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just a heads up, ADLR exiting the Russell 3000 index per June 29th
http://www.russell.com/indexes/membership/Reconstitution/Reconstitution_changes.aspx
Really impressive - especially considering that the luminal b type breast cancer has so few treatment options and such a tough prognosis. Roughly 25% of all mBC is luminal so my guess is that we'll see MRK move pretty fast now that they've got their new cancer trials network in place to run trials.
Not sure where your getting your numbers from but just yesterday Harvey reiterated projected cash at FYE of around $46mm. Yes, they were looking for a partner before the MRK restructuring....but,imo, the new deal removed any pressure to partner 534 at this time. Plus, waiting until the registration trial is approved and pts are being enrolled will only increase the value to a potential partner.
As far as trials for the other indications go, I'd like to see them focus their resources on getting the AP534 trial up and running and starting the Phase 1 trial for AP113 as soon as possible. Depending on when the Rida NDA is ultimately filed, I believe they'll be in a much better position to assess their capital needs going forward once the final analysis on Rida is out later this year. At that point, they'll certainly have the option to partner 534 but hopefully the decision will be one driven by market opportunity and not purely funding need. Of course if the rida results come in as expected, the company will likely receive $65mm in milestones in 2011. At that point, I would expect the market cap would better reflect having 2 drugs in Phase 3 with one well on its way to approval.
If the registration trial was a multi-arm, head to head trial, I would tend to agree with you regarding the need for a big pharma partner but in AP534's case the trial is fairly straight-forward. By way of example, take a look at the original sprycel or tasigna P3 trials which I believe will serve as a template for AP534's registration trial. My guess is that we're probably looking at a single arm trial with an enrollment of something around 400 pts which is far less than the Ridaforolimus SUCCEED trial.
Now that MRK has taken over 100% of the Rida development, I'm going to have to disagree with your characterization that ariad is underfunded/undercapitalized. In reality the balance sheet has never looked better with funding sufficient into 2H11 (and beyond if the rida regulatory milestones are met in 1H11).
So, imo, ariad seems well positioned in terms of both capital and personnel to tackle a single arm, multi-center AP534 trial on its own. I'm not suggesting they won't partner AP534 at some point, just that they don't need to at this juncture.
Don
In yesterday's presentation one thing I hadn't heard before is that 50% of Sprycel and Tasigna patients eventually progress. Tasigna and Sprycel combined currently generate $600mm in sales, however, that could grow significantly in coming years. And, with Gleevec coming off patent in 2015, Sprycel and Tasigna are already jockeying for first-line treatment approval which in turn would position AP534 as the defacto second line therapy.
http://www.novartis.com/newsroom/media-releases/en/2010/1421566.shtml
http://www.reuters.com/article/idUSN0413203020100605
Hi 2da, I just listened to the CC and Harvey sounded downright giddy, lol. I mean its been years since he's done one of these conferences and wasn't scrambling to raise more capital.
Based on Harvey's comments today (and on the ASCO results), it sure sounds like Merck will be starting a luminal B breast cancer trial with ridaforolimus and Merck's IGF-1R antibody, dalotuzumab. I'm looking for that news along with FDA approval for the AP534 registration trial soon.
By the way has anyone been following the ZIOP sarcoma trial. A review of their ASCO abstracts indicates that the chemo only arm had a PFS of 4.4 months (just under 18 weeks). While it's an apples-oranges situation, I was just wondering if any had any thoughts?
Don
John, I don't actively follow SPPI. In general the biotech sector has been under a lot of pressure recently as ASCO news fades and investor concerns about the direction of the overall market play out. I took a quick look at the SPPI technicals and, fwiw, it does appear to be putting in a double bottom with macd about to cross positive so, hopefully, the bleeding will stop soon.
Don
I just reviewed the Tasigna approval time-line and it looks like their Phase 3 trial started in March 2006. The trial was stopped early and accelerated approval was granted in Oct 2007, basically 18 months from first enrollment. http://www.clinicaltrials.gov/ct2/show/NCT00302016?term=Nilotinib&rank=49
fyi, the primary endpoint was a 40% MCyR in chronic phase patients. http://www.cancer.gov/cancertopics/druginfo/fda-nilotinib
Dough, check out slide 32 in the latest Ariad investor presentation. It's only preclinical data but the difference between Aria's ALK inhibitor and Pfizer's is pretty striking. AP113 acts faster at much smaller doses (which may indicate a better safety profile).
http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MzgzODg1fENoaWxkSUQ9Mzg1MjE4fFR5cGU9MQ==&t=1
Pfizer's ALK presentation was one of the plenary sessions at ASCO this year and the results from their phase 1 lung cancer trial is getting a lot of buzz (i can't remember the last time a phase 1 drug got a plenary session).
With AP113, Ariad is now proving out the value of their drug discovery pipeline. Much like AP534 which targets BCR-ABL, AP113 targets the ALK gene which is normally turned off in adults.
FYI, Abbot is now developing a test to detect the ALK gene mutation which will benefit ariad as they move 113 to clinical trial.
Hey 2da, great to see you here! Yahoo just got to the point where it wasn't worth the effort. Hopefully a few of the other refugees will join us and we can share our research/opinions/analysis without all the hassle.
As far as other biotechs go WHRT, HALO, GHDX, IDIX are also on my watch list.
Don
Great idea to look at clinicaltrial.gov Tasigna and Sprycel trials (for pts who initially failed Gleevec) to compare how long those trials ran to use as a gauge.
Given there is no approved treatment for pts with the T315I mutation, I believe Ariad will get approval to skip Phase 2, so, the next trial will be the pivotal, Phase 3 registration trial. As far as timing, based on the last cc, I'd say it's only a matter of weeks until we get FDA approval (although the recent pps sure doesn't seem to be reflecting that at the moment)
One thing that gives me a lot of confidence that the fda will approve the AP534 registration trial is the response that Omapro got from the FDA's Oncologic Drugs Advisory Committee earlier this year. Even though they got a complete response letter rejecting their NDA, 4 of the 7 panel members said "Omapro was effective against the disease" even though the MCyR was only 15%. At ASCO, Ariad reported a 57% MCyR in the same patient population (Chronic Phase CML patients with T315I mutation)
Audio from CEO's presentation at Canaccord Adams Cardiovascular Conference
http://webcast.newswire.ca/archive/canaccord20091110/world20091110.wma
Worldheart's slides from Canaccord Adams Cardiovascular Conference...good explanation of competitive products and Levacor's differentiation.
http://www.newswire.ca/en/webcast/pages/en/12927/whrt_canaccord20091110.pdf
In advance of Thursdays Jeffrey's conference, there's a new Investor Presentation available for download on Ariad's website. Here's a link to the pdf
http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MzgzODg1fENoaWxkSUQ9Mzg1MjE4fFR5cGU9MQ==&t=1
WHRT's market cap is roughly the same as it was when the current investors recapitalized the company approximately 2 years ago. Since then they've gotten the LVAD approved, started clinical trials, and begun generating revenue. Yet, you can buy in today at half of what insiders just paid in January.
When one considers that 100,000 patients need transplants each year but only 2,000 get them, I believe the market for LVAD's is going to grow significantly. Whether World Hearts device will be one of the winners remains to be seen but considering HTWR's market cap is over 800 million, I like the upside.
With the Levacor VAD Bridge-to-Transplant (BTT) clinical study underway, it's nice to see the company generating revenue. Based on the $556k booked in just the 1Q, it looks like their recovering around $185k per patient.
Currently the company has 3 medical centers participating but plans to bring on an additional 7 by the end of the summer which should result in more implants and greater revenue.
It appears you've got some smart venture capitalists who've recently put in $$$ at over $5 a share.
26-Jan-10 NEW LEAF VENTURES II, L.P.
Beneficial Owner (10% or more) 388,350 Direct Purchase at $5.15 per share. $2,000,002
26-Jan-10 MARXE AUSTIN W & GREENHOUSE DAVID M
Beneficial Owner (10% or more) 388,350 Indirect Purchase at $5.15 per share. $2,000,002
21-Jan-10 VENROCK ASSOCIATES V LP
Beneficial Owner (10% or more) 388,350 Indirect Purchase at $5.15 per share. $2,000,002
For all practical purpose, these investors have essentially taken the company private and have only left enough float to maintain nasdaq's listing requirements. Of course the downside is that there is very little liquidity and a lot of volatility.
Nice progress in a rapidly expanding market. In the past 18 months, the company has been recapitalized, hired a new ceo and relocated their HQ to the US. They've gotten their MagLev LVAD into a clinical trial and have successfully implanted patients in Oklahoma, Utah and Virginia. The company has a market cap of around $35mm while their primary competitor HTWR has a market cap of over $800. As WHRT's current 160 patient BTT clinical trial progresses, I believe their valuation will be "discovered" in the market place.
Emerging ventricular assist devices for long-term cardiac support
Nature Reviews Cardiology (February 2010)
Rajan Krishnamani, David DeNofrio & Marvin A. Konstam
The evolution of mechanical cardiac support has been fueled by an increasing need to support patients with end-stage heart failure. More than 100,000 patients are estimated to have severe, refractory (AHA/ACC stage D) heart failure. The prognosis in this group of patients is dismal, with a 4-year mortality of more than 50%. Of patients admitted to hospital with acute heart failure, the 1-year mortality is 30–50%. The option of cardiac transplantation is limited by organ availability and, as wait times have increased, the need for mechanical cardiac support as a bridge-to-transplant has also increased.
Innovations in ventricular assist device (VAD) technology has provided an alternative therapeutic option for patients with advanced heart failure. Initiated as a mechanical option to 'bridge' critically ill patients awaiting transplantation, VADs are being increasingly deployed as 'destination' devices to provide long-term support. With technical advances resulting in improved mechanical reliability, reduced postoperative morbidity and greater likelihood of patient acceptance, there is interest in expanding the applicability for destination VAD treatment beyond the current indication of severely ill patients who are not candidates for transplant. This Review examines the newer, third-generation VADs for mechanical cardiac support.
http://www.nature.com/nrcardio/journal/v7/n2/full/nrcardio.2009.222.html
hey surf, would you mind having an assistant moderator for the ARIA board?
Updated slides from today's ASCO presentation are available for download. Slide 9 shows a 58% MCyR for pts in the 30mg or higher cohort. This data indicates AP534 is more effective than either Tasigna or Sprycel even though the AP534 trial included a more resistant patient population than that enrolled in either the Tasigna or Sprycel trials.
http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-IRHome
Ariad's "AP24534 represents a potential significant advance for CML patients who have become resistant to currently available therapies and who are in great need of new treatment options.”
http://finance.yahoo.com/news/ARIAD-Presents-Updated-bw-1341332663.html?x=0&.v=1
When one considers that Tasigna and Sprycel achieved 35% and 45% MCyR's in pts who failed Gleevec, AP534's 67% MCyR in pts with the T315I mutation is quite remarkable.
Sure, it's neutral however based on the stocks reaction today it looks like some folks were hoping the trial would have met it's end point at the second look. However, the P3 pts were disease stable at time of enrollment so the fact that the trial wasn't stopped at the 2nd interim really isn't all that surprising.
They just "raised" $69 million from MRK and are fully funded thru 2H 2011 so more dilution was, fortunately, not necessary. As far as Rida failing, the Independent Data Monitoring Committee recommended that the trial "continue to its final analysis, without modification."
Based on the ASCO abstracts, AP534 appears to be far more effective than bosutinib. In CP pts who have failed 2 tki's(imatinib and dasatinib), bosutinib achieved a 42% MCyR.
In the data released today, AP534 achieved a 48% MCyR BUT the Ariad trial included pts in both the advanced and blast phase's of the disease while the bosutinib trial only included pts in the chronic phase. Bottomline - AP534 achieved a higher MCyR than bosutinib in a sicker patient population.
http://abstract.asco.org/AbstView_74_52695.html
AP534 ASCO Abstract
57% of chronic phase CML pts with the T315I mutation achieved a complete cytogenetic response. Compelling results.
http://abstract.asco.org/AbstView_74_53232.html
The recent pull back in GHDX is primarily due to the much slower than expected growth in their OncotypeDX Node-Negative Breast cancer test. The ceo attributed this to the economy ($3,500 test) and the "distraction" of their recent colon cancer test launch. However, their OncotypeDX Node-Positive test did not experience the same "distraction". The ceo attributed this to the positive clinical trial data their node positive test has been receiving as of late.
This could be a buying opportunity or it may indicate larger management issues, imo, it may take another quarter to know which.
In the most recent cc, Berger said the company would start a single arm, registration trial as soon as they received approval (irregardless of whether they had a partner). My take is that now that Merck has taken over development of Ridaforolimus, Ariad now has the resources (and the experience) to push forward on their own. Additionally, I suspect the AP534 trial will be significantly smaller than the Rida trial (650 pts) which may give Berger further confidence in initially pursuing the registration trial independently.
I suspect the decision on whether to ultimately partner AP534 will depend on the market opportunity 534 has not only as a second line drug but also as a potential first line treatment option for high risk pts such as those with the T315I mutation. Clearly, first line status would require large, head to head, multi-arm trials and significant resources (and the impact that Gleevec coming off patent in 2015 needs to be factored in). However if Ariad can reach approval based on a relatively small, single-arm trial with pts who have failed 2 TKI's or have the T315I mutation, then a partnership closer to NDA, imo, may optimize shareholder value.
fyi, the full abstracts will be publicly released on Thursday, May 20, at 6:00 PM (EDT).
http://chicago2010.asco.org/Abstracts/2010Abstracts.aspx
Thanks, Peter. I must have read the article but for the life of me I don't remember it...must be getting old. As you point out, pre-clinical is a long ways from first line treatment but it's nice to know that, after a series of starts and stops, ariad appears to be heading in the right direction.
fwiw, my take on rida is that it's potentially a lot more valuable to MRK in combination with several of their drug candidates (namely MK-0646 and MK-2206) than it is as a stand alone drug. That's why I'm hoping to see a restructuring of the partnership that results in additional cash for ariad. In the Barclays presentation, Berger was adamant that they wouldn't be doing another secondary...a refreshing change from the past now that the ceo has $3mm of his own money on the line.
Ariad's near term price is going to be largely driven by the upcoming second interim analysis for ridaforolimus but I suspect that most of the future upside will actually be driven by their second drug candidate AP534.
The Phase 1 data shows AP534 has real promise as a pan bcr-abl inhibitor. In a patient population that had failed 2 and sometimes 3 tki's, the cytogenetic response rates were much higher than tasigna and equaled that of sprycel. With Gleevec coming off patent in 2015, it's clear that Novartis is going to position tasigna as the new first line treatment. http://www.novartis.com/newsroom/media-releases/en/2009/1359764.shtml
One of the reasons I'm invested in ariad is that I believe they'll move quickly to become the standard second line option and, if they find the right partner, potentially first line. If 15 to 20% of CML patients become resistant due to mutations and AP534 works equally well in CP CML as well as in patients whose disease has mutated then I think there a good chance they may very well succeed. But here's my question, has anyone come across any pre-clinical data that may indicate that AP534 actually inhibits the oncogene from mutating at all? Why wait until you become resistant to the first line treatment if you can achieve the same or better CyR and prevent the mutation from occurring in the first place? I have no idea whether this is the case but I just thought I'd put it out there for discussion.
If I'm not mistaken Pfizer's PF1066 is the only ALK inhibitor currently in clinical trial. The AACR abstracts are out and although it's only pre-clinical data, in a direct comparison with PF1066 "AP26113 exhibited ~100-fold selectivity for ALK-positive lines compared with a ~10-fold selectivity for PF1066. At the highest doses tested, strong regressions were achieved with AP26113, but not PF1066."
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=70a76d65-6c78-4df3-91cc-af1e39942ea9&cKey=46d7d71e-b05e-4287-8e02-53a7f55339c1&mKey={0591FA3B-AFEF-49D2-8E65-55F41EE8117E}
yup, everyone reads the 50% revenue split and gets all excited but the fine print required ariad to fund 50% of the US expenses. That kept me from investing until a few of those pesky dilutive financings were out of the way. Speaking of financings, I've got their cash position down to less than 6 months ($41mm at FYE less $16mm quarterly burn equals around 27mm) so whatever they're going to do, they need to do it soon.
bladerunner, this is from one of the filings "approximately $27 million in milestone payments related to the start of Phase 3 clinical trials of ridaforolimus originally expected to be received in the fourth quarter of 2009 under the ridaforolimus collaboration agreement with Merck would likely be delayed until the first or second quarter of 2010."
So, I do think there have been disagreements beyond the decision to not move forward with the herceptin/rida breast cancer Phase 3 trial. (although I think that was partly influenced by competitive factors). I'm not saying that MRK has cold feet....quite the contrary as they recently started a new rida trial in Japan.
Ariad is in a somewhat awkward position vis-a-vis Merck. According to today's Cowen presentation, Ariad is still in negotiations with MRK regarding the 2010 development plan. Given the ASH data, I assume MRK has interest in AP534 but I think it's unlikely that Ariad would partner both rida and AP534 with MRK (partly because of the way MRK delayed $20+ million in milestone payments during the second half of last year). At the same time, it might be difficult to partner AP534 with someone other than MRK at the same time they are trying to re-negotiate the rida deal with MRK. You just know there's a lot more going on behind the scenes...hence the delay???
Well it all depends on your investment horizon doesn't it?. In the short run people who don't understand "biocrap speak" can certainly buy into the hype. It happens everyday and allows traders like yourself to take advantage. Over a longer time horizon I've found that understanding the science is actually an advantage but ymmv.