Well, good morning. Welcome. I am Dr. Phillip Chan, the Chief Executive Officer of CytoSorbents. Thank you very much for coming to the presentation today. I hope to give you an update on where we are and the value proposition that CytoSorbents represents. As a publicly traded company, please let me remind you of our Safe Harbor Statement for forward-looking statements. CytoSorbents is leading the prevention or treatment of life-threatening inflammation and other deadly conditions in both the intensive care unit as well as cardiac surgery, using our CytoSorb blood purification technology. At a glance, we are a U.S.-based international medical device company commercializing CytoSorb that is EU approved in 75 countries around the world.
We generated $37.1 million in total revenue as of the end of the trailing twelve months as of the end of the third quarter of 2023, $31.4 million in product sales, 72% product gross margins as of the end of Q3, and roughly 176 employees currently. We have now done more than 221 CytoSorb devices internationally since inception, and this is as of the end of the third quarter of 2023, treating cytokine storm and massive uncontrolled inflammation in a wide variety of life-threatening illnesses such as sepsis, burn injury, trauma, liver failure, pancreatitis, and many others. Also, we're also approved to remove bilirubin for the treatment of liver disease and myoglobin for the treatment of trauma.
And importantly, for today's discussion, we are also approved to remove blood thinners or antithrombotic drugs during cardiothoracic surgery that can cause unwanted and potentially even fatal bleeding. We are partnered with some of the leading multinational corporations in the world, including Fresenius Medical Care, the number one dialysis company in the world, B. Braun, the third-largest dialysis company in the world, and Terumo Cardiovascular, one of the top four cardiac surgery companies globally. That is one part of our business, but the second part of our business is really looking to open up the U.S. and Canadian markets for the first time.
We are nearing the final data analysis for the now completed pivotal U.S. and Canadian STAR-T randomized controlled trial, and this summer, plan to submit for U.S. FDA and Health Canada approval for DrugSorb-ATR, an equivalent polymer technology to CytoSorb, to reduce the severity of perioperative bleeding related to the blood thinner, Brilinta, in patients undergoing isolated CABG or coronary artery bypass graft surgery, commonly known as bypass surgery. CytoSorb has previously received FDA Breakthrough Device Designation for this application. So what does CytoSorb do and how does it work? In every single cartridge are hundreds of thousands of tiny porous polymer beads, roughly the size of a grain of salt, that act like tiny sponges to remove toxic substances from blood very efficiently.
You can see here a cross-section of our beads on the very right-hand side and a vast network of pores and channels that give each of our cartridges, which is roughly the size of a drinking glass, massive surface area of about seven football fields of surface area within a single cartridge. Massive capacity on which to bind things. We have 19 issued U.S. patents and multiple patents issued and pending worldwide, and we manufacture this ourselves at our manufacturing facility in Princeton, New Jersey.
The nice thing about our business model is that we are the razor blade that works in the razor blood pump infrastructure that exists in hospitals today, whether or not it's a dialysis or continuous renal replacement machine on the upper left-hand side, an extracorporeal membrane oxygenation machine on the upper right, cardiopulmonary bypass machine used in open heart surgery, or a hemoperfusion machine. People often ask why this is different from dialysis. Well, CytoSorb is very different from dialysis, but is very complementary to dialysis as well because it removes a different range of toxins. Dialysis works more like the kidney. When people have kidney failure, that's when people use dialysis, and it's good at removing small molecules, water-soluble substances, metabolic waste products, and other things.
But what it can't do is remove macromolecules that your other detoxification organ in your body uses, which is your liver. CytoSorb acts kind of like the liver, removing large molecules and fat-soluble substances and a wide range of inflammatory mediators like cytokines, bacterial toxins, and activated complement, liver toxins, and many other things that standard dialysis cannot remove. Because of that, we are expanding the dimension of blood purification. We're targeting deadly conditions that afflict millions of people. On the left-hand side here, you can see common everyday conditions that afflict people in every ICU around the world, which is either life-threatening infection, influenza, COVID, lung injury, trauma, burn injury, pancreatitis, cytokine release syndrome from cancer immunotherapy, liver failure, and many other illnesses.
We are removing the fuel to the fire of inflammation from the bloodstream that is driving this uncontrolled inflammation. In cardiac surgery, we're reducing inflammation in very complex cardiac surgeries to try to help improve outcomes, but we're also now removing blood thinners to try to reduce the risk of bleeding in patients on these agents. We are riding many macro trends in healthcare. The major one is the aging baby boomer population. Currently, there are over 1 billion people over the age of 60, and these are the people who are dying from life-threatening illnesses like sepsis, COVID, influenza, structural heart disease like valvular disease, coronary artery disease, trauma from falls, and many, many other illnesses. But another major trend that we have is the use of blood thinners.
You probably all know someone on aspirin or Xarelto or Eliquis or Brilinta or some other blood thinner designed to reduce that person's risk of heart attack and stroke. Millions of people are on these agents currently today. The problem is that if they have to undergo unscheduled surgery, they will bleed, and that is one of the major applications that we're targeting, specifically around the world, but also specifically in the United States. Another major disease state that we are looking to treat is liver disease. Amazingly, one in seven or one in eight people around the world have chronic kidney disease, and that has spawned a multi-billion-dollar industry led by Fresenius, Baxter, B. Braun, and many others.
But what you may not realize is that liver disease is even more prevalent, with one in five people having chronic liver disease from alcoholism, hepatitis, as well as obesity and causing fatty liver. This is an area as a liver replacement therapy, a liver support therapy, that we directly address. And then endocarditis, which is being driven by prosthetic heart valves like TAVR, but it's also being driven by the opiate crisis and the use of dirty needles, resulting in infected heart valves. Now, this is a slide that shows our marketed products and product pipeline. Our innovation has been driven by approximately $50 million in grants from the U.S. government. On the left-hand side, you can see CytoSorb. We'll talk a little bit more about ECOS-300CY and VetResQ. On the right-hand side, notably, is DrugSorb-ATR and another product called HemoDefend-BGA.
Now, ECOS-300CY is a device that is designed to be used with ex vivo organ perfusion in the solid organ transplant market. Many of you know that solid organ transplant is the main treatment option in advanced organ failure, but is limited by the availability of suitable and healthy organs. Ex vivo organ perfusion with temperature-controlled, oxygenated, nutrient-rich fluid or blood products is being increasingly used as an alternative after explanting from the donor, as an alternative to transporting the organ on ice, to improve functioning of the transplant organ and to salvage substandard ones that would normally be discarded, because they aren't functional and working well. However, ex vivo organ perfusion does not directly control inflammation with the organ that is core to the organ's dysfunction. That is what ECOS-300CY was approved to do in the European Union.
On the lower left-hand side here, you can see the ex vivo organ perfusion machine from one of our partners, Aferetica, and our product, that is, private labeled for this company, fits right into the machine. And as the organ is in transport and is being transported to the recipient, it is being perfused with fluid that is being purified by our technology. The goals and cited benefits of our ECOS-300CY technology in early data are that it reduces inflammatory mediators, it helps to recondition poorly functioning organs that would normally be discarded, increasing the donor pool of scarce organs, and has been demonstrated, at least in early studies, but very promising results, to reduce the rates of primary graft dysfunction. This is when the organ is transplanted into the patient and doesn't work. That's a disaster, right?
In lung transplant, that can be as high as 50%, right, within the first couple of years of the transplant. And because of that, we may be able to help improve outcomes as well. Now, VetResQ is for companion animals. If we polled this room, we'd probably see some common numbers, but the COVID pandemic has driven companion animal ownership, with 45% of U.S. households owning a dog and 26% owning a cat, according to the American Veterinary Medical Association. Companion animals are prone to a wide variety of medical emergencies, ranging from drug intoxication, from eating their owner's medications, to heatstroke, to sepsis and trauma, and many other illnesses. VetResQ brings the power of CytoSorb to the veterinary medicine with three sizes of cartridges intended to treat the full size range of companion animals.
In 2023, we had a limited but very successful launch of VetResQ to a number of regional veterinary medical centers, and in 2024, we will debut our integrated all-in-one solution that includes a hemoperfusion pump for vets. In our pipeline is HemoDefend-BGA, which has the promise of universal plasma. HemoDefend-BGA was developed to create universal plasma, which is plasma that does not need to be blood typed, to be given to patients. It can be given off the shelf regardless of their blood type by removing anti-A and anti-B antibodies that make plasma blood type specific. So we are going from a very complex blood type-specific plasma logistics to a very simple universal plasma that can be pulled off the shelf. And in collaboration with freeze-dried plasma providers, this could be made available to everyone without refrigeration.
Many applications of life-saving plasma include trauma resuscitation, treatment of critically ill patients, and component purification, if you know companies like Grifols, CSL Behring, Takeda, and others, who make clotting factors and derive albumin and IVIG from blood, from blood products, and from plasma, specifically. In the U.S. alone, more than 10,000 units of fresh frozen plasma are administered daily, or 3.6 million units per year. With now more than $17 million in funding from the U.S. Department of Defense, CytoSorbents has successfully developed and demonstrated a prototype HemoDefend-BGA adsorber that removes anti-A and anti-B antibodies from human plasma. Again, with the goal of having our off-the-shelf, one-size-fits-all blood type, independent universal plasma in every ambulance and every emergency room around the world.
We've now recently met with FDA in preliminary discussions with the goal of advancing HemoDefend-BGA to human clinical trial and commercialization. So getting back to our core business, though, of CytoSorb, what is our company's business model and our financial performance? As I mentioned before, we are distributed in 75 countries around the world, with closing in on 250,000 uses worldwide to date in critical care and cardiac surgery. We sell direct in 15 countries, Germany, Austria, Switzerland, the Benelux region, Scandinavia, Poland, as well as the U.K., with our own direct sales force. And then we sell through distributors in other places around the world, 60 other countries around the world. Roughly two-thirds of our business comes from critical care. Roughly half of all of our business comes from sepsis, the leading cause of death in the world.
one in five deaths are related to sepsis, which is the overzealous immune response to a life-threatening infection like COVID, like flu, like pneumonia, like strep pneumonia or other types of infections. About a third of our business comes from cardiac surgery. By geography, roughly 60% of our business comes from direct territories, while 40% of our business comes from distributors and partners. CytoSorb, as I mentioned, is a high-margin razor blade that fits into the blood pump infrastructure into hospitals around the world. We have blended historic gross margins of approximately 80%. Our, our margins dropped as we transitioned to a new manufacturing facility, but this year we believe it will get back to the 75%-80% range.
The average direct selling price is about $1,000 a cartridge, and we use typically 1-5 cartridges per patient, depending on the disease that we're trying to treat. In Germany, there are 400 hospitals that have more than 400 beds as a microcosm of the global opportunity. They typically see 10%-20% of their treatments as sepsis patients. At 3-5 cartridges per patient, that's $3,000-$5,000 per patient. Potential revenue per hospital for $1 million-$3 million for sepsis alone. We've already previously disclosed that one German hospital had more than $1 million in sales of CytoSorb, broadly adopting CytoSorb in critical care and cardiac surgery. This is our annual product sales. As you can see here, that we have had a historic CAGR of about 25%-26%.
That was core sales of CytoSorb, non-COVID sales that are in blue. In purple, you see our COVID sales. In 2022, there was a decline in sales that was related to kind of the post-COVID hangover, where we didn't have any more COVID sales because people weren't getting as sick because of vaccinations and Paxlovid, but also because of a drop in the euro to the dollar, and that actually hurt us quite a bit. In fact, on a constant currency basis, we would have been within 5% of our record core sales in 2021, had the currency been adjusted. In the first three quarters of 2023, you can see that we have had stable, roughly 11% growth. So what are our key goals for 2024?
The first one is to grow high-margin CytoSorb sales, and the second one is to get DrugSorb-ATR approved in the United States and Canada. We are targeting a return to significant growth. We won't go through this slide in much detail, but it represents kind of the gamut of different things that we are working on to help drive this growth. One of the key factors that will help us meet this growth is our new manufacturing facility that I told you about before. This has now capacity to make up to four to supply up to $400 million in CytoSorb sales, and this is based out of our Princeton, New Jersey, manufacturing facility. All of our products are being manufactured out of this facility currently, and again, expect to get back to that 75%-80% product gross margin range this year.
A second initiative that we have is our global marketing agreement with Fresenius Medical Care. We have had a partnership with Fresenius for many years, and it has evolved over the years. But Fresenius Medical Care, as I mentioned before, is the number one dialysis company in the world and the number one or number two player in critical care, next to Baxter. Last year, we announced a new expanded global marketing agreement with Fresenius, where CytoSorb became the feature technology for cytokine, bilirubin, and myoglobin removal on its critical care platform worldwide, excluding the United States, where they will be discussing our technology and publicizing our technology through many, many different avenues, including social media, including conferences, symposia, and other things.
Why this is important for both companies is it, again, is expanding the dimension of blood purification with excellent synergy between both companies. Today, Fresenius, with Baxter, dominates the kidney replacement market, people with kidney failure in the ICU, but that only represents about 10%-15% of patients in the ICU today. CytoSorb strengthens and broadens the focus on the lucrative critical care segment, as CytoSorb helps to address deadly inflammation and toxin overload that afflicts 40%-50% of patients in the intensive care unit, right? And thereby expanding the dimension of blood purification for Fresenius as well as for us. We want it to be a win-win for Fresenius, and we negotiated a 0.9% royalty to Fresenius, so that as we are successful, they are successful as well. And they're, we are very well aligned.
This came from the capital markets presentation from Fresenius last year, where they took their businesses and categorized them based on the Y-axis strategic value to Fresenius and on the X-axis growth potential. What you can see here is that critical care is one of the top three businesses that meet both of those criteria, which is one of the reasons why this partnership is so potentially synergistic. Now, this year, we will be last year, we had a foray on a standalone pump initiative with partner Nikkiso, a big Japanese blood pump manufacturer, dialysis company. But this year, we will be launching our own pump called the PuriFi Pump by CytoSorbents. Our standalone pump initiative is expected to bring our next-generation blood purification capability to countries that do not have a strong dialysis infrastructure.
So this will hopefully be launched in the near term. We're also expanding into new markets, and I mentioned to you about the opportunity in liver disease. This is a person you may know someone who has chronic liver disease with jaundice, yellow eyes, yellow skin. If a picture is worth a thousand words, here is our device before treatment of a liver disease patient, and this is our device after treatment of a liver disease patient. One of the most effective technologies for removing liver toxins on the market today, but not only does it remove liver toxins, it does what most other extracorporeal liver support therapies don't do, which is it removes cytokines.
Unlike all these other therapies like MARS and SPAD and others, this is very easy to set up, uses machines that exist in ICUs today, and it's just blood in, blood out. Very simple to implement. We believe we will—this product will finally deliver upon the promise of extracorporeal liver support. This is data from the COVID pandemic in the United States, where we were treating the sickest of the sick patients who failed mechanical ventilation because their lungs were so diseased. In many countries, those patients just died. But because of an innovation called ECMO, extracorporeal membrane oxygenation, a machine that can oxygenate blood outside of the body, these patients had a chance.
What you can see here is that red line showing that with ECMO alone, one in two patients typically were able to survive, but typically after a very prolonged time on ECMO as well as mechanical ventilation. What we showed is that using CytoSorb with ECMO, ECMO helps rest the lungs, helps get them off dangerous mechanical ventilation, right? But it doesn't do anything to remove the circulating cytokine storm that causes perpetual lung injury, right? You have to have the lungs heal to get off these life support machines, right? But that's what CytoSorb does. We call that enhanced lung rest, and I would predict that, in fact, this will be one of the ways that severe lung injury will be treated in the future. We are going to change the paradigm of treating lung injury.
No longer will people be on mechanical ventilation for weeks and weeks and weeks, only to be salvaged by ECMO at the end, but actually to try to treat them upfront and prevent all that damage from happening, reverse the damage to the lungs by the cytokine storm. So in the time remaining, I'd like to talk about the second opportunity, which is really the U.S. and Canadian opportunity: getting DrugSorb-ATR, which uses an equivalent polymer technology to CytoSorb, approved in the U.S. and Canada. And we're doing that based upon its CytoSorb's ability to remove the drug and to reduce bleeding events in patients that have to undergo unscheduled cardiac surgery on these agents.
So blood thinners, also known as antithrombotic drugs, are used by millions of people around the world, as I mentioned, to reduce the risk of heart attack and stroke, Brilinta, Xarelto, Eliquis. These are some of the largest-selling blockbuster drugs in the world. In fact, Eliquis is the number three non-COVID pharmaceutical in the world at $18 billion in worldwide sales.
The problem is, again, if they need unscheduled surgery, whether or not it's from a motor vehicle crash, and they're bleeding internally, or whether or not it's from someone bleeding in the brain because of these blood thinners, or if they're having a cardiac event and now they need open heart surgery, there is no. It's very difficult to reverse these agents, and there is no approved reversal agent in the United States or Canada, specifically for cardiac surgery, which is where we are focused. So how do we work? We plug right into the heart-lung machine that is keeping the patient alive during open heart surgery. CytoSorb does this in this picture. As you can see, DrugSorb does it the same exact way. Here's the use case. Someone comes into the hospital with having a heart attack.
As you guys know, the conventional wisdom is if you know someone's having a heart attack, first, you call nine one one. Second, you give them an aspirin, which is an a blood thinner, a weak blood thinner, but is designed to try to make that clot not expand, that is in the-- that's blocking the heart artery. But in the emergency room, they give you not only aspirin, but they give you a super aspirin like Brilinta or like Plavix. These patients go to the cath lab. 90% of these patients will typically get a stent, but 5%-10% of these patients will not be eligible for a stent because of multi-vessel disease, left main disease, intractable ischemia, maybe a complication from putting in the stent like a coronary artery dissection.
They need to now go to surgery to get a bypass, but if they go to surgery, they will bleed. The only accepted countermeasure is to have them wait. Just like if you went in for elective surgery, they say, "Stop taking your aspirin. Stop taking your blood thinner 3-5 days before." Right? Well, these patients who are having a heart attack that has not yet been fixed are now being asked to wait in the hospital 3-5 days on average, in ICU at $6,000 a day, on a hospital ward bed at $2,000-$3,000 a day, because the fear of bleeding because of these blood thinners is so great. Cardiac surgeons deal with this problem every single week. They have patients with this exact same problem, right?
But what DrugSorb-ATR is designed to do is, in fact, not have to wait, right? Or reduce the wait, to be able to get the critical surgery that they need without reducing... while reducing bleeding or preventing bleeding complications. Right? So what is the bleeding risk? We show here a comparison between the SWEDEHEART, which is the most complete cardiac surgery registry, including the use of blood thinners from Sweden. The data I will show you does not include patients treated with CytoSorb or DrugSorb-ATR, and compare that with our STAR Registry, which is our real-world data registry from the use of our therapy in Europe. Right? This is not the U.S. study. But on the left-hand side here, forget the orange for the moment, just look at the blue.
This is the risk of having a major life-threatening bleed if you have to go to surgery within 48 hours of getting Brilinta in the emergency room. You see here, the SWEDEHEART Registry, it's about 31% risk of having a massive bleed. In our real-world registry, summarizing CytoSorb usage in the first and second analyses, you can see 6% and 4.5%, a dramatic reduction in bleeding risk. So that really brought us to the U.S. and Canada, where we, in the U.S., we were awarded two FDA breakthrough device designations for this application, one for Brilinta and one for Eliquis and Xarelto, essentially a fast track from the FDA.
The STAR-T trial, the randomized controlled trial, was designed to evaluate perioperative bleeding complications associated with recent Brilinta administration, with or without the use of DrugSorb-ATR in the cardiopulmonary bypass circuit during cardiac surgery. Simply put, STAR-T was 140 patients enrolled at 30 centers undergoing cardiac surgery within two days of their last dose of Brilinta. They were randomized one to one with DrugSorb or without DrugSorb during cardiopulmonary bypass, and we were looking at primary safety endpoint, as well as primary efficacy endpoint of reduction in perioperative bleeding, looking at the gamut of perioperative bleeding, from fatal bleeding on one end to moderate to severe bleeding, to chest tube drainage, which measures the rest of the bleeding events.
What we showed, the trial finished last year, and in December, the Data Safety Monitoring Board reviewed the unblinded data on all 140 patients, demonstrated that it was safe. We met the primary safety endpoint. In December, we announced the top-line data from this trial, showing that we missed the primary efficacy endpoint of the study when we included all comers, not just isolated CABG patients, but people who thought they were having a heart attack, but really weren't. Things like aortic dissection or aortic valve, or valve replacement, valve damage and valve replacement, surgeries that are much more complex than isolated CABG that bleed a lot more. Because of this, we did not hit the primary endpoint, but in a pre-specified isolated CABG population, we demonstrated evidence of efficacy.
This represented more than 90% of patients in this study, and evidence of efficacy, including a reduction in serious bleeding events, which is what we intended to demonstrate in the first place. Now, most investors are not giving us the benefit of the doubt right now, which is why our stock is so low, but we do not view this trial as a failed study. We actually view this trial as a trial that can help support FDA and Health Canada approval, and now having completed additional data analysis, we are reaffirm our belief that DrugSorb-ATR has an excellent benefit to risk profile, demonstrating efficacy and reducing serious bleeding risk in the main target patient population, isolated CABG, and can support regulatory submission to FDA and Health Canada.
We have now submitted for a late-breaking presentation in a major upcoming conference in April and are currently under data embargo. However, we plan to subsequently have an analyst investor event with our study principal investigator shortly afterwards to review the data. From a timeline perspective, as you can see here, late-breaking presentation in April, STAR Registry, real-world data presentation in May, submission to FDA, summer of this year, submission acceptance 45 days later, Health Canada submission in the second half of 2024, FDA review process of 8-10 months, we can't guarantee how the FDA will review the data, but if we are successful, we anticipate mid-2025 for approval, beginning CytoSorb, beginning DrugSorb-ATR sales in U.S. and Canada in the second half of 2025, and then Health Canada drug approval in the second half of 2025 as well.
We would be addressing a $325 million total addressable market in the outset. As Brilinta goes off patent this year, we expect it to gain market share against its major competitor, Plavix, and hopefully driving the total addressable market to about $650 million. So today, CytoSorb drives our growth. CytoSorb forms the foundation of our company. It's EU approved and sold around the world, has generated more than $200 million in sales since launch. High-margin razor blade business, 80%+ historic gross margins, and strong validation from customers, partners, and government agencies. This is a product that addresses a $20 billion-$30 billion total addressable market worldwide in critical care, cardiac surgery, and liver and kidney disease.
And we believe that this gives us the profile of a biotechnology company, the upside of a biotechnology company, but with the lower risk profile of a high-margin medical device company with sales and a track record. Should STAR-T be successful. So that is a single engine of growth. But should STAR-T be successful, and we are able to drive U.S. and Health Canada approval, this will become a dual engine of growth, and at 90+% product gross margins, we anticipate a major contributor to our profitability. At this stage, we believe our company represents an exceptional value proposition. So with that, I'm a little over time, but happy to answer any questions that you may have, if we can exist. We can do so. Please. Why the majority of sales in Germany? Germany is actually where we started.
We did our first study in Germany, and so Germany is the third largest medical device market in the world, the largest by far in the European Union. So that is where we wanted to focus first. But that's really where we are in most of accounts, driving about 40% of our business. But now, if you have followed our company for a while, you've seen us expand internationally, where direct sales are now coming up the pike in other countries, and distributor sales are actually doing quite well as well. Any other questions? Okay. Well, let me let the next speaker go, and thank you very much, everyone. Appreciate it!