Replies to post #194815 on Avid Bioservices Inc (CDMO)

[cjgaddy]

Table of All 20 Bavi Trials (Ongoing & Enrollment-Completed) – Cancer & Viral. (Bavi-Treated counts only; doesn’t include the CTL-Only arms in randomized trials)…
FDC = “Final Data Collection Date for primary outcome measure” - est. from ClinicalTrials.gov.

 
 BAVITUXIMAB CANCER TRIALS A/O 10/28/14: (see http://PeregrineTrials.com ) 
   Spon Ph.  Drug         Disease         Init.  N(Bavi) Trial-Design   Sites     Enr-Comp. 
 A Co.  1A   Bavi/Mono    Solid Cancers  6/2005     26  1Arm/openlab    USA         6-2009 
 D Co.  1B   Bavi+Chemo   Solid Cancers 11/2006     12  1Arm/openlab    India       5-2007 
 E Co.  II   Bavi+CP      NSCLC/1stL     6/2008     49  1Arm/openlab    India      10-2009  
 F Co.  II   Bavi+CP      Breast/1stL    8/2008     46  1Arm/openlab    India       9-2009 
 G Co.  II   Bavi+Doce    Breast/Refr.   1/2008     46  1Arm/openlab    RepGA       5-2009            
 I Co.  2B   Bavi+Doce    NSCLC/2ndL     6-2010 79=>69# Random/blind    US24,Int29 10-2011 
 J Co.  2B   Bavi+CP      NSCLC/1stL     7-2010  86x.5  Random/openlab  US17,Int23  9-2011 
 K IST1 I/II Bavi+Soraf.  Liver(HCC)    12-2010     47  1Arm/openlab    UTSW(5)     9-2014 
 L Co.  2    Bavi+Gem.    Pancr./untr.   1-2011  70x.5  Random/openlab  US15,Ukr4   6-2012 
 N IST2 1    Bavi+Pac.    Breast/Her2-   1-2011     14  1Arm/openlab    ArizCC      4-2013 
 O IST3 1B   Bavi+CP      NSCLC/1stL     3-2011     25  1Arm/openlab    UNC+UPitt   9-2014 
 P IST4 1B   Bavi+Cabaz.  Prostate/2ndL  5-2011      4  1Arm/openlab    MUSC        Canc=3/13(SOC-chg) 
 Q Co.  0    I124-PGN650  CancerImaging  6-2012     12* 1Arm/openlab    WashUniv    FDC=4/15 
 R IST5 1B   Bavi+Cap+RAD Rectal         7-2012     18* 1Arm/openlab    UTSW        FDC=8/15 
 S IST6 1B   Bavi+Yervoy  Melanoma       4-2014 24x.67* Random/openlab  UTSW        FDC=3/16 
 T Co.  III  Bavi+Doce    NSCLC/2ndL    12-2013  582/2  Random/blind    146(Oct’14) Est=12/15 
 EST. TOTAL CANCER:(*ongoing trials est@25% comp)  427 (not incl. Ph.3 SUNRISE) 
 #Note: Bavi/1MG N=40 in Ph2/NSCLC trial cut by 25% due to CSM dose-switching of portion of 1MG/Bavi & Ctl arms. 
  
 BAVITUXIMAB VIRAL TRIALS COMPLETED:  
   Ph. Drug              Disease           Dosed            N 
 B 1A  Bavi/Mono/single  HepC              8/2005-2/2006   30 USA 
 C 1B  Bavi/Mono/repeat  HepC              6/2006-1/2007   24 USA 
 H 1B  Bavi/Mono/repeat  HCV-HIV Co-Inf’s  7-2007-1/2011   24 USA 
 M II  Bavi+Ribavirin    HepC/1st-line     1-2011-9/2011   44 RepGA (randomized) 
 TOTAL HEPC/HIV:                                          122 

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For Links to ClinicalTrials.gov protocols, see iBox:
http://investorshub.advfn.com/boards/show_ibox.aspx?boardid=2076











10-16-14 Peregrine ASM: Slides(42), Audio-Replay-Link, Attendee-Reports http://tinyurl.com/oyc3e5v

9-9-14 Qtly. Conf. Call (King/Hutchins/Shan/Lytle) Transcript http://tinyurl.com/ktrfswj
...CEO S.King: “In addition to our clinical trials, many of which have also have translational data points built in to tie together pre-clin. data with the clinic, we have also continued to build momentum in our pre-clin. collaborations which now number in the dozens. We are evaluating new combinations & dosing strategies combining bavituximab with chemotherapy, radiation, and immune-oncology approaches, including those targeting CTLA-4, PD-1, as well as other downstream immune checkpoints."

[cjgaddy]

10-30-14: Bavi+CP NSCLC/1L/Stage4 Ph1B-IST Interim-Data, MSTO’14/Chicago (PI=J.Grilley Olson/UNC, n=23, single-arm)…
• Bavi+CP => MOS=12.2mos, PFS=4.8mos, ORR=35%.
• Link & Poster Image below, as well as FTM’s 5-2013 Table of 20 Ph3 Historical Trial Comparators

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10-23-14 PR: Promising Data Presented at the Chicago Multidisciplinary Symposium on Thoracic Oncology From an IST of Peregrine’s Bavituximab in Combination with Pemetrexed & Carboplatin in Front-Line NSCLC
• Favorable Trends in Both Overall Response Rates of 35% and Median Overall Survival of 12.2 months Continue to Support Bavituximab's Potential in NSCLC
• Lead Immuno-Oncology Antibody Bavituximab in a Phase III Trial in Patients With Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=879373

TUSTIN, CA, 10/30/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP), today announced the presentation of data from the Phase Ib investigator-sponsored trial (IST) of its immunotherapy bavituximab in combination with the chemotherapies pemetrexed and carboplatin in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Data from this single-arm, open-label, multi-center trial show an overall tumor response (ORR) of 35%, a median progression-free-survival (PFS) of 4.8 months, and a median overall survival (OS) of 12.2 months. Favorable trends in ORR and OS continue to support bavituximab's potential in NSCLC.1-4 These data are presented in a poster session at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology being held at the Marriott Downtown Chicago Magnificent Mile in Chicago, Illinois [ http://tinyurl.com/p2l43mt ].

"While we continue to advance our SUNRISE Phase III trial in second-line NSCLC, data from this front-line trial are intriguing and warrant further investigation in a larger trial setting," said Joseph Shan, VP of Clinical & Regulatory Affairs of Peregrine. "These recent data add to the growing body of favorable combination data generated with bavituximab and chemotherapy agents as well as complementing the preclinical data emerging from our immuno-oncology program combining bavituximab with immune checkpoint inhibitors." 5-8

The poster titled: "A Phase Ib Study of Bavituximab Plus Carboplatin and Pemetrexed in Chemotherapy Naïve Stage IV Non-Squamous Non-Small Cell Lung Cancer" will be presented by Juneko Grilley-Olson, M.D., principal investigator of the trial and assistant professor, Dept. of Medicine, Division of Hematology and Oncology at the University of North Carolina at Chapel Hill. Results from 23 evaluable patients with advanced non-squamous NSCLC showed that the combination of bavituximab, carboplatin and pemetrexed was well-tolerated and clinically active. In this single-arm trial, patients treated with bavituximab in combination with carboplatin and pemetrexed achieved an objective response rate (ORR) of 35% (95% confidence interval (CI): 16.4 - 57.3%) as measured in accordance with RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In addition, data showed a current median PFS of 4.8 months (95% CI: 4.0 - 8.0 months) and a median OS of 12.2 months (95% CI: 8.0 - not estimable (NE) months). Most adverse events (AE) observed were consistent with the known safety profile of the chemotherapy agents with no dose-limiting toxicities (DLT) or unexpected AEs occurring. All patients experienced at least one AE. The most common treatment related AEs were thrombocytopenia, anemia, neutropenia, fatigue, nausea with most AEs being = Grade 2. The recommended Phase II dose of bavituximab in combination with carboplatin and pemetrexed is determined to be 3mg/kg.

Dr. Grilley-Olson stated: "I am pleased to be presenting these updated results to the oncology community given the encouraging data coming from this open-label trial in what is a difficult to treat disease. While these data come from a small number of patients the responses seen warrant further clinical examination including the conduct of randomized trials. In addition, the survival curve observed from this trial is consistent with those seen from other immunotherapy-based drug candidates."

Bavituximab is in Phase III development for the treatment of previously treated non-small lung cancer as part of the SUNRISE trial and is being evaluated in several solid tumor indications, including investigator-sponsored trials in breast cancer, liver cancer, rectal cancer and melanoma.

ABOUT THE PHASE IB TRIAL
This is a Phase Ib, open-label, single-arm, multi-center trial in 26 patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. These patients received up to six 21-day cycles of the drugs pemetrexed and carboplatin with weekly bavituximab (3 mg/kg) until progression or toxicity. The primary endpoints of the trial were to determine the safety, dose-limiting toxicity (DLT) and recommended Phase II dose of bavituximab in combination with carboplatin and pemetrexed in advanced non-squamous NSCLC. Secondary endpoints included assessment of overall response rate (ORR) measured by RECIST criteria, progression-free survival (PFS) and overall survival (OS).

More information on this trial can be found at www.ClinicalTrials.gov using Identifier NCT01323062. [ http://clinicaltrials.gov/ct2/show/NCT01323062 ]

The link to the poster [abstract #215] can be found from the front page of the company's website at: http://www.peregrineinc.com . [ http://www.peregrineinc.com/images/stories/pdfs/grilley-olson-2014.pdf ]

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 previously treated 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*
REFS:
1 Shtivelband M. et al. "Randomized, blinded, placebo-controlled phase II trial of docetaxel and bavituximab as second-line therapy in locally advanced or metastatic non-squamous non-small cell lung cancer." J Clin Oncol 31, 2013 (suppl; abstr 8095)

2 Chalasani P et al. Phase I clinical trial of bavituximab (Bavi) and paclitaxel (P) in patients (pts) with HER2-negative metastatic breast cancer (MBC). J Clin Oncol 31, 2013 (suppl; abstr 567)

3 Raghunadharao D. et al Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer Lung Cancer. Published Online: August 23, 2014 DOI: http://dx.doi.org/10.1016/j.lungcan.2014.08.010

4 Peregrine Pharmaceuticals. Peregrine Reports Promising 20.7 Month Median Overall Survival From Phase II Advanced Breast Cancer Trial. N.p., 24 Aug. 2011. Web. 24 Aug. 2011

5 Brekken R. Antibody-mediated blockade of phosphatidylserine enhances the anti-tumor activity of immune checkpoint inhibitors by affecting myeloid-derived suppressor cell (MDSC) and lymphocyte populations in the tumor microenvironment. Presentation at Cancer Research Institutes' "Cancer Immunotherapy: Out of the Gate" conference October 6, 2014. New York, New York

6 Hutchins J. Phosphatidylserine (PS)-Targeting Antibodies Enhance Activity of Immune Checkpoint Inhibitors by Repolarizing Immunosuppressive Immune Cells Populating the Tumor Microenvironment. Presentation at Cambridge Healthcare Institute's ImVacS 9th Annual Immunotherapies & Vaccine Summit. August 11, 2014. Boston, Massachusetts

7 Huang X et al. Phosphatidylserine-targeting antibody synergizes with anti-PD-1 antibody to inhibit tumor growth in K1735 mouse melanoma model. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl): Abstract nr LB-262. doi:10.1158/1538-7445.AM2014-LB-262

8 Gong J. et al, Targeting of phosphatidylserine by monoclonal antibodies enhances activity of immune checkpoint inhibitors in tumors. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl): Abstract nr 4978. doi:10.1158/1538-7445.AM2014-4978
CONTACT: Christopher Keenan, Peregrine Pharmaceuticals, Inc., [phone], [e-mail]

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K. 3rd IST Trial (Bavi+PemCarbo vs. Frontline NSCLC (Stage4), open-label Ph.1B, n=25)
Protocol: http://clinicaltrials.gov/ct2/show/NCT01323062
…10-30-14: Interim data n=23, MSTO’14: MOS=12.2mos, PFS=4.8mos, ORR=35% http://tinyurl.com/mll62c6
...9-9-14: Stage IV NSCLC IST Enrollment complete. http://tinyurl.com/ktrfswj
...4-2012: Clinicaltrials.gov shows 2nd site added: Univ. of Pittsburg
...4-2-12 AACR'12: "5pts. to-date, 3 have PR's" http://tinyurl.com/7yrwqm7 (see #1744)
...3-8-11: IST (NSCLC) initiated at UNC (PI= J.Grilley-Olson), ~25 patients - http://tinyurl.com/6b926ku

= = = = = = = = = =MSTO’14 POSTER IMAGE (Abstract #215):
10-30-14 MSTO’14/Chicago - J.Grilley-Olson’s Poster on Bavi+CP IST(UNC/U-Pitt) vs. Frontline State4 NSCLC), n=23, single-arm:
PDF: http://www.peregrineinc.com/images/stories/pdfs/grilley-olson-2014.pdf







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FTM’s 5-2013 table of 20 prev. Ph3’s in 1st-Line/NSCLC with chemo Ctl=CP (Carboplatin+Pemetrexed). Mean MOS for those 20 Ph3’s: Ctl=9.8mos, Treatment=10.1mos.
PPHM’s 10-30-14 PR indicates: MOS=12.1mos, ORR=35% (Bavi+CP, n=23, Stage4 1L-NSCLC)
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20 Ph3’s: MOS & HR results (Note Avastin improved CP-Only by 19%, to 12.3mos):

See FTM 5-7-13: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=87653916

[cjgaddy]

Nov6-9 SITC/2014 29th Annual-Meeting: Bavi+Sorafenib/Liver-Cancer IST/UTSW/Yopp “correlative studies” data and 3 poster presentations of followup data from AntiPS+AntiPD1/Melanoma+Breast preclin. studies, specifically how PS-targeting Mabs’ “enhance the activity of immune checkpoint inhibitors”. 4 Peregrine Posters total now appearing on the SITC conf. website…

Nov6-9: “SITC 2014 – 29th Annual Meeting”, National Harbor MD
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2014 Meeting: http://www.eventscribe.com/2014/sitc
“Known as the premier destination for scientific exchange, education and networking in the cancer immunotherapy community, attendees will be a part of more than 1,100 anticipated basic, clinical, and translational scientists from academia, gov’t, and industry, along with other top medical professionals from around the world, all dedicated to improving cancer patient outcomes through cancer immunotherapy.”
ABSTRACTS: “All abstracts submitted to the SITC 29th Annual Meeting will be published in the Journal for ImmunoTherapy of Cancer [ http://www.immunotherapyofcancer.org ], the official journal of SITC. This issue will be released on Thu. Nov. 6, 2014.”
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• A. FROM PPHM’S 9-9-14 PR: “Data from the company's immuno-oncology program, as well as clinical translational data aimed at assessing & measuring changes in immune response pre- and post-treatment from the Liver Cancer IST will be the subject of presentations at the SITC 29th Annual Meeting to be held Nov. 6-9, 2014.”
• B. Jeff Hutchins, PhD (VP, Pre-Clinical Dev., PPHM) - 9-9-14 PPHM Conf.Call: “Addl. data from the preclin. study presented at ImVacS [8-11-14, bavi+AntiPD1/BreastCancer – see http://tinyurl.com/lpjy3u7 & http://tinyurl.com/oueldme ], as well as a follow-up data from our Melanoma study [ie, pre-clin. Bavi+AntiPD1, not the Bavi+Ipilimumab(Yervoy)/Melanoma IST] will be presented at the 29th SITC Annual Meeting to be held in November.”

DETAILS – via http://www.eventscribe.com/2014/sitc/SearchByKeyword.asp
A. Poster# P214: “Correlative Studies of a Phase II Clinical Study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular [Liver] Carcinoma”
• UTSW-MC/Dallas: Adam Yopp MD[PI, Liver IST], Xianming Huang PhD, Rolf Brekken PhD
• PEREGRINE PHARM: Nikoletta Kallinteris MSc CCRP, Jeff Hutchins PhD, Kerstin Menander MD PhD, Steve King MSc
• UNIV. OF PENN: Xiaowei Xu MD PhD
• WISTAR INSTITUTE (Philadelphia): Dmitry Gabrilovich MD PhD

B1. Poster# P205: “Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances Activity of Immune Checkpoint Inhibitors in Breast Tumors”
PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Jian Gong MD PhD (Sr.Sci.), Van Nguyen PhD (Sci.), Shen Yin PhD (Post-Doc.), Rich Archer MS (Sr.Sci.), Emely Nguyen (intern), Jeff Hutchins PhD (VP/PreClinRES)

B2. Poster# P213: “Antibody-Mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy of Downstream Immune Checkpoint Inhibition in K1735 Mouse Melanoma”
• UTSW-MC/Dallas: Xianming Huang PhD, Dan Ye, Rolf Brekken PhD, Alan Schroit PhD
• PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Jian Gong MD PhD (Sr.Sci.), Van Nguyen PhD (Sci.), Shen Yin PhD (Post-Doc.), Rich Archer MS (Sr.Sci.), Jeff Hutchins PhD (VP/PreClinRES)
• UNIV. OF CALIF/IRVINE: Chris C.W. Hughes PhD [Prof.&Chair - http://darwin.bio.uci.edu/~cchughes ]

B3. Poster# P271: “Antibody-Mediated Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Targeted Therapy & Immune Checkpoint Inhibitors by Affecting Myeloid and Lymphocyte Populations in the Tumor Microenvironment”
• UTSW-MC/Dallas: Rolf Brekken PhD, Adam Yopp MD[PI, Liver IST], Xianming Huang PhD
• PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Nikoletta Kallinteris MSc CCRP, Joe Shan MPH (VP/Clin+RegAffairs), Kerstin Menander MD PhD, Jeff Hutchins PhD, Steve King MSc
• WISTAR INSTITUTE (Philadelphia): Dmitry Gabrilovich MD PhD [PPHM KOL/SAB: http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd ]
ABSTRACT:
The underlying cause for the failure of immune checkpoint blockade is the overwhelming, persistent and multifocal immune suppression in the tumor microenvironment. This is due to the absence of pre-existing antitumor Teff because of the action of important upstream immune checkpoints that recruit immunosuppressive cytokines (e.g., TGF-beta and IL-10) and tumor infiltrating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and M2 macrophages that can occupy up to 50% of the tumor mass.
The membrane phospholipid, phosphatidylserine (PS), is an upstream immune checkpoint. In normal non-tumorigenic cells, PS is segregated to the inner leaflet of the plasma membrane but becomes externalized to the outer leaflet of the plasma membrane in cells in the tumor microenvironment. PS is recognized and bound by PS receptors on immune cells where it induces and maintains immune suppression. PS-targeting agents block PS-mediated immunosuppression by multifocal reprograming of the immune cells in the tumor microenvironment to support immune activation. Antibody-mediated PS blockade reduces the levels of MDSC, TGF-beta, and IL-10 and increases the levels of TNF-alpha and IL-12. PS blockade also re-polarizes tumor-associated macrophages (TAM’s) from predominant M2 to predominant M1 phenotype, promotes the maturation of dendritic cells (DC’s) and induces potent adaptive antitumor T-cell immunity.
In a phase II clinical study [Bavi+Sorafenib/LiverCancer/HCC Ph.1/2 UTSW IST http://clinicaltrials.gov/ct2/show/NCT01264705 ], immunohistochemical evaluation of HCC tumor tissues post combination treatment indicated an increase of immune infiltrates; raising the potential of a clinically meaningful anti-tumor immune response. Pre-clinically, we demonstrate that PS targeting agents enhance the anti-tumor activity of anti-CTLA-4 and anti-PD-1 antibodies in immunocompetent models of melanoma (B16 and K1735) and breast (EMT-6) cancer and that tumor growth inhibition correlates with an increase in the infiltration of activated T cells and myeloid cells and the induction of adaptive immunity. In summary, PS blockade in combination with targeted therapy and other immune checkpoint inhibitors promotes a robust, localized, anti-tumor response and represents a promising strategy to enhance cancer immunotherapy.

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H. 1st Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer/HCC, open-label)
...Note: Sorafenib = Onyx/Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705 UTSW: http://tinyurl.com/mwdc2ql (5 sites: 3/UTSW, Parkland-Hosp, Dallas/VA, PI=Dr. Adam Yopp)
...4-4-12 AACR'12: Dr. Adam Yopp, "promising safety profile to-date" http://tinyurl.com/7yrwqm7 (see #5591)
...Feb'12-Sep’14 10+ times: CEO Steve King hints of future ex-US partner-driven Bavi+Sorafenib/LIVER trial in Asia: http://tinyurl.com/nkaxtcc
......Articles & Data describe Liver Cancer challenges in Asian populations: http://tinyurl.com/7z7o8j9 & http://tinyurl.com/7z99cy4
...12-1-10: PPHM's 1st IST (Liver Cancer) initiated at UTSW, ~56 patients - http://tinyurl.com/3xd3e6c
…Per S.King, 5-18-10/R&R, "We've had a lot of interest in running clinical trials with the compound from investigators who have either had prior experience with the drug or would like to study the drug in various settings. Potential IST indications include all the major solid tumor types. Of particular interest is Liver Cancer, in which we have a natural tie-in with our HCV program, Ovarian Cancer and Pancreatic Cancer, also very nicely supported by the prior data."

[cjgaddy]

PPHM at SITC’14: One Poster-Presentation Fri/NOV7, 3 Sat/NOV8 (Yopp/Liver/Translational/IST & Breast/Melanoma preclin.). All presentations 12:30-2:00pm each day...

Nov6-9 “SITC 2014 - 29th Annual-Meeting”: Bavi+Sorafenib/Liver-Cancer IST/UTSW/Yopp “correlative studies” data and 3 poster presentations of followup data from AntiPS+AntiPD1/Melanoma+Breast preclin. studies, specifically how PS-targeting Mabs’ “enhance the activity of immune checkpoint inhibitors”. 4 Peregrine Posters total now appearing on the SITC conf. website…

Nov6-9: “SITC 2014 – 29th Annual Meeting”, National Harbor MD
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2014 Meeting: http://www.eventscribe.com/2014/sitc
“Known as the premier destination for scientific exchange, education and networking in the cancer immunotherapy community, attendees will be a part of more than 1,100 anticipated basic, clinical, and translational scientists from academia, gov’t, and industry, along with other top medical professionals from around the world, all dedicated to improving cancer patient outcomes through cancer immunotherapy.”
ABSTRACTS: “All abstracts submitted to the SITC 29th Annual Meeting will be published in the Journal for ImmunoTherapy of Cancer [ http://www.immunotherapyofcancer.org ], the official journal of SITC. This issue will be released on Thu. Nov. 6, 2014.”
- - - - - - -
• A. FROM PPHM’S 9-9-14 PR: “Data from the company's immuno-oncology program, as well as clinical translational data aimed at assessing & measuring changes in immune response pre- and post-treatment from the Liver Cancer IST will be the subject of presentations at the SITC 29th Annual Meeting to be held Nov. 6-9, 2014.”
• B. Jeff Hutchins, PhD (VP, Pre-Clinical Dev., PPHM) - 9-9-14 PPHM Conf.Call: “Addl. data from the preclin. study presented at ImVacS [8-11-14, bavi+AntiPD1/BreastCancer – see http://tinyurl.com/lpjy3u7 & http://tinyurl.com/oueldme ], as well as a follow-up data from our Melanoma study [ie, pre-clin. Bavi+AntiPD1, not the Bavi+Ipilimumab(Yervoy)/Melanoma IST] will be presented at the 29th SITC Annual Meeting to be held in November.”

DETAILS – via http://www.eventscribe.com/2014/sitc/SearchByKeyword.asp
A. Poster# P236 (11-8-14 12:30-2:00): “Correlative Studies of a Phase II Clinical Study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular [Liver] Carcinoma”
• UTSW-MC/Dallas: Adam Yopp MD[PI, Liver IST], Xianming Huang PhD, Rolf Brekken PhD
• PEREGRINE PHARM: Nikoletta Kallinteris MSc CCRP, Jeff Hutchins PhD, Kerstin Menander MD PhD, Steve King MSc
• UNIV. OF PENN: Xiaowei Xu MD PhD
• WISTAR INSTITUTE (Philadelphia): Dmitry Gabrilovich MD PhD

B1. Poster# P228 (11-8-14 12:30-2:00): “Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances Activity of Immune Checkpoint Inhibitors in Breast Tumors”
PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Jian Gong MD PhD (Sr.Sci.), Van Nguyen PhD (Sci.), Shen Yin PhD (Post-Doc.), Rich Archer MS (Sr.Sci.), Emely Nguyen (intern), Jeff Hutchins PhD (VP/PreClinRES)

B2. Poster# P226 (11-8-14 12:30-2:00): “Antibody-Mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy of Downstream Immune Checkpoint Inhibition in K1735 Mouse Melanoma”
• UTSW-MC/Dallas: Xianming Huang PhD, Dan Ye, Rolf Brekken PhD, Alan Schroit PhD
• PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Jian Gong MD PhD (Sr.Sci.), Van Nguyen PhD (Sci.), Shen Yin PhD (Post-Doc.), Rich Archer MS (Sr.Sci.), Jeff Hutchins PhD (VP/PreClinRES)
• UNIV. OF CALIF/IRVINE: Chris C.W. Hughes PhD [Prof.&Chair - http://darwin.bio.uci.edu/~cchughes ]

B3. Poster# P227 (11-7-14 12:30-2:00): “Antibody-Mediated Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Targeted Therapy & Immune Checkpoint Inhibitors by Affecting Myeloid and Lymphocyte Populations in the Tumor Microenvironment”
• UTSW-MC/Dallas: Rolf Brekken PhD, Adam Yopp MD[PI, Liver IST], Xianming Huang PhD
• PEREGRINE PHARM: Bruce Freimark PhD (Dir/PreClinRES), Nikoletta Kallinteris MSc CCRP, Joe Shan MPH (VP/Clin+RegAffairs), Kerstin Menander MD PhD, Jeff Hutchins PhD, Steve King MSc
• WISTAR INSTITUTE (Philadelphia): Dmitry Gabrilovich MD PhD [PPHM KOL/SAB: http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd ]
ABSTRACT:
The underlying cause for the failure of immune checkpoint blockade is the overwhelming, persistent and multifocal immune suppression in the tumor microenvironment. This is due to the absence of pre-existing antitumor Teff because of the action of important upstream immune checkpoints that recruit immunosuppressive cytokines (e.g., TGF-beta and IL-10) and tumor infiltrating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and M2 macrophages that can occupy up to 50% of the tumor mass.
The membrane phospholipid, phosphatidylserine (PS), is an upstream immune checkpoint. In normal non-tumorigenic cells, PS is segregated to the inner leaflet of the plasma membrane but becomes externalized to the outer leaflet of the plasma membrane in cells in the tumor microenvironment. PS is recognized and bound by PS receptors on immune cells where it induces and maintains immune suppression. PS-targeting agents block PS-mediated immunosuppression by multifocal reprograming of the immune cells in the tumor microenvironment to support immune activation. Antibody-mediated PS blockade reduces the levels of MDSC, TGF-beta, and IL-10 and increases the levels of TNF-alpha and IL-12. PS blockade also re-polarizes tumor-associated macrophages (TAM’s) from predominant M2 to predominant M1 phenotype, promotes the maturation of dendritic cells (DC’s) and induces potent adaptive antitumor T-cell immunity.
In a phase II clinical study [Bavi+Sorafenib/LiverCancer/HCC Ph.1/2 UTSW IST http://clinicaltrials.gov/ct2/show/NCT01264705 ], immunohistochemical evaluation of HCC tumor tissues post combination treatment indicated an increase of immune infiltrates; raising the potential of a clinically meaningful anti-tumor immune response. Pre-clinically, we demonstrate that PS targeting agents enhance the anti-tumor activity of anti-CTLA-4 and anti-PD-1 antibodies in immunocompetent models of melanoma (B16 and K1735) and breast (EMT-6) cancer and that tumor growth inhibition correlates with an increase in the infiltration of activated T cells and myeloid cells and the induction of adaptive immunity. In summary, PS blockade in combination with targeted therapy and other immune checkpoint inhibitors promotes a robust, localized, anti-tumor response and represents a promising strategy to enhance cancer immunotherapy.
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H. 1st Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer/HCC, open-label)
...Note: Sorafenib = Onyx/Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705 UTSW: http://tinyurl.com/mwdc2ql (5 sites: 3/UTSW, Parkland-Hosp, Dallas/VA, PI=Dr. Adam Yopp)
...4-4-12 AACR'12: Dr. Adam Yopp, "promising safety profile to-date" http://tinyurl.com/7yrwqm7 (see #5591)
...Feb'12-Sep’14 10+ times: CEO Steve King hints of future ex-US partner-driven Bavi+Sorafenib/LIVER trial in Asia: http://tinyurl.com/nkaxtcc
......Articles & Data describe Liver Cancer challenges in Asian populations: http://tinyurl.com/7z7o8j9 & http://tinyurl.com/7z99cy4
...12-1-10: PPHM's 1st IST (Liver Cancer) initiated at UTSW, ~56 patients - http://tinyurl.com/3xd3e6c
…Per S.King, 5-18-10/R&R, "We've had a lot of interest in running clinical trials with the compound from investigators who have either had prior experience with the drug or would like to study the drug in various settings. Potential IST indications include all the major solid tumor types. Of particular interest is Liver Cancer, in which we have a natural tie-in with our HCV program, Ovarian Cancer and Pancreatic Cancer, also very nicely supported by the prior data."