Avid Bioservices Inc (CDMO)

[cjgaddy]

10-15-14/PR: Bavi/Ebola-Binding article in peer-reviewed Jrnl-of-Immunology-Res. (“Vaccines & Therapies for Biodefense Agents” special edition) – submitted=2/25/14, rev=6/20/14, accepted=9/3/14 – authors are Public Health England & PPHM researchers…

10-15-14: Data to Be Published in the Journal of Immunology Research Support Phosphatidylserine (PS) as a Potential Target in Ebola Infection
• Peer-Reviewed Data Show Peregrine Pharmaceuticals' PS-Targeting Antibody Bavituximab Exhibits Specific and Strong Binding to Ebola Virions and Ebola Virus-Infected Cells In Vitro
• Data Supplement Published Scientific Literature Suggesting the Important Role of PS in Ebola Infection in Viral Entry and Immune Suppression During Infection
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=876271

TUSTIN, CA 10/15/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM, PPHMP), today announced the publication of a peer-reviewed manuscript related to preclinical research demonstrating that the company's lead drug candidate bavituximab, a phosphatidylserine (PS)-targeting antibody, exhibits specific and strong binding to Ebola virions and Ebola virus (EBOV)-infected cells in vitro. These results will appear in the Vaccines and Therapies for Biodefense Agents special edition of the peer-reviewed Journal of Immunology Research in a manuscript titled: "Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions."

"The recent outbreaks of Ebola infections highlight the need for novel clinical treatments and new combinations that are effective in treating the disease. We have a number of active collaborations exploring the potential of PS-targeting antibodies in infectious diseases and the results just published, along with a growing body of scientific literature, support potential applications of our PS-targeting platform in virus infections including Ebola," said Jeff T. Hutchins, Ph.D. VP, Preclinical Research at Peregrine Pharmaceuticals. "Evolution has favored pathogenesis that exposes PS and these published results, along with other recently to be published data, have shown that PS is present during Ebola virus infection (1-3) and is important in the infection process. While our primary focus remains on advancing bavituximab in oncology, including our SUNRISE Phase III lung cancer trial, we believe these data warrant further collaborative investigation in Ebola and other infectious diseases including combinations with vaccines and active therapies that have shown promise."

The manuscript details the results from a study demonstrating that exposed PS allows for the specific binding of bavituximab to purified Ebola virions and EBOV-infected cells in vitro. Previous published studies have shown that surface exposure of PS antigen is a consequence of viral infection. Published results in other lethal viral hemorrhagic fever animal model (Pichinde virus infection model in guinea pigs)5 suggest that PS-targeting antibodies can bind to exposed PS and limit viral infection by initiating the removal of virions from the bloodstream through the induction of antibody-dependent cellular cytotoxicity (ADCC) as well as eliminate virus-infected cells.
"Our goal with this work was to continue exploring the potential of bavituximab in the antiviral arena and in this case, specifically in biodefense applications," said Cyril Empig, Ph.D., Associate Research Director at Peregrine Pharmaceuticals. "With the increased focus on Ebola, there is an opportunity to take advantage of the specificity of bavituximab for Ebola virus and develop therapeutics or treatment regimens that could neutralize the virus. In addition, recently reported genomic sequence variations in EBOV suggest that drugs targeting specific viral non-variant proteins or protein sequences are at risk of failure as a result of virus escape mutations.4 We believe that there are advantages to utilizing bavituximab in a treatment regimen against Ebola virus given its great specificity for Ebola virions and Ebola-infected cells, its potential to circumvent the problem of virus escape mutations given that it is targeting a host molecule rather than a virus protein or protein sequence, and the possible role of PS in immunosuppression during Ebola infection.1 Given these data, we are developing a plan to explore potential applications of bavituximab and PS-targeting antibodies in the treatment of Ebola."

A link to the provisional manuscript can be found on the front page of the company's website at http://www.peregrineinc.com
[ http://www.peregrineinc.com/images/stories/pdfs/dowall_et_al_2014.pdf ]

ABOUT BAVITUXIMAB: A TARGETED IMMUNOTHERAPY
Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. To date, bavituximab has been administered to over 600 patients worldwide and appears to be safe and well tolerated. Bavituximab's target, PS, is a highly immunosuppressive lipid molecule usually located inside the membrane of healthy cells, but "flips" and becomes exposed on the outside of virus-infected cells, virus particles themselves, as well as tumor cells and cells that line tumor blood vessels, creating a specific target for anti-viral and anti-cancer treatments. PS-targeting antibodies target and bind to PS and block this immunosuppressive signal potentially enabling the immune system to better recognize and fight tumors and infectious pathogens. Data published in peer-reviewed journals shows that PS-targeting antibodies such as bavituximab mediate important immune-stimulatory changes.5,6 As part of the SUNRISE trial, bavituximab is being evaluated in a Phase III, global, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and efficacy of bavituximab plus docetaxel as second-line treatment in patients with non-small cell lung cancer. Bavituximab is also currently being evaluated in several solid tumor indications, including breast cancer, liver cancer, rectal cancer and melanoma. For additional information about the SUNRISE trial please visit www.SunriseTrial.com or http://www.ClinicalTrials.gov using Identifier NCT01999673.

ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials for the treatment and diagnosis of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. The company is also advancing a molecular imaging agent, 124I-PGN650, in an exploratory clinical trial for the imaging of multiple solid tumor types. 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 third-party customers. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Safe Harbor *snip*

1 S. Bhattacharyya et al. 2013. Enveloped viruses disable innate immune responses in dendritic cells by direct activation of tam receptors. Cell Host Microbe. 14, 136-147, doi:10.1016/j.chom.2013.07.005.
2 S. Jemielity et al. 2013. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog. 9:e1003232.
3 K. Morizono et al. 2014. Role of Phosphatidylserine Receptors in Enveloped Virus Infection. J. Virol. 88: 4275-4290.
4 S.K. Gire et al., 2014. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science, doi: 10.1126/science.1259657.
5 Soares MM, King SW, Thorpe PE. Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nature Medicine 2008 Dec;14(12):1357-62.
6 Yi Yin, Xianming Huang, Kristi D. Lynn, and Philip E. Thorpe. Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation. Cancer Immunology Research; 1(4); 256-68.
Contact:
Christopher Keenan, Peregrine Pharmaceuticals, Inc., [phone] [e-mail]

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9-2014: Public Health England/PPHM article on Bavi/Ebola in Hindawi’s Jrnl-of-Immunology-Res – submitted 2/2014, accepted 9/2014. [Note: PGN401=Chimeric bavituximab]
9-3-14: Research Article: “Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions”
Journal of Immunology Research, Hindawi Pub.
Rec=2/25/14, Rev=6/20/14, Acc=9/3/14
Article: http://www.hindawi.com/journals/jir/raa/347903/
PDF: http://downloads.hindawi.com/journals/jir/raa/347903.pdf (18pgs)
Authors:
1/Public Health England**: Stuart D. Dowall, Victoria A. Graham, Christine Bruce, Linda Easterbrook, Roger Hewson
2/Peregrine Pharm: Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger
**NOTE: Public Health England (formerly, UK’s ‘Health Protection Agency’ - HPA became part of Public Health England in 2013)
https://www.gov.uk/government/organisations/public-health-england
ABSTRACT
Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus.
http://www.hindawi.com/journals/jir/raa/347903/
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[Note: PGN401=Chimeric Bavituximab, PGN635=Fully-Human Bavituximab]
• This appears at end of article body(pg.9): "This work was supported by the Transformational Medical Technologies program contract HDTRA1-08-C-003 from the Dept of Defense Chemical & Biological Defense program through the Defense Threat Reduction Agency (DTRA http://www.dtra.mil/ )."
• This on pg.8: "Due to PGN401 having been used for several human clinical trials in cancer, from Phase I to III [13, 20, 21], its repurposing of use for filovirus therapy through licensure or emergency use may present an attractive option. Due to the anticipated small market size of any anti-filoviral treatment, the use of therapies primarily designed for other conditions confer several advantages in reducing the costs of bringing an effective treatment to clinical use due to having already negotiated some of the steps required for regulatory approval. Future work to determine whether this approach elucidates any protective effect using in vivo models of EBOV infection is planned."

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11-16-2012: Antiviral-Res. by Bavi-AV collaborator HPA/UK on Bavi vs. EBOLA …”Virus induced externalization of PS raises the possibility that PGN401 (Bavi) has broad spectrum antiviral activity.”
Found by FTM 11-21-12: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=81719282
11-16-12 Antiviral Research
“Catheterized Guinea Pigs Infected with Ebola Zaire Virus Allows Safer Sequential Sampling to Determine the Pharmacokinetic Profile of a Phosphatidylserine-Targeting Monoclonal Antibody”
Stuart Dowall, Irene Taylor, Paul Yeates, Leonie Smith, Antony Rule, Linda Easterbrook, Christine Bruce, Nicola Cook, (((Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger <=PPHM))), Victoria Graham, Mike Dennis, Roger Hewson
a Health Protection Agency, Porton Down, Salisbury, Wiltshire UK
b Peregrine Pharmaceuticals, Inc.
Excerpt: “…Virus induced externalization of PS raises the possibility that PGN401 (Bavituximab) has broad spectrum antiviral activity. The advantages of targeting PS include drug pecificity for infected cells, and since PS is a feature of the host cell, effectiveness would potentially not be susceptible to viral escape mutations (Mir et al., 2009). One such application for a broad spectrum antiviral would be against biodefense pathogens, such as Ebola virus (EBOV)…”

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Back on 11-23-09, when the PeregrineInc website “SAB” page listed about a dozen collaborators, this was one of them:
• VHF - Health Protection Agency, Salisbury U.K.
(Note: UK’s ‘Health Protection Agency’ - HPA became part of Public Health England in 2013)

BAVITUXIMAB ANTI-VIRAL VHF NEWS:
11-16-11: Two AntiPS posters presented at DTRA's 2011 CBD S&T/Vegas http://tinyurl.com/7pc76qd
...1) Argentine Hemorrhagic Fever/UTexas. . .2) Bacteria Infections/DSTL Porton Down/UK & Thorpe/King/C.Empig/PPHM
11-16-10: PPHM Presents AntiPS/VHFs pre-clin. data at CBDS&T BioDef Conf./Orlando http://tinyurl.com/4ve6xcl
11-18-09: PPHM Presents AntiPS/VHFs pre-clin. data at DTRA/TMT Conf. http://tinyurl.com/ycrrwub