Vismodegib Breast Cancer; resistance

Prana's Parkinson's Drug Meets Michael J. Fox Foundation Development Milestone
PBT434 Advances Through IND Enabling Studies
Press Release: Prana Biotechnology – 17 minutes ago
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Prana Biotechnology Ltd.Prana Biotechnology Ltd.
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PRAN 1.7301 +0.0401

MELBOURNE, AUSTRALIA--(Marketwire -08/29/12)- Prana Biotechnology Limited (PRAN) (PBT.AX) announced today that its lead compound in development for Parkinson's disease (PD), PBT434, had progressed successfully though a series of preclinical development studies used to assess the suitability of a candidate compound for human clinical studies. The studies were funded by The Michael J. Fox Foundation (MJFF) 2011 Pipeline Program to support its 'Therapeutic Development Initiative.' The MJFF Program grant is milestone based. PBT434 achieved all of its milestones in preclinical toxicology studies, genotoxicity and safety pharmacology -- allowing the compound to be positioned for larger scale animal toxicology studies prior to commencing clinical trials.
PBT434 is a novel, orally available compound that easily crosses into the brain and is able to exert potent neuroprotective properties. Most particularly, it preserves the brain tissue in PD that degenerates over time, the substantia nigra. By preserving this tissue, Prana's scientists have demonstrated significant restoration of motor coordination and strength in animal models. PBT434 has been shown that it is able to impede the iron-induced oxidative damage and neurotoxic cascade that kills the substantia nigra. As such, PBT434's mechanism of action offers a novel disease modifying therapeutic strategy in contrast to the currently marketed symptomatic agents that, at best, serve to reduce the side effects of the disease rather than alter its course.
"Based on these efficacy studies and now the completion of this suite of preclinical development assessments, Prana will look to move PBT434 into longer term toxicology studies in parallel to our scale up manufacturing plans for PBT434. All being well, we could file an IND by the end of next year and commence clinical trials in 2014," said Mr. Geoffrey Kempler, Prana's Executive Chairman. "PBT434 also marks another product pipeline milestone for Prana to complement our two ongoing trials with PBT2 in Alzheimer's disease and Huntington disease," commented Mr. Kempler.
Parkinson's disease is a devastating illness which can result in not only the loss of muscle control, speech, balance and digestive functions; it may also impair a patient's psychiatric and cognitive function. With 4 million people affected worldwide, Parkinson's disease is the second most common neurological indication behind Alzheimer's disease. The current market size for drugs to treat Parkinson's disease is approximately $4 billion per year; however most currently available drugs primarily treat the symptoms and do not actually prevent the ongoing destruction of the substantia nigra in the brain and progression of the disease.
* The program grant title is 'PBT434, a novel neuroprotective drug for Parkinson's Disease; completion of pre-clinical studies to enable human clinical trials.'

I am convinced CRIS is garbage. Sick of waiting around for their incompetent management team to get their act together. Will be selling on any signs of strength as this company is a joke.

Cris has finally made through 5.00. How far can it go?

Debio 0932 HALO Study: CRIS (see link below)
http://www.debiopharm.com/images/stories/DownloadCenter/120329_FINAL_Poster_study_Debio_0932-201_ELCC.pdf

Are you buying it back now, BTH?

RE: ARIA

Technically speaking, me personally, I would like to buy it at the 200 DMA around 13.50ish, (OR) above $16.00. I know that sounds weird, but, I don't like it in between. I think it finds support at the 200 DMA. If not, it could go a lot lower (just on technical breakdown). Above $16 would be a pure momentum play, and breaking out.

'113 news would really get things ramping again.

At what point would you buy back in to Ariad? Have you done so already? I am holding some Cris, it seems to trade pretty consistently. It feels to me like it will go up soon from these levels.

Thanks for that in depth answer. I took some profits after Ridaforolimus got rejected by the FDA panel. I was shocked that Ariad went up after the rejection. It shows how hard it is to get anything through the FDA, and to conduct a valid, proper trial. There is so much potential for mistakes and errors along the way. Perhaps that is why even with so many promising drugs Cris is not higher.
I'm still holding about 2/3's of my Ariad, but may lighten up even more this week. I still feel like I should use mental stops on Ariad, but as some of the Ariad Hub writers always say, "know what you own," and it hasn't paid to use stops.
You have really toned down your criticism of Ariad, but I guess after the stock is up 5X this past year, there is not much to criticize.
Fortunately, my big winner this year has been Ariad and Apple. Apple has been amazing, as have been their products. To think that they will only sell 55 to 60 million I Pad 3's, as is forecast, is a joke. I think they could sell twice that worldwide. It is the most amazing thing I have ever held. They are going to earn over $50 per share in about a year. It is still cheap, although I am thinking about taking profits soon after a straight up run. Google is my next stock that I think will move quite a bit soon. I have had that one for several years. They will earn $45 per share next year. Intc is another one I like here. A correction is a possibility soon, though, and they all could take a hit.
To think that Ariad could really have two great cancer drugs that are properly tested and are effective, is quite an accomplishment. 113 could really be the key to their future and the stock price taking off, as well obviously as ponatinib. Rachel McMinn has been quite accurate in her assessment of Ariad. When she turns bullish that would be a great sign. It hasn't happened yet.
Cris is something that I will take seriously now, thanks to you. I'll start slowly, and get in soon. Thanks.

Yes, I took profits in ARIA. A little lower, between 15.60 and 14.55. I would be a buyer on strength again, as I still think the stock has a lot of upside (or, contrarily, on big macro weakness). '113 really is the key to another 10 point leg up; and, a hostile bid is always on the table - its really one of only a couple companies out there that have huge potential. I basically took profits because I want to wait and see what happens....and It was a great trade from the August lows. Still have a little though.

As far as CRIS. I truly believe the stock should be at least valued at 8-10 alone on their first drug, GDC-0449 (Erivedge). The BCC indication alone is actually a lot bigger than they are getting credit for right now. They got a broad FDA label on the drug which actually gives Doctors to possibly prescribe it in Gorlins patients and some operable cases as well. Theres a potential of 20k patients a year here... $7,500/month x 10 mos. IF they show any success in pacreatic, gastroesophogeal, or SCLC, or sarcoma, tack on another 500 million to $1 billion potential. GDC-0449 has the potential to be a $2 billion drug. The market is essentially giving no value to CUDC-101, or their three other compounds....its kind of a joke. CUDC-101 has the potential to begin a registration Phase 2 trial early next year....and it is given no value even though it has shown some really good early responses in refractory head and neck, and also refractory liver tumors. They also have a PI3K compound, and an HSP90 drug partnered with Debio which has shown some activity in NSCLC. All for a market cap of $350 million.

The only reason FMR, Wellington, etc., Baker, Sectoral, are not big in the name (IMO) is because its a lot easier to pick up a large chunk of stock in a financing, than it is to go to the open market. Look at their institutional ownership - for a company with a large revenue source in royalties going forward, and three other drugs, Sectoral, Baker Bros, FMR, Wellington, BB Biotech, Orbimed, BVF....none of these guys are in the name yet. No onwership at all. You want to be in before the start to pile in....IMO.

BTH, Do you feel like Cris has the potential to move like Ariad did this past year? Are you holding a lot of Cris, and did you take any profits in Ariad recently? Thanks.

AACR Abstracts

http://seekingalpha.com/article/460171-aacr-annual-oncology-meeting-a-look-into-various-abstracts?source=yahoo

CRIS

http://seekingalpha.com/article/445871-curis-potential-blockbuster-application-in-pancreatic-cancer?source=yahoo

Vismodegib

Brand name

http://www.trademarkia.com/erivedge-85369465.html

CRIS

http://ar.iiarjournals.org/content/32/1/89.abstract

I still own it. my guess...strength is because they have several big catalysts in the next six months. possible approval for vismodegib in both EU and US. IMO, revenues have been significantly underestimated by the Street for this drug should it be approved. And they have over 20 further NCI trials for vismodegib in pancreatic and other tumor types, with SCLC and pancreatic, and gastro likely to have results in the first half of 2012.... the pancreatic studies in combination with abraxis and gemzar have been getting a lot of buzz. Further, a readout from Roche in the operable BCC study is supposed to happen very shortly.

IMO, Roche should just buy them for $800 million. And buyout Ariad for $3.5 billion. That would make my 2012. LOL.

best of luck.

Why is cris so strong? Do you still have it BTH? Is it a buy here?

Curis FDA Pediatric Advisory Meeting November 1, 2011
GDC-0449

http://www.fda.gov/AdvisoryCommittees/Calendar/ucm274682.htm

Roche-Curis Vismodegib (Hedgehog) Pivotal Phase 2 BCC Study Commentary


I would like to have a discussion if the AE, SAEs will have a negative effect on the approval of this drug. Keep in mind, other than disfiguring surgury, there is absolutely no other treatment. Is 25% of patients experiencing an SAE enough to get a "no" from the FDA? There's no doubt this drug works for patients in this indication - the Hh pathway in basal cell cancer is mutated in 90% of these patients. Clinical Benefit in ~80% of patients in study. Bear in mind, the following link is efficacy pictures:

http://twitpic.com/6pt7k2

http://www.faqs.org/sec-filings/100108/CURIS-INC_8-K/g60971ex99_1s11gbgd.jpg



Further, 2 million cases of BCC in the US per year and <5% would be available for this drug - which would be 100,000 patients. Assume only 20% of those 100,000 (20,000 patients) get the drug per year. I am assuming based on recent BRAF drug @ $95,000/year, Vismodegib would be at least $75,000 per year. That's a $1.5 billion drug for Roche, just off this one indication in aBCC/mBCC - or at 5%-8% royalty, $75million-$120million/year for Curis off this small indication. Are my assumptions way off here? People continue to say this is a tiny indication, but, numbers wise, so is/was CML, and Gleevec is a multi-billion drug


September 29, 2011 (Stockholm, Sweden) — The investigational drug vismodegib, which has a novel mechanism of action (inhibiting the hedgehog signaling pathway), has shown "substantial clinical benefit" in advanced basal cell carcinoma, in both metastatic and locally advanced settings.

This finding comes from a pivotal trial of the product in 104 patients, presented here at the 2011 European Multidisciplinary Cancer Congress. The results were presented by Luc Dirix, MD, from the Iridium Kankernetwerk, Antwerp, Belgium, from a paper selected as a best abstract for the presidential session.

Vismodegib is "a potential new therapy" for advanced basal cell carcinoma, he told the meeting attendees. It is under development by Genentech/Roche, which has recently filed an approval application with the US Food and Drug Administration for its use in the treatment of inoperable advanced basal cell carcinoma.

The results from the pivotal trial were "totally convincing" and there were some "very spectacular responses" said Caroline Robert, MD, PhD, from the Institut Gustave Roussy in Paris, France, who acted as discussant for the paper.

"Vismodegib is a breakthrough for the treatment of advanced basal cell carcinoma," she said, but cautioned that "long-term tolerance is an issue."

This novel drug is the first in the class of hedgehog pathway inhibitors. This pathway is disrupted in about 90% of basal cell carcinomas; it is also affected in several other cancers, including medulloblastoma.

Advanced Cases Not Operable

Basal cell carcinoma is the most commonly diagnosed human cancer, with more than 2 million cases each year in the United States, Dr. Dirix noted.

Most cases are treated with surgery, he explained. However, a small proportion of patients (less than 5%) progress to locally advanced or even metastatic disease, for which there is currently no standard of care.

In a phase 1 study of 33 patients with advanced basal cell carcinoma, vismodegib showed a 55% response rate and was generally well tolerated (N Engl J Med. 2009;361:1164-1172). The results generated considerable excitement among scientists, and were heralded as a new era in the treatment of basal cell carcinoma.

Those results led to the pivotal phase 2 study conducted by Dr. Dirix's team. Patients recruited to this study had histologically confirmed basal cell carcinoma that was inoperable, or were patients for whom surgery would be significantly disfiguring, he explained. All patients had either locally advanced (n = 63) or metastatic (n = 63) disease, and all received treatment with vismodegib 150 mg orally until progression or until withdrawal from the study.

"Nearly all patients had some tumor shrinkage," Dr. Dirix reported.

Of the patients with locally advanced disease, 43% responded, and "many had huge responses with massive decreases in tumor size," he said. One patient had no evaluable basal cell carcinoma after treatment, he noted.

Patients with locally advanced disease, assessed by independent review, had an overall response rate of 43% (95% confidence interval [CI], 31% to 56%; P < .0001), and patients with metastatic disease had an overall response rate of 30% (95% CI, 16% to 48%; P = .0011).

Median time to progression was 9.5 months for both groups of patients, Dr. Dirix noted.

Adverse events that were reported in more than 30% of patients included muscle spasms, alopecia, taste disturbance, weight loss, and fatigue. Serious adverse events were reported in 26 patients (25%); in 4 patients the serious adverse event was considered to be related to the vismodegib. Fatal adverse events were reported in 7 patients (7%), but none were considered to be related to the drug.

In her discussion of the study, Dr. Robert drew attention to these tolerability findings. Most of the patients in this study could not tolerate the drug for more than 18 months, and overall, 25% of patients stopped therapy because of toxicity, she noted. My thoughts: would you rather suffer from side effects, or have a massive hole in your head? Did patients see tumor shrink dramatically and therefore decided that they were done with the drug because they didn't want to deal with hair loss, muscle spasms, etc etc.

In another study of vismodegib, conducted in 41 patients with Gorlin syndrome, about 30% stopped taking the drug because of adverse events, she added.

Dr. Robert speculated that there might be a use for vismodegib in the neoadjuvant treatment of advanced basal cell cancer, for example with patients taking it for 3 months or so to shrink their tumors and then undergoing surgery. "We need to explore other modalities," she said, and "surgery must always remain in the algorithm."

Dr. Robert also provided interesting insight into how the drug was developed. Cyclopamine, a chemical extracted from the corn lily, was found to be an inhibitor of the hedgehog pathway. Attention was drawn to this plant after it was noticed that sheep that fed on the flowers while they were pregnant gave birth to deformed offspring, with only 1 eye and brain malformations.

The trial was funded by Genentech/Roche, the companies that are developing vismodegib.

2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 1BA. Presented September 24, 2011.

8x8 Inc (EGHT) received bids on 1 or 2 of its 5 patent families, says Craig-Hallum

8x8 Inc (EGHT) in talks w 2 large phone carriers on VOIP deals...also in talks in regards to their patents w carrier - Craig-Hallum

tgt is $6 and $12 when deals get signed by craig hallum in this note

(source of the above is apparently from Craig-Hallum Institutional via StockTwits)

CRIS ABSTRACT 2011 Stockholm Congress (ECCO)


Hall A1 Date: 24-Sep-2011 From: 13:45 To: 15:35


14:15 BEST ABSTRACT: A Pivotal Multicenter Trial Evaluating Efficacy and Safety of the Hedgehog Pathway Inhibitor (HPI) Vismodegib in Patients With Advanced Basal Cell Carcinoma (BCC) 1BA
Speaker LBA: Dirix, L. (B)

GDC-0449 combination study with Gemcitabine

Stand Up For Cancer sponsored trial with Roche

Patient forum. Obviously, its only N=1, but, its worth exploring more

CRIS pancreatic



http://jnci.oxfordjournals.org/content/102/7/448.full.pdf

Exelixis Provides Update on Cabozantinib Development Activities

Timeline for reporting top-line data from EXAM extended by
approximately three months


Protocol for XL184-306 pivotal trial in CRPC submitted to FDA for
review


Management to hold conference call at 6:00 p.m. EDT/3:00 p.m. PDT
today





Business Wire
4:00 PM Eastern Daylight Time Jul 06, 2011
Exelixis, Inc. (NASDAQ:EXEL) today announced an update to the timing for reporting top-line data from the ongoing phase 3 pivotal trial of cabozantinib in patients with medullary thyroid cancer (MTC), known as the EXAM trial. The company has extended the timing to report top-line data from this trial by approximately three months. The timeline is being extended from the middle of this year to provide additional time for the trial to reach the pre-specified number of progression-free survival (PFS) events required for un-blinding of the data.

“We continue to be optimistic about a positive outcome for the EXAM trial. We believe the activity that cabozantinib has demonstrated in MTC as part of the ongoing phase 1 clinical trial of cabozantinib in this indication as well as the selection of MTC patients with rapidly progressing disease increase the possibility of a positive outcome for the EXAM study,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We also continue to advance the development program in castration-resistant prostate cancer (CRPC). The protocol for the XL184-306 pivotal trial using a combined endpoint of pain reduction and bone scan response was submitted to the U.S. Food and Drug Administration (FDA) in June for consideration of a special protocol assessment (SPA) and our goal is to initiate this trial by the end of 2011. Additionally, we are planning the XL184-307 and XL184-308 pivotal trials in the CRPC for overall survival and bone metastasis-free survival respectively and expect to initiate both of these trials in 2012.“

EXAM Trial Design

EXAM is an international, randomized, placebo-controlled, double-blinded study of cabozantinib in patients with unresectable, locally advanced, or metastatic MTC. Patients are randomized in a 2:1 ratio to receive cabozantinib or placebo administered at a daily dose of 175 mg. The study does not allow for cross-over from the placebo arm to cabozantinib. With an enrollment target of 315 patients and a planned event-driven analysis, the trial provides 90% power to detect a 75% increase in progression-free survival, the primary endpoint of the study. Additionally the study is designed to assess overall survival at a later time point once those events have been achieved, and is powered to detect a 50% improvement in survival compared with placebo. Exelixis is conducting this trial under a SPA from the FDA, which allows for full approval on the basis of PFS if the data are supportive. EXAM completed enrollment in the first quarter of 2011.

EXAM Patient Population

To best assess cabozantinib’s ability to impact progressive disease, enrollment in the EXAM trial was restricted to patients with rapidly progressing MTC, which was defined as evidence of progressive disease per RECIST comparing the baseline scan with an assessment obtained within the previous 14 months. Medullary thyroid cancer typically follows a slow path of progression, and patients may live for a period of years without their condition worsening. Patients after surgery who have stage I disease have median survival in excess of 10 years. Median survival in patients with stage IV disease (metastatic MTC) is two years. It is expected that median survival in EXAM’s patient population would be less than two years given that their disease is unresectable, locally advanced, or metastatic MTC that is actively progressing.

Phase 1 Experience in MTC

Data from the ongoing phase 1 clinical trial have been presented at several oncology and thyroid meetings over the past few years and the phase 1 clinical data was recently published in the Journal of Clinical Oncology in late May of this year. Investigators are still following a number of patients who are on continued study treatment.

The phase 1 trial enrolled a total of 37 patients with 35 patients being response evaluable. It showed a 29% rate of confirmed partial responses. These responses were generally durable with a response duration of up to 48+ months per the most recent update. Four patients are in continued response at the current time. Additionally, 15 patients (41%) had stable disease lasting longer than 6 months with some patients continuing on study 3+ years after study initiation. Activity was independent of both RET mutation status and prior treatment with tyrosine kinase inhibitors, including vandetanib.

NDA Filing Plans for MTC

As previously reported, the FDA has granted cabozantinib orphan drug designation and fast track status for MTC, and the latter confers several important benefits, including the potential ability to file a rolling New Drug Application (NDA). Given the extension of the timing for the un-blinding of the EXAM trial, Exelixis now plans to initiate a rolling submission in the fourth quarter 2011 by submitting key parts of the NDA, including the preclinical and chemistry, manufacturing and controls (CMC) information later this year, and expects to complete the file in the first quarter of 2012. Assuming a positive outcome in the EXAM trial, the Company currently anticipates a commercial launch of cabozantinib in MTC in the second half of 2012.

Conference Call and Webcast Information

Exelixis’ management will discuss the updated timeline for reporting top-line data from EXAM and provide an update on the comprehensive cabozantinib development program in MTC and CRPC during a conference call beginning at 6:00 p.m. EDT / 3:00 p.m. PDT today, Wednesday, July 6, 2011. To listen to a live webcast of the discussion, visit the Event Calendar page under Investors at www.exelixis.com.

An archived replay of the webcast will be available on the Event Calendar page under Investors at www.exelixis.com and via phone until 11:59 p.m. EDT on August 6, 2011. Access numbers for the phone replay are: 888-286-8010 (domestic) and 617-801-6888 (international); the passcode is 50152278.

About Cabozantinib

Cabozantinib is a potent, dual inhibitor of MET and VEGFR2. Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways. The therapeutic role of cabozantinib is currently being investigated across several tumor types. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:

Extensive apoptosis of malignant cells
Decreased tumor invasiveness and metastasis
Decreased tumor and endothelial cell proliferation
Blockade of metastatic bone lesion progression
Disruption of tumor vasculature
About Exelixis

Exelixis, Inc. is a biotechnology company committed to developing small molecule therapeutics for the treatment of cancer. Exelixis is focusing its resources and development efforts exclusively on cabozantinib, its most advanced solely-owned product candidate, in order to maximize the therapeutic and commercial potential of this compound. Exelixis believes cabozantinib has the potential to be a high-quality, differentiated pharmaceutical product that can make a meaningful difference in the lives of patients. Exelixis has also established a portfolio of other novel compounds that it believes have the potential to address serious unmet medical needs. For more information, please visit the company's web site at www.exelixis.com

Personally, I want to see a blow-off rally on big big volume before I take a lot, if not all, off the table. It has been a good run..I am not quite sure it's over yet.

I am up nearly 1,000% on some positions I took a long time ago. That's a lot, and it's not something I am going to be confortable with myself if those gains evaporate because I got greedy (a common mistake).

BTH, at what point would you take some profits in Ariad? This run has been amazing, but at some point it has to take a breather. Right now it is at 11.60. Who would have thought it could get here so quickly.

CURIS Article

http://www.xconomy.com/boston/2011/06/28/curis-and-genentech-unleash-the-hedgehog-to-fight-a-deadly-skin-cancer/

FGFR1 mutations in squamous cell lung cancer
Posted: 17 Jun 2011 07:53 AM PDT



“Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas.”
Dutt et al., (2011)
This snippet from a paper in PLoSOne caught my attention, because while we have seen a number of molecular targets identified and therapies developed for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.
Squamous cell carcinomas account for 25% of new lung carcinoma cases and 40,000 deaths per year in the United States, a not inconsiderable number of patients.
This isn’t a new finding per se, as we have discussed FGFR1 amplification in lung cancer previously on this blog. However, what was also interesting and novel about the paper, is that the authors went on to note:
“Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.”
In this study, the pan-FGFR inhibitor PD173074 (Pfizer) was used to test whether cell growth was attenuated or not. There are a number of FGFR inhibitors in development, which we discussed in the last blog post on this topic in December.
All this sounds very encouraging indeed, although there are caveats that should be stated, for example, preclinical research is no guarantee of success in the clinic and amplification of a mutation or gene (as opposed to mutation) does not mean that it is a driver of the disease – it could be a passenger or overexpression as a consequence of other things happening as a result of the tumour proliferation.
Still this is a promising finding well worth exploring, because as the authors rightly point out, “no FDA-approved targeted therapies for squamous cell lung cancer.”
The critical key to exploring mutations, amplifications and targeted therapies in the clinic going forward will be to have well designed iterative phase II trials with very careful patient selection based on the known biology to tease out the patients most likely to respond rather than catch-all studies where the chances of finding responders over non-responders is much lower.
Why do this? Overall, I think it is better to have high response rates in a small subset than a low response rate in an unselected population where people who have no chance of doing well are exposed to the systemic side effects unnecessarily.
We can see this trend clearly emerging with the well designed trials ELM4-ALK translocations for crizotinib, for example. Interestingly, ALK and lung cancer mutations (seen in adenocarcinomas) are very much in the news this month, following some excellent data at ASCO for Pfizer’s crizotinib that augers well for FDA approval and Ariad announcing that they are progressing their dual ALK-EGFR inhibitor, AP26113, into the clinic. Preclinically, this agent has also been shown to inhibit the T790M mutant that is resistant to EGFR inhibitors.
Oddly, Ariad’s other drug in phase II clinical development for CML, ponatinib, also inhibits FGFR and FLT3 as well as BCR-ABL, the critical target in CML; this will be an interesting company to watch out for over the next few years.


Source: Pharma Strategy Blog: FGFR1 mutations in squamous cell lung cancer

I don't like AMRN. Chart still has a big fat gap in it.

CEO kinda put the stock down by saying there wuold be no buyout or deal

Toe out on AIS. Will try to get in lower. ditto AMRN, AMLN.

I'm looking to sell my holding somewhere in the mid-teens in ARIA (purely based on technicals). I think ARIA drugs are great but I just think coming from the 2's to 15's, is enough and could be due for retracement of some sorts.

I do not know what I will be doing with that capital if I will be re-investing in equities, or real estate. The biggest problem I have with re-investing the capital in equities is finding a good place for it...considering the macro-market, and problems in the global economy (I really would like to liquidate everything in the near future and take a seat back and watch what happens). If QE3 comes back on the table, I would stay long everything personally.

BTW, people hate this market right now. If some sort of new stimulus comes on the table or they clear up the EU problem, yes, the market is definitely oversold here. 7 straight down weeks...c'mon....we are due for snapback at very least

Sell Ariad and buy goog and aapl? BTH, you really know biotech fundamentals and market technicals. A rare combination. The Ariad board seems to be so sure about much higher prices for aria. Nothing is that easy, usually. Is it possible that the fundamentals are so positive and yet not reflected in the price? At some point buying Google at 500, when they are going to earn $40 next year with $110 in cash is close to a lock long term, as far as I'm concerned. Buying Apple here is also very solid. I guess ariad is potentially a stock you can retire on if it truly goes to 20, 30 or 40. At what point would you sell it, and swtich out? As far as I'm concerned we are so oversold as to be right near a bottom, right here in the market.

FYI

http://www.pharmalive.com/magazines/randd/dl.cfm?articleID=10506

Thx. I'm gonna put a toe in on AIS. More on the LNKD puts.

I don't know anything about AIS. The chart looks like its shaping out nicely, however.

I like your LinkedIn idea, FWIW. I can't see why that company is trading at that valuation.

BTH, What do you think of AIS, great momentum it seems...

http://www.thestreet.com/story/11149936/3/4-stocks-setting-up-to-break-out.html

I like it as it is not oncology play.

FYI, I've got my toe in the water on shorting LNKD (via puts, the Nov 65's, and shorting the Euro, vis EUO (Ultrashort ETF), as much as I disdain ETF's.


Thinking about a play on qqq, but came late to the move, will watch it to see which way it's going, or will straddle.

Dalotuzumab failure

One more reason why Merck needs an MTOR to combine with their IGFR1:

Curis Presentation June 2011

New slides on CUDC-101

http://www.wsw.com/webcast/jeff60/cris/

Showing efficacy in liver cancer patient who has been through 2 SOC treatments.

In Vivo Combination Study Ridaforolimus

ASCO Poster

http://sherifmorgan.com/wp-content/uploads/2011/05/Morgan-and-Cranmer-ASCO-Poster-Final.pdf

Trials in Progress Poster Session

Lots of data in trials in progress.

http://www.asco.org/ASCOv2/MultiMedia/Virtual+Meeting?&vmview=vm_session_presentations_view&confID=102&sessionID=4169

GDC-0449 and FOLFOX in gastro

Ridaforolimus + MK-646 in breast cancer

Medco Health Solutions has added BCR-ABL testing to its personalized medicine portfolio, marking the tenth such offering under its DNA Direct clinical testing program.

The company said this week that it will offer MolecularMD's qRT-PCR BCR-ABL test to patients diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in order to monitor their response to tyrosine kinase inhibitors such as imatinib (Novartis's Gleevec), dasatinib (Bristol-Myers Squibb's Sprycel) and nilotinib (Novartis's Tasigna).

More than 95 percent of CML patients harbor a mutation in BCR-ABL, which is also called the Philadelphia chromosome. The protein produced by the BCR-ABL gene promotes cancer cell proliferation, and TKIs such as Gleevec, Sprycel, and Tasigna inhibit the activity of the mutated BCR-ABL protein to suppress the cancer's growth.

The National Comprehensive Cancer Network recommends BCR-ABL testing in CML patients at diagnosis to establish a baseline BCR-ABL level, every three months while a patient appears to be responding to treatment, and every three to six months once a patient achieves complete cytogenetic response.

Separately, Ariad Pharmaceuticals is using MolecularMD's ABL kinase domain sequencing technology to pick out best responders to its investigational BCR-ABL inhibitor ponatinib in the so called Ponatinib Ph+ ALL and CML Evaluation, or PACE trial. Using the test, researchers will give the drug to patients with mutant forms for BCR-ABL who are intolerant or resistant to Sprycel or Tasagnia or developed T315I mutations after receiving any tyrosine-kinase inhibitor, including Gleevec (PGx Reporter 03/30/2011).

Jane Barlow, vice president of clinical innovation at Medco, said in a statement that using BCR-ABL testing regularly to determine if a patient is exhibiting the appropriate response to the drug "can help ensure better clinical outcomes for the patient and reduce overall healthcare costs for the health plan."

Barlow told PGx Reporter that even though NCCN recommends quarterly BCR-ABL testing for patients taking TKIs, many physicians do not comply with these guidelines.

Medco researchers recently examined medical claims records of 359 CML patients who were treated with Gleevec and found that only 60 percent had evidence of at least one test performed at any time over the last one and a half years, while only 14 percent had BCR-ABL testing recorded on a consecutive quarterly basis.

"These findings are important in that regular BCR-ABL monitoring is needed to avoid delay in key decisions about CML treatment, as well as to help insure the best treatment outcome possible," Barlow said.

The company decided to launch the BCR-ABL testing program in order to address this "gap in testing to evidence-based guidelines," and also because "strict adherence to these medications is critical to the success of the treatment and thus can be life saving," Barlow said.

Medco will offer MolecularMD's BCR-ABL test as part of its DNA Direct clinical testing services. Once the pharmacy benefits manager identifies a patient in need of the test and secures a physician order, it will send a specimen collection kit directly to the patient. The patient's physician or phlebotomist then collects a blood sample and sends it to MolecularMD's CLIA-approved and CAP-accredited facility, where the test is performed.

MolecularMD will provide a quantitative report that will reference the International Scale, an internationally accepted standard for monitoring BCR-ABL transcript levels in CML patients. The report will also include information on the patient's adherence to therapy, which will assist the physician in "addressing any adherence barrier that might contribute to a loss of response to therapy or drug resistance," Medco said.

Barlow told PGx Reporter that the company is partnering with MolecularMD for BCR-ABL testing because of the company's "experience in this field," and the fact that the firm has "been at the forefront of research related to these medications and BCR-ABL testing."

MolecularMD founder Brian Druker, director of the Knight Cancer Institute at Oregon Health & Science University, led the clinical trials of Gleevec for CML.

Barlow also cited the fact that MolecularMD tests to the International Standard, "which allows for a more accurate comparison of test results from the same and different labs that also use the international standard."

Other companies offer laboratory-developed BCR-ABL tests, including Roche, Qiagen, and the Laboratory Corporation of America. Last year, Gleevec manufacturer Novartis began collaborating with Cepheid to develop a PCR-based BCR-ABL test on Cepheid's GeneXpert system that will also be compliant with the International Scale. The partners said they plan to seek clearance for the test through the US Food and Drug Administration, which would make it the first BCR-ABL test to gain FDA approval (PGx Reporter 10/13/10).

— Turna Ray contributed reporting to this article.