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It was: a drug which has been unsuccessful (sorry, not worthless.)
Read their first letter.
BREKKEN - Drivers of EMT and Immune Evasion
Authors and affiliations
Rolf A. Brekken Email author ,
Katarzyna Wnuk-Lipinska
Rolf A. Brekken1
Email author
Katarzyna Wnuk-Lipinska2
1. Hamon Center for Therapeutic Oncology Research and the Departments of Surgery and Pharmacology, UT Southwestern Medical Center, Dallas, USA
2. BerGenBio ASA, Bergen, Norway
Chapter
First Online: 27 May 2017
Abstract
The heterogeneity of tumor cells and the complexity of the surrounding microenvironment make the process of predicting patient outcome and selection of the most suitable treatment regimen very difficult. Over the past decades, many biomarkers have been evaluated for prognostic value. The advent of immune therapy as a frontline treatment for some cancers has moved immune phenotyping into the forefront of biomarker and predictive marker research. Here, we review some of the regulatory mechanisms of the host immune response and epithelial plasticity and highlight their potential as biomarkers of the hallmark of immune evasion.
Keywords
TAM receptors Phosphatidylserine EMT Immunosuppression Inflammation
https://link.springer.com/chapter/10.1007/978-3-319-39147-2_9
https://books.google.at/books?hl=de&lr=&id=Y1ovDwAAQBAJ&oi=fnd&pg=PR7&dq=brekken+rolf&ots=wkrpKokQTl&sig=Eubvbz2S0avSsFeUaAQYlpFFlqQ#v=onepage&q=Brekken&f=false
Investor Contact:
Stephen White
SW Investment Management LLC
(312) 765-7033
Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin.
Tripisciano C1, Weiss R1, Eichhorn T1, Spittler A2, Heuser T3, Fischer MB1,4, Weber V5,6.
Author information
1Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.Core Facility Flow Cytometry & Surgical Research Laboratories, Medical University of Vienna, Lazarettgasse 14, 1090, Vienna, Austria.Electron Microscopy Facility, Vienna Biocenter Core Facilities, Dr.-Bohr-Gasse 3, 1030, Vienna, Austria.Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria. viktoria.weber@donau-uni.ac.at.Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria. viktoria.weber@donau-uni.ac.at.
Abstract
Cells release diverse types of vesicles constitutively or in response to proliferation, injury, inflammation, or stress. Extracellular vesicles (EVs) are crucial in intercellular communication, and there is emerging evidence for their roles in inflammation, cancer, and thrombosis. We investigated the thrombogenicity of platelet-derived EVs, which constitute the majority of circulating EVs in human blood, and assessed the contributions of phosphatidylserine and tissue factor exposure on thrombin generation. Addition of platelet EVs to vesicle-free human plasma induced thrombin generation in a dose-dependent manner, which was efficiently inhibited by annexin V, but not by anti-tissue factor antibodies, indicating that it was primarily due to the exposure of phosphatidylserine on platelet EVs. Platelet EVs exhibited higher thrombogenicity than EVs from unstimulated monocytic THP-1 cells, but blockade of contact activation significantly reduced thrombin generation by platelet EVs. Stimulation of monocytic cells with lipopolysaccharide enhanced their thrombogenicity both in the presence and in the absence of contact activation, and thrombin generation was efficiently blocked by anti-tissue factor antibodies. Our study provides evidence that irrespective of their cellular origin, EVs support the propagation of coagulation via the exposure of phosphatidylserine, while the expression of functional tissue factor on EVs appears to be limited to pathological conditions.
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.esao2017.org/wp-content/uploads/2017/07/ESAO-IFAO-2017_PreliminaryDetailedProgram.pdf%3F&ved=0ahUKEwiss_CdpubVAhVFVxQKHb6gDII4KBAWCEEwCQ&usg=AFQjCNHCEDFY3KIGdNvlm9UPZSdOwfmavQ
https://www.ncbi.nlm.nih.gov/pubmed/?term=Tripisciano%3B%5BAuthor%5D+phosphatidylserine
Role of Phosphatidylserine-Derived Negative Surface Charges in the Recognition and Uptake of Intravenously Injected B16BL6-Derived Exosomes by Macrophages.
Matsumoto A1, Takahashi Y2, Nishikawa M1, Sano K3, Morishita M1, Charoenviriyakul C1, Saji H3, Takakura Y1.
Author information
1Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: ytakahashi@pharm.kyoto-u.ac.jp.Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract
Exosomes are cell-derived extracellular vesicles that function as intercellular delivery carriers. Our previous study demonstrated that macrophages in the liver contributed to the rapid clearance of intravenously administered B16BL6-derived exosomes from the systemic circulation in mice. Phosphatidylserine (PS) may be responsible for this clearance because it is exposed on the surface of exosomes and is recognized by macrophages. In this study, the role of PS exposed on the membranes of exosomes in the uptake of B16BL6-derived exosomes by macrophages was investigated. Negatively charged PS- or phosphatidylglycerol-loaded liposomes suppressed the cellular uptake of PKH67-labeled exosomes by macrophages, whereas phosphatidylcholine-containing liposome did not affect uptake. Subsequently, for the in vivo analysis, exosomeswere labeled with Gaussia luciferase, a reporter protein, or (3-125I-iodobenzoyl)norbiotinamide using exosome-tropic fusion proteins comprising the exosome-tropic protein lactadherin. The blood clearance of Gaussia luciferase-labeled exosomes after intravenous injection into mice was significantly delayed by the preinjection of PS- or phosphatidylglycerol-containing liposomes. Moreover, the accumulation of (3-125I-iodobenzoyl)norbiotinamide-labeled exosomes in the liver was decreased by the preinjection of PS-containing liposomes. These results indicate that the negative charge of PS in exosomal membranes is involved in the recognition and clearance of intravenously injected exosomes by macrophages.
https://www.ncbi.nlm.nih.gov/pubmed/27649887
Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.
Skotland T1, Ekroos K2, Kauhanen D2, Simolin H2, Seierstad T3, Berge V4, Sandvig K5, Llorente A6.
Author information
Abstract
BACKGROUND:
Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers.
METHODS:
A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls.
RESULTS:
Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes andexosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed.
CONCLUSION:
This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers.
Copyright © 2016 Elsevier Ltd. All rights reserved.
https://www.ncbi.nlm.nih.gov/pubmed/27914242
Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response.
Chapuy-Regaud S1, Dubois M2, Plisson-Chastang C3, Bonnefois T2, Lhomme S4, Bertrand-Michel J5, You B6, Simoneau S6, Gleizes PE3, Flan B6, Abravanel F4, Izopet J4.
Author information
1INSERM, UMR1043, Toulouse, France; Department of Virology, CHU Purpan, Toulouse, France; Toulouse University, Toulouse, France. Electronic address: chapuy-regaud.s@chu-toulouse.fr.INSERM, UMR1043, Toulouse, France; Department of Virology, CHU Purpan, Toulouse, France.Toulouse University, Toulouse, France; CNRS, UMR5099, Toulouse, France.INSERM, UMR1043, Toulouse, France; Department of Virology, CHU Purpan, Toulouse, France; Toulouse University, Toulouse, France.Toulouse University, Toulouse, France; MetaToul-Lipidomic Core Facility, INSERM, UMR1048, Toulouse, France.
Abstract
The hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide. Although HEV is a small, naked RNA virus, HEV particles become associated with lipids in the blood of infected patients and in the supernatant of culture systems. The egress of these particles from cells implies the exocytosis pathway but the question of the role of the resulting HEV RNA containing exosomes and the nature of the lipids they contain has not been fully addressed. We determined the lipid proportions of exosomes from uninfected and HEV-infected cells and their role in HEV spreading. We cultured a suitable HEV strain on HepG2/C3A cells and analyzed the population of exosomes containing HEV RNA using lipidomics methods and electron microscopy. We also quantified HEV infectivity using an infectivity endpoint method based on HEV RNA quantification to calculate the tissue culture infectious dose 50. Exosomes produced by HEV-infected HepG2/C3A cells contained encapsidated HEV RNA. These HEV RNA-containing exosomes were infectious but ten times less than stools. HEV from stools, but not exosome-associated HEV from culture supernatant, was neutralized by anti-HEV antibodies in a dose-dependent manner. HEV infection did not influence the morphology or lipid proportions of the bulk of exosomes. These exosomes contained significantly more cholesterol, phosphatidylserine, sphingomyelin and ceramides than the parent cells, but less phosphoinositides and polyunsaturated fatty acids.Exosomes play a major role in HEV egress but HEV infection does not modify the characteristics of the bulk ofexosomes produced by infected cells. PS and cholesterol enriched in these vesicles could then be critical for HEV entry. HEV particles in exosomes are protected from the immune response which could lead to the wide circulation of HEV in its host.
https://www.ncbi.nlm.nih.gov/pubmed/28483690
Characterization of Annexin V Fusion with the Superfolder GFP in Liposomes Binding and Apoptosis Detection.
Abbady AQ1, Twair A1,2, Ali B1, Murad H1.
Author information
1Department of Animal Biology, Faculty of Sciences, Damascus UniversityDamascus, Syria.
Abstract
Programed cell death is a critical and unavoidable part of life. One of the most widely used markers for dying cells, by apoptosis or pyroptosis, is the redistribution of phosphatidylserine (PS) from the inner to the outer plasma membrane leaflet. Annexin V protein is a sensitive and specific probe to mark this event because of its high affinity to the exposed PS. Beyond that, annexin V can bind to any PS-containing phospholipid bilayer of almost all tiny forms of membranous vesicles like blood platelets, exosomes, or even nanostructured liposomes. In this work, recombinant human annexin V was produced as a fusion with a highly fluorescent superfolder derivative of the green fluorescent protein (sfGFP) in Escherichia coli. The fusion protein(sfGFP-ANXV, 64 kDa), annexin V (ANXV, 40 kDa), and sfGFP (27 kDa) were separately produced after cloning their encoding genes in pRSET plasmid, and all proteins were expressed in a soluble form, then purified in high yields because of their N-terminal 6× His tag (~150 mg of pure protein per 1 L culture). Superiority of this fluorescent fusion protein over fluorescein-conjugated annexin V was demonstrated in binding to phospholipids (and their liposomes), prepared from natural sources (soya bean and egg yolk) that have different content of PS, by using different methods including ELISA, dot-blotting, surface plasmon resonance, and flow cytometry. We also applied fluorescent annexin V in the detection of apoptotic cells by flow cytometry and fluorescent microscopy. Interestingly, sfGFP-ANXV fusion was more sensitive to early apoptotic stressed HeLa cells than fluorescein-conjugated-ANXV. This highly expressed and functional sfGFP-ANXV fusion protein provides a promising ready-to-use molecular tool for quantifying liposomes (or similarly exosomes) and detecting apoptosis in cells.
https://www.ncbi.nlm.nih.gov/pubmed/28579961
Optoacoustic detection of early therapy-induced tumor cell death using a targeted imaging agent
August 2017 - with PS
https://www.google.at/url?sa=t&source=web&rct=j&url=http://clincancerres.aacrjournals.org/content/early/2017/08/18/1078-0432.CCR-17-1029.full-text.pdf&ved=0ahUKEwiE1sa-0ePVAhXM6xQKHRxsBAw4ChAWCCEwAg&usg=AFQjCNFPObh4hz8bv260tCcc7fZmstx-wQ
Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling
18 August 2017
http://www.nature.com/articles/s41598-017-08433-9
Now down more then 47% since 7/14/17 - unbelievable or as we say in Austria : "zum Kotzen".
Have a nice Weekend!
THEY DON'T WANT TO COMMUNICATE! That's the fine difference.
-45% from 7/14/17 till now
Yes - it seems they (BOD) are secured in all directions!
One question:
what is a "Golden Parachute" - I read that somewhere in the www and there was a connection to pphm. Can´t find it anymore.
Maybe this helps....I hope????
PEREGRINE PHARMACEUTICALS INC -- SC 13G/A - Edgar Filings
14-Aug-2017 20:45:41
NAME OF REPORTING PERSONS
Tappan Street Partners LLC
I.R.S. IDENTIFICATION NO. OF ABOVE PERSONS
(ENTITIES ONLY) EIN: 45-2662859
2 CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ?
(b) ?
3 SEC USE ONLY
4 CITIZENSHIP OR PLACE OF ORGANIZATION
Delaware, United States of America
NUMBER OF
SHARES
BENEFICIALLY
OWNED BY
EACH
REPORTING
PERSON
WITH:
5 SOLE VOTING POWER
0
6 SHARED VOTING POWER
2,231,577*
7 SOLE DISPOSITIVE POWER
0
8 SHARED DISPOSITIVE POWER
2,231,577*
9 AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
2,231,577
10 CHECK BOX IF THE AGGREGATE AMOUNT IN ROW 9 EXCLUDES CERTAIN SHARES ?
11 PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW 9
4.95%†
12 TYPE OF REPORTING PERSON
IA
------------------------------------------------
NAME OF REPORTING PERSONS
Tappan Street Partners Fund L.P.
I.R.S. IDENTIFICATION NO. OF ABOVE PERSONS
(ENTITIES ONLY) EIN: 45- 2663014
2 CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ?
(b) ?
3 SEC USE ONLY
4 CITIZENSHIP OR PLACE OF ORGANIZATION
Delaware, United States of America
NUMBER OF
SHARES
BENEFICIALLY
OWNED BY
EACH
REPORTING
PERSON
WITH:
5 SOLE VOTING POWER
0
6 SHARED VOTING POWER
1,540,000
7 SOLE DISPOSITIVE POWER
0
8 SHARED DISPOSITIVE POWER
1,540,000
9 AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
1,540,000
10 CHECK BOX IF THE AGGREGATE AMOUNT IN ROW 9 EXCLUDES CERTAIN SHARES ?
11 PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW 9
3.42%†
12 TYPE OF REPORTING PERSON
PN
--------------------------------------------------
NAME OF REPORTING PERSONS
Prasad Phatak
I.R.S. IDENTIFICATION NO. OF ABOVE PERSONS
(ENTITIES ONLY)
2 CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (a) ?
(b) ?
3 SEC USE ONLY
4 CITIZENSHIP OR PLACE OF ORGANIZATION
United States of America
NUMBER OF
SHARES
BENEFICIALLY
OWNED BY
EACH
REPORTING
PERSON
WITH:
5 SOLE VOTING POWER
67,107
6 SHARED VOTING POWER
2,231,577*
7 SOLE DISPOSITIVE POWER
67,107
8 SHARED DISPOSITIVE POWER
2,231,577*
9 AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
2,298,684*
10 CHECK BOX IF THE AGGREGATE AMOUNT IN ROW 9 EXCLUDES CERTAIN SHARES ?
11 PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW 9
5.10%†
12 TYPE OF REPORTING PERSON
IN
TAPPAN STREET Partners Holdings:
Security Name Value Held ($) Position % Portfolio % Outstanding
Peregrine Pharmaceuticals Inc 9.484.202,25 2.231.577,00 25,89% 4,95%
Adient PLC 6.864.900,00 105.000,00 18,74% 0,11%
Voya Financial Inc 6.086.850,00 165.000,00 16,62% 0,09%
Hill International Inc 4.680.000,00 900.000,00 12,78% 1,73%
Hudson Technologies Inc 4.647.500,00 550.000,00 12,69% 1,32%
Sparton Corp 3.958.200,00 180.000,00 10,81% 1,83%
Alphabet Inc 908.730,00 1.000,00 2,48% 0,00%
Avid Bioservices to Exhibit at The Bioprocessing Summit 2017 - GNW
16-Aug-2017 14:05
TUSTIN, Calif., Aug. 16, 2017 (GLOBE NEWSWIRE) -- Avid Bioservices, Inc., a wholly owned subsidiary of Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), today announced that the company will exhibit at the upcoming Bioprocessing Summit 2017, being held August 21-25, 2017 in Boston, MA. Avid will host a corporate booth (#403) in the conference’s exhibit hall, where it will showcase the company’s comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries.
At the Bioprocessing Summit 2017, the Avid team will be able to discuss the company’s innovative processes for generating a broad range of biopharmaceutical product types including monoclonal antibodies, highly-glycosylated recombinant proteins and enzymes, among others.
As part of its exhibit, Avid will provide a virtual tour of the company’s 42,000 square foot state-of-the-art Myford manufacturing facility, which is designated for late-stage clinical and commercial manufacturing. As previously announced, the company will soon be ready to offer new larger scale capacity from the two recently installed 2,000-liter, single-use bioreactors at the Myford facility. The Myford facility is designed with cutting-edge, single-use equipment to accommodate a fully disposable biomanufacturing process. A wide range of innovative features are incorporated into the new Myford facility including monolithic modular clean rooms, dedicated support utilities for each key processing area, and the industry’s most advanced single-use production systems and flexible solutions. Uni-directional process flows separate personnel and materials and provide assurance that the design meets the most stringent regulatory requirements for commercial biologics API manufacturing.
For more information on The Bioprocessing Summit 2017, please visit: http://www.bioprocessingsummit.com/
About Avid Bioservices, Inc.
Avid Bioservices, a wholly owned subsidiary of Peregrine Pharmaceuticals, provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 20 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, stability testing and regulatory strategy, submission and support. The company also provides a variety of process development activities, including cell line development and optimization, cell culture and feed optimization, analytical methods development and product characterization. For more information about Avid, please visit www.avidbio.com.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit www.peregrineinc.com.
Contacts:
Kelly Pisarev Lord
Avid Bioservices, Inc.
(800) 987-8256
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
Two Pore Guys Announces Positive Results from Pilot Point-of-Care Liquid Biopsy Study with UCSF - BSW
16-Aug-2017 13:30
Two Pore Guys Announces Positive Results from Pilot Point-of-Care Liquid Biopsy Study with UCSF
Handheld, Low-Cost Nanopore-based Technology One Step Closer to Patient Home Use
Two Pore Guys, Inc. (2PG) today announced positive results from its pilot liquid biopsy study with the University of California, San Francisco. The retrospective study confirmed the company’s handheld nanopore-based sensor technology detected cell-free, circulating tumor DNA (ctDNA) from blood and urine samples in patients with colorectal or pancreatic cancer whose tumors were previously confirmed via DNA sequencing of biopsied tissue to harbor a known point mutation called KRAS G12D.
Results of the study were presented yesterday at the Next Generation Dx Summit (http://cts.businesswire.com/ct/CT...) by investigator Andrew Ko, MD, a Professor of Hematology/Oncology and a specialist in gastrointestinal cancer at the UCSF Helen Diller Family Comprehensive Cancer Center.
This is the first time a hand-held testing system was used in a liquid biopsy test. In the nine-patient study, blood samples were provided by all patients and urine samples were also available from five patients. The KRAS G12D mutation was detected in all nine blood samples, but more importantly, the mutation was detected in all five urine samples, emphasizing the viability of a small, low-cost system that could be used without requiring blood draws. Even more significantly, the process directly determined the mutant allele frequency, which is essential for clinical use in determining therapeutic treatment. 2PG also performed comparison studies to predicate platform qPCR assays and obtained similar results.
“Two Pore Guys has developed a fascinating technology that really offers the promise of point-of-care liquid biopsy. I’m looking forward to its future potential in many different clinical capacities, including in the oncology arena,” said Dr. Ko. “Based on the results of this proof-of-concept study, we are one step closer toward using this technology more broadly, such as in a patient’s own home. While there is still a lot to be worked out, I and others in the cancer research field are tremendously excited about this approach.”
Trevor Morin, Ph.D., Chief Scientific Officer of Two Pore Guys commented, “A major focus of 2PG is being able to facilitate self-administered tests across a large number of biomarkers from easily collected biofluids, such as urine, saliva and nasal swabs. In this study, the ability to measure ctDNA from urine with sensitivity levels suitable for clinical decision-making is unprecedented for a device that anyone can use. It’s also a much faster, more cost-effective alternative to traditional methods, such as next generation sequencing (NSG), microarray analysis, and qPCR. We are proud to have developed the first handheld device for real-time cancer monitoring.”
Dan Heller, Chief Executive Officer of Two Pore Guys added, “One of the very exciting things about our innovation is that it provides the practical ability to do serial monitoring -- whether it be daily, weekly, or monthly clinicians can monitor the patient’s response to treatment. In our study, we demonstrated how mutation status can change over relatively short periods of time, suggesting a benefit for testing frequently. We are grateful to Dr. Ko and his patients for helping us demonstrate the power of our unique approach.”
2PG’s novel use of solid-state nanopores enables digital, single-molecule sensing in a small, inexpensive, and simple-to-use form factor. The devices transmit data wirelessly to authorized systems and cloud infrastructures, thereby enabling such uses as telemedicine, clinical trials for drug development, and global tracking of pathogens and diseases. Target uses include human and animal diagnostics, agriculture, food safety testing, environmental monitoring, regulatory, and defense.
The company has begun collaborating with companies across multiple markets that plan to develop tests for the platform, similar to how software developers make apps for smartphones. Specific assays are developed by third parties to detect virtually any kind of molecule. Even existing tests made for traditional centralized lab equipment can be adapted to 2PG’s platform, allowing for a potentially unlimited menu of high-sensitivity tests to reach the market. 2PG manufactures the reader devices and test strips that incorporate the reagents from a partner’s assays, which are then sold through master distributors.
About Two Pore Guys
Two Pore Guys (2PG) has developed a handheld, single-molecule sensing platform with the accuracy, precision, and sensitivity of reference lab equipment and sample-in, results-out capability. The core technology includes solid-state, nanopore-based sensors that can detect nucleic acids and proteins and other analytes in human, animal, agriculture, and environmental samples. The battery-operated device is ideal for point-of-use applications. The easy-to-use platform is designed to sync with a smartphone or computer for further analysis and data sharing, including integration with electronic health records. Founded in 2011, the company is based in Santa Cruz, Calif. More information is available at twoporeguys.com (http://cts.businesswire.com/ct/CT...)
.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170816005041/en/ (http://www.businesswire.com/news/home/20170816005041/en/)
Bioscribe, Inc. Nicole Litchfield, 415-793-6468 nicole@bioscribe.com (mailto:nicole@bioscribe.com)
Copyright Business Wire 2017
Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells
Published online:15 August 2017
Investor Name % Outstanding Position Position Change Filing Date
Ronin Trading, L.L.C. 8,43% 3.801.139,00 +627.748,00 12-07-2017
Tappan Street Partners LLC 4,95% 2.231.577,00 +575.358,00 11-07-2017
Kennedy Capital Management, Inc. 3,09% 1.394.066,00 +146.867,00 30-06-2017
The Vanguard Group, Inc. 2,28% 1.029.734,00 +146.788,00 30-06-2017
BlackRock Institutional Trust Company, N.A. 1,68% 755.003,00 -37.781,00 30-06-2017
Renaissance Technologies LLC 1,07% 481.150,00 +41.485,00 30-06-2017
Geode Capital Management, L.L.C. 0,50% 225.675,00 +20.319,00 30-06-2017
Bandera Partners LLC 0,45% 203.000,00 +203.000,00 30-06-2017
Wellington Management Company, LLP 0,44% 199.540,00 0 31-03-2017
Eqis Capital Management, Inc. 0,33% 150.396,00 +1.486,00 30-06-2017
Swartz (Eric S) 0,21% 96.017,00 0 12-08-2016
Brown Advisory Securities, LLC 0,18% 82.857,00 0 30-06-2017
Jacobs Levy Equity Management, Inc. 0,18% 82.414,00 -2.329,00 30-06-2017
QS Investors, LLC 0,16% 71.914,00 0 30-06-2017
California Public Employees' Retirement System 0,15% 68.543,00 0 30-06-2017
Phatak (Prasad) 0,15% 67.107,00 +67.107,00 11-07-2017
Northern Trust Investments, Inc. 0,14% 64.245,00 +5.515,00 30-06-2017
Commonwealth Financial Network 0,13% 60.751,00 +1.071,00 30-06-2017
Citadel LLC 0,11% 51.007,00 +21.628,00 30-06-2017
BlackRock Financial Management, Inc. 0,11% 51.003,00 -11.650,00 30-06-2017
Wells Fargo Advisors 0,11% 48.340,00 +15.679,00 30-06-2017
King (Steven W) 0,07% 33.247,00 +2.849,00 28-04-2017
BNY Mellon Asset Management 0,06% 27.569,00 0 30-06-2017
AQR Capital Management, LLC 0,06% 27.284,00 0 30-06-2017
Lytle (Paul J) 0,06% 26.291,00 +5.341,00 28-04-2017
Baxter Investment Management 0,05% 21.500,00 0 30-06-2017
Squarepoint Ops LLC 0,05% 20.871,00 +14.814,00 30-06-2017
Fussey (Shelley P M) 0,04% 19.415,00 +3.633,00 31-10-2016
Spark Investment Management LLC 0,04% 18.371,00 +18.371,00 30-06-2017
Susquehanna Financial Group, LLLP 0,03% 15.090,00 +15.090,00 30-06-2017
State Street Global Advisors (US) 0,03% 14.517,00 0 30-06-2017
Shan (Joseph S) 0,03% 13.440,00 +5.597,00 28-04-2017
Brandes Investment Partners, L.P. 0,03% 12.729,00 0 30-06-2017
Guggenheim Investments 0,02% 10.755,00 0 30-06-2017
Morgan Stanley & Co. LLC 0,02% 8.939,00 -51.819,00 30-06-2017
Level Four Advisory Services, LLC 0,02% 8.243,00 0 30-06-2017
Airain Ltd 0,01% 6.052,00 +6.052,00 30-06-2017
Bank of America Merrill Lynch (US) 0,01% 5.171,00 -82,00 30-06-2017
UBS Financial Services, Inc. 0,01% 5.047,00 +420,00 30-06-2017
Sigma Planning Corporation 0,01% 5.000,00 0 30-06-2017
J.P. Morgan Securities LLC 0,01% 4.286,00 0 30-06-2017
Millennium Management LLC 0,01% 4.129,00 -5.070,00 30-06-2017
Investment Centers of America, Inc. 0,01% 3.579,00 0 30-06-2017
Ballentine Partners, LLC 0,01% 3.572,00 +3.572,00 30-06-2017
Independent Financial Partners 0,01% 3.571,00 0 30-06-2017
Stifel Nicolaus Investment Advisors 0,01% 3.543,00 0 30-06-2017
Perceptive Advisors LLC 0,01% 3.476,00 0 30-06-2017
KCG Americas LLC 0,01% 2.976,00 -31.153,00 30-06-2017
GFC Advisers LLC 0,01% 2.857,00 0 31-12-2016
Sterling Global Strategies LLC 0,01% 2.857,00 +1.428,00 30-06-2017
Yeha - if you have them! Without them its difficult. So don't blame him.
PEREGRINE PHARMACEUTICALS INC -- SC 13G/A
EDG
08/14/2017 8:45 PM
http://pdf.reuters.com/htmlnews/8knews.asp?i=43059c3bf0e37541&u=urn:newsml:reuters.com:20170814:EDG_0001387131-17-004169
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PEREGRINE FALLS TO SIX-MONTH LOW AFTER SECOND LARGEST SHAREHOLDER GROUP DECRIES FIRING EMPLOYEES PPHM.O
MIDTRD
08/14/2017 5:37 PM
11:35 AM EDT, 08/14/2017 (MT Newswires) -- Ronin Trading and SW Investment Management and some other shareholders, the second largest shareholders in Peregrine Pharmaceuticals (PPHM) with an 8.8% stake, said the drugmaker's board members should begin cost cutting by reducing their own and management's 'preposterously high salaries.'
'We find it outrageous that Peregrine's board of directors and management chose to fire roughly 20% of the Company's employees while doing nothing to address their own unjustifiable and egregious compensation,' they said in a letter to shareholders on Monday.
If Peregrine proceeds with its plan to expand the board from four to up to seven members, the shareholder group said it will nominate additional highly qualified director candidates 'to ensure that control of the board does not remain with the incumbents or their hand-picked additions.'
Price: 3.30, Change: -0.20, Percent Change: -5.71
Copyright (c) 2017 MT Newswires, a Division of MidnightTrader, Inc. All rights reserved.
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© Thomson Reuters 2017. All rights reserved.
Investor Name % Outstanding Position Position Change Filing Date
Ronin Trading, L.L.C. 8,43% 3.801.139,00 +627.748,00 12-07-2017
Tappan Street Partners LLC 5,10% 2.298.684,00 +1.384.398,00 11-07-2017
Kennedy Capital Management, Inc. 3,09% 1.394.066,00 +146.867,00 30-06-2017
The Vanguard Group, Inc. 2,28% 1.029.734,00 +146.788,00 30-06-2017
BlackRock Institutional Trust 1,68% 755.003,00 -37.781,00 30-06-2017
Renaissance Technologies LLC 1,07% 481.150,00 +41.485,00 30-06-2017
Geode Capital Management, L.L.C. 0,46% 205.356,00 +49.259,00 31-03-2017
Bandera Partners LLC 0,45% 203.000,00 +203.000,00 30-06-2017
Wellington Management Company, LLP 0,44% 199.540,00 0 31-03-2017
Eqis Capital Management, Inc. 0,33% 150.396,00 +1.486,00 30-06-2017
Swartz (Eric S) 0,21% 96.017,00 0 12-08-2016
Jacobs Levy Equity Management, Inc. 0,19% 84.743,00 +7.200,00 31-03-2017
Brown Advisory Securities, LLC 0,18% 82.857,00 +82.857,00 31-03-2017
QS Investors, LLC 0,16% 71.914,00 0 31-03-2017
California Public Employees' 0,15% 68.543,00 0 30-06-2017
Northern Trust Investments, Inc. 0,14% 64.245,00 +5.515,00 30-06-2017
Commonwealth Financial Network 0,13% 60.751,00 +1.071,00 30-06-2017
Citadel LLC 0,11% 51.007,00 +21.628,00 30-06-2017
BlackRock Financial Management, Inc. 0,11% 51.003,00 -11.650,00 30-06-2017
Wells Fargo Advisors 0,11% 48.340,00 +15.679,00 30-06-2017
King (Steven W) 0,07% 33.247,00 +2.849,00 28-04-2017
JBC Editorial Board - Expertise Term: Phosphatidylserine
http://apps.asbmb.org/JBCboard/Default.aspx?KeyWordId=26086&KeyWordName=Phosphatidylserine
Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
Hartmann J1, Schüßler-Lenz M2,3, Bondanza A4, Buchholz CJ1,3.
Author information
1Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.Innovative immunotherapies, Ospedale San Raffaele, Milano, Italy.
Abstract
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. More than 200 CAR Tcell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.
© 2017 The Authors. Published under the terms of the CC BY 4.0 license.
KEYWORDS:
ATMPs; cancer; immunotherapy; regulatory issues; toxicities
https://www.ncbi.nlm.nih.gov/pubmed/28765140
Peregrine Announces Measures to Reduce Costs, Facilitate Profitability and Strengthen its Operations - GNW
Reductions in R&D, manufacturing and administrative personnel
Anticipated annual cost savings of over $7 million
TUSTIN, Calif., Aug. 11, 2017 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (Nasdaq:PPHM) today announced that it has reduced its overall workforce by 60 employees (or 20%) as part of its series of planned strategic actions to reduce costs and better position the Company to achieve overall profitability while it pursues strategic options for its research and development (R&D) assets. The Company expects the workforce reductions to result in a net cost savings of between $3.7 million and $4.3 million in fiscal year 2018 and more than $7 million in reduced annualized operating expenses beginning in fiscal year 2019.
As part of the cost saving initiatives, the Company reduced Peregrine’s R&D personnel by 50% to 11 employees, with the remaining staff supporting potential strategic alternatives for its R&D assets while continuing to assist with collaborative trials, the antibody discovery platform, and the exosome program. Personnel supporting the Avid Bioservices CDMO business, a wholly owned subsidiary of Peregrine Pharmaceuticals, was reduced by 20% to 184 employees to align operations with the reduction in forecasted revenues. In addition, selling, general and administrative (SG&A) personnel was reduced by 8% to 49 employees as the Company continues to pursue leaner support operations. The charge to earnings for these personnel reductions will be between $1.1 million and $1.7 million, all of which is expected to be incurred during the second quarter of fiscal year 2018.
“While this was a difficult decision, our board and management team believe it was a necessary step as we continue to evaluate strategic options to further strengthen our two distinct businesses and seek to maximize shareholder value,” said Steven King, president, chief executive officer and director of Peregrine and president of Avid Bioservices. “I would like to personally express my appreciation to the affected employees for their commitment and meaningful contributions to the Peregrine and Avid businesses. We remain committed to capitalizing on long-term opportunities available to our CDMO business and pursuing the best path forward for our R&D business.”
Last month, Peregrine announced that as part of its strategic review it intends to expand its board of directors to add new members with CDMO and biologics experience and to commence a search for a dedicated president to head its Avid CDMO business.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit www.peregrineinc.com.
About Avid Bioservices, Inc.
Avid Bioservices, Inc., a wholly owned subsidiary of Peregrine Pharmaceuticals, provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 20 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, Avid's services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, stability testing and regulatory strategy, submission and support. The company also provides a variety of process development activities, including cell line development and optimization, cell culture and feed optimization, analytical methods development and product characterization. For more information about Avid, please visit www.avidbio.com.
Forward–Looking Statements
This communication contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include those containing such words as “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “guidance,” “goal,” “intends,” “may,” “outlook,” “plans,” “projects,” “seeks,” “sees,” “should,” “targets,” “will,” “would,” or other words of similar meaning, including, without limitation, statements regarding Peregrine’s intent to increase the size of its Board of Directors and add independent members with CDMO and biologics experience, the company’s intent to initiate a search for a President to lead its wholly-owned CDMO subsidiary, Avid Bioservices, Inc., Peregrine’s plans for advancing its R&D business, as well as the expected timing for the foregoing matters. All statements that reflect Peregrine’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements and guidance regarding future financial results or operating performance. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties, and changes in circumstances that are difficult to predict. Although Peregrine believes that the expectations reflected in any forward-looking statements are based on reasonable assumptions, it can give no assurance that these expectations will be attained and it is possible that actual results may differ materially from those indicated by these forward-looking statements due to a variety of risks and uncertainties. Such risks and uncertainties include, but are not limited to the risk factors discussed in Peregrine’s Form 10-K for the year ended April 30, 2017, and other reports filed with the U.S. Securities and Exchange Commission (SEC). Peregrine disclaims any obligation to update publicly any forward-looking statements, whether in response to new information, future events or otherwise, except as required by applicable law.
Important Additional Information Peregrine intends to file a proxy statement with the Securities and Exchange Commission (SEC) in connection with the solicitation of proxies for Peregrine’s 2017 Annual Meeting (Proxy Statement) with an associated WHITE proxy card. Peregrine, its directors and certain of its executive officers will be participants in the solicitation of proxies from stockholders in respect of the 2017 Annual Meeting. Information regarding the names of Peregrine’s directors and executive officers and their respective interests in Peregrine by security holdings or otherwise is set forth in the Annual Report on Form 10-K of Peregrine, for the fiscal year ended April 30, 2017, filed with the SEC on July 14, 2017, and Peregrine’s proxy statement for the 2016 Annual Meeting, filed with the SEC on August 26, 2016. To the extent holdings of such participants in Peregrine’s securities are not reported, or have changed since the amounts described, in the 2016 proxy statement, such changes have been reflected on Initial Statements of Beneficial Ownership on Form 3 or Statements of Change in Ownership on Form 4 filed with the SEC. Details concerning the nominees of Peregrine’s Board of Directors for election at the 2017 Annual Meeting will be included in the Proxy Statement. BEFORE MAKING ANY VOTING DECISION, INVESTORS AND STOCKHOLDERS OF THE COMPANY ARE URGED TO READ ALL RELEVANT DOCUMENTS FILED WITH OR FURNISHED TO THE SEC, INCLUDING THE COMPANY’S DEFINITIVE PROXY STATEMENT AND ANY SUPPLEMENTS THERETO, BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION. Investors and stockholders will be able to obtain a copy of the definitive proxy statement and other documents filed by Peregrine free of charge from the SEC’s website, www.sec.gov. Peregrine’s stockholders will also be able to obtain, without charge, a copy of the definitive Proxy Statement and other relevant filed documents by directing a request by mail to Peregrine, Corporate Secretary’s Office, 14282 Franklin Avenue, Tustin, CA 92780, by calling Peregrine’s proxy solicitor, MacKenzie Partners, Inc., toll-free at (800) 322-2885, or from Peregrine’s website at www.peregrineinc.com.
Contacts:
Stephanie Diaz (investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
GlobeNewswire, Inc. 2017
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PEREGRINE PHARMACEUTICALS INC - ?AS PART OF COST SAVING INITIATIVES, COMPANY REDUCED PEREGRINE'S R&D PERSONNEL BY 50% TO 11 EMPLOYEES? - RTRS | News | Thomson Reuters Eikon
Thanks - I hate R....s!
Can´t find Peregrine at Eastern Capital Top Holdings - have I missed something OR wrong data???
Security Name % Portfolio
Alnylam Pharmaceuticals Inc 57,66%
Spectrum Pharmaceuticals Inc 9,33%
Cytokinetics Inc 7,91%
Exelixis Inc 6,81%
Resverlogix Corp 6,38%
TapImmune Inc 3,34%
Ibio Inc 2,75%
Vericel Corp 2,16%
Verastem Inc 1,05%
XOMA Corp 1,03%
Cyclacel Pharmaceuticals Inc 0,94%
Mirna Therapeutics Inc 0,63%
PLS help!
Then it´s "OLD" and we can forget it!?
Thanks
Hutschi
TUMOR IMMUNITY United States Patent Application 20170224793
Inventors:
Dranoff, Glenn (Lexington, MA, US)
Jinushi, Masahisa (Tokyo, JP)
Assignee:
Dana-Farber Cancer Institute, Inc. (Boston, MA, US)
Publication Date:
08/10/2017
Filing Date:
09/26/2016
5 CAR-T Stocks in Focus as NVS Drug Wins FDA Advisory Panel Vote NOVN.S - Zacks.com
18-Jul-2017 15:48:50
Jul 18, 2017
The CAR-T (chimeric antigen receptor T cells) space got a significant boost recently with an FDA advisory panel issuing a positive recommendation for an experimental treatment in this corner of the immune-oncology market. Last week, Swiss pharma giant, Novartis' NVS experimental CAR-T therapy, CTL019, got a unanimous (10-0) vote of approval from the FDA's Oncologic Drugs Advisory Committee (ODAC). Novartis is looking to get CTL019 approved for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). CTL019 is currently under priority review and timely approval would make it the first CAR-T cell therapy to be available.
How Does CAR-T Cell Therapy Work?
CAR-T falls under the ambit of cellular immunotherapy which involves using a patient's own immune cells to attack and get rid of harmful disease cells in the body.
The CAR-T approach involves -- the collection of a patient's T cells, their genetic modification outside the body, the incorporation of specific receptors which target cancer cells and finally, the re-infusion of the modified T cells back into the patient.
There is a lot of enthusiasm for CAR-T as early stage studies have shown that it can help achieve durable complete responses in some leukemias and lymphomas, including in patients who have suffered multiple relapses. But, CAR-T therapy comes with its own set of challenges including a high level of R&D investment as well as safety issues like serious immune toxicity (CRS) or neurotoxicity. Pricing could be an issue as well as these treatments will not come cheap.
However, these treatments have huge commercial potential and could well change the treatment paradigm.
5 CAR-T Stocks in Focus
Given the increased focus on this corner of the immune-oncology market and the possibility that a CAR-T drug could enter the market by year end, here is a look at 5 companies that are working on CAR-T cell treatments.
Kite Pharma, Inc. KITE :Santa Monica, CA-based Kite is a cell therapy company engaged in the development of innovative cancer immunotherapies with the goal of providing rapid, long-term durable response and eliminating the burden of chronic care. The company's focus is on CAR and T cell receptor (TCR) engineered cell therapies.
Kite is following close on the heels of Novartis where FDA approval of a CAR-T treatment is concerned. Lead pipeline candidate, axicabtagene ciloleucel, is currently under priority review in the U.S. for the treatment of patients with refractory aggressive non-Hodgkin lymphoma (NHL). A response from the FDA is expected by Nov 29, 2017. The company will be filing for EU approval in the third quarter. Axicabtagene ciloleucel targets the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias.
According to the company, the initial market opportunity for axicabtagene ciloleucel includes about 7,400 and 7,000 addressable CAR-T patients in the U.S. and Europe, respectively, while 7,800 new cases are diagnosed in Japan every year and 25,000 in key urban/eastern rural coastal areas of China.
Kite has had a strong run so far in 2017 with shares skyrocketing 128.1%, outperforming the Zacks-categorized Medical-Biomedical/Genetics industry which is up about 9%.
Bellicum Pharmaceuticals, Inc. BLCM :Houston, TX-based Bellicum is a clinical stage biopharma company working on novel, controllable cellular immunotherapies for different forms of cancer, including hematological cancers as well as solid tumors, and orphan inherited blood disorders. The company's proprietary chemical induction of dimerization (CID) technology platform is designed to potentially offer better safety and efficacy outcomes compared to other cellular immunotherapies.
The company's pipeline candidates include BPX-501 (an adjunct T-cell therapy for allogeneic hematopoietic stem cell transplantation, registration studies advancing in the EU while preparations are on for registration studies in the U.S.), BPX-601 (GoCAR-T candidate, for solid tumors, designed with the proprietary iMC activation switch to improve efficacy, phase I), and BPX-701 (high affinity TCR candidate, for solid tumors, designed with the CaspaCIDe safety switch, phase I).
Bellicum's shares are down almost 12% year-to-date (YTD), lagging the Zacks-categorized Medical-Drugs industry which is up 5.8% during this period.
Juno Therapeutics, Inc. JUNO :Seattle, WA-based Juno is another key player in the cellular immunotherapy area. Although the company suffered a major setback with the development of its erstwhile lead pipeline candidate due to safety issues (including patient deaths), Juno is now focusing on JCAR017, a CAR-T cell product that targets CD19.
Juno is looking to get JCAR017 on the market as early as 2018 for NHL. The company also has a strong partner in Celgene CELG .
Juno's shares are up 44.9% YTD.
ZIOPHARM Oncology, Inc. ZIOP :Boston, MA-based ZIOPHARM is a biotech company that uses innovative gene expression, control and cell technologies to provide safe, effective and scalable cell- and viral-based therapies for cancer and graft-versus-host-disease. ZIOPHARM's immune-oncology platform includes CAR-T as well as other adoptive cell-based approaches.
ZIOPHARM is advancing programs in multiple stages of development together with Intrexon's RheoSwitch Therapeutic System (RTS) technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index.
Within the CAR+ T programs, the company is continuing with a phase I second generation study of CD19 specific CAR+ T for lymphoid malignancies and expects to move third generation CD19 with mbIL15 towards an early-stage study evaluating point-of-care. Plans are also on to commence a phase I study with CD33-specific CAR+ T for relapsed/refractory acute myeloid leukemia (AML) this year.
ZIOPHARM's shares are up 9.5% YTD.
NantKwest, Inc. NK :NantKwest is a clinical-stage immunotherapy company focused on using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. The company's NK cell-based platform has been designed to induce cell death against cancer or infected cells by three different modes of action -- direct killing using activated NK cells (aNK); antibody-mediated killing using haNKs; and targeted activated killing using taNKs.
NantKwest's shares are up 19.2% so far in 2017.
While Kite, ZIOPHARM, Bellicum and NantKwest are all Zacks Rank #3 (Hold) stocks, Juno is a Zacks Rank #2 (Buy) stock. Meanwhile, you can see the complete list of today's Zacks #1 Rank (Strong Buy) stocks here .
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Novartis AG (NVS): Free Stock Analysis Report
Celgene Corporation (CELG): Free Stock Analysis Report
ZIOPHARM Oncology Inc (ZIOP): Free Stock Analysis Report
Kite Pharma, Inc. (KITE): Free Stock Analysis Report
Juno Therapeutics, Inc. (JUNO): Free Stock Analysis Report
NantKwest, Inc. (NK): Free Stock Analysis Report
Bellicum Pharmaceuticals, Inc. (BLCM): Free Stock Analysis Report
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Novartis CAR-T cell therapy CTL019 unanimously (10-0) recommended for approval by FDA advisory committee to treat pediatric, young adult r/r B-cell ALL - PR Newswire
12-Jul-2017 23:25:43
Novartis CAR-T cell therapy CTL019 unanimously (10-0) recommended for approval by FDA advisory committee to treat pediatric, young adult r/r B-cell ALLRecommendation based on review of CTL019 r/r B-cell ALL development program, including the pivotal Phase II global ELIANA trialA Biologics License Application (BLA) for this indication is under FDA priority review; if approved, CTL019 could become first CAR-T cell therapy availablePositive ODAC recommendation is latest milestone for CTL019 program that started through collaboration with the University of Pennsylvania PR Newswire
EAST HANOVER, N.J., July 12, 2017
EAST HANOVER, N.J., July 12, 2017 /PRNewswire/ -- Novartis announced today that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).
"The panel's unanimous recommendation in favor of CTL019 moves us closer to potentially delivering the first-ever commercially approved CAR-T cell therapy to patients in need," said Bruno Strigini, CEO, Novartis Oncology. "We're very proud to be expanding new frontiers in cancer treatment by advancing immunocellular therapy for children and young adults with r/r B-cell ALL and other critically ill patients who have limited options. We look forward to working with the FDA as they complete their review."
Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US(1). Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL that have relapsed multiple times or become refractory to treatment, the five-year disease-free survival is less than 10-30%(2,3,4).
The ODAC recommendation is based on review of the CTL019 r/r B-cell ALL development program, which includes the Novartis-led ELIANA study (NCT02435849), the first pediatric global CAR-T cell therapy registration trial. Findings from a US multicenter trial and a single site trial examining the safety and efficacy of CTL019 among pediatric and young adult patients with r/r B-cell ALL also supported the recommendation and the Biologics License Application (BLA)(5).
CTL019 was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Children's Hospital of Philadelphia (CHOP) was the first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.
"It is encouraging to see the FDA panel's recommendation and continued momentum behind this innovative therapy, which has potential to help young patients with relapsed/refractory B-cell ALL," said the Penn team's leader, Carl June, MD, the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn. "We look forward to continuing to work with Novartis to help make a lasting impact on the way this disease is treated."
"We know firsthand from treating children and young adults with relapsed/refractory B-cell ALL that they desperately need innovative medicines that provide a new approach to managing this aggressive disease," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, Director of the Cancer Immunotherapy Frontier Program and Chief of the Section of Cellular Therapy and Transplant at CHOP. "Today's vote in favor of CTL019 is a positive step and we appreciate Novartis' commitment to pediatric patients."
Earlier this year, Novartis submitted a BLA for CTL019 to the FDA, marking the first submission by Novartis for a CAR-T cell therapy. CTL019 previously received FDA Breakthrough Therapy designation and is under Priority Review by the FDA. The FDA will consider the vote as it reviews the BLA, although it is not obligated to follow the recommendation. Novartis continues to invest in the necessary infrastructure for the potential commercialization of CTL019, including manufacturing and the establishment of a network of certified treatment centers.
Novartis plans additional filings for CTL019 in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA) for the treatment of adults with r/r diffuse large B-cell lymphoma (DLBCL).
About CAR-T and CTL019
CAR-T is different from typical small molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient's blood and reprogrammed in the manufacturing facility to create T cells that are genetically coded to express a chimeric antigen receptor to recognize and fight cancer cells and other B-cells expressing a specific antigen.
ELIANA (NCT02435849) is the first pediatric global CAR-T cell therapy registration trial, with study enrollment having occurred across 25 centers in the US, Canada, EU, Australia and Japan.
Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.
About CTL019 Manufacturing
The Novartis leukapheresis process using cryopreservation allowed for manufacturing and treatment of patients from around the world. Cryopreserved leukapheresis involves removing white blood cells from a patient's blood and preserving them at very low temperatures. Cryopreserved leukapheresis gives physicians the flexibility to schedule apheresis at a time that is in the best interest of their patients. Novartis commercial manufacturing for CTL019 continues to build on its experience in its Morris Plains, New Jersey facility, which has already manufactured CTL019 for hundreds of patients in global clinical trials. Novartis believes that experience is important in cell therapy manufacturing, and the experience gained at the Morris Plains, New Jersey facility will be a foundation for commercial manufacturing of CAR-T therapies. Novartis has made and continues to make investments in manufacturing.
Disclaimer
This press release contains forward-looking statements, including "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for CTL019 and the other investigational products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that CTL019 or the other investigational products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that Novartis will successfully implement and maintain commercial manufacturing for CTL019 or the other investigational products described in this press release, or successfully build a network of treatment centers to offer CTL019 or the other investigational products described in this press release. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; our ability to successfully implement and maintain commercial manufacturing and build a network of treatment centers; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Located in East Hanover, NJ Novartis Pharmaceuticals Corporation is an affiliate of Novartis which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.
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References
1. Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics Review, 1975–2010. National Cancer Institute, April 2013; Section 28.9 (12).
2. Oudot, C.., Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March 2008; Volume 28 (9).
3. Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003;
123 (3).
4. Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and
adolescents with a second or third relapse of acute lymphoblastic leukemia
(ALL): a population-based analysis of the Austrian ALL-BFM
(Berlin-Frankfurt-Münster) Study Group. Journal of Pediatric
Hematology/Oncology. July 2013; 35 (5).
5. Novartis CTL019 ODAC Briefing Document.
Novartis Media Relations
Central media line: +41 61 324 2200 E-mail: media.relations@novartis.com
Eric Althoff Novartis Global Media Relations +41 61 324 7999 (direct) +41 79 593 4202 (mobile) eric.althoff@novartis.com Fiona Phillips Novartis Oncology Communications +1 862-778-7705 (direct) +1 862-217-9396 (mobile) fiona.phillips@novartis.com
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Will do that walk with you (from Austria) - but next spring (not so hot!)
FDA panel backs Novartis' pioneering new cancer gene therapy - Reuters News
12-Jul-2017 22:48:08
Adds comment from panelist, analyst
By Toni Clarke
July 12 (Reuters) - Novartis AG's NOVN.S pioneering new cancer drug won enthusiastic support from a federal advisory panel on Wednesday, paving the way for approval of the first U.S. gene therapy.
The panel unanimously recommended that the Food and Drug Administration approve the drug, tisagenlecleucel, for patients ages 3 to 25 with relapsed B-cell acute lymphoblastic leukemia (ALL), the most common form of U.S childhood cancer.
The drug uses a new technology known as CAR-T, or chimeric antigen receptor T-cell therapy, which harnesses the body's own immune cells to recognize and attack malignant cells.
In a clinical trial, 83 percent of patients who had relapsed or failed chemotherapy achieved complete or partial remission three months post infusion. After one year 79 percent of patients were still alive.
Patients with ALL who fail chemotherapy typically have only a 16 percent to 30 percent chance of survival.
"This is a potentially paradigm-changing type of benefit," said Dr. Brian Rini, a panelist and physician at Cleveland Clinic Taussig Cancer Institute.
The FDA is not obliged to follow the recommendations of its advisers but typically does so. The agency is expected to rule on the drug by the end of September.
Approval of tisagenlecleucel would have significant implications not only for Novartis but for companies developing similar treatments, including Kite Pharma Inc KITE.O, Juno Therapeutics Inc JUNO.O and bluebird bio Inc BLUE.O.
It would also advance a technique scientists have been attempting to perfect for decades and help lift the entire field of cell therapy. (Full Story)
"This will be a historic approval," said Brad Loncar, chief executive of Loncar Investments which runs the Loncar Cancer Immunotherapy ETF CNCR.O. "As an investor I've never seen anything like it. It's an entirely new way of treating cancer."
The product is made by extracting and isolating a patient's T cells, genetically engineering them to recognize and target cancer cells, and then infusing them back into the patient. Novartis said the entire process will take 22 days by the time it is launched.
The treatments are given just once and are expected to cost up to $500,000. Loncar said approval of tisagenlecleucel would represent an inflection point for investors.
"Any time a new technology crosses the finish line at the FDA, it gets noticed and I think you'll see a rush of investment and see these therapies be improved over time."
More than half of patients experienced a serious complication known as cytokine release syndrome (CRS) which occurs when the body's immune system goes into overdrive. Doctors were able to manage the condition and the syndrome caused no deaths.
The FDA expressed concern that the drug could cause new malignancies over the long term. Panelists generally felt that risk was low and they said Novartis's risk mitigation proposals were adequate.
Novartis is also testing the drug in diffuse large B-cell Lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, as is Kite.
Novartis's stock NVS.N closed up 1.5 percent at $83.21 in U.S. trading. The shares NOVN.S finished up 2.2 percent at 80.5 Swiss francs in Zurich before the vote was taken.
(Reporting by Toni Clarke in Washington; Editing by Lisa Shumaker)
(( toni.clarke@thomsonreuters.com ; 202-898-8340; Reuters Messaging: toni.clarke.thomsonreuters.com@reuters.net ))
Keywords: NOVARTIS-CANCER/ (UPDATE 1, PIX)
A Phase I Clinical Trial of the Phosphatidylserine-targeting Antibody Bavituximab in Combination With Radiation Therapy and Capecitabine in the Preoperative Treatment of Rectal Adenocarcinoma.
Meyer J1, Arriaga Y, Anandam J, Karri S, Syed S, Verma U, Abdelnaby A, Raja G, Dong Y, Beg M, Balch G.
Author information
1Departments of *Radiation Oncology †Internal Medicine ‡Surgery, University of Texas Southwestern Medical Center Dallas, TX.
Abstract
OBJECTIVES:
There is interest in improving the tumoricidal effects of preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers. The safety and toxicity profile of these combination regimens needs rigorous clinical evaluation. The primary objective of this study was to evaluate the toxicity of combining bavituximab, an antibody that targets exposed phosphatidylserine, with capecitabine and radiation therapy.
MATERIALS AND METHODS:
Patients with stage II or III rectal adenocarcinoma were enrolled on a phase I study combining radiation therapy, capecitabine, and bavituximab. A standard 3+3 trial designed was used.
RESULTS:
In general, bavituximab was safe and well tolerated in combination with radiation therapy and capecitabine in the treatment of rectal adenocarcinoma. One patient at the highest dose level experienced a grade III infusion reaction related to the bavituximab. One tumor demonstrated a complete pathologic response to the combination treatment.
CONCLUSIONS:
Bavituximab is safe in combination with capecitabine and radiation therapy at the doses selected for the study. Further clinical investigation would be necessary to better define the efficacy of this combination.
PMID: 28763330 DOI: 10.1097/COC.0000000000000401
https://www.ncbi.nlm.nih.gov/pubmed/28763330
Identification of lipid-phosphatidylserine (PS) as the target of unbiasedly selected cancer specific peptide-peptoid hybrid PPS1.
FROM MAY 2016!
Desai TJ1, Toombs JE2, Minna JD2,3,4,5, Brekken RA2,3,4,6, Udugamasooriya DG1,7.
Author information
1Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Abstract
Phosphatidylserine (PS) is an anionic phospholipid maintained on the inner-leaflet of the cell membrane and is externalized in malignant cells. We previously launched a careful unbiased selection targeting biomolecules (e.g. protein, lipid or carbohydrate) distinct to cancer cells by exploiting HCC4017 lung cancer and HBEC30KT normal epithelial cells derived from the same patient, identifying HCC4017 specific peptide-peptoid hybrid PPS1. In this current study, we identified PS as the target of PPS1. We validated direct PPS1 binding to PS using ELISA-like assays, lipid dot blot and liposome based binding assays. In addition, PPS1 recognized other negatively charged and cancer specific lipids such as phosphatidic acid, phosphatidylinositol and phosphatidylglycerol. PPS1 did not bind to neutral lipids such as phosphatidylethanolamine found in cancer and phosphatidylcholine and sphingomyelin found in normal cells. Further we found that the dimeric version of PPS1 (PPS1D1) displayed strong cytotoxicity towards lung cancer cell lines that externalize PS, but not normal cells. PPS1D1 showed potent single agent anti-tumor activity and enhanced the efficacy of docetaxel in mice bearing H460 lung cancer xenografts. Since PS and anionic phospholipid externalization is common across many cancer types, PPS1 may be an alternative to overcome limitations of protein targeted agents.
https://www.ncbi.nlm.nih.gov/pubmed/27120792