Good afternoon, everyone, and thank you for joining us at the H.C. Wainwright 26th Annual Global Investment Conference. My name is Sean Lee. I'm an Equity Research Analyst at the bank. At this conference, we have over 600 companies presenting in multiple tracks devoted to life sciences, cryptocurrency, fintech, technology, and telecommunications. To our next presentation, I would like to welcome Dr. Phillip Chan, who is the CEO of Cytosorbents.
Thank you very much, Sean, and it's a pleasure to be here to be able to present the Cytosorbents opportunity to all of you today, particularly as we are on the verge, next month, of submitting DrugSorb-ATR for marketing approval to the U.S. FDA, as well as Health Canada, as the first therapy to reduce perioperative bleeding risk in patients undergoing CABG surgery on the blood thinner, Brilinta, targeting an up to $650 million total addressable market opportunity in the United States and Canada alone. But there's so much more to the story, so please stay tuned. 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 the ICU and cardiac surgery using our Cytosorb blood purification technology.
At a glance, we're a NASDAQ-traded medical device company commercializing our EU-approved CytoSorb blood purification cartridge in 76 countries worldwide, with $37.2 million in total revenue, trailing 12 months as of the end of the second quarter of 2024, $32.9 million in product sales and 75% in product gross margins. More than 250,000 CytoSorb devices have been used cumulatively to date, around the world, with now over 1,000 publications, ranging from peer-reviewed journal articles, abstracts, posters, and case reports where CytoSorb is used or discussed, and roughly $50 million in grant and contract support from U.S. agencies like National Institutes of Health, Department of Defense, as well as Defense Advanced Research Projects Agency, more commonly known as DARPA.
And we are doing things like treating cytokine storm and massive uncontrolled inflammation in diseases like COVID, sepsis, ARDS, pancreatitis, liver failure, and many others. We're also reducing other toxins, such as bilirubin in liver disease and myoglobin in trauma, and have the application of removal of blood thinners from or also known as antithrombotic drugs, during cardiac surgery that can cause bleeding. We also are fortunate to have a number of major strategic partners, including leading multinational corporations like Fresenius Medical Care, the number one dialysis company in the world, B. Braun, the number three dialysis company in the world, and Terumo Cardiovascular, one of the top four cardiac surgery companies in the world.
This is our ex-US story, but importantly, as I mentioned earlier, we are pursuing U.S. FDA and Health Canada approval for DrugSorb-ATR, a second product, an investigational FDA Breakthrough Designated device to reduce the severity of perioperative bleeding in patients undergoing CABG, or coronary artery bypass graft surgery, by reducing the leading blood thinner, Brilinta. We believe our data from our pivotal trial, called the STAR-T trial, that has now been completed, support a favorable benefit to risk profile of the therapy and will be the basis of our FDA De Novo and Health Canada applications for marketing approval this quarter. What does CytoSorb do and how does it work? The heart of our technology is a biocompatible, highly porous polymer bead that acts like a tiny sponge to remove harmful substances from blood.
You can see a cutaway of our device here, filled with hundreds of thousands of these tiny, porous polymer beads, and on the right-hand side, a schematic cutaway of the bead, showing this vast network of pores and channels on which we are able to bind toxic substances very efficiently. The key to our technology is one that is highly biocompatible, so it can touch whole blood without bad things happening to it. But the other major advantage of our technology is that it has massive surface area, more than seven football fields of surface area in a single cartridge that is roughly the size of a drinking glass. 22 issued U.S. patents and multiple patents issued and pending worldwide, and we manufacture this at our state-of-the-art ISO 13485 certified facility in Princeton, New Jersey.
The nice thing about our business model is that this is a CytoSorb is plug-and-play compatible with the existing blood pump infrastructure that exists in hospitals today, whether or not it's a dialysis or CRRT pump in the intensive care unit, an artificial lung, also called an ECMO or extracorporeal membrane oxygenation pump in the ICU, a simple hemoperfusion pump, or a heart-lung machine, also called a cardiopulmonary bypass machine. People ask often: Why is this different from dialysis technology, which is widely regarded as the most common form of blood purification today? We are fundamentally different from, but complementary to dialysis technology because we remove a broad range of dissimilar toxins that dialysis does not remove well.
Dialysis, you may be aware, works like the kidney and tries to replace the kidneys when the kidneys fail by removal of small molecules, water-soluble substances, electrolytes, metabolic waste products, water-soluble drugs. But we are expanding the dimension of blood purification by helping to replace the liver and the removal of large molecules and fat-soluble substances, things like cytokines and cytokine storm, inflammatory mediators, bacterial toxins, liver toxins, proteins and peptides, as well as fat-soluble drugs. We are targeting deadly conditions that afflict millions of people. In critical care, we are removing the fuel to the fire of massive uncontrolled inflammation that is often associated with organ failure and death in many, many life-threatening illnesses that you can see here.
But in cardiothoracic surgery, we're also reducing inflammation, as well as blood thinners that are often causing complications in cardiac surgery, like sepsis, bleeding, shock, and others. We're also riding many major trends in healthcare. One of the major ones is the aging population, the fact that there are more than a billion people over the age of sixty worldwide, and because of the baby boomer population, they're just getting older. Sepsis, for example, is being driven by the aging population, and sepsis today accounts for one in every five deaths worldwide from any cause. But it's also driving things like structural heart disease, endocarditis, the use of prosthetic heart valves, coronary artery disease, falls and causing trauma, the need for, organ transplant or cytokine release syndrome in cancer immunotherapies. But another major trend is the use of blood thinners.
As you'll hear later, that millions of people are on these blood thinners worldwide to reduce their risk of heart attack and stroke. But again, what happens if someone needs to go for unscheduled surgery with these blood thinners on board? That's a major problem. They will bleed. Chronic liver disease amazingly afflicts one in five people worldwide, and millions of people are hospitalized every year for acute exacerbations of their chronic liver disease, which is something that we can help to treat. And then endocarditis is, again, another major problem being driven by the use of prosthetic heart valves that can get easily infected. That's what endocarditis means, infected heart valves.
Or because of the opiate crisis and the use of dirty needles, people shooting themselves up with bacteria that wind up on a heart valve and can destroy that heart valve in days. This is another area that we can help. So CytoSorb is not a black box. We don't just remove things, but we're also helping to alter human physiology. In particular, we are helping to reverse the shock that is caused by cytokine storm and deadly inflammation. Shock is a drop, a potentially fatal drop in blood pressure.
And we also are able to help fight against capillary leak syndrome that is often caused by cytokines and cytokine storm that cause a disruption of the endothelial tight junctions between cells lining the blood vessels, causing blood vessels to become leaky, ultimately, causing fluid to easily leak out of blood vessels into the surrounding tissues. When that happens in the lungs, for example, that can cause someone to drown from the inside out. But when it can happen anywhere in the body, it acts as a major barrier to gas and oxygen and carbon dioxide diffusion, for example. So reversal of shock is a key feature of Cytosorb usage, resulting in the ability to wean off vasopressors, restore both macro and microcirculation, reduce lactate, promote capillary leak reversal, enable fluid removal.
But it is also helping to create new avenues for organ support. One of those areas is enhanced lung rest, which we believe will become a new paradigm for the treatment of severe acute respiratory distress syndrome. You may be familiar that ARDS was the major reason why people died during the COVID pandemic from lungs that filled with fluid and basically, again, drowning from the inside out and not being able to survive. Our former Chief Medical Officer, Dr. Robert Bartlett, who was the pioneer of ECMO and our former Cytosorbents Chief Medical Officer for 10 years, had predicted that the use of ECMO, which is this artificial lung, would be able to help rest the lungs and prevent ventilator-induced lung injury.
But it doesn't do anything to stop the ongoing injury and capillary leak caused by cytokine storm. But that's exactly what CytoSorb can do. And in 100 patients in our CytoSorb therapy in COVID-19 registry, called the CTC Registry, where we worked to enhance lung rest with CytoSorb plus ECMO under FDA Emergency Use Authorization, we were able to achieve 74% 90-day survival in 100 consecutive COVID patients with refractory lung failure from five major U.S. ECMO centers. And you can see here that the survival, three out of four people survived 90 days versus with ECMO alone, as reported by the ELSO, or Extracorporeal Life Support Organization registry, only about one in two people survive, showing the potential amazing synergy that CytoSorb plus ECMO could have in helping lungs recover faster and aiding in survival.
And then continuing on in the avenue of, of organ support, as I mentioned, roughly one in every five people have chronic liver disease, and this is a picture of what someone looks like who has chronic liver disease. They're jaundiced because the skin and the eyes, for example, are accumulating toxins that the liver normally gets rid of. In this case, this would be bilirubin. But if a picture was worth a thousand words, look at our device before treatment of someone with chronic liver disease, and now look at our device after the treatment of someone with chronic liver disease. It just has massive capacity to bind these liver toxins, and in fact, we believe it's, in fact, the best extracorporeal liver support therapy on the market today around the world.
We are actively driving product sales, and we are selling CytoSorb through direct sales in 15 countries around the world and distributors in more than 60 countries. What you can see here is our annual product sales. The orange arrow here shows that we have historically grown at a CAGR of about 26%, even through the pandemic. During the pandemic, we benefited from roughly $16 million in excess sales related to COVID. When COVID went away with vaccinations and with Paxlovid, rate of critical illness related to COVID went away, and that's why you can see here no more sales related to COVID. In 2022, we were further impacted by the fall of the euro to the dollar, compared to 2021.
Without, on a constant currency-adjusted basis, core sales in 2022 would just have been shy of core sales in 2021. But what you can see here is that over time, we have been gradually getting back, despite that continued drop in the euro currency and despite some of the headwinds that we face related to COVID in the ICU markets because of staffing shortages throughout the world, we have been coming back. In 2023, core CytoSorb sales grew 10% over 2022, and we're off to a good start in 2024.
First half of this year, we announced $17.8 million in product sales, which is up 12% year over year, $32.9 million in trailing twelve-month sales, and 75% blended product gross margins, mixing higher-margin direct sales with lower-margin distributor sales. Why do we think that we can be one of the... Why we are one of the leaders in acute care blood purification and why we hope to dominate this segment is because today, all the major dialysis players are focused on the 10%-15% of patients who have failed kidneys, right? This is where the leaders, like Fresenius, Baxter, B. Braun, Asahi, Nikkiso, Nipro, JMS, and others are focused.
But in the intensive care unit, where we are focused as a company, is really on the 40%-60% of patients who are suffering from life-threatening inflammation and toxin overload, that is responsible for a lot of these common everyday diseases that you see in the ICU, like sepsis, pancreatitis, burn injury, trauma, liver failure, and many, many other illnesses, right? And this is one of the reasons why, we are partnered with Fresenius Medical Care, for example, to expand the dimension of blood purification in critical care. Now, targeting to the U.S. and Canadian markets, DrugSorb-ATR for blood thinner removal.
As I mentioned before, millions of people are on blood thinners to reduce their risk of heart attack and stroke, and Brilinta, Xarelto, and Eliquis are just some of the blockbuster drugs in this class that are used by millions of people around the world. The problem is that patients who require unscheduled, urgent, or emergent cardiothoracic surgery, and again, most of these patients are vascular patients who have a high risk of needing emergent or urgent cardiothoracic surgery. If they're on these blood thinners, they don't have time to wash out the drug like they would for an elective procedure, and they can develop serious bleeding complications, and currently there is no approved reversal agent in the United States or Canada for cardiac surgery.
In fact, CytoSorb is the only reversal agent found elsewhere in the world for the prophylactic reversal of these agents. So DrugSorb-ATR is an investigational device that uses an equivalent polymer technology to CytoSorb and installs easily into a heart-lung cardiopulmonary bypass machine. You can see how we are right here, central, to this circuit. As whole blood is pumped through the cartridge, it is designed to remove free drug during surgery from blood to reverse its blood-thinning effect. Because of this, FDA has granted two FDA breakthrough device designations for DrugSorb-ATR, highlighting the major unmet medical need and lack of effective therapies and provides for priority review of marketing submissions.
In 2020, we received breakthrough device designation for the removal of Brilinta, and in 2021, we received a breakthrough designation for the removal of the direct oral anticoagulants, Eliquis and Xarelto. So today, we'll focus predominantly on Brilinta, which is anticipated to be the subject of our first submission to FDA for approval. So this is the major use case for Brilinta. Someone coming into the hospital with a heart attack is immediately put on aspirin and a super aspirin as part of what's called dual antiplatelet therapy. This is very much along the lines of if someone you know has a heart attack at home, first thing you do is call nine one one. Second thing you do is give them an aspirin to thin the blood to prevent that clot from getting worse.
All these people will go to the cath lab, where 90% of patients will typically get a stent, but 5%-10% of patients will not be eligible for a stent, will ultimately need open heart surgery or CABG surgery. But if they go to surgery, ultimately they will bleed. And the only accepted therapy today is recommended by American Heart Association and American College of Cardiology is to sit and wait in the intensive care unit or step-down unit or on a hospital ward. But the main thing is to sit in the hospital while they're still having a heart attack, by the way, because they haven't fixed it, because they were not eligible for a stent, and to wash out the drug over the course of 3-5 days at a cost of thousands of dollars.
It can rise if they're staying in the intensive care unit, up to $30,000 in cost, to basically wash out the drug and then go to surgery. But with DrugSorb-ATR, our value proposition is that by binding the drug, we are actually accelerating that washout and making this whole waiting process in the hospital unnecessary and allowing patients to get the critical surgery that they need without delay, while reducing or preventing bleeding complications. And this has led us to running the pivotal randomized controlled trial called the STAR-T Trial, which is now completed. And this was led by luminaries in the field of cardiac studies, including Dr. Michael Mack, Dr. Richard Whitlock, and Dr. Michael Gibson, as the STAR-T investigators.
This was a 140-patient, 30-center study in the US and Canada, in patients undergoing cardiac surgery within two days of the last dose of Brilinta, either getting DrugSorb during surgery or not getting DrugSorb during surgery, and looking at safety as the primary safety endpoint, and then perioperative bleeding risk in a composite primary efficacy endpoint that covers the total gamut of perioperative bleeding, ranging from, in a hierarchical fashion, fatal bleeding, severe bleeding, moderate bleeding, and then mild to moderate bleeding. We don't have time to go over these data today, but to suffice it to say, we hosted a KOL event that is on the LifeSci Advisors website. Please feel free to copy this down.
This presentation will also be available to you, where you can click on this link, and it will bring you to a multi-hour presentation on this. But to suffice it to say, there were no safety concerns in the study. Imbalances in the number of high-risk non-CABG surgery patients led to missing the primary efficacy endpoint in the overall surgery population. However, severe bleeding endpoint was met in the CABG per-protocol population and overall in patients undergoing CABG. DrugSorb-ATR was associated with reduced bleeding severity by a universal definition of perioperative bleeding grade or chest tube drainage volume. The number needed to treat to avoid a major bleed was six patients, and it had a very favorable benefit-to-risk profile. And again, we plan to submit this in the United States and Canada this quarter.
So we believe that this is a major win-win market pull proposition for patients, surgeons, and hospital administrators. We believe it will enable us to target a $650 million total addressable opportunity in the United States and Canada. That, if we can expand that to other blood thinners like Eliquis and Xarelto, would double that market opportunity. And then, if we can expand this to all surgeries, a $2.2 billion opportunity overall in the United States and Canada. So we see tremendous opportunity in critical care and cardiac surgery, fueled by important demographic trends. We're at the forefront of innovation in critical care because of our ability to treat deadly inflammation that is core to so many diseases that can remove other toxins as well.
We are excited by our near-term operational progress with sales and product gross margins, but we are in particular excited that we are on the cusp of submitting for regulatory approval of DrugSorb-ATR in the U.S. FDA and Health Canada, which could be an inflection point for our company. By pushing its boundaries and driving innovation, we are committed to expanding the dimension of blood purification, setting the stage to truly transform medicine and create value for shareholders. With that, let me thank you very much for your attention and turn it over back to you, Sean.
Thank you, Phil, for a very productive and informative presentation. We appreciate the time and effort that went into preparing them, and we're very grateful to all of our presenters for your flexibility and your presence at our conference this year. Thanks again from the H.C. Wainwright team.
Thank you very much.