Mexico registration and marketing approval complete.

This is one of the reasons that the company started a few weeks ago ramping up manufacturing. It's not just for potential demand from COVID-19 usage. Fresenius has been selling their European inventory down and they will now be placing large stocking order(s) for Mexico. This and the fact that their sales in France, Finland and Czech Republic have been going well (per the last transcript). Once South Korea get approved Fresenius will be placing order(s) for that country as well. All this combined with the increase in demand from the direct sales efforts in Germany, bodes well for an extremely robust sales number for Q2.

A couple of people questioned whether this was the same case in which a press release was put out February 5th. I don't believe it is, even though it was at the same hospital and departments - Department of Pediatric Hematology and Oncology and Division of Nephrology and Dialysis, Department of Pediatrics, Bambino Gesù, Children’s Hospital, IRCSS, Rome, Italy. This case was an infant, the one previously reported was a 14 year old boy.

They said in the article that in Italy, about 400 children are affected by acute leukaemia every year, and I gather this must be one of the premier children's hospitals in the country for this kind of treatment.

Baby saved during CAR-T therapy

Published in Tarantino is an independent online magazine in Italy today!

Baby with leukemia was saved thanks to blood purification
https://www.iltarantino.it/mondo/bimbo-con-leucemia-salvato-grazie-alla-depurazione-del-sangue/

"A child with leukemia was saved thanks to the purification of the blood by the doctors of the Emergency Intensive Therapy and Pediatric Oncohematology of the Bambino Gesù Hospital in Rome. The therapy implemented by specialists avoided the complications of Car-T therapy. It is the first time in the world that this incredible result has been achieved and after 15 days the baby has been discharged from intensive care. The lethal effects that Car-T therapy usually has, to which leukemia patients are subjected, this time have been counteracted thanks to this new method.

The child saved with leukemia is suffering from acute leukemia

The new experimental treatment involves apheresis, which consists in purifying the patient's blood, and in the baby with leukemia the effects were so positive that the baby was saved and after two weeks he was able to exit intensive care. To carry out this experimental treatment, the doctors of the Emergency Intensive Therapy and Pediatric Oncohematology of the Bambino Gesù Hospital used a special filter called CytoSorb which allowed for perfect blood purification.

The child with leukemia that the team rescued suffers from acute leukemia, in a very serious form, very common in children. In Italy about 400 children are affected each year by acute leukemia. For all these young patients this result therefore represents a very important milestone, which cancels the deleterious effects of Car-T therapy. The apheretic therapy used by the team gave the desired results and allowed to save the child without compromising the organism and its natural defenses. This result could be an effective solution to keep the consequences of the treatment under control, without affecting its action."

Another tender order from Romania-Bucharest
Contract dated 3/26/20:

https://ted.europa.eu/udl?uri=TED:NOTICE:150620-2020:TEXT:FR:HTML&WT.mc_id=RSS-Feed&WT.rss_f=Technology+and+Equipment&WT.rss_a=150620-2020&WT.rss_ev=a

Similar in size to the last one I was able to find, 616,791.70 LEI (Romanian Leu) or approximately $140,566.83 USD.

NATIONAL INSTITUTE OF INFECTIOUS DISEASES PROF. DR. MATEI BALS
https://www.institutiimedicale.ro/spital/institutul-boli-infectioase-matei-bals-bucuresti/

ECMO vs CRRT usage

If you haven't read this yet, interesting observations from CG regarding the use of ECMO from yesterday's webinar. This might support why the Italy Brescia Renal COVID Task Force Guidelines to treat patients with severe COVID-19 infection and Stage 3 renal failure were specifically around continuous renal replacement therapy (CRRT).

"Everyone should go watch Dr. Alain Combes's "ECMO, yes, no, when?" session from yesterday's webinar. Dr. Combes is from a hospital in Paris, France. As of March 27th, there were only 154 COVID-19 patients on ECMO in all of Europe, nearly half (70) of which were in France. Italy had only 27; UK: 16; Spain: 12; Germany: 10; Belgium: 6; Portugal: 4; Austria: 3; Sweden: 2; Netherlands: 2; Poland: 1; Czech Republic: 1. Apparently, to be most effective, ECMO should be applied earlier (within 3 days), but based on the Q&A, it seems like ECMO will be way too resource intensive in both terms of hardware and human resources -- especially precious human resources -- to be widely used during a pandemic. Granted, probably some countries are too busy to respond to the ECMO survey, but we're talking tiny, tiny numbers of ECMO on a percentage basis -- only around 0.06% of all active COVID-19 patients in Europe. Yes, ECMO tends to be used for many days, but the effective CytoSorb market opportunity for COVID-19 via ECMO looks to be very minor, unfortunately. A bigger market opportunity for CytoSorb might be via CRRT for COVID-19 for patients with kidney issues. CRRT still requires hardware and human resources, but my understanding is that it's less resource-intensive than ECMO. I think this must be why the Italian national guidelines are only calling for CytoSorb use for COVID-19 patients with advanced kidney disease and CRRT."

fantom, my opinion is that you have to take this last update:

"to meet the growing demand for CytoSorb worldwide, our manufacturing facility is currently running 24 hours a day, seven days a week."

in the same context with the statement which was given in the last conference call:

"We're currently manufacturing CytoSorb and ramping manufacturing of CytoSorb to build inventory of devices should there be a need. Given the three year shelf life of our products this increase in inventory can be easily worked through with low risk based upon our underlying existing business.".

I think it is easy to link "growing demand" with "24x7" to interpolate that this is demand is reaching a max level (e.g. $80M). What they are doing is manufacturing as much as they can in order to always be ahead of the demand, even if that means having a lot of inventory (which is ok because of the shelf life).

What the impact is of this however is the consumption of working capital because they have to pay for all the raw materials and labor to build these devices. This will also have an impact on cash flow this quarter and next quarter.

B52T38, most recently during the Q2 2019 conference call Josh Jennings, one of the analysts, asked this question of Dr. Chan

"Josh Jennings
And are you still continuing to see strong growth out of Germany and I was just wondering I know it's probably hard to track each CytoSorb procedure with or case where CytoSorb is implemented in the therapy. But is there any kind of trend in terms of where you're seeing the growth in Germany in terms of indication cardiac surgery versus sepsis versus some other indication or is it more broad-based across oXiris indications knowing that there are numerous indications for CytoSorb?

Phillip Chan
I think it's a fairly broad-based, I would say that based upon our numbers roughly a third of our uses are in cardiac surgery and roughly two-thirds are in the intensive care unit either postoperative to cardiac surgery or for critical illnesses like sepsis, trauma, burning through and other things."

He turned it over to Christian to further expand on on his comments, but he did not directly address how oXiris may be impacting Cytosorb sales in Germany. However I found another post by CG that touches on this:

CG:
"Baxter seems to be going full bore investing in oXiris (again) -- funding trials, setting up a registry, etc. Remember, oXiris filters both endotoxin (maybe not as well as Toraymyxin) in addition to cytokines (maybe not as well as CytoSorb), so it does not seem like Baxter will be that interested in CytoSorb, especially if CytoSorb remains partnered with Fresenius. The competition from oXiris will likely continue to grow, and even though CTSO's management has yet to acknowledge it, I'm starting to wonder if Baxter's efforts with oXiris are contributing to some of the sales sluggishness with CytoSorb over the past 12 months since Q3 2018."

To be honest I have not done much research on some of the competing products. There is some information in the 10k but it is very limited and I don't have enough medical knowledge to ascertain some of the nuances. I did go back a little further and look at the Q4 2018 call transcript where Andrew D'Silva asked a question about Baxter's impact after recent Oxiris product updates. I have posted his question below.

"Andrew D'Silva
Okay, got it. Just a couple of more quick questions from me, so just from the competitive landscape, Baxter's oXiris product fairly recently got approval for cytokines as well. I was curious as to how you're viewing the competition and then has there been any sort of any material impact that you've noticed through that? And if so, what are you essentially trying to do to counter that at this point?

Phillip Chan
I think of the various competitive threats out there. Baxter as the one of the leading dialysis players in the world in critical care is probably the most relevant. Of course, we are partnered with Fresenius Medical Care, which is the largest dialysis company in the world and the number one or number two player next to Baxter in critical care all over the world.
That being said, Baxter acquired Gambro, which was the second leading dialysis player in the world, a number of years ago and inherited their acute care product line, which included oXiris Septex and a number of other acute care products.

oXiris was launched by Gambro back in 2009 as a - initially as an endotoxin filter. They had actually marketed another product called Septex, a high molecular weight cut off filter for the removal of cytokines. But Septex was ultimately not a successful product and ultimately is not being actively marketed anymore.

And oXiris also, despite being marketed for gram negative sepsis as an endotoxin filter, was also not highly successful and always in the shadow of another product called Toraymyxin which was - and I believe still remains the leading endotoxin removal filter out there.

But Toraymyxin has had issues because of a number of failed pivotal studies demonstrating no mortality benefit of endotoxin removal. That being said, recently, I think the expanded Baxter through some in-vitro data, expanded the label of oXiris to include cytokines, and all I would say is that just because you have a label for reduction in Cytokines doesn't mean that it will actually work.

And I think the clinical - the very long term clinical experience, 10 years of oXiris being in the market is perhaps indicative of the efficacy that the fact that it has not really taken off as a therapy is a reflection of its efficacy. And so, I think, yes, it creates some market confusion, some market noise, but I think that as that plays out, I think that we'll see how we deal against them, so."

So to me the bottom line in reading through all this and the recent Baxter partnership development is that CTSO is going to be gradually experiencing more competition both here and abroad than they have had in the past, so I believe 2020 is going to be a critical year for the company. In my opinion falling behind on the REFRESH II and Hemodefend trials is only going to make things that much harder in the future.

Sorry for the lengthy post.

Yeah, there were bits and pieces of this conversation buried in a couple of threads, so I consolidated the comments and posted them here. That was why it caught my eye. There is so much focus on this virus activities that some of these other noteworthy events that impact CTSO get lost.

I agree about your comments regarding that board. There is still a lot of 'noise', but I cut down on muting a couple of individuals who comprised the bulk of it and it is much more readable, although I do find it hard following the way Yahoo has it structured, filtered, and sorted (kind of sucks actually). But that has always been Yahoo.

I was planning on listening to that web cast and thanks for the reminder.

News of this partnership caught my eye as it has a direct impact on Cytosorbents here in the U.S. Below are a few comments from CG and a couple of others on YMB regarding this partnership:

CG:
"This deal is interesting for CTSO because it illustrates what a typical deal structure looks like with a major pharma / device company: upfront cash payment plus commitment for additional payments upon achieving critical milestones (e.g., regulatory approval). It also shows what a pre-cursor to an acquisition often looks like when a company sells out all their exclusive rights.

The upfront payment was relatively small ($5M), and Spectral still needs to raise money. Spectral announced a $10M public offering earlier this month, but just withdrew it last week because of all the turmoil. Everything is riding on Tigris, and results are 1-2 years away at the earliest.

Even though Baxter's existing product (Oxiris) can already filter both cytokines and endotoxin, CytoSorb does have one competitive advantage: CytoSorb does not require heparin for anticoagulation. Quoting from Baxter's website: "It is contra-indicated to use the oXiris set where patients present a known allergy to heparin or have type II thrombocytopenia caused by heparin (HIT Syndrome type II)."

Baxter's own product already filters both cytokines like CytoSorb and endotoxin like Toraymyxin: https://www.baxter.com/healthcare-professionals/critical-care/oxiris-critical-care";

Others:
"Since Cytosorb does not target endotoxin (yet), I think that Baxter would be very interested in partnering with or acquiring Cytosorbents because our focus is complementary and potentially synergistic with Spectral's product. Because CTSO is tied up with Fresenius, this is partnership is not surprising. Baxter seems to be hedging its bets."

Sorry but I haven't been following that story. I am reading back through the posts here and the article. I think the observations from kjpcrna are accurate in regards to HIPPA and what we would be able to find from the outside looking in. The connections between that trial site and this patient story do seem to point in that direction and are interesting.

I concur. Its funny how things have switched, now there is more informative content on YMB. Read a lot of CG's posts if you haven't already. Very objective, realistic and supported by facts.

For example I don't believe there have been any discussions on this board about the recent partnership of Baxter and Cytosorbent's competitor in the US - Spectral (I could be wrong and just missed it).

Sending tons of emails to Dr. Chan and complaining about the lack of press releases or responses from management, is not productive in my opinion.

Please disregard my previous post.

Apparently the hospitals already have a solution for those critically ill and dying, they are considering do-not-resuscitate orders for all the patients infected with COVID-19. The hospitals are citing that their staff is at high risk of getting exposed to the deadly virus as there is a low supply of protective equipment like masks and gloves.

Problem solved.

https://www.ibtimes.com/coronavirus-us-update-hospitals-consider-do-not-resuscitate-order-all-covid-19-2947068

Streamlined compassionate use program

In the press release Dr. Chan says he’s already fielded a number of requests from hospitals in the United States to use CytoSorb for COVID-19 patients via the FDA’s “compassionate use” or “expanded access” programs for therapies already proven safe for other conditions, and that the company is in discussions with the FDA to help make the therapy temporarily available where needed during this crisis. Well the FDA better wake up because it is going to take more than just streamlining that very restrictive process. We aren't talking about just a few cases here and there where the filters need to be supplied. Just this morning they are saying NY looks like a field hospital. At one hospital alone 12 people have died this week.

"In a 24-hour period this week, over a dozen coronavirus patients died at Elmhurst Hospital in Queens, New York, as multiple medical workers inside the public hospital told ABC News they are overwhelmed, treating "hundreds of COVID-19 patients."

Dr. Colleen Smith, an emergency care physician at the hospital, described the area where the COVID-19 patients are being treated as "a parking lot of stretchers." As one emergency care physician told ABC News plainly, "this is ground zero." The city health department sent out a release on Tuesday, calling the 545-bed hospital in Elmhurst "the center of this crisis."

The city of New York now has more than 17,000 coronavirus cases, nearly one-third of the nation’s total. The borough of Queens has the highest number, with over 5,000 cases. There have been 280 deaths in the city, according to officials."

Nice article. The author is right "...COVID-19 has now dialed up global attention on cytokine storms—and any effective therapies that could treat the sometimes deadly coronavirus-induced condition."

There have been more articles referencing cytokines and cytokine storm since this virus appeared on the scene, than I can remember. Associating Cytosorb with elevated cytokines rather than specifically to the virus is better for the company in the long run hence why Dr. Chan continues to emphasize this in all his communications.

Thanks for sharing.

From the press release "Meanwhile, we continue to update BARDA and the U.S. Joint COVID-19 Task Force with our progress. We seek support to scale our manufacturing, to subsidize our efforts to provide CytoSorb to hospitals for emergency use, and to help fund a clinical study in COVID-19 patients." It sounds like they have a good communication channel open with BARDA and the task force.

One of the arguments they need to make with the task force if it wasn't already called out in their proposal which was submitted, is referred to in the press release: "Physicians have described the lung injury caused by COVID-19 pneumonia as the worst they have seen from any respiratory viral infection in recent history, leading to an atypically long 2-4 week dependence on mechanical ventilation, if critically-ill patients can survive that long."

With the shortage of ventilators, beds and other types of hospital equipment, not to mention critical care staff, it is in the hospital's interest to provide a therapy that can dramatically reduce that 2-4 week stay, freeing up valuable resources. The company already has studies that show this information.

Price movement is a result of the unbalance between buyers and sellers. If there are more potential buyers than sellers, the buyers will have to pay a premium to get filled. Those who pay the highest price will be filled easier than those who want to buy cheap.
If there is a balance between buyers and sellers you can trade huge volumes without moving the prices. There are a lot of long term holders in this stock that have a lot of shares. I would not doubt there is a lot of unloading going on, plus there are a lot of day traders and swing traders playing these coronavirus stocks.

My statement was more around the visibility and representation of key opinion leaders who have adopted the therapy in Romania. Both Hungary and Romania have some of the company's top key opinion leaders, Prof. Zsolt Molnar and Dr. Dana Tomescu respectively. I don't have insight into sales into those countries but I know that both of these doctors speak at some very large conferences like SepsEast which is one of the most important critical care conferences in eastern and central Europe, drawing approximately 450 physicians and healthcare professionals from more than 25 countries. CytoSorbents is usually the exclusive Diamond Sponsor at the conference. They are both highly regarded and influential in their respective countries and have authored many of the case studies you see published.

You can do a search for Dr. Tomescu's name here and see there are quite a few (https://literature.cytosorb-therapy.com/)

Dr. Dana Tomescu is usually a speaker at the annual user conference.

While everyone is waiting on pending news of patient treatments, BARDA or the hiring of a new CMO, you might find this information a little lightheartening.

This was posted on the Romanian National News Agency AGERPRES web site today. The General Council of the Municipality of Bucharest (CGMB) approved, on Monday, the start of the procedures for the purchase of a dialysis device for the 'Victor Babes' Hospital for the prevention and spread of COVID- 19.

https://www.agerpres.ro/administratie/2020/03/23/cgmb-a-aprobat-demararea-procedurilor-pentru-cumpararea-unui-aparat-de-dializa-destinat-spitalului-victor-babes--472033

Several things about this article made me do a double-take and 'say what'???

First of all the article states "a dialysis device" (not plural) was purchased for the Victor Babes clinic ("the hospital's need to have as a medical equipment a hemofiltration device that can be used with Cytosorb filters to mitigate the effects of excess of cytokines that appear in ARDS (especially in the severe forms of COVID) and in the associated sepsis, the Association of the Bucharest Center for Dialogue will purchase the device for the 'Victor Babes' Hospital."

Secondly this has be the first time I have seen a dialysis machine purchased specifically for the use with Cytosorb filters - normally it's the other way around.

Thirdly, who the heck is 'Victor Babes'? Well apparently he was a Romanian physician, bacteriologist, academician and professor. One of the founders of modern microbiology. When you go to the clinics's web site the first thing you see is pretty nurses .... well I will leave that one alone.
http://www.spitalulbabes.ro/

By the way Romania has a total of 7 deaths due to coronavirus, and they are one of the leading countries in the use of Cytosorb.

Chloroquine Study Show 100% Cure Rate for Patients Infected with the Coronavirus

My guess is this could be what the FDA press conference is going to be about. On Monday night Laura Ingraham reported that a new study revealed the anti-viral medication chloroquine is successful in fighting the coronavirus. Laura invited Dr. Gregory Rigano, the co-author of the study to discuss the latest findings.

Dr. Rigano said their study found that those COVID-19 patients who took hydroxy-chloroquine were found free of the disease in 6 days. The patients were testing negative for the coronavirus in six days!

Dr. Rigano also said taking choroquine could act as a preventative.

Full peer reviewed study has been released by Didier Raoult MD, PhD https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub

About the trial: https://www.covidtrial.io/
Breaking update that was released: https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

"Do you have a source for the statement "As we also heard steroids are being used reflexively to try to control this inflammationto" ? "

Please reference the press release from March 12:

"The underlying cause for these complications is often a cytokine storm that results in a massive, systemic inflammatory response, leading to the damage of vital organs such as the lungs, heart, and kidneys, and ultimately multiple organ failure and death in many cases.  Steroids are being used reflexively to try to control this inflammation, despite WHO recommendations against using steroids in COVID-19 infection, and evidence from other coronavirus infections (e.g. SARS and MERS) and influenza that its use can delay viral clearance and increase mortality."

Here is a link

https://www.reuters.com/article/us-health-coronavirus-usa-trump/trump-to-hold-news-conference-to-discuss-fda-coronavirus-idUSKBN2151S0?feedType=RSS&feedName=domesticNews

I heard the same during his press conference today and he alluded it would be tomorrow (Thursday).

BARDA bypasses the laws of supply and demand by allowing none other than the federal government to pour hundreds of millions of dollars into procuring and advancing promising products. The problem is that this usually lures major players in the pharmaceutical industry to the trough. So these major players usually get the attention of those making the decisions of who to partner with. This and the fact that containment has been the priority of the administration so this is why BARDA is not accepting any proposals right now outside of diagnostics and testing. This is why you see on that list of EUA's all diagnostic and testing companies.

Typically I like to stick to posting things that are informational and try to remain independently objective. But here are a couple of thoughts and an opinion while waiting on some news.

In hindsight it looks like the delay of the REFRESH II and Hemodefend trials would have happened anyway as a result of this epidemic. Challenges would have arisen from quarantines, site closures, travel limitations, or other considerations if site personnel or trial subjects were to become infected with the virus, and these challenges would have have lead to difficulties in conducting these two clinical trials. Not only that but the company still hasn't hired a CMO yet. Having suspended REFRESH voluntarily not only saved the company a lot of expenses, but they did not have the personnel or resources to handle all these these issues while the trial was in-flight with all that is currently going on. I never thought I would say this but for once I am glad the company was late on something ;)

This being said, I think the big event for this year, if it were to occur would be getting news from BARDA and an FDA emergency use authorization. This is what I am hoping for. Getting updates from China or Italy on patient treatments, albeit great news, would only provide a one or two day boost to the stock price (as we have seen). I am also sure that this will have a longer term impact on increased sales. But in terms of the stock price and the current market, there are just too many people trying to get their money out due to the fear, and traders playing the volatility. BARDA/FDA news however would provide a significant catalyst I believe to sustain an upward move, assuming we hit the market bottom in the next week or so at least stabilize (we could see 15,000 potentially).

I would very much like to see the company on this list:

https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov

The FDA just announced two more EMU's for Hologic and LabCorp, right on the heels of Thermofisher - all diagnostics.

Thoughts or or other opinions welcomed.

Update on using Cytosorb as an adjuvant therapy (Aferetica)

Aferetica, the partner in Italy, released an update for physicians on their web site a couple of days ago:

https://www.aferetica.com/en/update-on-the-possible-use-of-cytosorb-in-patients-affected-by-covid-19/

As was acknowledged in the press release last week, there have been treatments of Cytosorb in Italy and the company is expected to be getting details around those soon.

Aferetica put this document on their web site to help inform clinicians who want to underake the therapy autonomously, and I thought there were a couple of interesting points Aferetica makes in the update.

First, it struck me that if physicians are deciding autonomously to use Cytosorb, does it mean that things have gotten so bad in Italy that they are not waiting around for hospital IRB or ethics committee sign-offs to use the device?

As we also heard steroids are being used reflexively to try to control this inflammationto, so Aferetica calls specific attention to the recent Cytosorb CRS case from Bambin Gesù Pediatric Hospital where Cytosorb was used successfully with the administration of Tocilizumab.

Interesting also that they have observed "increased aggregating and coagulating activity" in these patients and are advising physicians pay particular attention to the coagulation of the extracorporeal circuit and the impact on the filter from high levels of d-dimer, which is a small protein fragment present in the blood after a blood clot is broken up (I had to look this up). Hence they are advising that anticoagulation should be effective from the start of treatment.

REMOVE trial (https://www.drks.de/DRKS00013740)
I learned something new now. The studies posted on the German Clinical Trial Register, have the actual protocol documents attached to the entry. CG pointed this out on YMB.

I downloaded the .pdf for the REMOVE trial which is CTSO's largest randomized trial to date (288 patients) and looked through the doctors involved. Below was my response to him concerning one of the US doctors on the DSMB - Dr. Matthias Loebe. This guy has some very impressive credentials!


"@Techxen, Yeah, that looks like a new study that has yet to be registered anywhere else (like on clinicaltrials.gov). There's several planned trials that we've heard about at various conferences that we've yet to see appear on clinicaltrials.gov. In general, you can find a lot of information on the German clinical trials site. For example, for REMOVE, the whole clinical trial protocol is available (both v1 and v2), and I was able to determine that 2 of the 3 physicians on the DSMB are American, including Dr. John Kellum from U. of Pittsburg and Dr. Matthias Loebe from U. of Miami (the 3rd physician is Dr. Peter U. Heuschmann from U. of Wu¨rzburg in Germany).

@CG I didn't see that before that the trial protocols and approvals were actually attached to the entry. That is great information. I looked up Dr. Loeb because I have not seen his name attached to any previous Cytosorb studies, and it appears he graduated from medical school at the Free University Berlin Germany and did his internship at University Hospital in Zurich and residency at German Heart Institute in Berlin, so I see the German connection here. He has been around, previously serving as professor of cardiovascular surgery at Weill Cornell Medical College in New York City, and as Director and Chief of Thoracic Transplantation at the Methodist DeBakey Heart and Vascular Institute in Houston. He was also Surgical Director of the Center for Difficult Airway and Pleural Surgery at Baylor College of Medicine, which is home to one of the busiest heart, lung and heart-lung transplant programs in the country. He has developed groundbreaking cardiac surgery techniques in the U.S. and Germany and has performed vital research on organ replacement and lung disease, and his work has led to the implementation of second-generation ventricular assist devices. Having him on this board might be beneficial with his US connections."

http://www.med.miami.edu/news/dr.-matthias-loebe-joins-miami-transplant-institute

More details on this Swiss trial NCT04309591.

I asked CG over on the YMB if he knew anything about this trial and got this extremely detailed response. Some good information if you like to keep track of all the studies going on. I was not aware that the WHO also keeps track of all these studies as well. Germany has a list of 5 which can be found on their trial site: https://drks.de/drks_web/navigate.do?navigationId=search&reset=true

"@Techxen, I had not come across NCT04309591 before either. I recall CTSO's 7th International Users' Meeting had several discussions of clinical trials on the agenda, but I can no longer access the original agenda now that the meeting has been postponed. Note that NCT04309591 is a retrospective study, so it's an analysis of existing clinical data, which can be completed relatively quickly. Also, most major developed countries have their own country-specific registries for clinical trials. Switzerland is one such country. In Switzerland, all clinical trials or research projects must first pass an ethics review. They have a system called BASEC (Business Administration System for Ethics Committees) for ethics submissions (https://www.swissethics.ch/basec). After ethics approval, according to the BASEC FAQ, Swiss laws mandate that all clinical research projects "must be registered and published in a WHO primary register or on clinicaltrials.gov as well as in the supplementary federal database in the form authorised by the responsible ethics committees. The Swiss National Clinical Trials Portal (SNCTP: https://www.kofam.ch/en/home/) is the supplementary federal database for research projects carried out in Switzerland." Unfortunately, the BASEC site does not seem to be directly searchable itself. The BASEC ID for NCT04309591 is listed as 2019-01740 in the "Other Study ID Numbers" field of the record on clinicaltrials.gov. Unfortunately, searching on the SNCTP portal by either this BASEC ID or the NCT ID or just the "CytoSorb" keyword does not find this trial. Searching by all trials in Basel does not find it either. Thus, clinicaltrials.gov is likely the primary registry, and there's a delay before it will show up on SNCTP. Note that clinical trials registered on SNCTP will also have an identifier prefixed with "SNCTP."

Also, note that NCT04309591 is not the first trial to appear on clinicaltrials.gov as completed. NCT04226430 is another recent one from Turkey (University of Gaziantep) -- the first for the country, I believe -- that appeared on January 13, 2020. Unlike the Basel study, the Turkish one looks to have been a prospective study that ran for 1 year from June 2016 to June 2017. I have not tried to check, but "TF.18.43" in the "Other Study ID Numbers" field is likely a Turkey-specific reference to Turkey's clinical trial system. Source: https://clinicaltrials.gov/ct2/show/NCT04226430.

While researching the Swiss clinical trial system, I also learned that WHO (World Health Organization) has a searchable database that aggregates primary clinical registries from 17 different countries. It's called the International Clinical Trials Registry Platform (ICTRP): https://www.who.int/ictrp/search/en/. It's not a perfect and does not correctly identify all duplicate registrations, but using it, I was able to find China's clinical trial record for CytoSorb and COVID-19; the ICTRP record: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR2000030475, which links to the primary Chinese CTR record: http://www.chictr.org.cn/showproj.aspx?proj=50452.";

This observational/retrospective study was completed at the end of 2019 and what was odd was that this was first posted today on clinicaltrials.gov. First time I have seen a completed study posted after the fact.

It is a different study than the REMOVE trial (Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis (NCT03266302) which was a full blown Interventional study. Both studies had a 250 patient enrollment although the REMOVE trial over-enrolled by 38 additional patients bringing it to 288. The data readout in the next several months of the REMOVE study will be the big 'needle mover' assuming that the results are positive and statistically significant.

ClinicalTrials.gov Identifier: NCT04309591
Study Type : Observational
Actual Enrollment : 249 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Cytosorb Therapy in Cardiac Surgery - a Retrospective Study of Hemoadsorption in Patients With Endocarditis
Actual Study Start Date : October 18, 2019
Actual Primary Completion Date : December 4, 2019
Actual Study Completion Date : December 4, 2019

I had hoped to hear something soon from BARDA regarding a possible agreement as a therapeutic or other option within their countermeasure portfolio against the coronavirus. They have already signed up partnerships with several companies on the vaccine and diagnostics side of things and most recently with Regeneron for a therapeutic option to treat the virus for those who have contracted it. It does not look like that will happen for several more weeks.

Based on the recent comments from Dr. Chan that they have been in discussions with BARDA and the task force, I would think that they have completed their submission of their market research package and proposal (https://medicalcountermeasures.gov/app/barda/coronavirus.aspx), as well as completed a TechWatch meeting at this point if it was required (https://www.medicalcountermeasures.gov/Request-BARDA-TechWatch-Meeting/). Applications for proposals go through the existing BARDA BAA and EZBAA DRive program (https://drive.hhs.gov/partner.html). However as of this morning it says that in regards to the coronavirus countermeasures, the "are only accepting responses related to SARS-CoV-2 programs in Diagnostics (4.1A-C: Diagnostics, 4.2: Nonclinical Model Development/Screening, 4.3: COVID-19 Vaccines, and 4.4: Advanced Manufacturing Technologies." Which begs the question, was the company having these discussions and did they submit their information prior to this announcement?

It appears that the government right now is focused mainly on testing and prevention and not the treatment side of things, as part of containment and understandably so. If things get as bad as what some of these infectious disease experts say however, the government should be getting ahead of it by looking at options after contracting it, especially for the elderly and those with compromised immune systems.

Regarding any updates on Chinese web sites, I have not seen anything surface the past two days, and the clinical study (ChiCTR2000030475 ) that was registered in China still shows it has not started recruiting for the 19 patients. This is not unusual as there is usually a lag as a result of the information review and update process.

Forgot to post this link

Jafron's Coronavirus main page:

http://www.jafron.com/index.php?m=content&c=index&a=show&catid=96&id=989

B52T38, those are very good questions and ones that I wish I had an answer to. I referenced the commercialization potential from the CMS press release. CytoSorbents and CMS worked together to earn regulatory clearance just to get the devices imported into China under the "fast-track" review process established by the National Medical Products Administration of the People's Republic of China (NMPA) specifically to address the immediate needs of the coronavirus (COVID-19) pandemic. I cannot believe that Baker McKenzie would have brokered this deal between the companies or CMS agreed to it solely for humanitarian reasons if Cytosorb wasn't in some way potentially superior to the device from Jafron.

From what I have read about Jafron's cartridges (which is very limited) they are still undergoing various trials but apparently can be used in and outside of China. In fact Jafron struck up a deal with Saudi Arabia for not only their HA330 cartridge but along with their DX10 blood purification machine. http://www.jafron.com/index.php?m=content&c=index&a=show&catid=96&id=991

Jafron has so many cartridges each one with a different purpose and I believe HA380 is the latest 'new and improved' version. If you look at these products on the company's web site this might be an indication why Cytosorb is superior in that it can do what 7 of their cartridges do: http://www.jafron.com/index.php?m=content&c=index&a=lists&catid=103 (again I have not done an in-depth review and comparison of these with Cytosorb).

Here is Jafron's main Coronavirus web page featuring HA380/HA330, which is a very interesting read.

To cut Dr. Ronco some slack it does appear they have put his picture in several places on their web site as their 'advisor' and even too liberties of listing Professor Jean-Louis Vincent as 'being invited as the research consultants for the new observational study I posted about earlier.

Bottom line, is after reviewing their products and web site I have to believe that Cytosorb is indeed a superior product and maybe out of desperation this is why China Medical Systems saw this opportunity.

However the company may be fighting an uphill battle in China - Jafron's Chairman of the Board Dong Fan lists as first of his credentials is "Member of the Communist Party of China".

To further your analogy raptor, let's hope that after we 'pop to the surface' that when the corona tide goes out that we don't go with it.

Even though I am loving the exposure finally, I don't like seeing our name in the daily 'corona virus plays' on every stock board, in fact I cringe. We all know the company is much more than that and that is why Dr. Chan during each interview makes this very clear. The longer term and greater residual benefits coming out of this pandemic will be marketing approval and commercial collaboration in China with China Medical Systems and potential fast track here in the US with the FDA, not to mention the ripple effect on sales for other applications.

We need to keep the employees of Cytosorbents in mind including those in the US as well as the sales team in Germany. While Dr. Chan and the management team are handling all of the current government interactions, production and sales activities, they also have to manage and mitigate the impact that COVID-19 is having on their own employees. While we as investors are so focused on the potential 'opportunities' this epidemic might create in terms of additional sales and exposure, it won't mean that much if the Cytosorbent's production and sales personnel are impacted with possible shutdowns.

I don't want to stir up something here, and maybe this is just me, but the past couple of months I have seen Dr. Claudio Ronco (a key opinion leader for Cytosorb) authoring papers and publishing information on HA380.

For those of you that are not aware, HA380 is a hemoperfusion filter similar to Cytosorb that is manufactured by Chinese firm Jafron and sold in China.

http://www.jafron.com/index.php?m=content&c=index&a=show&catid=103&id=2800

Jafron's CA330 is supposed to be their improved version that targets more mid-molecular weight toxins and cytokines but I believe it is still in clinical studies. I posted some information about it here: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147235160

Dr. Ronco has been one of the key opinion leaders for Cytosorb for many years, but since the coronavirus has come on the scene he has co-authored an upcoming paper on the use of HA330 and publish some YouTube videos.

Largest study of sepsis cases in U.S. finds significantly greater burden than previously known.

Directly on the front page ("In the Spotlight") on the Department of Health and Human Services Public Health Emergency web site (this is the same sight that Cytosorbents used to submit their market research package for consideration as countermeasure for the virus).

https://www.phe.gov/Preparedness/pages/default.aspx

U.S. hospitals saw a 40 percent increase in the rate of Medicare beneficiaries hospitalized with sepsis over the past seven years, and in just 2018 had an estimated cost to Medicare of more than $41.5 billion for inpatient hospital admissions and subsequent skilled nursing facility care according to an unprecedented study by researchers from the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response (ASPR) and the Centers for Medicare & Medicaid Services (CMS) and collaborators from Acumen LLC of Burlingame, California.

Each year:
More than 1.7 million people in the U.S develop sepsis
Nearly 270,000 adult Americans die as a result of sepsis
More than $62 billion is spent on sepsis healthcare costs

It would be very short sighted of BARDA/HHS to look at Cytosorb only as a countermeasure against this coronavirus and not more broadly in the context of the huge sepsis problem that by their own study, appears to be growing exponentially in this country.

Looks like the information we surfaced on iHub over the weekend and discussed, and Canes forwarded to Dr. Chan, made it to their twitter feed as they posted it this morning.

@CytoSorbents Announces this weekend, a news story on https://t.co/JLXk3kFMFl came out briefly mentioning the use of CytoSorb at the Wuhan Tongj Hospital on COVID-19 patients. An excerpt from the translated article is below: pic.twitter.com/ykq2cKcRHl

— CytoSorbents (@CytoSorbents) March 9, 2020

Let's hope they have put a lid on the ATM as it was causing considerable overhang on the stock price the past couple of months with all the good news. With $13.3M+ raised they said they now have enough cash runway to support operations and clinical trials into at a minimum, mid-2021. If they have, then the timing would be great with press release(s) next week about these first patients treated and the stock price will have a chance to run. Fingers crossed.


From 10-K: "During the period from January 1, 2020 through March 2, 2020, the Company sold 2,435,086 shares pursuant to the Open Market Sale Agreement with Jefferies LLC and B. Riley FBR, Inc., at an average selling price of $5.64 per share, generating net proceeds of approximately $13,322,000.

Thanks martys and tell your wife thanks. Its good to know she could possibly help us out with translating other information we may find in the future.

Also, if you use common sense the hospitals only received the filters 8-10 days ago so how could the patients have died after 3 weeks? What it means that some of these patients were already in the ICU for a week or so before they administered the treatments.

I think the reason this is not clear is due to translation issues. I am not fluent in Chinese but when I read the statement below I interpret this to mean that the patients remained an average of 3 weeks after various treatments including Cytosorb for stabilization and ended up saving (prolonging) their lives.

"One of the patients successfully removed the trachea intubation, and the average course of 6 patients exceeded 3 weeks, prolonging the patient's life."

Remember these are not conditions that the filter has not worked on every before and there have been thousands of treatments and hundreds of these patients reported over the years and only a very few cases I have seen the patient died but this was due to other factors.

If you think about it - it would be pretty silly for a bunch of nurses and doctors to pose with thumbs-up around a bunch of patients who died.

You have to click the 'Expand the full text' link below the picture of the three doctors looking at that book. This is what I missed.