CytoSorbents Corporation (NASDAQ: CTSO) is a U.S. medical device company focused on treating life-threatening conditions in the ICU and cardiac surgery using blood purification. The company’s flagship product, CytoSorb®, is a blood purification cartridge approved in the European Union – with distribution in 75 countries around the world – to reduce cytokines and “cytokine storm” that can cause massive inflammation, organ failure and death in common critical illnesses such as sepsis, burn injury, trauma, lung injury, liver failure, pancreatitis, and cytokine release syndrome in cancer immunotherapy. These are conditions where the risk of death and cost of treatment are extremely high, yet few, if any, effective treatments are available. CytoSorb is also E.U. approved to reduce bilirubin and myoglobin in clinical situations such as liver disease and trauma, respectively. CytoSorb received FDA Emergency Use Authorization for use in adult, critically ill COVID-19 patients with imminent or confirmed respiratory failure and has been used to treat more than 7,600 COVID-19 patients in more than 30 countries. In 2020, CytoSorb was also approved in the E.U. to remove ticagrelor (Brilinta®, Brilique®) and rivaroxaban (Xarelto®), two leading antithrombotic drugs or “blood thinners,” during urgent and emergent cardiothoracic surgery. CytoSorb has been used in more than 212,000 human treatments to date.
CytoSorbents is also pursuing U.S. FDA and Health Canada approval of DrugSorbTM-ATR, an investigational blood purification technology using an equivalent polymer technology to CytoSorb, capable of removing multiple classes of blood thinners during cardiothoracic surgery. DrugSorb-ATR has already received two FDA Breakthrough Device Designations to remove the anti-platelet agent, Brilinta®, and to remove the direct oral anticoagulants, Eliquis® and Xarelto®. CytoSorbents has completed the U.S. and Canadian STAR-T (Safe and Timely Antithrombotic Removal of Ticagrelor), a randomized controlled trial among 30 centers in the U.S. and Canada, evaluating intraoperative use of DrugSorb-ATR during cardiothoracic surgery to reduce perioperative bleeding complications caused by Brilinta. Topline data are expected at the end of 2023 and if positive, the Company plans to file for FDA and Health Canada marketing approval in early 2024.
CytoSorbents’ blood purification technologies are based on advanced, biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Each polymer bead, approximately the size of a grain of salt, contains millions of pores and channels that can be modified to remove substances as small as drugs, to substances as large as antibodies from blood. These beads are synthesized at CytoSorbents’ ISO 13485 certified manufacturing facility in New Jersey. A companion product for the animal health market that uses similar technology to CytoSorb®, called VetResQ®, is now commercially available in the United States. Another related product is the ECOS-300CY® cartridge, approved in the E.U. for removal of cytokines in ex vivo organ perfusion systems for transplant. HemoDefend-RBC™ is a packed red cell transfusion filter designed to improve the safety and quality of transfused blood. CytoSorbents is also developing HemoDefend-BGA™, a filter designed to remove anti-A and anti-B antibodies from plasma, to create “universal plasma”, and whole blood. The Company has numerous other products under development based upon this unique blood purification technology, protected by 19 issued U.S. patents, multiple issued international patents, and a broad patent application portfolio pending, including CytoSorb-XL, K+ontrol, ContrastSorb, DrugSorb, and others.
CytoSorb®
CytoSorb® is approved in the European Union (E.U.) as an extracorporeal cytokine adsorber, indicated for use in clinical situations where cytokines are elevated (as in “cytokine storm”). It has been used in more than 212,000 treatments cumulatively to date. The goal of treatment is to control deadly systemic inflammation by reducing excessive cytokines and other inflammatory mediators from blood that “fuel the fire” of inflammation. Left unchecked, this uncontrolled inflammation can lead to organ injury, organ failure, and in many cases, death of the patient. This was very apparent during the COVID-19 pandemic where patients with the most severe inflammation were typically the ones that required mechanical ventilation, and were the ones a highest risk of death. The blood purification cartridge can be used with most types of extracorporeal blood pumps including standard hemodialysis machines, continuous renal replacement (CRRT) machines, heart-lung machines, and extracorporeal membrane oxygenation (ECMO) machines, in any situation where cytokines are elevated. This includes a diverse range of conditions where excessive cytokines and other inflammatory toxins are driving a potentially dangerous inflammatory response. These include acute critical illnesses such as sepsis and infection, burn injury, trauma, acute respiratory distress syndrome, severe acute pancreatitis, liver failure, influenza, cytokine release syndrome in CAR T-cell immunotherapy, and complications of cardiac surgery, as well as in other more chronic diseases such as cancer, cancer cachexia, autoimmune diseases, and others.
In April 2020, the U.S. FDA granted Emergency Use Authorization (EUA) to CytoSorb for use in COVID-19 patients, 18 years of age or older, in the intensive care unit, with imminent or confirmed respiratory failure. The EUA enables commercial availability of CytoSorb in all U.S. hospitals.* Data captured in the U.S. CytoSorb Therapy in COVID-19 (CTC) registry and published on 100 patients from 5 major U.S. hospitals, found that the combination of CytoSorb with ECMO to achieve “enhanced lung rest” in COVID-19 patients with refractory respiratory failure and ARDS, led to 74% 90-day survival. These patients were among the sickest in the hospital, yet demonstrated high survival.
CytoSorb is also E.U. approved for the reduction of bilirubin and myoglobin in clinical situations such as liver failure and severe trauma, respectively. CytoSorb® is also being used intra-operatively during open heart surgery in a bypass circuit in a heart-lung machine to reduce inflammatory mediators such as cytokines that are generated during the surgery and can lead to post-operative inflammation, blood pressure instability, and organ failure. In clinical studies, CytoSorb has also demonstrated the ability to reduce activated complement and plasma free hemoglobin during cardiac surgery.
In 2020, CytoSorb was also E.U. approved to remove ticagrelor (Brilinta, Brilique) and rivaroxaban (Xarelto), two leading antithrombotic drugs or “blood thinners” during urgent and emergent cardiothoracic surgery. The goal of this therapy is to reduce these drugs during surgery to reduce the risk of potentially serious perioperative bleeding.
CytoSorbents has shipped more than 212,000 CytoSorb devices to date with distribution established in 75 countries. The Company is strategically partnered with leading commercial players in critical care and cardiac surgery such as Fresenius Medical Care – the largest dialysis company in the world, B Braun – the third largest global dialysis company, Terumo Cardiovascular – a global leader in cardiac and vascular surgery, and Biocon – India’s largest biopharmaceutical company.
The Company is pursuing a dual pathway for FDA regulatory approval of CytoSorb in the United States. The first is to leverage its Breakthrough Designation, granted by the FDA in April 2020, to remove ticagrelor during urgent or emergent cardiothoracic surgery, with the goal of reducing the risk of deadly perioperative bleeding that this drug can cause. Ticagrelor is commonly administered to patients being admitted for signs and symptoms of having a heart attack, called acute coronary syndrome. The Company has now completed the U.S. and Canada STAR-T (Safe and Timely Removal of Ticagrelor) pivotal, randomized, controlled trial and expects to announce topline data later in 2023.
The second path for U.S. FDA approval is to remove the direct oral anticoagulants (DOACs), Eliquis and Xarelto, during cardiothoracic surgery with DrugSorb-ATR. The Company had paused the STAR-D pivotal RCT that was designed to demonstrate a reduction in perioperative bleeding risk using DrugSorb-ATR intraoperatively to remove these DOACs, to focus on the pivotal STAR-T trial, but intends to resume the STAR-D trial in the near future.
For more information, please visit www.cytosorb.com
*In terms of FDA Emergency Use Authorization, CytoSorb has neither been cleared nor approved for the indication to treat patients with COVID-19 infection. The CytoSorb device is authorized only or the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the CytoSorb device under under Section 564(b)(l) of the Act, 21 U.S.C § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.
DrugSorbTM-ATR
Millions of people around the world are on blood thinners to reduce their risk of heart attack and stroke. Those at high risk have had a previous stroke or heart attack or require anticoagulation for a stent, a heart valve, atrial fibrillation, peripheral vascular disease, or a myriad of other reasons. However, if a patient requires unscheduled surgery and does not have 3-5 days to discontinue taking the drug, the risk of severe and potentially fatal bleeding is very high. DrugSorbTM-ATR, is an investigational blood purification system in the U.S. that uses an equivalent polymer technology to CytoSorb to remove multiple classes of blood thinners during cardiothoracic surgery. It connects simply to a heart-lung machine blood circuit and removes these drugs while the surgery is ongoing. DrugSorb-ATR has already received two FDA Breakthrough Device Designations to remove the anti-platelet agent, Brilinta, and to remove the direct oral anticoagulants, Eliquis® and Xarelto, during cardiothoracic surgery, which highlights and acknowledges the lack of approved or cleared U.S. drugs, biologics, or devices that can address this major unmet clinical need. CytoSorbents has completed the U.S. and Canadian STAR-T (Safe and Timely Antithrombotic Removal of Ticagrelor), a randomized controlled trial among 30 centers in the U.S. and Canada, evaluating intraoperative use of DrugSorb-ATR during cardiothoracic surgery to reduce perioperative bleeding complications caused by Brilinta. Topline data are expected at the end of 2023 and if positive, the Company plans to file for FDA and Health Canada marketing approval in early 2024.
VetResQ®
VetResQ® is commercially available in the U.S. veterinary market as a blood purification therapy targeting the reduction of toxic inflammation in critically-ill cats, dogs, and other animals suffering that can occur from infection and sepsis, trauma, pancreatitis, Leptospirosis, and other common conditions. It is also suitable for the treatment of accidental drug intoxication from hydrophobic drugs.
ECOS-300CY®
The ECOS-300CY (Extracorporeal Organ Support) is an E.U. approved adsorption cartridge for use with ex vivo organ perfusion systems for organs destined for transplant to remove cytokines and other inflammatory mediators in the organ perfusate, with the goal of improving solid organ support or rehabilitation. CytoSorbents has partnered with Aferetica, manufacturer of the PerLife ex-vivo organ perfusion platform, and has made ECOS-300CY available on the platform exclusively as PerSorb®
HemoDefend-RBC™
HemoDefend-RBC™ is a development-stage blood purification technology platform for the blood transfusion industry intended to reduce transfusion reactions and safeguard the quality and safety of blood products. The HemoDefend technology utilizes the Company’s polymer bead technology to remove many substances, such as antibodies, free hemoglobin, potassium, cytokines, bioactive lipids, and inflammatory mediators that can cause potentially serious and sometimes fatal transfusion reactions. HemoDefend-RBC is designed to purify packed red blood cells.
HemoDefend-BGA™
HemoDefend-BGA™ is a development-stage purification technology that can remove anti-A and anti-B antibodies from plasma and whole blood, to enable “universal plasma,” and safer whole blood transfusions, respectively.
The Future of Blood Purification is Now
CytoSorb®, DrugSorbTM-ATR, VetResQ®, ECOS-300CY®, and HemoDefend™ are just some of the different sorbents the Company has designed for various medical applications. Applications of pipeline technologies include improved dialysis, the potential treatment of inflammatory and autoimmune disorders, treatment of severe hyperkalemia, and others. Additional information is available in the Investor Relations section.
CytoSorbents’ purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Its technologies have received non-dilutive grant, contract, and other funding of approximately $48 million from DARPA, the U.S. Department of Health and Human Services, the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), the U.S. Army, the U.S. Air Force, U.S. Special Operations Command (SOCOM), Air Force Material Command (USAF/AFMC), and others.
CytoSorbents operates through its wholly-owned subsidiary, CytoSorbents Medical Inc. (fka CytoSorbents Inc.), and conducts its European business through its wholly-owned subsidiary, CytoSorbents Europe GmbH, with daughter subsidiaries in the United Kingdom, Switzerland, and Poland. CytoSorbents Corporation converted from a Nevada Corporation to a Delaware Corporation in December 2014.
