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PM .68 vol 28200
• 04-Apr-2017 14:05:05 - PEREGRINE PHARMACEUTICALS HIGHLIGHTS CLINICAL DATA PRESENTATION AT AACR 2017 ANNUAL MEETING SUPPORTING POTENTIAL OF BAVITUXIMAB TO ENHANCE ANTI-TUMOR ACTIVITY OF IMMUNOTHERAPY
• 04-Apr-2017 14:05:55 - PEREGRINE PHARMAC- DATA SHOWED FOR PATIENTS IN STUDY'S BAVITUXIMAB PLUS DOCETAXEL TREATMENT ARM WHO RECEIVED SUBSEQUENT IMMUNOTHERAPY, MOS WAS NOT REACHED
• 04-Apr-2017 14:06:05 - PEREGRINE PHARMACEUTICALS INC - MOS WAS 13.0 MONTHS FOR PATIENTS IN STUDY'S PLACEBO PLUS DOCETAXEL ARM WHO RECEIVED SUBSEQUENT IMMUNOTHERAPY
PEREGRINE PHARMACEUTICALS INC - MOS WAS 13.0 MONTHS FOR PATIENTS IN STUDY'S PLACEBO PLUS DOCETAXEL ARM WHO RECEIVED SUBSEQUENT IMMUNOTHERAPY - Reuters News
Peregrine Pharmaceuticals Highlights Clinical Data Presentation at AACR 2017 Annual Meeting Supporting Potential of Bavituximab to Enhance Anti-tumor Activity of Immunotherapy - GNW
04-Apr-2017 14:05
SUNRISE Data Analysis Demonstrates Statistically Significant Overall Survival (OS) Improvement in Patients Receiving Bavituximab plus Docetaxel and Subsequent Immunotherapy Compared to Placebo plus Docetaxel and Subsequent Immunotherapy --
TUSTIN, Calif., April 04, 2017 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies, and advancing its proprietary R&D pipeline, today announced the presentation of results of a new analysis of the Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Data demonstrated that for patients in the study’s bavituximab plus docetaxel treatment arm who received subsequent immunotherapy, the median overall survival (mOS) was not reached, while mOS was 13.0 months for patients in the study’s placebo plus docetaxel arm who received subsequent immunotherapy [HR = 0.43; p=0.005]. These are the first clinical results reported supporting the hypothesis that bavituximab may modulate the tumor microenvironment to enhance the anti-tumor activity of immunotherapy agents. Data were presented by Peregrine scientists at the 2017 Annual Meeting of the American Association for Cancer Research (AACR), which is being held April 1-5, 2017 in Washington, D.C.
The presentation highlighted an analysis in which the company evaluated the impact of subsequent immunotherapy treatment, as well as patients’ pre-treatment interferon gamma (IFN-?) levels on overall survival. Overall, low peripheral IFN-? correlated with more favorable OS in the patients receiving bavituximab + docetaxel and is a biomarker of interest. Data were also analyzed by low versus high IFN-? levels. For patients with low pre-treatment IFN-? levels who received subsequent immunotherapy, those in the bavituximab plus docetaxel arm did not reach mOS compared to mOS of 12.1 months for the placebo plus docetaxel arm [HR = 0.24; p < 0.001].
“We are extremely encouraged by the results of these exploratory analyses which provide further clinical rationale for combining bavituximab and checkpoint inhibitors,” said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. “This will be the key focus for upcoming early phase clinical trials, which includes a study of bavituximab and pembrolizumab in head and neck cancer through our ongoing collaboration with the National Comprehensive Cancer Network.”
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. PS-targeting antibodies have demonstrated an ability to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses. Bavituximab is believed to override PS immunosuppressive signaling by blocking the engagement of PS with its receptors and sending an alternate immune activating signal.
Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with MSK with the goal of evaluating combinations of bavituximab with checkpoint inhibitors and other immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab's combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.
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.
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that median OS data from a clinical trial combining bavituximab with a checkpoint inhibitor will not be consistent with the data from the SUNRISE trial for those patients received subsequent immunotherapy following cessation of treatment with bavituximab and docetaxel and the risk that data from subsequent studies do not confirm that IFN-y is a predictive biomarker for patients who are more likely to benefit from a bavituximab containing therapeutic regimen. . The company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in our reports filed with the Securities and Exchange Commission including, but not limited to, our annual report on Form 10-K for the fiscal year ended April 30, 2016 as well as any updates to these risk factors filed from time to time in the company's other filings with the Securities and Exchange Commission. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
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
Cancer’s Achilles’ Heel: Apoptosis and Necroptosis to the Rescue
Article (PDF Available) in International Journal of Molecular Sciences 18(1) · December 2016
Achilles Heel of Cancer
Vladimir N. Pak*
Freelance researcher Toronto, Canada
Submission: March 17, 2017; Published: March 27, 2017
https://www.researchgate.net/publication/315703809_Achilles_Heel_of_Cancer
From 2015:
Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium
Subrahmanya D. Vallabhapurapu,1 Víctor M. Blanco,1 Mahaboob K. Sulaiman,1 Swarajya Lakshmi Vallabhapurapu,1 Zhengtao Chu,1,2 Robert S. Franco,1 and Xiaoyang Qi1,2
Author information ? Article notes ? Copyright and License information ?
Abstract
Viable cancer cells expose elevated levels of phosphatidylserine (PS) on the exoplasmic face of the plasma membrane. However, the mechanisms leading to elevated PS exposure in viable cancer cells have not been defined. We previously showed that externalized PS may be used to monitor, target and kill tumor cells. In addition, PS on tumor cells is recognized by macrophages and has implications in antitumor immunity. Therefore, it is important to understand the molecular details of PS exposure on cancer cells in order to improve therapeutic targeting. Here we explored the mechanisms regulating the surface PS exposure in human cancer cells and found that differential flippase activity and intracellular calcium are the major regulators of surface PS exposure in viable human cancer cells. In general, cancer cell lines with high surface PS exhibited low flippase activity and high intracellular calcium, whereas cancer cells with low surface PS exhibited high flippase activity and low intracellular calcium. High surface PS cancer cells also had higher total cellular PS than low surface PS cells. Together, our results indicate that the amount of external PS in cancer cells is regulated by calcium dependent flippase activity and may also be influenced by total cellular PS.
Keywords: phosphatidylserine, surface exposure, cancer cell biomarker, flippase, calcium
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741459/
PEREGRINE PHARMACEUTICALS SHARES ADD 7% PRE-BELL AS PRE-CLINICAL DATA SHOW POTENTIAL OF ANTI-TUMOR TREATMENT PPHM.O
MIDTRD
03/04/2017 2:40 PM
08:35 AM EDT, 04/03/2017 (MT Newswires) -- Peregrine Pharmaceuticals (PPHM) shares were higher 7% in pre-market trade as pre-clinical day showed the potential of the company's phosphatidylserine-targeting antibodies to enhance the anti-tumor activity of adoptive T cell transfer therapy without triggering any off-target toxicities.
'We believe that these findings may support potential applications for this combination in solid tumors in the future,' said Taha Merghoup, co-director of the Ludwig Collaborative Laboratory at Memorial Sloan Kettering Cancer Center which is collaborating with Peregine.
Additional results demonstrated that the PS-targeting antibodies decreased tumor-induced immunosuppression as evidenced by a decrease in immunosuppressive regulatory T cells and M2 macrophages.
Peregrine said it continues to advance its pre-clinical collaboration with MSK with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents.
'The intent behind this strategy is to focus our research and development spending to further validate bavituximab's combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner,' Peregrine said.
Price: 0.70, Change: +0.05, Percent Change: +7.31
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© Thomson Reuters 2017. All rights reserved.
187k at ask .65
PM .70 vol 20350
That news came from Reuters
Peregrine Pharmaceuticals Announces Presentation of Preclinical Study Results Highlighting Potential of PS-Targeting Antibodies to Enhance Anti-Tumor Activity of Adoptive T Cell Transfer Therapy with No Added Off-Target Toxicities - GNW
03-Apr-2017 14:05
Latest Findings from Ongoing Collaboration with Memorial Sloan Kettering (MSK) Support Potential Applications for Combining CAR T and Anti-PS in Treatment of Solid Tumors --
TUSTIN, Calif., April 03, 2017 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, today announced the presentation of positive new data from the company’s ongoing collaboration with researchers from Memorial Sloan Kettering Cancer Center (MSK). Presented preclinical study results highlighted the potential of the company’s phosphatidylserine (PS)-targeting antibodies to enhance the anti-tumor activity of adoptive T cell transfer therapy without triggering any off-target toxicities. Data were presented this morning by MSK researchers at the 2017 Annual Meeting of the American Association for Cancer Research (AACR), which is being held April 1-5, 2017 in Washington, D.C.
For this study, a team of MSK researchers led by cancer immunotherapy thought-leaders, Taha Merghoub, Ph.D. and Jedd D. Wolchok, M.D., Ph.D., evaluated and compared the anti-tumor activity and off-target toxicities of adoptive T cell transfer therapy in combination with either PS-targeting antibodies or anti-OX40 antibodies in mice with advanced melanomas. Whereas PS-targeting and anti-OX40 demonstrated comparable tumor regression when administered in combination with transferred adoptive T cells, only the PS-targeting combination achieved these results without any off-target toxicities. By contrast, the anti-OX40 treatment combination triggered off-target inflammatory destruction of healthy tissues.
“While adoptive T cell transfer remains one of the most exciting new approaches to treating cancer, to date the toxicity associated with the treatment has limited its potential. We are encouraged that these study results showed that the combination of anti-PS and adoptive T cell treatment led to enhanced anti-tumor effect without any evidence of additional off-target side effects,” said Taha Merghoub, Ph.D., co-director of the Ludwig Collaborative Laboratory at MSK. “We believe that these findings may support potential applications for this combination in solid tumors in the future.”
Additional study results demonstrated that the PS-targeting antibodies decreased tumor-induced immunosuppression as evidenced by a decrease in immunosuppressive regulatory T cells (Tregs) and M2 macrophages. This finding is consistent with Peregrine’s belief that bavituximab may modulate the immunosuppressive tumor microenvironment and enhance the activity of immunotherapy agents.
“These study results provide further support for our belief that anti-PS agents such as bavituximab can play an important role as part of combination cancer treatments. This is directly tied to the agents’ ability to modulate the tumor microenvironment to combat the immunosuppression that limits the activity of CAR T and immunotherapies,” said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. “Importantly, we are now also seeing evidence that this targeted modulation of the tumor microenvironment by anti-PS allows for enhanced activity of these other treatments without triggering any off-target toxicities. This is opposed to other conventional immunotherapies such as anti-OX40 with systemic mechanisms of action. We believe this advantageous tolerability profile will be a key benefit in positioning anti-PS agents for inclusion in optimal combination cancer regimens.”
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. PS-targeting antibodies have demonstrated an ability to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses. Bavituximab is believed to override PS immunosuppressive signaling by blocking the engagement of PS with its receptors and sending an alternate immune activating signal.
Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with MSK with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab's combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.
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.
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that the results from the pre-clinical studies are not replicated in human clinical trials and the risk that the company may not have or raise adequate financial resources from debt and/or equity financings and/or Avid's manufacturing operations to fund the further development of bavituximab. The company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in our reports filed with the Securities and Exchange Commission including, but not limited to, our annual report on Form 10-K for the fiscal year ended April 30, 2016 as well as any updates to these risk factors filed from time to time in the company's other filings with the Securities and Exchange Commission. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
Contacts:
Jay Carlson
Peregrine Pharmaceuticals, Inc.
(800) 987-8256
info@peregrineinc.com
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
GlobeNewswire, Inc. 2017
Understanding cell signaling in cancer stem cells for targeted therapy – can phosphoproteomics help to reveal the secrets?
Wolfgang Gruber†,
Tamara Scheidt†,
Fritz AbergerEmail authorView ORCID ID profile and
Christian G. HuberEmail author
†Contributed equally
Cell Communication and Signaling201715:12
DOI: 10.1186/s12964-017-0166-1
© The Author(s). 2017
Received: 22 December 2016
Accepted: 13 March 2017
Published: 29 March 2017
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-017-0166-1
Chimeric antigen receptors (CARs)–a cell and gene therapy perspective
Isabelle Riviere, Michel Sadelain
http://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(17)30155-7.pdf?bcsi_scan_1014b4c4c7c5e188=Q0tHcWLLqQWOKFNT3FSmaXtI++QuAAAAEDPKNQ==&bcsi_scan_filename=S1525-0016(17)30155-7.pdf
Tumor Immunoprofiling: HISTALIM Launches HISTOPROFILE - BSW
03-Apr-2017 11:00
Tumor Immunoprofiling: HISTALIM Launches HISTOPROFILE
Recent clinical data confirm the importance of patient stratification in the development of cancer immunotherapies. For instance Merck’success with Keytruda (Pembrolizumab, anti PDL-1) in lung cancer demonstrates that the patient screening according to the ligand overexpression of the therapeutic target is a winning strategy in immuno-oncology.
This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20170403005576/en/ (http://www.businesswire.com/news/home/20170403005576/en/)
Though the pertinence of personalized medicine in oncology cannot be argued, one must also consider that the reactivation of the immune system against tumors engage subtle and complex mechanisms, which can be more efficient when multiple pathways are simultaneously activated. This opinion is commonly shared by many researchers in immuno-oncology who engage clinical trials combining therapies against several targets.
If clinical results confirm the relevance of this approach, it will be necessary to qualify patients on the basis of multiple biomarkers. Given the fact that a biopsy can only be used on a few histological slides, an obvious conclusion arises: it becomes urgent to extract several markers from a single slide.
Positive progress of liquid biopsy and molecular biology could potentially address this issue. But these solutions do not allow to localize the marker, which is sometimes required. To get more precise information on the tumor microenvironment, the protein expression is not enough: associated morphologic information needs to be known.
Nowadays several clinical trials in immuno-oncology rely on multiplex immunohistochemistry to use a sufficient number of markers despite the scarcity of biological material. It can be anticipated that the routine histopathologic diagnostic will integrate multiplex analysis of markers so that pathologist can try this new challenge: characterize tumor immune profile from a single biopsy.
Cultural and technological barriers will have to be removed in order to let histopathology progress as fast as the innovations in immuno-oncology. For instance fluorescence revelation is not commonly used by the pathologists. Complex multiplex IHC staining require slide scanners compatible with multispectral imaging, which is not widely spread. Then the volume of data processed from multiplex staining will require to use image analysis solutions able to facilitate the pathologist’s diagnostic. This is a new paradigm for histopathology which is evolving toward a more subtle science than it was already, being source of “rich-data” for the treatment of patients.
This new generation histopathology, led by “augmented pathologists” and able to define the tumor immune profile from one single biopsy, is developed by HISTALIM
(http://cts.businesswire.com/ct/CT...) under the brand named HISTOPROFILE.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170403005576/en/ (http://www.businesswire.com/news/home/20170403005576/en/)
HISTALIM
(http://cts.businesswire.com/ct/CT...) : Press contact: Jean-Philippe Coton, +33619646737 CEO contact@histalim.com (mailto:contact@histalim.com)
Copyright Business Wire 2017
The cost of cancer: new drugs show success at a steep price - Reuters News
03-Apr-2017 08:00:00
By Deena Beasley
April 3 (Reuters) - Newer cancer drugs that enlist the body's immune system are improving the odds of survival, but competition between them is not reining in prices that can now top $250,000 a year.
The drugs' success for patients is the result of big bets in cancer therapy made by Bristol-Myers Squibb Co BMY.N, Merck & Co Inc MRK.N and Roche Holding AG ROG.S, among others in big pharma. The industry's pipeline of cancer drugs expanded by 63 percent between 2005 and 2015, according to the QuintilesIMS Institute, and a good number are reaching the market.
The global market for cancer immunotherapies alone is expected to grow more than fourfold globally to $75.8 billion by 2022 from $16.9 billion in 2015, according to research firm GlobalData. For a graphic, click http://tmsnrt.rs/2omboI1
"For cancer drugs in general ... it is hard for us to drive down cost," said Steve Miller, chief medical officer at Express Scripts Holding Co ESRX.O, the nation's largest manager of drug benefit plans for employers and insurers. "You don't want to be in the position of being told to use the second best cancer drug for your child."
Lawmakers on both sides of the aisle, as well as President Donald Trump, have been grappling with how to restrain rising prescription drug costs. They have talked about solutions ranging from more price negotiation to faster approval of new drugs, often invoking increased competition between drugmakers.
"Competition is key to lowering drug prices," Trump told pharmaceutical executives at an Oval Office meeting in January.
But that is not happening with new drugs called checkpoint inhibitors that work by releasing a molecular brake, allowing the immune system to recognize and attack cancer cells the same way it fights infections caused by bacteria or viruses.
For cancers like melanoma, the treatments can mean long-term survival for around 20 percent of patients L2N18F2CT.
Bristol's Yervoy, first approved in 2011, targets a protein known as CTLA-4. Other immunotherapies, including Bristol's Opdivo, Keytruda from Merck, Roche's Tecentriq, and Pfizer Inc's PFE.N Bavencio, involve a different protein called PD-1.
Other targets are being explored. Some new data will be presented this week in Washington at the American Association for Cancer Research's annual meeting.
Current checkpoint inhibitors each have a list price near $150,000 a year. A combination of Yervoy and Opdivo, approved by the Food and Drug Administration for advanced or inoperable melanoma, has a cost of $256,000 a year for patients who respond to the treatment.
Similar immunotherapies are in development at companies like AstraZeneca Plc AZN.L. Merck, which declined to comment on pricing plans, expects an FDA decision by May 10 on its combination of Keytruda and chemotherapy as an initial treatment for the most common form of lung cancer - by far the biggest market for cancer drugs L1N1F10WJ.
Pfizer said Bavencio, cleared by the FDA earlier this month to treat Merkel cell carcinoma, a rare type of skin cancer, has a price "comparable to other checkpoint inhibitors approved for different indications."
The pharmaceutical industry holds that discussion of prescription drug prices has to take into account the major investment required for innovation and discovery of new lifesaving drugs.
"UNRESTRAINED PRICING POWER"
Scientific progress, and pricing power, are driving pharmaceutical companies to emphasize oncology research.
"Most of the strategy on the part of pharmaceutical companies assumes unrestrained pricing power," said Dr. Peter Bach, director of Memorial Sloan Kettering's Center for Health Policy Outcomes in New York. "We don't see evidence that companies are pursuing cost-effective strategies."
Health insurers have had success in demanding price concessions in some drug categories - like diabetes, where several companies sell similar products and insurers are able to negotiate price discounts or rebates in exchange for coverage.
According to IMS, that tactic capped the overall rise in spending on diabetes medicines at 8 percent in 2015, compared with an increase of 30 percent in billed invoices. All of the invoice price growth for insulin was offset by price cuts, the institute said.
But discounting is much less common for newer, innovative cancer drugs, mostly given by injection and approved for defined patient populations.
Net price growth for branded oncology drugs averaged 4.8 percent in 2015, versus 6.4 percent for invoices, according to IMS.
Express Scripts' Miller and others said makers of new cancer medications enjoy pricing power due to coverage requirements, insurance plan structure and a lack of head-to-head comparison studies.
"Cancer drugs don't compete on price," said Dr. Aaron Kesselheim, a researcher at Harvard Medical School and author of several studies of drug pricing. "Drug companies have market exclusivity and we require payers to cover cancer drugs - Medicare has six protected classes, including cancer."
Medicare, the federal government's healthcare plan for seniors and the disabled, covers most prescription drugs under its "Part D" pharmacy benefits. The plans are required to cover all drugs in six classes: cancer, HIV, antidepressants, antispychotics, seizure disorders like epilepsy, and immune system suppressants for people undergoing organ transplantation.
Trump met recently with Representatives Elijah Cummings and Peter Welch, both Democrats, to discuss draft legislation allowing the government to negotiate Medicare drug prices - but the bill preserves the six protected classes.
In addition, drugs given by injection, including many cancer therapies, are covered under Medicare's main medical benefit.
Bristol disappointed investors when it did not pursue accelerated FDA review of the Opdivo/Yervoy combination for newly-diagnosed lung cancer - putting Merck ahead in the lucrative lung cancer market. L1N1F92MU
"All of the immunotherapies have similar price points," said Miller at Express Scripts. "When you stack therapies, it means more expense for patients and (health) plan sponsors."
(Editing by Edward Tobin)
(( ed.tobin@thomsonreuters.com; ))
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Immunovaccine to Present New Pre-clinical Combination Therapy Data at the AACR Annual Meeting
Study Designed to Assess Synergies of Combining DepoVax™-based Cancer Vaccines and Novel Monoclonal Antibody Immunotherapies
Halifax, Nova Scotia; March 24, 2017 – Immunovaccine Inc. (TSX: IMV; OTCQX: IMMVF), a clinical stage immuno-oncology company, today announced that new pre-clinical data on DepoVax™-based cancer vaccines will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, which will be held in Washington, D.C., from April 1-5.
Immunovaccine conducted this research in collaboration with Peregrine Pharmaceuticals (NASDAQ: PPHM) with the goal of analyzing the potential enhanced anti-cancer activity of combining DepoVax™-based cancer immunotherapies with Peregrine’s lead clinical product candidate bavituximab, an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS).
Details of the presentation are as follows:
Title: Phosphatidylserine-Targeting Antibodies Enhance Anti-tumor Activity of a Tumor Vaccine in a HPV-Induced Tumor Model
Date and time: Tuesday, April 4, 8:00 AM – 12:00 PM ET
Abstract number: 3657
Location: Section 26
Poster board number: 30
Immunovaccine Director of Research Dr. Genevieve Weir will present data analyzing the potential for enhanced anti-tumor responses of PS and PD-1 targeting antibody therapies when combined with an HPV16 peptide vaccine formulated in Immunovaccine’s proprietary DepoVax™ technology.
“Our work with Peregrine, and the research it has produced, fits squarely into our corporate objective of exploring clinical stage immunotherapies that may have synergistic effects when combined with our lead candidate, DPX-Survivac,” saidMarianne Stanford, PhD Vice President, Research for Immunovaccine “We look forward to discussing the results of this study, and its potential implications, with our colleagues in the scientific community at this year’s AACR meeting.”
About Immunovaccine
Immunovaccine Inc. is a clinical-stage biopharmaceutical company dedicated to making immunotherapy more effective, more broadly applicable, and more widely available to people facing cancer and infectious diseases. Immunovaccine develops T cell activating cancer immunotherapies and infectious disease vaccines based on DepoVax™, the Company’s patented platform that provides controlled and prolonged exposure of antigens and adjuvant to the immune system. Immunovaccine has advanced two T cell activation therapies for cancer through Phase 1 human clinical trials and is currently conducting a Phase 1b study with Incyte Corporation assessing lead cancer therapy, DPX-Survivac, as a combination therapy in ovarian cancer. An investigator-sponsored Phase 2 study is currently assessing the safety and efficacy of DPX-Survivac combined with an approved anti-PD-1 drug in advanced ovarian cancer. The Company is also exploring additional applications of DepoVax™, including DPX-RSV, an innovative vaccine candidate for respiratory syncytial virus (RSV), which has recently completed a Phase 1 clinical trial. The Company also has ongoing clinical projects to assess the potential of DepoVax™ to address malaria and the Zika virus. Connect at www.imvaccine.com.
Immunovaccine Forward-Looking Statements
This press release contains forward-looking information under applicable securities law. All information that addresses activities or developments that we expect to occur in the future is forward-looking information. Forward-looking statements are based on the estimates and opinions of management on the date the statements are made. However, they should not be regarded as a representation that any of the plans will be achieved. Actual results may differ materially from those set forth in this press release due to risks affecting the Company, including access to capital, the successful completion of clinical trials and receipt of all regulatory approvals. Immunovaccine Inc. assumes no responsibility to update forward-looking statements in this press release except as required by law.
Contacts for Immunovaccine:
MEDIA
Mike Beyer, Sam Brown Inc.
T: (312) 961-2502 E: mikebeyer@sambrown.com
INVESTOR RELATIONS
Pierre Labbe, Chief Financial Officer
T: (902) 492-1819 E: info@imvaccine.com
https://www.imvaccine.com/releases.php?releases_id=418
Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies
https://link.springer.com/article/10.1007%2Fs13317-017-0092-7
I think you know that:
http://www.abstractsonline.com/pp8/#!/4292/presentation/6260
96k at bid .6499
Bavi + herpes 1 and 2 - is this really from yesterday???
http://www.wdmac.com/tag/what-is-herpes-1-2/
METHODS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH AN ABNORMAL INFLAMMATORY RESPONSES
http://www.freepatentsonline.com/y2017/0056347.html
Search for Bavituximab
50 k Bid .66
"They" try everything to get pphm before weekend.
SL fishing - maybe
PM .68 vol 21073
PM .70 vol 200
Extracellular Vesicles as Therapeutic Agents in
Systemic Lupus Erythematosus
Astrazeneca - Must be an news-update from yesterday!
Astrazeneca to share its robust early science in oncology with the medical community at AACR 2017 AZN.L - ENP Newswire
29-Mar-2017 17:29:42
ENPNEWSWIRE-(C)2017 ENPUBLISHING
Release date- 28032017 - AstraZeneca, along with its global biologics research and development arm, MedImmune, will present the strength and depth of its translational science, which is expected to deliver the Company's next wave of innovative oncology medicines, at the American Association for Cancer Research (AACR) Annual Meeting in Washington DC, US, 1-5 April 2017.
In addition to demonstrating a robust early oncology portfolio in DNA Damage Response (DDR) and Tumour Drivers and Resistance, AstraZeneca will highlight the continued progress being made in early Immuno-Oncology (IO) and Antibody-Drug Conjugate (ADC) science.
Susan Galbraith, Senior Vice President, Head of Oncology, Innovative Medicines and Early Development (IMED) Biotech Unit, said: 'The progress we will report at AACR 2017 highlights the rapid growth of our highly-differentiated DNA Damage Response portfolio that targets a broad range of key molecular pathways. Presentations will also show our progress within Tumour Drivers and Resistance with the development of molecules targeting two key mechanisms that tumours use to resist cell death, namely MCL-1 and CDK9.'
David Berman, Senior Vice President, Head of Oncology Innovative Medicines at MedImmune, added: 'AACR 2017 is an exciting moment for our next-generation oncology portfolio, demonstrating how our broad biologics pipeline is targeting the multiple ways cancer evades the immune system. We will update on our scientific progress in cancer Immuno-Oncology, including predictive biomarkers of response to immune checkpoint inhibitors. We also look forward to presenting the first clinical trial results for our TLR 7/8 agonist, an important mechanism for immunologically-silent tumours, and to sharing updates from our Antibody-Drug Conjugate platform, a key pillar of AstraZeneca's oncology strategy.'
Shedding new light on Tumour Drivers and Resistance
AstraZeneca was a pioneer in the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for patients with non-small cell lung cancer (NSCLC) (Iressa, Tagrisso), and continues to work on the unmet needs of patients who fail to respond, or respond for limited periods, to these compounds. An expanding programme of tumour cell-death research is targeting upregulation of key proteins that cancer cells use to evade death, including myeloid cell leukaemia 1 (MCL-1) and cyclin-dependent kinase 9 (CDK9) and is leveraging the sophistication of macrocyles - larger, cyclic compounds - to address the complexity of protein interactions.
Presentations include:
.AZD4205, a potent inhibitor of Janus kinase 1 (JAK1), part of the JAK1/signal transducer and activator of transcription (STAT) axis, which is understood to play an important role in tumour escape from EGFR-targeted treatment (oral presentation; Abstract #979)
.The first preclinical data presented on AZD5991 demonstrating the tumour cell-killing potential of this potent, selective macrocylic inhibitor of MCL-1 in blood cancers (oral presentation; Abstract #DDT01)
.AZD4205 combined with Tagrisso (osimertinib) in patients with EGFR mutation-positive NSCLC to reduce residual tumour burden and prolong the benefit of osimertinib (Abstract #4046)
.Preclinical data supporting the potential of the CDK9 inhibitor, AZD5576, alone and in combination with AstraZeneca's potentially best-in-class Bruton's tyrosine kinase (BTK) inhibitor, acalabrutinib, in the treatment of non-Hodgkin lymphoma (Abstract #4295).
A leading DNA Damage Response (DDR) position
With one approved medicine and four candidates in clinical development, AstraZeneca is extending its leadership in medicines that target novel DDR deficiencies to selectively kill cancer cells, while minimising the impact on normal cells.
Four oral presentations will include the following data:
.Phase I/II studies exploring the combination of Lynparza (olaparib) and temozolomide (an alkylating chemotherapy) in patients with small-cell lung cancer (SCLC) following failure of prior chemotherapy (Abstract #CT048), and
.A Phase I study of Lynparza and the alpha-specific PI3-kinase inhibitor BYL719, in patients with recurrent ovarian and breast cancer (Abstract #CT008)
.Preclinical data uncovering a novel role for the bromodomain protein, BRD4, in regulating DNA replication-stress response, and the potential of the combination of the BRD4 inhibitor, AZD5153, and the ATR inhibitor, AZD6738, in the sustained delay of tumour growth (Abstract #1026)
.The European paediatric precision medicine programme in recurrent tumours showing first results from the MAPPYACTS molecular profiling trial aimed at increasing the number of targetable genomic alternations for DDR therapies (Abstract #CT004)
Preliminary results will also be reported from a Phase I dose-escalation study of the ataxia-telangiectasia and Rad3 related (ATR) inhibitor, AZD6738, in advanced solid tumours (PATRIOT Part A) (Abstract #CT084).
Immuno-Oncology (IO): Activating the immune system via multiple approaches
Presentations will illustrate the depth of AstraZeneca's IO capabilities beyond its comprehensive late-stage portfolio.
Key presentations include:
.Oral presentation of innovative computer modelling to identify tumour and immune cell interactions during disease progression to predict susceptibility to checkpoint inhibitors and other compounds (Abstract #975)
.Phase I data on the Toll-like receptor 7/8 (TLR7/8) agonist MEDI9197 in solid tumours (Abstract #CT091) and preclinical data showing its anti-tumour activity in combination with PD-L1 or CTLA-4 checkpoint inhibitors (Abstract #4697)
.Phase I/II data showing that high pre-treatment levels of interferon gamma gene signature are associated with greater benefit with durvalumab in patients with NSCLC and urothelial bladder cancer (Abstract #1773).
Antibody-Drug Conjugates: Sophisticated targeting of toxic payloads
AstraZeneca will share data demonstrating the potential of a range of ADCs in targeting cytotoxic treatments to tumour cells. These include preclinical data with toxic pyrrolobenzodiazepine (PBD) or tubulysin payloads in combination with multiple immunotherapies (Abstract #4596), and data on the potent anti-tumour activity of ADCT-401/MEDI3726 when targeting prostate-specific membrane antigen (PSMA) in prostate cancer models (Abstract #3111A).
NOTES TO EDITORS
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca's six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms - Immuno-Oncology, the genetic drivers of cancer and resistance, DNA Damage Response and Antibody-Drug Conjugates - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About MedImmune
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory, Cardiovascular & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca's three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, CA. For more information, please visit www.medimmune.com.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.
CONTACTS
PM .725 vol 500
Phosphatidylserine Sensing by TAM Receptors Regulates AKT-dependent Chemoresistance and PD-L1 Expression
http://mcr.aacrjournals.org/content/early/2017/02/09/1541-7786.MCR-16-0350
Sushil Kumar
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, Rutgers University, Biomedical and Health Sciences Center
Just seeing a "snake" on my screen
Phosphatidylserine and Related Lipids
http://www.lipidhome.co.uk/lipids/complex/ps/index.htm
Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity
Published online 2017 Mar 8.
Stanley G. Kimani,1,* Sushil Kumar,1,* Nitu Bansal,2,* Kamalendra Singh,3 Vladyslav Kholodovych,4,5 Thomas Comollo,1 Youyi Peng,2 Sergei V. Kotenko,1 Stefan G. Sarafianos,3 Joseph R. Bertino,2 William J. Welsh,a,2,5 and Raymond B. Birgeb,1
Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase
Article (PDF Available) in Cell Communication and Signaling 14(1) · September 2016 with 57 Reads
DOI: 10.1186/s12964-016-0142-1
1st Stanley Kimani
24.18 · EMD Millipore
2nd Sushil Kumar
19.67 · Rutgers New Jersey Medical School
3rd Viralkumar Davra
9.36 · Rutgers New Jersey Medical School
Last Raymond B Birge
https://www.researchgate.net/publication/307858743_Normalization_of_TAM_post-receptor_signaling_reveals_a_cell_invasive_signature_for_Axl_tyrosine_kinase
Abstract B119: Characterization of a phosphatidylserine, TAM receptor (Tyro3, Axl, Mertk), PDL1 axis in breast cancer
Article in Cancer Immunology Research 4(11 Supplement):B119-B119 · November 2016 with 23 Reads
DOI: 10.1158/2326-6066.IMM2016-B119
1st Canan Kasikara
11.95 · Rutgers New Jersey Medical School
2nd Sushil Kumar
3rd Ke Geng
9.25 · Rutgers New Jersey Medical School
4th Viral Davre
5th Cyril Empig
24.54 · Peregrine Pharmaceuticals, Inc.
6th Bruce Freimark
34.26 · PEREGRINE PHARMACEUTICALS, INC.
7th Michael Gray
8th Kyle Schlunegger
14.73 · Peregrine Pharmaceuticals
9th Jeff Hutchins
10th Sergei V. Kotenko
11th Raymond B. Birge
https://www.researchgate.net/publication/309624539_Abstract_B119_Characterization_of_a_phosphatidylserine_TAM_receptor_Tyro3_Axl_Mertk_PDL1_axis_in_breast_cancer
NO TEXT!!!
Parker Institute for Cancer Immunotherapy, Bristol-Myers Squibb and the Cancer Research Institute Announce Collaboration to Accelerate Immuno-Oncology Research - BSW
28-Mar-2017 12:59
Innovative collaboration model designed to accelerate next-generation precision cancer immunotherapy through network of leading research centers and top scientists
Collaboration will leverage efficiencies in cancer research to rapidly implement novel Immuno-Oncology clinical studies
Bristol-Myers Squibb is the first industry partner to join a collaboration with the Parker Institute and the Cancer Research Institute
The Parker Institute for Cancer Immunotherapy (http://cts.businesswire.com/ct/CT...) , Bristol-Myers Squibb Company
(http://cts.businesswire.com/ct/CT...) (NYSE: BMY) and the Cancer Research Institute (http://cts.businesswire.com/ct/CT...) (CRI) today announced a multi-year clinical research collaboration to coordinate and rapidly initiate clinical Immuno-Oncology (I-O) studies across the Parker Institute and CRI networks. Bristol-Myers Squibb will work closely with leading Parker Institute and CRI scientists and researchers, soliciting clinical research proposals from their networks and coordinating multi-site collaboration clinical studies to pursue some of the most difficult questions in cancer research. It will provide scientists with an ecosystem of advanced translational tools, precision immunotherapy and cutting-edge bioanalytical expertise to maximize learning and ensure the generation of high quality data to inform future development.
The Parker Institute is a novel collaboration model which includes industry, academic and philanthropic participants, focused on the shared goal of accelerating immunotherapy research to develop and deliver new treatment options for patients. CRI is a nonprofit organization dedicated to advancing laboratory and clinical research through its global network of academic, industry, and nonprofit partners with the goal of developing lifesaving immunotherapies for all forms of cancer.
The collaboration will build on the Parker Institute model that brings together the nation’s top research institutions to share resources, data and technology to accelerate research through unifying and managing clinical trial design and conducting clinical studies across multi-centers. The Parker Institute currently funds projects across its network of more than 60 laboratories and 300 researchers who work together to advance research and potentially develop new therapies. The Cancer Research Institute will support the collaboration with investment from its Clinical Accelerator venture philanthropy program and access to its global network of leading investigators from around the world.
“Bristol-Myers Squibb is initiating this unique collaboration with a goal of accelerating the identification and development of new treatment options for patients who are facing very serious disease,” said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. “We are excited to partner with the Parker Institute and the Cancer Research Institute to leverage the unique translational capabilities of their networks and explore novel mechanisms of action in the field of I-O.”
This is the Parker Institute’s first major agreement with a biopharma partner. The institute will continue to build key industry relationships critical for the success of its unique model.
“One of our goals is to help facilitate collaborations between academia and industry to help advance cancer research,” said Jeffrey Bluestone, Ph.D., CEO and president of the Parker Institute for Cancer Immunotherapy. “Partnering with Bristol-Myers Squibb, a renowned leader in the field of immuno-oncology development, is a major leap forward for us. We could not be more enthusiastic to start this collaboration, which we believe will accelerate the process of turning important lab discoveries by our investigators into the potential for much needed treatments for patients.”
“Unlocking the full potential of next-generation precision cancer immunotherapy requires the kind of coordination, resources, and logistical support that the Parker Institute and the Cancer Research Institute can offer our research partners, and collaboration with industry leaders like Bristol-Myers Squibb will be essential to hastening the development of new cancer immunotherapies,” said Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs at CRI.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com
(http://cts.businesswire.com/ct/CT...) or follow us on LinkedIn
(http://cts.businesswire.com/ct/CT...) , Twitter
(http://cts.businesswire.com/ct/CT...) , YouTube
(http://cts.businesswire.com/ct/CT...) and Facebook
(http://cts.businesswire.com/ct/CT...)
.
About Parker Institute for Cancer Immunotherapy
The Parker Institute for Cancer Immunotherapy brings together the best scientists, clinicians and industry partners to build a smarter and more coordinated cancer immunotherapy research effort. The Parker Institute is an unprecedented collaboration between the country’s leading immunologists and cancer centers, including Memorial Sloan Kettering Cancer Center, Stanford Medicine, the University of California, Los Angeles, the University of California, San Francisco, the University of Pennsylvania and The University of Texas MD Anderson Cancer Center. The Parker Institute network also includes more than 40 industry and nonprofit partners, more than 60 labs and more than 300 of the nation’s top researchers focused on treating the deadliest cancers.
The goal is to accelerate the development of breakthrough immune therapies capable of turning most cancers into curable diseases. The institute was created through a $250 million grant from The Parker Foundation. For more information, visit parkerici.org.
About the Cancer Research Institute
The Cancer Research Institute (CRI), established in 1953, is the world’s leading nonprofit organization dedicated exclusively to transforming cancer patient care by advancing scientific efforts to develop new and effective immune system-based strategies to prevent, diagnose, treat, and eventually cure all cancers. Guided by a world-renowned Scientific Advisory Council that includes three Nobel laureates and 26 members of the National Academy of Sciences, CRI has invested $336 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities, and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org (http://cts.businesswire.com/ct/CT...)
.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170328005529/en/
Immunogenic versus tolerogenic phagocytosis during
anticancer therapy: mechanisms and clinical
Translation
February 2016
https://www.researchgate.net/publication/295186555_Immunogenic_versus_tolerogenic_phagocytosis_during_anticancer_therapy_Mechanisms_and_clinical_translation
Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis
AstraZeneca to share its robust early science in Oncology with the medical community at AACR 2017 - CIS
28-Mar-2017 08:03
AstraZeneca
60 abstracts from early oncology portfolio including 7 oral presentations, across Tumour Drivers and Resistance, Immuno-Oncology, Antibody-Drug Conjugates and DNA Damage Response
Potential new medicines targeting cancer cell-death mechanisms highlight potential of emerging Tumour Drivers and Resistance research
AstraZeneca, along with its global biologics research and development arm, MedImmune, will present the strength and depth of its translational science, which is expected to deliver the Company’s next wave of innovative oncology medicines, at the American Association for Cancer Research (AACR) Annual Meeting in Washington DC, US, 1-5 April 2017.
In addition to demonstrating a robust early oncology portfolio in DNA Damage Response (DDR) and Tumour Drivers and Resistance, AstraZeneca will highlight the continued progress being made in early Immuno-Oncology (IO) and Antibody-Drug Conjugate (ADC) science.
Susan Galbraith, Senior Vice President, Head of Oncology, Innovative Medicines and Early Development (IMED) Biotech Unit, said: “The progress we will report at AACR 2017 highlights the rapid growth of our highly-differentiated DNA Damage Response portfolio that targets a broad range of key molecular pathways. Presentations will also show our progress within Tumour Drivers and Resistance with the development of molecules targeting two key mechanisms that tumours use to resist cell death, namely MCL-1 and CDK9.”
David Berman, Senior Vice President, Head of Oncology Innovative Medicines at MedImmune, added: “AACR 2017 is an exciting moment for our next-generation oncology portfolio, demonstrating how our broad biologics pipeline is targeting the multiple ways cancer evades the immune system. We will update on our scientific progress in cancer Immuno-Oncology, including predictive biomarkers of response to immune checkpoint inhibitors. We also look forward to presenting the first clinical trial results for our TLR 7/8 agonist, an important mechanism for immunologically-silent tumours, and to sharing updates from our Antibody-Drug Conjugate platform, a key pillar of AstraZeneca’s oncology strategy.”
Shedding new light on Tumour Drivers and Resistance
AstraZeneca was a pioneer in the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for patients with non-small cell lung cancer (NSCLC) (Iressa, Tagrisso), and continues to work on the unmet needs of patients who fail to respond, or respond for limited periods, to these compounds. An expanding programme of tumour cell-death research is targeting upregulation of key proteins that cancer cells use to evade death, including myeloid cell leukaemia 1 (MCL-1) and cyclin-dependent kinase 9 (CDK9) and is leveraging the sophistication of macrocyles – larger, cyclic compounds – to address the complexity of protein interactions.
Presentations include:
AZD4205, a potent inhibitor of Janus kinase 1 (JAK1), part of the JAK1/signal transducer and activator of transcription (STAT) axis, which is understood to play an important role in tumour escape from EGFR-targeted treatment (oral presentation; Abstract #979)
The first preclinical data presented on AZD5991 demonstrating the tumour cell-killing potential of this potent, selective macrocylic inhibitor of MCL-1 in blood cancers (oral presentation; Abstract #DDT01)
AZD4205 combined with Tagrisso (osimertinib) in patients with EGFR mutation-positive NSCLC to reduce residual tumour burden and prolong the benefit of osimertinib (Abstract #4046)
Preclinical data supporting the potential of the CDK9 inhibitor, AZD5576, alone and in combination with AstraZeneca’s potentially best-in-class Bruton’s tyrosine kinase (BTK) inhibitor, acalabrutinib, in the treatment of non-Hodgkin lymphoma (Abstract #4295). A leading DNA Damage Response (DDR) position
With one approved medicine and four candidates in clinical development, AstraZeneca is extending its leadership in medicines that target novel DDR deficiencies to selectively kill cancer cells, while minimising the impact on normal cells.
Four oral presentations will include the following data:
Phase I/II studies exploring the combination of Lynparza (olaparib) and temozolomide (an alkylating chemotherapy) in patients with small-cell lung cancer (SCLC) following failure of prior chemotherapy (Abstract #CT048), and
A Phase I study of Lynparza and the alpha-specific PI3-kinase inhibitor BYL719, in patients with recurrent ovarian and breast cancer (Abstract #CT008)
Preclinical data uncovering a novel role for the bromodomain protein, BRD4, in regulating DNA replication-stress response, and the potential of the combination of the BRD4 inhibitor, AZD5153, and the ATR inhibitor, AZD6738, in the sustained delay of tumour growth (Abstract #1026)
The European paediatric precision medicine programme in recurrent tumours showing first results from the MAPPYACTS molecular profiling trial aimed at increasing the number of targetable genomic alternations for DDR therapies (Abstract #CT004)
Preliminary results will also be reported from a Phase I dose-escalation study of the ataxia-telangiectasia and Rad3 related (ATR) inhibitor, AZD6738, in advanced solid tumours (PATRIOT Part A) (Abstract #CT084).
Immuno-Oncology (IO): Activating the immune system via multiple approaches
Presentations will illustrate the depth of AstraZeneca’s IO capabilities beyond its comprehensive late-stage portfolio.
Key presentations include:
Oral presentation of innovative computer modelling to identify tumour and immune cell interactions during disease progression to predict susceptibility to checkpoint inhibitors and other compounds (Abstract #975)
Phase I data on the Toll-like receptor 7/8 (TLR7/8) agonist MEDI9197 in solid tumours (Abstract #CT091) and preclinical data showing its anti-tumour activity in combination with PD-L1 or CTLA-4 checkpoint inhibitors (Abstract
#4697)
* Phase I/II data showing that high pre-treatment levels of interferon gamma
gene signature are associated with greater benefit with durvalumab in patients
with NSCLC and urothelial bladder cancer (Abstract #1773).
Antibody-Drug Conjugates: Sophisticated targeting of toxic payloads
AstraZeneca will share data demonstrating the potential of a range of ADCs in targeting cytotoxic treatments to tumour cells. These include preclinical data with toxic pyrrolobenzodiazepine (PBD) or tubulysin payloads in combination with multiple immunotherapies (Abstract #4596), and data on the potent anti-tumour activity of ADCT-401/MEDI3726 when targeting prostate-specific membrane antigen (PSMA) in prostate cancer models (Abstract #3111A).
– ENDS –