PPHM and Tarvacin discussion

[Preciouslife1]

Originally Posted by Kharma

The Bunny article and link

Your Bunny's Nose


Wisdom of the Crowd

It’s pretty funny, actually. These days, a lot of money managers would rather read the chat boards than they would use any of the sell-side’s research product. After all, SarbOx has stopped the flow of useful information from companies to the sell side analysts, and those analysts are too busy, too lazy, and too unimaginative to do the original work that’s required to fill that void.
Of course, when it comes to PPHM this "what to read" decision is a lot more easily made. Since PPHM lacks any analyst coverage, the chat boards are the only potential source of info and insight. So, with PPHM’s shares now completing their straight-line slide to penny stock land, what do the chat boards offer as an explanation for the decline?
A quick survey of the chat boards tells the story. Who is posting these days? We count five humorless, feeble pumpers (they know who they are). And we count five entertaining, high-quality cynics (again, they know who they are). And we see that the Science Boy pumper has created a second screen name so that he now has someone to talk to.

Otherwise, the rooms are pretty empty. There is a long list of formerly enthusiastic, knowledgeable, well-connected shareholders who have now seemingly fled the building. (Again, they know who they are).
Five pumpers, five cynics, and a few hangers on. Call it the Wisdom of the Crowd, and in this case, the crowd has fled.
Once in a while, a clueless soul will show up and innocently ask “Since all the data is so good, why is the stock getting hammered?”
Our response: Dude, you better examine the first part of your premise a little more closely.
For all the R&D done by the company, for all the PowerPoint slides presented by management, for all the desperate pumping on the chat boards, PPHM has really made very little progress in the clinic.
In fact, the ratio of talk to results is staggering in its magnitude.
And that explains the stock price far better than the ridiculous theories that the desperate pumpers cling to. Rather than repeat their theories here, we offer up a far more easily-understood explanation: The market has gotten it right. Call it the Wisdom of the Crowd.
Over half a year ago, we were the first to suggest that the wheels were coming off the Bavi development program. We were the first to ask if perhaps some investors had actually taken a look at the Phase 1a data and started to sell their stock. After all, “transient” effects do not a blockbuster make.
We’ll claim to have been early, alone, and right when we said this because since then, the selling pressure on the stock has never stopped. There have been nine months of unrelenting selling.
There’s no denying that the stock has traded like there has been a massive unwinding of positions taking place. And that does not happen when things are going swell.


How far less than swell are things going? Some dispassionate speculation:

The Bavi AC Phase I is at best late, and is at worst in limbo. Perhaps the slowdown is deliberate and is due to the fact that this lengthy trial (enrolling patients at the rate of barely more than one a month) is not going to impress anyone when it is completed and the results made public. It starts to look like the company has thrown a Hail-Mary pass to India in the hopes that it might provide some diversionary cover for the trial in the U.S. But if the results from the Hail-Mary can’t grab investor attention and if the U.S. trial does little more than demonstrate safety, then Bavi AC begins to look like a lengthy, highly dilutive program that, even if ultimately successful, will be a killer for the current penny stock shareholders in the coming months and years.
The Bavi AV Phase 1a and 1b results certainly did move along much faster, but the results failed to demonstrate anything other than the fact that more trials will be needed before anyone can claim that this program is on track for eventual success. The obvious next steps (a number of quick-hitter trials to seek out the right dosing, the right combos, etc.) are well known, but are beginning to be woefully late in starting. And “woe” is not what you want when management can’t communicate and when the stock is tanking.

And now, with the absence of decisive progress in the clinic, the company has put a huge shelf registration in place. Average daily volume has increased. Add it all up and it starts to look like another PIPE is underway.
If true, then the company has now joined the nine-month parade of sellers.
If true, then this signals that the company has not only failed to make decisive progress in the clinic to date, but sees nothing at hand that might move the stock higher in the coming months.
Who could blame the company for doing a PIPE now? Another Russell rebalancing looms in June. The markets are deteriorating. The stock is down. Cash is burning and future trials require funding. The company knows that the funding clock is ticking.
Given all that is known at the moment, it’s hard for us to see why management thinks “2007 could be a breakout year for Peregrine”. Given the timeline delays, paucity of useful data, and investor disinterest, we continue our long-running observation that “dead money” best describes the near-term outlook.
We continue to like the science and distrust the management. Profitable development of the science is likely beyond the ability and resources of the company. Given the company’s circumstances, the most logical thing to expect this year would be a partnering deal with a large pharma, or the outright sale of the company.
But that’s not for us to say. It’s up to management to prove it has a plan. The upcoming conference call would be a good place for them to start.
We don’t think they will do it.
Instead, we think the gameplan is delay (where is the June 2006 HIV announcement?) and obfuscation (like the PR for the 1b data) for the next year or two while a second-generation Bavi is prepared and works its way through the necessary preclinical tests. This is the worst-case scenario, and if true, it has ominous implications for the stock.

That one sided, non factual blog is worthless IMO as well as the opinion of many intelligent investors. However, since you chose to post that drivel here, understand that it is free game to be picked apart and held accountable now for its co.ntent here...

[Kharma]

Originally Posted by Preciouslife1

That one sided, non factual blog is worthless IMO as well as the opinion of many intelligent investors. However, since you chose to post that drivel here, understand that it is free game to be picked apart and held accountable now for its co.ntent here...

I look forward to a factual rebuttal of the Bunny Blog by you and your other many intelligent investors. Also I only posted the blog article as your Boil the Bunny post made absolutely no sense without referencing it.

Kharma

[Preciouslife1]

Thank you kharma or er joey for the "great"??? contribution to the knowledge base here.....blog??? Moi??? why would I have to blog anything when all the info on PPHM is public matter and fully accessible via the web and the IHUB.com info box, google, here, and many other sites like scirus etc.......the data will speak for itself and patience is a virtue that carries a lot of wait.......tick, tock....

[Preciouslife1]

Peregrine Pharmaceuticals Reports Financial Results for Third Quarter Fiscal Year 2007
Monday March 12, 7:00 am ET

TUSTIN, Calif., March 12 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a clinical stage biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus (HCV) infection, today announced financial results for the third quarter of fiscal year 2007 ended January 31, 2007. The company reported a consolidated net loss of $5,025,000 or $0.03 per basic and diluted share, compared to a consolidated net loss of $3,113,000 or $0.02 per basic and diluted share for the same prior year period. The increased net loss primarily reflects a decrease in revenues during the current quarter combined with a decrease in interest and other income that resulted from a large one-time payment received by Peregrine in the third quarter of fiscal year 2006.

"Avid built up a significant work-in-process inventory over the past quarter and was also engaged in providing manufacturing services for Peregrine's clinical stage products," noted Paul Lytle, chief financial officer of Peregrine. "As a result, we saw a temporary decrease in Avid revenues reported in the third quarter, but some of this decrease represents Avid revenue that has shifted into the current fourth quarter ending April 30, 2007. Based on production we have already completed, as well the anticipated near-term completion of in-process manufacturing services now underway, we believe our fourth quarter Avid revenues will be strong. We expect that total Avid revenues for this 2007 fiscal year will surpass the total we achieved in fiscal year 2006, and our current Avid revenue projections for fiscal 2008 look better yet."
Total revenues for the current quarter were $363,000 compared to $1,528,000 for the comparable quarter last year and were primarily generated from services provided by Avid Bioservices, the company's wholly owned contract manufacturing subsidiary.
Total costs and expenses were $5,643,000 in the third quarter of 2007 versus $6,010,000 in the same quarter in the prior year. The decrease in total expenses was primarily due to a decrease in the cost of goods expense reflecting lower contract manufacturing revenues at Avid, combined with a decrease of about 7% in SG&A expenses. These amounts were partly offset by a $613,000 increase in research and development expenses associated with the advancement of the company's clinical and preclinical product candidates.
Interest and other income was $267,000 during the current quarter, compared to $1,381,000 in the prior year quarter. In the third quarter of fiscal year 2006, the company received a one-time payment of approximately $1.2 million related to the collection of a note that had previously been deemed uncollectible. This payment was included in interest and other income in the third quarter of fiscal 2006. Excluding the collection of this note receivable, interest and other income increased in the current quarter compared to the prior year quarter, primarily reflecting interest earned on the company's strengthened cash position combined with higher prevailing interest rates. At January 31, 2007, the company had $20,114,000 in cash and cash eq.uivalents compared to $17,182,000 at fiscal year end April 30, 2006.
"We have made tremendous progress in our clinical programs during the first three quarters of fiscal year 2007, and the fourth quarter is shaping up to be a period of significant progress as well" said Steven W. King, president and CEO of Peregrine. "In the third quarter we initiated and nearly completed, with 11 of the anticipated 12 evaluable patients enrolled, the first clinical trial of bavituximab in combination with major chemotherapy drugs to treat solid cancers. We expect enrollment to be fully completed in the coming weeks and we will provide an update on the trial at that time."
"While moving bavituximab forward, we also advanced preparations to launch a Cotara® Phase II clinical trial in glioblastoma patients in India. We have now completed necessary manufacturing and regulatory filings related to producing the final drug product in India and expect that we will be able to initiate the trial shortly. While the process required to obtain approval for Cotara manufacturing in India has been extensive, we believe these efforts will help us advance the Cotara program much faster than would otherwise have been possible. Our clinical investigators are eager to initiate the trial and have already begun to identify potential subjects. We believe enrollment in this trial should proceed at a good pace. In a complementary development, our U.S. Cotara trial sponsored by NABTT is now starting to benefit from a patient outreach campaign Peregrine initiated this quarter, and we have already seen an increased activity level in the trial."
Mr. King continued, "Most importantly, last month we released positive initial results from our bavituximab Phase lb repeat dose trial in patients with HCV infection. Bavituximab appeared safe and well tolerated and showed encouraging signs of antiviral activity that appeared to be dose dependent. These were the two key objectives of the study and they were successfully achieved. We and our clinical investigators are pleased with these results, which lay the foundation for advancing bavituximab into the next set of HCV trials that we currently are finalizing. We intend to make more information about these plans public in the coming weeks." Mr. King concluded, "We are entering the home stretch of our fiscal year with excellent momentum in all our clinical programs. In addition, Peregrine has reported a number of other significant events since our last quarterly report. A product based on our targeted TNT technology was launched for lung cancer in China. Our European pharmaceutical partner initiated clinical trials with a novel TNT anti-cancer product licensed from Peregrine. We established our own subsidiary in China to increase our ability to leverage opportunities in this important new market and researchers affiliated with our company reported on a number of exciting preclinical developments that further strengthen our new drug pipeline. We believe this is an exciting time for the company and that our advancements should drive shareholder value as we move forward."
__________________

[Preciouslife1]

Posted by: freethemice
In reply to: NoneDate:3/11/2007 1:31:16 PM
Post #of 12235
Jazz, was this paper on one of your lists?

The Journal of Immunology, 2004, 173: 2985-2994.

Phosphatidylserine Regulates the Maturation of Human Dendritic Cells

Xiao Chen*, Kara Doffek*, Sonia L. Sugg and Joel Shilyansky,*
* Division of Pediatric Surgery and Division of Endocrine Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226

Phosphatidylserine (PS), which is exposed on the surface of apoptotic cells, has been implicated in immune regulation. However, the effects of PS on the maturation and function of dendritic cells (DCs), which play a central role in both immune activation and regulation, have not been described. Large unilamellar liposomes containing PS or phosphatidylcholine were used to model the plasma membrane phospholipid composition of apoptotic and live cells, respectively. PS liposomes inhibited the up-regulation of HLA-ABC, HLA-DR, CD80, CD86, CD40, and CD83, as well as the production of IL-12p70 by human DCs in response to LPS. PS did not affect DC viability directly but predisposed DCs to apoptosis in response to LPS. DCs exposed to PS had diminished capacity to stimulate allogeneic T cell proliferation and to activate IFN--producing CD4+ T cells. Exogenous IL-12 restored IFN- production by CD4+ T cells. Furthermore, activated CTLs proliferated poorly to cognate Ag presented by DCs exposed to PS. Our findings suggest that PS exposure provides a sufficient signal to inhibit DC maturation and to modulate adaptive immune responses.

Posted by: freethemice
In reply to: jazzbeerman who wrote msg# 12229Date:3/11/2007 2:29:08 PM
Post #of 12235
Jazz, I thought it looked familiar!
It is clear to me now how bavituximab can
induce a long-term response to PS-expressing
cells. It produces the combined effects of
both a therapeutic and preventive vaccine.
All for the price of one! This could be really
amazing.
I have been learning about all the different
mutations in cancers. There are so many pathways
that can be involved, and many of them have
cross-talk to other pathways. If you design a
"targeted" therapy to block a particular pathway
the cancer will just mutate until it finds another
path to proliferation, thus making your targeted
molecule worhtless. The more research that is done
the more it is realized just how complex this
problem is. I don't think the usual approach is
going to work at all. That is why Bavi is so great,
and different, and holds such promise.

[Preciouslife1]

By: jazzbeerman14 Mar 2007, 07:40 AM EDTMsg. 223498 of 223503
(This msg. is a reply to 223497 by jazzbeerman.)


AACR - BETABODIES
Abstract Number: 4089


Fusion proteins composed of mouse IgG2a Fc and mouse beta-2-glycoprotein 1 bind to endothelial cells with exposed phosphatidylserine



Troy A. Luster, Philip E. Thorpe. Unversity of Texas Southwestern Medical Center, Dallas, TX


A promising target on tumor vasculature is phosphatidylserine (PS), an anionic phospholipid that resides exclusively on the inner leaflet of the plasma membrane under normal conditions. We have previously shown that PS becomes exposed on the surface of viable endothelial cells (EC) in solid tumors. To target PS on tumor vasculature, a murine monoclonal antibody (3G4) was developed. 3G4 specifically localizes to the vasculature of solid tumors and inhibits growth of murine and human tumor xenografts. A chimeric version of 3G4 (bavituximab) is currently in clinical trials for treatment of solid tumor malignancies.
Recently we determined that 3G4 recognizes PS through the formation of a complex with plasma protein beta-2-glycoprotein 1 (b2GP1). b2GP1 is a 50 kDa glycoprotein composed of five domains, including the positively charged domain V that binds anionic phospholipids. However, the interaction of b2GP1 with anionic phospholipids is weak under physiological conditions. Importantly, we demonstrated that 3G4 enhances the avidity of b2GP1 for membrane surfaces with exposed PS through the formation of multivalent 3G4/b2GP1/PS complexes. This increased avidity of b2GP1 for PS is likely responsible for targeting of 3G4 to tumor EC with exposed PS.
We report here the construction of recombinant fusion proteins composed of mouse IgG2a Fc and mouse b2GP1. The Fc region is fused to the N-terminus of full-length b2GP1 or domain V only. This orientation was chosen to avoid interference with the lipid binding region in domain V of b2GP1, which is located at the extreme C-terminus of the protein. These compounds are generated as dimers, linked via disulfide bonds in the hinge region of the Fc tags. The dimeric construction provides the increased avidity necessary for these compounds to bind EC with exposed PS; thus, they behave in vitro much like the 3G4/b2GP1 complexes described previously. These Fc-b2GP1 compounds have potential as tumor therapeutic or imaging agents.

[Preciouslife1]

By: jazzbeerman 14 Mar 2007, 07:41 AM EDTMsg. 223500 of 223503
(This msg. is a reply to 223499 by jazzbeerman.)

AACR - human 2C3 (anti-VEGFr2)

("To bring 2C3 to the clinic we have developed fully human IgG constructs (Hu2C3) with the same specificity as 2C3")

Abstract Number: 2128


Blockade of tumor-derived VEGF activation of VEGF receptor 2 reduces macrophage infiltration into tumors and decreases me.tastasis in a pre-clinical orthotopic model of pancreatic cancer


Juliet G. Carbon, Shane E. Holloway, Andrew F. Miller, Anita Kavlie, Kyle Schlunegger, Jason B. Fleming, Rolf A. Brekken. UT Southwestern Medical Ctr., Dallas, TX, Affitech AS, Oslo, Norway, Peregrine Pharmaceuticals Inc, Tustin, CA, UT-MD Anderson, Houston, TX

Vascular endothelial growth factor (VEGF) is a primary stimulant of the development and maintenance of vascular networks in tumors. VEGF binds and activates VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), which are expressed on endothelial and other cell types. Most of the current anti-angiogenic strategies in clinical trials against pancreatic cancer block the activity of both receptors. We have developed 2C3, a mouse monoclonal (mAb) that selectively inhibits VEGF from binding and activating VEGFR2 but not VEGFR1. We propose that selective inhibition of VEGFR2 is an eq.uivalent anti-tumor strategy to the blockade of both VEGFR1 and VEGFR2. We tested this hypothesis in a murine orthotopic model of pancreatic cancer where we found that 2C3 augments the anti-tumor activity of chemotherapy and alone can reduce significantly me.tastatic spread of tumor cells. Furthermore, prolonged inhibition of tumor-derived VEGF with 2C3 results in decreased microvessel density, VEGFR2 expression, and macrophage infiltration. Importantly, we found that host macrophages in the tumor or isolated from the peritoneal cavity of tumor-bearing animals express VEGFR2, and VEGFR2 mediates VEGF-induced chemotaxis of these cells. These findings demonstrate that VEGFR2 dominates VEGF signaling in a tumor-bearing host, and that selective blockade of VEGFR2 achieves a potent anti-cancer effect. To bring 2C3 to the clinic we have developed fully human IgG constructs (Hu2C3) with the same specificity as 2C3. Hu2C3 binds VEGF with high affinity and blocks VEGF-induced activation of VEGFR2 in vitro. We have also found that Hu2C3 reduces the growth, vascularization, and macrophage infiltration of subcutaneous A673 tumors xeongrafts in mice. In summary, we have demonstrated that VEGF-VEGFR2 binding is critical for VEGF-induced infiltration of host macrophages into tumors, and selective blockade of this interaction is an attractive therapeutic strategy against pancreatic cancer.
__________________

[Preciouslife1]

By: jazzbeerman 14 Mar 2007, Msg. 223499 of 223506
(This msg. is a reply to 223498 by jazzbeerman.)

AACR - Humanized Bavituximab


Abstract Number: 4095



Selective targeting of cellular immune responses by chimeric and humanized monoclonal antibodies to
phosphatidylserine exposed in tumor vasculature


Monica Friedrich, Amy Brideau-Andersen, Bruce Freimark, Connie Chang. Peregrine Pharmaceuticals, Inc., Tustin, CA

Anionic phospholipids, principally phosphatidylserine (PS), become exposed on the external surface of vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. The murine antibody 3G4 has been previously shown to bind to anionic phospholipids in a b2-glycoprotein I (b2GP1)-dependent manner. This antibody inhibits tumor growth in a variety of rodent tumor models that may involve stimulating antibody-dependent cellular cytotoxicity (ADCC) toward tumor vessels. We have generated chimeric mouse/human (bavituximab) and humanized versions of 3G4 for the treatment of human cancer. In the present study, we evaluate the ability of the chimeric and humanized antibodies to exert anti-tumor effects through various mechanisms, including ADCC, on cellular targets expressing PS. We also compare binding kinetics to b2GP1 and demonstrate in vivo targeting to tumor blood vessels. In the presence of bavituximab or humanized 3G4, human peripheral blood mononuclear cells mediate specific killing of human tumor cells treated with paclitaxel or etoposide. Selective targeting of blood vessels within human MDA-MB-435 tumors in nude rats is shown following a single intravenous dose of bavituximab. No toxicities of bavituximab or humanized 3G4 are observed following intravenous administration in rats. The binding kinetics of both bavituximab and humanized 3G4 antibodies to b2GP1 are eq.uivalent using surface plasmon resonance. These data demonstrate that humanized 3G4 has comparable target recognition and effector function to bavituximab and, therefore, could be used to treat human cancer patients.

[Preciouslife1]

Posted by: cjgaddyDate:3/15/2007 1:35:17 PM
AACR 2007 (Apr14-18) – 10 PPHM-related Posters

“More than 17,000 scientists from all over the world will gather under the AACR’s banner in what has become the field’s most important intl. annual cancer research meeting.”
http://www.aacr.org/home/scientists/meetings--workshops/annual-meeting-2007/program-in-progress.aspx - click “ONLINE PROCEEDINGS”


http://www.investorshub.com/boards/read_msg.asp?message_id=17911547

1. #3273 (Apr16) ‘Vascular Targeting Antibody Improves Chemotherapy of Prostate Cancer’
Yi Yin, Xianming Huang, Jin He, Troy A. Luster, Philip E. Thorpe - UTSW-MC/Dallas
”Treatment with the combination [2aG4+Docetaxel] reduced the growth of small LNCaP & PC3 tumors by 80-82% and of well-established LNCaP & PC3 tumors by 92-94%. The antitumor effect of the combination treatment was significantly superior to that of the individual treatments (P < 0.01). The combination therapy was no more toxic to the mice than was docetaxel alone as judged by physical signs and body weight changes… The present results provide the foundation for using bavituximab plus docetaxel to treat prostate cancer patients.”
FULL ABSTRACT: http://www.investorshub.com/boards/read_msg.asp?message_id=17860805

2. #4089 (Apr17) ‘Fusion Proteins Composed of Mouse Igg2a Fc and Mouse Beta-2-Glycoprotein 1 Bind to Endothelial Cells with Exposed Phosphatidylserine’ [‘BETABODIES’]
Troy A. Luster, Philip E. Thorpe - UTSW-MC/Dallas
”Recently we determined that 3G4 recognizes PS through the formation of a complex with plasma protein beta-2-glycoprotein 1 (B2GP1)… 3G4 enhances the avidity of B2GP1 for membrane surfaces with exposed PS through the formation of multivalent 3G4/B2GP1/PS complexes. This increased avidity of B2GP1 for PS is likely responsible for targeting of 3G4 to tumor EC with exposed PS… We report here the construction of recombinant fusion proteins composed of mouse IgG2a Fc and mouse b2GP1… These Fc-B2GP1 compounds [‘BETABODIES’] have potential as tumor therapeutic or imaging agents.”
FULL ABSTRACT: http://www.investorshub.com/boards/read_msg.asp?message_id=17860821

The rest is in the first green link above for Ihub.com PPHM board...

[Preciouslife1]

28-Year Old Penn Patient, Undergoing Treatment for Deadly Brain Tumor, Stresses Importance of Clinical Trials >Aggressive brain tumors (glioblastoma multiforme, or GBM) that do not respond to traditional chemoradiation treatment may respond to Cotara®.>Cotara is a monoclonal antibody that targets the DNA of cancer cells and carries a radioactive isotope.>Cotara is delivered through a method called convection enhanced delivery (CED), which uses a catheter to bypass the blood-brain barrier and target the specific tumor site in the brain. >The Hospital of the University of Pennsylvania (HUP) is one of four sites participating in the clinical trail of Cotara.(PHILADELPHIA) – Physicians initially diagnosed Phil Marfuta, 28, with tension headaches, which seemed reasonable to him since he is a busy graduate student studying physics at Princeton University. However, as the days went on his headaches did not subside, and when a CT scan and an MRI revealed two tumors, Phil underwent emergency surgery at the Hospital of the University of Pennsylvania.
One of Phil’s tumors was a grade IV glioblastoma multiforme (GBM), which is the most aggressive form of primary brain tumor. Typically once diagnosed, the median survival time for a patient with a GBM is 12 months.
“That kind of news is the kind you don’t want to have to call your family and tell them about,” says Phil.
Phil’s tumors had stopped responding to traditional chemoradiation treatment and to a clinical trial that added an immune modulator to his therapy. That’s when he learned of the Cotara® trial.
About Cotara® and the Clinical Trial
Cotara is delivered through a method called convection enhanced delivery (CED).

Click on thumbnail
to view full-size image

Cotara is a monoclonalantibody that targets the DNA of cancer cells and carries a radioactive isotope to them, literally destroying the cancer cells from the inside out. GBMs are complicated to treat because filaments of malignant cells spread out like fingers from the tumor and take root deep in the surrounding tissue, making it difficult to remove them without damaging healthy brain cells. This approach targets the cancer cells, while sparing healthy tissue in the brain.
In November, 2006, Phil was treated in this clinical trial of Cotara. “It involved just catheters, so compared to a craniotomy, that sounded quite nice,” recalls Phil. To-date, Phil’s GBM has been stabilized
HUP is one of four sites participating in the clinical trail of Cotara, a biological “guided missile” for the treatment of GBM, a deadly form of brain cancer that is newly diagnosed in more than 10,000 Americans each year.
Phil feels very strongly about the importance of participating in clinical trials and has even posted an account of his experience on the Young Adults Surviving Glioblastoma’s Web site.
“I’m very passionate about science and I really enjoy finding things out and experimenting. By participating in this trial, somehow I feel like I’ve actually done something tangible to help other people who are basically going through the same thing that I am going through. That’s a small thing, but to me, it’s a very active step and it makes me feel good that there’s a contribution that I’ve made,” says Phil. “I sincerely wish that people would take that step and participate in these trials.”
A Different Approach for Treating Brain Tumors
“Based on the scientific rationale for Cotara, coupled with some positive but preliminary indications from previous trials, we believe it is important to study this approach as a new option for this deadly disease,” says Kevin D. Judy, MD, Associate Professor, Department of Neurosurgery at Penn.
“One challenge in treating brain tumors is the difficulty of delivering therapeutic agents to the brain through the blood-brain barrier (BBB) – the physical shield that serves to protect the brain and central nervous system from potentially dangerous or infectious agents,” says Myrna R. Rosenfeld, MD, PhD, Chief of Penn’s Division of Neuro-Oncology. Cotara is delivered through a method called convection enhanced delivery (CED), which uses a catheter to bypass the BBB and target the specific tumor site in the brain. “This method enables us to treat GBMs with local therapy that does not have side effects elsewhere in the body,” says Robert Lustig, MD, Clinical Associate Professor of Radiation Oncology at Penn.
The Objective of the Clinical Trial
The Phase 2 clinical trial is designed to evaluate a single Cotara infusion in patients with a first or second recurrence of GBM. The primary endpoints of the trial are to confirm safety and determine median survival time and median time to progression in patients treated with Cotara. Cotara has been granted orphan drug status and fast track designation by the U.S. Food and Drug Administration for the treatment of GBM.
Peregrine Pharmaceuticals, Inc., developers of Cotara, is working with the New Approaches to Brain Tumor Therapy (NABTT) to conduct the trial at Penn, Wake Forest University, Emory University, and the University of Alabama at Birmingham.

[Preciouslife1]

Snipets from the March CC compiled by CJG on IHUB.com:
http://www.investorshub.com/boards/r...ge_id=18005970

Roger Adams: Great report this quarter, gentlemen. My question concerns the Bavituximab cancer trial. I noticed you received increased interest from pharmaceutical co's after the AASLD report of that data. Based on what you've seen so far coming out of the combination therapy trial in India, are you anticipating an increase in cancer pharmaceutical partnering interest, after you report the 12 patient results?
SK: ”Yes, I think in general, every trial at this point we complete creates tremendous value. Particularly because Bavituximab is a completely new approach to treating not only solid tumors, but to treating HCV infection. So one of the questions any partner will have will revolve around safety. Clearly, we've now started to build a significant base of patients we've treated with the drug. The combination therapy studies we're doing in India I think help further drive interest, primarily because it's establishing safety as the drug will be used, and again, all biologics for cancer therapy are currently used in combination, so you're answering another question for the potential partner. Clearly, any signs of activity in that trial will be another positive, as we've [already] generated safety data, but now we have some, if you will, guideposts for future clinical development. So I think taken together, those 2 factors should help drive a lot of interest in the program, based on completing the study in India.”

Richard Feracusa, Merrill Lynch: Earlier you had mentioned the progress that Duke University had made with regard to HIV. It was quite impressive, and I know that they have received Gates Foundation money for HIV trials. Do you anticipate that they would conduct clinical trials, or you, or both?
SK: ”One thing to keep in mind is the goal of the group at Duke is to develop vaccines for HIV. Our drug, again, one of the areas of focus they have is, they believe these phospholipids, phosphatidylserine [PS] in particular, may be a very promising target for vaccine development. So the funding that's coming out of there is actually funding a lot of studies that are being done with bavituximab as a model for them to develop later on - vaccines, which would clearly take quite a long time. So whether or not they would support clinical trials is somewhat questionable. Those would probably be trials we would run, and clearly, as we're able to initiate this coinfected patient population we'll start to get some glimpses of at least how our drug interacts with the HIV infection, in an HCV setting. And so, I think from our standpoint, we're just viewing this as a real net-positive. They've given us access to data that we otherwise would not have been able to generate. We clearly, and I know that everyone would love to see the data from the Duke collaboration out there, we're obviously as anxious as anyone. The collaboration is going extremely well, the data we're generating is really helping us in the way we think about our development of bavituximab for HCV & HIV, so it's been a real successful collaboration, and we do look forward to hopefully a little bit later this year getting that data out there and really showing the progress, but in the meantime they're a very conservative group. We're more than happy to comply with their wishes as far as data release, although we certainly do take every opportunity to prod along the release of data when we get a chance.”

[Preciouslife1]

Dick Feracusa, Merrill Lynch: Do you see some sort of 3rd party endorsement of your technology in the near future?
SK: ”One of the real focus points for the company has been to develop relationships within the scientific, pharmaceutical and investor communities. We’ve had numerous discussions with big pharmaceutical companies, there continues to be tremendous interest, actually, in each one of our clinical programs: the bavituximab HCV program, the bavituximab cancer program as well as Cotara. So, really, we’re driving interest from the partnering front by continued contact with these companies. And these would be any company we feel would have the resources to adequately move the program forward. In addition to the partnering discussions we’ve also met with quite a number of analysts on Wall Street in order to pique interest in our key programs. We have seen that interest increase and particularly as we have advanced our clinical programs, and, on the scientific front, of course, making presentations such as at AASLD last year. The fact that we’ve been able to bring on some pretty high profile scientific advisors to help us with our clinical programs we believe will also help to raise the profile of our different programs. So really, that’s been our key focus areas. We think any of these can lead to “3rd party endorsement”, and that that will happen. Unfortunately we can’t necessarily control the timing of when that will happen, but certainly we’ve generated more than enough opportunities that we believe it’s only a matter of time until those endorsements start to come in.”
FOLLOWUP: Do you see any of these pharmaceutical companies that you’re talking to participating in one way or another in the various clinical programs?
SK: ”Absolutely, I think that would be our goal in finding a pharmaceutical partner and it’s not even necessarily just a worldwide type licensing agreement we’re talking about here, so we’ve had significant interest from pharmaceutical companies in different regions of the world who have an interest in actually taking bavituximab, in particular, and running their own clinical studies. And, of course, if we can get partners to run studies which we believe the data will be supportive of our overall efforts, then that’s a net benefit for the company. Because that means, #1, that we’re not having to fund those studies and yet we still get the same benefit from the clinical trials being run. So I think that we would definitely see any pharmaceutical partner taking a very active role in the clinical trials, whether that be on a regional basis, or on more of a global basis.”

[Preciouslife1]

Bavituximab HCV:
Last month we reported positive results from a Repeat-dose clinical study in 24 patients with chronic HCV infection, most of who had failed prior SOC treatments. Highlights of the data include a good safety profile and promising signs of anti-viral activity.
Positive safety data is particularly important, because Bavi represents a completely new approach to treating HCV. Potential pharmaceutical partners focus on the safety profile of new therapeutics, and as a result of now generating over 50 patients worth of safety data in HCV, we have seen a steady increase in partnering interest for the pgm. In addition, a positive safety profile in the aggressive dosing schedule we used during the trial should give us considerable flexibility in designing the next clinical studies. Signs of AV activity in this study were also particularly important. There appear to be a dose-dependence in the AV effects. This indicates that we are beginning to home in on optimal dosing levels, and determining optimal dosing levels is 2nd only to safety in early clinical studies, and it appears we have made a major step fwd this goal. We are currently evaluating scientific venues to present the data from this trial later this year. We, along with our clinical advisors, are very pleased with these results. We achieved our primary goal of achieving safety, while homing in on an optimal dosing level. These results have allowed us to work closely with our advisors to finalize new clinical protocols. These studies will establish optimal dosing frequencies, determine safety with common HCV therapies, and expand the potential patient population. Establishing the optimal dosing frequency, in other words how often to give Bavi in order to achieve optimal effects, is particularly important. Bavi specifically stimulates the immune system to attack the HCV infection. In order to get the best results, we want to work out a treatment schedule that best allows the drug to boost the immune response to the virus. This is similar to a vaccine, in which immunizations are given over an extended period of time in order to give the most robust protection. In fact, if vaccinations are given too frequently, it can actually be counter-productive, resulting in a less-robust response. Needless to say, working out the best treatment regimen for Bavi is our highest priority. Establishing the safety of Bavi with existing HCV therapies is a 2nd key goal. The current SOC and the intended use of all products in development is combination therapies, meaning that several drugs will be used together to treat the HCV infection. In order to set the stage for Ph.2 combo-therapy trials, we plan to initiate new clinical studies to establish the safety profile of Bavi with existing therapies. Expanding the patient population we are treating to potentially include HCV/HIV co-infected individuals is a 3rd focus area. This is an important patient population that represents up to 40% of total HCV patients, meaning that millions of HCV patients are HIV-positive. In addition, these patients are typically excluded from trials of new HCV therapeutics, representing a large potentially-untreated patient population. Our interest in this patient population has been further stimulated by solid evidence, thru our collab’s at Duke, that Bavi binds to HIV virus, binds to HIV-infected cells, and may have potent neutralizing effects on the virus. We plan to lay out our plans for each of these studies over the upcoming weeks as protocols are finalized and initiated.

Bavituximab Oncology:
Over the past few months, we initially and nearly completed a Bavi combo-therapy trial to treat advanced cancer patients in India. Enrollment in this study has gone extremely well, and we now have 11 of 12 evaluable patients. By ‘evaluable’, we are referring to patients that have received enough doses of drug to be included in the study - in this study, at least 4 of the intended 8 doses. We have already enrolled a patient that we anticipate will be our final patient in the study. Once the 12th patient has reached the evaluable milestone, we will close enrollment and provide an update on the study.
In addition to the India study, we are continuing our Ph.1 cancer trial in the U.S. [ http://www.clinicaltrials.gov/ct/show/NCT00129337 ], and have been able to make changes to the protocol that we expect will expedite completion of patient enrollment.
Data generated from the India and U.S. cancer studies should help set the stage for Ph.2 cancer trials we plan to initiate later this year.
In addition to the ongoing clinical studies, we have also been approached by a number of clinical investigators interested in conducting exploratory studies with Bavi. We are currently assessing the opportunities, and we anticipate moving fwd with proposals that will help advance the pgm. We have seen strong interest from potential pharmaceutical partners for the Bavi cancer pgm and believe the data generated by the ongoing studies will be a key value driver.

[Preciouslife1]

Cotara Brain Cancer Therapy:
We are pleased to report that the Cotara Glioblastoma [Ph.2] study in India should be starting shortly [ http://tinyurl.com/ybf5u2 ]. The rather lengthly & bureaucratic process of obtaining gov’t approval to mfg. our final Cotara product in India (the process of linking the TNT antibody to the radioisotope) is now complete, and relevant regulatory packages have been submitted. We expect final approval shortly, and then enrollment in the trial will proceed quickly, as our clinical sites have already begun identifying patients that could be suitable for the trial. In view of these factors, we believe that patient enrollment will proceed at a brisk pace. We will update you on this study as patient enrollment proceeds.
While preparing for the India study, we have also continued working with Cotara clinical sites in the U.S. to facilitate completion of the [NABTT] study, including a media outreach initiative. These efforts seem to be taking hold, as we have already seen enhanced activity in the trial.
We continue to see strong interest from potential partners for the Cotara pgm, and believe that data generated by the India Ph.2 study will drive tremendous value for the pgm.

Other Operational Highlights:
We recently announced 2 significant developments for our TNT pgm. These developments, along with advancements in our Cotara pgm, demonstrate the broad nature and potential for the TNT platform. These developments include:
• Initiation of a clinical trial, using a TNT-based product for cancer therapy by one of our pharmaceutical sub-licensees [ http://tinyurl.com/2zcjqr - could ‘licensee’ be Merck KGaA? See http://tinyurl.com/ywc8tm ]
• Launch of a TNT-based lung cancer drug in China [ http://tinyurl.com/ttlne ]
Although the launch of this product in China prompted legal action by the company to protect its rights to receive fair compensation, we believe these developments are a positive indicator of the potential of our TNT platform.
We also recently announced 2 significant developments for our VTA platform. Just to remind you, VTAs are agents that specifically target tumor blood vessels for treatment and diagnosis. The developments in our VTA pgm include:
• A collab. for Biotecnol to evaluate novel VTA therapeutics [Anti-PS Fusion Proteins http://tinyurl.com/yev7dm ]. These agents will use our targeting platform to deliver cytokines to tumor blood vessels. Cytokines are naturally-occurring molecules that stimulate the immune system. As a result of treatment with these novel agents, blood flow into the tumor will be shut off and the tumor will die from the lack of oxygen & nutrients. This general approach to treating tumors has already been validated by our collab’s at UTSW, further adding to our excitement over the pgm. As part of this collab, we will combine our proprietary Anti-PS targeting platform with Bopnesol’s novel cytokine constructs to produce new molecules that may have application in both cancer and virus therapies.
• The report by our collab’s that VTA-targeted Microbubbles could be used to identify which cancer patients are benefiting from costly anti-angiogenesis therapies such as Avastin [ http://tinyurl.com/v7mf9 & http://tinyurl.com/w4pe9 ]. This is a particularly encouraging technology since the approach uses Ultrasound technology, which is available in most Dr’s offices and it’s inexpensive. We are currently exploring app’s of this promising technology and will keep you informed as progress is made.
We also recently announced the formation of a wholly-owned subsidiary in China [ ‘Peregrine Beijing Pharmaceuticals Technology Development Ltd.’, http://tinyurl.com/y4vzbj ]. This subsidiary was established to give us flexibility as we explore business opportunities in China. We are currently evaluating our options for directly developing our products in China, as well as partnering opportunities. We have already begun prep’s for our initial ‘Clinical Trials Authorization’, or CTA, filing in China, and expect to proceed with the filing later this year. In addition, we have had partnering discussions with some of the largest pharmaceutical companies in China, who have expressed tremendous interest program. We will continue these opportunities as we move our pgms forward.

[Preciouslife1]

CFO Paul Lytle:
Q3/FY’07 q/e 1-31-07: netloss=$5.0mm, revs=$.4mm (primarily from Avid). For the same period LY, revs were $1.5mm, again mostly related to Avid. Although our revs were down this qtr, it is important to note that Avid was busy with in-process projects dedicated both to outside custs and to Peregrine. As a result, we expect to have an exciting 4th qtr. So far in the 4th qtr, we have released and/or shipped mfg. runs that should gen. close to $2mm in revenue, and this is only a/o the middle of March. We expect to gen. more rev in FY’07 than we did LY, and we are on track to accomplish this goal. Equally important, based on FY’08 projections from our existing custs [ex: Halozyme http://tinyurl.com/27toqx ], we believe next year could be a record year for Avid. Let me make crystal clear here that these are projections from our custs, rather than binding commitments, but when you include these runs in our projections, they indicate that Avid could gen. record mfg revs for Peregrine in FY’08. Also, Avid was actively engaged in providing mfg. services for Peregrine’s clinical-stage products, Cotara & Bavi, and continued its efforts with commercial scale-up services that will increase our production capabilities. This work will support our anticipated increased needs for clinical products as we advance our drug candidates into later-stage trials. Avid’s ability to timely develop, mfg., and deliver our products is what makes it such a valuable strategic asset for Peregrine… 2nd reason for increase in net loss this qtr: prior year had Interest&Income of almost $1.4mm, but most of this amt. reflected a 1-time collection of a $1.2mm note-rec. that had been previously deemed uncoll… Based on successes to date and the advances of our pgms in the clinic, R&D spending increased to $3.9mm.
BALANCE SHEET: Cash $20.1mm a/o 1-31-07. This qtr our cash was strengthened by $1.2mm from the exercise of 1.2mm warrants. This represented most of the warrants that are still o/s, and we now have a mere 423k warrants o/s with a avg strike price of $1.40/sh.
SHELF REGISTERATION STATEMENT: I want to emphasize to everyone that we are not in any discussions to sell a single share of stock to investors. Let me say this again. We are not in any discussions to sell a single share of stock. It is useful to note that our shelf reg. statement is really just a pre-approved line-of-credit that has the potential to allow us to obtain better fin. terms than we would otherwise receive if we raise capital using un-reg. shares. It also provides us greater flexibility, incl. possible strategic uses. There are a number of other opportunities we are pursuing to increase our capital resources that do not include the sale of shares to investors under the shelf. We are pursuing these now, and we will continue to pursue these avenues over the coming months.
In closing, we believe PPHM is well-positioned for success. We have 3 active clinical pgms for applications with considerable market potential, we have in excess of $20.1mm in cash on hand with a historical burn rate of ~$4.5mm/qtr (last 3 qtrs), we have released and/or shipped mfg. runs that should gen. over $1.9mm in Avid revs in the 4th qtr and this is only a/o mid-March, and Avid could achieve record revs in FY’08 based on current client projections. Taken together, we believe exciting times are ahead.