Dr.Hutchins(VP/Preclin-Res.) speaks today at 9amET at the 10th Annual Immunotherapy & Vaccine Summit (ImVacS 2015) in Boston – in session, “Combination Immunotherapy Strategies”…
Aug 24-28 2015: “CHI’s 10th Annual Immunotherapy & Vaccine Summit”, Boston CHI = Cambridge Healthtech Institute, http://www.healthtech.com “…This year's event has been expanded to 5 days with coverage on adjuvants, vaccine & immunotherapy technologies, immunomodulatory therapeutic antibodies for cancer, combination cancer immunotherapy, and T cell target discovery. ImVacS 2015 promises to be a must-attend event for commercial and academic entities to continue advancing immunotherapies and vaccines through technology and innovation.” Event: http://www.imvacs.com/ PGM: Rational Combination Cancer Immunotherapy (1 of 6) SESSION: COMBINATION IMMUNOTHERAPY STRATEGIES 8-26-15 9-9:30 Jeff T. Hutchins, PhD, VP/Preclin-Res., Peregrine Pharmaceuticals “Expansion and Activation of T Cells via the Targeting of the Immunosuppressive Ligand Phosphatidylserine (PS): Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy” SUMMARY: The underlying cause for the failure of current therapies is the persistent and multifocal immune suppression in the tumor microenvironment that drives the absence of pre-existing antitumor T cells. Bavituximab blocks PS-mediated immunosuppression (decreasing MDSCs) by reprograming immune cells in the tumor microenvironment to enhance anticancer activity. Pre-clinical, translational, and clinical results using bavituximab with conventional and immunotherapy combinations promotes a robust, anti-tumor T cell mediated response to enhance cancer therapy. http://ir.peregrineinc.com/events.cfm
8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow …See Images of Dr. Hutchins’ 29-screen Presentation Slideshow below…
8-26-15: Peregrine Pharmaceuticals Presents Data at Annual Immunotherapy and Vaccine Summit (ImVacS) Supporting Ability of Bavituximab to Mediate Anti-Tumor T Cell Responses Across Multiple Tumor Types • Increasing Activated T Cells in Tumors Demonstrates Potential Complement to anti-PD-1 and anti-PD-L1 Checkpoint Inhibitors • Clinical and Preclinical Studies Demonstrate Estimated Survival Curves that Plateau http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928906
TUSTIN, Aug. 26, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM, PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced the presentation of a range of clinical, translational and pre-clinical study results highlighting the ability of bavituximab, Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, to promote anti-tumor T cell mediated activity in several tumor types. The data were presented today by Jeff T. Hutchins, Ph.D., VP, Preclinical Research at Peregrine Pharmaceuticals and chairperson of the Combination Immunotherapy Strategies session at the 10th Annual Immunotherapy and Vaccine Summit (ImVacS), being held August 24-28, 2015 in Boston, Massachusetts.
Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine's PS signaling pathway inhibitor candidates, including bavituximab, reverse the immunosuppressive environment that many tumors establish in order to proliferate and fight cancer by activating macrophages and cytotoxic T cells in tumors. Preclinical data demonstrate that combining the enhanced T cell anti-tumor activity of bavituximab-like antibodies with checkpoint inhibitors, such as anti-PD-1 antibodies, results in significantly improved tumor control in multiple models of cancer.
Dr. Hutchins' presentation highlighted key findings from several recent bavituximab-focused studies including: • The potential of bavituximab to shift the tumor microenvironment from immuno-suppressive in which tumors evade immune detection to a state of immune activation in which the immune system recognizes and fights the tumor. Presented findings demonstrate that bavituximab-like antibodies significantly increase the prevalence of tumor infiltrating CD8+ T-cells and immune-activating cytokines, while decreasing macrophages and myeloid cells that allow the tumor to evade immune detection. This elucidation and confirmation of bavituximab's mechanism of action highlights the potential of bavituximab to enhance the anti-tumor effects of both chemotherapy and immune checkpoint inhibitors.
• Bavituximab increases the number of activated CD8+ cells in the tumor, which stimulates PD-1 expression, thereby upregulating the target for checkpoint inhibitors such as anti-PD-1 and anti-PD-L1. Importantly, translational study data across multiple cancers indicated that tumors with low PD-L1 or PD-1 expression on tumor infiltrating T cells showed promising signs of immune activation after treatment with bavituximab. This suggests the potential for bavituximab to activate a tumor specific immune response in patients with PD-L1 negative tumors that generally do not respond as well to PD-1 and PD-L1 inhibitors. By doing so, it is believed that bavituximab may hold potential to increase the number of patients able to respond to PD-1 and PD-L1 targeting immunotherapies. Furthermore, the combination of bavituximab-like antibodies and anti-PD-1 antibodies resulted in enhanced, synergistic anti-tumor activity in animal models of multiple tumor types, as compared to either agent alone. In some cases, complete tumor regressions were achieved, highlighting the anti-tumor potential of bavituximab in combination with checkpoint inhibitors such as anti-PD-1 antibodies.
• Results from several clinical and preclinical studies in a range of tumor types show that bavituximab and bavituximab-like antibodies, in combination with conventional therapy, have consistently demonstrated estimated survival curves that plateau.
"We continue to generate a broad collection of pre-clinical, translational and clinical data highlighting bavituximab's novel mechanism of action and synergistic activity for a range of combination treatments. These study results, particularly as they relate to the potential synergies between bavituximab and checkpoint inhibitors, create great excitement for us as we begin work with our new collaborators at Memorial Sloan Kettering Cancer Center and AstraZeneca, while continuing our long-standing relationship with the University of Texas Southwestern Medical Center where this technology was originally developed," said Dr. Hutchins. "By aligning with these world leaders in cancer immunotherapy to study novel immuno-oncology combination therapies, we are best positioning ourselves to maximize the potential role that bavituximab can play in this new era of innovative cancer treatments."
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to alter this immunosuppressive signal and sends an immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in anti-tumor immune responses.
ABOUT PEREGRINE PHARMACEUTICALS, INC. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment 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. 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. For more information, please visit http://www.peregrineinc.com . Safe Harbor *snip* Contacts: • Jay Carlson, Peregrine Pharmaceuticals, Inc., (800) 987-8256, info@peregrineinc.com • Stephanie Diaz (Investors), Vida Strategic Partners, 415-675-7401, sdiaz@vidasp.com • Tim Brons (Media), Vida Strategic Partners, 415-675-7402, tbrons@vidasp.com
= = = = = = = = = = = = = = = = = = = 8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors” http://tinyurl.com/owlxpsf Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor. …AZN’s Head/I-O(Robert Iannone): “Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers." Durvalumab (MEDI4736, anti-PD-L1) has a Net Present Value of $6.5B…
7-14-15 Qtly. Conf. Call (King/Shan/Hutchins/Lytle) Transcript http://tinyurl.com/nw2v5u6 ...CEO S.King: “We recently entered into collaboration with investigators at Memorial Sloan Kettering Cancer Ctr to continue expanding on this important work, as well as to explore other potential applications of bavituximab and other agents that target PS-signaling pathway.” 5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/qxu4w2x
= = = = = = = = = = = = = = = SCIENCE: "Evolution has favored pathogenesis that resembles apoptosis." Dr. Judah Folkman: ”This [Thorpe’s VTA research] is very promising and very elegant work... The whole goal is really 2-part, reducing the harsh side effects of cancer treatment, and reducing the chance that some cancer cells will evade treatment. That would be a big step in the next decade, and anti-vascular therapy will play a major role." (’97 & ’02 http://tinyurl.com/k5qe96g & http://tinyurl.com/n6vh9hp ) Peregrine's Bavituximab Clinical Trials website: http://PeregrineTrials.com BAVITUXIMAB MOA & CLINICAL DATA: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html ...Bavi Publications: http://www.peregrineinc.com/publications/publications.html ...Bavi Posters & Presentations: http://www.peregrineinc.com/publications/posters-and-presentations.html Bavi MOA: Video (3:34) added ~3-2014 http://vimeo.com/87116642 "Bavituximab: A Novel Immunotherapy Candidate Targeting an Upstream Immune Checkpoint to Fight Cancer" Bavi MOA: Video (1:33) on Bavi’s Immunotherapeutic MOA added to Youtube on 3-27-14 https://www.youtube.com/watch?v=Esewl35JD8s 5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7 BAVI MOA 2-9-15: PPHM/VP Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6 BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h BAVI MOA 8-28-14: Italy’s Dr. Federico Cappuzzo, Bavi/NSCLC profile article (DovePress OpenAccess, 7pgs) - http://tinyurl.com/n3oa7bc BAVI MOA 8-11-14: PPHM/VP Dr. Jeff Hutchins’ presentation at ImVacS "Immunotherapies & Vaccine Summit", Boston - PR: http://tinyurl.com/lpjy3u7 ; PDF(31 Slides): http://tinyurl.com/oueldme ...MLV’s Dr. George Zavoico’s 8-27-14 report on Dr. Jeff Hutchins’ 8-11-14 ImVacS/Boston Bavi MOA presentation: http://tinyurl.com/l3tw63c BAVI MOA 5-28-14: Dr. Rolf Brekken’s 47min CRI “Cancer Immunotherapy” webinar about Bavituximab as an Upstream/Global Immune Checkpoint Inhibitor – REPLAY: http://tinyurl.com/lxgftyx . . .CRI=Cancer Research Institute (NYC – Supported by BMS): http://www.cancerresearch.org - Facebook: http://tinyurl.com/pbmhb2z , https://twitter.com/CancerResearch . . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org . . .8-12-14: CRI adds Youtube links to the 5-28-14 CRI Immunotherapy webinar, incl. Dr. Brekken's talk "about Bavi and how it works against lung, liver, and other kinds of cancers" http://tinyurl.com/ps5h6h8 BAVI MOA 3-25-14: Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk (45 Slides) . . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade” (the 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken) 12-10-13: With recent scientific insights highlighting bavi’s immunostimulatory moa, these additions to PPHM’s SAB: Dimitry Gabrilovich, Scott Antonia, David Carbone**, Hakan Mellstedt http://tinyurl.com/mw776mk ......**A/o 9-2014, Dr. David Carbone (PPHM SAB/KOL) is President-Elect of IASLC https://www.iaslc.org/about-us/board BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5 ...“We are actively working towards initiating a clinical trial in the coming months to further investigate the potential synergistic effects of bavituximab and an approved [anti-CTLA-4] immunotherapy in patients with Melanoma." 10-28-13 IASLC/Sydney: “Immune Checkpoints in the Tumor Environment: Novel Targets & the Clinical Promise of Combined Immunotherapies” http://tinyurl.com/mjaweu5 …Symposium speakers: Scott J. Antonia/MD-PhD(H.Lee Moffitt CC), Dmitry I. Gabrilovich/MD-PhD(Wistar Inst), Rolf A. Brekken/PhD(UTSW), David E. Gerber/MD(UTSW) BAVI MOA: 8-19-13 Data Supporting Bavituximab’s Immunotherapy MOA Published in “Cancer Immunology Research” (AACR) - http://tinyurl.com/mhjftka (PDF) …“PS-Targeting Antibody Induces M1 Macrophage Polarization & Promotes Myeloid-Derived Suppressor Cell Differentiation” (Thorpe etal) BAVI MOA: 8-13-13 PPHM/VP Dr. Jeff Hutchins’ Presentation on the Downstream Immunostimulatory Effects/Moa of PS-targeting antibodies (like Bavi) at CHI’s “Immunotherapies Congress”/Boston http://tinyurl.com/m6h2tvt BAVI MOA: 10-12-12 NMB article on how Bavi "Induces Innate & Specific Anti-tumor Responses" http://tinyurl.com/cw9odb8 BAVI MOA: 5-1-12 Dr. Phil Thorpe's 46min talk at NYAS PS-Targeting Symposium http://tinyurl.com/9792gl5 . . .Symposium title: "Phosphatidylserine (PS) Asymmetry - Therapeutic Apps. in Cancer & Infectious Disease Symposium" . . .Replays of 5 speakers: Alan Schroit, Chris Reutlingsperger, David Ucker, Ari Helenius, Philip Thorpe
= = = = = = = = = = = = = = = = = 8-26-15: Jeff T. Hutchins (VP/Preclin-Res., Peregrine) - ImVacS 2015, Boston (Session: Combination Immunotherapy Strategies) Aug 24-28 2015: “CHI’s 10th Annual Immunotherapy & Vaccine Summit (ImVacS ’15)”, Boston CHI = Cambridge Healthtech Institute, http://www.healthtech.com “…This year's event has been expanded to 5 days with coverage on adjuvants, vaccine & immunotherapy technologies, immunomodulatory therapeutic antibodies for cancer, combination cancer immunotherapy, and T cell target discovery. ImVacS 2015 promises to be a must-attend event for commercial and academic entities to continue advancing immunotherapies and vaccines through technology and innovation.” Event: http://www.imvacs.com/ PGM: Rational Combination Cancer Immunotherapy (1 of 6) SESSION: COMBINATION IMMUNOTHERAPY STRATEGIES 8-26-15 9-9:30 Jeff T. Hutchins, PhD, VP/Preclin-Res., Peregrine Pharmaceuticals “Expansion and Activation of T Cells via the Targeting of the Immunosuppressive Ligand Phosphatidylserine (PS): Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy” SUMMARY: The underlying cause for the failure of current therapies is the persistent and multifocal immune suppression in the tumor microenvironment that drives the absence of pre-existing antitumor T cells. Bavituximab blocks PS-mediated immunosuppression (decreasing MDSCs) by reprograming immune cells in the tumor microenvironment to enhance anticancer activity. Pre-clinical, translational, and clinical results using bavituximab with conventional and immunotherapy combinations promotes a robust, anti-tumor T cell mediated response to enhance cancer therapy. http://ir.peregrineinc.com/events.cfm
SUNRISE at UTSW, “with lung cancer medical oncologist Dr. David Gerber leading the charge.” Goggle says updated 2 days ago, but my guess is the Bavi/Gerber ref. (the only example given) was already there…
UT SOUTHWESTERN MEDICAL CENTER – PATIENT CARE http://www.utswmedicine.org/cancer/programs/lung/ LUNG CANCER Lung cancer, the leading cause of cancer deaths in men & women in the United States, often grows silently without causing symptoms. This can be scary for those at high risk for the disease, such as smokers, but there’s reason for hope. Treatments are improving, and some lung cancer patients are living longer with the development of new drugs, early detection methods, and innovative techniques in surgery and radiation – all happening right here at UTSW Harold C. Simmons Comprehensive Cancer Center. UTSW-MC – the only National Cancer Institute (NCI)-designated cancer center in North Texas – is the place to go in North Texas for the diagnosis and treatment of lung cancer.
PIONEERING DRUG TREATMENTS UT Southwestern is a leader in new drug development for lung cancer, and through clinical trials our patients can gain access to treatments not available elsewhere. For example, bavituximab, an immunotherapeutic antibody developed by UT Southwestern researchers, is now being evaluated in a Phase III clinical trial [ http://www.utsouthwestern.edu/research/fact/detail.html?studyid=STU%20102013-077 ] for the treatment of NSCLC, with lung cancer medical oncologist David Gerber, M.D., leading the charge. [ http://profiles.utsouthwestern.edu/profile/53487/david-gerber.html ] In addition, our patients get special access to nationwide group trials for lung cancer because of an NCI grant given to only 30 research institutions in the U.S. …
Scott Antonia’s (Moffitt CC) 9-8-15 IASLC’15 Mini-Oral Presentation Slideshow (9pgs: Bavi Lung Translational Data) now on PeregrineInc.com, as is UTSW’s Dr. David Gerber’s poster overviewing the ongoing Ph.3 Bavi+Doce 2L/NSCLC “SUNRISE” trial – see below… (recall, UTSW’s Dr. Rolf Brekken gives an Oral Pres. tomorrow, Sept9, discussing, “previously announced study findings demonstrating that a combination of bavituximab and an anti-PD-1 antibody was more effective at reducing tumor burden in preclinical lung cancer models than either treatment alone.”)
Sept6-9 2015: “IASLC’s 16th World Conf. on Lung Cancer”, Denver http://wclc2015.iaslc.org/ “The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies. More than 7,000 delegates come from more than 100 countries to discuss the latest developments in thoracic malignancy research. Attendees include surgeons, medical oncologists, radiation oncologists, pulmonologists, radiologists, pathologists, epidemiologists, basic research scientists, nurses, allied health professionals, advocates, and patients.” http://www.iaslc.org/events/16th-world-conference-lung-cancer 2015 Exhibitor: Peregrine Pharm. (1 of 39) - booth #1724 (adjacent to Abbvie) - - - - - - - - - - - - - - - - - - - - - - - WCLC 2015 Track: Treatment of Advanced Diseases - NSCLC 9/7/15 9:30am-5:00pm, Exhibit Hall (Hall B+C) POSTER #P1.01-075: “Phase III, Randomized, Double-Blind Trial of Bavituximab Plus Docetaxel in Previously Treated Stage IIIb/IV Non-Squamous NSCLC (SUNRISE) (ID 1581) David R. Spigel, Joseph Shan, Alberto Chiappori, Ulrich Keilholz, Martin Reck, Martin Edelman, Manuel Domine, Keunchil Park, Tae Won Jang, Wu-Chou Su, Rachel E. Sanborn, Leora Horn, Rebecca Heist, Paul Mainwaring, David E. Gerber (UTSW) ABSTRACT… BACKGROUND: Exposed phosphatidylserine (PS) in the tumor microenvironment is highly immunosuppressive. PS binding to PS receptors on myeloid derived suppressor cells (MDSC) and M2 macrophages leads to production of anti-inflammatory cytokines such as TGF-B and IL-10. Bavituximab, a first-in-class PS-targeting monoclonal antibody, counters these effects, resulting in production of pro-inflammatory cytokines such as TNF-a and IL-12, maturation of dendritic cells and induction of tumor specific cytotoxic T lymphocyte (CTL) immunity. Docetaxel has also been shown to suppress MDSCs while increasing tumor antigens and T-cell mediated cytotoxicity, thereby enhancing bavituximab’s immunomodulatory effects. In a prior double-blind Phase II trial in 2nd line non-squamous NSCLC, bavituximab 3 mg/kg + docetaxel was well-tolerated and demonstrated 60% improvement (11.7 vs 7.3 mos) in median overall survival (OS) compared to control. METHODS: SUNRISE is a Phase III, double-blind trial where patients with previously treated Stage IIIb/IV non-squamous, non-small cell lung cancer are randomized in a 1:1 ratio to receive up to six 21-day cycles of docetaxel in combination with either weekly 3 mg/kg bavituximab or placebo, followed by maintenance with weekly bavituximab or placebo until progression or toxicity. Patients will be stratified by region (North America, Europe, or Rest of World), disease stage (IIIb or IV), and previous maintenance/targeted therapy (yes or no). This trial was initiated in Dec.2013 and accrual of 582 patients across 160+ sites in 14 countries is planned over 24 months. The primary endpoint is OS and 2 interim analyses are planned. Secondary endpoints include progression-free survival (PFS), overall response rate (ORR) and safety. Radiographic tumor response is centrally assessed every 2 cycles during combination therapy and every nine weeks during maintenance. Exploratory analysis will include the assessment of changes in circulating immune cells and cytokines to better understand the immunotherapeutic mechanism. RESULTS: Trial in progress CONCLUSION: Trial in progress POSTER: http://www.peregrineinc.com/images/stories/pdfs/iaslc_2015_sunrise.pdf From Peregrine’s 9-8-15 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=930479 "A large and growing body of research continues to support our belief that, as a fundamental checkpoint inhibitor, bavituximab may have the potential to broadly enhance the therapeutic activity of a range of cancer treatments including chemotherapy, radiation and immunotherapies. These latest data being presented at the World Conference on Lung Cancer specifically highlight this synergistic potential in the area of checkpoint inhibitors by clearly illustrating the manner in which bavituximab is able to induce the appropriate immune responses required for a successful therapeutic response to anti-PD-1 & anti-PD-L1 agents," said Steven W. King, President and CEO of Peregrine. "We look forward to continuing our investigation of bavituximab in combination with other immuno-oncology agents through our ongoing collaborations with AstraZeneca, the Memorial Sloan Kettering Cancer Center and UT Southwestern."
- - - - - - - - - - - - - - - - - - - - - - - WCLC 2015 Track: MINI ORAL #14 - Pre-Clinical Therapy (ID 119) Moderators: Lynnette Fernandez-Cuesta Adi F. Gazdar 9/8/15, 10:45am-12:15pm, Mile High Ballroom 2c-3c MINI-ORAL #14.07: “Bavituximab Activates CD8+ TILs in a 3D Ex Vivo System of Lung Cancer Patients Derived Tumors With Negative PD-L1 Expression” Soner Altiok, Melanie Mediavilla Valera, Jenny Kreahling, Nikoletta L. Kallinteris, David Noyes, Tiffany N. Razabdouski, Joseph Shan, Jeff Hutchins, Kerstin Menander, Scott J. Antonia (Moffitt CC) ABSTRACT… BACKGROUND: Bavituximab is a chimeric monoclonal antibody that targets the membrane phospholipid phosphatidylserine (PS) exposed on endothelial cells and cancer cells in solid tumors. Bavituximab blocks PS-mediated immune suppression and activates cytotoxic T lymphocyte anti-tumor responses. METHODS: Tissues from consented patients with adenocarcinoma of the lung were extracted at the time of surgical resection and disaggregated to characterize expression of immune checkpoint proteins such as PD-1, CTLA-4, LAG3, TIM3, BTLA and adenosine A2A receptor on both CD4+ and CD8+ tumor infiltrating cells by flow cytometry (FACS) and stained for PD-L1, CD68, and CD163 via immunohistochemistry (IHC). 3D tumor microspheres were prepared and treated ex vivo with an IgG control, F(ab)’2 version of bavituximab, bavituximab, docetaxel, anti-PD-1 or PD-L1 and combinations of bavituximab, anti-PD-1 or PD-L1 and docetaxel for 36 hours within an intact tumor microenvironment. A multiplex human cytokine assay was used to simultaneously analyze the differential secretion of cytokines. Additionally, a NanoString platform containing probes to quantitate 770 immune function genes was used to determine potential positive or negative associations between expression of immune function genes and TIL activation by treatment. In a few cases, the expanded TILs were tested in PDX models using the consented patient’s tumor. RESULTS: Bavituximab induces activation of TILs in 3D ex vivo tumor microsphere models of lung cancer, as demonstrated by a significant increase in IFN-y, TNF-a, and GM-CSF secretion. FACS, IHC, and NanoString gene function analysis read out assays revealed that this effect was associated with low PD-1 expression on CD8+ cells, negative PD-L1 expression in the stating biopsy tissue, and a conversion of the M2 to M1 macrophage phenotype. CONCLUSION: These data support the use of bavituximab as an immunomodulatory treatment in adenocarcinoma of the lung by enhancing the activation of CD8+ TIL derived from patients' tumors with negative PD-L1 expression; correlating with increased cytokine production by lymphoid cells and repolarization of myeloid cells from an immunosuppressive to an immune active state. SLIDESHOW (9 pgs.): http://www.peregrineinc.com/images/stories/pdfs/iaslc_2015_altiok.pdf From Peregrine’s 9-8-15 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=930479 ”For the study presented at the WCLC, researchers from Nilogen Oncosystems [<=Moffitt Startup: http://otmc.moffitt.org/startups.aspx ] and the H. Lee Moffitt Cancer Center, in collaboration with Peregrine, evaluated immune changes in 3D tumor microspheres generated from human NSCLC fresh tumors extracted at the time of surgery. These were tumor microspheres were treated with bavituximab alone, docetaxel alone, a combination of bavituximab and docetaxel, and a control. Bavituximab, alone and in combination with docetaxel, induced activation of tumor infiltrating lymphocytes as demonstrated by a statistically significant increase in key immune-stimulating cytokines such as IFN-y, TNF-a, and GM-CSF with a corresponding decrease in secretion of the immunosuppressive cytokine IL-10. Importantly, the bavituximab-affected immune response activity appeared to correlate with low PD-L1 expression on the tumor samples. "These new translational data suggest that bavituximab has the potential to activate a tumor specific immune response in patients with PD-L1 negative tumors that generally do not respond as well to immune checkpoint inhibitors. By doing so, it is believed that bavituximab may hold potential to increase the number of patients able to respond to PD-1 & PD-L1 targeting immunotherapies," said Jeff Hutchins, VP, Preclinical Dev. of Peregrine. "These findings continue to expand our collection of translational data supporting the mechanism of action for bavituximab and corroborate our wide range of previously published preclinical study results. Taken together, these data provide us with growing confidence for our bavituximab development programs, including the ongoing Phase III SUNRISE clinical trial in NSCLC which is evaluating the same treatment combination used in these studies."
- - - - - - - - - - - - - - - - - - - - - - - WCLC 2015 Track: ORAL #41 - Immune Biology, Microenvironment & Novel Targets (ID 159) Moderators: Sukhmani K. Padda, Raphael Nemenoff 9/9/15, 6:30-8:00pm, Four Seasons Ballroom F1+F2 ORAL #41.05: “Targeting Phosphatidylserine-Mediated Immune Suppression Enhances the Efficacy of Immune Checkpoint Blockade in Pre-Clinical Tumor Models” Rolf A. Brekken (UTSW), Bruce Freimark, Jian Gong, Carrie Baldwin, Van Nguyen, Michael Gray, Shen Yin, Jeff Hutchins, Alan Schroit, Xianming Huang (UTSW) ABSTRACT… BACKGROUND: Despite substantial progress, only a subset of cancer patients benefit from blockade of the PD-1 immune checkpoint. Multifocal immune suppression in the tumor microenvironment is the underlying cause for the limited efficacy of immune checkpoint blockade. Persistent immune suppression prevents the development of a robust T cell response to tumor specific antigens that is required for effective downstream immune checkpoint blockade. An underappreciated but significant contributor to immune suppression in tumors is the expression of the membrane phospholipid phosphatidylserine (PS) on the surface of tumor cells and tumor-derived microvesicles. PS is recognized by receptors on immune cells where it triggers the secretion of immune suppressive cytokines, prevents the differentiation of myeloid-derived suppressor cells (MDSCs) and inhibits dendritic cell (DC) maturation; events that prevent a productive anti-tumor T cell response. Bavituximab, a chimeric monoclonal antibody that targets PS and inhibits PS-mediated immunosuppressive signaling, drives immune activation by reducing the levels of MDSCs, by polarizing tumor-associated macrophages towards an M1 phenotype and by promoting the maturation of dendritic cells (DCs). METHODS: The efficacy of bavituximab, anti-PD-1 and combination therapy was evaluated in multiple syngeneic, pre-clinical tumor models. Treatment efficacy was determined by inhibition of tumor growth and by immunophenotyping of spleen and tumor infiltrating leukocytes. RESULTS: The combination of antibody-mediated PS and PD-1 blockade was significantly more effective in reducing tumor burden and promoting immune activation than single agent therapy. Combination therapy increased tumor infiltration of effector T-cells (Teff), increased the Teff:T regulatory cell ratio in the tumor and enhanced Teff function as determined by IFN-y, TNFa and granzyme B levels associated with Teff cells in the spleen and tumor. Furthermore combined blockade of PS and PD-1 signaling reduced the level of immune suppressive cells (e.g., MDSCs, M2 macrophages, and Treg) in the tumor microenvironment. CONCLUSION: These results raise the possibility that PS blockade with bavituximab can enhance the efficacy of anti-PD-1 therapy even in patients with tumors that are unresponsive to single agent immune checkpoint therapy.
= = = = = • RECALL: PPHM KOL/SAB Dr. David Carbone becomes President of IASLC 9-9-15 ( https://www.iaslc.org/about-us/board ). “…I also personally find it rewarding to participate in the global fight against cancer, and am honored to have been elected President of the IASLC, eff. Sept. 9, 2015." http://www.supportohiostate.org/site/TR?px=1009121&fr_id=1151&pg=personal • IASLC Faculty & Staff Disclosures: Heather A. Wakelee, MD - Grant/Research Support: Genentech/Roche, Lilly, Pfizer, Novartis, Exelixis, Xcovery, AstraZeneca, Clovis, Regeneron; Consultant: Peregrine. http://www.gotoper.com/conferences/ilc/meetings/15th-international-lung-cancer-congress “Associate Prof. of Medicine, Div. of Oncology; Faculty Director, Cancer Clinical Trials Office; Co-leader, Lung Cancer Disease Mgt Group, Stanford Univ. School of Medicine, Stanford CA”
= = = = = = = BAVI MOA 8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow http://tinyurl.com/qz64pzg …“Expansion & Activation of T Cells via the Targeting of the Immunosuppressive Ligand PS: Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy” 5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7 BAVI MOA 2-9-15: PPHM/VP Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6 BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h BAVI MOA 8-28-14: Italy’s Dr. Federico Cappuzzo, Bavi/NSCLC profile article (DovePress OpenAccess, 7pgs) - http://tinyurl.com/n3oa7bc BAVI MOA 8-11-14: PPHM/VP Dr. Jeff Hutchins’ presentation at ImVacS "Immunotherapies & Vaccine Summit", Boston - PR: http://tinyurl.com/lpjy3u7 ; PDF(31 Slides): http://tinyurl.com/oueldme ...MLV’s Dr. George Zavoico’s 8-27-14 report on Dr. Jeff Hutchins’ 8-11-14 ImVacS/Boston Bavi MOA presentation: http://tinyurl.com/l3tw63c BAVI MOA 5-28-14: Dr. Rolf Brekken’s 47min CRI “Cancer Immunotherapy” webinar about Bavituximab as an Upstream/Global Immune Checkpoint Inhibitor – REPLAY: http://tinyurl.com/lxgftyx . . .CRI=Cancer Research Institute (NYC – Supported by BMS): http://www.cancerresearch.org - Facebook: http://tinyurl.com/pbmhb2z , https://twitter.com/CancerResearch . . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org . . .8-12-14: CRI adds Youtube links to the 5-28-14 CRI Immunotherapy webinar, incl. Dr. Brekken's talk "about Bavi and how it works against lung, liver, and other kinds of cancers" http://tinyurl.com/ps5h6h8 BAVI MOA 3-25-14: Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk (45 Slides) . . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade” (the 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken) 12-10-13: With recent scientific insights highlighting bavi’s immunostimulatory moa, these additions to PPHM’s SAB: Dimitry Gabrilovich, Scott Antonia, David Carbone**, Hakan Mellstedt http://tinyurl.com/mw776mk ......**A/o 9-2014, Dr. David Carbone (PPHM SAB/KOL) is President-Elect of IASLC https://www.iaslc.org/about-us/board BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq
Lisa Stepp (PhD/MBA) joined Peregrine 3-2015 as “Sr. Dir./Medical Affairs” - formerly with Gilead, Allos, Genentech, and Wyeth. Here is a summary of her 2 known upcoming presentations (thx BioPh & BamB)...
Sep30-Oct2 2015: “EXL's 17th Medical Science Liaison Best Practices Congress”, SanDiego “Medical Science Liaisons (MSLs) are a vital part of medical affairs teams and, depending on the size of their company, have many interchangeable functions with other medical affairs professionals. Their main role is to support the dissemination of information to key opinion leaders (KOLs) in a way that not only answers essential medical questions but also strengthens product placement and regulatory compliance.” http://exlevents.com/17th-medical-science-liaison-best-practices-congress EXL Events: http://exlevents.com/about-us Agenda: http://exlevents.com/17th-medical-science-liaison-best-practices-congress/agenda Oct2 8:45–9am: CHAIRPERSON’S RECAP OF DAY2 - Lisa Stepp, Sr. Dir./Medical Affairs, Peregrine Pharmaceuticals Oct2 9-9:45am: “Strategic MSL Leadership to Improve Operations & Achieve Higher Retention of MSL Teams” - Lisa Stepp, PhD, MBA, Sr. Dir./Medical Affairs, Peregrine Pharmaceuticals, Inc. Oct2 3-3:45pm CLOSING REMARKS - Lisa Stepp, Sr. Dir./Medical Affairs, Peregrine Pharmaceuticals, Inc. Faculty(Lisa Stepp, 1 of 18): http://exlevents.com/17th-medical-science-liaison-best-practices-congress/faculty
Oct7 2015: “Perkin Elmer's Annual Imaging User Group Meeting”, Hopkinton MA http://go.perkinelmer.com/ImagingUserGroupMeetingTSC2015 Track: “Tissue Imaging – Quantitative Pathology Solutions” Oct7 9:30-12pm Presentation(1 of 6): Using Technology to Inform Clinical Trial Design, Lisa Stepp, PhD, Sr.Dir./Medical Affairs, Peregrine Pharmaceuticals
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine.
As part of the Phase II bavituximab and durvalumab combination trial, patients will be evaluated retrospectively for the correlation between their PD-L1 levels and clinical outcomes. This new study builds on the non-exclusive collaboration initiated between the companies in August 2015 [8-24-15: http://tinyurl.com/owlxpsf ] to conduct a Phase I/Ib basket clinical trial evaluating the combination of bavituximab and durvalumab with chemotherapy in multiple solid tumors.
Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment. In pre-clinical and translational clinical studies, the treatment increases activated T-cells in tumors and fights cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate. Durvalumab is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.
"In the short period of time that we have been working with AstraZeneca, we have been very impressed with the company's commitment to innovative translational efforts that will help us better understand the dynamics of tumor immunity and clinical response to durvalumab and bavituximab combination in a range of cancers," said Joseph Shan, MPH, VP, Clinical and Regulatory Affairs of Peregrine. "We expect this extension of our collaboration with AstraZeneca will allow us to run a much more cost-effective and time-efficient trial than would have been possible under our previously planned study using Opdivo as the combination drug in the same lung cancer population. This Phase II study offers several key advantages including a supply of durvalumab that will enable us to conduct a global trial that can enroll patients more rapidly. In addition, the expanded collaboration provides for a more cohesive clinical program utilizing the same PD-L1 and other biomarker analysis across both the new Phase II trial and the already planned Phase I/Ib study combining durvalumab and bavituximab in multiple indications."
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736) Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
ABOUT PEREGRINE PHARMACEUTICALS, INC. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment 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. 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. For more information, please visit http://www.peregrineinc.com .
ABOUT ASTRAZENECA AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: http://www.astrazeneca.com . Safe Harbor snip Contacts: Jay Carlson Peregrine Pharmaceuticals, Inc. (800) 987-8256 info@peregrineinc.com Stephanie Diaz (Investors) Vida Strategic Partners 415-675-7401 sdiaz@vidasp.com Tim Brons (Media) Vida Strategic Partners 415-675-7402 tbrons@vidasp.com
= = = = = = = = = = = = = = = = = = = = = = 8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”… Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor. AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
= = = = = = = = = = = = = = 8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial • Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736 http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488 TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
Peregrine and AstraZeneca will collaborate on a non-exclusive basis, to evaluate the combination of bavituximab and durvalumab with chemotherapy as a potential treatment in various solid tumors. The Phase I part of the trial is expected to establish a recommended dose regimen for the combination and the Phase Ib part of the trial will assess the safety and efficacy of the investigational combination. Under the terms of the agreement, the initial trial will be conducted by Peregrine.
Robert Iannone, Head of Immuno-Oncology, Global Medicines Development, at AstraZeneca said, "We believe that combination therapy in immuno-oncology has the potential to be a novel and highly effective approach to treating cancer. Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment. The treatment increases activated T-cells in tumors and fights cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate. MEDI4736 is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.
”Data generated to date have shown significant potential for combining bavituximab with agents targeting the PD-1/PDL-1 pathway and we're excited to further explore this approach in studies with AstraZeneca's durvalumab," said Steven W. King, President and CEO of Peregrine. "AstraZeneca is a recognized leader in the immuno-oncology field and this collaboration will play a key role as we continue to fully explore the potential of bavituximab in combination immunotherapies for a variety of clinical applications."
ABOUT BAVITUXIMAB: A Targeted Investigational Immunotherapy Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736) MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumor's immune-evading tactics. MEDI4736 is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
ABOUT PEREGRINE PHARMACEUTICALS, INC. *snip*
ABOUT ASTRAZENECA IN ONCOLOGY? Oncology is a therapeutic area in which AstraZeneca has a deep-rooted heritage. It will be potentially transformational for the company's future, becoming the sixth growth platform. Our vision is to help patients by redefining the cancer treatment paradigm and one day eliminate cancer as a cause of death. By 2020, we are aiming to bring six new cancer medicines to patients. Our broad pipeline of next-generation medicines is focused on four main disease areas - ovarian, lung, breast and haematological cancers. These are being targeted through four key platforms - immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.
ABOUT ASTRAZENECA *snip*
= = = = = = = = = = = = = = = = = = = Durvalumab (MEDI4736, anti-PD-L1) has a Net Present Value of $6.5B.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
= = = = = = = = = = = = = = = SCIENCE: "Evolution has favored pathogenesis that resembles apoptosis." Dr. Judah Folkman: ”This [Thorpe’s VTA research] is very promising and very elegant work... The whole goal is really 2-part, reducing the harsh side effects of cancer treatment, and reducing the chance that some cancer cells will evade treatment. That would be a big step in the next decade, and anti-vascular therapy will play a major role." (’97 & ’02 http://tinyurl.com/k5qe96g & http://tinyurl.com/n6vh9hp ) Peregrine's Bavituximab Clinical Trials website: http://PeregrineTrials.com BAVITUXIMAB MOA & CLINICAL DATA: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html ...Bavi Publications: http://www.peregrineinc.com/publications/publications.html ...Bavi Posters & Presentations: http://www.peregrineinc.com/publications/posters-and-presentations.html Bavi MOA: Video (3:34) added ~3-2014 http://vimeo.com/87116642 "Bavituximab: A Novel Immunotherapy Candidate Targeting an Upstream Immune Checkpoint to Fight Cancer" Bavi MOA: Video (1:33) on Bavi’s Immunotherapeutic MOA added to Youtube on 3-27-14 https://www.youtube.com/watch?v=Esewl35JD8s BAVI MOA 8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow http://tinyurl.com/qz64pzg …“Expansion & Activation of T Cells via the Targeting of the Immunosuppressive Ligand PS: Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy” 5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7 BAVI MOA 2-9-15: PPHM/VP Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6 BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h BAVI MOA 8-28-14: Italy’s Dr. Federico Cappuzzo, Bavi/NSCLC profile article (DovePress OpenAccess, 7pgs) - http://tinyurl.com/n3oa7bc BAVI MOA 8-11-14: PPHM/VP Dr. Jeff Hutchins’ presentation at ImVacS "Immunotherapies & Vaccine Summit", Boston - PR: http://tinyurl.com/lpjy3u7 ; PDF(31 Slides): http://tinyurl.com/oueldme ...MLV’s Dr. George Zavoico’s 8-27-14 report on Dr. Jeff Hutchins’ 8-11-14 ImVacS/Boston Bavi MOA presentation: http://tinyurl.com/l3tw63c BAVI MOA 5-28-14: Dr. Rolf Brekken’s 47min CRI “Cancer Immunotherapy” webinar about Bavituximab as an Upstream/Global Immune Checkpoint Inhibitor – REPLAY: http://tinyurl.com/lxgftyx . . .CRI=Cancer Research Institute (NYC – Supported by BMS): http://www.cancerresearch.org - Facebook: http://tinyurl.com/pbmhb2z , https://twitter.com/CancerResearch . . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org . . .8-12-14: CRI adds Youtube links to the 5-28-14 CRI Immunotherapy webinar, incl. Dr. Brekken's talk "about Bavi and how it works against lung, liver, and other kinds of cancers" http://tinyurl.com/ps5h6h8 BAVI MOA 3-25-14: Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk (45 Slides) . . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade” (the 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken) 12-10-13: With recent scientific insights highlighting bavi’s immunostimulatory moa, these additions to PPHM’s SAB: Dimitry Gabrilovich, Scott Antonia, David Carbone**, Hakan Mellstedt http://tinyurl.com/mw776mk ......**A/o 9-2014, Dr. David Carbone (PPHM SAB/KOL) is President-Elect of IASLC https://www.iaslc.org/about-us/board BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5 ...“We are actively working towards initiating a clinical trial in the coming months to further investigate the potential synergistic effects of bavituximab and an approved [anti-CTLA-4] immunotherapy in patients with Melanoma." 10-28-13 IASLC/Sydney: “Immune Checkpoints in the Tumor Environment: Novel Targets & the Clinical Promise of Combined Immunotherapies” http://tinyurl.com/mjaweu5 …Symposium speakers: Scott J. Antonia/MD-PhD(H.Lee Moffitt CC), Dmitry I. Gabrilovich/MD-PhD(Wistar Inst), Rolf A. Brekken/PhD(UTSW), David E. Gerber/MD(UTSW) BAVI MOA: 8-19-13 Data Supporting Bavituximab’s Immunotherapy MOA Published in “Cancer Immunology Research” (AACR) - http://tinyurl.com/mhjftka (PDF) …“PS-Targeting Antibody Induces M1 Macrophage Polarization & Promotes Myeloid-Derived Suppressor Cell Differentiation” (Thorpe etal) BAVI MOA: 8-13-13 PPHM/VP Dr. Jeff Hutchins’ Presentation on the Downstream Immunostimulatory Effects/Moa of PS-targeting antibodies (like Bavi) at CHI’s “Immunotherapies Congress”/Boston http://tinyurl.com/m6h2tvt BAVI MOA: 10-12-12 NMB article on how Bavi "Induces Innate & Specific Anti-tumor Responses" http://tinyurl.com/cw9odb8 BAVI MOA: 5-1-12 Dr. Phil Thorpe's 46min talk at NYAS PS-Targeting Symposium http://tinyurl.com/9792gl5 . . .Symposium title: "Phosphatidylserine (PS) Asymmetry - Therapeutic Apps. in Cancer & Infectious Disease Symposium" . . .Replays of 5 speakers: Alan Schroit, Chris Reutlingsperger, David Ucker, Ari Helenius, Philip Thorpe
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