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considering it's now 3.11X3.28 i think it's safe to assume the 2.29 was a mistake.
Interview of the doctors who performed the first Levacor implant at INTEGRIS Bapstist Medical Center earlier this year...amazing what you can find on youtube, lol.
2Da, in response to an analyst question earlier this year, Harvey stated that he expected a median pfs for the placebo arm of 4-5 months. So, assuming a median PFS of 20 weeks (in the P2 the overall trial population had a median PFS of 15 weeks) and a targeted increase of 33% we're looking for 26.6 weeks. Of course, the risk is that the placebo arm progresses more slowly than expected but the fact that the IDC recommended the trial continue should provide some confidence that the arms are diverging.
fyi, this press release provides some additional background behind rida's P3 trial design:
"the data from the overall survival analysis of the Phase 2 trial further support our Phase 3 trial design and strategy, which focuses on metastatic sarcoma patients who have experienced a favorable response to prior chemotherapy and have at least stable disease. We believe this well-defined patient population has the greatest likelihood of achieving sustained clinical benefit from treatment with a new molecularly targeted agent such as AP23573."
http://phx.corporate-ir.net/phoenix.zhtml?c=118422&p=irol-newsArticle_Print&ID=1010397&highlight=
Rick,
I've never seen the data broken out publicly but can only surmise that it was a factor in the P3 trial design.
Hi 2Da,
With both gleevec and tasigna, novartis is probably out. BMS could be interesting but risky in that 534 may end up with short shrift vis a vi sprycel. I'm also not in love with the idea of MRK in control of both rida and 534...basically that's akin to selling the company but without the benefit of shareholders getting paid.
Of course ariad could just partner non-US and keep 100% US but that would be a mistake, imo, in terms of maximizing the value of 534 (but it would facilitate Bergers goal of building a stand-alone oncology company)
To maximize 534's value you need multiple bidders but unfortunately none of the best players are a great fit. What do you think about Pfizer as a possibility?
In terms of timing, I think Ariad is perfectly capable of running the P3 trial themselves but there is little advantage in waiting. In fact, from a negotiating standpoint there may be an advantage in getting a deal done before the Rida results are in. My best guess is that they'll try to get something done before ASH.
I realize this sounds obvious but my hope is that Berger focuses on getting a partnership that maximizes the 534 opportunity. In the Merck deal, I think he was more focused on structuring a partnership that fulfilled his goal of building a stand-alone oncology company as opposed to one that maximized shareholder value (although the two goals are certainly not mutually exclusive). Hopefully he's learned a few things from the MRK partnership.
Ironically, while I didn't particularly like the original Merck structure for rida, i think similar terms would work fine for AP534. A deal that requires Ariad to fund 50% of the pivotal 534 registration trial isn't a major concern but running multi-arm trials against Gleevec/Tasigna/Sprycel down the road will be very expensive. Of course, once approved in the 2nd/3rd line, the company should have sufficient revenue to fund its share without further dilution but with Gleevec coming off patent in 2015 and Tasigna and Sprycel moving to front-line, I'd rather see them structure a deal that gets these trials started sooner rather than later.
A deal that generates +100mm upfront and retains 50% of the US would be a good starting place...especially with the right partner...but Novartis and BMS probably aren't a great strategic fit and they are the 2 leaders in CML.
At this stage, missing or beating earnings will have no impact on Aiad's stock price. It's a non-event.
Upcoming catalysts that should impact pps include:
1) Ridaforolimus final analysis
2) Start of AP534 trial
3) AP534 partnership
4) New Rida trials (such as Rida/Dalo P2)
5) Current Rida P2 results (endometrial, prostate, nsclc)
6) Filing AP113 IND
Both the Rida results and the start of the AP534 trial will happen soon enough. The closer we get, the harder the waiting becomes but there's little to be gained from guessing.
I'm really not interested in rehashing the same tired argument over the P2 trial design but if all mTors were the "same", as you put it, then I would have expected that the everolimus P2 sarcoma trial results would have been similar to ridas but they weren't even close. How about we just agree to disagree and wait for the final results?
As far as the difference between mTors, you can find the CEO's pertinent comments below:
"The biggest difference perhaps between temsirolimus and everolimus, and in turn that translates into a difference versus deforolimus, is that temsirolimus Torisel, the Wyeth drug, is predominantly – well, it is approved as an IV formulation given generally weekly, and is a – although there are some data in an oral tablet form, there are very limited data on temsirolimus given orally and it is largely developed and now marketed as an IV formulation.
On the other hand, everolimus is in a tablet form, using the dose and schedule that they put forth which is a daily dose of 10mg a day, and so there the differentiation with ARIAD’s product we are developing with Merck, namely deforolimus, is that our dose and schedule could not be more different. In fact, I would say the everolimus versus deforolimus difference in dosing schedule is as great as the difference between oral and IV.
We are dosing patients at 40mg a day five out of seven days, which results in very high exposure, very high and reliable inhibition of mTOR activity in pharmacodynamic studies, substantial blood levels and circulating levels of inhibitory mTOR activity, a different safety profile in terms of the incidents and timing and severity of mouth sores, you know, and I can go on.
So there are differences and there are similarities among these three drugs and I think until you have a head to head comparison in a randomized trial, it is very difficult to make real comparisons of their efficacy or even their safety profile. But on all fronts, we believe that deforolimus has a very solid and well-accepted both safety and efficacy profile based on the available clinical data to date, but that has really got to get assessed in a prospective randomized trial, which is what is going on."
Updating progress in sarcoma therapy with mTOR inhibitors - June 29, 2010 Annals of Oncology
http://annonc.oxfordjournals.org/content/early/2010/06/29/annonc.mdq307.full
"Sarcoma presents a different therapeutic challenge compared with other solid tumours both because of the limited success of traditional treatment approaches and because monitoring the response of sarcoma lesions to therapy is not straightforward. The PI3K–Akt–mTOR pathway is an exciting target for therapy in many types of solid malignancy and its blockade represents an opportunity to improve outcomes in poor prognosis sarcoma. Activation of the PI3K–Akt–mTOR pathway is implicated both in the establishment of tumours and as an alternative signalling pathway in the development of resistance to antineoplastic therapy via PI3k–Akt or PTEN. Promising results have been observed with mTOR inhibitors both as monotherapy and in combination with cytotoxic and targeted therapies, where mTOR blockade has been shown to circumvent the development of resistance.
The varying degrees of therapeutic success in different tumour types with the available synthetic rapamycin analogues indicate that they are not therapeutically equivalent (emphasis added), and consequently, more research is necessary to define where each agent fits into the treatment strategy for different cancers. Currently, encouraging prolongation of survival in soft tissue sarcoma has been observed with ridaforolimus, and phase III data are eagerly anticipated for this drug."
Hey 2da,
Since I've been in the stock, Harv has told anyone who would listen that he was building a stand alone oncology company. The original MRK deal certainly was structured to reflect that goal (to the shareholders detriment, imo). I'm perfectly happy to let MRK maximize the value of rida in the marketplace. Personally I think AP534 is a much better candidate to build a stand alone company around. Back of the envelope (and assuming a 50/50 partnership structure), I think AP534 alone could be worth around $12 a share as a 2nd line treatment.
the combination of staggered director elections and the inability of the shareholders (even a super majority) to call a "special" shareholders meeting makes a hostile bid a 2 year process. of course once a company is in play anything can happen.
With the board stacked with FOH (friends of Harvey), the staggered board may be more of an issue to a potential buyout than the poison pill. Shareholders would need to replace the majority of the board but Ariad has 3 director classes with only 2 directors up for election each year - so it would take two years to gain board control. To make it even more difficult, I don't believe Ariad shareholders have the ability to call a shareholders meeting in order to overide/speed up the process.
Form 4 filed - the Special Situations Fund continues to add shares.
4th center has now implanted World Heart's LVAD.
SALT LAKE CITY, July 6, 2010 (GLOBE NEWSWIRE) -- World Heart Corporation (WorldHeart) (Nasdaq:WHRT - News), a developer of mechanical circulatory systems, announced today that Jewish Hospital in Louisville, Kentucky, successfully implanted a Levacor(TM) Ventricular Assist Device (VAD) in the Bridge-to-Transplant (BTT) clinical study. This is the eighth implant of the Levacor VAD in the fourth implanting center in the study.
Dr. Mark Slaughter, Chief of the Division of Thoracic and Cardiovascular Surgery, Jewish Hospital/University of Louisville, and surgical co-Principal Investigator of the study at Jewish Hospital indicated, "I am excited by our initiation of patient enrollment in this study. We are pleased to provide a fully magnetically levitated VAD therapy to our late-stage heart failure patients. This is part of our ongoing efforts to find ways to reduce complications and improve outcomes."
Mr. J. Alex Martin, WorldHeart's President and Chief Executive Officer noted, "We are pleased to continue to expand the BTT clinical study at Jewish Hospital led by Dr. Mark Slaughter, a top thought leader in mechanical circulatory support therapy. "
As far as filling the gap goes, $2.58 was close enough for me. Looks like Santa came early this year and he's giving out cheap ARIA shares as presents.
Bladerunner,
Originally, there were four, phase 2 trials: endometrial, nsclc, breast and prostate. Last summer MRK decided not to pursure ridaforolimus in combination with Herceptin (the results were so/so and from a corporate standpoint it just didn't make a lot of economic sense). Considering how well ridaforolimus and Dalotuzumab (Merck's IGFR-1 inhibitor) performed in luminal B breast cancer, I think MRK made the smart choice in pursuing the combination therapy in breast cancer. I'd look for a follow-on Phase 2 rida+dalo trial to be announced next.
As far as the single-agent trials go, I think the endometrial trial is farthest along so hopefully MRK will provide additional data at some point this summer.
The Survey Results are In!
So far we've had 24 folks vote and the consensus is that if rida succeeds the stock will go up by $4.44 and if it fails the stock will drop by $.50. Here's how the results breakdown:
If the Rida trial meets its endpoint, the board expects ARIA, on average, to increase to $7.79 (median $7.75), or 133% from current levels. With the exception of one vote for $4, we seem to be a fairly optimistic bunch (no surprise there) with $10 or higher receiving the most votes.
On the downside, if the trial does not meet its endpoint the board expects the stock, on average, to decrease to $2.85 (median $2.43), or 15% from current levels. $2.50 received the most votes.
Thanks to everyone who participated in our first board survey and if anyone has any ideas for other surveys you would like to see please let me know.
...Don
Please take the Rida results Survey!
The final analysis of the Rida trial is going to move the stock but the big question is by how much? So here's everyone's chance to tell us what they think will happen to the share price if the SUCCEED trial is a success or if its not. Please note that the answers to this survey (and all iHub surveys) are anonymous. No one can see how any person voted.
You can find the survey here:
http://investorshub.advfn.com/boards/do_board_survey.asp?board_id=2047&Survey_Num=1
(don't forget to answer both questions)
P.S. Thanks to chazzz's post for the idea.
Thanks Au-530 and I hope you don't mind a few of us refugees from the yahoo board joining you here. If you got in about a year ago then your timing is great. In August of last year the CEO purchased $3mm in stock at $1.75 a share and both the volume, institutional interest, and pps have been moving up ever since. Imo, the next major catalysts include the start of the pivotal AP534 registration trial, the rida final analysis, and a new partnership is likely on the horizon.
You seem confused, AP464 showed potent inhibition of Bcr-Abl. It was only replaced by AP534 once AP534 was shown to also be effective against the T315I mutation.
The population of the EU is about 501 million people so, using a back of the envelope calculation, it looks like the 5 in 10,000 cut-off translates into no more than 250,000 cases.
I was surprised as well considering RCC is increasing....over 200k new cases diagnosed world-wide last time I checked. Anyway, here's the EU cut-off from the PR:
AVEO receives EMA orphan drug status in RCC.
http://finance.yahoo.com/news/AVEO-Pharmaceuticals-Inc-bw-161566803.html?x=0&.v=1
I guess that explains the 12.4 percent move yesterday.
What you clearly fail to appreciate is that with the advent of molecular targeted therapies, the treatment of cancer is undergoing a dramatic shift not seen since the advent of chemotherapy around 60 years ago.
The ability to identify the genetic and molecular signature of tumor cells has given companies like Ariad the ability to design drugs that specifically target the defective molecular pathways responsible for the cancer cell's abnormal properties. Take ALK for example, it's either present in adults or its not. And if it is present, then either AP113 is able to target it or its not. There's no guesswork here. It's no longer a question of whether a drug works or not its a question of how well it works and how safe it is. The same thing is true with AP534 - either the T315I mutation is present or its not and if it is we know that AP534 is able to target it very, very well.
Like many of your arguments, I find your characterization of this as vapor-ware to be far too simplistic.
It's not just that AP113 has shown increased potency at lower levels which may give it a better safety profile but more importantly that AP113 has shown to be effective against many of the ALK mutations that Pfizer's crizotinib has not. This should allow ariad to use the same fast-track regulatory pathway for AP113 that its been taking for AP534 - namely let Pfizers drug get approved in a first-line setting (and spend the $'s needed to commercialize the initial market) and then get AP113 initially approved in a second-line setting (at 6 months, 28% of pts progressed on crizotinib). Once Pfizer has created the initial market for their ALK inhibitor and AP113 gets approved in a second line setting, Ariad (and their partner) could then run the much more expensive head to head trials needed to move to a first line setting.
DewDiligence, I'm sorry that BiotechHedge has decided to bring this discussion over here so this will be my only comment on the matter.
Actually, BiotechHedge, not all your posts were deleted by me and the ones that were clearly violated IHubs TOS because they were either off-topic or contained personal attacks. On several occasions I invited you to repost without the offending language. The fact that you seem unable to defend your position without resorting to personal attacks actually says a lot more about you than me. Good day, sir.
Actually you've mischaracterized what I actually said. Here's my actual post:
You accuse someone of wild speculation then turn around and do the exact same thing yourself.
What part of the word "imply" did you not understand?
Spin it any way you want but the fact is that the DMC gave Ridaforolimus the go ahead after the second interim results. Any thing else is complete conjecture on your part.
Repeating the same unsupported claims again and again doesn't make them any more true. Once again I fail to see how having a positive second interim look is anything but, well, positive. It's just laughable to imply that rida somehow failed because it didn't reach it's end point EARLY. As I pointed out to you earlier, given that the patients enrolled in the P3 were disease stable, it's really not at all surprising that it may take longer for the rida arm to diverge. You can continue to spin that any way you want but so far you've offered no proof to support your claims. Case in point, the comment you made below: