The Taliban and their abuses against all women was not and will not be defeated with a strategy of hoping moderates will rise up. Moderates are neutral. They are neither for or against. Passively neutral, which is in effect endorsement. ISIS is very much tolerated in the region. ISIS rules parallel those of Saudi and the Taliban. Their behavior is acceptable by many moderates, tolerated. Money is coming from Saudi to fund ISIS, and this is tolerated. Iraq should have been claimed as US territory, built up and diluted with immigrants from around the world until sectarian violence was no longer a mathematical possibility. There are certainly enough resources to make this happen, and this would be my strategy for Iraq for the betterment of everyone. Allowing the current situation to continue will give rise for an opportunity to topple the USA. The US's sophistication is also its weakness. It would not take much, and they know this. Cripple air transport and the Nation falls. It is nice to be #1 but being on top is balanced on a razors edge with lots of enemies. We have a tiger by the tail with ISIS, and at some point they just might become regionally popular. Scary but true. They know how to win hearts and minds too and can turn on a dime with a new softer PR campaign giving out oil money to the poor and then returning to evil when they have total control.
ISIS is a radical Sunni jihad tolerated by most, excluding a rumored few civilian groups in places such as Mosul. The region is conditioned to submit to power, might, and fear. We will end up back on the ground, this time having to claim Iraq as our territory, govern it, and pump oil to pay the bill.
If we allow ISIS to maintain itself and organize terror strikes, including Ebola, on the US, they could actually win this thing. It is a real possibility. They have scientist and engineers too, some of which were educated in American graduate schools. We are quite fragile.
What you are suggesting is that war can be avoided. I wish you were right, but history says otherwise. It is just he way it is. This is going to end bad for them or bad for us.
Buddy of mine working on an Ebola vaccine with NIH. Short story - The monkey died. Funding was cut. Bavarian Nordic and other companies are working on vaccine. Ebola was part of Homeland Security, so Ebola awareness goes back to 911. "BIOLOGICAL ATTACK HUMAN PATHOGENS, BIOTOXINS,AND AGRICULTURAL THREATS". Enters through any minor cuts on skin. Not airborne supposedly...On alert for terrorists attempting to bring this thing in. This is what is on everyone's mind. Time to roll ISIS off the map along with any civilians tolerating them. Them or us, simple.
You had me at "basically agree".
What I have posted is simply common knowledge with specific examples.
Shall I point you to the data?
This was a simulated stroke model in rats. These models are more often than not extremely misleading.
For example, recently Zalicus also showed their Z160 pain medication worked fantastic in rat pain models, but it did nothing in humans in two different pain indications. The company sunk to the bottom of Boston Harbor.
Similarly, "Based on his early research, he co-founded Cambridge, MA-based Sirtris Pharmaceuticals, which GlaxoSmithKline ($GSK) bought in 2008 for $720 million. And anyone who has followed the Sirtris saga since then knows that Sinclair's early resveratrol findings (in a mouse model) have been called into question in studies from outside labs that couldn't replicate his tantalizing results."
The rodent models are almost always wrong, and less than 1% of drug candidates make it to market. These are the facts, not my opinion.
August 12, 2013
Map3 cellular allogeneic bone graft is a natural and safe alternative to autograft. Map3 provides a streamlined approach to bone grafting and supplies the three elements necessary for bone repair—osteogenesis, osteoinduction and osteoconduction—in a single allograft. Map3 incorporates multipotent adult progenitor cell-based (MAPC™-based) technology with stem cells isolated from the same donor as the other bone material. The MAPC technology, licensed from Athersys, Inc. for this orthopedic application, represents a distinctive type of stem cell with recognized angiogenic and immuno-modulatory properties. Once launched, map3 will be available in multiple configurations and sizes, providing bone grafting options for various bone repair, reconstruction and fusion procedures.
September 13, 2010
RTI Biologics and Athersys Announce Collaboration in the Orthopedic Market
Applying Complementary Stem Cell and Regenerative Medicine Technologies
ALACHUA, Fla. and CLEVELAND, Sep 13, 2010 (GlobeNewswire via COMTEX News Network) -- RTI Biologics Inc. (RTI) (Nasdaq:RTIX), a leading provider of orthopedic and other biologic implants, and Athersys Inc. (Athersys) (Nasdaq:ATHX), a leader in regenerative medicine and cell therapy research and development, announced today an agreement under which Athersys will provide RTI access to its Multipotent Adult Progenitor Cell (MAPC) technologies.
FIRST QUESTION (with follow ups):
For a phase 3 Crohn's disease trial based on positive phase 2 results in difficult to treat patients, Mesoblast/Osiris is infusing four doses of Prochymal over four visits during a two week period. They are having good luck with this strategy.
In contrast, the Pfizer phase 2 ulcerative colitis study using Multistem administered a single high dose resulting in no significant difference between placebo and Multistem to date.
Was expecting a single dose of Multistem to effectively treat long-term chronic UC patients too ambitious, and as a consequence of the failed trial, brand damaging for Athersys? Mesoblast seems to be on target for success with multiple dosing with fewer cells.
As this relates to the stroke trial, predictive clinical markers for stroke are available and being monitored by Athersys in the phase 2 trial. Why did Athersys not design the study to utilize these markers to possibly guide administration of a second or third dose, if needed, as Mesoblast is doing with Crohn's? If success is the goal, it would seem this extra effort would ensure success, as it has proven to do so for Mesoblast Crohns trials.
Can you describe the sample size calculation used for the Multistem stroke trial because at face value the trial size seems to be grossly under powered for this most challenging of indications, especially considering natural recovery, even though I know Athersys is selecting patients who do not recover on their own at 24-48 hours. Showing a significant difference compared to placebo relative to other stroke trials is difficult as seen in other trials which have failed because of high expectations of efficacy. With this in mind, can you provide some more color about the sample size calculation?
No, I would definitely ask the question, "Hey, thanks for the update guys. I see Pfizer drug Multistem through the mud and then everyone got bonuses. Mesoblast is giving four doses for a similar indication and getting positive results but you allowed Pfizer to administer only one dose, ensuring failure? No answer necessary, more of a comment on this point, but I have a question. Gil, what will you say if the stroke trial fails, ooops or my bad?
Ohmtaxi, Prochymal and Multistem are both going after bowel autoimmune. The difference is Osiris/Mesoblast are designing trials with four rounds of infusion which has proven successful, and they are in Phase 3 looking to go to market soon.
Meanwhile, Pfizer and Gil have designed and approved, respectively, a FAILED phase 2 UC trial. We keep waiting on a miracle to happen in which Pfizer explains the mystery of their wisdom in designing a failed trial. I am sure they just did not want to design a successful trial because they want to buy ATHX out at a low price! That's it! Or perhaps they "got what they wanted" in terms of defining biochemical success and will find another way to undercut Athersys.
Optimistically speaking, if they indeed liked what they saw, they should be designing a second Phase 2 very soon. Regardless, Osiris/Mesoblast are already beyond this.
With Pfizer, all we have left is hope.
Here you go Ohmtaxi.
Do you understand why the Mesoblast/Osiris data is relevant to the ATHX board now?
Competition is a good thing, and Multistem and Prochymal have a key common effect, increase in IL-4 and IL-10. This is good because Multistem is 1/4 the cost per dose with more cells.
Co-localization of transplanted MAPC and resident CD4+ splenocytes is associated with a global increase in IL-4 and IL-10 production and stabilization of the cerebral microvasculature tight junction proteins. (MAPC were obtained from Athersys, Inc. (Cleveland, OH).
Additionally, Prochymal up-regulates the production of beneficial anti-inflammatory cytokines, specifically interleukin-10 and interleukin-4.
Preliminary findings from the first human study of a monoclonal antibody to mucosal adressin cell adhesion molecule (MAdCAM), PF-00547,659, suggest that it might be useful for ulcerative colitis treatment.The homing of leukocytes to the gut mucosa is a known therapeutic target in IBD as shown by the development of natalizumab; however, this drug is associated with an increased risk of progressive multifocal leukoencephalopathy.
Mesoblast has an advanced program to develop Prochymal® (remestemcel-L, human mesenchymal stem cells for intravenous infusion) for the treatment of patients with refractory moderate to severe Crohn's Disease (CD).
Prochymal® has demonstrated immunomodulatory properties to regulate T-cell mediated inflammatory responses by inhibiting T-cell proliferation (demonstrated in a mixed lymphocyte reaction2) and down-regulating the production of the pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon gamma.
More critically, mesenchymal lineage stem cells have been shown to be capable of effective down-regulation of Th17 cells, reduction in IL-17 levels, and induction of FoxP3 regulatory T cells.
A Phase 3 multi-centered, double-blind, randomized, placebo-controlled trial is evaluating the safety and efficacy of Prochymal® in moderate to severe CD in patients who are resistant to steroid, immunosuppressant and a biologic therapy. The primary endpoint is the proportion of patients experiencing disease remission within 28 days of treatment with Prochymal®, compared to those patients receiving placebo.
Preliminary data from two interim analyses planned under the protocol has provided encouraging results. The Phase 3 trial is ongoing.
An alternative hypothesis is that Pfizer wanted to taint stem cells for UC to promote their own small molecule.
Pfizer Key Programs Registration / Phase 3
Xeljanz® (tofacitinib) – Ulcerative Colitis
Regardless, Pfizer designed the Multistem UC trial to fail because they knew Osiris required 4+ doses of Prochymal to provide therapeutic value.
Any way you cut it, Pfizer used Multistem with wreckless disregard for patients, and I am going on the record with this one. This study was beyond a reasonable long shot. One dose to treat patients is not responsible or fair to the patient. There is no excsure for this, especially without a multi dose followup option. Shame on Pfizer!
Pfizer is going directly after the small molecules secreted by Multistem. They wanted to see if there was a hint of efficacy. If so, they can leave Multistem and synthesize what Multistem produces to sell it as a combo small molecule therapy.
They do not plan to mess around with variable cell cultures that could become infected in bioreactors or deal with batch to batch (donor to donor) variation. I suspect they got what they wanted and will soon cut bait.
By designing trial to fail, they got their efficacy data in terms of a biochemical reponse and can drop Athersys and the patients like a sack of potatoes.
Pfizer screwed Athersys by giving a single dose.
They should have known better based on Osiris results.
Extended Evaluation of PROCHYMAL® Adult Human Stem Cells for Treatment-Resistant Moderate-to-Severe Crohn's Disease
This study has been completed.
Study Start Date: October 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
May 6, 2010
Osiris Restarts Phase III Prochymal Trial in Crohn Disease Following Interim Analysis
"To understand the significance of this trial, it is important to appreciate just how sick these patients were," said Dr. Onken. "On average, they had suffered with Crohn's disease for 14 years and were unable to find relief with currently available therapy. It was in this difficult-to-treat population that we observed clinical improvement upon administration of the stem cell therapy."
Drug: PROCHYMAL adult human mesenchymal stem cells
intravenous infusion four times over two weeks; possibly repeated once
Osiris would never approve a bowel treatment design using a single dose to cure long-term UC patients.
Take a look at the Osiris (now Mesoblast) treatment design from 2007. Four doses.
Pfizer knew one dose of Multistem would not work! What a scam!
Look below, Osiris used FOUR doses minimum to get results.
*****Drug: PROCHYMAL adult human mesenchymal stem cells
intravenous infusion FOUR times over two weeks; possibly repeated once*****
Pfizer set their trial up to fail.
Ohmtaxi and Biospy, use your ignore button if you do not like what you read. The point here is that any buy or sell is likely too early to be based on any insider knowledge. We simply are not far enough along. Insider knowledge is very much possible though as I have explained.
However, the study is grossly under powered, and I have seen insiders with knowledge of failure buy into disaster. So insider buying means "0". It never has, and it never will mean anything. Even total holding means nothing.
This is a risky one, so bet only what you can afford to lose and hope for the best. Disclosure: I am long and have been for longer than most on this board. I assure you this.
Was Pfizer's "impossible to succeed" Multistem phase 2 for UC trial design (as admitted by Gil) an accident?
Key Programs in Registration / Phase 3
Xeljanz® (tofacitinib) – Ulcerative Colitis, Psoriasis (oral), Psoriatic Arthritis