement compared to 50% of Xenazine-treated patients. The percentage of patients achieving reductions of at least 10, 6, and 3-points from baseline to Week 12.

In general, measures of functional capacity and cognition showed no difference between Xenazine and placebo. However, one functional measure (Part 4 of the UHDRS), a 25-item scale assessing the capacity for patients to perform certain activities of daily living, showed a decrement for patients treated with Xenazine compared to placebo, a difference that was nominally statistically significant. A 3-item cognitive battery specifically developed to assess cognitive function in patients with HD (Part 2 of the UHDRS) also showed a decrement for patients treated with Xenazine compared to placebo, but the difference was not statistically significant.

Xenazine include Box warning about possible Risk of Depression and Suicidality. In a 12-week, double-blind placebo-controlled study in patients with chorea associated with Huntington's disease, 10 of 54 patients (19%) treated with Xenazine were reported to have an adverse event of depression or worsening depression compared to none of the 30 placebo-treated patients. In two open-label studies (in one study, 29 patients received Xenazine for up to 48 weeks; in the second study, 75 patients received Xenazine for up to 80 weeks), the rate of depression/worsening depression was 35%.

In all of the HD chorea studies of Xenazine (n=187), one patient committed suicide, one attempted suicide, and six had suicidal ideation.

I agree with your posts…

http://www.fda.gov/Drugs/DrugSafety/ucm379554.htm The indications for use are limited to:
Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

BMO Today:
Our View:
1) Durability of ICLUSIG response in the salvage setting, in particular for patients with T315i mutation and few treatment options, is impressive but serious thrombotic and vaso-occlusive events remain a concern.
2) While ARIA has modeled a 40% reduction in thombosis/vaso-occlusive event risk for every 15mg reduction in dose, we would note that ARIA data interpretation has diverged widely from FDA.
3) With focus on prospects for re-introduction of ICLUSIG distribution, ARIA has indicated regular dialogue with FDA but we continue to expect an ODAC panel review before ICLUSIG comes back, and see real risk that additional clinical trial(s) will be required.

BMO Capital:Our View:
1) Feedback during a luncheon session with principal investigator Dr. Jorge Cortes suggests that cumulative risk of vaso- occlusive events is a big concern for ICLUSIG and that rates are clearly higher than for any other drug.
2) While early CV events are seen with other TKIs in CML, the pattern of increasing events over time is concerning to experts we talked to at the meeting.
3) Expert feedback during the CML luncheon session suggests that ARIA may need to do a controlled salvage study versus investigator choice and at a lower 15mg or 30mg dose to clarify the risk/benefit of the drug.
4) While there is clearly support for ICLUSIG coming back to patients, it is also clear that identification of an optimum dose may be key to its introduction.

https://ash.confex.com/ash/2013/webprogram/Paper62253.html https://ash.confex.com/ash/2013/webprogram/Paper62027.html

Cardio-Vascular Events Occurring On Ponatinib In Chronic Phase Chronic Myeloid Leukemia Patients, Preliminary Analysis Of a Multicenter Cohort https://ash.confex.com/ash/2013/webprogram/Paper59574.html

Debating the FDA Decision to Suspend Marketing and Sales of the Leukemia Drug Ponatinib (Iclusig) http://journals.lww.com/oncology-times/blog/onlinefirst/pages/post.aspx?PostID=902

, but Oppenheimer view after the Ariad crash was very positive, even before the crash, they have very positive info. about Ponatinib and AP26113, I posted here few notes from Oppenheimer which compare Ponatinib to Tasigna, and Ponatinib was better drug in their view… CS , and Barclays have negative view of Ariad…

Ariad: EMA’s Pharmacovigilance Risk Assessment Committee Starts In-Depth Review of Iclusig Safety; Further Changes to Label or a Recall are Still Possible
The European Medicine Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) announced that it has started an in-depth review of the benefits and risks of Iclusig, with a focus on vascular occlusive events. This follows PRAC's earlier recommendation in November supporting continued use of Iclusig with increased monitoring for SAEs. However, PRAC stated that an additional review of issues related to this increased risk was necessary to assess the need for further changes. As the review process continues and more data continues to emerge, we believe further changes to the label or a recall are still possible, in Europe as well as in the U.S.
The FDA investigation is ongoing, as of 10/31, the FDA found increased SAE rates (48% and 24% in PACE Phase I and II, respectively). U.S. Iclusig marketing and sales remain suspended, and while management remains confident that the hold will be lifted, we cannot rule out the possibility of recall at this time.
Elevated SAEs also found by other investigators: A study from French investigators (Nicolini et al., 2013 ASH meeting abstract #4020) found that in a cohort of 19 CML patients on Iclusig, 42% experienced CV events after a median of 8.5 months on drug, strikingly worse than a historical cohort of nilotinib-treated patients.
Source: Oppenheimer/Ferreiro, December 6, 2013

yes, because I was thinking that they answered these qustions already

http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Iclusig_20/Procedure_started/WC500157072.pdf

I have thought that you have been kidding, but now I know you're serious. So Good Luck!!!

so, can you explain me her valuations of Ariad $50 in March 2014? Which factor has what value? because maybe I can learn something interesting in valuation methodology …Clovis stocks are valued largely by sentimental, which is positive contrary to Ariad. The Purchase of a biotech stock is a investment. It's not an act of charitable giving to sufferers of target disease. As an investors, we are allowed to be disappointment and dispassionate in our evaluation…

"The day after the drug was withdrawn, 23 physicians signed a letter to Richard Pazdur, MD, director of the hematology and oncology products office at the FDA Center for Drug Evaluation and Research, asking the agency to speed up a process that would allow patients who were already using ponatinib to keep receiving it. The program went into effect within 3 days. "We understand the need for access to products for the treatment of serious and life-threatening diseases and that there are some patients who are currently receiving [ponatinib] who will require continued drug access," Dr. Pazdur wrote in response to the physicians' letter."."We support the FDA and the job they have to do," said Hans Loland, a computer systems analyst from Woodinville, Washington, who organized an Internet group for CML patients. "But we want a balanced approach."

agree with you…

If you read my posts, or ask Doug or others, you see that I was long… but after Ariad crash I have bearish view of Ariad( more realistic ),but that is only my view, more objective… now I see many post here try to pumping price to unrealistic price, seeing only positive side…so I try to show people here also other side of Ariad… if you are smart investor(investing in biotech is risky) you can balance this and know where you going, so you don't have big loss in the future…

I was long for five years, now I'm Neutral , more objective…

“The situation with ponatinib is very difficult,” Cortes told HemOnc Today. “Ponatinib provides benefit to a subset of patients who have not responded to treatment with other tyrosine kinase inhibitors or who harbor the T315Imutation and therefore have no other options. However, we also saw increased evidence of safety signals, and we can’t ignore that.” http://www.healio.com/hematology-oncology/hematologic-malignancies/news/online/%7B2b1d6109-030d-42e5-b795-2e678358a6f5%7D/ponatinib-demonstrated-activity-in-patients-with-cml-phall

Ariad: CHMP Opinion Keeps Iclusig on EU Market, Avoids Worst Case Scenario; EU Launch Plans Unaltered, U.S. Timelines Remain Unclear
New EU recommendations are more lenient on thrombotic events. The EMA has recommended: 1) Iclusig shouldn’t be used in patients with a history of heart attack or stroke unless the potential benefits outweigh the risks; 2) CV status of patients should be assessed and CV risk factors managed before starting therapy, as well as CV status monitored/optimized during treatment; 3) hypertension should be controlled during treatment and Iclusig discontinued if not; and 4) patients should be monitored for evidence of vascular occlusion/thromboembolism, and treatment should be discontinued immediately if this occurs.
New EU recommendations appear to allow for physician discretion. This is highlighted by quotes such “unless the potential benefits (of Iclusig) to patients outweigh the risks” when considering use in patients with a history of heart attack or stroke. It appears encouraging that the label puts the decision on which patients are appropriate candidates for Iclusig in the hands of docs. We also note that conditions related to blood clots, such as heart attacks/strokes, were already considered to be possible AEs of Iclusig and were listed in the EU product information, so this is not new. However, as more clinical data and commercial experience with the drug comes to light, further EU restrictions are still possible.
Ariad’s view of the EU market has not changed as a result of these new CHMP recommendations and, as such, the company is not altering its EU launch plans at this time. The company has taken a phased approach to its EU launch (based on the pricing/reimbursement process and approvals country by country). In 2014, Ariad expects to be able to offer additional EU launch insights/metrics.
The timing and next steps for Iclusig in the U.S. remain unclear. In the meantime, Iclusig should have a meaningful (and potentially controversial) presence at the upcoming ASH meeting from December 7-10 in New Orleans. We also anticipate '113 to enter a potentially pivotal Phase 2 trial for NSCLC in 1Q14.
Source: JPMorgan/Kasimov, November 22, 2013

If you read EMA http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/11/news_detail_001968.jsp&mid=WC0b01ac058004d5c1 there you can find:"In addition, in a recently discontinued phase III study that compared Iclusig with imatinib with a median treatment duration of 3 months, there was a higher number of occlusive vascular events reported in the Iclusig arm…" and it's take some times, probably 2 years to conduct new trial…

Be realistic guys, without first line, without probably second line, without US market, Ap26113 without EGFR, ROS1, Ariad will never get back to $22/share price=$4B market cap, in this price was included everything!, Now in 2013 Ariad earning will be probably $30M, next year how much? $40M-$70, so what is market cap for this? Be realistic …

http://www.forbes.com/sites/matthewherper/2013/06/23/the-fdas-cancer-czar-says-he-cant-approve-new-drugs-fast-enough/

Ariad: Cost Cutting Likely Not Enough; More Capital Required in 2014; AP-26113 Open-Label Phase II Trial to Start in 1Q14
Withdraw of Iclusig from the U.S. market necessitated a complete rethinking of Ariad's cost structure and priorities. We believe that Ariad's guidance for a 35% reduction in operating cash burn in 2014 is insufficient and represents only modest changes from its prior clinical priorities. Cost cutting items included:
? Winding down ongoing Iclusig trials (EPIC)
? Delaying the start of the SPIRIT 3 trial
? Prioritizing the preclinical pipeline to a single candidate with IND expected H2:14
? Focusing AP-26113 development on ALK+ NSCLC and not EGFRm
These changes are not significant enough to make a real difference in the overall business model. We question the continued investment in AP-26113, pending more safety data. We also question development plans for Iclusig in other indications such as GIST.
Updated Iclusig Launch Details:
No revenue from U.S. market. Iclusig is off the U.S. market as of Oct. 31st, and U.S. patients on the drug are no longer being charged (no sales allowed until marketing approval is reinstated). Drug sales/Rx will no longer be reflected in IMS data. We do not expect significant new patient accrual while the drug is officially off-market. Ariad made statements on the U.S. launch as of the end of October, 2013:
? Over 1,000 patients have been treated commercially since launch, up from 610 at the end of Q2; ARIA also noted that approximately 600 patients were still on drug at the end of October. These patients are allowed to stay on treatment through a single patient IND.
? Over 600 unique prescribers, up from 450 at the end of Q2.
? Cumulative Iclusig sales are slightly less than $40M since launch through Q3.
EU launch focused on EU-15 countries. In the EU, Ariad is selling drug in Germany, UK, and Austria. These countries represented a small portion of Q3 sales. The drug is currently being provided to patients in France, but sales are not being booked until pricing is determined within the next few months. Sales in other EU countries are expected by Q1:14, including Italy, Switzerland, Norway, Belgium, the Netherlands, and Denmark.
Japan filing to continue. Ariad reported that the Japanese Phase I/II trial is fully enrolled and that the company will continue with Japanese regulatory filings.
AP-26113 Open-label Phase II trial to start in Q1:14. Ariad is focusing AP-26113's clinical development solely on ALK+ NSCLC patients. This is a logical move given the lack of efficacy seen in other lung cancer treatment settings, such as EGFR and ROS mutants. Ariad is confirming safety of a 90mg/180mg dose titration schedule to move into pivotal trials. Since pulmonary AE's are typically seen at the beginning of treatment, the company believes that lowering dose at the beginning will improve the safety profile.
Ariad expects to start a single-arm pivotal Phase II study in Q1:14 on a focused population: ALK+, crizotinib failure with or without CNS involvement. We would not like to see Ariad move forward with AP-26113 until we have greater confidence in the pulmonary safety of the drug.
Source: Credit Suisse/Kantor, November 13, 2013 Oncology Indication: Hematologic

Ariad: EU CHMP Opinion on Iclusig Expected Next Week; Cash Operating Expense Likely to Decrease By 35% in 2014; Cash Should Support Operations Until Mid-2015
Ariad reported 3Q13 revenues of $16.8mn, which were in-line with consensus (source: FactSet). Starting 4Q, Iclusig revenues will drop as the company works with the FDA to lift its marketing suspension.
CHMP opinion expected next week: After reviewing updated data on Iclusig, the PRAC committee in Europe advised physicians and patients that treatment may continue with increased caution and monitoring on thrombotic events. The PRAC also advised that the product label be updated for increased warnings on cardiovascular risk and suggested an in- depth review of the benefit/risk profile of Iclusig. The CHMP will take this advice and meet on November 18-21 and issue its own opinion and potentially update the label. We view this as a risk for Iclusig sales in Europe.
Ariad plans to cut 40% of U.S. positions: Ariad announced a restructuring plan last week that will reduce positions in the U.S. by ~40%. These cost reductions will be taken across the board, from Iclusig marketing expenses, development activities for Iclusig and AP26113, discovery research, and G&A. Ariad will incur approximately $5 million in restructuring charges in 4Q13.
Cash expected to last thru mid-2015: Ariad ended 3Q13 with ~$294mn in cash and marketable securities. The company expects its cash operating expense to decrease by ~35% in 2014 and expects its cash to support operations thru mid-2015. This is based on the assumption that U.S. Iclusig marketing will not resume before mid-2015, which Ariad described as a worst-case scenario. We have assumed the marketing hold will be lifted in 3Q14 but sales in 2H14 will still fall below 3Q13 levels as we expect a much narrower label (for salvage therapy and T315i mutations). One upside potential is if Ariad increases the price of Iclusig significantly following the re-introduction of Iclusig.
Our 2013 EPS increases from a net loss of $1.59 to a net loss of $1.51 given the 3Q beat and lower expenses. We reduced our U.S. Iclusig sales estimates in 2014 and as a result, we are lowering our 2014 EPS to a net loss of $1.12 from $1.08.
Source: Barclays Capital/Huang, November 12, 2013 Oncology Indication: Hematologic