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Good morning Ms. “the Whale”/All! The only “ultimate public private partnership” I know of, beyond first phase of FDA clinical trials, is Relief Therapeutics (public) and NeuroRx (private). Does anyone know of any other public private partnership beyond first phase FDA clinical trials?
“...this ultimate public private partnership...”~ Rep Andy Harris, Md, Data Monitoring Comittee
You’ve got it badger (mc67). New eyes out there are reading...and when is our partner, Neuro Rx, going public? But, first things ($RLFTF) first!
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Quote ~
Well you know it’s like one of those extraordinary accidents, but some people say chance favors the prepared mind. And believe it or not vasoactive intestinal peptide, which is the active ingredient we’re working with, is a neuro endocrine peptide.~ Dr. Jonathan, Neuro Rx CEO
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=158252687
Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that binds to a member of the class II family of G protein-coupled receptors (GPCRs). It is widely expressed throughout the body and plays an important role in numerous biological functions. VIP acts via three different GPCRs: VPAC1, VPAC2, and PAC1, which have been identified in various tissues, including brain, lung, kidney, gastrointestinal tract, tongue, and also on immunocompetent cells such as macrophages and lymphocytes. There is mounting evidence that VIP expression and signaling is altered in numerous neurological disorders, and it is becoming apparent that VIP and its receptors could be therapeutic loci for the treatment of several pathological conditions of the central nervous system. In this review, we describe the pathology of several major neurological disorders and discuss the potential pharmacotherapeutic role of VIP and its receptors for the treatment of disorders such as Alzheimer’s disease, Parkinson’s disease, and Autism Spectrum Disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967653/
No worries, as long as there is freedom of expression and posters are not violating iHub rules, I will continue to post the $RLFTF positives, “The Searchers “ will post their findings, the “well wishers” will post their best wishes/prayers, and analytical minds will post their analysis.
What part of $RLFTF recent history you don’t like? This part?>>>>>>>>>>>>>>>>>>>>>>>>>>>
NeuroRx CEO Jonathan Javitt commented, “Now that we know VIP suppresses replication of the SARS-CoV-2 virus in human lung cells, based on the outstanding work of the Oswaldo Cruz Institute (Rio de Janeiro). We are optimistic that treatment with VIP will not only help patients on ventilators, but will help to stop the advancement of the virus in patients with earlier stages of COVID-19. By blocking cytokine synthesis in the lung cells and increasing the production of surfactant, which is key to the lung’s ability to transmit oxygen, we are hopeful that inhaled VIP will prove to be of clinical benefit across a wider array of patients suffering respiratory complications from COVID-19 infection.” https://www.oindpnews.com/2020/08/neurorx-gets-clearance-for-clinical-trial-of-inhaled-aviptadil-for-covid-19/
Bought me some more today...
NeuroRx gets clearance for clinical trial of inhaled aviptadil for COVID-19
The FDA has cleared an IND for NeuroRx to conduct a clinical trial of an inhaled formulation of its RLF-100 aviptadil in patients with moderate or severe COVID-19, the company said. NeuroRx recently announced that an intravenous formulation of RLF-100 has shown promising results in patients with severe COVID-19 and that researchers in Brazil have demonstrated that aviptadil can prevent replication of the SARS-CoV-2 virus in human lung cells.
NeuroRx is developing aviptadil for COVID-19 in partnership with Relief Therapeutics, which is also developing RLF-100 for the treatment of pulmonary sarcoidosis and pulmonary hypertension. RLF-100, a synthetic human vasoactive intestinal polypeptide (VIP), has been designated as a Material Threat Medical Countermeasure and has also received Fast Track designation.
According to the companies, the trial will begin around September 1 in hospitalized COVID-19 patients who have severe disease that has not yet progressed to respiratory failure. Depending on the results of that portion of the study, the trial would be expanded to include mild and moderate COVID-19 patients outside of the hospital setting.
NeuroRx CEO Jonathan Javitt commented, “Now that we know VIP suppresses replication of the SARS-CoV-2 virus in human lung cells, based on the outstanding work of the Oswaldo Cruz Institute (Rio de Janeiro). We are optimistic that treatment with VIP will not only help patients on ventilators, but will help to stop the advancement of the virus in patients with earlier stages of COVID-19. By blocking cytokine synthesis in the lung cells and increasing the production of surfactant, which is key to the lung’s ability to transmit oxygen, we are hopeful that inhaled VIP will prove to be of clinical benefit across a wider array of patients suffering respiratory complications from COVID-19 infection.”
https://www.oindpnews.com/2020/08/neurorx-gets-clearance-for-clinical-trial-of-inhaled-aviptadil-for-covid-19/
Facts salad!
VIP has a half life of about 2 minutes in the bloodstream...ok.
Your body has about 5.6 liters (6 quarts) of blood. This 5.6 liters of blood circulates through the body three times every minute. In one day, the blood travels a total of 19,000 km (12,000 miles)—that's four times the distance across the US from coast to coast. ~ PBS, heartfacts
CDC Study Puts Economic Burden of Asthma at More Than $80 Billion Per Year. Asthma costs the U.S. economy more than $80 billion annually in medical expenses, days missed from work and school, and deaths, according to research published online in the Annals of the American Thoracic Society.
~AJMC
Acquisition?? Possible this early??
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4 little words that mean so much! When Dr. Javitt said, "So, you know, we’re wondering, are we seeing the world’s biggest placebo effect, or are we really on to something", I took it to be a statement more so than a question. In other words, "world's biggest placebo effect" tells me everything I need to know about what he believes is true and that really is "THE" 64 million-dollar question for all of us longs. Either this trial is going to set the Guinness world record for placebo effect after all of these amazing patient improvements or they actually have an effective therapeutic for covid and just need to prove it further for the FDA.
Which do you think is more likely? This sets a new world record out of all the hundreds of thousands of trials or it gets approved?
My $ stays on RLFTF.~ from Pcilliterate post
A growing body of experimental evidence indicates that surfactant dysfunction may contribute to the airway obstruction of asthma. In fact, guinea pigs sensitized with ovalbumin and then challenged by aerosol exhibit altered performance of surfactant (2). Similarly, lung lavage fluid and sputum of patients with allergic asthma contain a surfactant with decreased surface activity (3, 4). Leakage of plasma proteins into the airways appears to play a fundamental role in surfactant inactivation (3, 5). Other invoked mechanisms include increased hydrolysis of surfactant phospholipids (6) and decreased synthesis of hydrophobic surfactant proteins (7).
https://www.atsjournals.org/doi/full/10.1164/rccm.2312019
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Surfactant and allergic airway inflammation
https://smw.ch/article/doi/smw.2013.13818
Besides the disease burden, COPD is also associated with substantial economic costs. In the European Union, the total direct costs for COPD are estimated to be about 3% (€38.6 billion) of the total health care budget
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1179-7
Cigarette smoke is an important risk factor for COPD and it is known to adversely affect surfactant. In a series of 20 smoker, non-asthmatic COPD patients compared with 5 nonsmoker healthy controls we found a marked decrease (about 6-7 times) of total phospholipids in bronchoalveolar lavage fluids.
https://www.karger.com/Article/PDF/196100
Think that RLFTF will help alleviate this condition?
The study is posted at https://clinicaltrials.gov/ct2/show/NCT04360096 . The first phase will commence with patients hospitalized for severe COVID-19 who do not yet have respiratory failure. If promising results are seen in the inpatient setting, the trial will expand to patients at home with mild and moderate COVID-19 in order to prevent the need for hospital admission.
https://news.yahoo.com/fda-grants-inhaled-ind-rlf-053000458.html
The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2
Liang Chen, Xiangjie Li, Mingquan Chen, Yi Feng, Chenglong Xiong Author Notes>>>>>>>>>>>>>>>>>>
Cardiovascular Research, Volume 116, Issue 6, 1 May 2020, Pages 1097–1100, https://doi.org/10.1093/cvr/cvaa078
Published: 30 March 2020>>>>>>>>
Abstract>>>>>>>>>>>>>>>>>>>>>>
A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2. https://academic.oup.com/cardiovascres/article/116/6/1097/5813131
BUDAPEST, Hungary (AP) — The number of new confirmed coronavirus cases spiked Friday in parts of eastern Europe, with Hungary and the Czech Republic registering all-time daily highs. Signs of the pandemic's resurgence were also evident in Britain and the Netherlands.
Hungarian Prime Minister Viktor Orban said his government was drafting a “war plan” to defend against the second wave of the pandemic. The plan's aim was “not for everyone to stay at home and bring the country to a halt ... but to defend Hungary’s functionality," Orban said.
The prime minister said measures meant to protect the economy and spur growth would be introduced in the coming weeks. In the second quarter of the year, Hungary's gross domestic product fell 13.6%, the worst drop in the region.
Orban reiterated the need to protect the elderly, one of the group's most at-risk during the pandemic, and authorities have banned most visits to retirement homes and hospitals to stem the spread of the virus.
Expanded access, sometimes called "compassionate use," is the use of an investigational medicine (i.e., one that has not been approved by Food and Drug Administration (FDA)) by a patient who cannot be enrolled in a clinical trial.
https://www.boehringer-ingelheim.us/innovation/clinical-trials/expanded-access-program
The fireman’s event was outside clinical trial (act of compassion) and not part of the clinical trial data deemed so important by Guilles Della Corte, MD and Relief Therapeutics Holding SA.
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Multinational Randomized Clinical Trials (MRCTs) are challenging
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But, despite the challenge, the need to conduct clinical research internationally is stronger than ever
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The increasing shift from expert opinion towards evidence-based medicine enhances the importance of MRCTs
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In addition, the demand of Health Authorities (HAs) for high quality data is also increasing, leading to favor MRCTs
https://www.academia.edu/33494364/PITFALLS_in_MULTINATIONAL_CLINICAL_TRIALS_pptx
PennyWorld, I posted this tip to get the ball rolling. Hopefully someone on this board is more savvy and can post a better tip than mine. Have a good day!
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There are high float and low float stocks. That can and does affect the price movement of a stock. If you're learning how to invest in the stock market with little money than float can be highly effective.
My preference is low float stocks (sub 10 million) for scalping stocks using hotkeys. I typically only hold for a few candle's because the bid ask spread is usually wide and I need to get in and out quick. I watch the volume and the price action and trade quickly.
Again, the price of the stock can change .40 cents in a few seconds, so you need to be quick. I use hotkeys on CMEG to day trade which is a customized version of DAS Trader and has no PDT rule.
Penny stocks are well known for doing this. Go and check a penny stock chart after a public offering. Here's another example below of OTlK's offering.
https://bullishbears.com/what-does-float-mean-in-stocks/
Benzinga Pro offers a Screener tool to find float. You can set parameters and filter for what you’re looking for such as:
-Specific dollar amount
-Float
-Float percentage
-Volume
-Shares outstanding
And so much more
There is an option to save the parameters you’ve chosen so it’s easily accessible for the next time.
https://pro.benzinga.com/blog/how-to-find-low-float-stocks/
Extracorporeal membrane oxygenation (ECMO) is a life support technique used in patients with respiratory and/or cardiac failure. The ECMO circuit consists of vascular cannulae, a pump and an artificial lung. Infections are among the most common complications associated with ECMO and have a significant impact on the mortality rate. Here we present a narrative literature review regarding the epidemiology, risk factors, pathogenesis and prevention of infectious complications during ECMO support. The prevalence of hospital-acquired infections during ECMO is 10-12% and their occurrence is likely to be more frequent compared with other critically ill patients. Coagulase-negative staphylococci, Candida spp., Enterobacteriaceae and Pseudomonas aeruginosa are the most frequently involved pathogens.
https://pubmed.ncbi.nlm.nih.gov/28528989/
Who picked that winner without mortality benefit at the tune of $70 million? Can we name him, her, them?
A clinical trial sponsored by the National Institutes of Health found that the drug shortens recovery times for many Covid-19 patients. However, remdesivir has not yet been proven to reduce mortality—to save lives. While the NIH trial found a numerical improvement in survival, the difference did not reach conventional thresholds of statistical significance or certainty; and a smaller study published in the Lancet also did not find an improvement in mortality. If remdesivir does not offer a mortality benefit, then the Institute for Clinical and Economic Review—an independent drug-pricing watchdog—puts the “value-based price benchmark” for the drug at $310 per treatment course. That’s about one-tenth its current price. Even if a mortality benefit from remdesivir were eventually confirmed, ICER pegs its value-based price at $2,500 to $2,800 per course, still 10 to 20 percent lower than what we pay right now.
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What about the cost of investment—does Gilead need to charge $3,120 for remdesivir to make up for all the time and money that the firm put into it? Even if it were appropriate to set a price based on a sunk cost—and most economists would argue that it’s not—remdesivir’s development has been buoyed by incredible amounts of government investment. The 2015 paper detailing the discovery of remdesivir was the product of a public-private partnership between scientists from Gilead, the US Army Medical Research Institute of Infectious Diseases, and the US Centers of Disease Control and Prevention; yet government employees were excluded from the molecule’s patent. Financially, remdesivir’s development has been directly supported by at least $70 million of taxpayer money—including funding for its initial discovery, studies of its effects on coronaviruses, and its Covid-19 clinical trials. Investment in remdesivir hasn’t been Gilead’s alone, and the drug’s price should accordingly reflect the contributions of taxpayer funds that offset the costs of its development and commercialization.~Wired
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Wired on Remdesivir...
<p>Remdesivir certainly has value, but the data right now supports a price lower than what its maker, Gilead Sciences, Inc., is charging. A clinical trial sponsored by the National Institutes of Health found that the drug shortens recovery times for many Covid-19 patients. However, remdesivir has not yet been proven to reduce mortality—to save lives. While the NIH trial found a numerical improvement in survival, the difference did not reach conventional thresholds of statistical significance or certainty; and a smaller study published in the Lancet also did not find an improvement in mortality. If remdesivir does not offer a mortality benefit, then the Institute for Clinical and Economic Review—an independent drug-pricing watchdog—puts the “value-based price benchmark” for the drug at $310 per treatment course. That’s about one-tenth its current price. Even if a mortality benefit from remdesivir were eventually confirmed, ICER pegs its value-based price at $2,500 to $2,800 per course, still 10 to 20 percent lower than what we pay right now.</p>
https://www.wired.com/story/the-us-is-paying-way-too-much-for-remdesivir/
EMCO
The ECMO team can decrease support even more or take away ECMO for minutes or hours to see if the patient needs to stay on ECMO.
You will hear the ECMO team talk about a “trial off.” The nursing staff will draw frequent labs to see how your loved one is doing. If everything looks good, the ECMO team will talk about removing ECMO.
If the test shows us the patient needs more time on ECMO, we can put them back on ECMO support. The medical team taking care of your loved one will walk you through what they are looking for each day.
Having issues with laptop and network device(s). Will reply asap. I do enjoy opportunities to speculate.
Influenza is among the nine deadliest viruses in the world.
During a typical flu season, up to 500,000 people worldwide will die from the illness, according to WHO. But occasionally, when a new flu strain emerges, a pandemic results with a faster spread of disease and, often, higher mortality rates.
The most deadly flu pandemic, sometimes called the Spanish flu, began in 1918 and sickened up to 40 percent of the world's population, killing an estimated 50 million people.
"I think that it is possible that something like the 1918 flu outbreak could occur again," Muhlberger said. "If a new influenza strain found its way in the human population,and could be transmitted easily between humans, and caused severe illness, we would have a big problem."
http://www.livescience.com/48386-deadliest-viruses-on-earth.html
Do you know of an NNVC insider posting on the NNVC board? Write an open letter to the CEO! Do it from Seeking Alpha! Here are some guidelines to help you out!
How to Write an Effective Complaint Letter to a CEO
By Ruth Mayhew
The adage about the squeaky wheel is often true when you want to resolve an issue where you've received poor service or a defective product. If you attempted to resolve your dissatisfaction with the store manager or customer service representatives, consider writing a letter to the company's CEO -- the chief executive officer. Taking time to write a letter that states your concerns, along with information that substantiates your claim, can work to your advantage.
Other People Are Reading
Gather all the information possible about your complaint. That can include previous correspondence with customer service representatives, payment records and evidence of a deficient product, poor service or other proof that substantiates your claim. Assemble your documents and information in chronological order to illustrate the period from when you first experienced the deficiency to the present.
Draft a chronology of events. If necessary, begin your chronology from the time you first subscribed to the service or initially purchased the product. Include pertinent information such as dates of service, product description, model and serial numbers. Refine your draft with specific information that asserts your right to a replacement product or repair service. For example, if you have experienced poor home telephone service, gather information about when you previously reported the service as well as technicians who attempted to repair your telephone service.
Research the company, including the specific product or service. Access online resources for user-generated information about satisfied and dissatisfied customers. Review their complaints and the course of action they followed to resolve their issues. Obtain information about the company from business databases and clearinghouses such as the Better Business Bureau. Depending on the industry, contact government resources for information on how to lodge a complaint. For example, the Federal Trade Commission is a resource for individuals with complaints against businesses.
Write the body of your letter, beginning with an introduction. Explain that you're writing to the CEO because you did not receive a satisfactory response from your previous contact with customer service or another representative of the company. Compose a pleasant introduction, free from sarcasm and anger. The best way to resolve matters is through cooperation, but sarcastic wit or letters written in a condescending manner will not receive the positive response you're seeking.
Insert your chronology. If necessary, pare down the details in your letter to maintain just the essential points. Your letter should also indicate you have additional information that you will gladly share in a telephone conversation or subsequent communication. Express your interest in resolving the matter as quickly as possible so as not to take up unnecessary resources. Include contact information and your availability for a telephone call or face-to-face meeting. Dispatch your letter or e-mail and retain a copy for your personal files.
Read more : http://www.ehow.com/how_8147371_write-effective-complaint-letter-ceo.html
When insider(s)/investor(s) buy, buy, buy...yes, we should pay attention and join! Do you have information that supports the idea Dr. Milton Boniuk is just throwing good money after bad? Who, Pump Terminator and his minimum wage crew? A hunch? We know who Ben McClure is but, who is Pump Terminator? In my view, his/her/their blog provided the "go-ahead" signal for the "bear attack" NanoViricides, Inc. CEO referred to in his letter to shareholder but again, Dr. Milton Boniuk, an independent director/insider, an astute/highly successful businessman, an entrepreneur, in addition to being an accomplished eye surgeon, educator, and administrator, buys repeatedly and confidently.
http://ih.advfn.com/p.php?pid=nmona&article=68529003
http://ih.advfn.com/p.php?pid=nmona&article=68325023
http://ih.advfn.com/p.php?pid=nmona&article=68296181
Why is it you can give a positive opinion about the impartiality of the "loanranger" poster but never ask him about Dr. Boniuk's NNVC stock sale, a sale that never came to past!?!
Red flag: Insiders aren't buying stocks
The stock market is having a terrific week. Momentum is giddy, except for this: the best informed people aren't buying stocks.
Smart investors keep an eye on what the so-called "insiders" are doing -- the CEOs, directors and company founders.
Typically, when the stock market tanks like it did in late August and September, top management will jump at the opportunity to buy cheap stock. It's the ultimate sign of confidence they believe better days are ahead.
But that's not what's happening.
"I've been very surprised," says David Santschi, CEO of TrimTabs Investment Research. "We were looking for a big pick up in insider buying. We didn't see it."
Enthusiasm from insiders has evaporated as the market dropped. It's a cautionary sign.
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http://money.cnn.com/2015/10/09/investing/insiders-are-not-buying-stocks/index.html
Enter Dr. Milton Boniuk, an independent director/insider, an astute and highly successful businessman and entrepreneur, in addition to being an accomplished eye surgeon, educator, and administrator...
If we have a similar platform technology (to destroy viruses) to that of BIND Therapeutics (for cancer), we may be using similar, if not the same source, for specialized/high tech equipment/instruments.
BIND Therapeutics has the patented Accurins(R) and NanoViricides Inc, has the patented nanoviricides(R).
BIND History
BIND Therapeutics was launched in 2007 as BIND Biosciences with the vision of revolutionizing the treatment of life-threatening diseases through the application of nanotechnology.
After two decades of research at MIT in the area of biomaterials and nanoparticle engineering, a number of critical technologies converged in the laboratory of Professor Robert Langer that would enable the development of therapeutic polymeric nanoparticles. Building on this convergence, Professor Omid Farokhzad of Harvard Medical School began collaborating with Professor Langer to apply combinatorial strategies to develop targeted nanoparticles for specific therapeutic applications.
This research, conducted in collaboration with the Koch Institute at MIT and Brigham and Women's Hospital-Harvard Medical School resulted in a the development of the Medicinal Nanoengineering platform, which enables the identification of the precise characteristics of an optimally engineered targeted nanoparticle for clinical applications. BIND Therapeutics was cofounded by Drs. Langer and Farokhzad for the purpose of developing and commercializing innovative and impactful pharmaceutical products based on the medicinal nanoengineering platform.
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www.bindtherapeutics.com/about/history.html
Microfluidic Platform for Combinatorial Synthesis and Optimization of Targeted Nanoparticles for Cancer Therapy (2013)
Taking a nanoparticle (NP) from discovery to clinical translation has been slow compared to small molecules, in part by the lack of systems that enable their precise engineering and rapid optimization. In this work we have developed a microfluidic platform for the rapid, combinatorial synthesis and optimization of NPs. The system takes in a number of NP precursors from which a library of NPs with varying size, surface charge, target ligand density, and drug load is produced in a reproducible manner. We rapidly synthesized 45 different formulations of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) NPs of different size and surface composition, and screened and ranked the NPs for their ability to evade macrophage uptake in vitro. Comparison of the results to pharmacokinetic studies in vivo in mice revealed a correlation between in vitro screen and in vivo behavior. Next, we selected NP synthesis parameters that resulted in longer blood half-life and used the microfluidic platform to synthesize targeted NPs with varying targeting ligand density (using a model targeting ligand against cancer cells). We screened NPs in vitro against prostate cancer cells as well as macrophages, identifying one formulation that exhibited high uptake by cancer cells yet similar macrophage uptake compared to non-targeted NPs. In vivo, the selected targeted NPs showed a 3.5-fold increase in tumor accumulation in mice compared to non-targeted NPs. The developed microfluidic platform in this work represents a tool that could potentially accelerate the discovery and clinical translation of NPs.
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We reported a new microfluidic platform for the rapid, combinatorial synthesis of targeted polymeric NPs. It was first demonstrated that NPs with a wide range of properties can be generated by making a small library comprised of NPs with size from 25-200 nm, zeta potential from -20 to +20 mV, ligand density from 0 to ~105 ligands/µm2, and drug loading from 0 to 5%. Subsequently, we showed the rapid NP development capabilities of the system by synthesizing 45 NP formulations of different sizes and PEG coverage, and screened them against macrophage uptake in vitro. Finally we investigated the relation between in vitro macrophage uptake and in vivo pharmacokinetics, where low macrophage uptake correlated with longer circulation time. Building upon the in vitro macrophage uptake screen, we synthesized and screened targeted NPs to identify a formulation that maximized specific uptake in vitro while minimizing macrophage uptake. We also investigated the tumor accumulation of TNPs versus NT-NPs of essentially identical biophysicochemical properties, where the TNPs showed 3.5-fold accumulation in tumor versus non-targeted ones. Three key advantages of our system over existing bulk synthesis include (i) from a small set of NP precursors one can rapidly synthesize a NP library with a wide range of distinct physicochemical properties; (ii) the NPs prepared have high batch-to-batch reproducibility; (iii) NPs can be prepared at different scales (e.g. microgram versus milligram) without varying substantially the NP properties. These advantages allow for both in vitro and in vivo screening with the goals of either accelerating the clinical translation of a specific formulation or obtaining deeper fundamental understanding on the correlation of NP properties and biological behavior.
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www.ncbi.nlm.nih.gov/pmc/articles/PMC3963607/
April 22, 2015
BIND Therapeutics Presents Data Highlighting Ability of Accurins to Control Biodistribution and Accumulate in Target Tissue at AACR Annual Meeting 2015
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CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine platform company developing targeted and programmable therapeutics called Accurins™, today announced that clinical and preclinical data from its oncology pipeline, including proprietary and collaboration programs, were presented at the American Association of Cancer Research (AACR) Annual Meeting 2015. The presentations include data from the Company's lead proprietary Accurin drug candidate, BIND-014, and the Accurin drug candidate AZD2811, which is being developed in collaboration with AstraZeneca.
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In a poster entitled, "Imaging Accurin-AZD1152 hQPA nanoparticle accumulation in pre-clinical tumours," data were presented that show the Accurin nanoparticle AZD2811 accumulates in tumors and achieves prolonged tumor drug exposure. This is the first time distribution of nanoparticles in tumors has been demonstrated.
-Imaging mass spectrometry analysis demonstrated that Accurin nanoparticle AZD2811 accumulates in preclinical tumor models and confirmed that the Accurin accesses the tumor and provides prolonged drug exposure and retention in the target tissue.
-Multiple imaging techniques demonstrated Accurin nanoparticle AZD2811 is still detected at nine days after nanoparticle administration, while no drug was detected 24 hours after the prodrug AZD1152 was administered.
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http://ir.bindtherapeutics.com/releasedetail.cfm?ReleaseID=907878
...about two months later...
June 23, 2015
BIND Therapeutics Announces FDA Authorization of First-in-Human Clinical Trial with AstraZeneca's Aurora B Kinase Inhibitor Accurin AZD2811
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- Collaboration with AstraZeneca results in second Accurin candidate to enter clinical development -
- Promising AZD2811 Data Demonstrating Tumor Growth Inhibition and Prolonged Drug Exposure Recently Presented at 2015 American Association of Cancer Research (AACR) Annual Meeting -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called Accurins™, today announced that the U.S. Food and Drug Administration (FDA) has authorized the use of AstraZeneca's Accurin AZD2811 in clinical trials under an investigational new drug (IND) application. BIND is collaborating with AstraZeneca on the development of AZD2811, an Aurora B Kinase inhibitor that has been shown to be active in both solid and hematological tumors in preclinical models, and the companies anticipate enrolling patients in a phase 1 clinical trial with AZD2811 in the fourth quarter of this year. BIND will earn a $4 million milestone payment upon first dosing a patient in a phase 1 clinical trial with AZD2811.
Preclinical data on AZD2811 were presented at the 2015 American Association of Cancer Research (AACR) annual meeting in April 2015, including data demonstrating promising in vivo and in vitro tumor growth inhibition as monotherapy in models of diffuse large B-cell lymphomas (DLBCL) and small cell lung cancer (SCLC). Additional data showed that AZD2811 delivers prolonged exposure to active drug while having the potential to adapt the dosing regimen, potentially achieving an improved therapeutic index. In addition, using mass spectrometric imaging, AZD2811 was shown to accumulate in tumors and achieve prolonged tumor drug exposure. This represents the first time distribution of nanoparticles in tumors has been demonstrated. Previously, preclinical tumor model data were presented showing that AZD2811 minimizes the bone marrow toxicity seen with the parent compound, which has limited the clinical utility of Aurora B kinase inhibitors as a class.
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BIND and AstraZeneca expect to enroll the first patient in a phase 1 clinical trial with AZD2811 in the fourth quarter of 2015. Under terms of the collaboration, AstraZeneca is responsible for clinical development and commercialization and BIND is responsible for conducting clinical manufacturing through at least the end of phase 2 clinical trials.
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ir.bindtherapeutics.com/releasedetail.cfm?ReleaseID=919006
About BIND Therapeutics factsheet:
»We design combinatorial libraries of targeted nanoparticles with precise and systematically varied biophysicochemical properties such as particle size, surface properties, ligand density, API load and release profile, using a unique self-assembly nanoparticle fabrication process to optimize each product-for example, to balance circulation time with effective targeting and binding for a
particular cell or tissue target.
»We engineer product candidates with optimal performance properties using an iterative process that includes in vitro drug release and cell binding along with in vivo PK, tolerability, biodistribution, targeting, and efficacy studies.
»We manufacture candidate Accurins from gram-scale laboratory experiments through kilogram-scale GMP clinical batches using robust, reproducible, and scalable processes
www.bindtherapeutics.com/pdfs/BINDfactsheet.pdf
Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.(2014)
Abstract
Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13-150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies.
FROM THE CLINICAL EDITOR:
Applications of nanoparticle synthesis with microfluidic methods are typically limited to in vitro studies due to low production rates. The team of authors of this proof-of-principle study reports on the successful parallelization of NP synthesis by 3D hydrodynamic flow focusing using a multilayer microfluidic system to enhance production rate without losing the advantages of reproducibility, controllability, and robustness.
www.ncbi.nlm.nih.gov/pubmed/23969105
Optimizing the discovery and clinical translation of nanoparticles: could microfluidics hold the key?
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Since the first demonstration of a liposomal drug carrier in 1970s [1], tremendous efforts have been directed at developing nanoparticle (NP) platforms for therapy and diagnosis of major diseases. A few US FDA-approved NPs have emerged, including liposome-based Doxil and albumin-based Abraxane for chemotherapy, and iron oxide NPs Feridex and Resovist for MRI [2,3]. Several other NP platforms are in clinical trials, including a targeted polymeric NP for treatment of prostate cancer [2–4]. Yet, there exist major bottlenecks that retard discovery and clinical translation of NPs [2–3,5]. First, rational design of NPs is nontrivial because of limited knowledge of how the physicochemical properties of NPs correlate with in vivo behavior. Therefore, current technology for optimization of NPs requires intensive in vitro and in vivo screening. Second, conventional batch-type bulk reactors are limited in their ability to reproducibly prepare high-quality NPs while tuning their physicochemical properties. Third, in vitro screens do not adequately model in vivo environments, considerably increasing the cost of in vivo screening.
In the past decade, the intersection of nanomedicine and the rapidly growing field of microfluidics – the science and technology of manipulating nanoliter to picoliter volumes of fluids in microscale channels [6] – has provided fresh approaches to tackle these challenges [5]. Microfluidic systems enable precise control of microscale environments, which finds use in chemical synthesis, chemical and biomolecular analysis, tissue engineering, and other applications. Now, microfluidics is playing a key role in synthesis and screening of NPs and in elucidating the interaction of NPs with cells and tissues, promising to accelerate the clinical translation of NPs [5].
The first major application of microfluidics for nanomedicine was for improving the quality of NPs though control of the reaction environment [5,7–8]. Microfluidic reactors enable rapid mixing of reagents, control of temperature, and precise spatiotemporal manipulation of reactions that are difficult, if not impossible, in larger reactors [7,9]. For example, amphiphilic molecules self-assemble into NPs by mixing with a nonsolvent in a process known as nanoprecipitation [2,5]. In this process, mixing time has a strong influence on the average NP size and the size distribution. In conventional bulk synthesis methods, mixing is heterogeneous and typically occurs on a time scale longer than the characteristic time scale for self-assembly, which results in large and polydisperse NPs. Controlled and homogeneous mixing in microfluidic synthesis methods results in smaller and uniform NPs [5,8]. Microfluidic control of reactions on the millisecond timescale has also enabled rapid nucleation followed by controlled growth and rapid quenching, leading to the synthesis of various inorganic NPs with improved spectral response for imaging applications [7,9]. This fine spatiotemporal control was achieved by using monodisperse droplets that serve as identical microscale reactors [9]. Droplets can be generated, combined, mixed and split in a controlled manner using microfluidic units. Since the reaction time of reagents directly correlates to residence time of the droplet in microchannel, it can be precisely controlled by tuning the residence time in a reaction area (e.g., heating zone) [10] or by adding a quenching agent at precise downstream locations [11]. Although microfluidics typically deals with small volumes, parallelized and high-throughput micro/millifluidic systems have also been developed to enable synthesis of high-quality NPs at larger scales [12–14]. Unlike batch reactors that require process optimization for scale-up, microfluidic devices typically operate in continuous process mode and do not require intensive process optimization for larger-scale production. These developments in synthesis and scale-up make a strong headway towards addressing the need for improved quality and consistency of NPs.
Microfluidics also enables precise and reproducible manipulation of the physicochemical properties of NPs, opening new avenues for high-throughput combinatorial NP synthesis and screening. For example, Chen et al. prepared a library of siRNA-containing lipid NPs with different chemical structures using a microchannel with groove structures for rapid and effective mixing of reagents [15]. This approach enabled in vitro and in vivo screening of lipid NP-mediated siRNA delivery to discover optimal lipids for silencing factor VII expression in mouse liver. Valencia et al. developed a microfluidic platform for rapid, combinatorial synthesis of a library of polymeric NPs by combining a multi-inlet micromixer for premixing NP precursors in a specified ratio and a downstream mixing unit for rapid nanoprecipitation [16]. Using high-throughput screening, this combinatorial synthesis method identified a targeted NP formulation that exhibited enhanced tumor accumulation in a mouse model of prostate cancer compared with an otherwise identical nontargeted NP. These results illustrate the potential of high-throughput microfluidic synthesis and screening to reduce costs by consuming smaller volumes of reagents while exploring a large parameter space of the physicochemical properties of NPs.
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http://www.futuremedicine.com/doi/full/10.2217/nnm.14.73
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In Iowa, one of the largest U.S. egg processors has started to buy foreign supplies for the first time. Elsewhere in the Midwest, a free-range egg producer says it may build automatic car washes to scour vehicles accessing its 60 farms. And nationally, agricultural workers are being urged to get flu shots.
Less than six months after the country’s worst-ever outbreak of avian influenza killed 48 million birds and cost taxpayers almost $1 billion, the American poultry industry is remaking itself to prepare for the likely return of the disease. The virus thrives in chilly weather and is carried across the country by wild birds that are just now beginning to migrate south.
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http://www.claimsjournal.com/news/national/2015/10/05/266119.htm
Report finds $1.2 billion in Iowa avian flu damage
Iowa took an economic hit of about $1.2 billion stemming from the death of more than 30 million hens and 1.5 million turkeys because of avian flu this past spring, according to a report commissioned by the Iowa Farm Bureau Federation (IFBF) released yesterday.
In addition, H5 avian flu affected thousands of poultry in multiple outbreaks in both Palestine and Nigeria.
Iowa study: 8,400 jobs lost
The Iowa study, conducted by Decision Innovation Solutions of Urbandale, Iowa, found that the avian flu outbreaks around the state—mostly caused by H5N2—resulted in 8,444 lost jobs, many of which will not be recovered.
It also noted an impact of $427 million in lost wages in addition to the jobs lost, as well as about $145 million in lost taxes. The firm estimated the total economic loss at $1.2 billion. The outbreaks affected the egg, chicken, and turkey industries in the state.
In May, Minnesota and Iowa experts put the total loss for the two states at around $1 billion, but several H5N2 outbreaks occurred in both states after that. Minnesota lost more than 9 million poultry to the virus, mostly turkeys. Nationwide, about 50 million birds died because of the outbreaks.
"Many layer operations affected by the outbreak expect to take 18-24 months before reaching pre-outbreak production levels," the report said. "Egg producers able to sell eggs, as well as consumers, can expect to be in an elevated price environment for at least the next 6-9 months. Turkey producers are predicted to be out of production for approximately 30 weeks."
"It's really astounding that we could lose half of our poultry flock in a couple of months," said Dave Miller, the IFBF's director of research and commodity services, according to a Des Moines Register story yesterday. "Recovery from this outbreak, which devastated Iowa egg and poultry farms, will not be swift."
The report concludes, "In addition to the lost revenue to producers, [highly pathogenic avian flu] also has many other adverse consequences on economic activity up and downstream such as lost business for feed suppliers, veterinarians, transportation, financial institutions, and decreases in government tax revenues."
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http://www.cidrap.umn.edu/news-perspective/2015/08/report-finds-12-billion-iowa-avian-flu-damage
Bird flu vaccine, under development, divides U.S. poultry industry
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Many countries have a strict policy of refusing to accept meat from nations using a vaccine because it can be difficult to discern through testing whether birds were infected with an active virus or were vaccinated, said James Sumner, president of the USA Poultry & Egg Export Council.
Even during the current outbreak which affected 15 states, about 10 trade partners banned poultry imports from the entire U.S., Sumner said.
Vilsack said it's uncertain when a vaccine would be ready for large-scale production. Even once stockpiled, a vaccination program would not begin until the USDA, consulting with affected states, decided it was necessary to control an outbreak.
http://www.cbsnews.com/news/bird-flu-vaccine-developed-for-chickens/
Hold your horses "Wild Bill",...news flash!
This technology works and has been proven over and over!
Enter Dr. Milton Boniuk (2013)...
The NanoViricides, Inc. PR clearly indicates they follow advice from the company, at the time, Australian Biologics. I quickly researched and provided an article with a link. From the article I underlined the following:
Opinion of an anonymous poster. What can I say,...weak? Just because other companies don't divide Safety/Tox Studies/GLP in phases does not mean it cannot be done? or do you have evidence to the contrary?
Here are the facts:
Dude...seriously, we have FluCide(TM)advancing from Phase 1 and Phase 2 of Safety/Toxicology Studies, there is no effective treatment out there for the shingles and we are accelerating development of topical HerpesCide(TM). Our nanomedicines go after the virus in the host, not to enhance the host's immune system which other drugs in the market are not very effective doing. Take a look at the Herpes video:
On Mar 31, 2015 - We are now progressing to a 1kg scale-up of FluCide(TM), and enabling in-process control instrumentation--- CMC studies to enable further scale-up from the current multi-100g scale of production to kg-scale production. CMC stands for "Chemistry, Manufacture, and Controls," and relates to being able to make the drug substance and the drug product in a reproducible fashion, batch after batch.
Bird Flu Vaccine Conditionally Approved, but Still Can’t Be Sold
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“U.S.D.A. has said no vaccine is to be used for highly pathenogenic avian influenza,” said Joel Harris, vice president for sales and marketing at Harrisvaccines, which was founded by his father, Dr. Hank Harris. “What this license does is that if they allow a vaccine to be used, we would immediately have a U.S.D.A.-licensed product available for producers.”
The H5N2 strain of avian influenza that did most of the damage in the spring is extremely virulent, moving from one or two birds to entire flocks within 24 to 48 hours. It is believed to have been spread by wild birds migrating north, and poultry and egg producers have been concerned that birds will bring it or another equally devastating strain back with them as they begin their migration south this winter.
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Harrisvaccines is continuing to test the efficacy of the vaccine, with one trial with turkeys underway and other planned for testing on adult hens and day-old chicks. Mr. Harris said the biggest drawback so far is that the vaccine must be injected, which is logistically complicated in operations involving tens and even hundreds of thousands of birds.
http://www.nytimes.com/2015/09/22/business/bird-flu-vaccine-conditionally-approved-but-still-cant-be-sold.html
It is possible that once NanoViricides, Inc. ships samples of FluCide(TM) to BASi for third and final phase of Safety/Toxicology Studies, the H5N2 strain may be among those used for additional efficacy studies, required to ascertain the broadspectrum nature of the drug candidate.
Unlike the dishonorable actions of sociopaths like John Dillinger and Pump Terminator...
In two days NNVC rose from $1.02 to a $1.55, that is a 50% move to the upside, on no material news! As we all know, NNVC is a small float stock. Just imagine what will happen on positive material news!
You mean like Rawnoc's touted marvel drug Fludase!?! Preclinical done quickly, in one fell swoop!
NexBio...
-A small-biotech that is privately-held
-with Fludase(TM) a first-in-class Influenza drug
-government begins to grease skids for the small-biotech, Aug 8, 2005?
-a 50m contract with the NIH, fast-tracked
Why would a privately-held company, that seemingly has everything going for them, would feel the urge to defraud the United States of America/taxpayers funded NIH? Cash-flow problems? with a 50m biologic-contract, how can that be?