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Post by mango on Apr 2, 2020 4:03:22 GMT -5
medium.com/@stkirsch/getting-large-rcts-done-asap-on-all-our-most-promising-options-is-the-best-way-to-end-the-covid-19-53bc842f4eff
Anyone know who this is working with Mannkind??
Micronized niclosamide
"A recent study highlighted niclosamide as one of just two “best drugs” to pursue from an in vitro screen over 50 FDA approved drugs. It has a super high selectivity index (SI): 176! It was shown 16 years ago to inhibit SARS-CoV replication. The problem though is bioavailability: taken as a pill, it just sits in the stomach. However, by micronizing the drug, it can be put in an inhaler and thus be delivered directly to the affected tissue. We already have the GMP micronized drug available; it just needs to be delivered using an inhaler vehicle. This can be used as a prophylaxis to avoid the risk of pulmonary fibrosis.
Niclosamide s hows several mechanisms of activity against flaviviruses — including endosome neutralization. It is likely that endosomes are main route of SARS and SARS-CoV2 entry — that’s how hydroxychloroquine and chloroquine are thought to act — good evidence for that in vitro in non-lung cell lines (not yet in lung cells). Another mechanism is intracellular acidification and inflammasome activation — along with mitochondrial uncoupling. Since mitochondrial uncoupling is how it kills parasites — this is likely mechanism of toxicity to human cells as well.
What’s really cool is we can eliminate most of the guesswork out of dose and frequency because we can now see exactly what is going on in real-time using CT. Watch this video: (video is in link)
So we just need a company with the technology to mix with excipients and deliver this in an inhaled form and a PI willing to trial it. Thanks to assistance from Laurie Glimcher, Greg Petsko, Nitin Joshi, Yohannes Tesfaigzi, Frances Laur, and Robert Rubin, we are currently working with Phil Kuehl at Lovelace Biomedical (and LRRI). We are also being helped by Michael Castagna, CEO of MannKind who makes the Afrezza insulin inhaler that I’ve personally used in the past with excellent results.
Even though the drug is FDA approved, because this drug is being delivered in a novel way, we have to start with a Phase 1b safety study in 20 patients, but we’ll likely be able to get a good feeling of effectiveness from that.
This treatment is a great match for the disease because it is targeted and lethal (SI=176).
The receptors for the virus are in the upper GI tract, which is where it begins life. It later migrates down your GI into both the stomach and the lungs. This is why people report stomach issues. Only late stage does it migrate to the bloodstream.
Niclosamide could also be tested in patients right now by prescribing niclosamide, though I’m not sure how you’d be able to assess the viral load in your stomach.
The nice benefit of this treatment is that it is targeted delivery and reduces viral shedding. This is important in both directions: up and down. It is the viral shedding that enables the virus to drop down into your lungs and stomach. So if we can kill it off early in the GI tract, we win. No lung infection! And in the reverse direction, it keeps you from spreading it. So you get a three-fer effect: it cures you, it prevents your lungs being impacted, and it prevents you from spreading the disease to others.
We need to test this for use in 3 different scenarios: pre-infection, post-infection, and onset of symptoms. It could be the perfect prophylactic.
All the credit for this idea goes to Lynda Chin and Gary Glick, CEO of First Wave Bio. They were working on a treatment for colitis and Lynda realized they could repurpose their niclosamide micronization efforts for SAR-CoV-2.
As for how I found out about this, it was just dumb luck. I’ve known Lynda and her husband, Ron DePinho, for 20 years and we accidentally got reconnected after all this time by Shyamali Singhal, Director of the Cancer Center at El Camino Hospital who I reached out to see how things were going at my local hospital. Shyamali said she was working with Lynda Chin on a joint project. I never thought it was the same Lynda Chin I met 20 years earlier! Oddly, I was simultaneously reaching out directly to Ron DePinho to get his thoughts (I thought Ron would not be overwhelmed but I was wrong). So it was just a really remarkable coincidence to re-make this double connection two separate ways after a 20 year hiatus! Not only a random reconnect after a 20 year hiatus, but the fact that Lynda happened to be involved in the same drug I had identified as promising earlier was simply a remarkable coincidence. When she mentioned niclosamide when we talked, my jaw dropped.
Who is the company or people being referred to that Mike Castagna is helping?
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Post by itellthefuture777 on Apr 2, 2020 4:04:33 GMT -5
My thoughts- The issue has been that Niclosamide as a pill has poor bioavailability. The stomach acid eats 95% of the active drug leaving only 5% to get to target. Also this drug has limited aqueous solubility so even in a saline solution (a shot) it doesn't get to target. Indeed, otherwise an effective solution for Parkinson's research moved away because they couldn't get the drug to reach target (Brain). Also Niclosamide was used to make those fat mice loose all the fat in their livers to reduce type 2 diabetes, but again my guess is poor bioavailability meaning it works great on a small mouse but again can't get to target in human very well. From all the above articles one can gather that Mannkinds known inert Nano particle FDPK or Technosphere can load Niclosamide self assemble it with increased bioavailability to hit the lung in the deep alveoli with applications even beyond Covid-19..... Could this be what Michael (the man)and team is working to achieve for humanity with Mannkind?
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Post by itellthefuture777 on Apr 2, 2020 4:18:29 GMT -5
medium.com/@stkirsch/getting-large-rcts-done-asap-on-all-our-most-promising-options-is-the-best-way-to-end-the-covid-19-53bc842f4eff
Anyone know who this is working with Mannkind??
Micronized niclosamide
"A recent study highlighted niclosamide as one of just two “best drugs” to pursue from an in vitro screen over 50 FDA approved drugs. It has a super high selectivity index (SI): 176! It was shown 16 years ago to inhibit SARS-CoV replication. The problem though is bioavailability: taken as a pill, it just sits in the stomach. However, by micronizing the drug, it can be put in an inhaler and thus be delivered directly to the affected tissue. We already have the GMP micronized drug available; it just needs to be delivered using an inhaler vehicle. This can be used as a prophylaxis to avoid the risk of pulmonary fibrosis.
Niclosamide s hows several mechanisms of activity against flaviviruses — including endosome neutralization. It is likely that endosomes are main route of SARS and SARS-CoV2 entry — that’s how hydroxychloroquine and chloroquine are thought to act — good evidence for that in vitro in non-lung cell lines (not yet in lung cells). Another mechanism is intracellular acidification and inflammasome activation — along with mitochondrial uncoupling. Since mitochondrial uncoupling is how it kills parasites — this is likely mechanism of toxicity to human cells as well.
What’s really cool is we can eliminate most of the guesswork out of dose and frequency because we can now see exactly what is going on in real-time using CT. Watch this video: (video is in link)
So we just need a company with the technology to mix with excipients and deliver this in an inhaled form and a PI willing to trial it. Thanks to assistance from Laurie Glimcher, Greg Petsko, Nitin Joshi, Yohannes Tesfaigzi, Frances Laur, and Robert Rubin, we are currently working with Phil Kuehl at Lovelace Biomedical (and LRRI). We are also being helped by Michael Castagna, CEO of MannKind who makes the Afrezza insulin inhaler that I’ve personally used in the past with excellent results.
Even though the drug is FDA approved, because this drug is being delivered in a novel way, we have to start with a Phase 1b safety study in 20 patients, but we’ll likely be able to get a good feeling of effectiveness from that.
This treatment is a great match for the disease because it is targeted and lethal (SI=176).
The receptors for the virus are in the upper GI tract, which is where it begins life. It later migrates down your GI into both the stomach and the lungs. This is why people report stomach issues. Only late stage does it migrate to the bloodstream.
Niclosamide could also be tested in patients right now by prescribing niclosamide, though I’m not sure how you’d be able to assess the viral load in your stomach.
The nice benefit of this treatment is that it is targeted delivery and reduces viral shedding. This is important in both directions: up and down. It is the viral shedding that enables the virus to drop down into your lungs and stomach. So if we can kill it off early in the GI tract, we win. No lung infection! And in the reverse direction, it keeps you from spreading it. So you get a three-fer effect: it cures you, it prevents your lungs being impacted, and it prevents you from spreading the disease to others.
We need to test this for use in 3 different scenarios: pre-infection, post-infection, and onset of symptoms. It could be the perfect prophylactic.
All the credit for this idea goes to Lynda Chin and Gary Glick, CEO of First Wave Bio. They were working on a treatment for colitis and Lynda realized they could repurpose their niclosamide micronization efforts for SAR-CoV-2.
As for how I found out about this, it was just dumb luck. I’ve known Lynda and her husband, Ron DePinho, for 20 years and we accidentally got reconnected after all this time by Shyamali Singhal, Director of the Cancer Center at El Camino Hospital who I reached out to see how things were going at my local hospital. Shyamali said she was working with Lynda Chin on a joint project. I never thought it was the same Lynda Chin I met 20 years earlier! Oddly, I was simultaneously reaching out directly to Ron DePinho to get his thoughts (I thought Ron would not be overwhelmed but I was wrong). So it was just a really remarkable coincidence to re-make this double connection two separate ways after a 20 year hiatus! Not only a random reconnect after a 20 year hiatus, but the fact that Lynda happened to be involved in the same drug I had identified as promising earlier was simply a remarkable coincidence. When she mentioned niclosamide when we talked, my jaw dropped.
Who is the company or people being referred to that Mike Castagna is helping? My guess? I know it was a Bayer drug..I know Bayer is investigating the drug for Covid-19 ..but they must already know the pill form isn't cutting it..so..hmm..then there is IMMIX...got to wonder...but..my guess is Michael..has a little Al in him..probably working on it 80 hours a day..hell he shut the whole pipeline down..to work on this..if this is what he's working on..hmm
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Post by itellthefuture777 on Apr 2, 2020 4:30:54 GMT -5
www.eurekalert.org/pub_releases/2020-03/g-af9032520.phpNews Release 25-Mar-2020 AI finds 9 potential COVID-19 drugs that can be used on humans immediately As of today, COVID-19 has infected more than 425,000 people; AI company Gero has reviewed the existing drugs and found potential coronavirus treatments; the list of drugs has been released to initiate urgent clinical trials and collaborations Gero Share Print E-Mail Singapore 25 March, -- Gero, the leader in AI-driven drug discovery, has used its AI platform to identify the potential anti-COVID-19 drugs. Six of them have been approved, three were withdrawn, and the other nine have been already tested in clinical trials for other indications. The emergency of the situation, as well as the legal and regulatory status of these agents, make it possible to start immediate clinical trials for most of the suggested drugs. Gero used its AI drug discovery platform to identify molecules with potential effects on the coronavirus replication. The fact that this time the potential treatments were found among the existing drugs marks a significant improvement over previous efforts to use AI to predict molecules active against COVID-19. The discovery makes it possible to start clinical trials in a matter of weeks. Some of the drugs have been well known for decades and approved in many countries for human or veterinary use, some of them even have confirmed effects against SARS-CoV and SARS-CoV-2 viruses, while others have not been known previously for any related effects. The drugs found to be potentially effective include: Niclosamide - an oral anthelmintic drug used to treat parasitic infections in millions of people worldwide. Niclosamide has been approved in Italy, the United States (now withdrawn), France, and some other countries. Nitazoxanide - a broad-spectrum antiparasitic and broad-spectrum antiviral prescription drug that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. Approved in the U.S., India, Mexico and some other countries. Niclosamide and Nitazoxanide have been recently recommended to be tried as COVID-19 treatment in patients. Afatinib - a prescription medicine approved in the U.S. for the treatment of patients with metastatic non-small cell lung cancer (NSCLC), along with 28 countries within the EU, China, and some other countries. Ixazomib - a prescription medicine used in combination with the medicines REVLIMID® (lenalidomide) and dexamethasone to treat multiple myeloma in patients who have received at least one prior treatment for their multiple myeloma. Approved in the U.S., EU and some other countries. Reserpine was originally isolated from the flower Rauwolfia serpentina in 1952. It was once used as a treatment for high blood pressure and psychotic episodes. It has been approved in Italy, Germany, France and some other countries. The list of potential anti-COVID-19 drugs also includes several senolytics. Senolytics (molecules that "kill" the so-called senescent or damaged cells) are attracting the growing interest from the academic world and the biotech industry for their potential against a range of age-related diseases and ageing itself. Although some of the drugs with anti-coronavirus potential have been approved for use on humans for other medical indications and are immediately available to the public, Gero strongly urges against self-treatment and reaffirms the necessity of acting in line with the national regulations, including the rules for off-label use of available drugs. ### About Gero Gero is a Singapore-based company that aims to discover new drugs targeting complex diseases using the next-generation artificial intelligence platform. Gero has managed to overcome limitations of the previous-generation AI by offering not just a correlation analysis of biological big data, but causative models built with the use of physics of complex dynamic systems in addition to advanced machine learning. The first time the capabilities of Gero approach have been showcased was for a such complex condition as ageing. The interventions designed by Gero AI have enabled life extension and rejuvenation of multiple species, including mammals, demonstrating unprecedented results for the entire field. One of the recent Gero publications on drug repurposing in ageing using machine learning techniques has been just credited as the most popular paper in 2019 in the Nature Research Journal - Scientific Reports. In 2019, Gero has also been named one of the most prominent players of the Artificial Intelligence in the Life Extension Market along with Google and IBM. The first Gero drug discovery project is in cancer supportive care targeting chemotherapy-induced frailty/accelerated ageing with further expansion into other ageing-related indications. Gero works with the researchers from top-tier institutions (Harvard Medical School, MIT, University of Edinburgh, National University of Singapore, Roswell Park Comprehensive Cancer Center etc.) to push forward research and develop therapeutics and extensively publishes results in peer-reviewed journals (list of publications). Gero work is supported by serial pharmaceutical investors, IT and AI entrepreneurs with previous exits to Facebook and Google. Gero AI platform is currently extensively used for drug discovery, drug repurposing, and in clinical decision support system projects. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is for the purpose of initiating collaborations for further research of identified compounds. The absence of a warning for a given drug or combination thereof should not be in any way construed to indicate safety, effectiveness, or appropriateness for any given patient. The Gero PTE LTD does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have any questions about the substances you are taking, check with your doctor, nurse, or pharmacist.
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Post by nylefty on Apr 2, 2020 9:20:49 GMT -5
Who is the company or people being referred to that Mike Castagna is helping? My guess? I know it was a Bayer drug..I know Bayer is investigating the drug for Covid-19 ..but they must already know the pill form isn't cutting it..so..hmm..then there is IMMIX...got to wonder...but..my guess is Michael..has a little Al in him..probably working on it 80 hours a day..hell he shut the whole pipeline down..to work on this..if this is what he's working on..hmm As I said earlier (in this thread) the Medium article was written by Steve Kirsch, who thanked Castagna for helping his efforts.
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Post by goyocafe on Apr 2, 2020 9:32:37 GMT -5
As I said earlier (in this thread) the Medium article was written by Steve Kirsch, who credited Castagna for helping his efforts. The impression I got is that Steve Kirsch is acting like an enabler. He seems well connected and is getting people from various organizations talking to each other. I read somewhere that he is also looking at ways to secure funding, perhaps from the COVID Relief bill, for some of the activities outlined in his article. I think it is pure coincidence and luck that Steve knows of Mannkind, and MC, through his use of Afrezza; at least that is how I understood the connection there.
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Post by mango on Apr 2, 2020 9:44:26 GMT -5
The article rings a bit suspect to me simply because the author omitted the who part. Why djd the author make it so mysterious and lacking?
We simply have no clue who the author was referring to because he left that part out.
Makes no sense, IMO.
Maybe someone that has the time can contact the author for clarity.
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Post by goyocafe on Apr 2, 2020 9:49:39 GMT -5
The article rings a bit suspect to me simply because the author omitted the who part. Why djd the author make it so mysterious and lacking? We simply have no clue who the author was referring to because he left that part out. Makes no sense, IMO. Maybe someone that has the time can contact the author for clarity. It certainly looks like Lovelace Biomedical is involved to some degree. I checked out their website yesterday and they are a not for profit contract research organization. I just hope Mike is making sure everyone knows about Technosphere and our manufacturing capabilities in the U.S.
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Post by nylefty on Apr 2, 2020 10:07:49 GMT -5
The article rings a bit suspect to me simply because the author omitted the who part. Why djd the author make it so mysterious and lacking? We simply have no clue who the author was referring to because he left that part out. Makes no sense, IMO. Maybe someone that has the time can contact the author for clarity. It certainly looks like Lovelace Biomedical is involved to some degree. I checked out their website yesterday and they are a not for profit contract research organization. I just hope Mike is making sure everyone knows about Technosphere and our manufacturing capabilities in the U.S. From the Lovelace website: We are closely working with collaborators to help identify treatments and vaccines to fight this infectious disease. We have also been awarded work due to our past history in working with the SARS virus in 2004. Our lab, built on a bio-secure facility, closed and far from the public, is operating and we are currently using our multi-disciplinary expertise to aid in the fight the world is facing.
As previously mentioned in a past communication, we have made our facilities safe by following the guidelines set forth by the Center for Disease Control, and the World Health Organization. We have made sure our non-essential employees can work from home, and we are practicing social distancing. Along with other organizations, our own adjustments and solutions make it possible for us to continue operating and remain a necessary part of helping to improve human health.
If you need our assistance in any preclinical research, including the fight against SARS-CoV-2, please be assured we are here to provide our vast knowledge and we will see your studies through. Please contact us!
All the best during these unfamiliar challenges as we navigate them together.
– Lovelace Biomedical
Follow us at:
/
www.twitter.com/lovelacebio
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Post by mnkdfann on Apr 2, 2020 11:17:57 GMT -5
Inquiring minds want to know, is Lovelace Bio named after Ada (the famous mathematician) or Linda (not a famous mathematician)?
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Post by itellthefuture777 on Apr 2, 2020 12:01:20 GMT -5
Niclosamide is made in Germany...happens to be the lowest death rate country..Roche..Bayer..Sigma-Aldrich...makes a lot of Niclosamide products..hmm do Germans use this drug more widely for something else?
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Post by rfogel on Apr 2, 2020 14:37:08 GMT -5
The article rings a bit suspect to me simply because the author omitted the who part. Why djd the author make it so mysterious and lacking? We simply have no clue who the author was referring to because he left that part out. Makes no sense, IMO. Maybe someone that has the time can contact the author for clarity. It mentions First Wave Bio -- www.firstwavebio.com/executive-team/ -- which appears to be a very small company. Perhaps telling is that the CEO's linkedin page makes no mention of his involvement with First Wave.
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Post by morfu on Apr 2, 2020 14:39:50 GMT -5
Niclosamide is made in Germany...happens to be the lowest death rate country..Roche..Bayer..Sigma-Aldrich...makes a lot of Niclosamide products..hmm do Germans use this drug more widely for something else? I am tempted to say no to that.. The low death rate has different reasons IMHO.. Germany seems to be at an earlier stage of the outbreak and did a better job of testing and delaying this virus (they learned a lot from Italy). Another reason in particular in comparison to Northern Italy is the age structure.. but everywhere most infected are NOT tested at all, so thee is a lot of uncertainties!
With these rates at different continents you easily compare apples to oranges..
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Post by itellthefuture777 on Apr 4, 2020 23:45:28 GMT -5
www.linkedin.com/posts/immix-biopharma_covid-supportclinicaltrials-ards-activity-6652373489170948096-zA4wLet's Beat This Thing Together! We are looking for partners to help advance our nanoparticles into clinical trials for critically ill Covid-19 patients. Preclinical data demonstrate their ability to suppress viral replication, cytokine storm and progression to ARDS. GMP manufactured product can be available in weeks. The goal is to stem the tide of mass hospitalizations and need for ventilators. #covid #supportclinicaltrials #ards #coronavirus19 #medicalresearch
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Post by goyocafe on Apr 5, 2020 0:28:35 GMT -5
www.linkedin.com/posts/immix-biopharma_covid-supportclinicaltrials-ards-activity-6652373489170948096-zA4wLet's Beat This Thing Together! We are looking for partners to help advance our nanoparticles into clinical trials for critically ill Covid-19 patients. Preclinical data demonstrate their ability to suppress viral replication, cytokine storm and progression to ARDS. GMP manufactured product can be available in weeks. The goal is to stem the tide of mass hospitalizations and need for ventilators. #covid #supportclinicaltrials #ards #coronavirus19 #medicalresearch Did they hire Hakam? Sounds like something he’d say.
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