Peregrine’s CEO S.King introduced by Jeremiah Shepard (Biotech Research Team, Credit Suisse)…
*end* . = = = = = = = = = = = = = = = = = = = = = = 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
= = = = TRANSCRIPT – 11-12-13 CEO Steve King, Credit Suisse: http://www.earningsimpact.com/Transcript/84453/PPHM/2013-Credit-Suisse-Healthcare-Conference STEVEN KING - PRESIDENT & CEO, DIRECTOR – PEREGRINE PHRAMACEUTICALS I would like to thanking the organizers for inviting us here today to give a presentation update on the company and sort of where we see short-term and long-term goals of the company coming together. So little bit about company itself so we currently have two ready for Phase III clinical programs bavituximab plus docetaxel in second-line non-small cell lung cancer. There is also another compound Cotara as a monotherapy in recurrent GBM. These are essentially unpartnered technologies and we have other partnering opportunities within our clinical and preclinical pipeline. And so, partnership opportunities are a big push for the company also we continue to advance our lead programs and bring along those pre-clinical programs. In addition, something a little bit different about the company is we did have a commercial manufacturing business called bio-services. This last fiscal year which ended April 30th we generated a little over $21 million in third part revenue and we are also guiding in that same range for this coming year. So, again this is a sustainable business which has really grown nicely over the last few years little bit about that later on the call. So really the company is all about our clinical pipeline and so as you see from the pipeline really big focus on Bavituximab is our lead clinical compound looking at the potential of this drug not just in non-small cell lung cancer we help to start our phase IIi by the end of the year but also in multiple other solid tumor indications including liver and breast cancers as well. In addition, we have an early stage imaging program based on that same targeting platform as well as Cotara which is also ready for Phase III in which we intend to initiate that Phase III study in conjunction with partnership. So, I'll spend most of the time talking about our lead compound and our lead target phosphatidylserine. So, the target for bavituximab which are the clinical compound is a molecule called phosphatidylserine which is actually present in every cell of the body. So normally phosphatidylserine is very tightly sequestered inside of cells so it's not available for binding on the outside so if you inject PS binding agency simply float around eventually clear the body through normal mechanisms. But our scientist discovered is that as solid tumors grow, the outgrow their blood supply and you end up with a unique environment which induces the exposure of PS on tumor blood vessels as well as tumor cells. What happens then when you give chemotherapy or radiation so common treatments for cancer in fact virtually anything that kills tumors is going to induce more expose of PS. The reason for that being and of the only normal circumstances in which PS becomes exposed is actually when cells die. And so obviously you give anti-cancer agents you now have cell die and more PS exposure. We then target that exposed PS with the monoclonal antibody again which we call Bavituximab and that antibody exerts anti-tumor effects. So first of all a bit about the effect of PS exposure. This is a very unique target and we are the leaders in developing compounds against this particular marker so again in normal cells there is no PS exposed. The only normal time again PS becomes exposes on apoptot cells it turns out that PS is not simply a component of the cellular membrane but actually is a signaling molecule. So, as PS becomes exposed on the outside of PS positive cells or apoptosis cells, it binds through a receptor presence on immune cells including M2 macrophages and and MDSCs or myeloid derived suppressor cells. And basically since two signals to these MDSCs one is to actually engulf and remove the dead dieing cell. The second actually is to dampen the immune response, because when cells die you do not need a robust immune response and so one of the second things that happens is it induces these MDFCs to increase expression of molecules like TGF beta IL-10 which further suppresses any additional immune responses. What our scientist have discovered is that PS in the tumor environment so in this case again we had tumor cells, tumor vessels which are expressing PS yeah the PS receptor interaction. And what happens is now inside the tumor environment where you do want a robust immune response, you're actually dampening the immune response again by inducing those MDSCs to increase levels of TGF-b and IL-10 so the body can't actually really generate a strong enough immune response.
And in fact it's been shown in multiple studies, published results that high levels of MDSCs in cancer patients are directly associated with pro prognosis of those patients again because the can't activate their system. So bavituximab works as an agent, it's injected into the blood stream, it localizes to the tumor environment again those tumor blood vessels and tumor cells. Where it does two things and this is the recent recoveries about the compound. The first is a block binding of PS to PS receptor so now you're taking away that signal so as you take away that signal you already inducing chances in immune system is interacting with the tumor. The second is because the antibody is actually made to illicit an immune response by binding to its receptor this FC portion of the antibody binding FC receptor now induces an activation of the immune system. So you are taking away the negative signal and actually now inducing an immune response. This includes a shutdown of expression of TGF beta IL-10. Expression of pro-inflammatory cytokines including IL-12 and TNF alpha. As a result we now see transformation of these MDFCs and M2 macrophages in the tumor fighting M1 macrophages with enhanced antibody dependent cytotoxicity activity. So again working with the antibody now to shutdown blood clot of the tumor. The second thing which is very important is actually causing the maturation of dendritic cells which can then present tumor antigens to cytotoxic T-cells which then also have anti-tumor effects so by simply interacting at this upstream checkpoint in the control of the immune system and activating the immune system at that point we now see these very dynamic effects taking place downstream. This is very well established data this is recently published fact in the October issue of the AACR immunotherapy journal but really the data shows that every step of this process has been validated and shown to take place again resulting in this very nice immune response at the end of the process. So, we've been advancing bavituximab in non-small cell lung cancer and our lead indication again is in second line non-small cell lung cancer. The combination partner here is docetaxel. One of the things you've always known about the drug even before even in last six which we truly understood the mechanism of action is it, this combination is very potent that is shown through in preclinical models, in early clinical results in breast cancer as well as in non-small cell lung cancer in which you've always seen a good safety profile and also very nice anti-tumor effect. And in fact in this metastatic breast cancer, clinical study we saw an overall survival almost double what's expected in that patient population and I'll go through the non-small cell lung cancer results which actually were the direct support for the phase III study that's coming on. And again we see many the reasons now we understand better of why we see these great synergic effects really are because there are so many synergies in the mechanism of action of docetaxel and Bavituximab . Docetaxel also decreases MDSC levels; again we have shown Bavituximab does the same thing. It actually creates more cellular degree for uptake by maturing dendritic cells so Bavituximab is causing the maturation of dendritic cells which can now take up these tumor antigens and present them to cytotoxic T-cells. In addition docetaxel increases the activity of the cytotoxic T-cells against the tumor. So again every step of the way we see nice synergies between bavituximab and docetaxel and making this a very, I think attractive combination for moving into advanced clinical studies. So the data that directly supported the Phase III study was from a second-line non-small cell lung cancer study. This is 121 patient double-blinded placebo-controlled. It was originally designed as a three-arm study with high dose bavituximab , low dose or placebo with docetaxel in all three arms of the study. Unfortunately when we were doing the final analysis of the study including some additional testing, we discovered that there had been some labeling issues between the 1 milligram per kilogram or low dose bavituximab and placebo arms of the study with no impact on the 3 milligram per kilogram arm so in fact we ended up just combining these two arms and what we think as a very conservative approach to analyzing the data into a single combined control arm. So, now we have a control arm that is a two to one randomization and secondly that also has active drug in it. But even without, we think the results are very pronounced with good improvements in overall tumor response rates and good trends and progression free survival but really mean overall survival being the key endpoint here because that becomes the basis for the Phase 3 study. So in fact you look at the capital myocurve from the study, you see a very nice separation of the two arms in the study with 11.3 versus, sorry 11.7 versus 7.3 months different in median overall survival between the two arms in the study. Very characteristic of what is seen in immunotherapies you see a late separation of the survival curves and then a long tail of the survival curve but again this is really become the hallmark of what you expect with immunotherapies and we did in fact in this study. In addition we see from the subset analysis that there were no single subsets which were driving the results. We see that in all the major the subsets of patients we see a nice line-up on the side of the Bavituximab 3 mg kilogram so showing again that we think patient population this should be very broadly utilized. So beginning earlier in the year we worked through a clinical design we presented this to the FDA that phase 3 trial plan is very straight forward it's about 600 patients randomized one to one in a double blinded placebo controlled study with 3mg Bavituximab or docatexal versus placebo docetaxel, primary endpoint overall survival, very similar patient criteria to the earlier clinical trial . Main exclusion is for non-squamous non-small cell lung cancer otherwise we are not selecting for any other particular genetic markers although we will do analysis at the end of day on some of those. [transcript prematurely ends ?]
Nov16 2013: 1-day Symposium on Lung Cancer in Manhattan Beach, CA – now listed on Peregrine Events page ( http://ir.peregrineinc.com/events.cfm ). Can’t tell as yet Peregrine’s role at this. Could it be that PS-targeting (incl. Bavi) will be discussed by a new KOL beyond the 2 new ones introduced at IASLC/Sydney on 10-28-13? IE, Scott J. Antonia/MD-PhD(H.Lee Moffitt CC) & Dmitry I. Gabrilovich/MD-PhD(Wistar Inst)…
Nov16 2013: “6th Annual Symposium on Personalized Therapies & Best Clinical Practices for Lung Cancer”, Manhattan Beach, CA Appears to be an educational initiative of IASLC… IASLC = Intl. Association for the Study of Lung Cancer ”…Now in its SIXTH consecutive year it utilizes a highly interactive clinical case-study format in a 1-day meeting with a faculty of the top lung cancer experts to provide you with the most current information and data for use in your practice today. Each of the presentations includes patient case studies where you make treatment selections based upon real-life scenarios, using the hand-held audience response system. And back by popular demand is the "Lunch with the Professors" where you can sit with the faculty expert of your choice. This Sixth Annual Symposium contains the summary of what you need to know for improving the outcomes of your patients. It includes highlights of the biannual Intl. Symposium on Lung Cancer by the IASLC conducted in Oct. 2013 in Sydney, Australia, only 2 weeks before this symposium. We urge you to review the agenda, faculty and other highlights regarding this symposium reviewed on this Website to fully understand and appreciate all of what this symposium has to offer you for only a very modest tuition…” …Symposium Co-chairs are Dr. Paul A. Bunn, Jr. and Dr. Roy S. Herbst http://www.iaslc.org/events/6th-annual-symposium-personalized-therapies-and-best-clinical-practices-lung-cancer More info: http://www.bmli.com/lungcancer/ (BMLI - “Case-based Learning”) BMLI Conf. Home: http://www.bmli.com/lungcancer/ Agenda: http://www.bmli.com/lungcancer/agenda.php
= = = = = = = = = = = = = = = = 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)
New Dec’13 PAN-EU article on Bavi/PS by Dr.Brekken (PPHM SAB) & Xianming Huang (former Phil Thorpe Lab; now Rolf Brekken Lab) which reviews bavituximab’s ability to reverse PS-mediated immunosuppression and initiate an effective adaptive antitumor activity… “Our results indicate that antibody-mediated PS blockade with bavituximab reverses PS-mediated immunosuppression and initiates therapeutically effective adaptive anti-tumor immunity. Thus, treatment with bavituximab in combination with a blockade of downstream immune checkpoints could result in robust and long-lasting anti-tumor immunity that significantly improves clinical outcomes.”
TEXT: Dec.2013, Pan European Network’s Science & Technology Journal “Revitalizing Tumor Immunity” – R.Brekken/X.Huang – UTSW/Dallas - - - - - - - - - Phospholipids are distributed asymmetrically in the plasma membrane of most normal eukaryotic cells. Unlike neutral phospholipids that are randomly distributed across the bilayer membrane, phosphatidylserine (PS) is predominantly localized in the inner membrane leaflet. The asymmetric distribution of PS is actively maintained by an ATP-dependent aminophospholipid translocase.
During apoptosis, PS is externalised to the outer plasma membrane leaflet where it functions as an ‘eat me’ signal that facilitates the recognition and clearance of dying cells. PS-dependent engulfment of apoptotic cells triggers a series of events that leads to the generation of potent immunosuppressive signals that quells any potential autoimmune responses. Thus, PS exposure represents an evolutionarily conserved mechanism of immune suppression.
Tumors have hijacked this biology such that exposure of PS in the tumor microenvironment is critical in maintaining the immunosuppressive state of tumors. Externalized PS is abundant in the tumor microenvironment: it is found on tumor vascular endothelial cells, on tumor-derived micro vesicles, and constitutively on some tumor cells. Moreover, the exposure of PS is increased significantly on tumor cells undergoing apoptosis in response to chemotherapy and radiotherapy. Externalized PS interacts with PS receptors on immune cells where it actively promotes expansion of immunosuppressive cells that enhance tumor progression and prevent induction of adaptive tumor immunity. Based on these observations we propose that PS exposure is an upstream immune checkpoint that is exploited by successful tumors.
PS blockade To explore the possibility of reversing the immunosuppressive effects of exposed PS, we raised a family of PS-targeting antibodies that bind PS with high affinity. For example, bavituximab, a chimeric PS targeting antibody is currently in multiple Phase II clinical trials. Data obtained in several preclinical tumor models indicate that antibody mediated PS blockade reactivates tumor immunity on multiple levels. It re-polarises tumor associated macrophages from an immunosuppressive to a tumoricidal phenotype, it decreases the presence of immunosuppressive myeloid derived suppressor cells (MDSCs) and promotes their differentiation, it promotes dendritic cell maturation into functional antigen presenting cells, and induces tumor specific cytotoxic T-cell immunity. Thus, antibody mediated PS blockade promotes innate and adaptive tumor immunity.
Impressive anti-tumor effects have been obtained in cancer patients by a blockade of immune checkpoints (e.g. antibodies specific for PD1, PD1L, and CTLA4). However, only a limited number of patients benefit these therapies. Mechanistic studies indicate that blockade of these immune checkpoints are most effective when there is a de novo or pre-existing anti-tumor immune response. Unfortunately, pre-existing tumor specific immune activity is limited in cancer patients because of the exposure of PS in the tumor microenvironment.
Our results indicate that antibody-mediated PS blockade with bavituximab reverses PS-mediated immunosuppression and initiates therapeutically effective adaptive anti-tumor immunity. Thus, treatment with bavituximab in combination with a blockade of downstream immune checkpoints could result in robust and long-lasting anti-tumor immunity that significantly improves clinical outcomes. - - - - - - - - - - For more information please see Yinet al 2013 Cancer Immunology Research doi:10.1158/2326-6066. [ 8-19-13: http://tinyurl.com/mhjftka ] *end article*
About: PAN EUROPEAN NETWORKS: SCIENCE & TECHNOLOGY ”Communication breakdown is the biggest threat to the scientific advancement of Europe. Both govts & scientists alike must engage in dialogue in order to effectively bridge the gap between funding & reality. It is widely known throughout both the academic & scientific communities of Europe that in order to do this there must be a uniform approach to dissemination; one which enables all policy makers & budget holders to acquire the necessary information needed to allocate funding. Pan European Networks: Science & Technology helps bridge the gap between the European Commission, EU funding agencies, govt. departments across Europe and the scientists & academics who are continually striving for success. We will provide exemplars of academic research across Europe, the European Union and individual nations covering R&D, Health and Environment & Sustainability, as well as featuring the key policy makers who can make a direct impact on the academic and scientific community. . . Having accumulated vast experience over many years, the team at Pan European Networks are devoted to providing the most relevant and up to date information for the use of not only the European Commission, but all government agencies and departments across the continent of Europe. Whether it is from a scientific, educational or groundbreaking news perspective, our goal is to make sure that both the public and private sectors have the ability to communicate at the same level. Our publications will give opportunity to some of the leading figures from across Europe to discuss current and future projects, policy change and problematic issues within science, technology, education, health, defense and wider governance.” http://www.paneuropeannetworks.com/science-publications/science-technology-publication/
ALSO, this most compelling quote from a new NATURE article (pub. 12-19-13), ”Bacteriology: A Caring Culture”, a special article on Dr. William Coley's** legacy and modern efforts to defeat cancer [ http://www.nature.com/nature/journal/v504/n7480_supp/full/504S4a.html?WT.ec_id=NATURE-20131219] " Hal Gunn (CEO, Qu Biologics) and his colleagues speculate that their SSIs reset the immune system by mimicking the beneficial effects of infection at a tumor site. In particular, they believe that SSI molecules alter the activity of macrophages, a type of cell involved in the early stages of an immune response. The SSIs, they say, cause macrophages to shift from a response involved in tissue repair and cancer growth to a response that promotes the destruction of abnormal cells." - - - - - - - - As my PHD Friend recently told me about the above quote => “Just what Bavi does!” **Dr. William B. Coley, a surgeon who made the first attempts at the non-surgical treatment of cancer through stimulation of the immune system. For this reason, Dr. Coley has become known as the "Father of Cancer Immunotherapy." http://en.wikipedia.org/wiki/William_Coley
By Djohn iHub #152767 12-20-13: I found this helpful in understanding the 12-2013 Brennan/Huang Pan-EU article… 8-27-10: “Macrophages: The 'Defense' Cells That Help Throughout the Body” http://www.sciencedaily.com/releases/2010/08/100826141232.htm
= = = = = = 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." O. 6th IST Trial: Bavi+Ipilimumab(Yervoy) vs. Adv.Melanoma (Ph1b, random, open-label, 2arms, n=24) Protocol (UTSW): http://www.clinicaltrials.gov/ct2/show/NCT01984255 (Est Start: Jan.2014) …Note: Ipilimumab = BMS’s “Yervoy” (anti-CTLA-4) http://www.yervoy.com
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
PPHM’s Bruce Freimark (Dir./ProdDev) speaking 1-30-14 at GTC’s “Novel Immunotherapeutics Summit 2014” in SanDiego. Title: “PS-Targeting Antibodies Enhances Activity of Immune Checkpoint Inhibitors and Re-activates Immune System in Tumors”… http://tinyurl.com/mv5rd8a
Jan30-31 2014: “GTC’s Novel Immunotherapeutics Summit 2014”, SanDiego Overview: http://www.gtcbio.com/conference/novel-immunotherapeutics-summit-overview 4 Concurrent Sub-Conferences: • 12th Cytokines & Inflammation • 6th Immunotherapeutics & Immunomonitoring <=B.Freimark/Bavi • 2nd Immunogenicity & Immunotoxicity • Inaugural Innate Immunity “The immune system plays a central role not only in fighting infections, but also in many other diseases and medical conditions including cancer. The study of the immune system has led to significant findings in many fields of medicine & biology and has resulted in the discovery of novel and unique substances and reagents that are now widely used for diagnosis, evaluation, and therapy of different malignant diseases. The development of prophylactic and therapeutic vaccines, as well as innovative combinatorial immunotherapeutic approaches has substantially decreased mortality and increased life expectancy, improved life expectancy and the well being of the millions of patients. Leading experts from the scientific & clinical arenas and industry will present about novel findings and developments in the constantly changing area of immunological assays and procedures. They will also discuss recent advances in immunotherapy, as they relate to various immunotherapy modalities, specific cancers, cell subsets, animal models, and tumor microenvironment. Potential clinical feasibility and commercial potential of the newest data obtained from leading biomedical research laboratories will also be discussed.” GTC = GTC Global Technology Community ( http://www.GTCBIO.com ) Agenda: http://www.gtcbio.com/conference/immunotherapeutics-and-immunomonitoring-agenda Brochure PDF: http://www.gtcbio.com/preview/immunotherapeutics_summit_2014.pdf - - - - - - - - - - - 6th Immunotherapeutics & Immunomonitoring Conf. Jan30 Session: “Novel Therapeutics & Targets” (Moderator: Steffen Walter, Immatics Biotech.) 1-30-13 5:25pm: Bruce Freimark, Peregrine Pharm. (PPHM’s Dir./ProdDEV): “Phosphatidylserine Targeting Antibodies Enhances Activity of Immune Checkpoint Inhibitors and Re-activates Immune System in Tumors” SUMMARY: Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells (ECs) and tumor cells. PS exposure becomes enhanced in response to chemotherapy, irradiation, and oxidative stresses in the tumor microenvironment. PS exposure in tumors promotes an immunosuppressive microenvironment which includes the recruitment of myeloid derived suppressor cells, immature dendritic cells, and M2-like tumor associated macrophages as well as the production of anti-inflammatory cytokines. Bavituximab, a chimeric PS-targeting antibody, is being used in combination with chemotherapy to treat patients with solid tumors in multiple late-stage clinical trials. Binding of PS targeting antibodies on tumor ECs, tumor cells and their secreted microparticles increase the presence of M1-like macrophages and cytokine responses that reverse the immunosuppressive PS mediated checkpoint, thereby enhancing anti-tumor immunity. Using multiple tumor models in mice, we demonstrate PS targeting antibodies enhance the anti-tumor activity of multiple forms of therapy including anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies. Tumor growth inhibition correlates with infiltration of immune cells in tumors and induction of adaptive immunity. The combination of these mechanisms promotes strong, localized, anti-tumor responses without the side-effects of systemic immune activation.
1-6-14/PR: FDA Grants Fast-Track for BAVI in 2L/NSCLC Note: 12-30-13 announcement of init. of Ph3 pivotal "SUNRISE" (BAVI+Doxy, n=600, > 100 sites) trial shown at end...
1-6-14: Peregrine Pharmaceuticals Receives FDA Fast Track Designation for Its Immunotherapy Bavituximab as a Potential Treatment of Second-Line Non-Small Cell Lung Cancer · SUNRISE Pivotal Phase III Trial of Bavituximab in Second-Line NSCLC Underway
TUSTIN, Jan 6, 2014: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), today announced that the company has received Fast Track designation by the U.S. Food and Drug Administration (FDA) for its lead investigational immunotherapy bavituximab for the potential treatment of second-line non-small cell lung cancer (NSCLC). Recently, the company initiated SUNRISE, a pivotal Phase III clinical trial comparing bavituximab plus the chemotherapy docetaxel against placebo plus docetaxel in this indication.
"The fast track designation is a milestone for the SUNRISE trial program and represents a step closer to bringing bavituximab to the market," said Robert Garnick, Ph.D., head of regulatory affairs at Peregrine. "We are very pleased that the FDA has recognized the potential of this novel therapy as a treatment for this serious and devastating type of cancer and look forward to working closely with them to ensure the most efficient review process."
The Fast Track programs of the FDA are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Fast track status enables a sponsor to have more frequent and timely communication and meetings with the FDA regarding product development plans and may also result in eligibility for priority review of New Drug Applications. Fast track designation does not apply to a product alone but a combination of a product and specific indication.
SUNRISE ("Stimulating ImmUne RespoNse thRough BavItuximab in a PhaSE III Lung Cancer Study") is a Phase III, global, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and efficacy of bavituximab plus docetaxel in patients with second-line non-small cell lung cancer (NSCLC). The trial is evaluating bavituximab plus docetaxel versus docetaxel plus placebo in approximately 600 patients at more than 100 clinical sites worldwide. Patients with Stage IIIb/IV non-squamous, NSCLC who have progressed after standard front-line treatment are eligible for enrollment. Patients will be randomized into 1 of 2 treatment arms. All patients will receive up to six 21-day cycles of docetaxel (75 mg/m2) plus weekly infusions of either bavituximab (3mg/kg) or placebo until progression or toxicity. The primary endpoint of the trial will be overall survival. For additional information about the SUNRISE trial please visit http://www.sunrisetrial.com or ClinicalTrials.gov using Identifier NCT01999673. [ http://www.clinicaltrials.gov/ct2/show/NCT01999673 ]
About Bavituximab: A Targeted Immunotherapy Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but "flips" and becomes exposed on the outside of cells that line tumor blood vessels, creating a specific target for anti-cancer treatments. PS-targeting antibodies target and bind to PS and block this immunosuppressive signal, thereby enabling the immune system to recognize and fight the tumor. These data detailing the immune-stimulatory mechanism of action of PS-targeting antibodies, such as the company's lead drug candidate bavituximab, are the subject of a manuscript published in the October 2013 issue of the American Association for Cancer Research (AACR) peer-reviewed journal, Cancer Immunology Research [Pub. Online 8-19-13 http://tinyurl.com/mhjftka ]. Bavituximab is currently being evaluated in several solid tumor indications, including non-small cell lung cancer, breast cancer, liver cancer and rectal cancer with a trial in advanced melanoma anticipated to initiate in the near future.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead immunotherapy candidate bavituximab while seeking a partner to further advance its novel brain cancer agent Cotara®. 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* Contact: Christopher Keenan or Jay Carlson, Peregrine Pharmaceuticals, (800) 987-8256, info@peregrineinc.com
= = = = = = = = = = = = = = = = = = = = = 12-30-13: "Peregrine Pharmaceuticals Initiates SUNRISE Pivotal Phase III Clinical Trial of Bavituximab in Second-Line Non-Small Cell Lung Cancer” · Company Launches http://www.SunriseTrial.com to Assist Patients and Physicians http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=816379 TUSTIN, 12/30/13: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), today announced the opening to enrollment of its SUNRISE trial at leading oncology centers in the United States. SUNRISE is a pivotal Phase III clinical trial comparing the company's investigational immunotherapy bavituximab plus the chemotherapy docetaxel against placebo plus the chemotherapy docetaxel in patients with second-line non-small cell lung cancer (NSCLC). This trial will enroll approximately 600 patients from more than 100 medical centers worldwide.
"The design of the SUNRISE trial was based on the compelling Phase II data [6-3-13/ASCO’13: Final Data Ph.II 2L/NSCLC http://tinyurl.com/my8qxw7 ] demonstrating encouraging improvement in overall survival in patients with second-line NSCLC. Furthermore, peer-reviewed published data support that bavituximab and docetaxel share highly compatible mechanisms of action that we believe hold promise for improved patient outcomes," (1-6) said Joe Shan, MPH, VP of Clinical & Regulatory Affairs at Peregrine. "We believe harnessing the body's natural immune system to fight cancer will be an integral part to conquering this deadly disease. Multiple peer-reviewed published data support bavituximab's immunotherapy mechanism of action whereby the targeted monoclonal antibody blocks an immune checkpoint responsible for immune suppression at the local tumor environment, thereby allowing the immune system to recognize and fight this deadly disease."
"This is a significant milestone for the company as patients with advanced non-small cell lung cancer who have progressed on a prior treatment have few therapeutic options, and new approaches to managing their disease are in demand," said Steven King, CEO of Peregrine. "As part of our plan to provide patient and physicians with the necessary information regarding this trial, today we launched the http://SunriseTrial.com web portal to serve as a gateway for trial parameters and additional resources. We anticipate that in executing our global plan we can enroll the majority of patients in this trial from the United States and Western Europe."
SUNRISE ("Stimulating ImmUne RespoNse thRough BavItuximab in a PhaSE III Lung Cancer Study") is a Phase III, global, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and efficacy of bavituximab plus docetaxel in patients with second-line NSCLC. The trial will evaluate bavituximab plus docetaxel versus docetaxel plus placebo in approximately 600 patients at clinical sites worldwide. Patients with Stage IIIb/IV non-squamous, NSCLC who have progressed after standard front-line treatment are eligible for enrollment. Patients will be randomized into 1 of 2 treatment arms. All patients will receive up to six 21-day cycles of docetaxel (75 mg/m2) plus weekly infusions of either bavituximab (3mg/kg) or placebo until progression of toxicity. The primary endpoint of the trial will be overall survival. For additional information about the SUNRISE trial please visit http://www.SunriseTrial.com or ClinicalTrials.gov using Identifier NCT01999673. [ http://www.clinicaltrials.gov/ct2/show/NCT01999673 ]
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead immunotherapy candidate bavituximab while seeking a partner to further advance its novel brain cancer agent Cotara®. 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* REFERENCES [See: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html & http://www.peregrineinc.com/technology/bavituximab-oncology.html ] 1. Yin et al. “Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation”, Cancer Immunology Research. 2013 Oct 1 (4):256-68. 2. Fabbri et al. “Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: a cytometric study” BMC Cell Biol. 2006 Jan 26;7:6. 3. Gong et al. “Measuring response to therapy by near-infrared imaging of tumors using a phosphatidylserine-targeting antibody fragment” Mol Imaging. 2013 Jun 1;12(4):244-56. 4. Huang et al. “A monoclonal antibody that binds anionic phospholipids on tumor blood vessels enhances the antitumor effect of docetaxel on human breast tumors in mice” Cancer Res. 2005 May 15;65(10):4408-16. 5. Kodumudi et al. “A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers” Clin Cancer Res 2010;16:4583-94. 6. Hodge et al. “Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death”. Int. J. Cancer: 2013; 133(3):624-36. CONTACT: Christopher Keenan or Jay Carlson - Peregrine Pharmaceuticals, (800) 987-8256, info@peregrineinc.com
= = = = = = = = = = = = = = BAVITUXIMAB PHASE III TRIAL: ( http://www.SunriseTrial.com ) A. Phase III Bavi+Doce vs. 2nd-Line NSCLC "SUNRISE" (randomized, double-blind, placebo-ctl'd, n=582) Protocol: http://www.clinicaltrials.gov/ct2/show/NCT01999673 (Start=Dec2013 Est PrimaryComp=Dec2016) 1-6-14: FDA grants FAST TRACK status to Bavi in 2ndLine NSCLC http://tinyurl.com/l799ukk 12-30-13: Pivotal Ph.3 ‘SUNRISE’ NSCLC Trial Initiated (n=~600, sites=~100) http://tinyurl.com/kdjb9qz 5-20-13: FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ...S.King: “We will now focus on starting the Ph.III trial while continuing ongoing partnering discussions.” …R.Garnick: “This was a highly collaborative effort with the FDA; this trial, when combined with Bavi’s supporting data to date, could be sufficient to support a future BLA submission."
= = = = = = = = = = = = = = = = = = = = = = = = = PRIOR (2010-2011) PHASE II 2nd-LINE NSCLC BAVI+DOCE TRIAL (n=121): F. LEAD IND: Phase IIb Bavi+Doce vs. 2nd-Line NSCLC (randomized, double-blinded, placebo-ctl'd, n=120, 'registrational') Protocol: http://clinicaltrials.gov/ct2/show/NCT01138163 (24 U.S. + 15 India + 2 RepGA + 7 RussianFED + 5 Ukraine = 53 as of 8-12-11) Enrolled Oct2010 - Oct2011 at 40 global sites (per J.Shan 9-7-12 webcast ( http://tinyurl.com/8cn87la ) 8-2012: Compare Bavi+Doce's MOS=11.7mos (Bavi/3mg) to the 4 Curr-Approved 2Line/NSCLC Drugs http://tinyurl.com/cgnkvpa • Taxotere/docetaxel => MOS=6.3mos (meta-analysis of 5 trials, 865 pts) • Altima/pemetrexed => No diff. vs. Docetaxel (Ph.3 non-inferiority vs. Doce, 571 pts) • Tarceva/erlotinib => MOS=5.3mos (TITAN Ph.III n=424 trial - see http://tinyurl.com/8w8lo93 ) • Iressa/gefitinib => "Iressa does not improve OS" 6-3-13/ASCO’13: Final Data Ph.II 2L/NSCLC http://tinyurl.com/my8qxw7 …60% improvement in MOS: Bavi/3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined Bavi/1mg + DoxyOnly arms), HR=.662, P=.113 5-20-13: FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ...S.King: “We will now focus on starting the Ph.III trial while continuing ongoing partnering discussions.” …R.Garnick: “This was a highly collaborative effort with the FDA; this trial, when combined with Bavi’s supporting data to date, could be sufficient to support a future BLA submission." 2-19-13: Topline Data Update from 2nd-Line NSCLC Trial after data discrepancies review http://tinyurl.com/ansqcea …60% improvement in MOS: 3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined 1mg & Doxy+placebo arms), HR=.73, p=.217 6-5-13: FTM's table of MOS data in 15 prior Doxy 2nd-Line NSCLC trials (Bavi's 60% MOS Improvement is Tops) http://tinyurl.com/m886ctb 1-25-13: MLV's George Zavoico recaps 2ndLine/NSCLC data errors & current status of PPHM's review http://tinyurl.com/b9u4pk8 ...GZ: "This means that patients randomized into the high dose arm were administered Bavi correctly, whereas some of the patients in the placebo arm were administered low dose Bavi and some in the low dose Bavi arm were administered placebo. More importantly, the findings suggested that the MOS of 13.1 mos. in the high dose arm was likely to be valid. Even by historical measures, this is a remarkable result, since docetaxel's product insert lists the MOS of NSCLC patients receiving this widely used drug as 2nd-Line therapy in 2 trials as 5.7 & 7.5 mos. In effect, adding Bavi doubled the MOS. In our view, this was an extraordinary stroke of luck. If the high dose arm had been affected by the coding discrepancy, Peregrine would have been in a completely different & unfortunate position… Moreover, Peregrine must determine how best to present its case to the FDA. Will the historical controls be sufficient to justify moving Bavi into a Phase III pivotal trial, or will Peregrine have to pool the results of the placebo & low-dose arms and use that as a comparator to argue for moving ahead? A simple average of the placebo & low-dose arms results in a new control MOS of about 8.4 mos., still several months less than that of the high dose arm. This quick analysis results in about a 5-mo. survival advantage, a substantial prolongation for patients with second-line NSCLC and likely to justify moving Bavi into a pivotal Phase III trial in 2013, in our view." 1-7-13 PPHM PR - Review Update: "discrepancies are isolated to the placebo and 1 mg/kg arms; no evidence of discrepancies in the 3 mg/kg arm… Peregrine is taking a very conservative approach toward analyzing the results by combining the placebo & 1mg/kg arms into one treatment arm (control arm), and comparing to the 3mg/kg arm. This analysis indicates that the 3 mg/kg arm continues to show favorable TRR's, PFS, and OS over the new combined control arm. Peregrine expects to announce more detailed results from the analysis in the near term when it is completed." http://tinyurl.com/asup54d 9-24-12: Major Discrepancies found in 2nd-Line NSCLC Ph.2B Treatment Group Coding by Indep. Third-Party Vendor http://tinyurl.com/8r9zcqy …"Investors should not rely on clinical data that the company disclosed on or before Sept. 7, 2012 from its Ph.2 Bavi trial in patients with 2nd-Line NSCLC or any presentations or other documents related to this Ph.2 trial." 9-24-12: Peregrine sues CSM Over Bavi Ph.2B 2nd-Line NSCLC Clinical Trial Mix-Up http://tinyurl.com/8fpgngu …CSM = Clinical Supplies Management Inc., Fargo ND http://www.csmondemand.com ...1-17-13: Peregrine's lawsuit against CSM for "breach of contract & negligence" SERVED http://tinyurl.com/a7zrgys …9-10-12 CEO Steve King, QtlyCC ( http://tinyurl.com/8nkwrml ) ……"These are truly remarkable results (statistically doubling MOS) that are not only great for the pgm… but also great news for the NSCLC patients in the trial…" …9-10-12 Robert Garnick (Head/Reg), QtlyCC ( http://tinyurl.com/8nkwrml ) ……"The NSCLC data we announced 9-7-12 has far exceeded our expectations, and I hope that you're as excited as I am with bavituximab's potential. I feel strongly that Peregrine should be recognized for having the corporate courage to conduct the rigorous, randomized placebo-controlled Phase II trial that provided these robust data and that provide the basis for us to plan for a pivotal Phase III program." ...9-7-12: PPHM Press Release about Dr. Gerber's plenary at ASTRO/Thoracic/Chicago: http://tinyurl.com/96wrrso …"The interim data showed a statistically significant improvement in OS (Hazard Ratio 0.524, p-value .0154) and a doubling of MOS (12.1/13.1mos. vs. 5.6mos.) in the Bavituximab-containing arms compared to the [Docetaxel] ctl-arm." ......VP Joe Shan's 15min. Webcast & Slideshow recapping Dr. David Gerber's 9-7-12 ASTRO/Chicago Plenary: http://tinyurl.com/96wrrso …8-15-12 CEO Steve King, Wedbush/NYC ( http://tinyurl.com/8mhrtld ) ......"As we're sitting here today, we have still not reached the # of events for MOS in either of the Bavituximab arms - and, in fact, we still have patients that are on treatments." Q&A: "it's going to be a very positive MOS result, it's just a matter now of magnitude." …7-16-12 CEO Steve King, QtlyCC ( http://tinyurl.com/cs7spbz ) ......"The strength of this 2nd-Line NSCLC data (esp. MOS trends) in this large area of high unmet medical need has also sparked a surge in partnering discussions that has included over 15 in-person partnering meetings since that time with major players in oncology, with all discussions ongoing and addl. parties showing interest. Our goal for the program is to position ourselves, along with a potential partner, to initiate Ph3 by mid-2013, which means an EOP2 meeting by yr-end'12. It would be ideal to have a partner on board to participate in the EOP2 meeting, and we have communicated this to interested parties and they agree." …7-16-12 Robert Garnick (Head/Reg), QtlyCC ( http://tinyurl.com/cs7spbz ) ……"We've been working very hard and very actively on the next steps in our Bavi 2nd-Line NSCLC pgm, given the favorable data that we've seen. As you can imagine, with data like this, there are many things that we need to consider. One consideration is that, should the data continue to trend the way it is, particularly in survival, this opens a door for potential discussions around a pathway for Accelerated Approval. At this point, all options are being considered, with Peregrine working towards the most efficient path forward from a regulatory standpoint." Q&A: "…all in all, I think the data is extremely compelling and I think it makes a really good case. Certainly, I think, I've seen a lot of Ph2 & Ph3 data, and this is as compelling Ph2 data as I've ever seen. So, I'm very comfortable proposing a meeting with the FDA for Q4'12." …7-12-12 CEO Steve King, JMP-Conf/NYC ( http://tinyurl.com/csdclwb ) ……"Re: 2nd-Line/NSCLC trial, the most thrilling thing is the fact that, even though we'd reached MOS for the ctl-arm(Doce) at end of Apr'12 of LESS THAN 6MOS, the majority of patients are still alive (today) in both Bavi arms, and we expect that to continue for some period of time still. Ph3 planning is underway already; our goal is to start this Ph3 by mid'13, meaning an EOP2 meeting with the FDA in Q4'12; our goal is to bring a partner on board, ideally in time for that EOP2 meeting, certainly before the beg. of the Ph3 trial." …5-21-12: TopLine data n=117 for Bavi/3mg+Doce arm: ORR=17.9%/PFS=4.5mos (vs. CTL 7.9%/3mos) http://tinyurl.com/73aeyxj ......Importantly, MOS for CTL-arm "< 6 mos", but not yet reached in both Bavi arms. ...10-6-11: Enrollment complete. http://tinyurl.com/3m9re39 ...7-14-11/CC: Enrollment was taking longer than expected; have amended protocol; expanding to ~45 sites, expect enroll. comp. "early in Q4/2011", data unblinding 1H'12. http://tinyurl.com/6k6y2as …3-17-10/Roth, CEO S.King: "We refer to this trial as a Registrational Phase II Study, because we believe that if we have results anywhere near approaching what we saw in the earlier [India] study, it could be a conduit for Accelerated Approval." ...6-4-10: Ph.2b randomized reg. trial Open for enrollment: http://tinyurl.com/25v22qk ……"up to 120 refractory patients at ~30 clinical sites; goal: fully-enroll by mid'11, topline data by y/e'11."
In the 7-14-14/CC, Steve Worsley (VP/BusDev) adds IDO to CTLA-4 & PD-1 as a checkpoint target for which Peregrine is “seeking collaborators”. First time I’ve heard IDO inhibitors mentioned by Peregrine. Didn’t take much searching to tie it IMO to Peregrine KOL’er Dr. Scott Antonia (clearly “Mr. IDO” – see below) of the H. Lee Moffitt Cancer Center in Tampa. See if you don’t agree…
= = = = = = = = = = = = = = = = 7-14-14/CC: Steve Worsley (VP/BusDev) said that Peregrine is “seeking collaborators that build on other checkpoints of pathways such as PD-1, IDO, immune-stimulatory drugs, and even vaccines…” • Incyte’s immune checkpoint inhibitor INCB24360 is an oral inhibitor of IDO1 (indoleamine dioxygenase-1) – http://www.incyte.com • NewLink Genetics’ immune checkpoint inhibitor indoximod is an oral inhibitor of IDO (indoleamine 2,3-dioxygenase) – http://newlinkgenetics.com NG-website: IDO pathway inhibitors are another class of immune check point inhibitors akin to the recently developed antibodies targeting CTLA-4 & PD-1 that represent potential breakthrough approaches to cancer therapy.
= = = = = = = = = = = = = = = = = 3-6-2012/Jrnl-NCI: “Most researchers assumed that these immune-suppressive effects of IDO were unique to pregnancy. But a cancer connection appeared in 2002, when oncologist Scott Antonia, MD/PhD, at the H. Lee Moffitt Cancer Center in Tampa FL, reported that an IDO inhibitor delayed growth of human lung cancer cells implanted into mice.” http://jnci.oxfordjournals.org/content/early/2012/02/20/jnci.djs152.full
7-14-14 Conf. Call – SA Transcript: http://tinyurl.com/me4o2v9 Steve Worsley, Prepared Remarks (VP/Business Dev.): “Today I will speak to our strategy as it pertains partnering as it has greatly evolved over the last 2 years, partly due to 2 events, the 1st of those being the Phase II experience in Sept. 2012 and the 2nd, the subsequent data from Phil Thorpe’s lab validating the immune-stimulatory mechanism of bavituximab. When taken together, partnering should be thought of in a very different light than in early 2012. Essentially there are 2 partnering buckets that we’d like to fill. As it is clear that we were able to efficiently execute the SUNRISE Phase III trial, our goal is to seek a partner to assist us in advancing bavituximab into indications into the mid-stage clinical trials that have shown early clinical promise that Jeff & Joe alluded to. We believe that data to date supports several indications which we’re including in our discussion. We are also seeking collaborators that build on what we’ve just heard from Joe & Jeff regarding other checkpoints of pathways such as PD-1, IDO, immune-stimulatory drugs, and even vaccines. These will be very early stage collaborations, aimed at enhancing the data to emerge from the ongoing Phase Ib IST in advanced Melanoma. We continue to have discussions with numerous potential partners and updating them with new data as it emerges from the program. If they’re in an immune-oncology space or have a drug candidate that can be leveraged by the immune-stimulatory mechanism of bavituximab, they’re certainly on our radar. This past quarter with data from Keystone at AACR in hand, we were able to engage several prominent companies. This is a process that takes time and should not be rushed. We have a clear idea of how we want to advance bavituximab and a key will be to find a partner aligned with that vision. We are working as efficiently as possible, we appreciate your patience and we look forward to updating you as to the progress in this area.”
= = = = = = = = = = = = = 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)
= = = = = = = = = = = = = = = = = PR 10-15-13: “Symposium at IASLC World Conference on Lung Cancer to Highlight Novel Immune Checkpoints Including Peregrine Pharmaceuticals' Bavituximab PS Target” • Symposium's Lead Presenter Dmitry Gabrilovich, MD, PhD, Accomplished Clinical Immunologist to Be Accompanied by Panel of Key Thought Leaders From Fields of Oncology, Immunology and Lung Cancer • Peregrine's Lead Product Candidate Bavituximab Represents the First in a New Class of Immunotherapeutics That Targets the Novel PS Upstream Checkpoint http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=797251
TUSTIN, CA 10/15/13: Peregrine Pharmaceuticals (NASDAQ: PPHM) today announced that participants at the International Association for the Study of Lung Cancer's (IASLC) 15th World Conference on Lung Cancer to be held October 27-30, 2013 in Sydney, Australia will discuss novel immunotherapy checkpoint inhibitors including Peregrine's novel target phosphatidylserine (PS). The conference is the world's largest meeting dedicated to lung cancer and other thoracic malignancies and brings together more than 5,000 delegates from across the medical and scientific professional spectrums from more than 100 countries.
The symposium titled: "Immune Checkpoints in the Tumor Environment: Novel Targets and the Clinical Promise of Combined Immunotherapies" will focus on the identification of new immunosuppressive targets in tumors and the potential for improved clinical outcomes through multiple immune checkpoint blockade. The event will take place in Parkside Ballroom B, Conference Level 1 of the Sydney Convention and Exhibition Centre on Monday, October 28th from 7:00-8:00 AM AET. The program for the symposium is as follows:
Moderator: Scott J. Antonia, MD, PhD Associate Professor in the Department of Interdisciplinary Oncology and the Co-Program Leader of the Immunology Program at the H. Lee Moffitt Cancer Center, Tampa, Florida
PRESENTATIONS: Dmitry I. Gabrilovich, MD, PhD Professor in Cancer Research and Program Leader, Translational Tumor Immunology at The Wistar Institute, Philadelphia, Pennsylvania "Myeloid-Derived Suppressor Cells as Negative Regulator of Immune Responses in Cancer"
Rolf A. Brekken, PhD Effie Marie Cain Research Scholar in Angiogenesis Research and an Associate Professor, in the Departments of Surgery and Pharmacology at the Hamon Center for Therapeutic Oncology, University of Texas Southwest Medical Center, Dallas, Texas "Engagement of Phosphatidylserine (PS) by PS-Targeting Antibodies Blocks a Global Immunosuppressive Checkpoint in the Tumor Microenvironment Inducing Multiple Downstream Anti-Tumor Response Mechanisms"
David E. Gerber, MD Associate Professor of Internal Medicine in the Hematology-Oncology Division at the University of Texas Southwestern Medical Center, Dallas, Texas "Clinical Experience and Prospects with Checkpoint Immunotherapy in Lung Cancer" Peregrine will also be hosting convention visitors at Exhibit Booth #702.
"This conference brings together thought leaders from all over the world and in particular this symposium will bring together a set of key opinion leaders to focus on the current understanding of tumor immune checkpoints and the therapeutic potential of combining upstream and downstream immune checkpoint blockers. We are pleased that part of this discussion will focus on the recent data validating bavituximab's PS as global immunosuppressive checkpoint," said Kerstin Menander, MD, PhD, Head of Medical Oncology at Peregrine Pharmaceuticals. "Drs. Gabrilovich and Antonia are recognized leaders in the immunotherapy community and we are particularly pleased that they agreed to participate in the symposium. Their insights into new approaches for immunotherapy combination therapy studies will be extremely valuable as we continue to advance our bavituximab program toward its first such clinical trials."
ABOUT THE PRESENTERS Scott J. Antonia, M.D., Ph.D. Dr. Antonia is currently the Department Chair & Program Leader of the Thoracic Oncology Department Associate Professor in the Department of Interdisciplinary Oncology and Program Leader of the Immunology Program at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. He is also a Professor of Oncology at the University of South Florida College of Medicine in Tampa. Prior to being named chair of Thoracic Oncology in 2010, he was associate chairman of the Sarcoma Department. He joined the Moffitt Cancer Center in 1994. Dr. Antonia received his M.D. and his Ph.D. in Immunology from the University of Connecticut Health Center in Farmington, Connecticut. In addition, he completed an internal medicine residency at Yale University School of Medicine and pursued additional training at Yale through a medical oncology fellowship and post-doctoral fellowship in Immunobiology. Dr. Antonia's work focuses on translational research. Using his molecular biology and cellular background in the development of immunotherapeutic strategies for the treatment of cancer patients, he has developed strategies designed to thwart the immunosuppressive mechanisms used by tumors to evade T-cell mediated rejection. Dr. Antonia has published papers in several peer-reviewed journals, including Science, Clinical Cancer Research, Current Opinions in Oncology, and Cancer Research. [ http://www.moffitt.org/research--clinical-trials/individual-researchers/scott-j--antonia-md-phd ]
Dmitry I. Gabrilovich, M.D., Ph.D. Dr. Gabrilovich is currently the Christopher M. Davis Professor in Cancer Research and Program Leader, Translational Tumor Immunology at The Wistar Institute, Philadelphia, Pennsylvania. The Wistar Institute is the nation's first independent institution devoted to medical research and training and has been designated a National Cancer Institute Cancer Center in basic research. Dr. Gabrilovich's lab is focused on understanding the mechanisms of tumor-associated immunosuppression as well as on the development of new effective cancer immunotherapeutics. Prior to joining Wistar, Dr. Gabrilovich was the Robert Rothman Endowed Chair in Cancer Research and Head, Section of Dendritic Cell Biology at the H. Lee Moffitt Cancer Center in the Department of Immunology and a Professor of Oncologic Sciences and Molecular Medicine at the University of South Florida in Tampa, Florida. Prior to this, Dr. Gabrilovich was a Research Fellow at the Imperial College in London, United Kingdom and at the University of Texas Southwestern Medical Center in Dallas, Texas. Dr. Gabrilovich earned his M.D. from Kabardino-Balkarian State University Medical School in Nalchik, Russia and his Ph.D. in Immunology from the Central Institute of Epidemiology in Moscow. He has over 25 years of experience, extensive knowledge in this field and has more than 180 peer-reviewed publications. [ http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd ]
Rolf A. Brekken, Ph.D. Dr. Brekken is the Effie Marie Cain Research Scholar in Angiogenesis Research and an Associate Professor, in the Departments of Surgery and Pharmacology, a Principal Investigator in the Hamon Center for Therapeutic Oncology Research, and a member of Simmons Comprehensive Cancer Center, University of Texas Southwest Medical Center in Dallas, Texas. Dr. Brekken received his Bachelor of Arts degree from Luther College in Decorah, Iowa and his Ph.D. (Cell and Molecular Biology) from UT Southwestern Graduate School of Biomedical Sciences. He completed his postdoctoral training in the Department of Vascular Biology at the Hope Heart Institute in Seattle, Washington where he studied how the extracellular matrix contributes to vascular function in and growth of tumors. He is an author on over 100 peer reviewed scientific papers and is a senior editor of Cancer Research. Research in the Brekken laboratory is funded by the NCI, the American Cancer Society, the Mary Kay Foundation and CPRIT as well as several biopharmaceutical companies. [ http://profiles.utsouthwestern.edu/profile/10808/rolf-brekken.html ]
David E. Gerber, M.D. Dr. Gerber is currently an Associate Professor of Internal Medicine in the Hematology-Oncology Division at the University of Texas Southwestern Medical Center in Dallas, Texas where he joined the faculty in 2007. Dr. Gerber earned his M.D. from Cornell University Medical College in New York, New York, and completed his internship and residency in Internal Medicine at the University of Texas Southwestern Medical Center in Dallas, Texas. He completed his fellowship in medical oncology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Dr. Gerber is board certified in Internal Medicine and Medical Oncology. Dr. Gerber is particularly interested in lung cancer and is highly active in related research. His research has generated over 40 peer-reviewed publications. He has authored two books and 12 book chapters on this topic and his studies have contributed to invitations to lecture both nationally and internationally. [ http://profiles.utsouthwestern.edu/profile/53487/david-gerber.html ]
PPHM SRB/KOL David Carbone (Ohio-St) speaking 11-22-14, ESMO Symposium on Immuno-Oncology, in session titled, “Immune Checkpoint Inhibitors in Lung Cancer”…
= = = = = 12-10-2013 QTLY FINANCIALS PRESS RELEASE . . . BAVITUXIMAB IMMUNOTHERAPY DEVELOPMENT PROGRAM Data from preclinical studies showing that tumor growth inhibition of a PS-targeting antibody equivalent to bavituximab and an anti-CTLA-4 combination therapy in a mouse melanoma model was superior to either antibody alone were recently presented at Society for Immunotherapy of Cancer (SITC) Annual Meeting [BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5 ]. Peregrine is exploring the potential to combine bavituximab with other immunotherapies such as PD-1 antibodies & CTLA-4 targeted approaches and has initiated several proof-of-concept studies to support recent mechanism data. In advance of this, multiple proof-of-concept preclinical studies are now underway with data anticipated over the next few months. Peregrine anticipates the initiation of a single-center Phase Ib IST of bavituximab plus an approved anti-CTLA-4 antibody in patients with advanced melanoma in early CY2014. With recent scientific insights highlighting bavituximab's immunostimulatory MOA, Peregrine announced today the following additions to its Scientific Advisory Board. The company plans to utilize the expertise of its new advisors to help guide the development of its novel immunotherapeutic candidate bavituximab:
Dimitry I. Gabrilovich, MD, PhD Dr. Gabrilovich is currently the Christopher M. Davis Professor in Cancer Research and Program Leader, Translational Tumor Immunology at The Wistar Institute, Philadelphia, Pennsylvania. Prior to joining Wistar, Dr. Gabrilovich was the Robert Rothman Endowed Chair in Cancer Research and Head, Section of Dendritic Cell Biology at the Moffitt Cancer Center in the Department of Immunology and a Professor of Oncologic Sciences and Molecular Medicine at the University of South Florida. Prior to this, Dr. Gabrilovich was a Research Fellow at the Imperial College in London, United Kingdom and at the Univ. of Texas SW Medical Center in Dallas, Texas. Dr. Gabrilovich earned his M.D. from Kabardino-Balkarian State University Medical School in Nalchik, Russia and his Ph.D. in Immunology from the Central Institute of Epidemiology in Moscow.
Scott J. Antonia, MD, PhD Dr. Antonia is currently the Dept. Chair & Program Leader of the Thoracic Oncology Department Associate Professor in the Department of Interdisciplinary Oncology and Program Leader of the Immunology Program at the H. Lee Moffitt Cancer Center> and Research Institute in Tampa, Florida. He is also a Professor of Oncology at the Univ. of South Florida College of Medicine in Tampa. Dr. Antonia received his M.D. and his Ph.D. in Immunology from the Univ. of Connecticut Health Center in Farmington, Connecticut. In addition, Dr. Antonia completed an internal medicine residency at Yale University School of Medicine and pursued additional training at Yale through a medical oncology fellowship and post-doctoral fellowship in Immunobiology.
DAVID CARBONE, MD, PhD Dr. Carbone is currently a Professor of Medicine in the Division of Medical Oncology at The Ohio State University's Ohio State's Comprehensive Cancer Center at the James Cancer Hospital and the Solove Research Institute both in Columbus, Ohio. Prior to joining Ohio State University, he served on the faculty of the Univ. of Texas SW Medical Center in Dallas, Texas and Vanderbilt University's Thoracic & Head & Neck Cancer Program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. Dr. Carbone received his M.D. and Ph.D. degrees in Molecular Biology and Genetics from Johns Hopkins Univ. in Baltimore, Maryland.
Hakan Mellstedt, MD, PhD Dr. Mellstedt, is currently a Professor of Oncologic Biotherapy at the Karolinska Institute and Cancer Centre Karolinska at the Karolinska Univ. Hospital in Stockholm, Sweden. Prior to this, he was Professor of Experimental Oncology at Uppsala Univ. and head of the Department of Experimental Oncology, Department of Oncology, Uppsala University Hospital in Uppsala, Sweden. He was also the Administrative Director of Cancer Center Karolinska. Dr. Mellstedt has served as a Consultant in Internal Medicine to the Seraphimer Univ. Hospital in Stockholm, Sweden as a Senior Consultant to the Department of Oncology, Karolinska Univ. Hospital, Sweden and as a Senior Consultant to the Sophiahemmet Hospital in Stockholm. Dr. Mellstedt received his M.D. and his Ph.D. degrees from the Karolinska Institute. He is Board Certified in Internal Medicine, Hematology & Oncology. http://www.peregrineinc.com/about-us/medical-and-scientific-advisors.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 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 . . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org 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 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
PPHM SAB'ers Drs. Brekken+Gabrilovich June16-19 WISTAR “Myeloid Suppressors” Conf. In Philadelphia. General Sponsors are: Peregrine & Genentech.
Jun16-19 2016: “WISTAR's Regulatory Myeloid Suppressor Cells Conf.”, Philadelphia “From Basic Discovery To Therapeutic Application” http://myeloidsuppressors.com “This conference will focus on the pathological functions of myeloid-derived suppressor cells, dendritic cells, macrophages and neutrophils, and provide a forum for in-depth discussion of the most pressing issues associated with the biology & clinical application of these cells. The conference will bring together scientists from academia & industry interested in the basic and translational aspects of these cells in cancer and other pathological conditions.” OVERVIEW: Myeloid cells are comprised of populations of mature terminally differentiated macrophages, dendritic cells and neutrophils, as well as immature myeloid cells including granulocytes, monocytes, and myeloid progenitors. These cells are evolutionarily designed to protect the host from bacteria and viruses by utilizing mechanisms of innate & adaptive immunity. They are also major contributors to tissue remodeling after injuries or resolved inflammation. In cancer, chronic infections, and inflammation, these cells are undergoing extensive changes, which make them immunosuppressive, able to actively promote angiogenesis, tumor cell invasion, and formation of pre-metastatic niches. Recent data demonstrates the association of accumulation of these cells in cancer patients and clinical outcomes of the diseases. With the development of novel immunotherapeutics, it became apparent that regulatory myeloid cells play a major role in limiting therapeutic efficacy of treatment. This conference is focused on pathological functions of myeloid-derived suppressor cells, dendritic cells, macrophages and neutrophils. The specific goals of this meeting are to develop a better understanding of the mechanisms regulating the accumulation of these cells, markers that allow for detection of these cells in cancer patients and patients with chronic infections & inflammation, and approaches to therapeutic targeting of these cells. ABSTRACTS: titles & authors will be posted on the conference website before the conference begins. No data will be posted online before the conference. - - - - - - - Conf. Chair: Dmitry Gabrilovich, MD, PhD [PPHM SAB] Keynote: Robert A. Weinberg, Whitehead Inst. for Biomedical Research, MIT 40 Speakers, including: Rolf A. Brekken [PPHM SAB], UTSW-MC/Dallas Dmitry I. Gabrilovich [PPHM SAB], The Wistar Institute, Philadelphia
TWO GENERAL SPONSORS: PEREGRINE & GENENTECH (Session: Juno, Galera; Day: Syndax)
= = = = = = = = = = = = = = = = = = = = = 11-9-15 SITC'15: New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w ...Also, collab. with Dr. Bernard Fox (Immunotherapist/Earle A. Chiles Res.Inst.) on new Immuno-Profiling Clinical Test (Opal 6-plex quantitative IF Assay), PPHM roundtable with Raymond Birge (Rutgers), Douglas Graham (Emory), Dmitry Gabrilovich (Wistar), Rolf Brekken (UTSW), Maria Karasarides (AstraZeneca) - ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.”
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
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
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)
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