What is Tarvacin™ and Peregrine Pharmaceuticals

[Knee-Oh]

Well done.

Crimony. Hopefully it's onward and upward now. We've all taken enough of a beating for one lifetime.

[Preciouslife1]

This could be the biggest science discovery of my lifetime if it works against all these viruses and cancer at the same time," says Paul Lytle, Peregrine's chief financial officer. "If you went out and tried to develop vaccines for all these viruses, it could take hundreds of years." When Lytle and his colleagues think of role models, they point to Genentech Inc. in South San Francisco, whose pioneering anti-cancer drug Avastin has posted sales of $640 million since its approval early last year.

((("You want to model yourself on the people who have been successful," says Steven King, Peregrine's chief executive officer. If the early claims about Tarvacin are borne out, he sees no reason Peregrine couldn't be catapulted from money-losing research mode into the pharmaceutical big leagues.))))

[Preciouslife1]

Tarvacin™ (pronounced Tar-və-sin) is a chimeric (human/murine) monoclonal antibody directed against aminophospholipids. Tarvacin™ is Peregrine's first product under its anti-phospholipid therapy technology platform. Anti-phospholipid therapy is a novel approach to treating cancer, viral infections and certain ocular diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed on the outside of the cellular membrane in response to certain disease states such as virally infected cells and cancer.



ANTI-PHOSPHOLIPID THERAPY

Cell Membrane Organization as an Indicator of Normal and Abnormal Physiology

The human body is composed of over a trillion cells, each a microscopic compartment. These cells are each enclosed in a highly specialized membrane that maintains their integrity and function. The main role of a cell membrane is to act as a selective barrier to the passage of molecules, allowing some molecules to cross while excluding others.

The cell membrane consists of a double layer of lipid molecules called a lipid bilayer. The basic building blocks of the cell are the phospholipids, chain-like molecules having a hydrophilic (water-attracted) head at one end and a hydrophobic (water-repelled) tail at the other. To form a cell membrane, phospholipids are organized in the lipid bilayer such that the hydrophilic heads are oriented toward the internal and external surfaces of the membrane. As a result of the attraction to polar water molecules outside and inside of the cell, the hydrophobic tails are located in the middle of the bilayer.

Depending on the chemical structure of the head region, phospholipids can be classified under several different subtypes, including aminophospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), and choline-containing phospho­lipids. In normal, healthy cells, there are a number of mechanisms that keep the heads of amino­phospholipids facing the interior of the cell and choline-containing phospholipids facing the exterior of the cell.

Peregrine Pharmaceuticals and its collaborators at the University of Texas Southwestern Medical Center at Dallas and the Foundation Fighting Blindness have been studying changes in the organization of the cell membrane during certain disease states, such as cancer, viral infection and the development of ocular disease. They have extended the understanding of how malignant transformation and viral infection cause disruption of the mechanisms that maintain normal membrane organization resulting in aminophospholipids such as PS and PE to “flip” from the interior to the exterior surface of the cell. Peregrine and its collaborators have leveraged this research to develop a new class of targeted therapeutics referred to as Anti-Phospholipid Therapy.

[Preciouslife1]

Quick commentary: As it is getting towards the middle of February, we grow ever closer towards the first release of human clinical data on the 27th of February at the HCV conference in Boston. This will accelerate almost every aspect of the Tarvacin platform exponentially if the safety and dosing data is excellent. If they report or hint at efficacy, all the better. This post will be deleted after the conference as this thread is purley about Tarvacin information and not meant for posts other then that to be included...exciting times ahead IMO....PL1
Feb27: “2nd Annual Viral Hepatitis Disc. & Dev. Conf.”, Boston http://tinyurl.com/9eb2v
..Joseph Shan, Dir. of Clinical & Reg. Affairs 1:50pm: ***"Initial Results from a Phase 1 Trial of Tarvacin"***
..Conf.SAB: IDENIX, GILEAD, BMY, MERCK, PFIZER, INTERMUNE, SCHERING-PLOUGH

[Preciouslife1]

Clinical Trial Results Show that Peregrine's First-In-Class Anti-Viral Agent Tarvacin(TM) is Safe and Well-Tolerated in HCV Patients
Monday February 27, 7:00 am ET

http://biz.yahoo.com/prnews/060227/nym115.html?.v=26

- First Human Data Demonstrating the Safety of Tarvacin(TM) Will Be Presented Today at the 2nd Annual 'Viral Hepatitis in Drug Discovery and Development' Conference -

BOSTON and TUSTIN, Calif., Feb. 27 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a biopharmaceutical company with a portfolio of innovative, clinical stage product candidates for viral diseases and cancer, today announced that it will present top line data demonstrating that its first-in-class anti-viral compound Tarvacin(TM) Anti-Viral appeared safe and well-tolerated in a Phase l study in chronic hepatitis C virus (HCV) infected patients. Initial results from the Phase l study will be presented at 1:50 pm EST today at the Strategic Research Institute's 2nd Annual "Viral Hepatitis in Drug Discovery and Development" conference in Boston.
Tarvacin Anti-Viral is the first in a new class of anti-phosphotidylserine (PS) immunotherapeutics that targets and binds to cellular components that are normally not present on the outside of cells, but which become exposed on certain virally infected cells and on the surface of enveloped viruses. Tarvacin helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells.
The primary goals of the Phase l study were to determine the safety profile and distribution properties of Tarvacin in patients with chronic hepatitis C viral infections. The data will support initiation of repeat dose and combination therapy trials that the company expects to begin later this year. In the ascending, single dose trial, 24 patients with chronic HCV who had either failed or who no longer responded to standard-of-care treatment were administered Tarvacin Anti-Viral. The drug was well tolerated, with no serious adverse events reported at any of the four dose levels tested, and no potential dose limiting toxicities were observed. Reported adverse events were mild, infrequent, transient and likely not drug-related.
"Demonstrating the safety of the new approach is a critical step in developing a first-in-class therapeutic, so this Phase l data indicating that Tarvacin appears to be safe and well-tolerated is a key milestone for the program," said Steven W. King, president and CEO of Peregrine. "Completing this study ahead of schedule with the safety profile observed should help us to expedite advancing the Tarvacin Anti-Viral HCV clinical program into repeat dose and combination therapy studies this year."
Tarvacin Anti-Viral has shown promise in preclinical studies in a variety of anti-viral and biodefense applications. Anti-PS agents attach to phospholipids found on the surface of virus particles, including HCV, influenza and other virus strains, as well as on the outer surface of human host cells infected with these viruses. Anti-PS immunotherapeutics are believed to work by helping stimulate the body's natural immune defenses to destroy both virus particles and infected cells. The targeted phospholipids are not exposed on healthy cells, which are therefore not affected by anti-PS agents. Since the targeted phospholipids are derived from the host rather than from the virus itself, anti-PS immunotherapeutics are expected to have broad activity against a variety of virus strains and to be less subject to the development of anti-viral drug resistance.
"Tarvacin represents a completely new approach to treating HCV infections, and these initial positive safety data are promising," said Dr. Eliot W. Godofsky, principal investigator of the Phase l study. "While there are a number of new HCV drugs in development, Tarvacin's unique mechanism has the potential to combat the virus in a novel way. In addition, it's potential for use in combination regimens to control and ultimately cure HCV warrants further investigation."
Single administration of anti-viral agents is not generally expected to have a significant effect on HCV viral titers as a result of rapid virus production and turnover. However viral titer data are being collected as part of the Tarvacin study design and are currently being analyzed. These data will be discussed in an appropriate future scientific forum along with final safety data from the Phase I trial.
Based on the good safety observed in the highest dose of Tarvacin tested, Peregrine may assess one additional dose level by adding another cohort to the existing HCV study through a protocol amendment. This addition is not expected to affect the timing of the new studies now being planned.
Similar to their anti-viral mechanism, anti-PS immunotherapeutics also bind to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, and they have shown promise in a number of preclinical cancer models. Tarvacin Anti-Cancer is in Phase l clinical trials for the treatment of advanced refractory solid tumor cancers.
About Peregrine Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and viral diseases. The company is pursuing three separate clinical trials in cancer and anti-viral indications with its lead product candidates Tarvacin(TM) 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 .

Congratulations to all PPHM shareholders. This now opens the door for all future TarvacinAV trials to be expedited by the FDA review process...nice....PL1

[Preciouslife1]

Clinical Trial Results Show that Peregrine's First-In-Class Anti-Viral Agent Tarvacin(TM) is Safe and Well-Tolerated in HCV Patients
Monday February 27, 7:00 am ET

http://biz.yahoo.com/prnews/060227/nym115.html?.v=26

- First Human Data Demonstrating the Safety of Tarvacin(TM) Will Be Presented Today at the 2nd Annual 'Viral Hepatitis in Drug Discovery and Development' Conference -

BOSTON and TUSTIN, Calif., Feb. 27 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a biopharmaceutical company with a portfolio of innovative, clinical stage product candidates for viral diseases and cancer, today announced that it will present top line data demonstrating that its first-in-class anti-viral compound Tarvacin(TM) Anti-Viral appeared safe and well-tolerated in a Phase l study in chronic hepatitis C virus (HCV) infected patients. Initial results from the Phase l study will be presented at 1:50 pm EST today at the Strategic Research Institute's 2nd Annual "Viral Hepatitis in Drug Discovery and Development" conference in Boston.
Tarvacin Anti-Viral is the first in a new class of anti-phosphotidylserine (PS) immunotherapeutics that targets and binds to cellular components that are normally not present on the outside of cells, but which become exposed on certain virally infected cells and on the surface of enveloped viruses. Tarvacin helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells.
The primary goals of the Phase l study were to determine the safety profile and distribution properties of Tarvacin in patients with chronic hepatitis C viral infections. The data will support initiation of repeat dose and combination therapy trials that the company expects to begin later this year. In the ascending, single dose trial, 24 patients with chronic HCV who had either failed or who no longer responded to standard-of-care treatment were administered Tarvacin Anti-Viral. The drug was well tolerated, with no serious adverse events reported at any of the four dose levels tested, and no potential dose limiting toxicities were observed. Reported adverse events were mild, infrequent, transient and likely not drug-related.
"Demonstrating the safety of the new approach is a critical step in developing a first-in-class therapeutic, so this Phase l data indicating that Tarvacin appears to be safe and well-tolerated is a key milestone for the program," said Steven W. King, president and CEO of Peregrine. "Completing this study ahead of schedule with the safety profile observed should help us to expedite advancing the Tarvacin Anti-Viral HCV clinical program into repeat dose and combination therapy studies this year."
Tarvacin Anti-Viral has shown promise in preclinical studies in a variety of anti-viral and biodefense applications. Anti-PS agents attach to phospholipids found on the surface of virus particles, including HCV, influenza and other virus strains, as well as on the outer surface of human host cells infected with these viruses. Anti-PS immunotherapeutics are believed to work by helping stimulate the body's natural immune defenses to destroy both virus particles and infected cells. The targeted phospholipids are not exposed on healthy cells, which are therefore not affected by anti-PS agents. Since the targeted phospholipids are derived from the host rather than from the virus itself, anti-PS immunotherapeutics are expected to have broad activity against a variety of virus strains and to be less subject to the development of anti-viral drug resistance.
"Tarvacin represents a completely new approach to treating HCV infections, and these initial positive safety data are promising," said Dr. Eliot W. Godofsky, principal investigator of the Phase l study. "While there are a number of new HCV drugs in development, Tarvacin's unique mechanism has the potential to combat the virus in a novel way. In addition, it's potential for use in combination regimens to control and ultimately cure HCV warrants further investigation."
Single administration of anti-viral agents is not generally expected to have a significant effect on HCV viral titers as a result of rapid virus production and turnover. However viral titer data are being collected as part of the Tarvacin study design and are currently being analyzed. These data will be discussed in an appropriate future scientific forum along with final safety data from the Phase I trial.
Based on the good safety observed in the highest dose of Tarvacin tested, Peregrine may assess one additional dose level by adding another cohort to the existing HCV study through a protocol amendment. This addition is not expected to affect the timing of the new studies now being planned.
Similar to their anti-viral mechanism, anti-PS immunotherapeutics also bind to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, and they have shown promise in a number of preclinical cancer models. Tarvacin Anti-Cancer is in Phase l clinical trials for the treatment of advanced refractory solid tumor cancers.
About Peregrine Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and viral diseases. The company is pursuing three separate clinical trials in cancer and anti-viral indications with its lead product candidates Tarvacin(TM) 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 .

Congratulations to all PPHM shareholders. This now opens the door for all future TarvacinAV trials to be expedited by the FDA review process...nice....PL1

[Preciouslife1]

The new name for Tarvacin is Bavituximab FYI.
The new name was unveiled during the Conference Call conducted
by CEO Steven King and CFO Paul Lytle.

So Bavituximab it is now. What nickname will we give this Tuxi? Tuximab?
Bavi? BadTaxiCab? Great CC IMHO.

PL1

[igorok2005]

To whom it may concern

Dear colleagues, I look for he possibility to stain phosphatidylserine in mice. Do you have a relevant antibody? Let me know please when it is available.

Best regards Dr. Igor Kobsar
Würzburg University
igorkobsar@mail.ru

Originally Posted by Preciouslife1

http://www.peregrineinc.com/***********************************.php?mi=Mzk=
Tarvacin™ Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses.
Tarvacin binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply.

This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the Tarvacin does not bind to them. This targets the Tarvacin to the malignant cells and potentially minimizes unwanted side effects. For more scientific information about Tarvacin Anti-Cancer, click here.

Solid Cancer Phase I Clinical Trial. Peregrine is currently conducting a clinical trial in patients with advanced solid tumor malignancies that have failed to respond to available treatments. As of December 2005, the trial is underway at five sites nationwide. The clinical trial is designed to accommodate up to 28 patients with advanced solid tumors who are no longer responsive to standard cancer treatments.

This is an open-label, dose escalation study. The objectives are to (1) determine the safety and tolerability of Tarvacin administered intravenously to patients with advanced cancer; (2) characterize Tarvacin’s activity in the body and; (3) define the maximum tolerated and/or maximum effective dose.

“We are committed to making cancer history by both discovering and helping to develop new cancer therapies. We look forward to working with Peregrine to further assess the potential of this innovativeapproach to treating this challenging disease.”

Nuhad K. Ibrahim, M.D.
associate professor of medicine at
M.D. Anderson Cancer Center and a
principal investigator of the
Tarvacin Anti-Cancer study

If you are a health care provider interested in referring a patient or learning more about these clinical trials, please send an email correspondence to Peregrine Pharmaceuticals at clinicalaffairs@peregrineinc.com or visit ClinicalTrials.gov.

If you are a patient interested in participating in one of these trials, please have your personal physician send an email correspondence to Peregrine.

[Preciouslife1]

You can order anti-PS abs for your purposes from a typical supply houses. Or why not Annexin V? Peregrine Pharmaceuticals has their
MAb's in trials and most likely would not sell any to you. Try some of these:

http://www.bendermedsystems.com/31.html
http://www.abcam.com/index.html?c=3295

Annexin V: Annexin V is the cause of a syndrome called the antiphospholipid antibody syndrome with abnormal blood clotting.
The annexins are a family of proteins first described in 1990. All of the annexin proteins share the property of binding calcium and phospholipids. Annexin V normally forms a shield around certain phospholipid molecules that blocks their entry into coagulation (clotting) reactions. In the antiphospholipid antibody syndrome, the formation of this shield is disrupted by the abnormal antibodies. Without the shield, there is an increased quantity of phospholipid molecules on cell membranes, speeding up coagulation reactions and causing the abnormal blood clotting characteristic of the antiphospholipid antibody syndrome.

Dr Kobsar, I hope this helps and if you would like to discuss this more. please us the other PPHM thread here as this is an info only
thread in intention. Thank you and my email address is:
braveheart1@hushmail.com and is fully encrypted for safety.

PL1

[Preciouslife1]

This from the AACR annual meetings in Washington, DC.

AACR Sun-Tue: 8 PPHM Posters

AACR Annual Meeting, April 1-5 2006, WASH DC
http://www.aacr.org/default.aspx?p=5731 - click “PROCEEDINGS ONLINE”

PPHM POSTER PRESENTATIONS:
Apr2 #570: Anti-PS/2aG4 + Irradiation treats brain tumors (Thorpe)
Apr2 #1053: Irradiation increases externalization of PS+PE (Thorpe)
Apr3 #2123: 3G4+Cisplatin potential in treating breast cancer (Thorpe)
Apr3 #2179: 3G4/PS interaction dependent on B2GPI (Thorpe/Schroit)
Apr3 #1986: New molecules NHS76:tTF & Tarv:tTF target tumors (PPHM)
Apr4 #4779: VEA/PEP(IL2) increases uptake of therapeutics (PPHM)
Licensing Partners:
Apr2 #1171: Anti-PSMA conjugates yield complete tumor regression (MEDAREX)
Apr4 #3722: VEGF121/rGel is cytotoxic to osteoclast precursor cells (SUPG)
==Not sure if PPHM-related:
Apr29. #1751: ”Plasmin-Cleaved B2GP is a Regulator of Angiogenesis” (Alan Schroit)

PL1

[Preciouslife1]

Peregrine Pharmaceuticals Announces New DOD Grant to Study Bavituximab (Tarvacin) in Breast Cancer
Tuesday April 25, 7:00 am ET - Researchers at UT Southwestern Medical Center Awarded Competitive, Peer-Reviewed Grant for Preclinical Studies in ********************static Breast Disease - - Will Assess Bavituximab's Utility as an Immunoconjugate for Imaging and Therapy - - Bavituximab Research Studies Underway Funded by 5 Grants Totaling $3.6 Million -
TUSTIN, Calif., April 25 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a biopharmaceutical company with a portfolio of innovative, clinical-stage product candidates for hepatitis C virus and cancer, today announced the U.S. Department of Defense (DOD) has awarded a new grant totaling $460,000 to its collaborators at the University of Texas Southwestern Medical Center at Dallas to study Peregrine's first-in-class anti-phospholipid (PS) agent bavituximab (formerly Tarvacin) as an imaging and therapeutic agent for recurrent breast cancer. Bavituximab is currently in a Phase I clinical trial for advanced refractory solid tumors.

In this new project, bavituximab will be labeled with radioactive isotopes to assess its potential as an imaging agent to identify tumor ********************stases and as a radioimmunoconjugate to treat ********************static disease. Despite recent medical advances in management of recurrent breast cancer, the prognosis remains poor for many patients and 40,000 women in the U.S. die from ********************static breast disease each year.
Bavituximab is a monoclonal antibody that binds selectively to cells that line tumor blood vessels. It has already shown promising activity in preclinical models of breast cancer. Previously published data in Cancer Research showed that a mouse *************************alent of bavituximab in combination with docetaxel resulted in a 93% inhibition of human breast cancer growth in mouse cancer models. At the AACR Annual Meeting earlier this month, researchers reported that combination treatment with a bavituximab *************************alent and cisplatin doubled survival time in a preclinical model of cisplatin-resistant breast cancer. Bavituximab's phospholipid target has been shown to be amplified when exposed to radiation, and recent preclinical studies also presented at AACR demonstrated that bavituximab plus radiation was significantly more effective in a brain cancer model than either therapy alone.
"Data from this project could open the door for use of bavituximab as an agent to identity, measure and ultimately destroy the ********************stases that kill most cancer patients," said Steven W. King, president and CEO of Peregrine. "We are particularly pleased since this is the third competitive, peer-reviewed grant awarded by DOD with the potential to expand the clinical applications of bavituximab. We look forward to the results of these studies that will assess its utility as a new class of imaging and therapeutic agents for breast cancer."
Bavituximab works by binding to certain phospholipids, specific components of the cell structure that are usually located inside normal cells, but which become exposed on the outside of cells that line the blood vessels of tumors, creating a highly 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. By linking bavituximab to an isotope to form a radioimmunoconjugate, researchers hope to be able to use it to image tumor cells for diagnosis and disease management, as well as to destroy additional cancer cells as a result of the radiation the radioimmunoconjugate transports to the tumor blood vessels.
"This new DOD project will enable us to assess bavituximab's utility for both tumor detection and therapy in breast cancer," said Ralph Mason, Ph.D., professor of radiology at UT Southwestern and a principal investigator of the study. "Since bavituximab's unique target is expressed on blood vessels in tumors but not in normal tissues, it may have both safety and efficacy advantages compared to other antibodies. We are eager to assess the utility of a bavituximab radioimmunoconjugate for the identification and treatment of ********************static breast disease."
The Department of Defense manages the Congressional Special Interest Medical Research Programs (CSI) encompassing breast, prostate, and ovarian cancers, neurofibromatosis, military health, and other areas. Since fiscal year 1992, CSI programs have handled approximately $3.4 billion in Congressional appropriations for peer-reviewed research aimed to prevent, control, and cure disease. Breast cancer is among the most commonly diagnosed cancers in women and remains a leading cause of cancer deaths. Currently, there is no cure for ********************static breast cancer.
Similar to its mechanism of action in cancer, bavituximab also targets phospholipids exposed on the cell surface when the cell is infected with certain viruses, mobilizing the immune system to attack and destroy both the viruses and the infected cells. In February Peregrine successfully completed planned enrollment in a Phase l clinical trial of bavituximab for the treatment of chronic hepatitis C virus infection, reporting that the drug appeared to be safe and well tolerated. Repeat dose and combination therapy studies are now being planned. Bavituximab is also in pre-clinical studies for potential use against influenza, HIV, cytomegalovirus and other life-threatening viruses.
About Peregrine 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 infection. The company is pursuing three separate clinical trials in cancer and hepatitis C virus infection with its lead product candidates bavituximab (formerly Tarvacin) and Cotara®. 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]

About Anti-Phospholipid Therapy in the Treatment of Viral Diseases


Bavituximab(TM) is Peregrine's first product under its anti-phospholipid therapy technology platform. Anti-phospholipid therapy is a novel approach to treating cancer, viral infections and certain ocular diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed on the outside of the cellular membrane in response to certain disease states such as virally infected cells and cancer. A large number of viruses significant to global health and security possess an "envelope" derived from their host cell membrane. Since viruses lack the means to maintain structural organization of the envelope, amino-phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) become exposed on the surface of these viruses, making them a potential therapeutic target. Peregrine Pharmaceuticals, together with its collaborators, has developed a series of monoclonal antibodies, including Bavituximab(TM), directed against aminophospholipids to take advantage of this property.

Pre-clinical studies using Bavituximab(TM) for the treatment of viral diseases have yielded promising results in Lassa fever, influenza, and cytomegalovirus, which are included in a viral category called enveloped viruses. Based on Bavituximab's(TM) anti-viral mechanism, the drug has potential for the treatment of enveloped viruses including Hepatitis B and C, Human Immunodeficiency Virus (HIV), herpes, influenza including SARS and Avian flu and potential bioterrorism threats such as Marburg virus and Lassa fever.

PL1...THE TRUTH.





Never believe that a few caring people can't change the world. For, indeed, that's all who ever have.
— Margaret Mead

[Preciouslife1]

BAVITUXIMAB – AMA/USAN Generic Nomenclature Statement

Newly Approved USAN - 5/1/06
STATEMENT ON A NONPROPRIETARY NAME - USAN COUNCIL

BAVITUXIMAB
PRONUNCIATION bav i tux’ i mab
THERAPEUTIC CLAIM anti-cancer and anti-viral
CHEMICAL NAME Immunoglobulin G1, anti-(phosphatidylserine) (human-mouse monoclonal ch3G4 heavy chain), disulfide with human-mouse monoclonal ch3G4 K-chain, dimmer
STRUCTURAL FORMULA DIQMTQSPSS LSASLGERVS… *snip*
MOLECULAR FORMULA C6446 H9946 N1702 O2042 S42
MOLECULAR WEIGHT 145.3 kDa
TRADEMARK None
MANUFACTURER Peregrine Pharmaceuticals, Inc.
CAS REGISTRY NUMBER 648904-28-3
http://www.ama-assn.org/ama1/pub/upload/mm/365/bavituximab.pdf

4/24/2006: Tarvacin (chimeric mab 3G4) will henceforth be referred to by its generic name, BAVITUXIMAB, to avoid confusion with OSI’s anti-cancer drug Tarceva. New, separate trade names will be identified for BavituximabAC and BavituximabAV, "a process which has now begun".
http://www.peregrineinc.com/***********************************.php?mi=MTc=&appAction=--PRINT&Id=ODQ2NjQ5

[Preciouslife1]

Peregrine Pharmaceuticals' Bavituximab Shows Potential Activity Against Avian Flu in Initial Testing


- Initial Data Presented at ASM Meeting Show Complete Inhibition of Viral Replication in H5N1 In Vivo Model -
TUSTIN, Calif. and ORLANDO, Fla., May 24, 2006 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. , a biopharmaceutical company with a portfolio of innovative, clinical stage product candidates for the treatment of hepatitis C virus (HCV) infection and cancer, today announced that its lead anti-viral compound bavituximab (formerly Tarvacin) completely inhibited replication of a laboratory strain of the H5N1 virus, commonly known as avian flu, in fertilized chicken eggs, an in vivo model for influenza anti- viral activity. These preliminary findings will be reported today at the 106th general meeting of The American Society for Microbiology (ASM) in Orlando, Florida by Dr. Philip Thorpe, a member of the Peregrine Scientific Resource Board and professor of pharmacology at the University of Texas Southwestern Medical Center at Dallas. Bavituximab, a monoclonal antibody with unique anti-viral and anti-cancer properties, has already demonstrated good tolerability in a Phase l trial in patients with HCV infection.
http://ad.doubleclick.net/ad/PharmaL...4882399343 7?
"This first set of results showing that bavituximab appears to have inhibited H5N1 viral replication in the fertilized egg model and the supportive data confirming that bavituximab binds to H5N1 viral particles are encouraging," said Dr. Thorpe. "These early data support the view that bavituximab may be active against H5N1 and other common strains of influenza."
The H5N1 studies reported by Dr. Thorpe were conducted at a number of independent research laboratories. Peregrine has also been collaborating with other researchers to evaluate the potential of bavituximab delivered by different routes of administration to treat infections caused by influenza A, the viral family that includes the H5N1 strain. Peregrine has ongoing studies to evaluate various delivery methods and treatment regimens to treat influenza in a number of in vivo models, including well-established mouse and ferret models. These studies include assessments of bavituximab delivered by nasal inhalation, a form of delivery expected to be more effective than systemic delivery alone for respiratory viruses that lodge deep in the lungs.
"These early experimental data suggesting that bavituximab may have activity against the avian flu, along with preliminary data recently generated showing signs of activity in a ferret model of influenza A infection, give us momentum and direction as we pursue a variety of preclinical initiatives to assess the anti-viral potential of bavituximab," said Steven W. King, president and CEO of Peregrine. "With a repeat dose safety study in HCV patients expected to begin next month, we should be well-positioned to initiate clinical trials for bavituximab in additional indications once we have sufficient preclinical data in hand."
Bavituximab is an antibody that attaches to specific cellular components called phospholipids found on the surface of virus particles, including influenza and certain other virus strains, as well as on the outer surface of human host cells only when they are infected with these viruses. Bavituximab helps stimulate the body's natural immune defenses to destroy both the virus particles and the infected cells, without affecting healthy cells. Bavituximab is in Phase 1 clinical trials for hepatitis C virus infections and for solid tumor cancers. A Phase 1b repeat dose study in HCV patients is expected to start in June.
Dr. Thorpe's ASM presentation, Broad-Spectrum Anti-Virals, is scheduled for May 24th at 10:00am in Room 208A as part of a symposium on Bioterrorism: Challenges and Opportunities.
About Peregrine
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 trials in cancer and HCV infection with its lead product candidates bavituximab (formerly Tarvacin) 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.
http://www.medadnews.com/News/Index.cfm?articleid=343757

http://www.rxpgnews.com/research/pharmacology/antivirals/bavituximab/article_4319.shtml

http://www.businessweek.com/ap/financialnews/D8HQB6783.htm?campaign_id=apn_home_down&chan=db

[Preciouslife1]

Peregrine's Bavituximab Shows Promising Anti-Viral Activity and Signs of Prolonged Anti-Viral Effect in Single Dose Monotherapy HCV Trial

- First Human Efficacy Data From Phase Ia Trial Indicates Encouraging Anti-Viral Activity for First-in-Class Targeted Anti-PS Agent -

- Repeat Dose Phase Ib Trial of Safety and Biodistribution in HCV Patients Underway -

- Enrollment of Additional High Dose Patient Cohort in Phase Ia Trial Complete -

TUSTIN, Calif., June 7 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus infections, today reported top-line results on the effect of bavituximab (formerly Tarvacin) on viral RNA serum titers when administered as single dose monotherapy in a Phase Ia study in patients with chronic hepatitis C virus (HCV) infection. In this analysis, bavituximab showed signs of anti-viral activity at all four study dose levels, and it also showed evidence of a prolonged anti-viral effect.

These preliminary efficacy data follow positive safety data from the Phase Ia study that Peregrine reported on February 27, 2006, indicating that bavituximab was well tolerated, with no dose limiting toxicities observed. Peregrine also announced today two additional milestones in the bavituximab HCV clinical program. First, the company has completed the treatment phase of an additional, higher dose cohort that was added to the Phase Ia HCV study after the first four cohorts were complete, and second, it has begun dosing patients in a new Phase Ib repeat dose study in HCV patients.

In the Phase Ia study, more than 90% of the subjects were infected with the genotype 1 form of HCV, which is the most common and difficult to treat strain of the virus. All participants had failed or relapsed after receiving standard-of-care treatments. Subjects were administered bavituximab at 0.1, 0.3, 1 or 3 milligram per kilogram (mg/kg) of body weight.

After a single dose of bavituximab, among patients treated with the higher 1mg/kg and 3mg/kg dose levels, 50% achieved a greater than 75% (0.6 log) reduction in serum HCV RNA with a maximum 97% (1.5 log) reduction. These patients had an average reduction in serum HCV RNA levels of 0.8 log during the course of the 12-week follow-up period. Signs of anti-viral activity were seen at all dose levels including the initial dose of 0.1mg/kg. Even at this low dose, one-third of patients experienced a greater than 75% (0.6 log) reduction in serum HCV RNA levels.

Bavituximab also showed signs of durable anti-viral activity after a single dose, with some subjects achieving a greater than 80% (0.7 log) reduction in viral load by day four and maintaining a greater than 60% reduction in serum HCV levels up through the end of the study at week 12.

"This preliminary evidence of anti-viral activity in this first-in-human single dose study of bavituximab is very encouraging," said Dr. Eliot W. Godofsky, principal investigator of the Phase Ia study, and director of the University Hepatitis Center in Sarasota Florida. "Bavituximab is a potentially novel approach to treating chronic hepatitis C infection, one with a unique mechanism of action that should complement both existing and investigational therapies in development. Based on its safety profile to date and these promising signs of anti-viral activity, we look forward to working with Peregrine to assess bavituximab in the repeat dose trial, as well as its potential for use in combination regimens to control and ultimately eradicate HCV."

These initial efficacy findings for a single dose of bavituximab are noteworthy for several reasons. First, the rapid virus production and turnover characterizing HCV infection typically limit the impact of a single dose of any anti-viral drug. Second, preclinical data supports that bavituximab's unique mechanism of action, which mobilizes the body's immune system to attack the hepatitis C virus, is likely to be most effective when administered as part of a multiple dose regimen. Third, most other investigational drugs for HCV infection have reported initial efficacy results following multiple dose or combination regimens that include standard-of-care therapies. In this study bavituximab was administered as monotherapy to patients who had failed standard treatment. In view of these factors, the anti-viral activity demonstrated in this single dose, monotherapy study is all the more encouraging.

"We are delighted with these first positive indicators of bavituximab's anti-viral potential in HCV patients," said Steven W. King, president and CEO of Peregrine. "The initial human results for this first-in-class novel agent are very promising. Its excellent overall safety profile to date, early evidence of anti-viral activity and signs of prolonged duration of activity give additional impetus to our efforts to advance bavituximab as a potential new therapy for the treatment of HCV and other serous viral infections."

Joseph Shan, Peregrine's executive director of clinical and regulatory affairs, added, "These first efficacy results in humans are particularly exciting because researchers did not expect to see much anti-viral activity after a single dose of drug, based on our experience in lethal animal disease models such as Lassa fever. Bavituximab demonstrated good anti-viral activity in these studies, but only after administration of multiple doses. Based on the results reported today, the drug's anti-viral potential may be even more promising in humans than the animal models suggest."

Patients in the fifth dosing cohort (6mg/kg) of the Phase Ia HCV study are currently in the 12-week follow-up period, and data from this group will be available later this year. The repeat dose Phase Ib HCV study that is underway is designed to evaluate multiple doses of bavituximab for safety as well as assessing changes in serum HCV RNA levels. Enrollment in this study is expected to be completed by the end of the year.

About the Bavituximab Phase Ia Clinical Trial

The primary objective of the Phase Ia study was to determine safety and pharmacokinetic (PK) properties of bavituximab single dose monotherapy. Changes in viral HCV RNA levels were monitored as a secondary goal of the trial. Under the initial protocol, a total of 24 HCV infected patients were treated in cohorts of six with a single intravenous dose of bavituximab as a monotherapy at 0.1, 0.3, 1 or 3mg/kg, and the patients were monitored for safety, pharmacokinetics and viral load changes for 12 weeks. Based on the positive safety profile at the highest planned dose, a fifth cohort of six patients at 6mg/kg was added. Dosing at 6mg/kg has been completed and subjects are currently in the 12-week follow-up period. Bavituximab appears to be well tolerated to date at all dose levels, including the 6mg/kg dose level.

About the Bavituximab Phase Ib Clinical Trial

The primary objective of the multi-center Phase Ib study is to determine safety and pharmacokinetic properties of bavituximab as a multiple dose monotherapy. Changes in serum HCV RNA levels and selected cytokines will be monitored. The trial will enroll up to 24 patients (4 cohorts of 6 patients) with each cohort receiving 4 doses of bavituximab over a 14-day period. Patients will then be followed for 12 weeks. The dosing regimen for this study was based on safety, PK and viral load data collected during the Phase Ia clinical trial. Patient treatment in the Phase Ib trial has been initiated.

About Bavituximab

Bavituximab (formerly Tarvacin) is the first investigational agent in a new class of anti-phosphotidylserine (PS) immunotherapeutics that targets and binds to cellular components that are normally not present on the outside of cells, but which become exposed on certain virally infected cells and on the surface of enveloped viruses. Bavituximab helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells. Similar to the proposed anti-viral mechanism, anti-phospholipid immunotherapeutic agents also bind to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, having shown promise in a number of preclinical cancer models. Bavituximab is in Phase l clinical trials for the treatment of advanced refractory solid tumor cancers.
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