151

Re: Narsoplimab generally

Omeros needs to do the trial to show that Narso is a treatment for this.

from the Women's heart center at Cedar-Sinai hospital:

https://www.cedars-sinai.org/programs/h … sting.html

Just add Narso to the list of treatments:

Endothelial Function Testing

The endothelium is a thin membrane that lines the inside of the heart and blood vessels. Endothelial cells release substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function and platelet (a colorless substance in the blood) adhesion.

Endothelial dysfunction has been shown to be of significance in predicting stroke and heart attacks due to the inability of the arteries to dilate fully. The dysfunction may be a result of high blood pressure, diabetes, high cholesterol and smoking.

Studies have shown that endothelial dysfunction precedes the development of artherosclerosis, a chronic disease characterized by abnormal thickening and hardening of the arterial walls with resulting loss of elasticity. Artherosclerosis may cause a stroke or heart attack.
What Tests Are Used to Determine Endothelial Function

Acetylcholine endothelial function and adenosine coronary flow reserve tests enhance a physician's ability to diagnose and treat patients with endothelial dysfunction. The two-step test consists of:

    Administration of the drug adenosine, which normally causes the small vessels of the heart to dilate, is injected into one of the coronary arteries and the amount of blood flow is measured.
    Next, the drug acetylcholine, which normally causes dilation in the large arteries, is injected and the amount of blood flow is again measured.

If either test shows decreased blood flow to the heart muscle, a diagnosis of endothelial dysfunction and microvascular disease can be made. With evidence of insufficient blood flow to the heart muscle and open coronary arteries, medical treatment can be directed at the specific problem.

Physicians also may use non-invasive procedures to determine an artery's health and elasticity:

    Carotid Duplex Ultrasound: Ultrasound is a procedure that uses sound waves to "see" inside the body. Carotid Duplex Ultrasound is performed to evaluate symptoms including dizziness, loss of memory, stroke, loss of control of muscles and other findings that might result from narrowing or blockage of the vessels (carotid arteries) on either side of the neck.
    Pulse Wave Velocity (PWV). PWV measures, via ultrasound, the flow of blood from the carotid artery to the femoral artery (the chief artery of the thigh). By calculating the time of travel of the pulse wave, imaging specialists can determine if any blockage exists.
    Pressure Pulsation Signal. The pressure pulsation signal, using a blood pressure cuff combined with a graphic computer display, measures diastolic, systolic and mean artery pressure.

Treating Endothelial Dysfunction

Endothelial dysfunction responds favorably to a healthful diet and exercise. Exercising to maintain a healthy weight decreases a person's risk of developing certain diseases, including type 2 diabetes and high blood pressure.

Aerobic Exercise: The heart is a muscle and needs a good workout. Aerobic exercise gets the heart pumping and quickens breathing, resulting in a more efficient delivery of oxygen-carrying blood cells. Strength and flexibility training are of benefit too. Patients should always check with their physician before instituting a new exercise regimen or ratcheting up their existing routine.

Pharmacologic interventions may include:

    ACE inhibitors used for treating high blood pressure and heart failure
    Nitrate therapy
    Lipid-lowering pharmaceuticals used for managing blood cholesterol levels
    Alpha-beta blockers for blood pressure management
    Novel therapies that include ranolazine, aminophylline and experimental therapies

External counter pulsation (ECP) therapy is another treatment option. Lying on a table or bed, pressure cuffs are fitted to the patient's thighs, hips and calves. The cuffs inflate and deflate in sync with the patient's heart rhythm, supplying the heart with extra oxygen-rich blood in the resting phase. The extra blood supply stimulates growth of the surrounding blood vessels, improving the supply of blood to the heart.

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 am following this up because it is worrying if something can compete with Narso MOA.
=======================
Nafamostat

https://pubchem.ncbi.nlm.nih.gov/compound/Nafamo
Cite
Download
PubChem CID    4413
Structure   
Nafamostat_small.png
Nafamostat_3D_Structure.png
Find Similar Structures
Molecular Formula    C19H17N5O2
Synonyms   
Nafamostat

81525-10-2

Nafamostat [INN]

UNII-Y25LQ0H97D

Nafamstat

More...
Molecular Weight   
347.4 g/mol

Dates   
Modify
2021-03-27

Create
2005-03-25

Nafamostat is a broad-spectrum, synthetic serine protease inhibitor, with anticoagulant, anti-inflammatory, mucus clearing, and potential antiviral activities. Upon administration, nafamostat inhibits the activities of a variety of proteases, including thrombin, plasmin, kallikrein, trypsin, and Cl esterase in the complement system, and factors VIIa, Xa, and XIIa in the coagulation system. Although the mechanism of action of nafamostat is not fully understood, trypsinogen activation in the pancreas is known to be a trigger reaction in the development of pancreatitis. Nafamostat blocks the activation of trypsinogen to trypsin and the inflammatory cascade that follows. Nafamostat may also decrease epithelial sodium channel (ENaC) activity and increase mucus clearance in the airways. ENaC activity is increased in cystic fibrosis. In addition, nafamostat may inhibit the activity of transmembrane protease, serine 2 (TMPRSS2), a host cell serine protease that mediates viral cell entry for influenza virus and coronavirus, thereby inhibiting viral infection and replication.

NCI Thesaurus (NCIt)
Nafamostat is a member of benzoic acids and a member of guanidines.

Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.
==============================
https://www.eurekalert.org/pub_releases … 032420.php

NEWS RELEASE 30-MAR-2020
Nafamostat is expected to prevent the transmission of new coronavirus infection (COVID-19)
THE INSTITUTE OF MEDICAL SCIENCE, THE UNIVERSITY OF TOKYO

     
IMAGE
IMAGE: NAFAMOSTAT, AN EXISTING SAFE DRUG, MAY INHIBIT ENTRY OF SARS-COV-2. view more

CREDIT: IMAGE: 2020 THE UNIVERSITY OF TOKYO.

Nafamostat mesylate (brand name: Fusan), which is the drug used to treat acute pancreatitis, may effectively block the requisite viral entry process the new coronavirus (SARS-CoV-2) uses to spread and cause disease (COVID-19). The University of Tokyo announced these new findings on March 18, 2020.

According to the new research, Nafamostat can prevent the fusion of the envelope of the virus with host cell surface membranes, the first step in infection with the causative virus SARS-CoV-2. Nafamostat can inhibit the membrane fusion at a concentration less than one-tenth that of Camostat mesylate (brand name: Foypan), which was recently identified by a German group as an inhibitor of SARS-CoV-2 infection (Reference 1).

Both Nafamostat and Camostat were developed in Japan as treatments for pancreatitis and some other diseases. These drugs have been prescribed in Japan for many years and have adequate clinical data with regard to safety.

The University of Tokyo plans to launch clinical trials in April 2020 in order to evaluate the effectiveness of these two drugs for treating COVID-19.

Search for therapeutics from existing drugs that have been confirmed to be safe (drug repurposing) seems to be extremely worthwhile

Professor Jun-ichiro Inoue and Assistant Professor Mizuki Yamamoto of the Research Center for Asian Infectious Diseases of the Institute of Medical Science, the University of Tokyo, have identified Nafamostat as a strong candidate to fight COVID-19.

Even after the World Health Organization's declaration of a pandemic, no drug has yet been shown to be effective for treating COVID-19 caused by the new coronavirus (SARS-CoV-2). The development of effective drugs is an urgent issue.

"Considering that SARS-CoV-2 infection is already spreading worldwide, drug repurposing (*1), which searches for therapeutics among existing drugs with established safety records, seems to be extremely worthwhile," Inoue said.

The genomic RNA of coronaviruses such as SARS-CoV-2 is surrounded by an envelope composed of a lipid bilayer and envelope proteins. SARS-CoV-2 initiates human cell entry after the Spike protein (S protein) present on the envelope binds to a cell membrane receptor ACE2 (*2). The S protein is cleaved into S1 and S2 by a human cell-derived protease (proteolytic enzyme) that is assumed to be Furin. S1 then binds to its receptor, ACE2. The other fragment, S2, is cleaved by TMPRSS2 (*3), a human cell surface serine protease, resulting in membrane fusion. According to Hoffmann et al., ACE2 and TMPRSS2 are essential in airway cells for SARS-CoV-2 infection (Reference 1).

The research group already reported in 2016 that Nafamostat effectively inhibits MERS-CoV S protein-initiated membrane fusion. The researchers did this using the Dual Split Protein (DSP) reporter fusion assay (*4) to screen a library consisting of 1,017 FDA-approved drugs. This screening result, together with experimental data from MERS-CoV infection of cultured airway epithelial cell-derived Calu-3 cells (*5), led them to propose that Nafamostat could be effective at inhibiting MERS-CoV infection (Reference 2).

In the present study, they newly established a SARS-CoV-2 S protein-initiated fusion assay and found that in the concentration range from 10 to 1000 nM, Nafamostat suppressed SARS-CoV-2 S protein-initiated fusion utilizing 293FT cells (derived from human fetal kidney) (*6) ectopically expressing ACE2 and TMPRSS2. Then, a similar experiment was performed using Calu-3 cells, which are considered an appropriate model for the cells SARS-CoV infects in humans. Low concentrations in the 1-10 nM range of Nafamostat significantly suppressed membrane fusion. This is almost the same as the concentration range for inhibition of membrane fusion by the MERS-CoV S protein.

The research group also compared the effects of Nafamostat and Camostat. They found that Nafamostat inhibited SARS-CoV-2 S protein-initiated fusion at a concentration less than one-tenth that needed for Camostat. Based on the above explanation, they concluded that Nafamostat is the most effective drug against SARS-CoV-2 S protein-initiated fusion among the protease inhibitors used in clinical practice and tested so far.

Future potential of Nafamostat and Camostat

Nafamostat is administered clinically by intravenous infusion. The research group speculated that the blood concentration of Nafamostat after administration would exceed the concentration needed experimentally to inhibit membrane fusion via the SARS-CoV-2 S protein. Therefore, it is expected that Nafamostat will prevent SARS-CoV-2 from entering human cells. Camostat is an oral drug. Blood levels after oral administration may be inferior to Nafamostat.

"Both drugs could be used alone, or in combination with other antiviral drugs that target separate processes needed for virus production, such as RNA replication or viral protein processing," said Inoue.

###

Research Notes

(*1) drug repurposing: An attempt to find new effective uses for existing drugs whose safety in humans has already been adequately established in clinical practice.

(*2) ACE2: Angiotensin converting enzyme 2, which catalyzes the conversion of angiotensin II to angiotensin 1-7. ACE2 acts as a receptor for both SARS-CoV and SARS-CoV-2.

(*3) TMPRSS2: Transmembrane protease, serine 2. A serine protease present in the cell surface membrane. The SARS-CoV-2 coronavirus S protein is said to undergo proteolysis by TMPRSS2 after binding to the host receptor. Absent protein degradation, membrane fusion cannot proceed. Nafamostat is thought to inhibit S protein-initiated membrane fusion by inhibiting TMPRSS2 activity.

(*4) fusion assay system: A DSP (Dual Split Protein) reporter is used to detect fusion. DSP is a chimeric protein of split Renilla luciferase and split GFP (DSP1-7, DSP8-11), which has neither activity by itself, but can regain both GFP and luciferase activity upon self-association via its split GFP domain to a partner protein. By expressing these two proteins in separate cells, fusion between the cells can be quantified based on restored GFP and luciferase activity.

(*5) Calu-3 cells: Human bronchial epithelial cell-derived immortalized cells established from human lung cancer. It is used for functional analysis of respiratory cells. These cells are our appropriate model for the lung epithelial cells that SARS-CoV2 and MERS-CoV actually infect.

(*6) 293FT cell: an immortalized cell line derived from human fetal kidney. It has excellent properties such as fast cell growth and easy gene transfer.

References

1. Hoffmann et al. Cell 181, 1-10 (2020) https://www.sciencedirect.com/science/a … via%3Dihub

2. Yamamoto et al. Antimicrob Agents Chemother 60, 6532-6539 (2016) https://aac.asm.org/content/60/11/6532

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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

153

Re: Narsoplimab generally

Is it OK to ask Greg what he thinks of this drug, as to being a competitor of Narsoplimab?

154

Re: Narsoplimab generally

I already sent him an email, asking, Avi.

I expect he will answer this one but it may be by a phone call and there may be a delay if he's busy.

I will report once I hear something.

Obviously, this is a potentially worrisome bit of information because some large Pharma may want to license or just produce generic nafamostat if/when they see a way around Omeros patents, especially if narsoplimab gets approved and starts getting successful.

Being the ONLY drug to inhibit the MASP2 and thereby control the Lectin Pathway (LP) is valuable. Seeing other things that affect MASP2 and LP suggests there is less defense against other drug companies... and that all these companies trying to compete downstream or on other pathways of complement will wise up sooner or later and potentially cause us problems.

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

155

Re: Narsoplimab generally

Sure, I figured, but wanted to ask anyway to be sure.  It'll be interesting to hear what he has to say.  Greg knows more about the science of all of this.  Let's just wait to see what he says.....

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Re: Narsoplimab generally

This is from the 10K

"MASP-2 Program - Narsoplimab (OMS721). We hold worldwide exclusive licenses to rights in connection with
MASP-2, the antibodies targeting MASP-2 and the therapeutic applications for those antibodies from the
University of Leicester, MRC and Helion. As of February 10, 2021, we exclusively controlled 24 issued patents
and 40 pending patent applications in the U.S., and 568 issued patents and 385 pending patent applications in
foreign markets, related to our MASP-2 program. Our MASP-2 and narsoplimab patents have terms that will
expire as late as 2037 and, if currently pending patent applications are issued, as late as 2040"

This is apparently weaker than I thought.
And I do not like the phrase "in connection with".

Where do with control access to LP by having exclusive rights to the MASP2 target?

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

157

Re: Narsoplimab generally

I am concerned about these and asked Greg about Famostat, but have received no reply yet. I also asked (separately) about the Chinese application for a MASP2 inhibitor and he responded  the same day that OMER is aware of this and unconcerned. There is an oral version of Famostat (which is given IV) called Camostat (approved name is FOYAN).

Camostat mesylate is approved to treat Pancreatitis and supposedly inhibits cancer metastasis. It is a Serine Protease Inhibitor, like Narsoplimab. But it is a chemical and not a Biologic, like Famostat. I do not know if it would be considered to be a MASP2 inhibitor but I aim to find out.

I think these target the Lectin pathway but the more suitable nafamostat is less specific in its anti-protease activity than is needed for an action-specific drug. https://www.jimmunol.org/content/185/7/4169

Camostat is related to Famostat (aka commercial name: FUSAN and FUTHAN), which lasts much longer (but not very long) and is now being tested against CV19. Famostat is approved since 1986 in Japan for treating pancreatitis (inflamed pancreas that damages the organ and may lead to Type 1 diabetes). Famostat seems a more likely competitor to Narso than Camostat.

Camostat mesylate is a glycosylphosphatidylinositol-anchored serine protease inhibitor. It inhibits airway epithelial sodium channel function and it is reported to inhibit the generation of TGF-beta. It is currently being researched as a potential treatment for COVID-19.

This paper from 2010 has an interesting claim: https://www.jimmunol.org/content/185/7/4169

"In conclusion, we have produced, to our knowledge, the first lectin pathway-specific SP inhibitors. These selective MASP inhibitors are valuable tools for basic research aiming to explore the detailed mechanism of complement activation in different physiological situations as well as they can serve as lead molecules for subsequent drug development process."

Narsoplimab was not mentioned by name in the paper.

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

158

Re: Narsoplimab generally

This is certainly interesting.  Do the initial patents for Narso date back to 2010?

I wonder if those companies ever tried these drugs for more general kidney disease as is being considered for narso.

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Re: Narsoplimab generally

The other drugs seem to be less specific (nafamostat and camostat) and they are used in Japan for approved indications but the article seem to talk only about pancreatitis.

Nafamostat is being used in a CV19 trial.

I found other MASP2 inhibitors mostly of non-human antibodies that are probably used in research with animals.

I am trying to make sense about what this means. I think it means OMER has USA and COMPOSITION OF MATTER, and MANUFACTURING patents, but not the exclusive right to drug MASP2 or the Lectin pathway in some different way.

Given that ALXN must know about the other inhibitors available and surely wanted to hurt its competitor or eventual competitor, they could have licensed or bought one of these drug candidates or drugs, but they apparently didn't, which perhaps means that somehow Omeros has more protection than the 3 classes I mentioned.

I am looking into these possibilities so we don't get overconfident about what we have been led to believe about Omeros' complement drugs.

Nafamostat is in trial for Covid now, so in some sense that could be good news if nafam's MOA s like narso's but just not as specific and robust.

We shall see.

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

160

Re: Narsoplimab generally

This is 100 microliters of MASP-2, Human, mAb 8B5.
https://www.hycultbiotech.com/media/catalog/product/placeholder/default/Antibody_vial_4.jpg

It costs $552 here:
https://www.hycultbiotech.com/hm2190-100ug

There are 1,000,000 micrograms in a gram (and a billion in 1kg).

There are 10,000 of these little vials in 1 gram of MASP2i.

That means, if you buy a gram's worth of these you'd pay $5,520,000.

Obviously the 100 microliter vial i to use for mice or rats in the lab.

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

161

Re: Narsoplimab generally

Alan, are you thinking OMER has the U.S. due to where they are in terms of approval process with the FDA, or because of IPR protection?

I'd be surprised if a company would patent IP (IP generically, not just drugs or biologics) in only their home country and not try in a major market such as the U.S.  If OMER has patents in the U.S. then the patent office should have examined prior art, so perhaps these companies either didn't try to patent in the U.S., or didn't succeed due to OMER having already granted patents. 

If OMER demonstrates an effective use of MASP2 inhibitors and gets approval from the FDA that the other companies either didn't realize, or didn't pursue through trials, is there actual legal protection in the U.S., or does OMER merely have a first mover advantage.  If the other companies have IP in other country ahead of OMER, can they either file in the U.S. based on that earlier work and assert here, or can they easily follow in OMER footsteps once the way is paved.  The fact that another similar drug is as far or further along with covid might speed this up.  Hopefully OMER was actually ahead of the other companies discovery wise.

I imagine Greg is all over this,

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Re: Narsoplimab generally

Omeros has patents worldwide according to what they say.
But it is much more complicated than they.

They should have very strong protection on the narso molecule (composition) and manufacture and patents on its USE. The other agents I have found are NOT the same, for instance not monoclonal antibodies or fully humanized.

It seems like the other drugs that are serine protease inhibitors are much less specific in their action within the body, which tends to makes them less useful to treat specific problems and more likely to mess up other things that give them a more dangerous profile.

If someone like Alexion has not snapped these drugs up for themselves, we have tot think that they really aren't better than narsoplimab, even though nafamostat and camostat are approved in Japan for pancreatitis. Japan has an odd approval  protocol that is more about price and less about efficacy.

I will be paying more attention to IP as things unfold.

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

163

Re: Narsoplimab generally

The only dose-dependent patient characteristic for narso is patient weight

https://www.onclive.com/view/weight-bas … n-hsct-tma

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

164

Re: Narsoplimab generally

IgAN competition will be first with a probably worse drug.

http://www.trustintelligence.com/viewto … 5590#p5590

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

165

Re: Narsoplimab generally

That isn't good for OMEROS stock price in the short term.

166

Re: Narsoplimab generally

Been known for a long time...and Omer is up today (so is CALT of course).

The 2 biggest OMER catalysts don't include IgAN at this point and the low market cap of OMER says that the Market is not actively discounting the value of much at all now, not even what will happen in the next 6 months. Not even that the AVERAGE BLA after submission has an 85% chance of approval, much less a deadly indication and a drug that saves at least half those who would have died.

We'd be much better off if the Market actively discounted future business prospects.

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

167 (edited by enthusd 2021-04-28 18:53:01)

Re: Narsoplimab generally

I feel really bad for one of the women I work with who is Indian. Her mother, father, and several nieces, who live in India, all came down with Covid by attending a funeral.

Her mom and others have recovered but her dad is in the process of getting severe Covid, dropping oxygen levels, and a fear of lung infection, quite possibly the blood clots make it seem like a lung infection, or he might also actually have one.  She mentioned there are hundreds of people waiting to get chest X-rays. They can’t even keep up with that there, let alone have enough oxygen

168

Re: Narsoplimab generally

Must be horrible to have almost the rest of your immediate family be sick, much less clinging to life.
The pandemic has caused record human suffering.

And those with money are leaving to get care elsewhere.
Many doing it when sick.

I read somewhere that at least one plane from India to Canada had half the passengers test positive. We can almost bet that most of the ones that didn't test positive, will, because of that flight.

There are many East-Asians in Canada, especially in BC around Vancouver. It spreads through their neighborhood and beyond.

I could not understand why it took so long for India to have major problems given the huge crowded cities and poor sanitation. When you think of it, the inhabitants probably have a very experienced immune system.

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

169

Re: Narsoplimab generally

Supposedly India had a very strict lockdown protocol originally and the relaxed it when cases were so low around the end of last year

170

Re: Narsoplimab generally

Interesting that human discipline, even in a dangerous situation, has its limits.
I suppose this is why the Armed Forces break down people's personality and personal idiosyncrasies as part of training them to be disciplined under horrible conditions for extended periods.

And the politicians....

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

171

Re: Narsoplimab generally

https://wglv4y2mfymb2wapa6zo3csk44-ac5f … o-farmaco/

An article about the phase 3 IgAN trial of narsoplimab, in Italy starting (translated to English).

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

172

Re: Narsoplimab generally

PDUFA delay of 2/3 months = "goal extension"
fda.gov/media/101907/download 

"Nevertheless, the rate of goal extensions was slightly lower in the Program than in the baseline, and a higher proportion of Program applications with a goal extension received first-cycle approval. Within the Program, applications with a goal extension also exhibited a higher first-cycle approval rate than applications without a goal extension (89.7% [n=39], 76.5% [n=132], p = 0.072). 28 This is in accordance with the Commitment Letter expectation that, except for rare cases, goal extensions are to be used when the amendment can be expected to resolve the deficiencies in the current cycle. Applications with goal extensions, on average, took 3.74 months longer (p = <0.001)29 to reach first-cycle approval than applications without goal extensions. This is generally less than would be experienced with a first-cycle CR followed by resubmission and a second review cycle."

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

See this http://www.trustintelligence.com/viewto … 6683#p6683
and the link that Jim posted on the post just prior.

Narso treatments, in IgAN and HSCT tend to all reduced dosing with steroids, or their elimination.
The high doses of steroids used in India to fight CV19, is probably partially because generic steroids are a cheap treatmnt (along with heparin which is also cheap) and they cannot afford something like narso, given they have too many people and not enough money.

But steroids is standard of care for CV19 outside of India too, and for the same basic reasons it is used in India.
I am surprised we have not heard of these fungal fatalities outside of India, but perhaps they are being classified as something that is NOT CV19-related deaths, by a system that seeks to see the Pandemic Death Rate decline (byalmost any means possible).

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

This patent has been approved (having been allowed, some time ago).
Filed:    August 14, 2018
============
https://patft.uspto.gov/netacgi/nph-Par … ANM/Omeros

Methods for treating and/or preventing graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with hematopoietic stem cell transplant

Abstract
In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with a hematopoietic stem cell transplant. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.

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

175

Re: Narsoplimab generally

Omeros has applied for a new trademark. It is for Narso's patient support program (which I presume charges less for narso treatment).
It is:
https://uspto.report/TM/90739907/mark.png

you can get the bare bones details about the application, here:
https://uspto.report/TM/90739907

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

176

Re: Narsoplimab generally

Does this imply YARTEMLEA is narso's new name?

177

Re: Narsoplimab generally

yes, I reported this was likely, long ago.
Yesterday's filing clinches it.

I don't like it.

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

178

Re: Narsoplimab generally

So many names are taken. I'm not even sure how to pronounce that new name. wink

179

Re: Narsoplimab generally

"NAR-SEW"
<ggg>

I would have gone with something short.
Instead of Yartemlea (accent on the second e, I presume), why not just

Temlea

There are a slew of naming rules and consideration, given the large number of languages.

As an amusing example, when this company tried to market its Big John's beans in Canada it had to make a French label. It may have employed someone from their France office, because they came up with Gros Jos as the name of the lumberjack.

It had to be withdrawn in Canada and relabeled because "Gros Jos" in Quebec slang is 'Big Breasts'.

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

180

Re: Narsoplimab generally

Yartemlea pivotal trail data will be presented on Jun11th at the European Hematology Association Congress "Corporate Analyst Meeting".

This was copied from the alert from my brokers.
I did not know there was a Corporate Analyst Meeting at these things.

I am not expecting any effect on the share price unless some of the Analysts suddenly get impressed by the trial...or they ask questions that reveals things of interest that lead to a Analyst upgrade or a higher price projection by an analyst.

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

181

Re: Narsoplimab generally

I will pay you twice the next TIPS renewal fee if your can pronounce Yartemlea correctly (you get ten tries).  What a goofy name.

182

Re: Narsoplimab generally

I just did it, Jim.
When can I expect the transfer?

It is YAR-TEM-LEÉ-A

Raymealta would sound better to me and it uses the same letters.
or
Raymelata would allow for fewer pronunciation variations.
or
Yamelatra if they need it to start with a Y.

BTW, unsurprisingly, Biden 2022 budget "Wish List" includes Medicare being able to negotiate with drug companies to reduce drug cost.

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

183

Re: Narsoplimab generally

Nah, sorry, I don't believe you. That pronunciation sounds like a hippie gal I dated in the 1970s.

184

Re: Narsoplimab generally

The data from FDA actions in approving new drugs and indications are clear.
At about the half-way point to the PDUFA, the primary reviewer has considered everything in the application. The full committee has a meeting an decides what to do, next.

If they will approve the drug they may ask for more information. 
When they get the information back.... the look at it.
If they are planning on approving the drug, the can declare the added information to be a "Major Amendment" to the BLA/NDA. The regulations say this gives them an extra 3 months before the PDUFA.
And then they approve.

The drugs they do not want to approve, they just give a CRL (a refusal) and don't ask for more information, or after they get the new information they request, the look at it and then issue a Complete Response Letter (CRL).

from ST yesterday (there are over 30 cases of this since 2005), by @Peter_Cowling
***********
$OMER    got a Major Amendment. 

Historically, going back to 2005, every single drug that gets a Major Amendment, gets FDA approval. 

EVERY SINGLE ONE! 

This includes stuff like BIIBs Alz. drug, which got approval today, despite it seeming unlikely.

Drugs the FDA doesn't like right now gets a CRL, those that it does got a Major Amendment.

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

185

Re: Narsoplimab generally

I wrote to Greg yesterday to ask him whether the narso HSCT CUP was active *not whether it was open but whether it was treating HSCT patients whose MDs ask for the drug.

I mentioned  that I thought the CUP being active was a good way to help the launch once it was approved.

I am not surprised there has been no reply yet. I doubt there will be one.
I wrote because I fear overconfidence and a slow roll-out and shareholder disappointment, just as I expect him to keep number secret until the Q4 is reported in March 2022.

I really don't want to be concerned about the number of patients treated for another 9 months.
I could have a baby by then!

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

186

Re: Narsoplimab generally

OMEROS ANNOUNCES PRELIMINARY RESULTS FROM PHASE 1 CLINICAL TRIAL OF OMS906
-- Results show good safety and PK/PD profile consistent with low-dose, once-monthly subcutaneous dosing --

SEATTLE--(BUSINESS WIRE)--Jun. 9, 2021-- Omeros Corporation (Nasdaq: OMER), a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, immunologic diseases (e.g., complement-mediated diseases and cancers) and central nervous system disorders, today announced preliminary results from the Phase 1 clinical trial of its MASP-3 inhibitor OMS906. The ongoing trial is designed as a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) and subcutaneous (SC) administration of OMS906 to healthy adult volunteers. OMS906 has been well tolerated at all doses tested. Preliminary human PK and PD data are consistent with once-monthly SC dosing.

MASP-3, the key activator of the alternative pathway of complement, converts pro-complement factor D (pro-CFD) to mature CFD. Inhibition of MASP-3 by OMS906 in nonhuman primates reduces systemic levels of mature CFD to below the threshold of detection, correspondingly blocking the alternative pathway of complement. The OMS906 Phase 1 clinical trial design consists of both single- and multiple-ascending dose cohorts. Pharmacodynamic response to OMS906 in the Phase 1 trial is being assessed by quantitation of mature CFD in plasma. In the single-ascending dose stage, 48 subjects have been evaluated to date across a series of IV and SC doses. Findings include:

OMS906, administered up to 5 mg/kg, has been well tolerated at all IV and SC doses tested with no apparent safety signals
Single 3 mg/kg IV dose of OMS906 suppresses mature CFD below minimum detectable levels for 4 weeks
Single lowest SC dose of OMS906 suppresses mature CFD at or below minimum detectable levels for 4 weeks
Dose-dependent PK/PD profile across all cohorts is favorable and supports low-dose, once-monthly or less frequent subcutaneous dosing
The study is ongoing with additional single- and multiple-dose cohorts to determine the pharmacologic dose range and optimal frequency for subcutaneous administration.

“The data from the Phase 1 clinical trial to date confirm our expectations for the role and dosing of OMS906 in humans,” said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. “The data validate, in humans, the function of MASP-3 – the key activator of the alternative pathway – as a regulator of CFD and support the potential of OMS906 as a safe and long-acting therapeutic for the treatment of alternative pathway-related diseases and disorders. Omeros has built a strong intellectual property position around MASP-3 inhibition, and we look forward to completing the current study and advancing to a Phase 2 clinical trial as quickly as possible.”

About Omeros’ MASP-3 Inhibitor Program

The complement system plays a key role in inflammation and becomes activated as a result of tissue damage or microbial infection. Omeros’ MASP-3 inhibitor program includes potent molecules selectively inhibiting mannan-binding lectin-associated serine protease-3 (MASP-3), the protein activator of the alternative pathway of complement (APC). APC inhibitors are thought to have preventive or therapeutic effects across a broad range of diseases including paroxysmal nocturnal hemoglobinuria, hemolytic uremic syndrome (HUS), atypical HUS, traumatic brain injury, arthritis, wet age-related macular degeneration, ischemia-reperfusion injury, transplant-related complications and other immune-related disorders. Omeros is developing both antibody and small molecules to block MASP-3. Through its growing intellectual property position, Omeros exclusively controls inhibitors of the protein activator of the alternative pathway (MASP-3) and, with its OMS721 program, inhibitors of the effector enzyme of the lectin pathway (MASP-2), allowing the company to target with unprecedented precision diseases caused by dysregulation of one or both of these pathways.

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

These are VERY good results.
And Greg has kept certain things quiet.
Many lucrative indications.... and complete block of MASP3 is great.

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

188

Re: Narsoplimab generally

OMEROS’ NARSOPLIMAB PIVOTAL TRIAL DATA SHARED IN ORAL PRESENTATION AT 2021 ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
-- Data on Organ Function Improvement Presented by Chief of Adult Bone Marrow Transplant Service at Memorial Sloan Kettering --

SEATTLE--(BUSINESS WIRE)--Jun. 14, 2021-- Omeros Corporation (Nasdaq: OMER) today announced that data on organ function improvement from its pivotal trial of narsoplimab for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) were shared during an oral presentation at the virtual edition of the 26th Congress of the European Hematology Association (EHA). The presentation, entitled Narsoplimab (OMS721) Treatment Contributes to Improvements in Organ Function in Adult Patients with High-Risk Transplant-Associated Thrombotic Microangiopathy, was delivered last Friday by Miguel-Angel Perales, M.D., Chief of Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center. The organ function improvement data presented underscore the potential of narsoplimab as a significant advance in the treatment of often fatal HSCT-TMA.

The trial’s findings include:

The study population was high-risk, with 93 percent having multiple risk factors for poor outcomes, and highly reflective of “real-world” clinical practice
At baseline:
75% of patients had kidney dysfunction
57% had neurologic dysfunction
18% had pulmonary dysfunction
50% had multiple organ TMA involvement
86% had significant infection
68% had graft versus host disease (GVHD)
61% of the intent-to-treat (ITT) population (any patient receiving at least 1 dose of narsoplimab) and 74% of the per-protocol (PP) population (those patients receiving ≥ 4 weeks of dosing) responded to narsoplimab based on improvement in laboratory TMA markers (platelet count improvement and reduction in LDH levels) and clinical status (organ function or freedom from transfusion)
74% of eligible patients in the ITT population experienced improvement in organ function (67%, 50% and 100% in kidney, neurologic, or gastrointestinal function, respectively); 77% of eligible patients in the PP population experienced organ function improvement
48% of eligible patients in the ITT population and 55% in the PP population experienced freedom from transfusion
Narsoplimab was well tolerated in this very sick population
The most common adverse events were pyrexia, diarrhea, vomiting, nausea, neutropenia, fatigue, and hypokalemia, all common in HSCT
Six patients died during the core study period due to causes common in HSCT
There were no study discontinuations due to non-fatal adverse events
Detailed data and findings from the study are being submitted to a peer-reviewed scientific journal for publication.

Dr. Perales’ question-and-answer panel discussion for his presentation is scheduled for Tuesday, June 15, at 1:00-1:45 pm CEST/7:00-7:45 am EDT and will be available to registered attendees through the EHA Congress virtual platform.

In severe cases of HSCT-TMA, mortality can exceed 90 percent and, even in those who survive, significant morbidity is common with chronic organ injury often persisting. There is no approved treatment for HSCT-TMA. A Biologics License Application for use of narsoplimab in the treatment of HSCT-TMA is under Priority Review by the US Food and Drug Administration (FDA) with a Prescription Drug User Fee Act action date of October 17, 2021.

About Hematopoietic Stem Cell Transplant-associated Thrombotic Microangiopathy

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a significant and often lethal complication of stem cell transplantation. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by conditioning regimens, immunosuppressant therapies, infection, graft-versus-host disease, and other factors associated with stem cell transplantation. Endothelial damage, which activates the lectin pathway of complement, plays a central role in the development of HSCT-TMA. The condition occurs in both autologous and allogeneic transplants but is more common in the allogeneic population. In the United States and Europe, approximately 25,000 to 30,000 allogeneic transplants are performed annually. Recent reports in both adult and pediatric allogeneic stem cell transplant populations have found an approximately 40-percent incidence of HSCT-TMA, and high-risk features may be present in up to 80 percent of these patients. In severe cases of HSCT-TMA, mortality can exceed 90 percent and, even in those who survive, long-term renal sequalae (e.g., dialysis) are common. There is no approved therapy or standard of care for HSCT-TMA.

About Narsoplimab

Narsoplimab, also known as “OMS721,” is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2.

A biologics license application (BLA) is under priority review by the U.S. FDA for use of narsoplimab in the treatment of HSCT-TMA, and the drug is in Phase 3 clinical programs for immunoglobulin A (IgA) nephropathy and atypical hemolytic uremic syndrome (aHUS). Narsoplimab is also being evaluated for the treatment of COVID-19 as part of the I-SPY-COVID-19 platform trial sponsored by Quantum Leap Healthcare Collaborative. The FDA has granted narsoplimab breakthrough therapy designations for HSCT-TMA and for IgA nephropathy; orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of HSCT-TMA and for the treatment of IgA nephropathy; and fast track designation for the treatment of patients with aHUS. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in HSCT and for treatment of primary IgA nephropathy.

About Omeros Corporation

Omeros is a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting inflammation, immunologic diseases (e.g., complement-mediated diseases and cancers) and central nervous system disorders. Its commercial product OMIDRIA® (phenylephrine and ketorolac intraocular solution) 1%/0.3% continues to gain market share in cataract surgery. Omeros’ lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application under priority review by FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. Narsoplimab is also in multiple late-stage clinical development programs focused on other complement-mediated disorders, including IgA nephropathy, atypical hemolytic uremic syndrome and COVID-19. OMS906, Omeros’ inhibitor of MASP-3, the key activator of the alternative pathway of complement, is in a Phase 1 clinical trial, and the company’s PDE7 inhibitor program OMS527, targeting addiction and movement disorders, has successfully completed a Phase 1 trial. Omeros’ pipeline holds a diverse group of preclinical programs including a proprietary-asset-enabled antibody-generating technology and a proprietary GPCR platform through which it controls 54 GPCR drug targets and their corresponding compounds. One of these novel targets, GPR174, modulates a new cancer immunity axis recently discovered by Omeros, and the company is advancing GPR174-targeting antibodies and small-molecule inhibitors. For more information about Omeros and its programs, visit www.omeros.com.

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

189 (edited by Alan Robert Ross 2021-06-14 09:04:05)

Re: Narsoplimab generally

The above presentation is part of Omeros' marketing project to acquaint European transplant/hematology doctors with narsoplimab. Dr. Perales is very good at explaining and clearly someone who believes in narsoplimab. He probably speaks more than just English and Spanish, as well.

Note that Greg gives a presentation at a Biotech Conference tomorrow.

OMEROS TO PRESENT AT THE BOFA 2021 NAPA BIOPHARMA VIRTUAL CONFERENCE
SEATTLE--(BUSINESS WIRE)--Jun. 9, 2021-- Omeros Corporation (Nasdaq: OMER), today announced that Gregory A. Demopulos, M.D., chairman and chief executive officer, will present at the BofA 2021 Napa BioPharma Virtual Conference next week. The fireside chat with Bank of America analyst, Geoff Meacham, PhD, is scheduled for Tuesday, June 15, 2021 at 4:30 p.m. EDT.

The presentation will be webcast. The live and archived webcasts can be accessed at https://investor.omeros.com/upcoming-events. The archived webcast will be available for 30 days.

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

190

Re: Narsoplimab generally

An Update on the Current State of Management and Clinical Trials for IgA Nephropathy

https://www.mdpi.com/2077-0383/10/11/2493/htm

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

191

Re: Narsoplimab generally

New patent application published https://appft.uspto.gov/netacgi/nph-Par … 0210189009

Claims


1. A method for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer or an angiogenesis-dependent benign tumor comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis, wherein the MASP-2 inhibitory agent is a MASP-2 inhibitory monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:6.

2. The method of claim 1, wherein the subject is suffering from an angiogenesis-dependent cancer selected from the group consisting of: solid tumor(s), blood borne tumors, high-risk carcinoid tumors, and tumor metastases.

3. The method of claim 2, wherein the subject is suffering from one or more solid tumors and the method comprises administering an amount of MASP-2 inhibitor effective to inhibit tumor angiogenesis.

4. The method of claim 3, wherein the subject is suffering from or at risk for tumor metastases and the method comprises administering an amount of MASP-2 inhibitor effective to inhibit tumor metastases.

5. The method of claim 1, wherein the subject is suffering from an angiogenesis-dependent benign tumor(s) selected from the group consisting of hemangiomas, acoustic neuromas, neurofibromas, trachomas, carcinoid tumors, and pyogenic granulomas.

6. The method of claim 1, wherein the antibody or fragment thereof is selected from the group consisting of a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody and a human antibody.

7. The method of claim 1, wherein the composition is administered subcutaneously, intraperitoneally, intra-muscularly, intra-arterially, intravenously, or as an inhalant.

8. A method of inhibiting tumor angiogenesis comprising administering to a subject with cancer an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis.

9. The method of claim 8, wherein the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof.

10. The method of claim 9, wherein the MASP-2 inhibitory agent is a MASP-2 monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:6.

11. The method of claim 9, wherein the antibody or fragment thereof is selected from the group consisting of a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody and a human antibody.

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

192

Re: Narsoplimab generally

Could narso treat Bipolar disorder????
======================
Clin Psychopharmacol Neurosci
. 2021 May 31;19(2):269-281. doi: 10.9758/cpn.2021.19.2.269.
Are Mannan-binding Lectine Serin Protease-2 and Alpha-1-microglobulin and Bukinin Precursor the Potential Biomarkers of Manic Episode? A Study via Urinary Proetomic Analysis
Cem Cerit 1, Mehmet Sarıhan 2, Ömer Nart 3, Murat Kasap 2, Hilmi Yaşar 1, Gürler Akpınar 2
Affiliations expand
PMID: 33888656 PMCID: PMC8077062 DOI: 10.9758/cpn.2021.19.2.269
Free PMC article
Abstract
Objective: Investigating the molecular basis of bipolar disorder (BD) is crucial in terms of developing effective treatment strategies as well as objective laboratory-based diagnostic tools for the disease.

Methods: We examined the urine samples of BD patients both in manic episode and after remission and compared their urinary protein profiles with the controls. Twelve patients and twelve controls (C group) included to the study. Urinary samples of patients were first collected during manic episode (M group) and then after remission (R group). Two-dimensional gel electrophoresis (2-DE) coupled to MALDI-TOF/TOF massspectrometry approach and Western blot analysis were used.

Results: Alpha-1-microglobulin and bukinin precursor (AMBP), Mannan-binding lectine serin protease-2 (MASP-2), and Ig gamma-1-chain displayed significant increases in their abundance in the urine protein pool of M group in comparison to the C and R groups. Alpha-1B glycoprotein and prostaglandin-H2 D-isomerase (PGD2) levels were significantly higher in the urine protein pool of the M and R groups in comparison to the C group. Annexin A1 was downregulated significantly in the urine protein pool of the M group in comparison to the C group.

Conclusion: Intensities of MASP-2 and AMBP proteins discriminated manic episode from remission period and healthy controls indicating that these proteins may be candidate biomarkers for manic episode. The decrease in Annexin A1 and increase in Ig gamma-1 chain levels appeared to be associated with "Manic Episode" while the increase in PGD2 and alpha-1B glycoprotein levels appeared to be associated with "Bipolar Disorder".

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

193

Re: Narsoplimab generally

Link to the full study with supporting data and photos is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858935/

194

Re: Narsoplimab generally

Thanks.
Note the study was an assessment of MAP level, not a trial to assess treatment.
This is probably just a possible addition to be future potential indications for narso.
And there are lots of other that could be easier to assess.

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

195

Re: Narsoplimab generally

There have been reference in the Chinese media about drug companies there have a MASP2 drug.

Connoa Biotech: with CM338/MASP-2 AB https://med-china-com-cn.translate.goog … ax,nv,elem

and this one, which could be the same since they have the same CM338:
en.keymedbio.com
https://www.kirkland.com/news/press-rel … g-ipo-of-k

I have forwarded the information to Greg, who has said OMER was opening up trial sites in the Phase IgAN trial.
I don't expect a reply from him, but he may thank me and then I will ask whether they can do this and get away with it... or how foolproof is the patent protection.

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

196

Re: Narsoplimab generally

KeyMed Bio had something on the web at one point, but it is no longer there.
It describes work on their MASP2 inhibitor and comparing it to narsoplimab.

They claimed superiority to a "narsoplimab analog" which makes it even more concerning to us...although it may that they can't be stopped in China. Presumably OMER patents are good elsewhere and everywhere. Omers has a legal dept with multiple lawyers, in addition to a Patent dept. with more of them, and outside legal representatives that do a lot of Biotechs.

I'd like to know whether this really look like we lose the Chinese market... and I wonder about the Chinese trial sites Omeros was trying to open in China.

Here is the material found. Please do no show this to anyone or talk about it. Hopefully Greg will at least comment.
Chinese companies have been know to lie and say they have things as large as forests and coffee shops and not have them, so this needs to be investigated more thoroughly.

********************from KeyMed Bio, probably from their IPO document*****
"Favorable preclinical results: Our preclinical studies indicated that, in comparison with narsoplimab analog, CM338 is more than 50-fold potent in inhibiting the lectin pathway. We are assessing the toxicity of CM338 in monkeys, and no severe adverse event has been observed. We expect to submit an IND application for IgA nephropathy to the NMPA in 2021."

https://webcache.googleusercontent.com/ … &gl=de
[2:26 PM, 7/9/2021] +49 176 63251355:

"Competitive Advantages•Higher binding to MASP-2 with strong potencyOur preclinical study demonstrated that CM338 binds to MASP-2 across species with much higher binding affinity than narsoplimab analog (36.4 pM vs. 7.15 nM to humanMASP-2), as illustrated by the figures below. This renders our CM338 advantageous overnarsoplimab analog in that we could evaluate CM338 in different animal species forpharmacology, PK and toxicity."

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

197

Re: Narsoplimab generally

https://www.jimmunol.org/content/177/6/4211

Mannose-Binding Lectin Contributes to the Severity of Guillain-Barré Syndrome
Karin Geleijns, Anja Roos, Jeanine J. Houwing-Duistermaat, Wouter van Rijs, Anne P. Tio-Gillen, Jon D. Laman, Pieter A. van Doorn and Bart C. Jacobs
J Immunol September 15, 2006, 177 (6) 4211-4217; DOI: https://doi.org/10.4049/jimmunol.177.6.4211
ArticleFigures & DataInfo & Metrics PDF
Abstract
In Guillain-Barré syndrome (GBS), complement activation plays a crucial role in the induction and extent of the postinfectious immune-mediated peripheral nerve damage. Mannose-binding lectin (MBL) activates the complement system via the lectin pathway after recognition of repetitive sugar groups on pathogens. We investigated whether the MBL2 genotype, serum MBL level, and MBL complex activity are associated with the development and severity of GBS. Single nucleotide polymorphisms in the promoter region (−550 H/L and −221 X/Y) and exon 1 (A/O) of the MBL2 gene were determined in 271 GBS patients and 212 healthy controls. The frequencies of the H allele, HY promoter haplotype, and HYA haplotype, which are related to high MBL activity, were all increased in GBS patients compared with healthy controls (p ≤ 0.03), particularly in severely affected GBS patients (MRC-sum score <40) (p ≤ 0.02). Severe weakness was also associated with high MBL concentrations and MBL complex activity in sera from GBS patients (p < 0.01). The MBL2 B allele was associated with functional deficiency and relatively mild weakness. These results support the hypothesis that complement activation mediated by MBL contributes to the extent of nerve damage in GBS, which is codetermined by the MBL2 haplotype.

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

198

Re: Narsoplimab generally

Perhaps a Narso chaser for a post J&J vaccine rare complication?

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Re: Narsoplimab generally

A bit of limon after the tequila.
At 1 person/100k per year, given the damage done to the lives of people with GBS, the US addressable market is 3500 per year. Add in Canada, Aus/NZ and Europe, plus Japan, maybe 9000

Lots more money in CV19 and LongCV

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