51 (edited by dorcse 2021-01-19 16:28:38)

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Understood. 

I've been thinking over the comments Greg has made regarding patients treated in Italy with Narso.  No doubt those patients were critical and most certainly on death's door.  Greg's additional comments recently regarding strikingly similar efficacious results in other Covid patients treated with Narso is of particular interest.  Absent has been certain hedging comments to indicate Narso has not worked in certain critical Covid patients but has in others. I'm not inferring that Greg has explicitly said Narso will work for every critical Covid patient.  I'm just fascinated by the bullish comments without qualifiers.  Additional comments regarding the notable absence of sequelae in the Narso treated patients is remarkable and very encouraging. 

Certainly appears there is good reason to be encouraged that these types of results could carry over to the referenced study participants. Here's hoping so for reasons far beyond Omeros as an investment opportunity.

52

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I've noticed that too, Ed.  I cannot recall ever hearing (reading) of a patient treated with Narso and it didn't work.  I've thought about it.  Is Narso too good to be true?  Ha, that would be a good basher attack, wouldn't it.  Too good to be true.  But we are at the mercy of believing that Greg knows what he is doing.  If he didn't, I seriously doubt we'd be here at this particular junction.

We've been critical of Greg in the past, I know I have.  But I've never given up, I'm not the only one, bottom line here for me is that I think Greg is to be trusted.  I doubt he could pull the wool over Alan's eyes.  I think all of us here have a decent BS indicator.  Based on all we have read, about Narso and the other drug candidates, I think it's safe to say that Narso is a good drug.  We will shortly find out just how good.

According to Alan, we might make the Pro Bowl.

53

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I am not so sure that Greg couldn't fool me, if he wanted to. Of course, if I thought he couldn't it would be more likely he could.

There are lies of omission as well as commission, so surely every CEO lies by omission as part of the job.

As good CEO that lies, doesn't as much lie as to say something in a way that the listener uses to confuse (lie to) him or herself. More of a mislead instead of a blatant lie. A misdirection instead of a lie. A "no comment" instead of an unpleasant answer.

Starting aHUS for OMS721 was a misdirection and it will be the third or later narso approval. IMO PNH is yet another similar situation, where will will not necessarily be the first approval for OMS906. I think I understand WHY he has done this and that it was not a lie when it was decided.

A Biotech trying to grow seeks to get approvals but they are few and far between. Between approvals, milestones and revenues, a CEO must produce Press Releases that herald share-price sustaining PROGRESS. Both aHUS and PNH disorders are known money makers thanks to Alexion, for which the Omeros drug appear to have an advantage. Omeros did not have to explain the disease or convince the Market there was a lot of profit in it.

Compare to HSCT-TMA and IgAN. The more letters the fewer people know what it is. IgAN is called Berger's Disease. Ever hear of it? I asked Greg why he didn't use it and his answer was, 'nobody knows what it is'. As if everyone knows what IgAN is.

When you want to cure a disease nobody ever heard of, it is easy to be ignored and berated or UNrated. Going for a known indication, publicly, knowing you will be trying to develop the treatment for a disorder that has no treatment and kills people, is smart.

Many foolish shareholders continue to ask about aHUS. Why is there no news. Will they ever complete the trial (started in 2017 as I recall)? Did OMER stop enrolling? etc.

1. it makes no difference
2. ALXN has been doing its best to get every person with the disease on their drug, probably discounting it, to keep people from enrolling in a trial.
3. every company has priorities and the smart company picks achievable priorities that will be lucrative and, hopefully provide positive news-flow along the way.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

54

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

If they increase enrollment to 100/week, and need 50 patients per drug that is 250 patients overall.

Say all the drugs work equally well, so that none get an enrollment advantage, that would mean that all drugs are fully enrolled within about 3 weeks. 

We don't know the Narso protocol, but I thought the effect was relatively quick.  Say 1 week at the outside for Narso to perform magic and make the very sick much better, certainly off vent or not progressing to a vent. 

That would put an interim readout for Narso to be about 4 weeks.  If Narso does better than average it may be faster if they can make a conclusion about benefit within a week. 

How long will the follow-up period be?

55

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Don't know the follow-up period and the 10 will not do equally well.

In addition, I presume they have an independent monitoring committee that is unblinded and can stop an arm of the trial if a drug is killing people or curing everyone, prior to full enrollment.

I seem to recall 3 or 4 weekly infusions were given in Bergamo. Who knows what dosing protocol did the best in the other Compassionate Use experience since Bergamo. It makes sense for them to try different things along the way.

Nobody wants these trials to take months, much less years if the people treated normally die within weeks. Of course, though, we do not know whether all the drugs in the 10 "arms" will be treating patients with the same severity of the disease. Some may treat people who are put on oxygen for the first time. Others may be treating those who graduate from O2 to a CPAP, while other may only be give to those who have been anesthetized, intubated, and ventilated.

I/we have to do some searching to see if the information is or becomes available.
https://www.ispytrials.org/i-spy-platform/resources

Perhaps,  after it starts, Omeros will file the trial with clinicaltrials.gov (although I have my doubts, because I am guessing that they will not be taking volunteers from the general public.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

56

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I took a look at the slide showing the 6 patients that Narso was used on.  It is illuminating.  There were 6 to 8 doses for each patient, lasting between 14 and 25 days.  The best outcomes were reached in about 20 days to discharge, and all within 34 days, except one which had a prolonged intubation period and took 90 days for discharge.

My earlier assumptions appear way to optimistic.  It should be obvious though that the patients are getting better within about 10 days from start of treatment, so any data monitoring committee should know quickly if Narso is working and hopefully feed more patients to the Narso trial.

57

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Alan Robert Ross wrote:

More like the tryouts for a Pro team, with aspirants of widely varying abilities and specialties.

so the question becomes what is the value with narso fully approved, but NOT for covid. (ie, hopefully, the "worst" case scenario)

that was the investment thesis pre-covid, in any event.

my fear is some of the current excitement is covid-related, and the price could drop in the dumps again if that fails, even though we know a $25/share price made sense with just narso (x covid).

obviously, if narso hits a home run (or even a double) with covid, the sky's the limit, but i don't want to pin my hopes on that

58

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Narso HSCT-TMA revenue will likely fix that.

Analyst upgrades may help and I still doubt the analysts will give narso for covid much value until there is trial data.

JPM coverage initiation won't hurt.

If narso is approved before July 18th, it will be an added boost.

The stock price history is not an enviable one. Lately it changed and the stock price has advanced each and every market day in 2021. That run can't last forever and surely there will be some profit-taking by traders.

On the other hand, Omeros is still way undervalued compared to peers. Most companies in Phase 3 in its sector have higher market cap, without any approved drugs. The stats says that 85% of all BLA submissions, at the stage before they are accepted, get approved. Narso was accepted AND given Priority review.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

59

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

from ST:
05:34 AM
$OMER
I-Spy Covid-19 Trial Primary Outcome Measures  :

Identify agents that will result in substantial improvements to the clinical condition of participants with COVID-19 [ Time Frame: Up to 28 days ]

Time to achieve durable change in COVID-19 to ordinal level 4 or less for at least 48 hours

From what we know so far, Narsoplimab achieved this aim to 100% with the first 6 dosed patients. We should finish the I-Spy trial with flying colors, especially since it has become clear that additionally given supportive agents, on their own, never reached this consistently rapid improvement. And fast.
https://charts.stocktwits.com/production/original_275188496.jpg

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

60

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

CV19 Sequelae is a large problem but the size and details have not really gotten systematic attention...yet. If CV19 starts to be controlled, Sequelae will get more of the limelight because the problem will be huge and expensive, IMO. It is even possible that the vaccination could play a positive or negative role... and should be investigated by collecting longterm data on 1000s of people, to try to find out.

This, of course, impacts narso, which seems to be an effective treatment.

from Stat:
Covid-19 long-haulers, tell your story

“Long Covid syndrome” is the collection of lingering symptoms that plague people who have recovered from their Covid-19 infections but are far from returning to their normal lives. Dozens of clinics have opened across the U.S. to help people cope with brain fog, muscle weakness, numbing fatigue, mystifying loss of smell and taste, or depression. Medical experts still can’t explain or prevent the phenomenon, but they’re trying. In a new blog post, NIH Director Francis Collins urges “long-haulers” to contribute what they know to a patient-led survey. “It’s essential for us to learn all we can about how SARS-CoV-2 ... leads to such widespread symptoms. It’s also essential that we develop ways to better treat or prevent these symptoms."

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

61

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Some info about the Bergamo treatment regimen

"D-dimer and aspartate aminotransferase – all markers of endothelial/cellular damage and/or inflammation – were significantly elevated. Narsoplimab treatment was begun within 48 hours of initiation of mechanical ventilation and was dosed twice weekly for two to four weeks."

https://www.bioworld.com/articles/49662 … mall-trial

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

62

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

People on IV and ST have posted about the new increased focus on TREATMENTS for CV19 by the Biden Administration, unlike the Trump Admin.

With narsoplimab already in the ISPY trial and preparing to start dosing in about a week from Monday, the help from Govt. that Omeros needs is to expedite approval AND manufacturing.

Unless Omeros is paying for a huge batch of 20,000 liters instead of the 2,000L ones it now orders, this needs to be done for the FDA to approve the process. A CV19 approval for narso, in other words, comes with logistical production issues that take time to solve. This is so because it takes time for the narso to be produced/grown and for the regulatory oversight to happen.

Given OMER has already produced a number of batches surplus to what's needed for the HSCT-TMA launch, I am sure OMER has enough for the CV19 trial with some left over... and I presume they have more batches on order. If the use of narso for Covid takes off they will/may need lots of 20,000L reactor-vessels full to satisfy demand.

Biden Admin wrote:

Prioritize therapeutics and establish a comprehensive, integrated COVID-19 treatment discovery and development program. Effective treatments for COVID-19 are critical to saving lives. The federal government will establish a comprehensive, integrated, and coordinated preclinical drug discovery and development program, with diverse clinical trials, to allow therapeutics to be evaluated and developed rapidly in response to COVID-19 and other pandemic threats. This includes promoting the immediate and rapid development of therapeutics that respond to COVID-19 by developing new antivirals directed against the coronavirus family, accelerating research and support for clinical trials for therapeutics in response to COVID-19 with a focus on those that can be readily scaled and administered, and developing broad-spectrum antivirals to prevent future viral pandemics.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

63

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

This is a refreshing change that the Biden administration will follow the science which will save lives and work with industry to develop treatments which will still be needed even with a vaccine.   Just like you have treatments for things like the flu you will still need treatments for Covid 19.

National Strategy for the COVID-19 Response and Pandemic Preparedness

https://www.whitehouse.gov/wp-content/u … edness.pdf

64

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

This shows that CV19 cardiac injury is due to TMA... and what do you think will make that not happen?

I wonder how much narso might be needed to successfully pretreat people BEFORE the damage, to prevent it.
*************************
Microthrombi As A Major Cause of Cardiac Injury in COVID-19: A Pathologic Study
Dario Pellegrini, Rika Kawakami, Giulio Guagliumi, Atsushi Sakamoto, Kenji Kawai, Andrea Gianatti, Ahmed Nasr, Robert Kutys, Liang Guo, Anne Cornelissen, Lara Faggi, Masayuki Mori, Yu Sato, Irene Pescetelli, Matteo Brivio, Maria Romero, … See all authors
Originally published22 Jan 2021https://doi.org/10.1161/CIRCULATIONAHA.120.051828Circulation. ;0
Abstract
Background: Cardiac injury is common in hospitalized patients with COVID-19 and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with SARS-CoV-2 remain uncertain.

Methods: We conducted a systematic pathologic analysis of 40 hearts from hospitalized patients dying of Coronavirus Disease 2019 (COVID-19) in Bergamo, Italy to determine the pathologic mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury.

Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. As compared to subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and shorter symptom onset to admission. The incidence of severe coronary artery disease (i.e., >75% cross sectional narrowing) was not significantly different between those with and without necrosis. 3/14 (21 .4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction defined as ≥1 cm2 area of necrosis while 11/14 (78.6%) showed evidence of focal (> 20 necrotic myocytes with an area of ≥ 0.05 mm2 but <1 cm2) myocyte necrosis. Cardiac thrombi were present in 11/14 (78.6%) cases with necrosis, with 2/14 (14.2%) having epicardial coronary artery thrombi while 9/14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19 positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19 infected patients presenting with ST-segment elevation myocardial infarction (STEMI). Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19 positive and negative STEMI patients.

Conclusions: The most common pathologic cause of myocyte necrosis was microthrombi. Microthrombi were different in composition as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to coronary thrombi retrieved from COVID-19 positive and negative STEMI patients. Tailored anti-thrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

65

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

In addition to the above report, I posted one in the Pandemic section about treatment with heparin to reduce clotting. There is a limit to the amount of heparin you can give before it kills the patient from internal bleeding. Scientific studies tell us what needs to be used: a MASP2 inhibitor

Otherwise known as Narsoplimab.
============================
Study suggests mannose-binding lectin associated with thrombosis, coagulopathy in severe COVID-19
08.09.2020
12:17
17
Researchers have identified a mechanism they believe explains why so many critically ill patients with coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications despite pharmacological thromboprophylaxis.

In a cohort of 65 patients with severe COVID-19 in intensive care, Oskar Eriksson, MD, University Hospital, and Uppsala University, Uppsala, Sweden, and colleagues observed a subset of patients that had strongly elevated mannose-binding lectin (MBL) plasma levels when they were admitted to the intensive care unit (ICU).

The 9 (14%) patients who developed symptomatic thromboembolism despite receiving thromboprophylaxis had significantly higher MBL levels than patients who did not experience a thromboembolic event (median 1,233 kU/L vs 470 kU/L; P=.0054).

In addition, MBL was strongly correlated to plasma D-dimer levels, a well-known marker of COVID-19 coagulopathy. No relationship was found between MBL and markers of cardiac (N-terminal fragment of probrain natriuretic peptide) or respiratory function (PO2/FiO2 ratio), nor with markers of inflammation (C-reactive protein, interleukin-6, or ferritin).

“MBL circulates in complex with the serine proteases mannose-associated serine protease (MASP)-1 and MASP-2, which activate the complement cascade upon MBL target binding.The MASPs intriguingly display coagulation factor-like substrate specificities and are activated during blood clotting. MASP-1 promotes clot formation by multiple mechanisms, including direct activation of factor XIII (FXIII) that cross-links fibrin,” the authors explained.

“The standard choice for thromboprophylaxis in COVID-19 patients is low-molecular-weight heparin (LMWH), which preferentially targets FXa. Here, MBL-associated MASPs could act as a LMWH bypass mechanism to directly promote fibrin formation, and indeed, all the TE events in our study occurred despite thromboprophylaxis,” the authors added.

The study, published in Thrombosis and Haemostasis, did not find a relationship between plasma MBL levels and survival, need for mechanical ventilation, or acute kidney injury.

All patients in the study received thromboprophylaxis with either dalteparin sodium (n=64) or apixaban (n=1). Of the 9 patients in the study who developed a symptomatic thromboembolic event during their time at the ICU, 2 were arterial thrombosis (stroke or myocardial infarction) and 7 were pulmonary embolisms (PEs). Interestingly, patients who developed PE all had MBL levels above the 95th percentile compared with control patients.

“We have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients,” the authors concluded. “Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for thromboembolic events.”

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

66

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

In addition to the above report, I posted one in the Pandemic section about treatment with heparin to reduce clotting. There is a limit to the amount of heparin you can give before it kills the patient from internal bleeding. Scientific studies tell us what needs to be used: a MASP2 inhibitor

Otherwise known as Narsoplimab.
============================
Study suggests mannose-binding lectin associated with thrombosis, coagulopathy in severe COVID-19
08.09.2020
12:17
17
Researchers have identified a mechanism they believe explains why so many critically ill patients with coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications despite pharmacological thromboprophylaxis.

In a cohort of 65 patients with severe COVID-19 in intensive care, Oskar Eriksson, MD, University Hospital, and Uppsala University, Uppsala, Sweden, and colleagues observed a subset of patients that had strongly elevated mannose-binding lectin (MBL) plasma levels when they were admitted to the intensive care unit (ICU).

The 9 (14%) patients who developed symptomatic thromboembolism despite receiving thromboprophylaxis had significantly higher MBL levels than patients who did not experience a thromboembolic event (median 1,233 kU/L vs 470 kU/L; P=.0054).

In addition, MBL was strongly correlated to plasma D-dimer levels, a well-known marker of COVID-19 coagulopathy. No relationship was found between MBL and markers of cardiac (N-terminal fragment of probrain natriuretic peptide) or respiratory function (PO2/FiO2 ratio), nor with markers of inflammation (C-reactive protein, interleukin-6, or ferritin).

“MBL circulates in complex with the serine proteases mannose-associated serine protease (MASP)-1 and MASP-2, which activate the complement cascade upon MBL target binding.The MASPs intriguingly display coagulation factor-like substrate specificities and are activated during blood clotting. MASP-1 promotes clot formation by multiple mechanisms, including direct activation of factor XIII (FXIII) that cross-links fibrin,” the authors explained.

“The standard choice for thromboprophylaxis in COVID-19 patients is low-molecular-weight heparin (LMWH), which preferentially targets FXa. Here, MBL-associated MASPs could act as a LMWH bypass mechanism to directly promote fibrin formation, and indeed, all the TE events in our study occurred despite thromboprophylaxis,” the authors added.

The study, published in Thrombosis and Haemostasis, did not find a relationship between plasma MBL levels and survival, need for mechanical ventilation, or acute kidney injury.

All patients in the study received thromboprophylaxis with either dalteparin sodium (n=64) or apixaban (n=1). Of the 9 patients in the study who developed a symptomatic thromboembolic event during their time at the ICU, 2 were arterial thrombosis (stroke or myocardial infarction) and 7 were pulmonary embolisms (PEs). Interestingly, patients who developed PE all had MBL levels above the 95th percentile compared with control patients.

“We have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients,” the authors concluded. “Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for thromboembolic events.”

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

67

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

A week from tomorrow, narso enters the ISPY CV19 trial.

I am very confident of the result.
Why?

Do YOU know what makes me confident?
I think it is better if you think about what we know and don't know to see how YOU analyze the situation.

And then I will explain my reasoning.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

68

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I share the confidence, largely due to the stellar prior results and the strong scientific support for the link to TMA like MOA.

69

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

We agree and I see some more reasons... or perhaps they are only more specific related reasons....

Give it some thought....

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

70

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

We agree and I see some more reasons... or perhaps they are only more specific related reasons....

Give it some thought....

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

71

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I agree based on the earlier although small test that were done back in Italy last spring AND the fact that Greg agreed to agree and publicly acknowledge Naso going into the ISPY CV19 trail.  Up until this time Greg has been very hesitant to say much about Narso and it being a treatment for CV19 and doing any real testing on it treating CV19, why was has that changed?  Because Greg has confidence that he knows that the test results will show.

72

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Just to add to that, Greg referred to similar "striking" results in COVID-19 patients treated under CUP since initial 6 in Italy.

73

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Yes, you guys are focusing on what has changed in Greg's progression from suppressing any public mention of narso and Covid, no matter who make it... and escalating what he says publicly.

I have already told you that everything Greg says in public, if prepared in advance, is vetted by the in-house legal team & regulatory dept. and TWO legal teams outside (the regular outside council and the FDA/Regulatory consultant's lawyers).   

Ask yourselves whether this is arbitrary and you have to think it is not. Greg has made some strikingly positive assertions about Covid and HSCT-TMA being separate causes of the same syndrome, which Narso has been treating, turning 85% fatality to 85% survival.

He has NOT used the typical weasel-words about narso MAY do this or COULD BE x or y. He has been making definitive statements.

When do scientist make definitive statement if they are not going off-reservation and becoming a "promoter" like some many managements that have been activity touting that their own drugs may be a treatment for Covid?

The answer is simple.
When they have proof.

Do any of you think there has been no Covid research going on in Omeros and its affiliated laboratories in Cambridge, etc.?

Where did OMER devise the dosage and timing of treatments, if not from the ongoing CUP patients data supplementing what was learned in Bergamo the first time around?

Think about it some more and look for signs that should affect our expectations.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

74 (edited by alaskasalmonfisher 2021-01-24 12:58:10)

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I am late to this party but my answer would have been that Omeros has already tested Narsoplimab privately in conditions the same as the ISPY trial.  IOW, this is already old news for the company.  Narso works, it'll work in a trial which is testing Narso in a way that Narso has already been tested before.  Been there, done that.  Old news, boring, time to git 'er done.

75

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

i would agree with Avi, but we have to keep in mind what Alan said a few days ago. ISPY is like being invited to the playoffs. yes, the drug has promise, but so do all the other contestants who make it to that level - what are there 10 of them? perhaps Narso is good, but others are better. It ain't over 'til it's over.

76

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I think Avi is probably right, although the N humans treated this way is likely small. There is surely animal work from Schweible. Remember the often postponed talk he was giving at Cambridge? That was animal model proof, IMO, they had completed, probably in late spring.

Steven has a good point. It makes a difference who the competitor is, and I suppose it may make a difference on the price. But will the take a treatment that cuts deaths by 1/3 instead of one that cuts deaths and sequelae by 2/3, if the latter is 2, 3 or 4 times the price?

We don't know that.
But we know that the Lectin pathway of complement is causing the TMAs and there are ZERO of the other 9 drugs that affect that pathway... and while there may be blood thinners in the trial, nothing else thins the blood by stopping the excessive clotting at as close to the source, in the immune system that is trying to staunch blood flow from an (nonexistent) injury.

The Adaptive randomizatin used by ISPY means that the drugs that do the best get more patients faster. So, we want (expect?) to see the narso arm enrolled very fast.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

77 (edited by dorcse 2021-01-24 15:52:32)

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

If the government is paying for the drugs, I don't think price is much of an issue.  They just committed up to 2.6 billion more for additional doses of the Regeneron cocktail.  They had already paid $450 million for doses in the first contract last year  Ironically this comes at a time when antibody treatments are likely to be much less effective as the new Covid-19 variants become prevelant.  I should add that Regeneron cliams they took virus mutations into account when developing their cocktail.  They say it is effective.  We'll have to wait and see.

If I believe complement inhibition is key (I do) and Omeros has the only complement inhibitor in the trial, why would I think other drugs would be likely to compete or be more efficacious?  I don't.

78

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I am generous, so I am willing to split the prize with Steven.  As regards the playoffs, remember as Alan has just said, and we have read this before, that the lectin pathway is closest to the origin of trouble in humans, caused by the virus.  Nobody else has a drug that works at the level that narsoplimab does.  And even though it's the playoffs, the Government is constrained in choosing their team of candidates by what is actually out there.  They are going through a process, and I'm all for going through a good process.  The results of this ISPY test are going to be very very interesting.

What would be REALLY interesting is to know if any of the people supervising this trial already have some personal thought as to which drug will be the best.  Of course they have to be objective in a scientific trial, but that doesn't mean that they can't already have formed a private opinion of the matter, if they've read the performance to date of every drug, and the rigorousness of each of the drugs' trials.

79

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I agree with Ed, with the caveat that other drugs could work, at least somewhat, for less severe patients or to keep the illness milder.

For example, an anti-viral could work in theory and some do work, but only a little. The historical problem is that you need to take the anti-viral before exposure or in the first 48 hours, which happens to be the asymptomatic period for CV19, so you don't take the drug in time because you don't know you have the virus yet.

Avi, a double blind test makes the investigators bias moot, because investigators do not know what patient is getting the real drug (although they probably suspect). When the outcome is life or death, there is not much of a placebo effect, although surely many of the drugs being tested are not going to be tested on the most severe cases.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

80

Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I agree with Ed, with the caveat that other drugs could work, at least somewhat, for less severe patients or to keep the illness milder.

For example, an anti-viral could work in theory and some do work, but only a little. The historical problem is that you need to take the anti-viral before exposure or in the first 48 hours, which happens to be the asymptomatic period for CV19, so you don't take the drug in time because you don't know you have the virus yet.

Avi, a double blind test makes the investigators bias moot, because investigators do not know what patient is getting the real drug (although they probably suspect). When the outcome is life or death, there is not much of a placebo effect, although surely many of the drugs being tested are not going to be tested on the most severe cases.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

The other day, I was discussing an interesting possibility with my Britalian friend. I asked he what he thought would happen if it finally hit the consciousness of the world that a cure for the virus' effect that kill people is the BIG problem (not really the virus and minor symptoms) and that Narso was the BEST TREATMENT.

Has Greg planned for that possibility?
IOW, not that it will be used on people ONLY when they have a 50% to 75% chance of dying within the next few weeks... but for everyone with a severe case. potentially with a smaller amount of treatment for everyone who tests positive.

If the world decides narso is the best hope for a mutating virus that may not be banished by herd immunity, that you can get more than once, as the virus mutates, but that stops it from killing people and stops the TMAs that can cause organ damage and make you sick (and closer to death, later).

Surely, Dr. Schwaeble has done animal trials given does to less sick infected individuals and seen they get no sequelae.

How can Omeros produce enough?
The govt. could through their war powers act.

How can Omeros charge a price that may be appropriate for treating 5000 HSCT-TMA patients a year, when they may treat 50 to 100 million a year in the USA and up to 1 billion in the rest of the world?

Impossible.
Omeros would go from being a hero and a household word, with its CEO getting the Nobel Peace Price... to a devil withholding a cure when millions are expected to die over the years.

My solution is for the USA or the UN or a consortium of countries to BUY NARSOPLIMAB OUTRIGHT, ramp up production and distribute it free of charge.

If this doesn't happen, India and China, and perhaps other countries would break the patent and produce it illegally (except it would be made legal in the countries that ignore the patent.

How much is it worth?

The US has already 'wasted" TRILLIONS in support payments, subsidies and pork because of its inadequate efforts against the virus.

Would Narso be worth $500 Billion? $100 Billion?
Would Omeros sell for that and use the money to develop the rest of the pipeline? Would they at least pay a $100/share dividend (~$6 to7 Billion) to each shareholder?

Face it.... Narso takes a 85% death rate for HASCT-TMA and makes it into a 85% survival rate for all those who live long enough to get the full treatment.

In the US alone that is about 5000 to 8000 people per year. HSCT-TMA killed about 85%...4,000 to 7,000. CV19 can kill over 4000, in the US along, IN A DAY.

Covid, in the first year, in the US alone, has killed about 500,000.

Not worth $100B or more?
And cheap at that price, given what it costs to allow CV19 and its variants to spread virtually unchecked.

Granted I am extending logical deduction in an ILLOGICAL world, but sooner or later the continuing death toll may cause some people to actually THINK there's a better way.

What do you think?

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

I think there is some middle ground.  I think Narso should be treating the people that get the bad symptoms and have to go to the hospital.  Those are the people with the highest risk of death and permanent or long lasting injury.  I've known quiet a few people that have gotten Covid 19 and it hasn't been a big thing and they have recovered with no to little symptoms in days and returned to their normal level of activities.  So I don't think it benefits anyone to treat them at this point with Narso and maybe not even in the future.  So I think the percentage that will need Narso will be very small however 5% of 5 billion people is a LOT of people and allows Omeros to charge a high enough price and make a great profit without bankrupting the world with its treatment.  I do think over time that the virus will weaken and our immune systems will get better at fighting it off however it will still be an issue probably forever and a treatment will be needed for those few that get it bad.  Similar to how there are treatments for the flu which kills tens of thousands every year in the US.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

There have been quite a few people who got mild cases and 1 to 6 months later they get sequelae that either kill them, give them a stroke, a heart attack, kidney damage etc. Many of the ones who die are not credited with dying from CV19... especially in Red States.

Until the data is collected someplace with a National System, to find out the specifics of why some get a too strong complement response during infection or after, you can't effectively target accurately.

CV19 is not a disease that, if you survive the initial bout, you are free and clear. The future cost to the health care system is going to be huge, but nobody is paying attention to that, for obvious reasons, among them, they don't want to think of more bad stuff that could happen in the indistinct future.

I should add that, treating only those who are hospitalized would be a huge undertaking and very expensive if narso is priced as if it is an orphan drug.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Interesting discussion guys.

This may also be of interest.  Laura Esserman, head of I-SPY COVID, recently took part in the Clinical Trials Transformation Initiative (CTTI) video presentation regarding "The Fastest Path to Effective Covid-19 Treatments:  Using Master  Protocol Studies."

Her description of the criteria for critical patients treated in the I-SPY COVID trial, drug agents to be used and results they are looking for just SCREAMS Narsoplimab. 

I took Laura's 5 minute segment and uploaded it to my Drive.   It's worth a look.

https://drive.google.com/file/d/17nOfB3 … sp=sharing

If interested in the full presentation:

https://vimeo.com/502342017

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Nice Ed!
I can't recall how many times I have written about all the wasted effort, expenses, and local reviews and timelines that ruins the potentially "fast" trials.

Glad to see that the Pandemic urgency is cutting through the red tape, somewhat.

And it does sound like what Omeros seems to positioning themselves for... even though, IMO, it should work to eliminate sequelae in less severely affected patients.

The results can't be too fast for the 4000 Americans dying every day. And I am presuming that Omeros keeps on ordering more narso to be made.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Omer could license Narso for covid to the USG, and get perhaps a $1000 royalty for each person treated.  Record keeping should be pretty easy.  They could even have a tiered system, where the USG guarantees say 1 million doses for $10K and 100 million for say $1K. 

Omer retains ownership of Narso and maintains the ability to sell for TMA, IgAN, etc.  When covid has run its cource the USG stops buying in bulk.

What is the shelf life of Narso?  There could easily be leakage where TMA/IgAN/other patients get the cheap version of Narso, but how likely is it that thousands of unused doses can just sit in storage for years to be worked off?

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Not info they will make public, I presume

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

BARDA, DOD backing of I-SPY COVID trial highlights continued need for new therapies
BY LAUREN MARTZ, SENIOR EDITOR
DEC 16, 2020 | 5:20 PM -05
Vaccines are here, but the pandemic is far from over and BARDA and DOD are supporting the search for therapies to help the sickest COVID-19 patients by funding a mechanism that’s proving to be most efficient in identifying effective treatments.

HHS’s Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense are contributing $66.5 million to expand the I-SPY COVID platform trial through an agreement with its sponsor, Quantum Leap Healthcare Collaborative.

The funding will double the number of trial sites from 20 to 40, and will add three additional treatments to the adaptive platform study, which is already evaluating razuprotafib from Aerpio Pharmaceuticals Inc. (NASDAQ:ARPO), cenicriviroc from AbbVie Inc. (NASDAQ:ABBV), Otezla apremilast from Amgen Inc. (NASDAQ:AMGN) and Firazyr icatibant from Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK).

The I-SPY COVID trial was launched to identify treatments for acute respiratory distress syndrome (ARDS) caused by COVID-19 using the same trial infrastructure behind the I-SPY-2 study, a long-running and productive adaptive platform trial for breast cancer.

Potential new therapeutic candidates that target the host response to the virus will be assessed by a panel of federal and academic experts, and the idea is that promising therapies emerging from the Phase II trial could be directed into late-stage studies such as the NIH’s ACTIV master protocols.

The expansion of I-SPY COVID is the second major push for new therapies for hospitalized patients since positive Phase III vaccine data readouts. A group of industry peers made a similar commitment to continued therapeutic development with the launch of the COMMUNITY platform trial earlier this month.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

That article is about 6 weeks old.  Is the implication that Narso is one of the 3 additional drugs to be tested?

Hopefully a PR is out on Feb 1 once the trial gets started if all the info we've heard is correct.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

It gives some background, is all. I think they are adding 5 new drugs. Testing may start Feb 1, but PR will NOT necessarily be the same day, Maybe a few days after the start.

The ISPY organization oversees PR, and many layers of lawyers will vet what is released.

Could be Monday or days after. There never was a fixed start day released.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

During the Trump Administration, promotions of unproven, mostly ineffective treatments probably made people think there was not effective treatment that stopped people from dying. Part of this is because there is no very effective treatment the stops a viral infection once you have been infected for a couple of days. As we know, narso has no effect on the virus... and the virus itself doesn't kill people. The way people react to the virus is what kills them and what causes dangerous sequelae.

NYTimes published an article today recognizing that the US Govt. neglected developing effective treatments in favor of vaccines:
======================
How the Search for Covid-19 Treatments Faltered While Vaccines Sped Ahead

By Carl Zimmer

Vaccine development exceeded everyone’s expectations. But the next few months will still bring many sick people — and doctors have woefully few drugs with which to treat them.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Here's that complete NY Times article.

Nearly a year into the coronavirus pandemic, as thousands of patients are dying every day in the United States and widespread vaccination is still months away, doctors have precious few drugs to fight the virus.

A handful of therapies — remdesivir, monoclonal antibodies and the steroid dexamethasone — have improved the care of Covid patients, putting doctors in a better position than they were when the virus surged last spring. But these drugs are not cure-alls and they’re not for everyone, and efforts to repurpose other drugs, or discover new ones, have not had much success.

The government poured $18.5 billion into vaccines, a strategy that resulted in at least five effective products at record-shattering speed. But its investment in drugs was far smaller, about $8.2 billion, most of which went to just a few candidates, such as monoclonal antibodies. Studies of other drugs were poorly organized.  The result was that many promising drugs that could stop the disease early, called antivirals, were neglected. Their trials have stalled, either because researchers couldn’t find enough funding or enough patients to participate.

At the same time, a few drugs have received sustained investment despite disappointing results. There’s now a wealth of evidence that the malaria drugs hydroxychloroquine and chloroquine did not work against Covid. And yet there are still 179 clinical trials with 169,370 patients in which at least some are receiving the drugs, according to the Covid Registry of Off-label & New Agents at the University of Pennsylvania. And the federal government funneled tens of millions of dollars into an expanded access program for convalescent plasma, infusing almost 100,000 Covid patients before there was any robust evidence that it worked. In January, those trials revealed that, at least for hospitalized patients, it doesn’t.

The lack of centralized coordination meant that many trials for Covid antivirals were doomed from the start — too small and poorly designed to provide useful data, according to Dr. Janet Woodcock, the acting commissioner of the Food and Drug Administration. If the government had instead set up an organized network of hospitals to carry out large trials and quickly share data, researchers would have many more answers now.

“I blame myself to some extent,” said Dr. Woodcock, who has overseen the federal government’s efforts to develop Covid drugs.

She hopes to tame the chaos with a new effort from the Biden administration. In the next couple of months, she said, the government plans to start large and well-organized trials for existing drugs that could be repurposed to fight Covid-19. “We are actively working on that,” Dr. Woodcock said.

Brand-new antiviral drugs might also help, but only now is the National Institutes of Health putting together a major initiative to develop them, meaning they won’t be ready in time to fight the current pandemic.

“This effort will be unlikely to provide therapeutics in 2021,” Dr. Francis Collins, the head of the N.I.H., said in a statement. “If there is a Covid-24 or Covid-30 coming, we want to be prepared.”

Even as the number of cases and deaths have surged around the country, the survival rate of those who are infected has improved significantly. A recent study found that by June, the mortality rates of those hospitalized had dropped to 9 percent from 17 percent at the start of the pandemic, a trend that has been echoed in other studies. Researchers say the improvement is partly because of the steroid dexamethasone, which boosts survival rates of severely ill patients by tamping down the immune system rather than blocking the virus. Patients may also be seeking care earlier in the course of the illness. And masks and social distancing may reduce viral exposure.

When the new coronavirus emerged as a global threat in early 2020, doctors frantically tried an assortment of existing drugs. But the only way to know if they actually worked was to set up large clinical trials in which some people received placebos, and others took the drug in question.

Getting hundreds or thousands of people into such trials was a tremendous logistical challenge. In early 2020, the N.I.H. narrowed its focus to just a few promising drugs. That support led to the swift authorization of remdesivir and monoclonal antibodies. Remdesivir, which stops viruses from replicating inside cells, can modestly shorten the time patients need to recover, but has no effect on mortality. Monoclonal antibodies, which stop the virus from entering cells, can be very potent, but only when given before people are sick enough to be hospitalized.

Hundreds of hospitals and universities began their own trials of existing drugs — already deemed safe and widely manufactured — that might also work against the coronavirus. But most of these trials were small and disorganized.

In many cases, researchers have been left on their own to set up trials without the backing of the federal government or pharmaceutical companies. In April, as New York City was in the throes of a Covid surge, Charles Mobbs, a neuroscientist at Icahn School of Medicine at Mount Sinai, heard about some intriguing work in France hinting at the effectiveness of an antipsychotic drug.

Doctors at French psychiatric hospitals had noticed that relatively few patients became ill with Covid-19 compared with the staff members who cared for them. The researchers speculated that the drugs the patients were taking could be protecting them. One of those drugs, the antipsychotic chlorpromazine, had been shown in laboratory experiments to prevent the coronavirus from multiplying.

The virus’s path through Los Angeles is unequal.
The U.S. has Covid-19 vaccines but few treatments. What happened?
The doctors tried to start a trial of chlorpromazine, but the pandemic ebbed — temporarily, it turned out — in France by the time they were ready. Dr. Mobbs then spent weeks making arrangements for a trial of his own on patients hospitalized at Mount Sinai, only to hit the same wall. “We ran out of patients,” he said.

If doctors like Dr. Mobbs could tap into nationwide networks of hospitals, they would be able to find enough patients to run their trials quickly. Those networks exist, but they were not opened up for drug-repurposing efforts.

Many scientists suspect that the best time to fight the coronavirus is early in an infection, when the virus is multiplying quickly. But it’s particularly hard to recruit trial volunteers who are not in a hospital. Researchers have to track down people right after they’ve tested positive and find a way to deliver the trial drugs to them.

At the University of Kentucky, researchers began such a trial in May to test a drug called camostat, which is normally used to treat inflammation of the pancreas. The scientists thought it might also work as a Covid-19 antiviral because it destroys a protein that the virus depends on to infect human cells. Because camostat comes in pill form, rather than an infusion, it would be especially useful for people like the trial volunteers, many of whom lived in remote rural areas.

But the researchers have spent the past eight months trying to recruit enough participants. They have had trouble finding patients who have recently received a Covid diagnosis, especially with the unpredictable rise and fall of cases.

“This has been the source of the delays for essentially all of the trials around the world,” said Dr. James Porterfield, an infectious disease clinician at the University of Kentucky College of Medicine, who is leading the trial.

While doctors like Dr. Porterfield have struggled to carry out studies on their own, a few drugs have become sensations, praised as cure-alls despite a lack of evidence.

The first supposed panacea was hydroxychloroquine, a drug developed for malaria. Television pundits claimed it had healing powers, as did President Trump. Rather than start one large, well-designed trial across many hospitals, doctors began a swarm of small trials.

“There was no coordination, and no centralized leadership,” said Ilan Schwartz, an infectious disease expert at the University of Alberta.

Nevertheless, the F.D.A. gave the drug an emergency clearance as a treatment for people hospitalized with Covid. When large clinical trials finally did begin delivering results, it turned out that the drug provided no benefit — and might even do harm. The agency withdrew its authorization in June.

Many scientists were left embittered, considering all that work a waste of precious time and resources.

“The clear, unambiguous and compelling lesson from the hydroxychloroquine story for the medical community and the public is that science and politics do not mix,” Dr. Michael Saag of University of Alabama at Birmingham wrote in November in the New England Journal of Medicine.

Now another drug is becoming popular before there’s strong evidence that it works: the parasite-killing compound ivermectin. Senator Ron Johnson, Republican of Wisconsin, who extolled hydroxychloroquine in April, held a hearing in December where Dr. Pierre Kory testified about ivermectin. Dr. Kory, a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee at the time, called it “effectively a ‘miracle drug’ against Covid-19.” Yet there are no published results from large-scale clinical trials to support such claims, only small, suggestive ones.

Even if the federal government had set up a centralized trial network, as it is trying to do now, scientists would have still faced some unavoidable hurdles. It takes time to do careful experiments to discover promising drugs and then to confirm that they’re really worth investigating further.

“In drug development, we’re used to 10-to-15-year runways,” said Sumit K. Chanda, a virologist at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif.

In February, Dr. Chanda and his colleagues began a different kind of search for a Covid-19 antiviral. They screened a library of 13,000 drugs, mixing each drug with cells and coronaviruses to see if they stopped infections.

A few drugs proved promising. The researchers tested one of them — a cheap leprosy pill called clofazimine — over several months, doing experiments in human lung tissue and hamsters. Clofazimine fought off the virus in the animals if they received it soon after being infected.

Now, nearly a year after he started his research, Dr. Chanda is hoping he can get funding for the most difficult part of drug testing: large and randomized clinical trials that can cost millions of dollars. To complete this stage efficiently, researchers almost always need the backing of a large company or the federal government, or both — as happened with the large clinical trials for the new coronavirus vaccines.

It’s unclear how the Biden administration’s new drug-testing effort will choose which drug candidates to support. But if trials begin in the next few months, it’s possible they could reveal useful data by the end of the year.

Pharmaceutical companies are also beginning to fund some trials of repurposed drugs. A study published this week in Science found that a 24-year-old cancer drug called plitidepsin is 27 times more potent than remdesivir at halting the coronavirus in lab experiments. In October, a Spanish drug company called PharmaMar reported promising results from a small safety trial of plitidepsin. Now the company is preparing to start a late-stage trial in Spain to see if the drug works compared with a placebo.

The pharma giant Merck is running a large, late-stage trial on a pill called molnupiravir, originally developed by Ridgeback Biotherapeutics for influenza, which has been shown to cure ferrets of Covid-19. The trial’s first results could emerge as early as March.

Experts are particularly eager to see this data because molnupiravir may be effective in treating more than just Covid-19. In April, scientists found that the drug could also treat mice infected with other coronaviruses that cause SARS and MERS.

Any antivirals that may emerge in 2021 won’t save the lives already lost to Covid-19. But it’s possible that one of those drugs may work against coronavirus pandemics to come.

Noah Weiland and Katie Thomas contributed reporting.

Carl Zimmer writes the “Matter” column. He is the author of thirteen books, including “She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity.”

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Woodcock admits the system has been dysfunctional yet she was in charge and she, or the NYTimes neglect to mention The Federal Warp Speed trials which didn't find much and the ISPY (NGO) that is trying to cut thru the red tape that exists in each and every institution involved from the FDA to individual hospitals.

Developing new medicines is always about quality of life and death, even when there is no pandemic. Yes the system encourages bureaucracy. Much more was spent on vaccines than this article suggests... including money to make the drugs before they were approved. I also object to pushing antivirals, because there has been decades of research and no antiviral works well after the patient has already been infected for a few days. It has known for a year that the first couple of days, nobody has symptoms, so they are not treated. Some people may develop symptoms much later or not at all, but be capable of spreading the virus.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

The link to the ISPY CV19 trial (still doesn't include narso).

https://clinicaltrials.gov/ct2/show/NCT … amp;rank=1

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

Interesting new article posted to Medscape/WebMD today.

COVID-19 Virus May Prompt Body to Attack Itself

Brenda Goodman

February 02, 2021

An international team of researchers studying COVID-19 has made a startling and pivotal discovery: The virus appears to cause the body to make weapons to attack its own tissues.

The finding could unlock a number of COVID's clinical mysteries. They include the puzzling collection of symptoms that can come with the infection; the persistence of symptoms in some people for months after they clear the virus, a phenomenon dubbed long COVID; and why some children and adults have a serious inflammatory syndrome, called MIS-C or MIS-A, after their infections.

"It suggests that the virus might be directly causing autoimmunity, which would be fascinating," says lead study author Paul Utz, MD, who studies immunology and autoimmunity at Stanford University in Stanford, CA.

The study also opens the question of whether other viruses might also break the body's tolerance to itself, setting people up for autoimmune diseases like multiple sclerosis, rheumatoid arthritis, and lupus later in life.

Utz says he and his team are next going to study flu patients to see if that virus might also cause this phenomenon.

"My prediction is that it isn't going to be specific just to SARS-CoV-2. I'm willing to bet that we will find this with other respiratory viruses," he says.

The study comes on the heels of a handful of smaller, detailed investigations that have come to similar conclusions.

The study included data from more than 300 patients from four hospitals: two in California, one in Pennsylvania, and another in Germany.

Researchers used blood tests to study their immune responses as their infections progressed. Researchers looked for autoantibodies -- weapons of the immune system that go rogue and launch an attack against the body's own tissues. They compared these autoantibodies to those found in people who were not infected with the virus that causes COVID.

As previous studies have found, autoantibodies were more common after COVID -- 50% of people hospitalized for their infections had autoantibodies, compared to less than 15% of those who were healthy and uninfected.

Some people with autoantibodies had little change in them as their infections progressed. That suggests the autoantibodies were there to begin with, allowing the infection to burn out of control in the body.

"Their body is set up to get bad COVID, and it's probably caused by the autoantibodies," Utz says.

But in others, about 20% of people who had them, the autoantibodies became more common as the infection progressed, suggesting they were directly related to the viral infection, instead of being a preexisting condition.

Some of these were antibodies that attack key components of the immune system's weapons against the virus, like interferon. Interferons are proteins that interfere with a virus's ability to copy itself. Taking them out is a powerful evasive tactic, and previous studies have shown that people who are born with genes that cause them to have lower interferon function, or who make autoantibodies against these proteins, appear to be at higher risk for life-threatening COVID infections.

"It seems to give the virus a powerful advantage," says study author, John Wherry, PhD, who directs the Institute for Immunology at the University of Pennsylvania.

"Now your immune system, instead of having a tiny little hill to climb, is staring at Mount Everest. That really is devious."

"I'm not aware of another viral infection where that happens," he says.

In addition to those that counterpunch the immune system, some people in the study had autoantibodies against muscles and connective tissues that are seen in some rare disorders

Utz says they started the study after seeing COVID patients with strange collections of symptoms that looked more like autoimmune diseases than viral infections -- skin rashes, joint pain, fatigue, aching muscles, brain swelling, dry eyes, blood that clots easily, and inflamed blood vessels.

"One thing that's very important to note is that we don't know if these patients are going to go on to develop autoimmune disease," Utz says. "I think we'll be able to answer that question in the next 6 to 12 months as we follow the long haulers and study their samples."

Utz says it will be important to study autoantibodies in long haulers to see if they can identify exactly which ones seem to be at work in the condition. If you can catch them early, it might be possible to treat those at risk for enduring symptoms with drugs that suppress the immune system.

What this means, he says, is that COVID will be with us for a long, long time.

"We have to realize that there's going to be long-term damage from this virus for the survivors. Not just the long haulers, but all the people who have lung damage and heart damage and everything else. We're going to be studying this virus and it's badness for decades," Utz says.

Sources
BioRxiv, Jan. 29, 2021.

Paul Utz, MD, professor, immunology and rheumatology, Stanford University, Stanford, CA.

John Wherry, PhD, chair, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia.

WebMD Health News © 2021

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It screams for N---------B!!!

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

That is a very interesting article.  I hadn't heard the term autoimmunity before.  Scary stuff

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Re: Narsoplimab, MASP2, Lectin Pathway & COVID

To be honest, after I read the article, I thought that the authors had discovered something on their own, that had already been discovered by someone else earlier in time.  I am wondering if the authors are not aware of Narsoplimab and Omeros.

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Jim, I think you have heard about autoimmune diseases here on TIPS for many years, just that they were not always labelled as such.

Psoriasis, eczema, IBS, Crohn's disease, rheumatoid arthritis, Lupus, celiac disease, diabetes mellitus type 1, Graves' disease, multiple sclerosis are the most well know.

I have written about the 1918 Flu Pandemic killing young victims because they had the strongest immune response and their immune systems attacked their own body.

Endothelial Inflammation Syndrome (EIS) is one of the autoimmune problems and that is what narso treats. IMO, this include many cardiovascular problems that are caused by INFLAMMATION of the linings of the vessels. I think narso can treat cardiovascular problems, and will someday.

original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.

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Yes, we've discussed autoimmune disorders, bit I hadn't heard the term autoantibodies (incorrectly copied from other post).  I don't know if this is new, or just a cool term to reflect the reality of the cause of autoimmune issues.