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Topic: Narsoplimab generally

https://charts.stocktwits.com/production/original_256762716.jpg

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

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Re: Narsoplimab generally

Alan, I will be interested to know how pricing for Narso for TA-TMA will work under CMS.  When Greg talks about a billion dollar opportunity for Narso in TA-TMA (US and Europe), what part of that revenue is from Medicare?

I guess it would help to breakdown the age categories of patients undergoing HSCT first.  How many 65 and over on a yearly basis in the US?  Not sure this has been broken down before, has it?

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Re: Narsoplimab generally

Alan, in your post above the document speaks of Narso as a "manna binding lectin...."  Is that correct as to spelling?  Should it be "mannin?"  I do not recall seeing the word "manna" before.  My point being that I don't want some competitor or bad actor taking advantage of a spelling mistake or some other logistical error to get a foot hold into Omeros' business.

4 (edited by Alan Robert Ross 2020-11-15 21:03:10)

Re: Narsoplimab generally

I don't know if it is a typo, Avi.

Ed, Greg didn't say WHEN. There are a load of indications and IgAN is a large addressable market, especially if you look worldwide. Is Greg including CV19 sales? After all, he's very confident that TZ-TMA and CV19 are mainly the same.

Peter's ST-linked spread-sheet seems to indicate that they have about a $B worth (retail) of inventory if they can sell each does for enough $

not the asterixed numbers refer to the public source in which OMER or Greg provided the information.
======================
A Supply       
       
A1 Manufacturing       
Litres (known *1)    2000   
Titer (2-6)    2   
Purification (70-80)    70%   
Per Batch    2800    grams
       
Batches (known *2)    11   
Grand total    30800    grams
       
A2 Dosing       
Dose    0.004    grams i.e. 4mg
Average weight    85    kgs
Dose per patient    4   
Opening inventory    22,647    patients
       
       
B Demand       
       
TMA 2021 sales       
TA TMA Transplants    10000    Total per year
TMA incidence (20-40)    40%   
Pentration (0-100)    100%   
Months on market    8    Approved April 2021
Tottal TMA Sales    2,667   
       
IGAN trial (known *3)    450   
       
Total Consumed 2021    3,117   
       
C Inventory       
Opening inventory less consumed    19,530   
Percentage of opening    86%
************Notes***************
Notes           
*1    Singapore per SEC disclosure.  Singa has a 2 and 20k reactor.  We're not producing at 20k volumes.       
*2    Per omer PRs.  The first batch of five includes three lots used for CMC testing.  Per omer PR, these lots can be used commercially once approved.       
*3    Per clinical trails entry, at 225 per arm.       

************some rational*********
They specifically disclosed their manu agreement is with Lonza Singapore.  Lonza Singapore can produce batches in 2k or 20k litres.  We are not at 20k.  Titer size and purification percentages are based on known industry rates.  For the purposes of calculations here, they are set at the lowest of those rates.  Dose at 4mg per kg is most often quoted.  85kg could possibly be on the low side, but I'm comfortable using it for these purposes - move it up otherwise.

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

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Re: Narsoplimab generally

We should view Pete's number above (which have been supplemented by details a couple of times) as an indication of 2 things:

Omeros Intent and Plan.

I think we can guess that Omeros is going to continue to pay Lonza to produce more narso, probably at the ongoing rate, pending the amount used for sale and trials and inventory that will need to be maintained according to FDA requirements.

OMER would not produce so much excess product unless they were serious about a trial for CV19 and to have the inventory to be able to get FDA approval to treat this new indication... and sell the drug, on or off label.

I presume they are preparing for either the off-label alternative, and EUA (emergency use authorization) and/or an actual pivotal clinical trial followed by a BLA. If I were them, I'd be thinking of stages and getting a EUA first and turning it into a full approval. And all of this depends upon what kind of govt. support they can arrange to subsidize the production of narso and/or the price to be charged and the level of illness severity that narso will treat.

IOW, lots of moving parts and no way to be confident in making a per dose charge for the average dose and patient.   

The one BIG point that is made by Pete's model is that Omeros has much more than enough product than is needed for the year 2021 unless they can use/sell 100s of % more than they would with only an approval for HSCT-TMA and that is presuming that TA-TMA is FDA approved by the end of April ("early") 2021.

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

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Re: Narsoplimab generally

Alan, I went back and listened to the Cantor presentation from September.  Here is how Greg put it regarding market Narso specifically for TA-TMA:  "We see a market opportunity in excess of a billion dollars for TA-TMA in the US and in Europe."

So he is not speaking broadly about revenue from other potential indications, but TA-TMA only when he uses that revenue number.  So no, I don't think he is including any COVID-19 or other presumed EIS indications in that revenue projection. How long it takes to get to a billion dollars in TA-TMA, I agree we do not know.

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Re: Narsoplimab generally

Thanks Ed.
That is interesting.
Especially because Europe has more transplants AND is likely to want a lower price on narso... and because Greg is not working on the EU submission until he gets the US one done (I will believe it when I see it, because I have toned down my expectations, give the track record).

To be prudent I must add caution that $1 billion a year REVENUE for just TA-TMA is not the same as "...a market opportunity in excess of a billion dollars for TA-TMA in the US and in Europe."

Presumably he is talking about 100% market penetration at an unknown price and probably with clinical indications that trigger the use of narso to be more to prophylactic than being "a last-ditch attempt to save a patient's life".

In the US, he can price narso based upon  the overall saving for the Insurer(s), based upon normally spending in excess of $1 million for each of the ~80% of patients who die because they do not get narso.

In Europe the National Health plans will want to make narso standard of care for some specified clinical criteria so that their total system saves money net of narso cost. We have never seen an estimate of that but it is surely less than the average US patient in the same position.

10,000 patients at average price of $100,000 equals $1B. For simplicity, if I presume penetration so that there is 5k patients in the US and the same in EU, but that in the US the cost is$150,000 and the cost in EU is $50,000, you still get $1 Billion.

The Market Opportunity may be assuming the peak sales in (say) 2025 or 2030, at which time there would be 10,000 patients because the number of transplants increase each year (although that would reverse if better treatments were found for the cancer that is usually the cause of the transplant. CAR-T research focuses on these bone-marrow-related/blood cancers.

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

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Re: Narsoplimab generally

All excellent points Alan.  I do admit I get a bit excited when I hear Greg talking about a billion dollars revenue opportunity.  In my mind it was a big deal when annual Omidria revenue looked like it could be on track to approach 15% of that (before pass through expired, of course.)

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Re: Narsoplimab generally

Omidria is a good example.
Is has similarities to narso.

Europe will pay lots less for Omidria than the US.
Which is why Greg does not sell it in Europe.

Walmart makes more money than Tiffany.

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

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Re: Narsoplimab generally

note the date of this article and figure out why it is on this thread
******************************************************
FDA Gives Fast Approval to Gleevec in Treatment of CML
May 31, 2001
Volume 15, Issue 6


Novartis recently announced that the United States Food and Drug Administration (FDA) approved its signal transduction inhibitor Gleevec (imatinib mesylate) as an oral therapy for the treatment of patients with chronic myeloid leukemia (CML) in

Novartis recently announced that the United States Food and Drug Administration (FDA) approved its signal transduction inhibitor Gleevec (imatinib mesylate) as an oral therapy for the treatment of patients with chronic myeloid leukemia (CML) in the blast crisis, accelerated phase or in chronic phase after failure of interferon-alpha therapy. The effectiveness of Gleevec, also known as STI 571, is based on overall hematologic and cytogenetic response rates.

The FDA granted Gleevec a priority review and approved the drug after only a 2 ½-month review time, making this the fastest approval to market any cancer treatment.

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

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Re: Narsoplimab generally

Only a 2 1/2 month review time.....Let's see if Narsoplimab can top that.

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Re: Narsoplimab generally

I presume that is AFTER acceptance.
I am still looking for more.

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

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Re: Narsoplimab generally

I found the approval letter to Novartis from the FDA dated May 10, 2001.  Some interesting information in it

- NDA sent to/received by FDA on Feb 27 2001
- FDA acknowledged receipt of submissions dated:

Mar 9, 14, 30
Apr 4, 5, 10, 12, 13, 19, 23, 24
May 1, 4, 8, 10

The May 10 letter says the FDA completed the review of the application, as amended, according to regs for accelerated approval.  Those regs require further adequate and well controlled studies to verify clinical benefit. 

The FDA also laid out 8 additional study items that Novartis committed to in a May 8th letter (2 days before approval).

It seems that Novartis was in very regular communications with the FDA after submitting the NDA, and that they had a lot of work to do even avter approval.

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Re: Narsoplimab generally

interesting.
The FDA seems like it can make exceptions on their normal timeline when the drug candidate can save lives.

If you compare HSCT-TMA with cancer, the death toll from the TMA is about as bad as Pancreatic cancer in terms of outcome and TMA sufferers may die faster.

If someone could find a way to get 80% of pancreatic cancer patients to survive instead of about 5% to 10%, the FDA would likely try to get it on the market. BTW, I am ignoring the less deadly type of pancreatic cancer, which I think Steve Jobs had. He likely would have survived if he had not gotten some new age treatment and gotten scientific treatment instead.

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

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Re: Narsoplimab generally

Ed posted this material onCV19 sequelae and how narso could potentially fix the problem, or PREVENT it. Problem with that is the cost and the need for OMER to run a trial to show that injecting people with CV19, maybe even mild cases, before there is damage, will prevent the damage, compared to those who get placebo injections.

I don't get the impression that Greg is planning this kind of trial for the initial indication. Almost surely he will go for critically ill people who are most likely to die within a month, IMO.
=====================
Acute Kidney Injury (AKI) in COVID-19 patients.  A COVID-19 related sequelae that early treatment with Narso could help prevent or reduce in severity?

Ziyad Al-Aly, MD, lead investigator on the study, commented on the findings in a related press release.

“This is the first national study of AKI in COVID-19, and it told us that AKI is very common,” he said. “It was also striking to see that nearly half of the veterans with AKI left the hospital with unresolved AKI — meaning that they will likely need long-term follow-up and care, they will also likely suffer long-term consequences lasting their lifetime. Their kidneys are scarred by COVID-19. Unresolved AKI and its long-term consequences are going to be part of the ‘long-haul COVID-19.’”

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

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Re: Narsoplimab generally

Good points Alan. 

As the study referenced has established a high national incidence of AKI among COVID-19 patients, my thought was, could Omeros capture data it gets from any Narso trial it does (may do) to show reduced incidence of AKI in survivors? 

Greg has already been talking about the lack of sequelae in the small number of CUP patients treated with Narso.  Just hoping they could capture reduced AKI incidence data to show that potential benefit.

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Re: Narsoplimab generally

We agree. I have been concerned about the sequelae from the initial hearing about them, especially since kidney dialysis alone in the US, makes up 9% of the total medicare budget! Imagine MILLIONS more people needing dialysis, and then there is liver TMA, brain TMA, heart TMA and clots in blood vessels, in the eyes, etc.

That's why I purposely prompted Greg to discuss it with me today, as I related on the General OMEROS thread.

Greg's view is that the vaccines will help narsoplimab become a success by REDUCING the addressable population. He said that, not me. He probably sees that it is more possible to use an expensive treatment if fewer people need it. My impression is that he sees narso as TREATING sequelae but I'd like to see people treated to avoid the damage and the resultant life-long scars that would still raise the demand for dialysis and other after-the-fact treatment.

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

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Re: Narsoplimab generally

If the price to manufacture narso is as high as that model you discussed, then we would need a 10X or 50X  reduction in mfg cost to make narso widely available I think.

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Re: Narsoplimab generally

That doesn't compute.
You mean a 50% to 90% manufacturing cost reduction, I presume.

With a doubling of half-life of narso, you could get a 50% cost of goods reduction. 90% is probably impossible.

On the other hand your thesis itself is not necessarily valid.
The reason I say that is because it is NOT the ABSOLUTE cost of naro that counts.

What counts is the average NET COST TO SUCCESSFULLY TREAT a type of patient.
A rational determination can only be made by looking at what other care alternatives cost, presumable also including some CREDIT for saving thelife of the patient.

How much does it cost to start treating with narso as soon as a patient qualifies for a CPAP machine... to their discharge? And how does that compare with the cost of treating with the standard of care until discharge or death?

IMO the reason Greg seems to be gravitating towards treating the patients most likely to die is because the overall cost to the system is lower because there are less patients to treat and the effect of successful treatment is more obvious and important than significantly cutting the hospital stay from X days to ~X-3 days. I think treating the sickest patients will be first and then perhaps the use of narso will spread, with all the politicians and wealthy getting narso much earlier, should they come down with Covid.

If I were Jeff Bezos or a Governor infected with Covid, even with a mild case, I'd like some prophylactic narso to preclude later sequelae.

If Greg secures substantial monetary support from the Govt., it is surely expected that the Govt. will want profit margin concessions. In return, OMER may want a minimum sales-volume guarantee that will compensate for making narso available so cheaply, even for all other indications.

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

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Re: Narsoplimab generally

Alan Robert Ross wrote:

We agree. I have been concerned about the sequelae from the initial hearing about them, especially since kidney dialysis alone in the US, makes up 9% of the total medicare budget! Imagine MILLIONS more people needing dialysis, and then there is liver TMA, brain TMA, heart TMA and clots in blood vessels, in the eyes, etc.

That's why I purposely prompted Greg to discuss it with me today, as I related on the General OMEROS thread.

Greg's view is that the vaccines will help narsoplimab become a success by REDUCING the addressable population. He said that, not me. He probably sees that it is more possible to use an expensive treatment if fewer people need it. My impression is that he sees narso as TREATING sequelae but I'd like to see people treated to avoid the damage and the resultant life-long scars that would still raise the demand for dialysis and other after-the-fact treatment.

Agreed and thanks Alan.  I actually missed your post over at the general OMEROS thread, so I did not know you recently spoke with Greg.  Good stuff!

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Re: Narsoplimab generally

https://pubmed.ncbi.nlm.nih.gov/32721954/

Case Reports Nephron
. 2020;144(9):453-458. doi: 10.1159/000508841. Epub 2020 Jul 28.
Inhibition of the Lectin Pathway of the Complement System as a Novel Approach in the Management of IgA Vasculitis-Associated Nephritis
Haresh Selvaskandan 1 2, Chee Kay Cheung 3 4, John Dormer 5, David Wimbury 4, Maria Martinez 3, Gang Xu 3, Jonathan Barratt 3 4
Affiliations expand
PMID: 32721954 DOI: 10.1159/000508841
Abstract
IgA vasculitis can present as a glomerulonephritis histologically indistinguishable from IgA nephropathy (IgAN). In IgAN, the alternative and lectin pathways mediate glomerular injury and contribute to kidney function decline. Narsoplimab is a monoclonal antibody against mannan-binding lectin serine peptidase 2 (MASP-2), a key component of the lectin pathway. It is being evaluated in a phase III trial in IgAN (NCT03608033). Histopathological similarities with IgAN suggest lectin pathway activation also occurs in IgAV-associated nephritis (IgAVN). Here, we report the first ever case of narsoplimab use for the treatment of IgAVN.

Keywords: Complement system; IgA nephropathy; IgA vasculitis; Lectin pathway; Rapidly progressive glomerulonephritis.

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

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Re: Narsoplimab generally

Is this slowing down the approval of narso that we expect to happen so quickly?
====================
http://www.trustintelligence.com/viewto … d=795#p795

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

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Re: Narsoplimab generally

That article indicates reasons for delays are "mainly due to facility inspection requirements made more difficult by pandemic travel restrictions."  I think this has already been done at Lonza?

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Re: Narsoplimab generally

Ahhhhhhhhhhh, there's the rub.
You may be correct... and there may be no delay. We could set a record, if they FDA tells reviewers don't waste time on something once you have enough to approve it.

Otherwise, 2 things:

1. "mainly" not 'only'. There may be staff shortages because people are working on Covid or may HAVE CV19

2. What about Narso for CV19?

The 2k L reactor is not going to be a batch for CV19.
The 20K

Production and Logistics may be as big a problem for narso as data that shows it works.

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

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Re: Narsoplimab generally

https://www.cms.gov/files/document/fy-2 … -day-1.pdf

Fiscal Year (FY) 2022 Inpatient Prospective Payment System (IPPS)
New Technology Add-on Payment (NTAP) Virtual Town Hall Meeting
Tuesday, December 15, 2020
***Please click this URL to join.***
https://cms.zoomgov.com/j/1602047237?pw … dxdzNOQT09
Or join by phone:
Dial: US: +1 669 254 5252 or +1 646 828 7666
Webinar ID: 160 204 7237
Passcode: 949958

December, 15
2:35-2 :50pm Narsoplimab  -  a fully human monoclonal  antibody for the treatment of hematopoietic  stem cell transplant-associated  thrombotic  microangiopathy  (HSCT-TMA).
Presenter: Miguel-Angel Perales, MDChief,  Adult  Bone Marrow Transplantation Service Associate Member Memorial Sloan  Kettering Cancer Center

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

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Re: Narsoplimab generally

In the CMS presentation by Dr. Perales, he said it would be unethical to treat patients with anything else (taking a well-deserved swipe at Soliris & Ultomiris).

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

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Re: Narsoplimab generally

There is getting too much material about narso and what it can do... to study everything. Here is another.
*************************
https://www.gotoper.com/conferences/hsc … t-outcomes

"Integrating New Data to Improve Patient Outcomes

is a 1-hour live webcast highlighting current and emerging options for hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA). This educational program features expert faculty specializing in adult and pediatric hematologic oncology and transplantation, who will use patient case discussions to explore evolving concepts in the management of HSCT-TMA. This activity will highlight areas of uncertainty among the medical community involved in transplantation and illustrate the application of new data in various clinical situations. Participants will have an opportunity to pose questions to the panel and gain insight into the impact of new treatment strategies on HSCT-TMA."

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

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Re: Narsoplimab generally

It doesn't seem to be filtering to the broader investment community, or long finds, at least in a way that they find overwhelmingly convincing enough to spur them to action.

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Re: Narsoplimab generally

A ST poster found a presentation about narso for IgAN by Amar Sethi, Omer Senior Medical Director, Clinical Science, on YouTube.
He starts just before the 44 minute mark in the series of presentations, apparently designed for people with IgAN or for their families.

https://www.youtube.com/watch?v=od8Vg7M … e=youtu.be

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

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Re: Narsoplimab generally

The video above was done in November, at which time, Omeros was still recruiting.

At the end Omeros is thanked for their generous support of the Foundation that is trying to help these patients recover and not lose their kidneys/function, and go on dialysis...and die.

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

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Re: Narsoplimab generally

for full article: https://www.frontiersin.org/articles/10 … 04512/full

Front. Immunol. | doi: 10.3389/fimmu.2020.604512

Does the lectin complement pathway link atypical Kawasaki disease and SARS- CoV-2? Provisionally accepted

Anastasia Polycarpou, Sofia Grigoriadou,  Linda S. Klavinskis and  Steven H. Sacks*
School of Immunology and Microbial Sciences, King's College London, United Kingdom, The Royal London Hospital, United Kingdom

Abstract
Out of the mire of the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, a new clue on pathogenesis has emerged regarding multisystem inflammatory disease in children with evidence of endotheliitis and microvascular thrombosis, with striking similarities to Kawasaki disease. Here we consider whether the complement system could underpin these connections, in particular the lectin pathway - the most recent and perhaps least understood of the three main activation pathways known to unleash the complement cascade. We have evaluated the published evidence linking the complement system with both Kawasaki disease and COVID-19 associated acute respiratory distress syndrome (ARDS) and we conclude that the complement system could be a therapeutic target for the Kawasaki-like syndrome triggered by SARS-CoV-2.


Introduction:
The complement cascade has a significant role in host defence. Activation of complement via the classical and alternate pathways has long been recognised. More recently, the lectin complement pathway has defined a new means of pathogen recognition via carbohydrate motifs on the pathogen surface that can bind vertebrate lectins, resulting in enzymatic activation of complement and also the coagulation system on endothelial surfaces to cause thrombosis [1]. Pertinently, the surface structures of SARS-CoV-2 are rich in carbohydrate residues recognised by lectins [2].
Lectin pathway involvement in COVID-19
The hallmarks of lectin pathway involvement ¬– increased detection of Mannose binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) alongside cleavage products of complement C4 and C3 ¬– are found co-localized with SARS-CoV-2 in post-mortem lung tissue from adult COVID-19 patients [3]. The alveolar epithelium, a primary target of SARS-CoV-2, locally produces complement-activating lectins such as collectin-11 and ficolin-1 providing a tentative site for complement deposition. Indeed, lectin pathway components (MBL, MASP-2, C4d and C3d) are also co-localized with the SARS-CoV-2 envelope protein in adjacent blood vessels, where endotheliitis and thrombus formation are evident [3]. It should be emphasized that activation of the lectin pathway through MBL-MASP and ficolin-MASP binding to glycan structures, which are present on the SARS-CoV-2 envelope, may lead to the generation of blood clots similar to those generated by thrombin [4]. Moreover, elevated plasma collectin-11 levels have been associated with the risk of disseminated intravascular coagulation (DIC) [5]. These findings provide the first circumstantial evidence of complement involvement in adult COVID-19. Although not proving causation, they have provided rationale for targeting the complement system in COVID-19 [6] and the initiation of clinical trials of complement inhibitors.
Comparison of multisystem inflammatory syndrome in children following SARS-CoV-2 infection with Kawasaki disease
While childhood COVID-19 is usually asymptomatic or mild, several recent published reports document a hyper-inflammatory syndrome associated with thrombotic tendency, multi-organ involvement and a high rate of positivity for SARS-CoV-2 [7-13]. This syndrome has resemblance to Kawasaki disease, first recognized in Japan in 1967, which is associated with several viral infections including coronaviruses [14] and presents as an acute vasculitis of children under five, characterized by fever, lymphadenopathy and coronary artery involvement in up to 25% [15]. In comparison, patients with the Kawasaki-like paediatric variant of COVID-19 (MIS-C) are generally older, often presenting with severe respiratory and gastrointestinal symptoms. Two recent studies that reported a large number of patients with confirmed or suspected cases of multisystem inflammatory syndrome noted positivity for SARS-CoV-2 by RT-PCR or antibody testing in 70% and 99% respectively [11, 12]. The majority of children in all studies reported to date had increased markers of myocardial injury, many had echocardiogram abnormalities and/or prominent echogenic coronary arteries while 14% in the English study [8] and 9% in the two large American cohorts [11, 12] also had coronary aneurysms. In addition, increased coagulation markers were noted in a significant proportion of patients when measured, while acute kidney injury occurred in 22% of admitted children in the English cohort [9]. Thus, the clinical and laboratory findings in multisystem inflammatory syndrome in children (MIS-C) following infection with SARS-CoV-2 have considerable overlap with Kawasaki disease and with adult COVID-19.
Links between MIS-C and Kawasaki disease with the complement system
A viral etiology is implicated in adult and paediatric COVID-19 and Kawasaki disease. The wide range of viruses including SARS-Coronaviruses (CoV) interacting with carbohydrate-recognition molecules such as collectin-11 [16] and MBL [17] makes it highly likely that the lectin complement pathway is triggered. Moreover, MBL gene polymorphism associates with Kawasaki disease and its cardiovascular abnormalities [18-20] and MBL has been directly implicated in the pathogenesis of a murine model of vasculitis imitating Kawasaki disease [21]. A dual role for MBL has been proposed in Kawasaki disease depending on the age of the patient, with a pathogenic role favoring disease progression and endothelial damage in older children [20]. Additionally, plasma MASP-1 concentration at the onset of the illness was predictive of the length of recovery time for coronary artery lesions [22]. There is evidence that activation of MASP-1 in the early stage of Kawasaki disease provokes a local vascular inflammatory reaction, resulting in the consumption of MASP-1 [22]. Another lectin pathway component, ficolin-1, demonstrates reduced serum levels after successful intravenous immunoglobulin (IVIG) treatment in Kawasaki patients [23]. This study provided support for direct interaction of IVIG with ficolin-1, giving rise to the captivating idea that at least one mechanism of treatment effectiveness of IVIG in Kawasaki disease is due to reduction of ficolin-1 level in the serum [23].
Other pathways of complement activation may be involved. Complement activation by immune complexes in Kawasaki disease suggests dependence on the classical pathway of complement activation in the development of vasculitis [24]. However, elevation of plasma levels of activation marker C4d in patients with Kawasaki syndrome, which has been previously reported to be diagnostic of the classical pathway [24], could also be downstream of the lectin pathway since C4 is a component of both complement pathways [25]. C-reactive protein (CRP) may further enhance the localized deposition of complement in the vessel wall, since gross elevation of CRP occurs in the acute phase of Kawasaki disease (and COVID-19) and this protein can mediate classical pathway activation of complement [26, 27]. A study in Kawasaki disease demonstrated that complement factor B (essential for alternative pathway activation) is likely to have a contributory effect [28]. Other proteomic studies have identified strong associations of the complement and coagulation cascades with Kawasaki disease [29]. Multiple different components of innate immunity may be active during MIS-C, Kawasaki syndrome and COVID-19 such as type I interferon (IFN) [30, 31], which may be a downstream effect of complement activation or may occur independently. The lectin pathway could therefore be the initial immune trigger after engaging the virus; initiating the complement cascade, while induction of type I IFN could be a secondary response. Independent of which of the two systems is activated first, thrombotic microangiopathy may be a resulting manifestation [32].
Discussion
At this early stage in our understanding of how SARS-CoV-2 leads to hyperinflammatory syndrome, the evidence linking complement activation with endothelial injury and thrombosis is undeniable though largely circumstantial. More-definitive experimental data is needed to support complement-based therapeutic approaches and to inform on the most appropriate therapeutic targets and whether these involve ligand-recognition (lectin and classical) or amplification (alternative) pathways, or core components (C3 and C5) or the terminal effector pathway (i.e. C5a or C5b-9). It is hoped that this opinion article will stimulate early interest in these possibilities. The pandemic of SARS-CoV-2 disease and its aggressive presentation in a subgroup of children also brings into line a better understanding of the pathogenesis of sporadic Kawasaki disease and the potential for targeting the complement system in both conditions.

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

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One of the guys in the email group sent this around and then he posted it on ST. I was tempted to reply and tell him I think his conclusion is correct by that the reason he is giving from this is based uon the assumption that FDA and CMS collaborate on speeding approval and/or use of drugs. I see no evidence they do, certainly his evidence is not strong evidence.

CMS does not approve drugs and the FDA has repeatedly shown they are expediting approval. This fellow is an insecure but (he says) a higher successful specialized accountant who writes accounting opinions about how much was suffered in patent infringements.

Anyway, I decided not to rain on his due diligence, which is positive.  Those of us who can read the tea leaves already know that FDA wants the drug approved and Omeros presented narsoplimab to the CMS, in 2020 because it did not want to lose reimbursement by waiting until approved in 2021, at which time a CMS application would have kicked in on Jan. 1st of the FOLLOWING year.  CMS is not designed for the benefit of drug makers.
********************
As I think just about all of us know, on Tuesday Dr. Perales presented on Narso TMA for consideration for separate/non-packaged payment, at a town hall meeting held by CMS (https://www.cms.gov/files/document/fy-2 … -day-1.pdf).  Dave B. and I were talking about how this seemed to be a pretty big deal, since it would seem to be putting the cart before the horse to be evaluating Narso-TMA for payment (consistent with the Sept CMA-DHHS discussion about ICD coding for reimbursement for Narso-TMA), prior to approval, or even acceptance of the BLA.  It sure seems that the FDA is trying to get Narso fast-tracked.  But one issue on which neither Dave nor I was clear was the stati of the other drugs/devices being discussed at the Tuesday town hall.  So I decided to research that.  Here is what I found:

Ellipsys (vascular access system)
FDA approved in 2018
https://vascularnews.com/fda-approves-ellipsys/

Rapid ASPECTS (neuroimaging analysis device)
FDA approved in 2020
https://neuronewsinternational.com/rapi … rance-fda/

Aidoc Briefcase for PE (artificial intelligence-based triage and notification technology for suspected Pulmonary Embolism) 
FDA approved 2019
https://medcitynews.com/2019/05/aidoc-g … ning-tool/

Note that the "Viz" technologies are related to Rapid ASPECTS and also appear to have been approved 
https://www.accessdata.fda.gov/cdrh_doc … 193658.pdf

INDIGO Aspiration Tubing
FDA approved 2020
https://www.accessdata.fda.gov/cdrh_doc … 192981.pdf

Veklury (remdesivir)
FDA Approved 2020
https://www.fda.gov/drugs/drug-safety-a … ectiveness

At that point I decided I had seen enough, having gone through many of the other items discussed, and all of them had received FDA approval prior to being part of this discussion.  This reconfirmed my opinion that Narso is soon to be accepted and approved, for TMA as an initial indication, and hopefully a wide use on the label (opening the door for COVID use).

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

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Re: Narsoplimab generally

Alan, if Narso is approved for TMA on the label, how does FDA let doctors know that Narso is also approved for off-label use?  Is it just accepted tradition that any newly approved drug can be used for off-label use?  Or does the label specifically say, in addition to approval for TMA, that off-label use is also approved and/or acceptable - meaning if the label does not say that, then Narso cannot be used off-label.

Short version of my question.  When Narso is approved for TMA, is it automatically OK for doctors to start using Narso to treat Covid?

34

Re: Narsoplimab generally

Yes.
OMER cannot promote the drug for Off-Label use.

An MD may use any approved drug for anything... but s/he could be sued by the patient for malpractice.

Scientific literature and articles about the MOA and the effect of the drug in trial or CUP programs or skuttlebutt, may lead to off-label use.

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

35

Re: Narsoplimab generally

Off label use is a viable perhaps if they can have some public studies showing potential and effectiveness and get insurers to cover it

36

Re: Narsoplimab generally

LIFE insurers should pay for it.

Which brings up the point that there should be a rules that, if you are going to have medical insurance the life insurer should write it.

The question for many sick people is do you treat or allow the person to die. It maybe cheaper for the medical insurer to refuse to approve treatment, while this would cost the company that insures a person's life.

As a result a sane system would be to pay only one company who is supposed to keep you alive, and if they fail, they need to pay a lump sum to your heirs that will make them think twice before allowing you to die when there is life-saving treatment available.

Back to OMEROS:

I think you may neglect to appreciate that OMER doesn't think it is feasible to treat everyone now. It cannot make enough narso to supply those who need it, now, for probably for a year or more. It can only make enough extra for a very limited #patients.
Maybe 500 or 1000 per Q.
It does not want to sell those doses at a low markup and chance ruining the profit for HSCT-TMA or IgAN.

I am pretty certain OMER wants Govt. help to make a lot of Narso, because only a large volume makes it worthwhile to treat people at a reasonable price.

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

37

Re: Narsoplimab generally

Omeros tweeted this old article tonight. For the whole article, you can get it, here:
https://pubmed.ncbi.nlm.nih.gov/24892262/

Omeros is looking for markers that will identify people who are having HSCT-TMA problems and need narso. This may be one.

Biol Blood Marrow Transplant
. 2014 Sep;20(9):1407-17. doi: 10.1016/j.bbmt.2014.05.022. Epub 2014 Jun 2.

Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes

Lawrence Chang 1, David Frame 2, Thomas Braun 3, Erin Gatza 1, David A Hanauer 4, Shuang Zhao 5, John M Magenau 6, Kathryn Schultz 7, Hemasri Tokala 8, James L M Ferrara 1, John E Levine 1, Pavan Reddy 6, Sophie Paczesny 9, Sung Won Choi 10

PMID: 24892262 PMCID: PMC4142041 DOI: 10.1016/j.bbmt.2014.05.022

Abstract
Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.

Keywords: Cytokine storm; Engraftment syndrome; Hematopoietic cell transplantation.

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

38

Re: Narsoplimab generally

https://s3.amazonaws.com/gotoper-com/_media/_image/TMA_HSCT20_Banners_547x185.png

Tuesday, February 9, 2021

Live, Interactive Webcast!

8:30 AM – 9:30 AM CST

Overview
Case Discussions in HSCT-TMA: Integrating New Data to Improve Patient Outcomes is a 1-hour live webcast highlighting current and emerging options for hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA). This educational program features expert faculty specializing in adult and pediatric hematologic oncology and transplantation, who will use patient case discussions to explore evolving concepts in the management of HSCT-TMA. This activity will highlight areas of uncertainty among the medical community involved in transplantation and illustrate the application of new data in various clinical situations. Participants will have an opportunity to pose questions to the panel and gain insight into the impact of new treatment strategies on HSCT-TMA.

Benefits of Attending
Gain knowledge of emerging drug targets
Get insights regarding diagnosing HSCT-TMA
Hear challenging patient case scenarios
Learn about current and evolving treatments

Acknowledgment of Commercial Support
This activity is supported by an educational grant from Omeros.

Target Audience
This educational program is directed toward hematologists, medical oncologists, researchers, and investigators who treat or are interested in the treatment of hematologic malignancies. Other allied health care professionals, including nurse practitioners, physician assistants, and nurses involved in the treatment and management of patients with hematologic malignancies, will also be invited to participate.

Learning Objectives
Upon completion of this activity, participants will be able to:

Review current diagnostic criteria for HSCT-TMA and ways to differentiate it from other stem cell transplant–associated complications with overlapping symptoms
Assess the role of dysregulated complement activation in the pathogenesis of HSCT- TMA
Discuss the rationale concerning the application of complement targeted therapies, including MASP-2 inhibitors, in the treatment of HSCT-TMA
Evaluate recent clinical trial data concerning the effectiveness of emerging therapies in the treatment of HSCT-TMA
Program Chair
Sergio A. Giralt, MD, FACP
Sergio A. Giralt, MD, FACP
Professor of Medicine
Weill Cornell Medicine
Melvin Berlin Family Chair in Multiple Myeloma
Deputy Head, Division of Hematologic Malignancies
Attending Physician, Adult BMT Service
Adult Bone Marrow Transplant Service
Memorial Sloan Kettering Cancer Center
New York, NY

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

39

Re: Narsoplimab generally

A petient in the IgAN trial talks about his condition and enrolling

https://unfilteredakc.com/2020/10/28/wh … -vacation/

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

40

Re: Narsoplimab generally

This 2017 patent about the anti-angiogenesis of narso (likely to be useful against macular degeneration and similar causes of blindness AND in cancer, covers a lot of ground in describing how the complement system works.

The system is complicated, but you really can't get a better idea of why narso has so much potential unless you get a better grasp on the whole system (which also will help you understand why Greg is so confident that Omeros' complement drugs will be better tan those of the competition... which increasingly are being bought out by larger entities that DO understand.

So why are they buying the companies with sub-optimal treatments?
Because they can't buy Omeros until the market price allows them to make a high enough bid.

I suggest you keep the link to this patent for access to Complement background info (because the past tells us that this website will not be available forever, perhaps not even for as as long as the info will be needed.
=====================
link: https://patents.justia.com/patent/10870708

Methods for inhibiting angiogenesis in a subject in need thereof
Mar 31, 2017 - University of Leicester
In one aspect, the present invention provides methods for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from, or at risk for developing, an angiogenesis-dependent disease or condition, comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis. In some embodiments of these aspects of the invention, the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof.

Description
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of Provisional Application No. 62/315,857, filed Mar. 31, 2016, all of which are hereby incorporated by reference in their entirety.

STATEMENT REGARDING SEQUENCE LISTING
The sequence listing associated with this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into the specification. The name of the text file containing the sequence listing is MP_1_0239_US2_Sequence_Listing_20170321_ST25. The text file is 115 KB, was created on Mar. 21, 2017, and is being submitted via EFS-Web with the filing of the specification.

BACKGROUND
The complement system provides an early acting mechanism to initiate, amplify and orchestrate the immune response to microbial infection and other acute insults (M. K. Liszewski and J. P. Atkinson, 1993, in Fundamental Immunology, Third Edition, edited by W. E. Paul, Raven Press, Ltd., New York), in humans and other vertebrates. While complement activation provides a valuable first-line defense against potential pathogens, the activities of complement that promote a protective immune response can also represent a potential threat to the host (K. R. Kalli, et al., Springer Semin. Immunopathol. 15:417-431, 1994; B. P. Morgan, Eur. J. Clinical Investig. 24:219-228, 1994). For example, C3 and C5 proteolytic products recruit and activate neutrophils. While indispensable for host defense, activated neutrophils are indiscriminate in their release of destructive enzymes and may cause organ damage. In addition, complement activation may cause the deposition of lytic complement components on nearby host cells as well as on microbial targets, resulting in host cell lysis.

The complement system has also been implicated in the pathogenesis of numerous acute and chronic disease states, including: myocardial infarction, stroke, ARDS, reperfusion injury, septic shock, capillary leakage following thermal burns, postcardiopulmonary bypass inflammation, transplant rejection, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, and Alzheimer's disease. In almost all of these conditions, complement is not the cause but is one of several factors involved in pathogenesis. Nevertheless, complement activation may be a major pathological mechanism and represents an effective point for clinical control in many of these disease states. The growing recognition of the importance of complement-mediated tissue injury in a variety of disease states underscores the need for effective complement inhibitory drugs. To date, Eculizumab (Solaris®), an antibody against complement component C5, is the only complement-targeting drug that has been approved for use in man. Yet, C5 is one of several effector molecules located “downstream” in the complement activation cascade, and blockade of C5 does not inhibit activation of the complement system. Therefore, an inhibitor of the initiation steps of complement activation would have significant advantages over a “downstream” complement inhibitor.

Currently, it is widely accepted that the complement system can be activated through three distinct pathways: the classical pathway, the lectin pathway, and the alternative pathway. The classical pathway is usually triggered by a complex composed of host antibodies bound to a foreign particle (i.e., an antigen) and thus requires prior exposure to an antigen for the generation of a specific antibody response. Since activation of the classical pathway depends on a prior adaptive immune response by the host, the classical pathway is part of the acquired immune system. In contrast, both the lectin and alternative pathways are independent of adaptive immunity and are part of the innate immune system.

The activation of the complement system results in the sequential activation of serine protease zymogens. The first step in activation of the classical pathway is the binding of a specific recognition molecule, C1q, to antigen-bound IgG and IgM molecules. C1q is associated with the C1r and C1s serine protease proenzymes as a complex called C1. Upon binding of C1q to an immune complex, autoproteolytic cleavage of the Arg-Ile site of C1r is followed by C1r-mediated cleavage and activation of C1s, which thereby acquires the ability to cleave C4 and C2. C4 is cleaved into two fragments, designated C4a and C4b, and, similarly, C2 is cleaved into C2a and C2b. C4b fragments are able to form covalent bonds with adjacent hydroxyl or amino groups and generate the C3 convertase (C4b2a) through noncovalent interaction with the C2a fragment of activated C2. C3 convertase (C4b2a) activates C3 by proteolytic cleavage into C3a and C3b subcomponents leading to generation of the C5 convertase (C4b2a3b), which, by cleaving C5 leads to the formation of the membrane attack complex (C5b combined with C6, C7, C8 and C-9 polymers, also referred to as “MAC”) that can disrupt cellular membranes leading to cell lysis. The activated forms of C3 and C4 (C3b and C4b) are covalently deposited on the foreign target surfaces, which are recognized by complement receptors on multiple phagocytes.

The first step in activation of the complement system through the lectin pathway is the binding of lectin pathway-specific pattern recognition molecules to their target ligands. This process initiates the activation of lectin pathway-specific serine protease proenzymes that in turn initiate the complement cascade. The pattern recognition molecules in the lectin pathway comprise a group of carbohydrate-binding C-type lectins, i.e., mannan-binding lectin (MBL), collectin-11 (CL-11, also known as CL-K1), collectin-10 (CL-10, also known as CL-L1), and three different ficolins, i.e., H-ficolin, M-ficolin and L-ficolin that bind to acetylated structures of carbohydrates and proteins through fibrinogen-like binding domains (J. Lu et al., Biochim. Biophys. Acta 1572:387-400, (2002); Holmskov et al., Annu. Rev. Immunol. 21:547-578 (2003); Teh et al., Immunology 101:225-232 (2000), J. Luet et al., Biochim Biophys Acta 1572:387-400 (2002); Hansen et al, J. Immunol 185(10):6096-6104 (2010), and Hendriksen et al., J Immunol 191(12):6117-27, 2013).

Ikeda et al. first demonstrated that, like C1q, MBL could activate the complement system upon binding to yeast mannan-coated erythrocytes in a C4-dependent manner (Ikeda et al., J Biol. Chem. 262:7451-7454, (1987)). MBL, a member of the collectin protein family, is a calcium-dependent lectin that binds carbohydrates with 3- and 4-hydroxy groups oriented in the equatorial plane of the pyranose ring. Prominent ligands for MBL are thus D-mannose and N-acetyl-D-glucosamine, while carbohydrates not fitting this steric requirement have undetectable affinity for MBL (Weis et al., Nature 360:127-134, (1992)). The interaction between MBL and monovalent sugars is extremely weak, with dissociation constants typically in the single-digit millimolar range. MBL achieves tight, specific binding to glycan ligands by avidity, i.e., by interacting simultaneously with multiple monosaccharide residues located in close proximity to each other (Lee et al., Archiv. Biochem. Biophys. 299:129-136, (1992)). MBL recognizes the carbohydrate patterns that commonly decorate microorganisms such as bacteria, yeast, parasites and certain viruses. In contrast, MBL does not recognize D-galactose and sialic acid, the penultimate and ultimate sugars that usually decorate “mature” complex glycoconjugates present on mammalian plasma and cell surface glycoproteins. This binding specificity is thought to promote recognition of “foreign” surfaces and help protect from “self-activation.” However, MBL does bind with high affinity to clusters of high-mannose “precursor” glycans on N-linked glycoproteins and glycolipids sequestered in the endoplasmic reticulum and Golgi of mammalian cells (Maynard et al., J. Biol. Chem. 257:3788-3794, (1982)). Therefore, damaged cells are potential targets for lectin pathway activation via MBL binding and more recent work has shown that CL-11 is another lectin pathway recognition subcomponent that initiates lectin pathway activation on distressed or damaged cells (Farar et al., J Clin Invest 126:1911-1925, 2016).

The ficolins possess a different type of lectin domain than MBL, called the fibrinogen-like domain. Ficolins bind sugar residues in a Ca++-independent manner. In humans, three kinds of ficolins (L-ficolin, M-ficolin and H-ficolin) have been identified. The two serum ficolins, L-ficolin and H-ficolin, have in common a specificity for N-acetyl-D-glucosamine; however, H-ficolin also binds N-acetyl-D-galactosamine. The difference in sugar specificity of L-ficolin, H-ficolin, CL-11, and MBL means that the different lectins may be complementary and target different, though overlapping, glycoconjugates. This concept is supported by the recent report that, of the known lectins in the lectin pathway, only L-ficolin binds specifically to lipoteichoic acid, a cell wall glycoconjugate found on all Gram-positive bacteria (Lynch et al., J. Immunol. 172:1198-1202, (2004)). The collectins (i.e., MBL, CL-11, CL-10 and CL-11/CL-10 complexes) and the ficolins bear no significant similarity in amino acid sequence. However, the two groups of proteins have similar domain organizations and, like C1q, assemble into oligomeric structures, which maximize the possibility of multisite binding.

The serum concentrations of MBL are highly variable in healthy populations and this is genetically controlled by polymorphisms/mutations in both the promoter and coding regions of the MBL gene. As an acute phase protein, the expression of MBL is further upregulated during inflammation. L-ficolin is present in serum at concentrations similar to those of MBL. Therefore, the L-ficolin branch of the lectin pathway is potentially comparable to the MBL arm in physiological importance. MBL and ficolins can also function as opsonins, which allow phagocytes to target MBL- and ficolin-decorated surfaces (see Jack et al., J Leukoc Biol., 77(3):328-36 (2004), Matsushita and Fujita, Immunobiology, 205(4-5):490-7 (2002), Aoyagi et al., J Immunol, 174(1):418-25(2005). This opsonization requires the interaction of these proteins with phagocyte receptors (Kuhlman et al., J Exp. Med. 169:1733, (1989); Matsushita et al., J Biol. Chem. 271:2448-54, (1996)), the identity of which has not been established.

Human MBL forms a specific and high-affinity interaction through its collagen-like domain with unique C1r/C1s-like serine proteases, termed MBL-associated serine proteases (MASPs). To date, three MASPs have been described. First, a single enzyme “MASP” was identified and characterized as the enzyme responsible for the initiation of the complement cascade (i.e., cleaving C2 and C4) (Matsushita et al., J Exp Med 176(6):1497-1502 (1992); Ji et al., J Immunol. 150:571-578, (1993)). It was subsequently determined that the MASP activity was, in fact, a mixture of two proteases: MASP-1 and MASP-2 (Thiel et al., Nature 386:506-510, (1997)). However, it was demonstrated that the MBL-MASP-2 complex alone is sufficient for complement activation (Vorup-Jensen et al., J Immunol. 165:2093-2100, (2000)). Furthermore, only MASP-2 cleaved C2 and C4 at high rates (Ambrus et al., Immunol. 170:1374-1382, (2003)). Therefore, MASP-2 is the protease responsible for activating C4 and C2 to generate the C3 convertase, C4b2a. This is a significant difference from the C1 complex of the classical pathway, where the coordinated action of two specific serine proteases (C1r and C1s) leads to the activation of the complement system. In addition, a third novel protease, MASP-3, has been isolated (Dahl, M. R., et al., Immunity 15:127-35, 2001). MASP-1 and MASP-3 are alternatively spliced products of the same gene.

MASPs share identical domain organizations with those of C1r and C1s, the enzymatic components of the C1 complex (Sim et al., Biochem. Soc. Trans. 28:545, (2000)). These domains include an N-terminal C1r/C1s/sea urchin VEGF/bone morphogenic protein (CUB) domain, an epidermal growth factor-like domain, a second CUB domain, a tandem of complement control protein domains, and a serine protease domain. As in the C1 proteases, activation of MASP-2 occurs through cleavage of an Arg-Ile bond adjacent to the serine protease domain, which splits the enzyme into disulfide-linked A and B chains, the latter consisting of the serine protease domain.

MBL can also associate with an alternatively spliced form of MASP-2, known as MBL-associated protein of 19 kDa (MAp19) or small MBL-associated protein (sMAP), which lacks the catalytic activity of MASP-2. (Stover, J Immunol. 162:3481-90, (1999); Takahashi et al., Int. Immunol. 11:859-863, (1999)). MAp19 comprises the first two domains of MASP-2, followed by an extra sequence of four unique amino acids. The function of Map19 is unclear (Degn et al., J Immunol. Methods, 2011). The MASP-1 and MASP-2 genes are located on human chromosomes 3 and 1, respectively (Schwaeble et al., Immunobiology 205:455-466, (2002)).

Several lines of evidence suggest that there are different MBL-MASP complexes and a large fraction of the MASPs in serum is not complexed with MBL (Thiel, et al., Immunol. 165:878-887, (2000)). Both H- and L-ficolin bind to all MASPs and activate the lectin complement pathway, as does MBL (Dahl et al., Immunity 15:127-35, (2001); Matsushita et al., J Immunol. 168:3502-3506, (2002)). Both the lectin and classical pathways form a common C3 convertase (C4b2a) and the two pathways converge at this step.

The lectin pathway is widely thought to have a major role in host defense against infection in the naïve host. Strong evidence for the involvement of MBL in host defense comes from analysis of patients with decreased serum levels of functional MBL (Kilpatrick, Biochim. Biophys. Acta 1572:401-413, (2002)). Such patients display susceptibility to recurrent bacterial and fungal infections. These symptoms are usually evident early in life, during an apparent window of vulnerability as maternally derived antibody titer wanes, but before a full repertoire of antibody responses develops. This syndrome often results from mutations at several sites in the collagenous portion of MBL, which interfere with proper formation of MBL oligomers. However, since MBL can function as an opsonin independent of complement, it is not known to what extent the increased susceptibility to infection is due to impaired complement activation.

In contrast to the classical and lectin pathways, no initiators of the alternative pathway have been found to fulfill the recognition functions that C1q and lectins perform in the other two pathways. Currently it is widely accepted that the alternative pathway spontaneously undergoes a low level of turnover activation, which can be readily amplified on foreign or other abnormal surfaces (bacteria, yeast, virally infected cells, or damaged tissue) that lack the proper molecular elements that keep spontaneous complement activation in check. There are four plasma proteins directly involved in the activation of the alternative pathway: C3, factors B and D, and properdin.

Although there is extensive evidence implicating both the classical and alternative complement pathways in the pathogenesis of non-infectious human diseases, the role of the lectin pathway is just beginning to be evaluated. Recent studies provide evidence that activation of the lectin pathway can be responsible for complement activation and related inflammation in ischemia/reperfusion injury. Collard et al. (2000) reported that cultured endothelial cells subjected to oxidative stress bind MBL and show deposition of C3 upon exposure to human serum (Collard et al., Am. J Pathol. 156:1549-1556, (2000)). In addition, treatment of human sera with blocking anti-MBL monoclonal antibodies inhibited MBL binding and complement activation. These findings were extended to a rat model of myocardial ischemia-reperfusion in which rats treated with a blocking antibody directed against rat MBL showed significantly less myocardial damage upon occlusion of a coronary artery than rats treated with a control antibody (Jordan et al., Circulation 104:1413-1418, (2001)). The molecular mechanism of MBL binding to the vascular endothelium after oxidative stress is unclear; a recent study suggests that activation of the lectin pathway after oxidative stress may be mediated by MBL binding to vascular endothelial cytokeratins, and not to glycoconjugates (Collard et al., Am. J. Pathol. 159:1045-1054, (2001)). Other studies have implicated the classical and alternative pathways in the pathogenesis of ischemia/reperfusion injury and the role of the lectin pathway in this disease remains controversial (Riedermann, N.C., et al., Am. J. Pathol. 162:363-367, 2003).

A recent study has shown that MASP-1 (and possibly also MASP-3) is required to convert the alternative pathway activation enzyme Factor D from its zymogen form into its enzymatically active form (see Takahashi M. et al., J Exp Med 207(1):29-37 (2010)). The physiological importance of this process is underlined by the absence of alternative pathway functional activity in plasma of MASP-1/3-deficient mice. Proteolytic generation of C3b from native C3 is required for the alternative pathway to function. Since the alternative pathway C3 convertase (C3bBb) contains C3b as an essential subunit, the question regarding the origin of the first C3b via the alternative pathway has presented a puzzling problem and has stimulated considerable research.

C3 belongs to a family of proteins (along with C4 and α-2 macroglobulin) that contain a rare posttranslational modification known as a thioester bond. The thioester group is composed of a glutamine whose terminal carbonyl group forms a covalent thioester linkage with the sulfhydryl group of a cysteine three amino acids away. This bond is unstable and the electrophilic glutamyl-thioester can react with nucleophilic moieties such as hydroxyl or amino groups and thus form a covalent bond with other molecules. The thioester bond is reasonably stable when sequestered within a hydrophobic pocket of intact C3. However, proteolytic cleavage of C3 to C3a and C3b results in exposure of the highly reactive thioester bond on C3b and, following nucleophilic attack by adjacent moieties comprising hydroxyl or amino groups, C3b becomes covalently linked to a target. In addition to its well-documented role in covalent attachment of C3b to complement targets, the C3 thioester is also thought to have a pivotal role in triggering the alternative pathway. According to the widely accepted “tick-over theory”, the alternative pathway is initiated by the generation of a fluid-phase convertase, iC3Bb, which is formed from C3 with hydrolyzed thioester (iC3; C3(H2O)) and factor B (Lachmann, P. J., et al., Springer Semin. Immunopathol. 7:143-162, (1984)). The C3b-like C3(H2O) is generated from native C3 by a slow spontaneous hydrolysis of the internal thioester in the protein (Pangburn, M. K., et al., J. Exp. Med. 154:856-867, 1981). Through the activity of the C3(H2O)Bb convertase, C3b molecules are deposited on the target surface thereby initiating the alternative pathway.

Very little is known about the initiators of activation of the alternative pathway. Activators are thought to include yeast cell walls (zymosan), many pure polysaccharides, rabbit erythrocytes, certain immunoglobulins, viruses, fungi, bacteria, animal tumor cells, parasites, and damaged cells. The only feature common to these activators is the presence of carbohydrate, but the complexity and variety of carbohydrate structures has made it difficult to establish the shared molecular determinants which are recognized. It has been widely accepted that alternative pathway activation is controlled through the fine balance between inhibitory regulatory components of this pathway, such as Factor H, Factor I, DAF, and CR1, and properdin, which is the only positive regulator of the alternative pathway (see Schwaeble W. J. and Reid K. B., Immunol Today 20(1):17-21 (1999)).

In addition to the apparently unregulated activation mechanism described above, the alternative pathway can also provide a powerful amplification loop for the lectin/classical pathway C3 convertase (C4b2a) since any C3b generated can participate with factor B in forming additional alternative pathway C3 convertase (C3bBb). The alternative pathway C3 convertase is stabilized by the binding of properdin. Properdin extends the alternative pathway C3 convertase half-life six to ten fold. Addition of C3b to the alternative pathway C3 convertase leads to the formation of the alternative pathway C5 convertase.

All three pathways (i.e., the classical, lectin and alternative) have been thought to converge at C5, which is cleaved to form products with multiple proinflammatory effects. The converged pathway has been referred to as the terminal complement pathway. C5a is the most potent anaphylatoxin, inducing alterations in smooth muscle and vascular tone, as well as vascular permeability. It is also a powerful chemotaxin and activator of both neutrophils and monocytes. C5a-mediated cellular activation can significantly amplify inflammatory responses by inducing the release of multiple additional inflammatory mediators, including cytokines, hydrolytic enzymes, arachidonic acid metabolites, and reactive oxygen species. C5 cleavage leads to the formation of C5b-9, also known as the membrane attack complex (MAC). There is now strong evidence that sublytic MAC deposition may play an important role in inflammation in addition to its role as a lytic pore-forming complex.

In addition to its essential role in immune defense, the complement system contributes to tissue damage in many clinical conditions. Thus, there is a pressing need to develop therapeutically effective complement inhibitors to prevent these adverse effects.

It is well established that angiogenesis is implicated in the pathogenesis of a variety of disorders including solid tumors and metastases, and ocular neovascular diseases such as age-related macular degeneration (AMD), proliferative diabetic retinopathy and neovascular glaucoma.

In view of the role of angiogenesis in many diseases and disorders, there is also a pressing need to develop therapeutically effective angiogenesis inhibitors.

SUMMARY
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

In one aspect, the present invention provides methods for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from, or at risk for developing, an angiogenesis-dependent disease or condition, comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis. In some embodiments of these aspects of the invention, the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof. In further embodiments, the MASP-2 antibody has reduced effector function. In some embodiments, the MASP-2 inhibitory agent is a MASP-2 inhibitory peptide or a non-peptide MASP-2 inhibitor.

In another aspect, the present invention provides compositions for inhibiting the adverse effects of angiogenesis, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier. Methods are also provided for manufacturing a medicament for use in inhibiting the adverse effects of angiogenesis in living subjects in need thereof, comprising a therapeutically effective amount of a MASP-2 inhibitory agent in a pharmaceutical carrier. Methods are also provided for manufacturing medicaments for use in inhibiting angiogenesis for treatment of each of the conditions, diseases and disorders described herein below.

The methods, compositions and medicaments of the invention are useful for inhibiting the adverse effects of angiogenesis in vivo in mammalian subjects, including humans suffering from an acute or chronic pathological condition or injury as further described herein.

In another aspect of the invention, methods are provided for inhibiting angiogenesis in a mammalian subject suffering from an angiogenesis-dependent disease or condition comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis. In some embodiments, the angiogenesis-dependent disease or condition is an angiogenesis-dependent cancer, such as, for example, an angiogenesis-dependent cancer selected from the group consisting of solid tumor(s), blood borne tumors, high-risk carcinoid tumors, and tumor metastases. In some embodiments, the angiogenesis-dependent disease or condition is an angiogenesis-dependent benign tumor, such as, for example, an angiogenesis-dependent benign tumor selected from the group consisting of hemangiomas, acoustic neuromas, neurofibromas, trachomas, carcinoid tumors, and pyogenic granulomas. In some embodiments, the angiogenesis-dependent disease or condition is an ocular angiogenic disease or condition, such as, for example, an ocular angiogenic disease or condition selected from the group consisting of age-related macular degeneration (AMD), uveitis, ocular melanoma, corneal neovascularization, primary pterygium, HSV stromal keratitis, HSV-1-induced corneal lymphangiogenesis, proliferative diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, corneal graft rejection, neovascular glaucoma, and rubeosis.

In another aspect, the present invention provides methods of treating a subject suffering from an ocular angiogenic disease or condition selected from the group consisting of AMD, uveitis, ocular melanoma, corneal neovascularization, primary pterygium, HSV stromal keratitis, HSV-1-induced corneal lymphangiogenesis, proliferative diabetic retinopathy, diabetic macular edema, retinopathy of prematurity, retinal vein occlusion, corneal graft rejection, neovascular glaucoma, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neuromyelitis optica and rubeosis, comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis.

In another aspect, the present invention provides methods of inhibiting tumor angiogenesis comprising administering to a subject with cancer an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis.

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

41

Re: Narsoplimab generally

Abstracts submitted for presentation will be embargoed by the author(s) and the 2021 TCT Meetings Digital Experience, upon submission.

The embargo will be lifted and abstracts will be made available for viewing at 2PM CT on Monday, January 11, 2021

https://tct.confex.com/img/tandem/2021/banner.jpg
26 - Narsoplimab (OMS721), a Masp-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA)

Monday, February 8, 2021
3:45 PM - 4:00 PM
Authors
Samer K. Khaled
City of Hope National Medical Center
Jaap Jan Boelens
MSK Kids, Memorial Sloan Kettering Cancer Center
Mitchell S. Cairo
New York Medical College
Richard Champlin
The University of Texas MD Anderson Cancer Center
Rafael F. Duarte
ICO/Hospital Duran I Reynals
Sergio A Giralt
1275 York Avenue
Mehdi Hamadani
Medical College of Wisconsin
Vincent T. Ho
Dana-Farber Cancer Institute
Jeffery C Laurence
Weill Cornell Medicine
Nelson Leung
Mayo Clinic
Sebastian Mayer
Weill Cornell Medicine
Wlodzimierz Mendrek
Maria Sklodowska-Curie National Research Institute of Oncology
Olaf Penack
Charité - Universitätsmedizin Berlin
Miguel-Angel Perales
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College
Jameela Sathar
Ampang Hospital
Michael Scordo
Memorial Sloan Kettering Cancer Center
Sumithira Vasu
The Ohio State University
Alessandro Rambaldi
USC Hematology and Laboratory of Cell Therapy “G. Lanzani”, Ospedali Riuniti, Bergamo (Italy)


View Related
https://tct.confex.com/tct/2021/meeting … aper/17019

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

42

Re: Narsoplimab generally

Quite a list of authors! ....... (understatement)

43

Re: Narsoplimab generally

Overview of IgAN by OMER collaborator, Dr Jonathan Barratt of University of Leicester, but funded by Calliditas (a competitor).

A ST poster suggested it "could well be an infomercial about Narsoplimab. Doesn't mention any therapeutic - there is none - but it helps to get an idea about IgAN if you have none."

https://thebalancingact.com/behind-the- … phropathy/

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

44

Re: Narsoplimab generally

The Complement 3 Glomerulopathy Market is Expected to Gain Momentum during the Study Period 2017-30 With a CAGR of 30%,
January 13, 2021, 8:30 AM GMT-5

The Complement 3 Glomerulopathy Market is Expected to Gain Momentum during the
       Study Period 2017-30 With a CAGR of 30%, estimates DelveInsight

  PR Newswire

  LAS VEGAS, Jan. 13, 2021

The Complement 3 Glomerulopathy (C3G) Market is set to grow substantially
owing to the current treatment practices (mainly off-label treatments), launch
of pipeline therapies, increase in funding, better awareness programmes and
advent of novel biomarkers for better diagnosis.

LAS VEGAS, Jan. 13, 2021 /PRNewswire/ -- DelveInsight's ' Complement 3
Glomerulopathy Market  Report 2030 ' report delivers an in-depth understanding
of the Complement 3 Glomerulopathy, historical and forecasted C3G
epidemiology, and current treatment practices. The report proffers a detailed
coverage of the Complement 3 Glomerulopathy market drivers, market barriers
and unmet medical needs that are expected to shape the C3G market outlook in
the next decade in the United States, EU5 (Germany, Spain, Italy, France, and
United Kingdom) and Japan.

Some of the highlights of the Complement 3 Glomerulopathy Market  report: 

  * The present Complement 3 Glomerulopathy market has no approved therapy .
    The treatment market is dominated by off-label prescription drugs such
    Immunosuppressant, Steroids, Renin–angiotensin–aldosterone system
    Inhibitors (RAAS), and other supportive therapies (also including Antibody
    regimens: Eculizumab and Rituximab).
  * The growth of the C3G market size is driven by a few potential emerging
    players, which are investigating their product candidates in the phase II
    clinical developmental stage, namely, Alexion Pharmaceuticals (Danicopan),
    Omeros Corporation (Narsoplimab), Apellis Pharmaceuticals (Pegcetacoplan),
    and Novartis Pharmaceuticals (LNP023 (TBD)).
  * The current C3G market possesses no emerging therapies in their phase III
    developmental stage.
  * The expected launch of C3G pipeline therapies, Danicopan (Alexion
    Pharmaceuticals), Narsoplimab (Omeros Corporation), Pegcetacoplan (Apellis
    Pharmaceuticals) and LNP023 (Novartis Pharmaceuticals), shall accelerate
    the growth of the C3G market size in the coming years.

For more insights into the market landscape, visit Complement 3 Glomerulopathy
therapeutic landscape

Complement 3 Glomerulopathy (C3G) is a rare, chronic renal disease that
hinders the normal filtering mechanism of the kidneys attributable to excess
accumulation of C3G proteins. The total diagnosed C3G prevalence in the 7MM
(the US, EU5 (the UK, Italy, Germany, Spain, and France) and Japan) in 2020 is
estimated to be approximately 8,456 . Years of research have demonstrated that
the condition can have two identifiable types, namely Dense Deposit Disease
(DDD) and C3 Glomerulonephritis (C3GN). However, as per the C3G
epidemiological analysis, C3GN is more prevalent than DDD . Furthermore, 6,032
cases of C3GN and 2,424 cases of DDD were reported to be found in the 7MM.

The Complement 3 Glomerulopathy Market Report provides historical as well as
forecasted epidemiological analysis segmented into:

  * Total Diagnosed Prevalent Population of Complement 3 Glomerulopathy
    (C3G),
  * Type-specific Diagnosed Prevalent Population of Complement 3
    Glomerulopathy (C3G)
  * Age-specific Diagnosed Prevalent Population of Complement 3 Glomerulopathy
    (C3G)

Request for sample for more insights @ Complement 3 Glomerulopathy Market 

Complement 3 glomerulopathy Therapeutic Market

The present Complement 3 Glomerulopathy market is majorly dominated by
off-label prescription drugs. The therapeutic market majorly consists of
immunosuppressants, steroids, renin-angiotensin-aldosterone system inhibitors
(RAAS), and other supportive therapies, including antibody regimens such as
Eculizumab and Rituximab. Furthermore, C3G patients undergo reno-protective
measures, including lifestyle advice, an angiotensin-converting enzyme
inhibitor or angiotensin-receptor blocker to control hypertension and
proteinuria, and lipid-lowering treatment. These medications can improve the
protective effect of immunosuppressive medication. Plasma therapy offered
seemed to have a mixed response as it may be beneficial in C3G patients who
have AKI but not in patients with C3 nephritic factors.

Current Therapies

  * Immunosuppressants
  * Steroids
  * Renin-angiotensin-aldosterone system Inhibitors (RAAS)
  * Other Supportive Therapies (also including Antibody regimens: Eculizumab
    and Rituximab)

The C3G therapy market has major unmet needs owing to a serious lack of
C3G-specific medications. Almost half of the C3G patients undergo kidney
transplantation. Even after kidney transplantation, in around 67–90% and
clinically in 50–60% of patients, C3G relapsed. Although clinical trials are
underway to find an efficient and potential curative option, the enrolment in
the clinical studies owing to the rarity of the disease poses another hurdle.

The emerging C3G market  possesses an intermediate pipeline with key pharma
companies developing several therapies in different stages of development
including Alexion Pharmaceuticals, Omeros Corporation, Apellis
Pharmaceuticals, Avacopan, Novartis, Amyndas Pharmaceuticals, Visterra among
others.

The present Complement 3 Glomerulopathy drug market has no approved therapy,
therefore, the upcoming therapies in the market expected to get launched in
the next decade shall fuel the market size growth and bring more opportunities
for the key pharmaceutical companies investigating their molecules for C3G.
Several organizations such as WeC3G, National Kidney Foundation (NKF),
American Society of Nephrology (ASN), Kidney Disease: International Global
Organization (KDIGO), Japanese Society of Nephrology (JSN), among others are
working vigorously to make people better aware of the condition, its
therapeutic options and diagnosis. Since, the clinical presentation of ICGN
and PIGN is more or less similar to that of C3G, there are often chances of
differential diagnosis leading to delay in right treatment option. Therefore,
there is a requirement for better diagnostics modalities in the Complement 3
Glomerulopathy Market. However, the advent of novel biomarkers in the coming
future is anticipated to overcome this challenge.

Know more about the report offerings @ C3G Therapeutics Market

Complement 3 Glomerulopathy Pipeline Therapies

  * Danicopan (Alexion Pharmaceuticals)
  * Narsoplimab (Omeros Corporation)
  * Pegcetacoplan (Apellis Pharmaceuticals)
  * ChemoCentryx (Avacopan)
  * LNP023 (Novartis Pharmaceuticals)

Scope of the Report

  * Geography Covered : 7MM - The United States, EU5 (Germany, France, Italy,
    Spain, and the United Kingdom), Japan.
  * Study Period : 3-year historical and 11-year forecasted analysis
    (2017-2030).
  * Markets Segmentation : By Geographies and By Therapies (Historical and
    Forecasted, Current and Upcoming)
  * Companies Covered : Alexion Pharmaceuticals, Omeros Corporation, Apellis
    Pharmaceuticals, Avacopan, Novartis, Amyndas Pharmaceuticals, Visterra
    among others.
  * Analysis : Comparative and conjoint analysis of emerging therapies,
    Attribute Analysis.
  * Case Studies
  * KOL's Views
  * Analyst's View

Request for a Webex demo of the report @ Complement 3 Glomerulopathy Market
Landscape 

Table of Contents

1  Key Insights
2  Complement 3 Glomerulopathy Market Overview at a Glance
3  Executive Summary of Complement 3 Glomerulopathy
4  Disease Background and Overview: Complement 3 Glomerulopathy
5  Algorithm for diagnosis and management of C3G
6  Complement 3 Glomerulopathy Epidemiology and Patient Population
7  Country Wise Complement 3 Glomerulopathy Epidemiology
8  Complement 3 Glomerulopathy Treatment
9  KDIGO Guidelines for diagnosis and management of Glomerular Disease: MPGN
   and C3G
10 Recognized Establishments
11 C3G Market Unmet Needs
12 Complement 3 Glomerulopathy Emerging Therapies
13 Key Market Forecast Assumptions
14 Attribute Analysis
15 C3G 7 Major Market Analysis
16 US Market Outlook
17 EU5 Market Outlook
18 Japan Market Outlook
19 KOL Views
20 Complement 3 Glomerulopathy Case Reports
21 C3G Market Drivers
22 C3G Market Barriers
23 SWOT Analysis
24 Appendix
25 DelveInsight Capabilities
26 Disclaimer
27 About DelveInsight

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Logo: https://mma.prnewswire.com/media/108226 … t_Logo.jpg

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

45

Re: Narsoplimab generally

They refer to Narso as in P2.  Are they describing a different indication than TMA?

46

Re: Narsoplimab generally

It is in Phase 2 for CV19 and the BLA for TA-TMA is Phase 2 data from a Phase 2 trial that was accepted by the FDA as a pivotal trial.

I have been using this as an important fact that the Shorts refuse to acknowledge. You can't just submit and NDA or BLA on Phase 2 data, unless the FDA allows you (and probably encourages you). FDA would have never accepted any part of the BLA, had they not awarded BTD and agreed in advance to a BLA with set criteria that would constitute success.

Most drugs don't have such a big improvement over standard of care, in any Phase.

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

47

Re: Narsoplimab generally

Joe Baffo posted this on ST a few minutes ago.
Hope he's right. It will save a lot of time and lives.

Joe Baffo wrote:

The label will be widened IMHO for ALL Endothelial injuries, all.

To quote John Lenin, "Imagine".

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

48

Re: Narsoplimab generally

Well, that's just it.  Is this simply his own personal opinion?  Does he have a connection somewhere, like inside FDA, who has given him this information?  Nice to read of course, but better to hear it from Greg.....who can't say anything like this before FDA releases the label.

49

Re: Narsoplimab generally

alaskasalmonfisher wrote:

Is this simply his own personal opinion?

Yup ....... he said, "IMHO"

I believe it could and likely should happen.  No other treatment comes close to narso's efficacy.

50

Re: Narsoplimab generally

I have been suggesting that would be the simplest and fastest way to get relief to people for many months, but obviously others have concluded it would be great, not just for OMER.

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