Avid Bioservices Inc (CDMO)

[cjgaddy]

Genentech studying Imaging using PGN635(Fhu-Bavi) for the potential “detection of tumor response to therapy”. 9 Genentech co-authors of new paper pub. 10-12-2012 in Nuclear Medicine & Biology, which acknowledges Dr. Philip Thorpe & Peregrine, and states in the article, “the presented PS-targeting antibody (89Zr-PGN635) has a potential to become a broadly applicable imaging agent indep. on cancer type since PS is a generic component of the plasma membrane.”… [Thanks, FTM – great find]…

Note: 89Zr-PGN635 is a different imaging agent than used in the ongoing Imaging trial, which uses 124I-PGN650 ( http://clinicaltrials.gov/ct2/show/NCT01632696 ).
…Recall:
• PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.); Genentech studying 89Zr-PGN635 as a Tumor Imaging Agent, “indep. of cancer type”
• PGN632 is the Duke-PPHM-HIV candidate=11.31=AT005 (B2GPI-indep.); also being studied by PPHM+LSU vs. Ocular Herpes (Acute HSV-1 Keratitis), see http://tinyurl.com/cax9a4p
• PGN650 is a human F(ab’)2 fragment that targets PS expression (1st ref’d in AACR’12 #2452) – see http://tinyurl.com/76nqqkm . 124I-PGN650 is Peregrine’s PS-Imaging candidate, whose IND clinical filing was announced 4-3-12, and whose n=12 trial started 6-2012.
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Note: PGN632 (Duke/HIV preclin’s) binds to PS indep. of B2-glycoprotein I (B2GPI), unlike Bavi & FH-Bavituximab(PGN635) which depend on B2GPI as a binding intermediary.

= = = = = = = = = = =Found by FTM #99257:
10-12-2012: “ImmunoPET Imaging of Phosphatidylserine in Pro-Apoptotic Therapy Treated Tumor Models”
Nuclear Medicine & Biology - Rec. 6-29-12; Rev. 9-6-12; Acc. 9-6-12; Pub. Online 10-12-12
Annie Ogasawara, Jeff N. Tinianow, Alexander N. Vanderbilt, Herman S. Gill, Sharon Yee, Judith E. Flores, Simon-Peter Williams, Avi Ashkenazi, Jan Marik
Genentech Research & Early Dev. (gRED), [Dept. of Biomedical Imaging], Genentech Inc., S.SanFran
http://www.sciencedirect.com/science/article/pii/S0969805112002302
or: http://www.nucmedbio.com/article/S0969-8051(12)00230-2/abstract
ABSTRACT
An immunoPET imaging probe for the detection of phosphatidylserine (PS) was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma half-life of a probe based on a full-length antibody coupled with a residualizing radionuclide would be able to catch the wave of drug-induced apoptosis and lead to a specific accumulation in apoptotic tumor tissue.
METHODS: The imaging probe is based on a 89Zr-labeled monoclonal antibody PGN635 targeting phosphatidylserine.
[Note: PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.) - see http://tinyurl.com/cparu & http://tinyurl.com/6ql5nf ].
The probe was evaluated pre-clinically in 4 tumor xenograft models: one studied treatment with paclitaxel to trigger the intrinsic apoptotic pathway, and 3 others interrogated treatment with an agonistic death-receptor monoclonal antibody to engage the extrinsic apoptotic pathway.
RESULTS: High accumulation of 89Zr-PGN635 was observed in treated tumors undergoing apoptosis reaching 30 %ID/g and tumor-to-blood ratios up to 13. The tumor uptake in control groups treated with vehicle or imaged with a non-binding antibody probe was significantly lower.
CONCLUSIONS: The results demonstrate the ability of 89Zr-PGN635 to image drug-induced apoptosis in animal models and corroborate our hypothesis that radiolabeled antibodies binding to intracellular targets transiently exposed on the cell surface during apoptosis can be employed for detection of tumor response to therapy.
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From the end of Discussion Section: ”the presented PS-targeting antibody (89Zr-PGN635) has a potential to become a broadly applicable imaging agent independent on cancer type, since PS is a generic component of the plasma membrane.”
From Acknowledgments: ”We would like to thank Philip Thorpe [UTSW, Peregrine SAB] and Nicholas van Bruggen [Associate Director of the Biomedical Imaging Group at Genentech] for helpful discussions, Peregrine Pharmaceuticals, Inc. for providing PGN635...”

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M. Tumor Imaging & Dosimetry trial of I124-PGN650 (FH-Bavi) in Adv. Solid Tumors (Ph0, open-label, 1arm, n=12)
Protocol: http://clinicaltrials.gov/ct2/show/NCT01632696 (1 U.S. site as of 6-28-12)
..."I124-PGN650 is the Fab end of PS-targeting mab PGN635 (FH-Bavi) joined to the PET imaging radioisotope iodine-124, a new approach to imaging cancer."
...6-28-12: Trial added to Trials.gov, 1st site "recruiting" (Wash.UnivSM/St.Louis)
…4-3-12: Peregrine Launches PS-Targeting Clinical Imaging Pgm (AACR'12 #2452) http://tinyurl.com/7p7jovt & http://tinyurl.com/7yrwqm7

IMAGING APPLICATIONS Of PS-TARGETING MABS:
10-12-12: Genentech studying Imaging using PGN635(Fhu-Bavi) for the potential “detection of tumor response to therapy”. http://tinyurl.com/8wvem9y
…Nuclear Medicine & Biology, Genentech's Jan Marik, “ImmunoPET Imaging of PS in Pro-Apoptotic Therapy Treated Tumor Models”
4-3-12: Peregrine Launches PS-Targeting Clinical Imaging Program (AACR'12 #2452) http://tinyurl.com/7p7jovt & http://tinyurl.com/7yrwqm7
…PPHM "recently filed an IND" with FDA for an Imaging trial using 124I-PGN650, ~12pts.
...6-28-12: Trial added to trials.gov: http://clinicaltrials.gov/ct2/show/NCT01632696 - see CANCER TRIALS ABOVE for more details.
12-2011: Thorpe Article on FH-Bavi/Optical-Imaging in Translational Oncology http://tinyurl.com/7vcnbz2
11-14-11: Dr. Bruce Freimark presents PS IMAGING poster at AACR-NCI-EORTC Conf./SanFran http://tinyurl.com/89hpydn
9-12-11: Drs. Thorpe & Freimark present PS IMAGING posters at World Imaging Congress/S.Diego http://tinyurl.com/3uv5rgr
9-9-11: PS IMAGING potential discussed in Qtly. Conf. Call: http://tinyurl.com/3q7hzjh
4-2011/Neoplasia: Dr. Thorpe 9-pg. article on Exposed-PE/Imaging http://tinyurl.com/5uoy6fh
…Dr. Thorpe: "PE also has potential as a marker for Imaging human malignancies."
4-6-11/AACR'11: Tumor Imaging Applications of PS-Targeting Antibodies http://tinyurl.com/68p9zs4
…Steve King: "Molecular imaging is a growing field and represents an entirely new development opportunity for our first-in-class PS-targeting antibody platform… our antibodies labeled with imaging tracers hold potential for illustrating exposed PS in a clinical oncology setting, imaging PS as a companion diagnostic with bavituximab therapy, as well as ultimately assessing patient response to a range of cancer therapies."
3-14-11: Dr. Thorpe discusses PS IMAGING in Conf. Call: http://tinyurl.com/4p4hqr5
…Dr. Thorpe: "The quality of the images is quite extraordinary. The antibody homes to tumor blood vessels beautifully in all tumors that we've seen with really very, very little of a staining seen in other tissues, and that's just what you'd like to see in a diagnostic - we are looking at that very seriously. And also, that binding is correlated to response, both with radiotherapy & chemotherapy. So again, we have the possibility of making a diagnostic that would be predictive of response. We are evaluating that possibility at this time... Duramycin binds PE; binding PE expands our coverage of our broad aminophospholipid-targeting platform, so it really dovetails very beautifully with the existing antibody portfolios. It's expanding our desire to explore different phospholipids as potential targets for therapy & diagnosis… PE is phosphatidylethanolamine and it is the brother of PS. So where PE goes, so does PS and vice versa. So the 2 lipids co-segregate normally on the inside surface of the plasma membrane, but in activated cells or apoptotic cells or stress cells, both lipids flip, and both are potential targets for therapeutics or diagnostics… Duramycin is a little peptide, that's a small molecule and has quite different qualities from an antibody in terms of penetrants. So we're intrigued to see how it plays out, too."
6-24-09 U.S. Patent #7,550,141 granted: Anti-PS for Tumor Imaging: http://tinyurl.com/ln9ub8
3-3-08: Thorpe/Mason C.C.R. (AACR) article on Arsenic-labeled Bavi for Imaging Tumors: http://tinyurl.com/32jbfl
…3-5-08 Chemistry World followup article on CCR Bavi+Arsenic/IMAGING: http://tinyurl.com/4m4lbse
2006/SMI: Thorpe/Mason, "Optical Imaging of Exposed PS in Tumors" http://tinyurl.com/42nh7d9
…"We believe optical imaging with Bavituximab holds great promise for assessing PS expression, and therapeutic activity in vivo and optimizing treatment protocols."