PPHM and Tarvacin discussion

[Preciouslife1]

Peregrine Pharmaceuticals Completes Patient Enrollment in Bavituximab Combination Therapy Trial in Advanced Cancer Patients
Thursday March 22, 7:00 am ET

- More than Half of Study Patients Completing Treatment and Assessed for Tumor Progression to Date Have Demonstrated Stable Disease or Objective Response -

TUSTIN, Calif., March 22 /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 that enrollment of the planned 12 evaluable patients in its Phase lb cancer trial has been completed. This trial at clinical sites in India is designed to assess the safety of bavituximab in combination with common chemotherapy agents in advanced cancer patients with me.tastatic disease who had failed prior therapy. Data from this study are expected to support the initiation of Phase II cancer trials later this year.

To date, the safety profile of bavituximab in combination with chemotherapy appears similar to that seen in advanced cancer patients undergoing chemotherapy treatment alone. Nine patients have completed their course of therapy and have been assessed for tumor response at the eight week scheduled MRI or CT scan. Of these, more than half of the patients achieved either disease stabilization or an objective tumor response. "Disease stabilization" is defined as less than a 20% increase in the size of the tumor up to a 30% reduction in tumor size, while "objective response" is defined as greater than a 30% reduction in tumor size. Both stable disease and objective response are considered potential signs of anti-tumor activity. Patients demonstrating either an objective tumor response or stable disease have been offered continued treatment with the combination regimen on a compassionate use basis.

"We are encouraged by the results seen to date in this first test of bavituximab in combination with common chemotherapy regimens," said Steven W. King, president and CEO of Peregrine. "Achieving stable disease and objective responses in these very ill advanced cancer patients is a promising sign, and we look forward to reporting top-line results as soon as patient follow-up and data analysis are complete. We are optimistic that these results, in combination with data from our ongoing U.S. Phase l cancer trial, will support advancing bavituximab into more extensive combination therapy cancer trials later this year."

The Phase Ib open label trial is designed to characterize the safety, tolerability and pharmacokinetics of bavituximab given in combination with standard chemotherapy regimens including docetaxel, gemcitabine and carboplatin/paclitaxel. These regimens are commonly used for treating major solid cancers, and the enrolled patients include those with breast, ovarian and lung cancers. Study patients are considered enrolled and evaluable for safety analysis after completing four of the planned eight weekly doses of bavituximab in combination with chemotherapy. The chemotherapy agent was administered for up to eight weeks on its standard prescribed administration schedule. Patients are also being evaluated for tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) parameters, receiving CT or MRI scans prior to therapy and at week eight, although this assessment is not a formal endpoint of the study.

Study participants are being followed for an additional four weeks after their last dose of bavituximab. Patients with stable or improved disease may continue with chemotherapy and bavituximab on a compassionate use basis. The trial is being conducted according to International Conference on Harmonization (ICH) and Good Clinical Practices (GCP) guidelines.

Bavituximab is a monoclonal antibody that targets and binds to a phospholipid called phosphatidylserine, which is located on the inside of normal cells but which becomes exposed on the outside of the cells that line the blood vessels of tumors, creating a specific target for anti-cancer treatments. Bavituximab is currently in clinical trials in the U.S. and India for the treatment of solid tumors and in the U.S. as a treatment for chronic hepatitis C infection. Extensive preclinical data demonstrate good anti-tumor activity in a variety of tumor types, especially when bavituximab is administered in combination with chemotherapy or radiation.

About Peregrine Pharmaceuticals

Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing five separate clinical trials in cancer and HCV infection in the U.S. and India with its lead product candidates bavituximab and Cotara®. Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com.

[Preciouslife1]

Posted by: jazzbeerman
In reply to: NoneDate:3/29/2007 7:53:19 AM
Post #of 12692
Collaboration for AIDS Vaccine Discovery

a few excerpts-

Overview

The Global HIV Vaccine Enterprise was established in 2003 as a collaborative global effort to promote the development of a safe and effective HIV vaccine. The Gates Foundation has set out to advance this mission by contributing more than $287 million in support of HIV vaccine development and discovery. The Foundation awarded funds to eleven consortia that will focus on novel methods in HIV vaccine design and five central laboratories and data analysis facilities that will provide state-of-the-art technologies to evaluate HIV vaccine candidates. These sixteen grants are collectively known as the Collaboration for AIDS Vaccine Discovery (CAVD).

Dr. Barton Haynes, Director of the Duke Human Vaccine Institute (DHVI) and Director of the Center for HIV/AIDS Vaccine Immunology leads one of the Vaccine Discovery Consortia (VDC) titled, “Broadly Reactive Neutralizing Antibodies: Novel Strategies for Vaccine Design.” The goal of this VDC is to develop a vaccine that elicits neutralizing antibodies against HIV, currently a major hurdle in HIV vaccine research. With the assistance of this grant and in conjunction with CHAVI studies, Dr. Haynes and his colleagues will pursue several novel design strategies including using recombinant vectors to deliver immunogens and using autoantigens to elicit antibody responses.

http://humanvaccine.duke.edu/modules/grant_spt/index.php?id=6#Overview

Haynes VDC Mission and Goals

The goal of the Haynes Vaccine Discovery Consortia is to acquire proof of concept data that manipulation of the immunoregulatory controls of B cell immune responses to HIV-1 Env, coupled with enhanced immunogen design, can lead to safe induction of broadly reactive neutralizing antibody responses. We are using a two armed approach to the problem of induction of antibodies that broadly neutralize HIV.

First, the Kelsoe, Haynes and Thorpe laboratories are developing immunogen formulations that trigger B cells normally tolerant to the desired Envelope epitopes and regions. Garnett Kelsoe is determining the origins, development, physiology, and fates of marginal zone, transitional and B1 B cell populations in animal models including mice and non-human primates. To do this, the Kelsoe group has develop a “Marginal Zone B Cell Mouse” that is a reconstituted mouse that contains predominantly all MZ B cells for immunization and immunoregulation studies. Haynes is determining the role of tolerance mechanisms, T regulatory cells and TLR signaling on control of broadly reactive B cell activation, and Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine(PS) autoantibodies to protection from HIV infection. With Norm Letvin, a protection trial is planned to determine if anti-PS antibodies can prevent infection or early viral destruction of the immune system in acute SIV infection.

Second, the Harrison, Alam, Spicer, Shaw, Robinson and Hahn laboratories are developing immunogens that are more “native” and will preferentially induce the desired antibody types. These include HIV Env immunogens with a spectrum of affinities for binding to broadly reactive neutralizing antibodies, and immunogens with low entropic barriers to Mab binding and therefore are thermodynamically stable. Steve Harrison and group are expressing and characterizing single-chain Fvs from 4E10, 2F5 and 2G12 Mabs. With these genes he is carrying out directed mutation of single-chain Fvs and dissecting lipid and protein contributions to binding and Mab neutralization. He will use the Fvs in co-crystallization efforts with trimeric gp120/gp41 constructs. Munir Alam is designing gp41 peptide lipid conjugates using 4E10 and 2F5 epitpes peptides. He is characterizing the binding kinetics, and thermodynamic properties of 4E10 and 2F5 binding to peptide-lipid conjugates. Haynes is characterizing the carbohydrates of HIV-1 Env produced in T cells and macrophages, and is determining methods for making these “autoantigens” immunogenic. Spicer is studying the lipid-peptide conjugates for their structures by NMR. George Shaw and Beatrice Hahn have constructed HIV-1/HIV-2 chimeras with HIV-2 neutralizing determinants in HIV-1 scaffolds, to study the neutralization of HIV-2. They are constructing novel immunogens with HIV-1 and 2 scaffolds and virus like particles for formulation with adjuvants developed in this VDC by Haynes and colleagues.

http://humanvaccine.duke.edu/modules/grant_spt/index.php?id=11


Southeast Regional Center of Excellence for Emerging Infections and Biodefense

Dr. Barton Haynes, Dr. Greg Sempowski, and Dr. Herman Staats are investigating the role of a new lymphocyte population, called T regulatory cells, in modulating host responses to vaccines. In their study titled, “Ligand Interactions in Innate Immune Systems,” they determined that T Regulatory cell depletion at the time of vaccination can enhance T and B cell responses.

http://humanvaccine.duke.edu/modules/grant_spt/index.php?id=3


HIV, TB, and Malaria Vaccine Development for Africa (PO1)

In 2002, Dr. Barton Haynes received a PO1 grant from the NIH titled, “HIV, TB, and Malaria Vaccine Development for Africa.” Through this PO1, DHVI investigators are attempting to develop a trivalent vaccine for HIV, TB and malaria for children.

Dr. Haynes, Dr. Larry Liao, Dr. David Montefiori, Jae-Sung Yu, and James Peacock are currently working on PO1 Project 4 titled, “HIV Neutralizing Antibody Immunogens for Expression in Attenuated Mycobacteria.” A significant part of the project involves generating recombinant vaccinia viruses (rVV) that will allow investigators to express recombinant HIV-1 envelope proteins, HIV-1 gp120 and gp140. They can then induce neutralizing antibodies against the HIV-1 primary isolates derived from these proteins in order to determine which isolates produce the best immune responses in guinea pigs. The Molecular and Immunology Core (Core C) led by David Montefiori, Larry Liao, Feng Gao, and Herman Staats is collaborating on the Project in the development of optimal HIV-1 immunogens.

Investigators are also contributing to this vaccine development by expressing HIV-1 gp120 and gp140 in Mycobacterium smegmatis (rSmeg), BCG and attenuated MTB in order to determine their ability to induce anti-HIV T cell responses at systemic and mucosal sites.

Finally, DHVI investigators focused on studying the relationship between cardiolipin and HIV-1 immunity. Current vaccines derived from HIV-1 envelope proteins have not been able to successfully induce broadly reactive neutralizing antibodies in HIV-1 infected patients. HIV-1 patients can, however, produce polyclonal antibodies when their B cells react with the endogenous phospholipid called cardiolipin. Investigators hypothesized that cardiolipin could, therefore, induce an immune response to human monoclonal antibodies. In order to test their theory, they assayed two rare MAbs with broadly neutralizing activity, 2F5 and 4E10, along with 33 other anti-HIV-1 MAbs for cardiolipin and other autoantigen reactivities. They found that 2F5 and 4E10 both reacted with cardiolipin while the 33 other MAbs did not. Future plans include studying the rare number of patients with SLE and anti-phospholipid syndrome (APS) who developed HIV-1 infection to find out if they make anti-membrane proximal antibodies, which neutralize HIV.

http://humanvaccine.duke.edu/modules/grant_spt/index.php?id=4

[Preciouslife1]

Collaboration for AIDS Vaccine Discovery

OVERVIEW:


The Global HIV Vaccine Enterprise was established in 2003 as a collaborative global effort to promote the development of a safe and effective HIV vaccine. The Gates Foundation has set out to advance this mission by contributing more than $287 million in support of HIV vaccine development and discovery. The Foundation awarded funds to eleven consortia that will focus on novel methods in HIV vaccine design and five central laboratories and data analysis facilities that will provide state-of-the-art technologies to evaluate HIV vaccine candidates. These sixteen grants are collectively known as the Collaboration for AIDS Vaccine Discovery (CAVD).

Dr. Barton Haynes, Director of the Duke Human Vaccine Institute (DHVI) and Director of the Center for HIV/AIDS Vaccine Immunology leads one of the Vaccine Discovery Consortia (VDC) titled, “Broadly Reactive Neutralizing Antibodies: Novel Strategies for Vaccine Design.” The goal of this VDC is to develop a vaccine that elicits neutralizing antibodies against HIV, currently a major hurdle in HIV vaccine research. With the assistance of this grant and in conjunction with CHAVI studies, Dr. Haynes and his colleagues will pursue several novel design strategies including using recombinant vectors to deliver immunogens and using autoantigens to elicit antibody responses.

Dr. David Montefiori, a DHVI Investigator, will lead the “Comprehensive Antibody Vaccine Immune Monitoring Consortium,” an international network of laboratories that will conduct diagnostic testing to determine the immunogenicity of viable vaccine candidates. Specifically, this consortium with be evaluating the capacity of vaccine candidates to elicit neutralizing antibodies, therefore, Dr. Montefiori’s work will complement the vaccine discovery consortium led by Dr. Haynes. As one of the goals of the vaccine discovery consortia is to induce broadly cross-reactive neutralizing antibodies, this consortium will help establish a standardized evaluation systemto which all of the central facilities will adhere in order to communicate a broad spectrum of results more efficiently.
http://humanvaccine.duke.edu/modules...?id=6#Overview

Posted by: jazzbeerman
Date:3/28/2007 9:25:34 PM
Post #of 12692


"First, the Kelsoe, Haynes and Thorpe laboratories are developing immunogen formulations that trigger B cells normally tolerant to the desired Envelope epitopes and regions. Garnett Kelsoe is determining the origins, development, physiology, and fates of marginal zone, transitional and B1 B cell populations in animal models including mice and non-human primates. To do this, the Kelsoe group has develop a “Marginal Zone B Cell Mouse” that is a reconstituted mouse that contains predominantly all MZ B cells for immunization and immunoregulation studies. Haynes is determining the role of tolerance mechanisms, T regulatory cells and TLR signaling on control of broadly reactive B cell activation, and Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine(PS) autoantibodies to protection from HIV infection. With Norm Letvin, a protection trial is planned to determine if anti-PS antibodies can prevent infection or early viral destruction of the immune system in acute SIV infection."

(Norm Letvin is "the man" at Harvard, and Chief of the Division of Viral Pathogenesis at the Beth Israel Deaconess)...

-------------

AND - coincidentally- they're also talking about VLP's with "adjuvants".... (IMO, as I've mentioned before - anti-PS coated VLP's should be a logical and very promising immunogen candidate.)

"George Shaw and Beatrice Hahn have constructed HIV-1/HIV-2 chimeras with HIV-2 neutralizing determinants in HIV-1 scaffolds, to study the neutralization of HIV-2. They are constructing novel immunogens with HIV-1 and 2 scaffolds and virus like particles for formulation with adjuvants developed in this VDC by Haynes and colleagues."

[Preciouslife1]

***Peregrine Pharmaceuticals Comments on Lawsuit***


TUSTIN, Calif., March 30 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus (HCV) infection, today commented on a cross-complaint filed by Cancer Therapeutics Laboratories Inc. (CTL) and discussed in a press release issued yesterday by CTL.
Peregrine had previously filed a lawsuit against CTL on January 12, 2007 alleging various breaches of contract in relation to a license agreement between the two companies that granted CTL certain rights to Peregrine's tumor necrosis therapy (TNT) technology for development and commercialization in China. The lawsuit followed repeated attempts by Peregrine over a number of years to obtain adequate information concerning a purported agreement that CTL made with MediPharm Biotech Pharmaceutical Co., Ltd and/or Shanghai MediPharm Biotech Co., Ltd. (MediPharm), a company that has now launched Peregrine's proprietary TNT-based product in China for the treatment of lung cancer.
"We filed this lawsuit to protect the rights of Peregrine and its shareholders," stated Steven W. King, president and CEO of Peregrine. "CTL has clearly breached its obligations under our license agreement, and we believe that this cross-complaint filed today by CTL is uneq.uivocally without merit and completely preposterous. We have an obligation to protect the assets of our company and to build shareholder value, and we intend to pursue all necessary avenues to safeguard our interests in this case."
Peregrine had licensed certain rights to the company's TNT technology platform for development and commercialization in China exclusively to Cancer Therapeutics Laboratories, with the stipulation that CTL was permitted to sublicense these rights only to a single Chinese pharmaceutical company (the sublicensee). Under this agreement, CTL formed a joint venture in the name of Shanghai Brilliance Cancer Pharmaceutical Co. Ltd., to serve as the sublicensee. Under the terms of the agreement, Peregrine was entitled to one-half of the profits received by CTL and a portion of CTL's equity in the joint venture. To date, Peregrine has not received any financial consideration from CTL under the agreement, nor had Peregrine received any information or documentation pertaining to the joint venture before filing the lawsuit. This absence of information includes the failure to reveal how MediPharm came to be given rights to develop and market Peregrine's proprietary TNT-based technology in China, since only one sublicensee was permitted under the agreement and CTL had already designated Shanghai Brilliance Cancer Pharmaceutical Co. as that sublicensee.
Peregrine is vigorously pursuing its remedies under the lawsuit and may expand its claims in the complaint based on discovery and investigation since it filed the action. The company is also exploring alternative avenues for commercialization of its TNT technology platform in China.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs in cancer and HCV infection in the U.S. and India with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

[Preciouslife1]

***Science of Oncology Symposia***

**Future Symposia Tentative Schedule**

Date Speaker Title:
April 3, 2007Philip Edward Thorpe, PhD
Professor of Pharmacology
Serena Simmons Distinguished Chair in Cancer Immunopharmacology
Simmons Comprehensive Cancer Center and Hamon Center for Therapeutic Oncology Research
University of Texas Southwestern Medical SchoolCancer Therapy with Antibodies Against Phospatidylserine on Tumor Vasculature

April 10, 2007 Ben Suttle, PhD
GlaxoSmithKline Pharmacodynamic Modeling From Mouse to Man for Pazopanib Dose SelectionApril 17, 2007April 24, 2007

May 1, 2007 Stephen H. Friend, MD, PhD
Executive Vice President, Advanced Technologies and Oncology
Merck Research Laboratories
Merck & Co., Inc.May 8, 2007Thea Tlsty, PhD
Professor of Pathology

University of California, San Francisco May 15, 2007 May 22, 2007 May 29, 2007 June 5, 2007 June 12, 2007 June 19, 2007 Frank Calzone, PhD
Scientific Director, Oncology Research
Hematology/Oncology Research
Amgen, Inc.
Inhibition of endocrine IGF-1 signaling in normal murine tissues and human tumor xenografts with an anti IGF-1R monoclonal antibody (AMG 479)June 26, 2007
http://www.cancer.duke.edu/modules/SOS43/index.php?id=6
Slipperypete on IHUB posted about this speech by Dr. Thorpe.....

[Preciouslife1]

Data Presented at AACR Meeting Shows Peregrine's Selective Anti-VEGF Antibodies are as Effective as Avastin(R) in Preclinical Cancer Models
11:29 a.m. 04/16/2007


********Peregrine's Antibodies that Selectively Inhibit VEGF Receptor 2 Could Potentially Have Advantages over Non-Selective Approaches - - These Results Along with Data Presented on a Fully Human Antibody Support Advancing Peregrine's Anti-VEGF Program towards Clinical Trials - LOS ANGELES and TUSTIN, Calif., Apr 16, 2007 /PRNewswire via COMTEX/ -- - Peregrine's Selective Anti-VEGF Antibodies Inhibited Tumor Growth By 90% In a Preclinical Cancer Model - ******

- Peregrine's Antibodies that Selectively Inhibit VEGF Receptor 2 Could Potentially Have Advantages over Non-Selective Approaches -

- These Results Along with Data Presented on a Fully Human Antibody Support Advancing Peregrine's Anti-VEGF Program towards Clinical Trials - ************************************************** ********

LOS ANGELES and TUSTIN, Calif., April 16 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (PPHM) a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, today reported that preclinical data presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) showed that its monoclonal antibody 2C3, which selectively blocks vascular endothelial growth factor (VEGF) from binding to the second of the two VEGF receptors, demonstrates potent anti-cancer efficacy in a preclinical orthotopic model of pancreatic cancer. In this model, treatment with 2C3 reduced the growth of pancreatic tumors by 90%. The researchers also assessed the anti-tumor activity of 2C3 and the marketed anti-cancer agent Avastin(R) in a number of preclinical cancer models. The anti-tumor activity of 2C3, which only blocks VEGF receptor 2 (VEGFR2) compared favorably to that of Avastin, which blocks VEGF binding to both VEGF receptor 1 (VEGFR1) and VEGFR2.

VEGF is a primary stimulant of the development and maintenance of the blood vessels needed by tumors to survive and grow. It is thought to work by binding to and activating two receptors that are expressed on endothelial and other types of cells. The series of studies reported today tested the hypothesis that selectively inhibiting VEGFR2 is an equally effective anti-tumor strategy to blocking both receptors. Most of the anti-angiogenic agents currently being developed or marketed for cancer, such as Avastin, block the activity of both VEGF receptors.

"The success of Avastin underscores the potential of blocking VEGF as a major strategy for fighting solid cancers," said Steven W. King, president and CEO of Peregrine. "The finding that our selective anti-VEGF antibody demonstrates potent anti-tumor effects in preclinical models of pancreatic cancer is important both for our understanding of the underlying physiology of cancer and because selective VEGF inhibitors may ultimately prove to have advantages compared to non-selective approaches. Now that we have also demonstrated that a fully human anti-VEGF antibody (R3) is comparable to our earlier murine versions, we intend to accelerate our anti-VEGF program, with the goal of initiating clinical trials as soon as next year."

In support of the observed anti-tumor effects of 2C3, the researchers reported that tumor-associated macrophages, immune system cells found in the tumors and peritoneal cavities of these animals, preferentially express VEGFR2, which appears to dominate the VEGF signaling that promotes tumor progression and me.stastasis in this model of pancreatic cancer.

In this pancreatic cancer model, 2C3 significantly reduced the me.tastatic spread of tumor cells as monotherapy and also augmented the anti-tumor activity of chemotherapy when administered in a combination regimen. In addition, when given for a prolonged period, 2C3 produced decreased microvessel density, decreased expression of the VEGFR2 receptor and decreased tumor-associated macrophage invasion, which was consistent with the finding that the VEGFR2 receptor dominates VEGF-induced macrophage recruitment into tumors.

The researchers also tested an eq.uivalent fully human monoclonal antibody, R3, in similar pancreatic cancer models, where it significantly reduced the growth, vascularization and macrophage infiltration of pancreatic tumors in mice. These positive results using a fully human antibody support Peregrine's intent to advance its anti-VEGF program towards clinical trials.

This research, which was conducted under the direction of Dr. Rolf Brekken, assistant professor of surgery at UT Southwestern Medical Center in Dallas, was supported in part by a sponsored research agreement with Peregrine Pharmaceuticals. The fully human antibody R3 used in these studies was developed in collaboration with Affitech AS of Norway. These studies were also supported in part by a postdoctoral fellowship from the Susan G. Komen for the Cure, the Effie Marie Cain Scholarship in Angiogenesis Research and the Department of Surgery at UT Southwestern.

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, Apr 16, 2007, 8:00 AM -12:00 PM PDT

About Peregrine Pharmaceuticals

Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs for HCV infection and a range of solid cancers in the U.S. and India with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. ( www.avidbio.com ), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com .

[Preciouslife1]

PPHM: Presents Positive Preclinical Data for Monoclonal Antibody 2C3
11:33 a.m. 04/16/2007

Ridgeland, MS, APR 16, 2007 (EventX/Knobias.com via COMTEX) -- By Fain Hughes, fhughes@knobias.com

Peregrine Pharmaceuticals, Inc. (PPHM) announced that preclinical data presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) showed that its monoclonal antibody 2C3, which selectively blocks vascular endothelial growth factor (VEGF) from binding to the second of the two VEGF receptors, demonstrates potent anti-cancer efficacy in a preclinical orthotopic model of pancreatic cancer. In this model, treatment with 2C3 reduced the growth of pancreatic tumors by 90%. The researchers also assessed the anti-tumor activity of 2C3 and the marketed anti-cancer agent Avastin(R) in a number of preclinical cancer models. The anti-tumor activity of 2C3, which only blocks VEGF receptor 2 (VEGFR2) compared favorably to that of Avastin, which blocks VEGF binding to both VEGF receptor 1 (VEGFR1) and VEGFR2.

VEGF is a primary stimulant of the development and maintenance of the blood vessels needed by tumors to survive and grow. It is thought to work by binding to and activating two receptors that are expressed on endothelial and other types of cells. The series of studies reported today tested the hypothesis that selectively inhibiting VEGFR2 is an equally effective anti-tumor strategy to blocking both receptors.

[Preciouslife1]

Vascular targeting antibody improves chemotherapy of prostate cancer


Yi Yin, Xianming Huang, Jin He, Troy A. Luster, Philip E. Thorpe. UT Southwestern Medical Center, Dallas, TX

We hypothesized that combining a novel vascular-targeting antibody, 2aG4, with docetaxel should increase the potency and therapeutic index of docetaxel for the treatment of prostate cancer. Phosphatidylserine (PS) is an anionic phospholipid located normally on the inner leaflet of the plasma membrane in mammalian cells. In the tumor microenvironment, PS becomes externalized on vascular endothelium. The monoclonal antibody 2aG4 binds PS and promotes an inflammatory response against tumor blood vessels, resulting in vessel destruction by ADCC and retardation of tumor growth. Male SCID mice were injected with LNCaP or PC3 prostate cancer cells into the hind flanks. Docetaxel (10 mg/kg), 2aG4 (4 mg/kg) alone or in combination were administered at different time points. Treatment with the combination reduced the growth of small LNCaP and PC3 tumors by 80-82% and of well-established LNCaP and 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. Treatment of tumor-bearing animals with the combination therapy further reduced microvessel density in the tumor compared with tumors from single regimen treated animals. Moreover, serum PSA levels in combination treated mice also registered a greater decrease (P < 0.05) as compared to that in docetaxel alone or 2aG4 alone treated LNCaP xenograft animals. Bavituximab, a chimeric version of 2aG4, is currently being combined with standard chemotherapy to treat patients with various types of cancer. The present results provide the foundation for using bavituximab plus docetaxel to treat prostate cancer patients.

[Preciouslife1]

Posted by: cjgaddy
In reply to: NoneDate:4/16/2007 8:28:28 PM
Post #of 13152
PPHM 1ST Compared 2C3 & Avastin in 2003

On May 20, 2003, Peregrine Pharmaceuticals provided a comparison of 2C3, its VEGF antiangiogenesis antibody, to other VEGF compounds, like Genentech’s AVASTIN:

“Peregrine Clarifies Its Anti-Angiogenesis VEGF Antibody and Vascular Targeting Agents Compared to Other VEGF Antibodies”
May 20, 2003: Peregrine Pharmaceuticals provided its investors today with clarification of its VEGF anti-angiogenesis antibody 2C3 compared to Genentech's (Nasdaq: DNA) Avastin and other VEGF compounds. Although they are similar, there are several important distinctions between 2C3 and other VEGF antibodies under development.

2C3 is an antibody that blocks the interaction of Vascular Endothelial Growth Factor (VEGF) with one of its key receptors. VEGF is a primary stimulant of tumor angiogenesis. Peregrine's researchers have developed a monoclonal antibody (2C3) that blocks VEGF from binding to VEGF receptor 2 (KDR/Flk-1) but not VEGF receptor 1 (FLT-1/flt-1). Avastin and other VEGF antibodies block both VEGF receptors.

Inhibiting VEGF receptor 2, but not VEGF receptor 1, is a key difference in the anti-tumor activity of 2C3. VEGF receptor 2 has been shown to be the main receptor that cancer cells use to grow new vessels, whereas VEGF receptor 1 is utilized for normal cellular function of macrophages and monocytes. An inhibitor of VEGF that selectively blocks the function of VEGF receptor 2 should not interfere with macrophage infiltration into tumors, which is an important part of the body's defenses against cancer. This is potentially a significant difference of 2C3 over other VEGF inhibitors that block VEGF binding to both receptors and may provide a better safety profile.

In a recent publication in Angiogenesis, treatment in a me.tastatic breast cancer model, 2C3 inhibited by 75% the establishment of tumor colonies and reduced tumor burden in the lungs of mice injected intravenously with human breast cancer cells. Of particular interest, 2C3 also inhibited the expression of VEGF receptor 2. This dual effect further inhibits the ability of cancer cells to use VEGF to grow tumor vessels. No toxicity was observed in any of these studies.

Peregrine president and CEO Steven King said, "Our 2C3 antibody has several potentially important differences than other VEGF antibodies under development. The ability to block a main receptor that cancer cells use to grow new blood vessels while at the same time not inhibiting a receptor that is used by the body to naturally fight cancer is potentially a very important development and may improve the safety profile of this compound compared to other VEGF antibodies. We are currently developing a fully human antibody for this technology that can be evaluated for use in human clinical studies."

Anti-angiogenesis Agents:
Every cancer begins its existence as a tiny cluster of abnormal tumor cells growing in an organ. Without its own blood supply to bring in oxygen and nutrients, the tumor cannot grow larger than 1-2 millimeters in diameter (about the size of a small pea). While this early stage of tumor growth can last for month or even years, eventually a few cancer cells gain the ability to produce proteins known as angiogenic growth factors. These 'growth factors' are released by the tumor into nearby tissues, and they stimulate new blood vessels to sprout vigorously from existing healthy blood vessels, into the tumor.

Anti-angiogenic therapy is a new form of cancer treatment using drugs called 'angiogenesis inhibitors' that specifically halt new blood vessel growth, stabilize the patient and in some cases shrink tumors. Anti-angiogenesis agents work by blocking growth factors that are responsible for tumor growth. One difficulty facing this new class of drugs is that there are many different growth factors that are responsible for tumor angiogenesis. Developing drugs which block all of the growth factors simultaneously has been elusive.

[Preciouslife1]

About Vascular Target Agents - The Next Generation of Cancer Therapy:
Vascular Targeting Agents are designed to go one step further than anti-angiogenesis agents by completely destroying the existing blood network of the tumor versus stopping the growth of new tumor blood vessels. In pre-clinical animal studies, VTAs have shown to be potent anti-cancer agents that act by cutting off the supply of oxygen and nutrients to tumor cells by causing blood clots to form within the tumor's blood supply network. VTAs localize within the tumor vasculature by selectively binding to the flat endothelial cells that line tumor blood vessels. Once the VTA binds to its target, it initiates thrombosis (blood clotting) through a coagulation cascade, which leads to complete clotting of the tumor blood vessels within a matter of minutes. Because blockage of a single capillary results in the destruction of thousands of tumor cells, only a small quantity of VTAs localized in the tumor's vascular system may cause an avalanche of tumor cell death.

VTAs offer several advantages as potentially powerful anti-cancer treatments. By targeting receptors unique to tumor cell vasculature, VTAs can kill tumors by cutting off oxygen and nutrients without causing damage to surrounding healthy tissue. Additionally, VTAs reduce the risk of potential side effects by operating at lower dosages than traditional cancer therapies because they do not need to penetrate the innermost layer of a tumor to take effect. Lastly, while drug resistance caused by the instability and mutability of cancer cells is a significant problem with conventional therapies that target tumor cells, cells targeted by VTAs do not mutate to become drug resistant.


AVASTIN TIMELINE:
9-12-06: Avastin approval slowed by FDA - Feds requested further data on the use of the drug for advanced breast cancer
9-23-05: Genentech Stops Enrolling Avastin Ovarian Study due to greater occurrences of gastrointestinal perforations than shown in previous studies of the drug.
4-16-05: Avastin helps those with breast cancer Genentech Inc.'s pioneering colon cancer is already
11-29-05: Avastin helps sickest patients Genentech's novel colon cancer-fighting drug helped some of the patients stay alive 2 months longer than expected
Avastin sales totaled $554.5 million in sales in 2004.
2-26-04: FDA approves cancer fighter Avastin (for colon cancer)
**5-20-03: PPHM PR COMPARES 2C3 VS. AVASTIN
5-19-03: Encouraging results with cancer drug Avastin extended the lives of some of the colon cancer patients. Company's stock soaring nearly 45%.

[Preciouslife1]

Data Presented at AACR Meeting Shows Bavituximab *************************alent Plus Docetaxel Reduces Growth of Both Hormone-Dependent and Hormone-Independent Prostate Cancer by Up to 94 Percent in Preclinical Studies


- Combination Therapy Significantly Decreased Tumor Blood Vessel Density and Serum PSA Levels in Prostate Tumors -- Docetaxel One of Chemotherapies Being Studied in Combination With
Bavituximab in Phase Ib Clinical Study That Recently Completed Enrollment -
LOS ANGELES and TUSTIN, Calif., April 17 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, today announced that preclinical data presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) confirms that a mouse *************************alent to Peregrine's novel monoclonal antibody bavituximab given in combination with docetaxel decreased the growth of common forms of prostate cancer significantly more than either agent alone. This increase in anti-tumor efficacy was achieved with no apparent increase in toxicity. Researchers also observed that in one tumor model, the combination significantly decreased the level of serum PSA, a biomarker for prostate cancer, and in both tumor types tested it was more effective in decreasing the density of the microvessels needed to support tumor growth and development.
"This data reaffirms the potential of bavituximab for the treatment of prostate cancer in combination with docetaxel and is particularly timely since we recently completed enrollment in our first human trial of bavituximab in combination with anti-cancer agents including docetaxel," said Steven W. King, president and CEO of Peregrine. "We look forward to assessing further bavituximab's anti-cancer potential in our ongoing clinical trials, as well as in new combination therapy clinical studies we will be initiating later this year."
In this study, the anti-phosphatidylserine (anti-PS) monoclonal antibody 2aG4 (a mouse *************************alent antibody to bavituximab) was administered to male mice that had been injected with common forms of hormone dependent and hormone independent tumor cells. Docetaxel and 2aG4 alone or in combination were administered at different time points. Treatment with the combination regimen reduced the growth of small tumors by 80% to 82% and of well-established tumors by 92% to 94%. The anti-tumor effect of the combination regimen was significantly superior to that of the individual treatments (P < 0.01). Yet the combination therapy was no more toxic to the mice than was docetaxel alone as judged by physical signs and body weight changes.
Tumor microvessel density, which is correlated with tumor growth rates, was further reduced in tumors treated with the combination regimen compared with tumors from single agent-treated animals. In addition, serum PSA levels in combination-treated mice registered a significantly greater decrease (P < 0.05) in one of the tumor models compared to the decrease seen in either the docetaxel-treated or 2aG4-treated animals.
Bavituximab is a targeted monoclonal antibody that binds to a phospholipid called phosphatidylserine, which is located on the inside of normal cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors, thus creating a specific target for anti-cancer treatments. Once bound to the tumor blood vessels, bavituximab alerts the body's immune system to attack the tumor's blood supply, stopping the flow of oxygen and nutrients to the tumor cells and resulting in tumor cell death. As an anti-cancer immunotherapeutic, bavituximab may have broad potential in a wide variety of solid cancers. It is currently in Phase Ia cancer safety trials as a monotherapy and in a Phase Ib trial in combination with docetaxel and other chemotherapy agents in patients with advanced solid cancers, including prostate, breast and lung cancer. Interim data indicate that more than half of the cancer patients in this study who have completed treatment to date were assessed as demonstrating stable disease or an objective response.
Prostate cancer is the most commonly diagnosed cancer in men, accounting for 30% of all male cancers, and it is second only to lung cancer as a leading cause of cancer deaths in men. Currently, there is no cure for locally advanced or ********************static prostate cancer.
This research, which was conducted under the direction of Dr. Philip Thorpe at the University of Texas Southwest Medical Center at Dallas, was supported in part by a sponsored research agreement with Peregrine Pharmaceuticals and by a grant from the U.S. Department of Defense (DOD PC05031 grant). Preliminary data from this study was first presented at a scientific meeting in December 2006.
Number 3273: Vascular Targeting Antibody Improves Chemotherapy of Prostate Cancer, Yi Yin, Xianming Huang, Jin He, Troy A. Luster, Philip E. Thorpe. UT Southwestern Medical Center, Dallas, TX, Apr 16, 2007, 1:00 PM - 5:00 PM
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs for HCV infection and a range of solid cancers in the U.S. and India with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

[Preciouslife1]

Press Release Source: Peregrine Pharmaceuticals, Inc.

Data Presented at AACR Meeting Show Peregrine's Bavituximab eq.uivalent Can Generate Curative Immune Responses as Part of a Vaccine-Like Regimen in Preclinical Models of Aggressive Brain Cancer
Wednesday April 18, 9:45 am ET
--Immunization with a Bavituximab eq.uivalent and Irradiated Tumor Cells Increased Long-Term Survival to 57% From 0% in Controls in a Preclinical Model of Brain Cancer--
--Survival Data Suggest that 99.99% of Tumor Cells in These Animals Were Destroyed--
--Provides Proof of Concept that Peregrine's Anti-PS Antibodies can Reverse the Immune Response Inhibition Caused by Cancer--


LOS ANGELES and TUSTIN, Calif., April 18 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, today announced preclinical studies presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) showed that 2aG4, a mouse eq.uivalent to the company's anti-phosphatidylserine (PS) antibody bavituximab has vaccine- like activity and can generate curative responses in an aggressive model of brain cancer. Researchers also presented data demonstrating that this improvement in survival was likely attributable to the ability of 2aG4 to enable the treated animals to mount an effective immune response against this difficult to treat cancer.


To confirm that the bavituximab eq.uivalent 2aG4 acted by enhancing anti- cancer immune responses, researchers injected rats with irradiated glioma cells (inactivated tumor cells) along with 2aG4. This regimen was intended to protect the animals from a subsequent challenge with a large lethal dose of tumor cells -- 10,000 times the number required to produce lethal disease in this model.

Among the animals pre-treated with the 2aG4-treated irradiated cells, 57% achieved long-term survival, versus 0% of animals receiving no prior treatment (P > 0.01). The key role of the bavituximab eq.uivalent's anti-PS activity in protecting these animals was illustrated by the fact that a group receiving irradiated control antibodies that did not block PS only achieved a 16% long- term survival rate.

These data are particularly noteworthy because the glioma cells used in the study are highly aggressive -- fewer than 10 cells can fuel development of a lethal tumor. In addition, the researchers calculated that in order to achieve the long-term survival observed in the animals receiving the 2aG4 regimen, more than 99.99% of the glioma cells contained in the challenge dose would have had to have been destroyed by the immune system. These results indicate that the 2aG4 vaccine-like regimen resulted in a strong immune response to the cancer not seen in controls.

"These exciting data suggest a potential new application for bavituximab and our anti-PS antibody platform as part of a cancer vaccine regimen that aims to restore the ability of the patient's own immune system to recognize and fight cancer," said Steven W. King, president and CEO of Peregrine. "Based on these promising results, we are continuing our evaluation of these vaccine-like regimens containing bavituximab for potential application to a variety of cancers."

Study data further showed that administering the combination of 2aG4 and irradiated tumor cells to the glioma cell-challenged animals resulted in a robust immune response, including enhanced cross-presentation of tumor antigens, increased expression of inflammatory anti-cancer cytokines and enhanced recognition and phagocytosis of tumor cells by macrophages. A key result was the fact that inclusion of the bavituximab eq.uivalent in the regimen appeared to reverse suppression by tumor cells of the ability of dendritic cells to "present" cancer cells for destruction by the immune system. In these studies, the animals receiving 2aG4-treated irradiated cells showed increased antigen presentation of PS positive tumor cells by dendritic cells, as well as an increase in the number of cytotoxic T cells enabling the animals' immune systems to attack the tumor cells directly. These results are key signs of a strong immune response.

"We believe that a key mechanism of action of our anti-PS agents is that they block the immune-suppressing effects of phosphatidylserine in conditions such as cancer," said Dr. Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center and a member of the Peregrine Scientific Resource Board. "These new studies in animal models of aggressive brain cancer are the strongest evidence yet that this is the case. We are eager to explore further the promising immune-enhancing activity demonstrated by our anti-PS antibody against this lethal cancer."

Bavituximab is a targeted monoclonal antibody that binds to a phospholipid called phosphatidylserine (PS), which is normally located on the inside of cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors. Once bound to tumor blood vessels, bavituximab alerts the body's immune system to attack the tumor's blood supply, stopping the flow of oxygen and nutrients to the tumor cells and resulting in tumor cell death. PS is also thought to play a role in suppressing the body's immune response to cancer. PS blockers may have the potential to help reverse this suppression and enable the immune system to attack the cancer more effectively. As an anti-cancer immunotherapeutic, bavituximab may have broad potential in a wide variety of solid cancers. It is currently in Phase Ia cancer safety trials as a monotherapy and in a Phase Ib trial in combination with docetaxel and other chemotherapy agents in patients with advanced solid cancers, including prostate, breast and lung cancer. Based on interim data, more than half of the cancer patients in this study who have completed treatment to date were assessed as demonstrating stable disease or an objective response.


This research was conducted under the direction of Dr. Thorpe and postdoctoral researcher Dr. Jin He at UT Southwestern Medical Center in Dallas.

This work was supported in part by the Meredith C. Chestler Foundation, the Childhood Brain Cancer Foundation and the Gillson Longenbaugh Foundation and by a sponsored research agreement with Peregrine Pharmaceuticals Inc.

Number 4091: Enhancing the immunogenicity of glioma cells with anti- phosphatidylserine antibody, Jin He, Troy A. Luster, Philip E. Thorpe. UT Southwestern Medical Center, Dallas, TX, Apr 17, 2007, 8:00 AM - 12:00 PM EDT

[Preciouslife1]

Data Presented at AACR Meeting Shows Peregrine's Immunocytokine Fusion Proteins Reduce Growth of B-Cell Lymphoma Tumors by 85% in Preclinical Studies

- New Studies Confirm That Fusion Proteins Made by Combining Cytokines With Peregrine's Anti-PS Antibodies Demonstrate Increased Anti-Tumor Activity With No Observable Toxicity - - These Immunocytokine Fusion Proteins Were Developed Using Peregrine's Proprietary Vascular Targeting Agent (VTA) Technology Platform - - B-Cell Lymphoma Represents a New Potential Disease Category for Peregrine -
LOS ANGELES and TUSTIN, Calif., April 18, 2007 /PRNewswire-FirstCall via COMTEX/ -- Peregrine Pharmaceuticals, Inc. (PPHM), a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus infection, today reported that data presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) showed that fusion proteins combining the anti-cancer cytokines alpha interferon and interleukin 2 (IL-2) with 2aG4, a bavituximab *************************alent, demonstrated potent anti-cancer activity in preclinical models of B-cell lymphoma and melanoma. In these studies, the antibody-cytokine fusion proteins generated a robust anti-tumor response without any observable toxicity. These immunocytokine fusion proteins incorporating antibodies that target the blood vessels of tumors are new preclinical candidates under Peregrine's proprietary Vascular Targeting Agent (VTA) technology platform.

The use of VTAs to deliver cytokines specifically to tumor targets is an appealing approach since the anti-cancer utility of cytokines such as interferons and interleukin 2 has been limited by their short half-life and the systemic toxicity seen at high doses. VTA immunocytokines aim to overcome these problems by combining the immunomodulatory activity of the cytokine with the tumor specificity of a targeted antibody.

In these proof of principle studies, VTA immunocytokines were created by combining type I interferon and interleukin 2 with 2aG4, an anti-phospholipid antibody similar to Peregrine's bavituximab. The resulting immunocytokine fusion proteins were capable of selectively targeting tumor blood vessels and displayed potent anti-cancer effects in a number of tumor models without causing any observable toxicity. The studies also showed that different forms of the VTAs could be combined, and that the combination of 2aG4-IL-2 with 2aG4-alpha interferon was significantly more effective in inhibiting tumor growth than either agent alone. In a preclinical model of B-cell lymphoma, tumor growth was inhibited by 85% in the combination-treated group compared with 60% and 65% in animals treated with either 2aG4-IL-2 or 2aG4-alpha interferon, respectively.

"These new data reaffirm the broad potential and versatility of our Vascular Targeting Agent platform for cancer therapy," said Steven W. King, president and CEO of Peregrine. "We have long thought that our anti- phospholipid antibodies would be ideal for the delivery of cytokines for cancer therapy based on their inherent immunostimulatory effects combined with the anti-tumor effects of the cytokines themselves. We are especially pleased with the strong anti-tumor activity observed in a model of B-cell lymphoma, the first non-solid cancer we have successfully addressed using our VTA technology. We are now assessing our options to further develop and commercialize these cytokine fusion proteins for cancer and potentially, viral infections."

The new class of fusion protein agents falls under Peregrine's VTA technology platform for cancer therapy that includes over 200 patents and patent applications covering broad concepts of tumor therapy using agents that target tumor blood vessels. Because interferon is currently part of standard- of-care therapy for virus infections including chronic hepatitis C, Peregrine also intends to assess the utility of the new class as a second-generation treatment for viral infections.

This work was supported by Susan G. Komen for the Cure and a sponsored research agreement with Peregrine Pharmaceuticals Inc.

Number 3539: Inhibition of Tumor Growth by Targeting Cytokines to Phosphatidylserine (PS) on Tumor Vascular Endothelium, Xianming Huang, Dan Ye, Troy Luster, Jin He, Shuzhen Li, Linda Watkin, Janie Iglehart, Philip Thorpe, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

[Preciouslife1]

Posted by: jazzbeerman
In reply to: NoneDate:4/19/2007 8:00:01 AM
Post #of 13215
Soares & Thorpe at AAI May 19th
Hope they bring something new. The abstract (below) is the Pichinde info we're familiar with.

I'm looking forward to seeing Dr's Soares/Thorpe anti-PS/viral paper...
Dr. Godofsky's AASLD presentation last Oct. contained a few slides that mentioned a Soares viral paper was in the works..


here's the upcoming AAI abstract:

ANTIBODY-MEDIATED TARGETING OF “INSIDEOUT”
ANIONIC PHOSPHOLIPIDS IN VIRAL DISEASE

Melina Soares, Sameer Syed, Gustavo Barbero, Philip E
Thorpe. Pharmacology, University of Texas Southwestern
Medical Center, 2201 Inwood Road, NC7.304, MC 9041,
Dallas, TX, 75390

The anionic phospholipid phosphatidylserine (PS) is found
exclusively in the inner leaflet of the plasma membrane of
resting mammalian cells. We hypothesized that certain
events that occur during virus replication (eg cell activation
or membrane rearrangement) would trigger the exposure of
anionic phospholipids on the outer surface of virus infected
cells and subsequently on the enveloped viruses
that bud out of these virus- infected cells. We further
hypothesized that these exposed anionic phospholipids
would serve as targets for anti-viral therapy. We
demonstrate here that anionic phospholipids become
exposed on the enveloped Pichinde Virus (a model virus
for Lassa Fever virus, a potential bioterrorism agent) and
on Pichinde virus-infected cells. To detect anionic
phospholipids, we used a chimeric monoclonal antibody,
bavituximab, that binds anionic phospholipids in a B2-
glycoprotein I dependent manner. We show that
bavituximab treatment is able to cure overt disease in
guinea pigs lethally infected with Pichinde virus.
Bavituximab treatment reduced the amounts of virus in
multiple tissues and caused direct clearance of virus from
the blood. Direct clearance of free virus and antibodydependent
cellular cytotoxicity of virus-infected cells
appear to be the major mechanisms that contribute to the
anti-viral effect of bavituximab. Bavituximab-treated
survivors were immune to reinfection. Furthermore, the
murine version of bavituximab, 3G4, shows therapeutic
efficacy in a lethal murine model for human
cytomegalovirus. Our study demonstrates the promise of
anionic phospholipids as targets for new broad-spectrum
anti-viral drugs.

[Preciouslife1]

Peregrine Pharmaceuticals Highlights Significant Advances in the Company's Clinical and Preclinical Cancer Programs Presented This Week at the AACR Annual Meeting


- New Study Demonstrated the Clinical Potential of Peregrine's Unique Selective Anti-VEGF Antibodies, Which Were as Effective as Avastin(R) in Animal Cancer Models - Trials Could Begin as Soon as Next Year - - Robust Anti-Tumor Data Confirmed Broad Versatility of Clinical Stage Anti-PS Agent Bavituximab in Three Separate Applications-in Combination with Chemotherapy for Prostate Cancer, as Part of a Vaccine-Like Approach for Malignant Brain Cancer and as Vascular Targeting Agent (VTA) Components of Peregrine's Immunocytokine Fusion Proteins - - Preclinical Data Showing Fusion Proteins Reduced Growth of B-Cell Lymphoma by 85% Represented Critical Validation for VTA Immunocytokines and a Potential New Indication for Peregrine's Cancer Program - - Additional Presentations Reported Encouraging Progress in Peregrine's VTA Coaguligand Program, Vasopermeation Enhancement Agent (VEA} Program and in Efforts to Develop 2nd-Generation Fully Humanized Anti-PS Antibodies -

TUSTIN, Calif., April 20, 2007 /PRNewswire-FirstCall via COMTEX News Network/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus infection, today reported that data from multiple studies presented at the recent Centennial Annual Meeting of the American Association for Cancer Research (AACR) reinforced the versatility and broad anti-cancer potential of bavituximab, its clinical stage targeted anti- phospholipid (PS) monoclonal antibody; provided important new preclinical data confirming the potential anti-tumor efficacy of the company's selective VEGF inhibitors; provided validating data for its immunocytokine fusion proteins developed using the company's proprietary Vascular Targeting Agent (VTA) technology; and highlighted the clinical potential of Peregrine's earlier stage VTA and Vasopermeation Enhancement Agent (VEA) cancer platforms. "We are extremely pleased with the quality, breadth and diversity of the studies we were selected to present at this historic Centennial AACR Annual Meeting," said Steven W. King, president and CEO of Peregrine. "We believe these studies are a testament to the scientific, medical and commercial potential of our core technology platforms. In particular, multiple studies presented data that support the broad anti-cancer utility of our anti-phospholipid platform, including our lead product candidate bavituximab, in a variety of applications and indications. Research confirming the versatility of our anti-PS antibodies in different anti-cancer combinations is especially encouraging. In addition, we also presented data that supports advancement of potentially important anti-cancer development programs based on our selective anti-VEGF, VTA and VEA technologies. These positive developments in our clinical and preclinical programs reinforce our belief that the future for Peregrine has never been brighter, and we look forward to progressing these programs both on our own and with partners and collaborators going forward."
Highlights of seven of Peregrine's AACR presentations this week follow.
Peregrine's Selective Anti-VEGF Antibody Program
Drugs blocking vascular endothelial growth factor (VEGF) are proving very successful as anti-cancer agents, and for the first time researchers presented animal data on Peregrine's anti-VEGF antibodies that selectively block binding to the second of the two VEGF receptors. Current anti-VEGF drugs such as Avastin(R) block binding to both receptors, yet in preclinical studies comparing Peregrine's selective anti-VEGF antibody to Avastin, the selective antibodies compared favorably on all efficacy parameters assessed, inhibiting tumor growth by 90% in preclinical cancer models. Antibodies with greater selectivity may have advantages in clinical use since they have the potential to only inhibit angiogenesis while not impairing other functions of VEGF. Additional data that was presented showing the efficacy of Peregrine's fully human selective anti-VEGF antibody (R3) is expected to help facilitate the progress of this program towards clinical trials.
Broad Applicability and Versatility of Bavituximab, Peregrine's Targeted Anti-PS Antibody
Researchers affiliated with Peregrine presented a number of preclinical studies demonstrating the versatility and broad anti-cancer utility of bavituximab in major cancer models. They also reported data validating bavituximab's unique mechanism of action and supporting potential new applications of Peregrine's anti-PS technology platform. These included:
* Data supporting the potential use of bavituximab to enhance immune responses to existing tumors and as a potential enhancement to cancer vaccines. In a challenging model of aggressive brain cancer, 57% of animals immunized with a bavituximab eq.uivalent and irradiated, inactivated tumor cells achieved long-term survival compared to 0% in untreated animals and only 16% survival in animals receiving inactive tumor cells with an antibody that does not block PS. To achieve this survival result, the vaccine-like bavituximab regimen is estimated to have enabled these animals to destroy 99.99% or more of the huge tumor cell challenge they were given. These impressive results provide important confirmation of the ability of bavituximab's anti-PS mechanism to reverse the immune system inhibition caused by cancer and offer another potential application for bavituximab and Peregrine's other anti-PS antibodies. * Data demonstrating the potent anti-cancer efficacy of bavituximab in combination with chemotherapy. A bavituximab eq.uivalent in combination with the common cancer chemotherapy docetaxel reduced the growth of both hormone-dependent and hormone-independent prostate cancer by up to 94%. Bavituximab is currently being assessed in a Phase lb cancer clinical trial that includes patients receiving docetaxel. Prostate cancer is one of the most common cancers affecting men and is a leading cause of cancer deaths. * Data supporting use of anti-PS antibodies as the targeting agent for immunocytokine fusion proteins based on Peregrine's VTA platform. Their ability to target phospholipids primarily expressed on the surface of tumor blood vessels enables bavituximab-like antibodies to also serve as targeting agents for Peregrine's Vascular Targeting Agent (VTA) technology platform. Studies presented at AACR assessed the anti-cancer properties of VTA-based immunocytokine fusion proteins. These are combinations of vascular targeting agents such as bavituximab and immune system-stimulating cytokines such as interferon and interleukin-2. Peregrine's immunocytokine fusion proteins showed robust anti-tumor efficacy in animal models of melanoma and B-cell lymphoma, without the signs of toxicity that have limited the wide use of cytokines as anti-cancer agents. In particular, the 85% reduction in tumor growth observed in the B-cell lymphoma model serves as an important validation of Peregrine's VTA immunocytokine approach, and hematological cancers such as lymphoma also represent potential new cancer indications for the company.