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Free Float Free Float % Shares Outstanding
246.370.634 82,76% 297.709.478
Investor Rank Investor Name Latest Filing Date % O/S
1 Eastern Capital, Ltd. 30-10-2015 8,88%
2 Ronin Capital, L.L.C. 09-03-2017 7,95%
3 Kennedy Capital Management 31-12-2016 2,54%
4 Fondren Management, L.P. 31-12-2016 1,51%
5 The Vanguard Group, Inc. 31-12-2016 1,45%
6 BlackRock Institutional Trust 31-12-2016 1,44%
7 Renaissance Technologies LLC 31-12-2016 0,83%
8 Wellington Management Company, 31-12-2016 0,47%
9 Eqis Capital Management, Inc. 31-12-2016 0,39%
10 Geode Capital Management 31-12-2016 0,37%
Extracellular vesicles isolation and their biomarker potential: are we ready for testing?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326637/
Targeting Membrane Lipid a Potential Cancer Cure?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253362/
Old one??? - Published online 2017 Jan 23
Deciphering the role of ectosomes in cancer development
and progression: focus on the proteome
Magdalena Surman1 · Ewa Stepien2 · Dorota Hoja-Lukowicz1 · Malgorzata Przybylo1
Received: 28 November 2016 / Accepted: 11 March 2017
© The Author(s) 2017. This article is an open access publication
http://paperity.org/p/79316974/deciphering-the-role-of-ectosomes-in-cancer-development-and-progression-focus-on-the
Some PS in there
TIM-3 as a Target for Cancer Immunotherapy and
Mechanisms of Action
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.mdpi.com/1422-0067/18/3/645/pdf&ved=0ahUKEwjc9_D87OLSAhXJWiwKHRJHAAUQFgghMAI&usg=AFQjCNGGHlg3V78XT1lpfAuR9zTimoW8XQ
Deciphering the role of ectosomes in cancer development and progression: focus on the proteome
Clinical & Experimental Metastasis, Mar 2017
http://paperity.org/p/79316974/deciphering-the-role-of-ectosomes-in-cancer-development-and-progression-focus-on-the
The Unique Molecular and Cellular
Microenvironment of Ovarian Cancer
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.imt.uni-marburg.de/mueller/Papers/Worzfeld_2017.pdf&ved=0ahUKEwjhy5mB6OLSAhXFFZoKHdoXBlQ4FBAWCDIwCA&usg=AFQjCNFW3cx6aYSTG9NscrbcjnSjv16spQ
Bodywide immune response important for fighting cancer
https://med.stanford.edu/news/all-news/2017/01/bodywide-immune-response-important-for-fighting-cancer.html
Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of cancer
http://pubs.rsc.org/en/content/articlehtml/2017/sc/c6sc03738k
Phosphatidylserine Exposed by Cancer Cells Plays the Key Role in
the Development of New Antitumor Drugs
Riedl S.1
, Rinner B.2
, Novak A.2
, Tumer S.1
, Lohner K.1
, and Zweytick D.1
1
Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences,
Graz, Austria
2
Core-Facility Flow Cytometry, Center of medical research, Graz, Austria
Every year millions of people are diagnosed with cancer. Chemotherapy is the standard
treatment but chemotherapeutics can hardly discriminate between cancer and healthy
cells consequently causing severe side effects. In the FWF project P20760-B11, we
enforce a weapon derived from innate immune system against cancer cells in the form
of small cationic peptides that will target specifically the cancer cell without binding to
specific receptors or inner cell targets. LF11, a short peptide stretch derived from
human Lactorferricin, exhibiting antibiotic, antifungal, antiviral and anti-tumor activity, is
taken as a parent peptide and is further optimized in its activity and selectivity towards
cancer cells. This is provided by the interaction of the cationic peptides with cancer cells
that expose the negatively charged phospholipid phosphatidylserine (PS) in the outer
leaflet of their plasma membranes, which in healthy cells only comprise neutral lipids.
Within in vitro studies plasma membranes of melanoma (different tumor development),
prostate-, brain- (primary cell line) and kidney cancer cells and their healthy
counterparts were characterized for presence or absence of PS exposure by flow
cytometry and fluorescence microscopy. Selectivity of LF11 derived peptides for model
membranes was improved by structure-activity relationship studies using Differential
Scanning Calorimetry (DSC), Fluorescence spectroscopy and further techniques.
These biophysical investigations on model membranes revealed that some peptides
have specific impact on the lipid membrane of cancer cells. From the outcome of the
first screening with model membranes 2 peptides (the most active non acylated and its
N-acylated form) were chosen for cytotoxicity studies with cancer and non cancer cells.
These experiments revealed that the N-acylated peptide induced lysis of cancer cells at
a similar level as Melittin (bee venom), that is known to be toxic for cancer cells, as well
as for non cancer cells, whereas the N-acylated derivative of Lactoferricin was shown to
be less toxic for non cancer cells than Melittin.
Acknowledgement: Dr. Schaider*, Dr. Hofmann-Wellenhof*, Dr. Augustin, Dr. Asslaber
(LKH Graz, dermatology*, urology, pathology)
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.eurofedlipid.org/meetings/archive/graz/5872/5872_0402.pdf&ved=0ahUKEwjQxP_2zuDSAhWoE5oKHXUcAZIQFggdMAA&usg=AFQjCNGZ1hHy_WfEcDyn3LAWS_hX3fFJ1Q
Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides
http://onlinelibrary.wiley.com/doi/10.1002/psc.2963/full
WORLD-FIRST LIQUID BIOPSY FOR BLOOD CANCERS PROMISES LESS INVASIVE, MORE PRECISE AND EFFECTIVE TREATMENTS
https://www.petermac.org/news/world-first-liquid-biopsy-blood-cancers-promises-less-invasive-more-precise-and-effective
Thanks for that MH!
Great sighn
New Brunswick 'liquid biopsy' cancer-testing technology goes global
The value of monitoring circulating immune cells
for the prediction of the evolution
of patients with cancer
https://www.google.at/url?sa=t&source=web&rct=j&url=http://simposiobiopsialiquida.com/wp-content/uploads/2017/02/28.-10.15-10.30-Garcia-Foncillas.-Valor-del-seguimiento-de-las-celulas.pdf&ved=0ahUKEwjF35molt7SAhUFDJoKHT9JBpMQFgg8MAk&usg=AFQjCNEOg_frjUNUMvCy8fvA4JnBxa3lpQ
Scientists Device Blood Test to Detect Cancer and Locate Tumour
http://food.ndtv.com/health/scientists-device-blood-test-to-detect-cancer-and-locate-tumour-1667050?desktop=true
How a simple blood test may hold the key to detecting cancer
A blood test for cancer? Simple liquid biopsy could identify where in the body a tumour exists
http://www.dailymail.co.uk/health/article-4286510/A-blood-test-cancer.html
Architectural Control of Cytotoxic T-Cell Function
Name: Morgan Huse
Organization: Memorial Sloan Kettering Cancer Center
City/Province: New York
State: New York
Country: USA
Date/Time:
Thursday, March 30, 2017 11:00am - 12:00pm
https://calendar.nih.gov/app/MCalInfoView.aspx
Innate Lymphoid Cells in Metabolic Disease
Name: Joseph Sun, Ph.D.
Title: Associate Professor of Immunology
Organization: Memorial Sloan Kettering Cancer Ctr./Weill Cornell Medical College
City/Province: New York
State: New York
Country: U.S.A.
Date/Time:
Friday, March 24, 2017 10:00am - 11:00am
https://calendar.nih.gov/app/MCalInfoView.aspx
Cell Death and Inflammation (K2)
joint with the meeting on Integrating Metabolism and Immunity (E4)
Scientific Organizers: Seamus J. Martin and John Silke
May 29—June 2, 2017
Royal Dublin Society, Dublin, Ireland
https://www.keystonesymposia.org/17K2
Tissue Responses to Dying Cells
Shigekazu Nagata, IFReC, Osaka University, Japan
Exposure of Phosphatidylserine to the Cell Surface
Inflammation and Cancer
Registered attendees can view abstracts starting on 04/29/2017
Concert Hall
Frances R. Balkwill, Barts Cancer Institute, Queen Mary University of London, UK
Inflammation in the Tumor Microenvironment
Scott W. Lowe, Memorial Sloan-Kettering Cancer Center, USA
Inflammatory Regulators and Cancer Progression
Not so bad
Pphm is in the air
You can now buy 69K at .71
A Programmed Nanoparticle with Self-Adapting for Accurate Cancer Cell Eradication and Therapeutic Self-Reporting
http://www.thno.org/v07p1245.htm
DATE: 09/03/2017 !!!!!
Ronin Capital 9,20% or 23,67 M Shares
Reuters
They must have bought another 1%
AH .72
ASTRAZENECA PLC - LYNPARZA PHASE III SOLO-2 DATA DEMONSTRATE PROGRESSION-FREE SURVIVAL BENEFIT IN BRCA-MUTATED OVARIAN CANCER AS MAINTENANCE THERAPY
PUBT
14/03/2017 7:33 PM
Lynparza reduced risk of disease progression by 70% with an investigator-assessed progression-free survival of 19.1 vs 5.5 months with placebo
Blinded independent central review showed impressive progression-free survival of 30.2 months vs 5.5 months with placebo
Lynparza tablets demonstrated a safety profile generally consistent with previous studies, including a low incidence of haematological toxicity
14 March 2017
AstraZeneca today presented results from the Phase III SOLO-2 trial demonstrating a significant improvement in progression-free survival (PFS) in germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed ovarian cancer patients treated with Lynparza (olaparib) tablets (300mg twice daily) compared with placebo in the maintenance setting. The trial met its primary endpoint of investigator assessed PFS (HR 0.30; 95% CI 0.22 to 0.41; P <0.0001; median 19.1 months vs 5.5 months).
PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P <0.0001).
Additionally, a statistically-significant benefit in time to second progression or death (PFS2) was also seen in patients treated with Lynparza (HR 0.50; 95% CI 0.34 to 0.72; P=0.0002; median not reached vs 18.4 months) compared with placebo, as well as improvements in other key secondary endpoints.
Progression-Free Survival by investigator and BICR assessment:
Analysis Median progression-free survival, months Hazard ratio
Investigator-assessed analysis Lynparza 19.1 0.30 (95% CI, 0.22-0.41), P <0.0001
Placebo 5.5
Blinded Independent Central Review Lynparza 30.2 0.25 (95% CI, 0.18-0.35), P <0.0001
Placebo 5.5
These results, presented at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer in National Harbor, USA, build upon prior data in this setting, demonstrating the benefit of Lynparza as a maintenance therapy in relapsed ovarian cancer. Eric Pujade-Lauraine, Head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, AP-HP and Principal Investigator of SOLO-2, said: 'Today's results are very encouraging, as they build upon previous trials examining Lynparza in platinum-sensitive relapsed BRCA-mutated ovarian cancer. Most importantly, patients were able to maintain quality of life while experiencing an impressive delay in disease progression, demonstrating the benefits of Lynparza tablets for these women whose cancer is often difficult to treat.' Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: 'We are extremely pleased with the results from SOLO2, which support the potential benefit of Lynparza tablets as a maintenance therapy for patients with relapsed ovarian cancer. The tablet formulation may offer patients a reduced pill burden for Lynparza and a safety profile that is generally consistent with previous trials. We will work with regulatory authorities to make Lynparza tablets available to patients as quickly as possible.' The safety profile for patients treated with Lynparza tablets during the trial was consistent to those observed with the currently-approved capsule formulation. Any adverse events (AE) Grade ≥3 were reported in 36.9% of patients treated with Lynparza and in 18.2% of patients who received placebo. The most common non-haematological AEs reported at a frequency of ≥20% were nausea (75.9% [grade ≥3, 2.6%]), fatigue/asthenia (65.6% [grade ≥3, 4.1%]), and vomiting (37.4% [≥3, 2.6%]). The most common haematological AEs reported in the Lynparza arm versus placebo were anaemia (43.6% [grade ≥3, 19.5%]), neutropenia (19.5% [grade ≥3, 5.1%]), and thrombocytopenia (13.8% [grade ≥3, 1.0%]). The 300mg twice-daily tablet dose reduces the pill burden for patients from sixteen capsules to four tablets per day.
NOTES TO EDITORS
About SOLO-2
SOLO-2 was a Phase III, randomised, double-blind, multicentre trial designed to determine the efficacy of Lynparza tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d'Investigateurs National pour l'Etude des Cancers de l'Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomised to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.
About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. It is approved by regulatory authorities in the EU and US for the treatment of women with BRCAm ovarian cancer. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. In a previous study Lynparza capsules were shown to result in a significant improvement in PFS compared to placebo in platinum-sensitive, relapsed ovarian cancer (PSR OC) patients (HR 0.35; 95% CI 0.25-0.49; p <0.0001) as well as in the subgroup of patients whose tumours harbour BRCA mutations (HR 0.18; 95% CI 0.10-0.31; p <0.0001).
About ENGOT
ENGOT (European Network for Gynaecological Oncological Trial groups) is a research network of the European Society of Gynaecological Oncology (ESGO) and was founded in 2007. Currently, ENGOT consists of 19 cooperative groups from 15 European countries. ENGOT's ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science, and enabling every patient in every European country to access a clinical trial. ENGOT coordinates and promotes multinational clinical trials within Europe on patients with gynaecological cancer. This coordination is particularly relevant for academic clinical trials, translational research, research on rare diseases, and for clinical trials sponsored by the industry.
About GINECO
GINECO (Groupe d'Investigateurs National pour l'Etude des Cancers de l'Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCA (Institut National du Cancer or French NCI) for developing and conducting gynaecological and advanced breast cancer clinical trials at the national and international level. The network is nationwide with 700 specialized investigators belonging to more than 150 public or private oncology units. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). GINECO was the ENGOT leading group for SOLO-2 trial.
About AstraZeneca in ovarian cancer Worldwide, ovarian cancer is the 7 most commonly diagnosed cancerand the 8 most common cause of cancer death in women. The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations.AstraZeneca is committed to the continued development of our R&D portfolio for ovarian cancer, with a focus on improved care for all patients, including the development of targeted therapies for patients with specific gene mutations such as BRCA.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that have the potential to transform patients' lives and the Company's future. With at least 6 new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advancing 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 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 http://www.astrazeneca.com and follow us on Twitter @AstraZeneca.
AstraZeneca plc published this content on 14 March 2017 and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on 14 March 2017 18:33:15 UTC.
Original document
https://www.astrazeneca.com/media-centre/press-releases/2017/lynparza-phase-iii-solo-2-data-demonstrate-progression-free-survival-benefit-in-brca-mutated-ovarian-cancer-as-maintenance-therapy-14032017.html
Public permalink
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Harnessing the Immune System to Fight Cancer
From Nov.2016!
Harnessing the Immune System to Fight Cancer
Steve Cara expected to sail through the routine medical tests required to increase his life insurance in October 2014. But the results were devastating. He had lung cancer, at age 53. It had begun to spread, and doctors told him it was inoperable.
A few years ago, they would have suggested chemotherapy. Instead, his oncologist, Dr. Matthew D. Hellmann of Memorial Sloan Kettering Cancer Center in New York, recommended an experimental treatment: immunotherapy. Rather than attacking the cancer directly, as chemo does, immunotherapy tries to rally the patient’s own immune system to fight the disease.
Uncertain, Mr. Cara sought a second opinion. A doctor at another major hospital read his scans and pathology report, then asked what Dr. Hellmann had advised. When the doctor heard the answer, Mr. Cara recalled, “he closed up the folder, handed it back to me and said, ‘Run back there as fast as you can.’”
Many others are racing down the same path. Harnessing the immune system to fight cancer, long a medical dream, is becoming a reality. Remarkable stories of tumors melting away and terminal illnesses going into remissions that last years — backed by solid data — have led to an explosion of interest and billions of dollars of investments in the rapidly growing field of immunotherapy. Pharmaceutical companies, philanthropists and the federal government’s “cancer moonshot” program are pouring money into developing treatments. Medical conferences on the topic are packed.
All this has brought new optimism to cancer doctors — a sense that they have begun tapping into a force of nature, the medical equivalent of splitting the atom.
“This is a fundamental change in the way that we think about cancer therapy,” said Dr. Jedd Wolchok, chief of melanoma and immunotherapeutics services at Memorial Sloan Kettering.
Hundreds of clinical trials involving immunotherapy, alone or combined with other treatments, are underway for nearly every type of cancer. “People are asking, waiting, pleading to get into these trials,” said Dr. Arlene Siefker-Radtke, an oncologist at the University of Texas M.D. Anderson Cancer Center in Houston, who specializes in bladder cancer.
The immune system — a network of cells, tissues and biochemicals that they secrete — defends the body against viruses, bacteria and other invaders. But cancer often finds ways to hide from the immune system or block its ability to fight. Immunotherapy tries to help the immune system recognize cancer as a threat, and attack it.
Doctors tried a primitive version of immunotherapy against cancer more than 100 years ago. It sometimes worked remarkably well, but often did not, and they did not understand why. Eventually, radiation and chemotherapy eclipsed it.
Researchers are now focused on two promising types of immunotherapy. One creates a new, individualized treatment for each patient by removing some of the person’s immune cells, altering them genetically to kill cancer and then infusing them back into the bloodstream. This treatment has produced long remissions in a few hundred children and adults with deadly forms of leukemia or lymphoma for whom standard treatments had failed.
The second approach, far more widely used and the one Mr. Cara tried, involves mass-produced drugs that do not have to be tailored to each patient. The drugs free immune cells to fight cancer by blocking a mechanism — called a checkpoint — that cancer uses to shut down the immune system.
These drugs, called checkpoint inhibitors, have been approved by the Food and Drug Administration to treat advanced melanoma, Hodgkin’s lymphoma and cancers of the lung, kidney and bladder. More drugs in this class are in the pipeline. Patients are clamoring for checkpoint drugs, including one, Keytruda, known to many as “that Jimmy Carter drug” which, combined with surgery and radiation, has left the former president with no sign of recurrence even though melanoma had spread to his liver and brain.
Checkpoint inhibitors have become an important option for people like Mr. Cara, with advanced lung cancer.
“We can say in all honesty to patients, that while we can’t tell them we can cure metastatic lung cancer right now, we can tell them there’s real hope that they can live for years, and for a lot of patients many years, which really is a complete game-changer,” said Dr. John V. Heymach, a lung cancer specialist and chairman of thoracic/head and neck medical oncology at M.D. Anderson.
Yet for all the promise and excitement, the fact is that so far, immunotherapy has worked in only a minority of patients, and researchers are struggling to find out why. They know they have their hands on an extraordinarily powerful tool, but they cannot fully understand or control it yet.
One Patient’s Story
Mr. Cara, an apparel industry executive from Bridgewater, N.J., had non-small-cell lung cancer, the most common form of the disease. The diagnosis shattered what had been an idyllic life: a happy marriage, sons in college, a successful career, a beautiful home, regular vacations, plenty of golf.
In December 2014, he began treatment with two checkpoint inhibitors. They cost about $150,000 a year, but as a study subject he did not have to pay.
These medicines work on killer T-cells, white blood cells that are often described as the soldiers of the immune system. T-cells are so fierce that they have built-in brakes — the so-called checkpoints — to shut them down and keep them from attacking normal tissue, which could result in autoimmune disorders like Crohn’s disease, lupus or rheumatoid arthritis. One checkpoint stops T-cells from multiplying; another weakens them and shortens their life span.
As the name suggests, checkpoint inhibitors block the checkpoints, so cancer cannot use them to turn off the immune system.
Mr. Cara took drugs to inhibit both types of checkpoints. Every two weeks, he had intravenous infusions of Yervoy and Opdivo, both made by Bristol-Myers Squibb. He had no problems at first, just a bit of fatigue the day after the infusion. He rarely missed work.
But turning the wrath of the immune system against cancer can be a risky endeavor: Sometimes the patient’s own body gets caught in the crossfire. About two months into the treatment, Mr. Cara broke out in a rash all over his arms, back and chest. It became so severe that he had to go off the drugs. A steroid cream cleared it up and he was able to resume treatment — but with only one drug, Opdivo. Doctors stopped the other in hopes of minimizing the side effects.
heckpoint inhibitors can take months to begin working, and sometimes cause inflammation that, on scans early in treatment, can make it look like the tumor is growing. But Mr. Cara’s first scans, in March 2015, were stunning.
His tumor had shrunk by a third.
By August, more than half of the tumor had vanished. The rash came back, however, and worsened. Steroids worked again, but in October a far more alarming side effect set in: breathing trouble.
Doctors diagnosed pneumonitis, a lung inflammation caused by an attack from the immune system — a known risk of checkpoint drugs. Continuing the treatment posed too great a danger.
Mr. Cara stopped the infusions, but the months of treatment seemed to have transformed his cancer to stage 2 from stage 4, meaning that it was now operable. This spring surgeons removed about a third of his right lung, and discovered that the cancer was actually gone.
“No cancer was seen in any of the tissue they took out,” Dr. Hellmann said. “‘One hundred percent treatment effect,’” he read from the pathology report. “It was pretty cool.”
Immunotherapy had apparently wiped out the disease. “It’s amazing. Unbelievable,” Mr. Cara said.
As of now, he needs no further treatment, but he will be monitored regularly. He is back to work, and golf.
“He’s had the best possible response,” Dr. Hellmann said. “I hope that remains permanent. Only time will tell, and I think he’s conscious of that.”
Mr. Cara acknowledged, “Is there something in the back of me that says this thing never goes away, it could come back any time? Sure. But it’s not the main thing I think. I’m young, I’m strong, I’m healthy, my pathology report came back clean.”
He considered framing that pathology report.
But, he said, “I don’t want to jinx myself.”
Drugs Help Some, but Not Others
When checkpoint inhibitors work, they can really work, producing long remissions that start to look like cures and that persist even after treatment stops. Twenty percent to 40 percent of patients, sometimes more, have good responses. But for many patients, the drugs do not work at all. For others, they work for a while and then stop.
The vexing question, and the focus of research, is, why?
One theory is that additional checkpoints, not yet discovered, may play a role. The hunt is on to find them, and then make new drugs to act on them.
Despite the gaps in knowledge, checkpoint inhibitors are coming into widespread use and are being tried in advanced types of cancer for which standard chemotherapy offers little hope.
One example is anal cancer, a painful disease that carries a stigma because it is often linked to the sexually transmitted human papillomavirus or HPV, which also causes cervical cancer.
Lee, 59, who asked that her last name be withheld to protect her privacy, found out in 2014 that she had the disease, and that it had spread to her liver.
“I was told I’d be dead in 12 to 18 months with treatment, six months with no treatment,” she said.
Chemotherapy and radiation at a hospital near Dallas brought a remission that lasted only a few months. The cancer spread to her lungs.
Bedridden and in severe pain, she entered an immunotherapy trial at M.D. Anderson. In May 2015 she began receiving Opdivo every two weeks. The tumors in her liver and lungs have shrunk by about 70 percent. She is back at work.
While the drugs initially were given only to people with advanced disease, especially those who had little to lose because chemotherapy had stopped working, Dr. Heymach of M.D. Anderson predicted that soon some patients — including some with earlier stages of lung cancer — will receive checkpoint inhibitors as their first treatment.
Immunotherapy is also enabling doctors to help patients in unexpected ways.
Until recently, surgeons were reluctant to operate on people with advanced cancer because they knew from experience that it would not lengthen the patient’s life. But checkpoint inhibitors are changing that. For instance, some patients have taken checkpoint inhibitors for an advanced cancer that had spread around the body, and wound up with only one stubborn tumor left. They then have had it surgically removed and have gone years without a relapse.
“Time has slowed down to the point where you can pay attention to individual tumors, since you’re not running to put out the fire of wholesale systemic progression,” Dr. Wolchok said.
If there is a potential downside to the advances, Dr. Hellmann said, it is that the buzz about immunotherapy has led some patients to think chemotherapy is passé.
“Immunotherapy represents a hugely important new tool, but chemotherapy can work too and has been the backbone of the way we’ve treated patients with lung cancer,” he said. “Immunotherapy is not a replacement for that. It’s a new weapon.”
One of his patients, a 60-year-old man with lung cancer that had spread to his brain, was eager to try immunotherapy instead of chemotherapy. After having radiation treatment for one brain tumor, he began treatment with two checkpoint inhibitors.
But they did not work. So his doctors switched to chemotherapy. “He’s had a tremendous response,” Dr. Hellmann said.
He said it was impossible to tell whether the immunotherapy could have had some delayed effect and worked synergistically with the chemotherapy. Clinical trials are now trying to resolve that question.
But the potential for dangerous side effects cannot be overemphasized, doctors say. A 2010 article in a medical journal reported that a few melanoma patients had died from adverse effects of Yervoy.
In addition to causing lung inflammation, checkpoint inhibitors can lead to rheumatoid arthritis and colitis, a severe inflammation of the intestine — the result of an attack by the revved-up immune system that over-the-counter remedies cannot treat. Patients need steroids like prednisone to quell these attacks. Fortunately — and mysteriously, Dr. Wolchok said — the steroids can halt the gut trouble without stopping the immune fight against the cancer. But if patients delay telling doctors about diarrhea, Dr. Wolchok warned, “they could die” from colitis.
Checkpoint inhibitors can also slow down vital glands — pituitary, adrenal or thyroid — creating a permanent need for hormone treatment. Mr. Cara, for instance, now needs thyroid medication, almost certainly as a result of his treatment. Doctors have reported that a patient with a kidney transplant rejected it after taking a checkpoint inhibitor to treat cancer, apparently because the drug spurred his immune system to attack the organ.
Another of Dr. Hellmann’s lung-cancer patients, Joanne Sabol, 65, had to quit a checkpoint inhibitor because of severe colitis. But she had taken it for about two years, and it shrank a large abdominal tumor by 78 percent. Patients like her are in uncharted territory, and doctors are trying to decide whether to operate to remove what is left of her tumor.
“I have aggressive cancer, but I’m not giving in to it,” Ms. Sabol said. “It’s going to be a big battle with me.”
Coley’s Toxins
Dr. William B. Coley, an American surgeon born in 1862, is widely considered the father of cancer immunotherapy. But he practiced a crude form of it, without understanding how it worked.
Distressed by the painful death of a young woman he had treated for a sarcoma, a bone cancer, in 1891, Dr. Coley began to study the records of other sarcoma patients in New York, according to Dr. David. B. Levine, a medical historian and orthopedic surgeon.
One case leapt out at him: a patient who had several unsuccessful operations to remove a huge sarcoma from his face, and wound up with a severe infection, then called erysipelas, caused by Streptococcal bacteria. The patient was not expected to survive, but he did — and the cancer disappeared.
Dr. Coley found other cases in which cancer went away after erysipelas. Not much was known about the immune system, and he suspected, mistakenly, that the bacteria were somehow destroying the tumors. Researchers today think the infection set off an intense immune response that killed both the germs and the cancer.
Dr. Coley was not alone in believing that bacteria could fight cancer. In a letter to a colleague in 1890, the Russian physician and playwright Anton Chekhov wrote of erysipelas: “It has long been noted that the growth of malignant tumors halts for a time when this disease is present.”
Dr. Coley began to inject terminally ill cancer patients with Streptococcal bacteria in the 1890s. His first patient, a drug addict with an advanced sarcoma, was expected to die within weeks, but the disease went into remission and he lived eight years.
Dr. Coley treated other patients, with mixed results. Some tumors regressed, but sometimes the bacteria caused infections that went out of control. Dr. Coley developed an extract of heat-killed bacteria that came to be called Coley’s mixed toxins, and he treated hundreds of patients over several decades. Many became quite ill, with shaking chills and raging fevers. But some were cured.
Parke-Davis and Company began producing Coley’s toxins in 1899, and continued for 30 years. Various hospitals in Europe and the United States, including the Mayo Clinic, used the toxins, but the results were not consistent.
Early in the 20th century, radiation treatment came into use. Its results were more predictable, and the cancer establishment began turning away from Coley’s toxins. Dr. Coley’s own institution, Memorial Hospital (now Memorial Sloan Kettering Cancer Center) instituted a policy in 1915 stating that inpatients had to be given radiation, not the toxins. Some other hospitals continued using them, but interest gradually waned. Dr. Coley died in 1936.
Chemotherapy, developed after World War II, was another blow to his methods. And in 1965, the American Cancer Society added Coley’s toxins to its list of “unproven” treatments. (The toxins were later taken off the list.)
After Dr. Coley’s death, his daughter, Helen Coley Nauts, studied some 800 case records that he had left behind, and became convinced that he was onto something important. She tried to rekindle interest in his work, but she was thwarted by doctors who opposed it, including some with high rank at Sloan Kettering. However, in 1953 she founded the Cancer Research Institute in New York, a nonprofit that has become a significant supporter of research on the interplay between cancer and the immune system. The group awarded more than $29.4 million in scientific grants in 2015, and its advisory board includes Dr. Wolchok and the scientist credited with developing the first checkpoint inhibitor, James P. Allison.
Source:NY Times
OLD?
Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies
David J. Byun,
Jedd D. Wolchok,
Lynne M. Rosenberg
& Monica Girotra
Affiliations
Contributions
Corresponding authors
Nature Reviews Endocrinology 13, 195–207 (2017) doi:10.1038/nrendo.2016.205 Published online 20 January 2017 Corrected online 06 February 2017
http://www.nature.com/nrendo/journal/v13/n4/full/nrendo.2016.205.html
•14-Mar-2017 12:39:21 - PEREGRINE PHARMACEUTICALS SHARES DOWN 8.9 PCT AT $0.70 IN LIGHT PREMARKET TRADE AFTER RESULTS ON MONDAY
PEREGRINE PHARMACEUTICALS INC- INCREASING ITS MANUFACTURING REVENUE GUIDANCE FOR FULL FY 2017 FROM $50 - $55 MLN, TO $60 - $65 MLN
RTRS
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PEREGRINE PHARMACEUTICALS REPORTS FINANCIAL RESULTS FOR THE THIRD QUARTER OF FISCAL YEAR 2017 AND RECENT DEVELOPMENTS
GNW
13/03/2017 9:05 PM
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Avid Revenue Guidance Increased to $60 - $65 Million for Full FY 2017 and Contracted Backlog of Future Business Currently at $70 Million --
Multiple Preclinical Studies Demonstrating Bavituximab’s Ability to Enhance Activity of Immune Stimulating Therapies Accepted for Presentation at AACR --
TUSTIN, Calif., March 13, 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 financial results for the third quarter of fiscal year (FY) 2017 ended January 31, 2017, and provided an update on its contract manufacturing business, preclinical and clinical pipeline, and other corporate developments.
Highlights Since October 31, 2016 "During the third quarter, Avid’s revenue growth continued, which is a strong indicator of the increasing value of this contract development and manufacturing organization (CDMO) business. The steady growth of this business over the past 5 years has been remarkable and we are pleased to see the trend continuing as we move through a number of process validations for clients, which we expect to spur further growth in the future as some or all of those products move to commercialization. We see Avid as a tremendously important asset with solid upside potential that is often overlooked as a value driver for the overall organization. With projected revenue of over $60 million for the current fiscal year, this is already a strong business in an industry that is expecting substantial growth over the next decade and we are excited about the future of the company,” stated Steven W. King, president and chief executive officer of Peregrine, and president of Avid Bioservices. "An important component of our Avid growth strategy is capacity expansion within our Myford facility. We are currently on track to install two 2,000-liter bioreactors in the facility within the next few months with a book of business for the reactors already in place. We believe the total capacity potential of the facility, when operating in campaign mode, can exceed more than $75 million annually bringing us to well over $100 million in total potential revenue between our two manufacturing facilities, and giving us adequate capacity to continue Avid revenue growth through FY 2018.
“As we look to the future, based on current operations and projected demand from our existing clients, we have also recently secured additional space within the same building as our Myford facility for which we already have use as part of our existing operations but would also allow us to further expand capacity based on committed business. While we will only begin converting the space into manufacturing capacity once client commitments and other necessary financing is in place, this puts us in an excellent position for continuing to grow the business beyond the coming fiscal year.”
Mr. King continued, "During the quarter, we also achieved a number of goals on the development front. These efforts are highlighted by the three clinical trials under our collaboration with the National Comprehensive Cancer Network (NCCN) which are advancing as planned, and we expect at least two of the trials to be initiated by mid-year. Additionally, we and our collaborators will be presenting a number of studies at the upcoming AACR annual meeting including data from researchers at Memorial Sloan Kettering that support the ability of PS-targeting agents, including bavituximab, to significantly impact the tumor microenvironment, creating a more favorable environment for checkpoint inhibitors. Additionally, our collaborators at the University of Texas Southwestern Medical Center published positive proof-of-concept data for our recently-licensed exosome-based cancer detection platform, which could have broad potential for patients with cancer. Even though we have reduced our R&D expenditures, we are pleased that collaborations such as these are allowing us to continue the advancement of our therapeutic and diagnostic programs as we continue to evaluate the best ways for moving our bavituximab and other PS-targeting programs forward. The combined efforts of growing the Avid biomanufacturing business and these important collaborations are allowing us to make great strides on all fronts."
Avid Bioservices Highlights
"The Avid business continues to build momentum. During the third quarter of FY 2017, contract manufacturing revenue increased 61% to $10.7 million compared to the third quarter of FY 2016. Given this performance, and our expected fourth quarter results, we are increasing our full FY 2017 revenue guidance from $50 to $55 million, to $60 to $65 million," stated Paul Lytle, chief financial officer of Peregrine. "We are also pleased to report that we recently leased 42,000 square feet within the same building as our Myford facility, allowing us to leverage existing oversized utilities and infrastructure that should allow us greater operational efficiency and overall cost savings. While we design the new facility within this new space, it’s important to note that our two existing commercial facilities have sufficient capacity to continue to grow our contract manufacturing revenue in FY 2018.”
The company is increasing its manufacturing revenue guidance for the full FY 2017 from $50 - $55 million, to $60 - $65 million.
Avid's current manufacturing revenue backlog is $70 million, representing estimated future manufacturing revenue to be recognized under committed contracts. This backlog primarily covers revenue to be recognized during the remainder of fiscal year 2017 and fiscal year 2018. Clinical Development Highlights
The three clinical trials under the collaboration with the NCCN are advancing as planned.
Moffitt Cancer Center—A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy for Unresectable Hepatitis C Associated Hepatocellular Carcinoma. This protocol is approved and patient screening is expected soon.
Massachusetts General Hospital Cancer Center—Phase I/II Clinical Trial of Bavituximab with Radiation and Temozolomide for Patients with Newly Diagnosed Glioblastoma. This trial is on track to be initiated by mid-calendar 2017.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins—Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck. This trial is on track to be initiated by mid-calendar 2017.
The company is continuing its comprehensive biomarker analysis of data collected in the Phase III SUNRISE trial.
Through this analysis, and as reported previously, Peregrine scientists have identified a correlation between overall survival and pre-treatment levels of the biomarker, beta-2 glycoprotein-1 (ß2GP1).
The results of an analysis of pre-treatment interferon gamma (IFN-?) will be the subject of a presentation at AACR entitled: IFN-? Analysis in Blood and Tissue as a Potential Prognostic and/or Predictive Biomarker
Research Highlights
Peregrine scientists and collaborators from Memorial Sloan Kettering Cancer Center will present preclinical results from multiple studies at the upcoming AACR meeting in April. Each study evaluates the use of a bavituximab equivalent in combination with immune stimulating therapies. The following abstracts will be presented:
Memorial Sloan Kettering: Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model
Memorial Sloan Kettering (initial findings presented at SITC): Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation and Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma
Peregrine (initial findings presented at the 2016 Society for Immunotherapy of Cancer Meeting): Combinational Activity of LAG3 and PD-1 Targeted Therapies is Significantly Enhanced by the Addition of Phosphatidylserine Targeting Antibodies and Establishes an Anti-Tumor Memory Response in Murine Triple Negative Breast Cancer
Collaborators from the University of Texas Southwestern Medical Center at Dallas, recently published positive proof-of-concept findings for Peregrine’s recently licensed exosome-based cancer detection platform in the peer-reviewed journal, Oncotarget. Results demonstrated that those patients with malignant ovarian cancer displayed significantly higher blood PS exosome levels than those with benign tumors, and the malignant and benign groups displayed significantly higher blood PS exosome levels than the healthy subjects.
Financial Highlights and Results
Peregrine continues to execute its previously-announced strategy to reach sustained profitability by increasing contract manufacturing revenue while decreasing research and development expenses, with the goal of reaching profitability 15 months from now. During the first nine months of FY 2017, the company made significant progress toward this goal with contract manufacturing revenues increasing 55% compared to the first nine months of FY 2016 and research and development expenses decreasing by 50% compared to the first nine months of FY 2016.
Contract manufacturing revenue from Avid's biomanufacturing services provided to its third-party customers increased to $10,747,000 for the third quarter of FY 2017 compared to $6,672,000 for the third quarter of FY 2016.
Total costs and expenses for the third quarter of FY 2017 were $18,544,000, compared to $23,576,000 for the third quarter of FY 2016. For the third quarter of FY 2017, research and development expenses decreased 60% to $5,989,000, compared to $15,156,000 for the third quarter of FY 2016. Cost of contract manufacturing increased to $7,974,000 in the third quarter of FY 2017 compared to $3,896,000 for the third quarter of FY 2016, primarily due to an increase in the cost of contract manufacturing associated with higher reported revenue. Also contributing to this increase and impacting gross margins for the period is the higher cost of operating the new Myford facility as well as the higher cost associated with performing process validation runs during the quarter. For the third quarter of FY 2017, selling, general and administrative expenses increased slightly to $4,581,000 compared to $4,524,000 for the third quarter of FY 2016 primarily due to the company's growing manufacturing business.
Peregrine's consolidated net loss attributable to common stockholders was $9,216,000 or $0.04 per share, for the third quarter of FY 2017, compared to a net loss attributable to common stockholders of $18,227,000, or $0.08 per share, for the same prior year quarter.
Peregrine reported $41,528,000 in cash and cash equivalents as of January 31, 2017, compared to $61,412,000 at fiscal year ended April 30, 2016. More detailed financial information and analysis may be found in Peregrine's Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.
Conference Call
Peregrine will host a conference call and webcast this afternoon, March 13, 2017, at 4:30 PM EDT (1:30 PM PDT).
To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Peregrine Pharmaceuticals conference call. To listen to the live webcast, or access the archived webcast, please visit: http://ir.peregrineinc.com/events.cfm.
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. (http://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 http://www.peregrineinc.com.
About Avid Bioservices
Avid Bioservices provides a comprehensive range of process development, high quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 15 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 http://www.avidbio.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 biomarker data does not support the development of a specific profile for patients who will receive therapeutic benefit from treatment with bavituximab, the risk that one or more of the NCCN grant funded investigator-initiated clinical studies may experience initiation and/or enrollment delays, the risk that data from one or more of the NCCN grant funded investigator-initiated clinical studies does not support further evaluation, the risk that the results from the pre-clinical studies are not replicated in human clinical trials, 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 risk that Avid's revenue growth may slow or decline, the risk that the company does not achieve profitability in 15 months, the risk that Avid may experience technical difficulties in processing customer orders, including delays in third party release testing, which could delay delivery of products to customers, revenue recognition and receipt of payment, the risk that one or more existing Avid customers terminates its contract prior to completion or reduces its demand for manufacturing services, and the risk that the new manufacturing facility will not be operational in 2019, due to construction or other delays or causes, including the inability to raise the capital to construct the facility. 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.
PEREGRINE PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (UNAUDITED)
THREE MONTHS ENDED JANUARY 31, NINE MONTHS ENDED JANUARY 31,
2017 2016 2017 2016
REVENUES:
Contract manufacturing revenue $ 10,747,000 $ 6,672,000 $ 39,726,000 $ 25,574,000
License revenue — 37,000 — 329,000
Total revenues 10,747,000 6,709,000 39,726,000 25,903,000
COSTS AND EXPENSES:
Cost of contract manufacturing 7,974,000 3,896,000 26,477,000 13,245,000
Research and development 5,989,000 15,156,000 21,580,000 43,264,000
Selling, general and administrative 4,581,000 4,524,000 14,625,000 13,839,000
Total costs and expenses 18,544,000 23,576,000 62,682,000 70,348,000
LOSS FROM OPERATIONS (7,797,000 ) (16,867,000 ) (22,956,000 ) (44,445,000 )
OTHER INCOME (EXPENSE):
Interest and other income 25,000 34,000 71,000 691,000
Interest and other expense (2,000 ) (14,000 ) (2,000 ) (14,000 )
Total other income, net 23,000 20,000 69,000 677,000
NET LOSS $ (7,774,000 ) $ (16,847,000 ) $ (22,887,000 ) $ (43,768,000 )
COMPREHENSIVE LOSS $ (7,774,000 ) $ (16,847,000 ) $ (22,887,000 ) $ (43,768,000 )
Series E preferred stock accumulated dividends (1,442,000 ) (1,380,000 ) (3,558,000 ) (3,448,000 )
NET LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS $ (9,216,000 ) $ (18,227,000 ) $ (26,445,000 ) $ (47,216,000 )
WEIGHTED AVERAGE COMMON SHARES OUTSTANDING:
Basic and Diluted 260,811,553 227,389,225 248,407,470 209,549,670
BASIC AND DILUTED LOSS PER COMMON SHARE $ (0.04 ) $ (0.08 ) $ (0.11 ) $ (0.23 )
PEREGRINE PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS
JANUARY 31, 2017 APRIL 30, 2016
Unaudited
ASSETS
CURRENT ASSETS:
Cash and cash equivalents $ 41,528,000 $ 61,412,000
Trade and other receivables 5,883,000 2,859,000
Inventories 33,829,000 16,186,000
Prepaid expenses and other current assets 1,747,000 1,351,000
Total current assets 82,987,000 81,808,000
Property and equipment, net 24,143,000 24,302,000
Restricted cash 600,000 600,000
Other assets 3,587,000 2,333,000
TOTAL ASSETS $ 111,317,000 $ 109,043,000
LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES:
Accounts payable $ 7,696,000 $ 8,429,000
Accrued clinical trial and related fees 3,127,000 7,594,000
Accrued payroll and related costs 5,637,000 5,821,000
Deferred revenue 26,367,000 10,030,000
Customer deposits 26,210,000 24,212,000
Other current liabilities 941,000 1,488,000
Total current liabilities 69,978,000 57,574,000
Deferred rent, less current portion 1,325,000 1,395,000
Commitments and contingencies
STOCKHOLDERS' EQUITY:
Preferred stock—$0.001 par value; authorized 5,000,000 shares; 1,647,760 and 1,577,440 issued and outstanding at January 31, 2017 and April 30, 2016, respectively 2,000 2,000
Common stock—$0.001 par value; authorized 500,000,000 shares; 271,068,464 and 236,930,485 issued and outstanding at January 31, 2017 and April 30, 2016, respectively 271,000 237,000
Additional paid-in capital 571,904,000 559,111,000
Accumulated deficit (532,163,000 ) (509,276,000 )
Total stockholders’ equity 40,014,000 50,074,000
TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $ 111,317,000 $ 109,043,000
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
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Next step up
Rapid Imaging of Tumor Cell Death in vivo using the C2A domain of Synaptotagmin-I
February 16, 2017
André A. Neves,
Bangwen Xie,
Sarah Fawcett,
Israt S Alam,
Timothy H Witney,
Maaike M de Backer,
Julia Summers,
William Hughes,
Sarah McGuire,
Dmitry Soloviev,
Jodie Miller,
William J Howat,
De-en Hu,
Tiago B Rodrigues,
David Y Lewis and
Kevin M Brindle
-
Author Affiliations
Cancer Research UK Cambridge Institute, University of Cambridge, United Kingdom
For correspondence or reprints contact: André A. Neves, Cancer Research UK Cambridge Institute, University of Cambridge, Li-Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom. E-mail: andre.neves@cruk.cam.ac.uk
Abstract
Cell death is an important target for imaging the early response of tumors to treatment. We describe here validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of Synaptotagmin-I. Methods: The capability of near infrared fluorophore-labeled and 99mTechnetium- and 111Indium-labeled derivatives of C2Am for imaging tumor cell death, using planar near infrared fluorescence (NIRF) imaging and single photon computed tomography (SPECT) respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft. Results: The fluorophore labeled C2Am derivative showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (2-5%). There was a significant correlation (R>0.9, P<0.05) between fluorescently-labeled C2Am binding and histological markers of cell death, including cleaved caspase-3, whereas there was no such correlation with a site-directed mutant of C2Am (iC2Am) that does not bind phosphatidylserine. 99mTc-C2Am and 111In-C2Am also showed favorable biodistribution profiles, with predominantly renal clearance and low non-specific retention in liver and spleen at 24 h after probe administration. 99mTc-C2Am and 111In-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3× and 2.2× respectively at two hours and 7.3× and 4.1× respectively at twenty-four hours after administration. Conclusion: Given the favorable biodistribution profile of 99mTc- and 111In-labelled C2Am, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation.
http://jnm.snmjournals.org/content/early/2017/02/15/jnumed.116.183004
Detection of phosphatidylserine in the plasma membrane of single apoptotic cells using electrochemiluminescence
Accepted 12th February 2017
http://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra28031e
Contextual Pre-Conditioning and Sustained Conditioning of Cells Dictate Cell-Target Therapeutic Outcome in Tumor Cell Apoptosis/Anti-Apoptosis
http://medcraveonline.com/IJRRT/IJRRT-02-00023.pdf