Avid Bioservices Inc (CDMO)

[cjgaddy]

Two Anti-PS Ocular posters at ARVO’12 Annual Mtg./FtLaud.
• #D1015 is Peregrine researchers (with LSU & Xavier Univ. involvement) testing PGN632+Zirgan vs. HSV-1 Keratitis
• #D1120 is Dr. Thorpe & colleagues (with Mayo Clinic involvement) testing PGN632 & PGN635 vs. AMD (Advanced Age-Related Macular Degeneration)
…Recall:
PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.)
PGN632 is the Duke-PPHM-HIV candidate=11.31=AT005 (B2GPI-indep.)

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5-10-12 PR: “Researchers Present Data Highlighting Potential of Peregrine's PS-Targeting Antibodies to Treat Ocular Herpes Infections and Macular Degeneration
• Preclinical Data Further Expands Therapeutic Potential of PS-Targeting Platform”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=672304

TUSTIN, CA: 5/10/12: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment and diagnosis of cancer and infectious diseases, today announced that researchers have highlighted promising preclinical data at the 2012 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) investigating the potential of Peregrine's fully human PS-targeting antibodies, PGN632 and PGN635, to treat ocular herpes infections and macular degeneration, respectively.

In a poster presentation [D1015] titled, “Efficacious Outcome of an Ophthalmic Formulation of Phosphatidylserine-binding Monoclonal Antibody in a Rabbit Model of Acute HSV-1 Keratitis”, academic researchers showed that the direct PS-binding antibody PGN632 is at least as efficacious as an approved therapy in reducing corneal scores and in minimizing ocular disease symptoms in an animal model of herpes infection of the eye. No visual toxicity was associated with the PGN632 antibody therapy.

"This is the first time our antibodies have been tested against HSV-1 in an established animal model. Data from this study further broadens the potential of our PS-targeting platform in the area of viral disease," said Cyril Empig, Ph.D., associate director, infectious diseases, at Peregrine. "With herpes simplex keratitis affecting approximately 450,000 people in the U.S. alone, 20,000 new cases diagnosed each year and with resistance to approved therapies increasing, our approach of targeting a non-mutatable host lipid molecule holds broad potential in this indication. We are pleased to see the high level of interest from the academic community in this promising application of our technology, and look forward to continuing collaborations to advance these studies to further assess PGN632 in this serious disease as well as other diseases caused by HSV-1 and HSV-2."

In a second poster presentation [D1120] titled, “Anti-phosphatidylserine Antibodies As A Potential New Therapy Against Choroidal Neovascularization”, researchers demonstrated that in an animal model of age related macular degeneration, PS is exposed on the surface of new blood vessels in the retina, and that the PS-targeting antibody, PGN635, can significantly reduce the size of laser-induced choroidal neovascularization (CNV).

Philip Thorpe, Ph.D., senior author of the study and inventor of Peregrine's PS-targeting antibody technology commented, "While current therapies for age-related macular degeneration have brought an improvement in clinical outcomes, new retinal blood vessel growth remains active, multiple injections are needed for years and some patients are resistant to the current approved therapy or show a decrease in response to therapy over time. Data from these studies appear quite promising and we plan to advance the work into combination studies with the currently approved age-related macular degeneration therapy to investigate potential synergistic therapeutic effects."

Copies of posters presented are available at: http://ir.peregrineinc.com/events.cfm

ABOUT HERPES SIMPLEX KERATITIS
According to the National Eye Institute, herpes simplex keratitis is a leading cause of corneal opacification in the United States, other industrialized countries, and developing nations throughout the world. An estimated 450,000 people in the United States can develop recurrent episodes of the disease and about 46,000 episodes of HSV eye infection every year. Herpetic eye disease is the most common infectious cause of corneal blindness in this country.

ABOUT AGE-RELATED MACULAR DEGENERATION (AMD)
According to the Macular Degeneration Association, age-related Macular Degeneration (AMD) is a disease of the retina that affects central vision and can lead to blindness in older people. AMD is the leading cause of legal blindness in Americans age 65 and older. As the population ages, AMD is becoming a more significant public health problem. Approximately 9.1 million people in the United States older than 40 suffer from AMD.

ABOUT PEREGRINE PHARMACEUTICALS
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and infectious diseases with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine's lead PS-targeting candidate, bavituximab, is currently being evaluated in seven clinical oncology trials, with preliminary data from a double-blind Phase II trial in second-line non small-cell lung cancer patients expected in the second quarter. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Safe Harbor *snip*
Contact:
Christopher Keenan or Jay Carlson, Peregrine Pharmaceuticals, Inc., [phone], [e-mail]

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May6-10 2012: “ARVO 2012 Annual Meeting”, Fort Lauderdale
ARVO = Association for Research in Vision & Ophthalmology (founded in 1928; 12,500 members)
”Translational Research: Seeing The Possibilities - The 2012 ARVO Annual Meeting is the world's largest gathering of international eye & vision researchers. The Meeting will promote collaboration between basic & clinical scientists while exploring how basic research translates to effective prevention, diagnosis and treatment.”
http://www.arvo.org/sites/annual-meeting/2012

Two Ocular Anti-PS (PGN632 & PGN635) posters are being presented…
PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.)
PGN632 is the Duke-PPHM-HIV candidate=11.31=AT005 (B2GPI-indep.)

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Presentation #1 - Program#/Poster# 6155/D1015
“Efficacious Clinical Outcome of an Ophthalmic Formulation of Phosphatidylserine- binding Monoclonal Antibody in a Rabbit Model of Acute HSV-1 Keratitis” [PGN632=11.31]
Thurday, May 10, 2012, 8:30-10:15am
Session # 526, “Cornea/Anterior Segment Infection and Inflammation I”
Christian Clement 1A, Hilary W. Thompson 1B, Partha S. Bhattacharjee 2, Harris E. McFerrin, Jr. 2, Walter J. Lukiw 3, Kara Corbin-Lickfett 4A, Cyril J. Empig 5, Kyle Schlunegger 4, James M. Hill 1A
1 LSUHSC, New Orleans, LA (1A=Ophthalmology, 1B=School of Public Health)
2 Biology, Xavier University of Louisiana, New Orleans, LA
3 Neuroscience & Ophthalmology, LSU Hlth Sci Ctr, New Orleans, LA; A/Ophthalmology
4 Peregrine Pharmaceuticals, Inc., Tustin, CA
5 Peregrine Pharmaceuticals Inc., Tustin, CA
FULL Poster Image: http://www.peregrineinc.com/images/stories/pdfs/arvohsv.pdf






ABSTRACT (D1015):
PURPOSE: Phosphatidylserine (PS) is a phospholipid found on the internal leaflet of the plasma membrane of normal cells which becomes exposed externally following infection with enveloped viruses. Monoclonal antibodies (mAbs) that recognize PS have the potential to bind infected cells, target them for clearance, and stop infection. The efficacy of the PS-targeting mAb PGN632 given topically was assessed in a rabbit model of HSV-1 keratitis.
METHODS: Corneas were inoculated bilaterally with 2x106 PFU of HSV-1 strain McKrae following corneal scarification and placed in balanced groups based on slit-lamp examination (SLE) scores (5 rabbits per group). Treatment groups were (1) PGN632, (2) Zirgan (.15% ganciclovir), (3) combination of PGN632+Zirgan (ophthalmic solution followed by ointment), and (4) vehicle. Treatments were given 4 times daily starting 3 days post infection (PI) and continued for 4 consecutive days. SLE was done daily in a masked fashion and eyes were clinically scored daily for epithelial keratitis, stromal damage, scleral inflammation, ocular neovascularization, eyelid inflammation, friability of vasculature, inflammatory discharge, and excessive tearing. Scoring was done each day prior to treatment. SLE and clinical symptomatic scoring were continued on PI days 8, 9, and 10, after drug treatment stopped.
[Note: Sirion Therapeutics’ Zirgan (ganciclovir) is an antiviral drug. It slows the growth and spread of the cytomegalovirus (CMV). Zirgan ophthalmic gel is used to treat eye ulcers caused by the herpes simplex virus. http://www.drugs.com/zirgan.html ]
RESULTS: PGN632, Zirgan, and combination PGN632+Zirgan treatments resulted in significant reduction of corneal SLE scores (P< 0.05; p values from generalized linear model analysis of scores) and significantly lower clinical scores (P< 0.05) compared with the vehicle. No ocular toxicity was observed in any drug treatment group.
CONCLUSIONS: Our data show that the PS-targeting mAb PGN632 is at least equally efficacious compared with Zirgan in reducing corneal SLE scores and minimizing the ocular clinical symptoms. By providing symptomatic relief in addition to reducing corneal SLE scores, PGN632 could become a drug of choice for treatment of ocular herpes.
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Support: NIH EY06311

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Presentation#2 - Program#/Poster# 443/D1120
“Anti-phosphatidylserine Antibodies as a Potential New Therapy Against Choroidal Neovascularization” [1N11=PGN635 & 11.31=PGN632]
Sunday, May 6, 2012, 8:30-10:15am
Session #114, “AMD: New Drugs, Delivery Systems and Mechanisms”
…[AMD = Age-Related Macular Degeneration]
Rafael Ufret-Vincenty 1, Bogale Aredo 1, Kaiyan Zhang 1, Cynthia X. Wang 1, Shusheng Wang 1, Jose Pulido 2, Philip E. Thorpe 1
1 Ophthalmology, UTSW-MC/Dallas
2 Ophthalmology, Mayo Clinic, Rochester, MN
FULL Poster Image: http://www.peregrineinc.com/images/stories/pdfs/arvo1.pdf
…[Note that the poster PDF ref’s testing with both 1N11=PGN635 and 11.31=PGN632]




ABSTRACT (D1120):
PURPOSE: Despite the dramatic changes in clinical outcomes brought by anti-VEGF agents, additional drugs directed against different targets in the neovascular process are needed. This may allow for combination therapies that could potentially eradicate choroidal neovascularization (CNV). In normal cells the aminophospholipid phosphatidylserine (PS) is almost exclusively localized to the inner leaflet of the cell membrane’s lipid bilayer. Endothelial cells of tumor neovasculature lose their capacity to maintain PS asymmetry. Anti-PS antibodies bind to the newly exposed phosphatidylserine in the outer leaflet of the tumor vascular endothelium, mediating antibody-dependent cell-mediated cytotoxicity, and causing the collapse of the tumor neovasculature. Radiotherapy increases the exposure of PS in tumor vasculature, enhancing the antitumor effects of anti-PS antibodies. We propose to evaluate if there is also exposure of PS in CNV, and if anti-PS antibodies can treat CNV.
METHODS: We induced CNV in B6 mice using the laser model. Immunostaining for PS was done after perfusing mice with an anti-PS antibody and paraffin-embedding the eyes. We tested the effect of intravitreal anti-PS antibodies alone, or in combination with eye radiation, on the CNV size as measured with ICAM-2 staining.
RESULTS: Paraffin sections of eyes perfused with an anti-PS antibody stained positive for PS. The staining co-localized with ICAM-2-stained CNV, demonstrating that PS was exposed on the choroidal neovascular membranes. The anti-PS antibody (11.31) led to a 52% reduction in the laser-induced CNV size (p=0.02) when injected intravitreally. We have established a system for irradiation of the eyes. We will show data on the effect of radiation alone or in combination with anti-PS antibodies on the neovascular complex.
CONCLUSIONS: Anti-phosphatidylserine antibodies may have therapeutic value in wet AMD alone or in combination with radiation or anti-VEGF agents.
• Commercial Relationships: All NONE, except: Philip E. Thorpe, Peregrine (P)
• Support: Unrestricted Research-to-Prevent-Blindness [RPB] Dept Grant [ http://www.rpbusa.org/rpb/grants/grants ], Core grant to Dept of Ophthalmology (EY020799* =NIH), Disease Oriented Clinical Scholars Grant to RUV
[ *EY020799: NIH/2 P30 EY020799-02 to Jerry Young Niederkorn, see: http://www.utsouthwestern.edu/edumedia/edufiles/departments_centers/ophthalmology/grants/jan-2012-ophthalmology-active-grants.pdf . . . also, several ref’s to EY020799 here (Dr. Christopher W. Cowan, UTSW): http://www.utsouthwestern.edu/facultydata/78546/files/CWCowan%20CV%2011-2011.pdf . . Google EY020799: many more refs.]