Gone for good.
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Did any one see this? Three new sites added to the imaging study, although they are not recruiting yet.
University of Arkansas Medical School
City of Hope National Medical Center
Johns Hopkins Medical School
http://www.clinicaltrials.gov/ct2/show?term=Bavituximab+OR+Peregrine&recr=Open&rank=5
I agree. Every first-line trial that includes survival has the same problem. There are statistical methods
to deal with this. Nothing different about the bavi first-line NSCLC trial.
You just opened a can of worms!
The only way I can see to do this is to have a trial which is a combined first-line and second-line trial.
The idea would be that patients that progressed after first-line treatment would then be offered
second-line treatment. So, if the first-line is carboplatin + paclitaxel (CP) vs. bavi + CP, then in
second-line the choices would be docetaxel vs bavi + docetaxel. Ethical constraints make
it difficult to devise a more straight forward test.
RRdog,
As you know, the final MOS for first-line NSCLC is what matters here. I am curious as to why your
estimate for the increase in MOS seems to have been reduced from previous estimates. I have learned
from the pancreatic trial that using just the time since the enrollment closed is not a good indicator of
the final MOS number. Throw in the time between when 50% and 70-80% of the patients have died (maturing
of the data) and the estimate for MOS can be off by quite a bit. My guesstimate is that the 50% level was
reached at the end of 2012, and we are now in the maturing phase. So my guess is for a MOS of 15-16 months.
Assuming the control MOS is close to the mean of past control arms (about 10 months) I estimate about a
50% increase in MOS. That is the best I can do with such a lack of data as we have.
I am expecting something like a 50% increase in MOS based on this analysis I presented back in Jan.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=83747030
This may be less than what some of you have been expecting, but an increase that size would be historic.
Remember this chart and that the 19% increase in MOS seen with Avastin +CP is the biggest so far.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=84897119
Do you really think the powers to be (the Banksters) are going to let someone they
don't control become head of the SEC? It is all rigged. There could be a few show trials.
http://kunstler.com/blog/2013/03/fortress-of-lies.html
EXACTLY. Prison time and not just for the guys at the bottom.
Washington, D.C., March 15, 2013 — The Securities and Exchange Commission today announced that Stamford, Conn.-based hedge fund advisory firm CR Intrinsic Investors has agreed to pay more than $600 million to settle SEC charges that it participated in an insider trading scheme involving a clinical trial for an Alzheimer’s drug being jointly developed by two pharmaceutical companies.
http://www.sec.gov/news/press/2013/2013-41.htm
Yes, there was in the poster from last year, but it was incomplete since the enrollment
had not yet completed. At the time there were 34 in the gem control arm and 32 in the
bavi + gem arm. In the Cowen presentation last week the totals were given as again 34 in
the control arm and 36 in the bavi + gem arm, so the last 4 patients enrolled went to the
treatment arm, In addition, the percentage totals in the poster for the bavi + gem arm did
not add to 100%. It will be interesting to see what PS score those last 4 patients had.
Hopefully at ASCO we get to see everything.
See Cowen slide 13
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=85315415
I would agree with you. The abraxane trial had PS-0 60% PS-1 40%. Both trials treated
only metastatic patients. That trial still only resulted in a 1.8 month increase in MOS,
or a 27% increase, and a HR of 0.72.
Here I used SPSS to simulate a trial which would have the same MOS values and HR as the
Peregrine Bavi trial.This would also be consistent with the fact that the PS 2
patients would die off very quickly and reduce the MOS, that may be also why the MOS of
the control arm is very low also. It will be very interesting to see the subgroup data
for the Peregrine trial. Hopefully the PS 0/1 group would do much better.
It says here that after hours 326,155 shares traded, up 0.09.
Isn't that a lot more than usual?
CP, I don't think you made any mistakes intentionally, but by not checking "facts" before posting them then
all kinds of false implications are created. I did think the sabotage story was nonsense until there was
some real evidence that it was true, then I believed it. To just state such serious allegations without
evidence does not help things, it just confuses them. Let's leave it at that, shall we?
You were wrong about Piper Jaffray. You could have easily checked the facts instead of relying on a faulty memory
of some previous post. This is how false rumors get spread.
My last post on this.
You could at least spell her name correctly, Dr. Menander, before you link her into some conspiracy.
This is how the wrong people get implicated. Very sloppy!
It was probably on the list because CP was looking at both of them! LOL
CP, you are totally wrong here. Piper Jaffray did not acquire Archway, they served as financial
advisors for the deal, see below. I found this in 10 seconds on Google! Why are you posting wrong things??
This is totally irresponsible of you.
http://www.thedeal.com/content/private-equity/investcorp-acquires-archway-marketing-for-300m.php
Investcorp acquires Archway Marketing for $300M
by David Carey | Published July 6, 2012 at 12:23 PM ET
Investcorp purchased Archway Marketing Services Inc. for about $300 million, giving Archway's private equity backers a handsome gain on their 3-1/2-year-old investment, two people familiar with the matter said.
New York private equity shop Tailwind Capital LLC, Archway's 80% owner, reaped slightly less than a 200% profit on its roughly $50 million equity investment, these people said.
Black Canyon Capital LLC of Los Angeles netted a comparable gain on its 10% stake, they added.
Investcorp, a Bahrain-based bank and alternative asset manager, edged other suitors in an auction run by Robert W. Baird & Co., according to the sources. The price equates to about 11 times trailing Ebitda.
The deal, which closed Monday, is expected to be announced early next week, a source said.
Executives at Investcorp, Tailwind and Black Canyon did not immediately return messages seeking comment.
Rogers, Minn.-based Archway provides marketing logistics and fulfillment services to fast food chains, retailers, consumer goods and financial services companies. Its bread-and-butter business is to transport marketing brochures, signs and displays for point-of-sale product promotions. Its clients include Taco Bell, Subway, General Motors Co., MillerCoors, Loew's Cos. and American Eagle Outfitters.
The company operates 4 million square feet of warehouse and production facilities in 14 cities in the U.S. and Canada.
Tailwind and Black Canyon bought Archway from Cravey Green & Wahlen Inc., an Atlanta PE firm, in November 2008, after a deal to sell Archway to a blank-check company fell through. The price wasn't disclosed.
Archway later made three bolt-on purchases, buying Resolve Corp.'s supply chain management unit in 2009 for $18 million; Corporate Services Inc. in 2011 for $30 million, and Synq Solutions Inc. for $27 million earlier this year.
Ebitda jumped from $11 million to $27 million and revenue from $100 million to $279 million while Tailwind and Black Canyon owned it, a source said.
Investcorp was planning to raise a $175 million senior debt package through GE Capital Corp. and ING Groep NV to finance its purchase, Standard & Poor's Leveraged Commentary & Data reported last week.
The package consisted of a $30 million, five-year revolving credit facility, a $35 million delayed-draw term loan and a $110 million, six-year term, LCD said.
Davis Polk & Wardwell LLP was Archway's legal adviser.
Investcorp turned to Piper Jaffray & Co. for financial advice. Gibson, Dunn & Crutcher LLP was its legal counsel.
CP, all I see on the Linkedin webpage is that
Abstracts for the AACR meeting next month.
Number: 1244
Title: Phosphatidylserine-targeting antibody reactivates tumor immunity and destroys tumor vasculature in mice
Presentation
Time: Monday, Apr 08, 2013, 1:00 PM - 5:00 PM
Location: Hall A-C, Poster Section 5
Author
Block: Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe. UT Southwestern Medical Ctr., Dallas, TX
Abstract
Body:
The immunosuppressive lipid, phosphatidylserine (PS), becomes exposed on tumor blood vessels and tumor cells responding to therapy. The
exposed PS contributes to the immunosuppressed tumor microenvironment. Bavituximab is a phosphatidylserine (PS)-targeting antibody that
is being combined with chemotherapy in clinical trials in cancer patients. Here, we tested the hypothesis that innate immunity against cancer
can be elicited by combining chemotherapy with a monoclonal antibody that indirectly binds exposed phosphatidylserine (PS). We used a
murine version of bavituximab, 2aG4, plus docetaxel to treat prostate tumors in mice. Combination treatment markedly retarded tumor
growth, prolonged survival times and delayed progression to androgen-independent disease. Antibody treatment reduced the presence of
myeloid-derived suppressor cells (MDSCs) in the tumors and caused macrophages to repolarize from the immunosuppressive,
proangiogenic M2-like state into a tumoricidal M1-like state. The reactivated macrophages destroyed antibody-coated tumor vasculature
and tumor cells. Addition of 2aG4 to MDSCs in vitro caused them to differentiate into M1-like macrophages and DCs. Thus, PS-targeting
antibodies appear to reactivate innate immunity in tumors resulting in tumor growth inhibition.
Number: 2850
Presentation
Title: Predicting anti-tumor responses to phosphatidylserine targeting antibodies using tumor imaging
Presentation
Time: Tuesday, Apr 09, 2013, 8:00 AM -12:00 PM
Location: Hall A-C, Poster Section 21
Author
Block:
Jian Gong1, Richard Archer1, Van Nguyen1, Christopher C.W. Hughes2, Jeff Hutchins1, Bruce Freimark1. 1Peregrine Pharmaceuticals, Inc.,
Tustin, CA; 2University of California, Irvine, Irvine, CA
Abstract
Body:
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor
vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment.
Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune
system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A
chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II
trials. Fully human antibody PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (ß2GP1) in the same manner as bavituximab.
Using human PC-3 prostate tumor xenografts in SCID mice, we demonstrate that targeting of PS in tumors by PGN635 is enhanced by
chemotherapy. Combination of PGN635 with docetaxel inhibited tumor growth compared to the control IgG plus docetaxel group (p<0.05).
Near-infrared optical imaging of PS in tumors with PGN650, an F(ab')2 antibody fragment of PGN635, showed tumor growth inhibition in
mice treated with docetaxel correlates with PS expression levels in the tumors. Maximal uptake of the PS imaging was observed when
chemotherapy was given 24 hours before the imaging probe.
Number: 4326
Presentation
Title: Phosphatidylserine-targeting ‘betabodies’ for the treatment of cancer
Presentation
Time: Tuesday, Apr 09, 2013, 1:00 PM - 5:00 PM
Location: Hall A-C, Poster Section 36
Author
Block:
Xianming Huang1, Dan Ye1, Troy Luster2, E. Sally Ward1, Philip Thorpe1. 1UT Southwestern Medical Ctr., Dallas, TX; 2Human Genome
Science, Maryland, MD
Abstract
Body:
Bavituximab is a chimeric monoclonal antibody that is being combined with chemotherapy to treat patients with lung or pancreatic cancer in
randomized Phase II clinical trials. Bavituximab targets the immunosuppressive lipid, phosphatidylserine (PS), which becomes exposed on
the outer membrane surface of tumor blood vessels and tumor cells in tumors responding to therapy. The antibody acts by destroying tumor
vasculature and by reactivating tumor immunity. Here, we generated new PS-targeting therapeutics by fusing domains of the PS-binding
plasma protein, mouse ß2-glycoprotein I (ß2GP1), to the Fc region of mouse IgG2a. Such ‘betabodies’ potentially have the following
advantages: they bind directly to PS, and do not require a cofactor protein (ß2GP1) for binding; they can be made fully human; they are
smaller in size (100 KDa); and they have slower blood clearance rates. A construct was generated that bound strongly to PS-expressing
cells and plates, localized to tumor vascular endothelium in vivo, and had a ß-phase blood half-life of approximately five days after
intravenous injection into mice as compared with one day for a murine version of bavituximab, 2aG4. Betabodies could potentially be the
next generation of PS-targeting cancer therapeutics.
Number: 5166
Presentation
Title: Membrane phospholipid asymmetry mediates the selective packaging of protein factors in cancer microparticles
Presentation
Time: Wednesday, Apr 10, 2013, 8:00 AM -12:00 PM
Location: Hall A-C, Poster Section 24
Author
Block: Songwang Hou1, Carol Williams2, Ming Zhao1. 1Northwestern University, Chicago, IL; 2Medical College of Wisconsin, WI
Abstract
Body:
Objective: Growing evidence indicates that cancer cell-derived microparticles (MPs) play important regulatory roles on cellular and system
levels. These activities are attributed to protein factors inside MPs. It has been known that contents in MPs are not a passive representation
of the host cell, but a collection of factors packaged in a selective fashion. In the current study, we hypothesize that membrane phospholipid
dynamics promotes the selective packaging of protein factors by modulating the electrostatic density inside MPs.
Methods: The dynamics of phospholipid species across the membrane bilayer, including phosphatidylethanolamine (PE), phosphatidylserine
(PS) and phosphatidylinositides (PIs) are characterized using specific molecular probes. We used exogenous probes, Duramycin and bovine
lactadherin, to stain the presence of PE and PS, respectively, on the outer surface of MP membrane. Endogenously expressed probes
include GFP-tagged C2 domain of lactadherin (LacC2-GFP), and GFP-tagged 2PH-PLCdelta, are used to assess the relative density of PS
and PI, respectively, in the inner leaflet of MP membranes. We examined the distribution of small Rho GTPases, including RhoA, Cdc42 and
Rac1, using GFP-labeled reporters. To further examine the electrostatic interactions, we used RhoA mutants with the polybasic amino acids
mutated to Gln. Additionally, we constructed a GFP-PBR to validate the electrostatic-dependent packaging mechanism.
Results: PE is externalized to the outer surface of MPs. This is correlated with a greater density of negatively charged phospholipids,
particularly PS, in the inner leaflet. The process is independent of apoptosis or the generation of apoptotic bodies. The redistribution of PE to
the MP surface is correlated with an elevated presence of small GTPases in a PBR-dependent manner. Mutation of PBR abolished RhoA
uptake in MPs. The incorporation of PBR to GFP significantly enhanced GFP localization in MPs. Conclusion: PE externalization to MP
surface likely results in a greater density of negatively charged phospholipids, including PS, and to a lesser extent, PIs. An elevated density of
anionic phospholipids provides an electrostatic attraction for membrane-associated proteins to MPs. This may provide a general mechanism
for the selective sequestration of signal transduction factors in cancer cell-derived MPs.
I don't understand what they mean here since PGN650 is the Fab part of PGN635 and is used
in the 125I-PGN650 imaging molecule. It is not a "better" bavi since it can not bind to
macrophages, DCs using the Fc-gamma receptor, since it doesn't have one.
Bob,
I only used trials that have a control arm with docetaxel only. Also the number 11.7 months
is not the issue it is the increase from the control arm (60%) that is bigger than any other trials.
FTM
I only used trials that have a control arm with docetaxel only. Also the number 11.7 months
is not the issue it is the increase from the control arm (60%) that is bigger than any other trials.
Patrick, everything is OK, you do believe me don't you? I don't have any confidence that they
actually know what is going on.
I am just going to wait this thing out because I truly believe that bavi works, and works very well.
Exactly. I keep thinking of Deep Capture. It has become totally obvious what is happening.
Sunstar, at this point I agree with you. There is nothing to do but to let the legal process continue.
I agree with this completely.
Yes, but I would think the plan would be for it not to be found. Would it have been found
if the trial had failed? Would Peregrine do a complete review of all the data in preparation
for an end-of-phase II meeting with the FDA if the trial had failed? That is when it was
found and despite the attempt at sabotage the results were still good enough to move
forward. I don't think the people behind this expected that to happen.
That is all I have left to say about this.
But how would that hurt CSM? Trials fail all the time because the treatment doesn't
work. If the sabotage had caused the trial to fail would CSM suffer? No, they get paid
regardless of the outcome. So who would benefit if the trial failed?
That was a quote from the e-mail Bob Jonson got from Chris.
I would think that money is the usual motive. Which means check for people with big debts.
During the cold war the people who sold out the USA did it for money, not ideological reasons.
Having big debts, or a gambling habit, make you a bad security risk.
I don't remember reading anything other than "she was no longer an employee", if so she
could have left in Sept 2011 and had plenty of opportunity.
What makes you think she knows who was behind it? That would be pretty dumb to let her know.
The enrollment in the second-line trial ended Oct 6, 2011. There was plenty of time from
the time the enrollment started on June 4, 2010.
Chris did say: "This was a deliberate action by one individual at CSM",
that means it was sabotage, not just a mistake, there is no way around it.
It seems that the share price of PPHM can be manipulated at will by the big money boys.
That makes me think, like you, that the intent of the sabotage was to make the trial fail.
Why go to the trouble unless you wanted to have bavi fail, and with it Peregrine.
I think that the ex-employee at CSM probably has no idea who is behind this.
Anonymous cash drops and such could ensure that. Maybe something happened that wasn't
in the plan so that the sabotage was not fully implemented, or that bavi works so well
that even the sabotage was not enough to make it look bad, or some combination of both.
Was he involved?
About the Author
William W. Henry shares the story of a sting going down from the perspective of a man in the know. Over a twenty-eight-year career in the financial world, he was investigated for alleged securities violations by numerous regulatory agencies, none of which were ever able to prosecute him. He ultimately achieved white collar felon status in 2003 when he pled guilty to one count of accessory after the fact, involving charges of conspiracy to commit wire fraud-a plea he provided in exchange for the federal prosecutor dropping all charges against his closest friend.
The man behind Peregrine? Is the timing of his death just coincidence?
http://thefinaledition.com/article/major-admiral-sir-peregrine-staves-lord-mucus-vc-mc-aa-aaa-104.html
The first abstract I listed may be preclinical but addresses a very relevant question.
Predicting anti-tumor responses to phosphatidylserine targeting antibodies using tumor imaging
You have to do the basic research to back up the clinical research. There hasn't been anything published
on this specific topic so it should be very interesting.