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We have a number of products commercialized and in development based on this technology platform.
−Removed: Our flagship product, CytoSorb®, is already commercialized, and is being investigated to reduce deadly uncontrolled inflammation and dangerous substances in hospitalized patients around the world, with the goal of preventing or treating multiple organ failure, bleeding, and other potentially fatal complications.
+Added: Our flagship product, CytoSorb®, is already commercialized, and is being used to reduce deadly uncontrolled inflammation and dangerous substances in hospitalized patients around the world, with the goal of preventing or treating multiple organ failure, bleeding, and other potentially fatal complications.
Organ failure is the cause of nearly half of all deaths in the ICU, with little to improve clinical outcome.
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FDA marketing approval.
+Added: The first clinical trial, STAR-T, is underway and currently enrolling patients.
+Added: We currently anticipate that the second clinical trial, STAR-D, which was previously postponed, will resume patient enrollment once the STAR-T trial is completed.
We believe CytoSorb has the potential to be used in many other inflammatory conditions, including the treatment of autoimmune disease flares, and other applications in cancer, such as cancer cachexia.
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In addition to CE Marking, we also achieved ISO 13485:2003 Full Quality Systems certification, an internationally recognized quality standard designed to ensure that medical device manufacturers have the necessary comprehensive management systems in place to safely design, develop, manufacture and distribute medical devices in the EU.
−Removed: We manufacture CytoSorb at our manufacturing facilities in New Jersey for commercial sales abroad and for additional clinical studies, the expansion of which we officially completed in June 2018.
−Removed: Upon expanding our facility we quadrupled our manufacturing capacity and completed an audit upgrade from an ISO 13485:2003 certification to an ISO 13485:2016 certification.
+Added: In the past, we manufactured CytoSorb at our older manufacturing facilities in New Jersey for commercial sales abroad and for additional clinical studies.
+Added: Upon expanding our facility in June 2018, we quadrupled our manufacturing capacity and completed an audit upgrade from an ISO 13485:2003 certification to an ISO 13485:2016 certification.
In late June 2012, following the establishment of our European subsidiary, CytoSorbents Europe GmbH, a wholly-owned operating subsidiary of CytoSorbents Corporation, we began the commercial launch of CytoSorb in Germany.
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The new production facility was designed to support annual sales of up to $400 million while improving product gross margins and allowing space for future product line expansions.
−Removed: We expect to complete the certification audit in the first half of 2022, and commercial production of CytoSorb is expected to commence in the second half of 2022.
+Added: The new production facility successfully passed its E.U.
+Added: notified body audit in early 2022, and received ISO 13485 certification from its E.U.
+Added: notified body in September 2022, clearing the way for full manufacturing of CytoSorb, DrugSorb-ATR, ECOS-300CY from this site.
In August 2021, the Company announced that it was granted a second Breakthrough Device designation for its DrugSorb-ATR Antithrombotic Removal System by the U.S.
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In October 2021, the Company also received full FDA approval of an IDE application to conduct a double-blind, randomized, controlled clinical study for up to 120 patients entitled, “Safe and Timely Antithrombotic Removal – Direct Oral Anticoagulants (STAR-D),” in the United States to support FDA marketing approval.
+Added: This trial is currently paused until the anticipated completion of the STAR-T trial.
+Added: If FDA marketing approval is obtained for either the removal of ticagrelor or direct oral anticoagulants indications, the device would be marketed as DrugSorb-ATR in the United States.
+Added: The DrugSorb-ATR Antithrombotic Removal System is based on the same polymer technology as CytoSorb.
+Added: In May 2022, the Company announced that it entered into a 3-year preferred supplier agreement with the private German hospital network, Asklepios, making CytoSorb available without restrictions to all of the approximate 170 healthcare facilities across 14 states throughout Germany at which Asklepios operates.
+Added: This includes Asklepios Klinik St.
+Added: Georg in Hamburg, Germany, which pioneered the use of CytoSorb to remove antithrombotic drugs during cardiothoracic surgery and is well-known for their seminal publication on CytoSorb use for this application during emergency cardiac surgery in patients at high risk of bleeding.
+Added: In June 2022, the Company announced that, following a successful pilot program in three countries, the Company signed an expanded non-exclusive agreement with Nikkiso Europe GmbH (“Nikkiso”) to distribute Nikkiso’s PureADJUST stand-alone hemoperfusion pump and accessories in a total of 14 countries.
+Added: In addition to securing the rights to sell Nikkiso’s stand-alone pump and accessories in Germany, Austria, and Luxembourg, the Company entered into an expanded multi-country reseller agreement with Nikkiso covering the following countries:
+Added: Belgium, Bosnia and Herzegovina, Croatia, Finland, France, Iceland, Lichtenstein, Poland, Serbia, Slovenia and Switzerland.
+Added: The Company will provide field support services in these countries.
+Added: In August 2022, the Company entered into a Marketing Agreement (the “Marketing Agreement”) with Fresenius Medical Care Deutschland GmbH (“Fresenius”), which expands the Company’s strategic partnership with Fresenius by establishing a multi-stage global collaboration to combat life-threatening diseases in critical care.
+Added: The Marketing Agreement provides for the combined marketing and promotion of CytoSorb with Fresenius’ critical care products by Fresenius’ marketing organization worldwide, excluding the United States.
+Added: The Marketing Agreement has an initial term of three years, with an automatic renewal for an additional two years at the end of such initial term, subject to earlier termination by either of the parties (the “Term”).
+Added: Compared to the prior co-marketing agreement between the parties, the Marketing Agreement intends to increase the commitments from both parties and to ensure an ongoing and consistent level of marketing and promotional activity specifically focused around CytoSorb, where Fresenius will actively market and promote CytoSorb as the featured blood purification therapy for removal of cytokines, bilirubin, and myoglobin on its critical care platforms.
+Added: Specifically, the Marketing Agreement provides that various Fresenius-led in-person, virtual, social media, and web-based marketing programs and events will feature the CytoSorb therapy and highlight the cooperation between the two companies in the field of critical care during the Term.
+Added: To help support the increased marketing and promotional efforts of the expanded collaboration, CytoSorbents has agreed to subsidize a portion of the marketing costs through a royalty payment to Fresenius Medical Care based on CytoSorb sales in the intensive care unit on Fresenius Medical Care platforms, excluding the United States.
+Added: In addition to strengthening and expanding the global marketing of CytoSorb, the Company and Fresenius also plan to work together to bring new innovative solutions to the market.
+Added: The Marketing Agreement also includes the certification of compatibility of CytoSorb for usage on Fresenius’ current critical care platforms.
+Added: Certain initial activities have been completed with the formal of this program expected to occur sometime in 2023.
In addition, there are many investigator-initiated and additional Company sponsored trials that are currently planned, enrolling, or completed in Europe and in other countries abroad, using our blood purification technology that may provide valuable information regarding the use of the device in the treatment of different conditions such as sepsis, cardio-pulmonary bypass surgery, liver failure, COVID-19, organ transplant and many others.
If successful, these studies may help to drive additional usage and adoption of our blood purification technologies.
−Removed: As of March 1, 2022, our European commercialization team included 107 people.
We have complemented our direct sales efforts with sales to distributors and/or strategic corporate partners.
−Removed: For more information regarding our distributors and strategic partners, refer to the Sales and Marketing section in Iitem 1 of this Report.
+Added: For more information regarding our distributors and strategic partners, refer to the Sales and Marketing section in Item 1 of this Report.
Overall, we have established either direct sales or distribution (via distributors or strategic partners) of CytoSorb in more than 75 countries worldwide.
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and EU combined including, for example, coronary artery bypass graft surgery, valve replacement surgery, heart and lung transplant, congenital heart defect repair, aortic reconstruction, and left ventricular assist device (“LVAD”) implantation.
−Removed: Cardiac surgery can result in inflammation and the production of high levels of inflammatory cytokines, activation of complement, and cause hemolysis, leading to the release of toxic plasma free hemoglobin.
+Added: Cardiac surgery can result in inflammation and the production of high levels of inflammatory mediators, such as cytokines, activated complement, and toxic plasma free hemoglobin released by hemolysis.
These can lead to post-operative complications such as respiratory failure, circulatory failure, and acute kidney injury.
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Direct Anticoagulants Removal During Cardiac Surgery
+Added: Temporarily paused
United States
−Removed: Real world outcomes in COVID-19 patients under the EUA
−Removed: Evaluation of Patients Suffering From Acute Liver Failure
+Added: CytoSorb in COVID-19 patients on ECMO under EUA
+Added: Refractory Septic Shock Patients
+Added: International
STAR Registry
Real world outcomes in antithrombotic removal
+Added: International
COSMOS Registry
−Removed: Real world outcomes across multiple critical care applications
+Added: Real world outcomes in multiple critical care applications
For further detailed information regarding our clinical trial strategy, see the section entitled “Clinical Studies” of this Item 1 of this Report.
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See the section entitled “Government Research Grants” of this Item 1 of this Report for information regarding the specific grants.
+Added: In 2023, our goal is to successfully complete the STAR-T trial, finalize our data analysis, and file for U.S.
+Added: FDA and Health Canada regulatory approvals.
+Added: We are preparing for commercialization of DrugSorb-ATR in the U.S.
+Added: In addition, we are seeing improvements in market conditions, and we are focused on a return to sales growth in our existing markets.
Corporate History
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In December 2005, MedaSorb Technologies, LLC converted from a limited liability company to a corporation, called MedaSorb Technologies, Inc.
−Removed: CytoSorbents Corporation was incorporated in Nevada on April 25, 2002 as Gilder Enterprises, Inc., and was originally engaged in the business of installing and operating computer networks that provided high-speed access to the Internet.
−Removed: On June 30, 2006, we disposed of our original business, and pursuant to an Agreement and Plan of Merger, acquired all of the stock of MedaSorb Technologies, Inc., in a merger, and the business of MedaSorb Technologies, Inc.
−Removed: became our business.
+Added: Separately, Gilder Enterprises, Inc., was incorporated in Nevada on April 25, 2002, and was originally engaged in the business of installing and operating computer networks that provided high-speed access to the Internet.
+Added: On June 30, 2006, Gilder Enterprises, Inc disposed of its original business, and pursuant to an Agreement and Plan of Merger, acquired all of the stock of MedaSorb Technologies, Inc., in a merger, and the business of MedaSorb Technologies, Inc.
+Added: became its business.
Following the merger, in July 2006, we changed our name to MedaSorb Technologies Corporation.
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All references to “us”, “we”, or the Company, on or after December 3, 2014, refer to CytoSorbents Corporation, a Delaware corporation.
−Removed: Our executive offices are located at 7 Deer Park Drive, Suite K, Monmouth Junction, New Jersey 08852, and our telephone number is (732) 329-8885.
+Added: CytoSorbents Corporation uplisted to, and began trading on, the NASDAQ Capital Markets on December 23, 2014.
+Added: Our executive offices are located at 305 College Road East, Princeton, New Jersey 08540, and our telephone number is (732) 329-8885.
Our website address is http://www.cytosorbents.com .
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We are not including the information contained at http://www.cytosorbents.com , or at any other website address, as part of, or incorporating it by reference into, this Annual Report on Form 10-K.
−Removed: We have been engaged in research and development since our inception and have raised approximately $215 million from investors.
−Removed: These proceeds have been used to fund the development of multiple product applications and to conduct clinical studies, to establish in-house manufacturing capacity to meet commercial and clinical testing needs, expand our intellectual property through additional patents, and to develop extensive proprietary know-how with regard to our products.
+Added: We have been engaged in research and development and product commercialization and have raised approximately $215 million from investors as of December 31, 2022.
+Added: These proceeds have been used to fund the development of multiple product applications, to conduct clinical studies, to establish in-house manufacturing capacity to meet commercial and clinical testing needs, expand our intellectual property through additional patents, to develop extensive proprietary know-how with regard to our products and to commercialize our products internationally.
We have raised funds through various means including convertible note offerings, equity transactions, and term loans.
−Removed: Our most significant financing transactions are discussed below.
+Added: Our most recent financing transactions are discussed below.
July 24, 2020 Offering
−Removed: On July 24, 2020, the Company closed an underwritten public offering of 6,052,631 shares of its common stock at a public offering price of $9.50 per share (the "Offering").
+Added: On July 24, 2020, the Company closed an underwritten public offering of 6,052,631 shares of its common stock at a public offering price of $9.50 per share (the “Offering”).
The Company completed the Offering pursuant to the terms of an Underwriting Agreement, dated as of July 21, 2020, by and among the Company and Cowen and Company, LLC and SVB Leerink LLC, as representatives of the several underwriters named therein.
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Shelf Registration
−Removed: On July 26, 2018, the Company filed a registration statement on Form S-3 with the SEC (as amended, the “2018 Shelf”).
−Removed: The 2018 Shelf, which was declared effective on August 7, 2018, enabled the Company to offer and sell, in one or more offerings, any combination of common stock, preferred stock, senior or subordinated debt securities, warrants and units, up to a total dollar amount of $150 million.
−Removed: The 2018 Shelf terminated automatically upon the 2021 Shelf (as defined below) being declared effective on July 27, 2021.
On July 14, 2021, the Company filed a registration statement on Form S-3 with the SEC, which was amended on July 20, 2021 and declared effective by the SEC on July 27, 2021 (as amended, the “2021 Shelf”).
The 2021 Shelf enables the Company to offer and sell, in one or more offerings, any combination of common stock, preferred stock, senior or subordinated debt securities, warrants and units, up to a total dollar amount of $150 million.
−Removed: Open Market Sale Agreement with Jefferies LLC and B.
−Removed: Riley FBR, Inc.
−Removed: On July 9, 2019, the Company entered into an Open Market Sale Agreement (the “Sale Agreement”) with Jefferies LLC and B.
−Removed: Riley FBR, Inc.
−Removed: (each an “Agent” and, together, the “Agents”), pursuant to which the Company could sell, from time to time, at its option, shares of the Company’s common stock having an aggregate offering price of up to $25 million through the Agents, as the Company’s sales agents.
−Removed: All shares of the Company’s common stock offered and sold, or to be offered and sold under the Sale Agreement would have been issued and sold pursuant to the Company’s 2018 Shelf by methods deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended, in block transactions or if specified by the Company, in privately negotiated transactions.
−Removed: On April 20, 2020, the Company and the Agents entered into an amendment to the Sale Agreement (the "Amendment") to provide for an increase in the aggregate offering amount under the Sales Agreement, such that as of April 20, 2020, the Company could offer and sell Shares having an additional aggregate offering price of up to $50 million under the Sale Agreement, as amended by the Amendment (the "Amended Sale Agreement").
−Removed: Subject to the terms of the Amended Sales Agreement, the Agents were required to use their commercially reasonable efforts consistent with their normal sales and trading practices to sell the shares of the Company’s common stock from time to time, based upon the Company’s instructions (including any price, time or size limits or other customary parameters or conditions the Company may impose).
−Removed: The Company was required to pay the Agents a commission of up to 3.0% of the gross proceeds from the sale of the shares of the Company’s common stock sold thereunder, if any.
−Removed: The Company has also agreed to provide the Agents with customary indemnification rights.
−Removed: During the year ended December 31, 2019, the Company sold 191,244 shares pursuant to the Amended Sale Agreement, at an average selling price of $4.11 per share, generating net proceeds of approximately $762,000.
−Removed: During the year ended December 31, 2020, the Company sold 4,110,625 shares pursuant to the Amended Sale Agreement, at an average selling price of $6.64 per share, generating net proceeds of approximately $26.5 million.
−Removed: There were no sales pursuant to the Amended Sale Agreement during the year ended December 31, 2021.
−Removed: In the aggregate, the Company has sold 4,301,869 shares pursuant to the Amended Sale Agreement, at an average selling price of $6.53 per share, generating net proceeds of approximately $27.2 million.
−Removed: The Company may no longer offer and sell additional shares of the Company’s common stock under the Amended Sale Agreement following the declaration of effectiveness of the 2021 Shelf on July 27, 2021.
Open Market Sale Agreement with Jefferies LLC
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The Company is required to pay the Agent a commission of up to 3.0% of the gross proceeds from the sale of the shares of the Company’s common stock sold thereunder, if any.
−Removed: There were no sales pursuant to the Sale Agreement during the year ended December 31, 2021.
+Added: There were no sales pursuant to the Sale Agreement during the years ended December 31, 2022 and 2021.
Research and Development
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Army ($100K Phase I SBIR;
−Removed: $50K Phase I option, $803K Phase II SBIR, $443K Phase II enhancement, $1.1M 2 nd Phase II), the U.S.
+Added: $50K Phase I option, $803K Phase II SBIR, $443K Phase II enhancement), the U.S.
Air Force $3.0M Rapid Innovation Fund, the Congressionally Directed Medical Research Program Office, (“CDMRP”, $718K), the National Heart, Lung and Blood Institute and USSOCOM ($203K Phase I SBIR;
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$3.0M Bridge SBIR), the Joint Program Executive Office – Chemical and Biological Defense, (JPEO-CBD), ($150K Phase I and Phase I option, $1.0M Phase II), the U.S.
−Removed: Army Peritoneal dialysis/mesh packing for hyperkalemia ($150K Phase I SBIR, $1.0M Phase II, $1.5 M 2 nd Phase II), Universal Plasma ($150K Phase I and 1.0M Phase II STTR;
−Removed: $2.9M Defense Health Agency, US Army and CDMRP Phase III STTR;
+Added: Army Peritoneal dialysis/mesh packing for hyperkalemia ($150K Phase I SBIR, $1.0M Phase II, $1.5M Sequential Phase II), Universal Plasma ($150K Phase I and 1.0M Phase II STTR;
$2.9M US Army and CDMRP Rapid Innovation Fund;
−Removed: and a $1.1M US Army contract), New Jersey Technology Business Tax Certificate Program for research related expenses ($6.5M), and others to further develop our technologies for sepsis, trauma and burn injury, and blood transfusions, respectively.
+Added: $1.1M US Army Sequential Phase II;
+Added: and $4.3M JWMRP), Lipopolysaccharide Adsorption In Sepsis (National Institution of General Medical Sciences $282K), the U.S.
+Added: Air Force program ($75K), New Jersey Technology Business Tax Certificate Program for research related expenses ($6.7M), and others to further develop our technologies for sepsis, trauma and burn injury, and blood transfusions, respectively.
Some payments are based on achieving certain technology milestones.
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Our hemocompatible adsorbent technology helps to address this shortcoming by removing toxins and toxic compounds largely untouched by dialysis technology.
−Removed: Our polymer adsorbent technology can remove drugs, bioactive lipids, inflammatory mediators such as cytokines, free hemoglobin, toxins, and immunoglobulin from blood and physiologic fluids depending on the polymer construct.
+Added: Our polymer adsorbent technology can remove many different substances from whole blood and physiologic fluids, including for example, drugs, bioactive lipids, inflammatory mediators such as cytokines, free hemoglobin, and bacterial toxins, immunoglobulin, bilirubin, and myoglobin, depending on the polymer construct.
The technology has been used in a wide variety of acute healthcare applications including, but not limited to, the adjunctive treatment and/or prevention of sepsis;
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The cartridges incorporate industry standard connectors at either end of the device, which connect directly to the extracorporeal circuit (bloodlines) in series with a dialyzer as a standalone device.
−Removed: The extra-corporeal circuit consists of plastic blood tubing, our blood filtration cartridges containing adsorbent polymer beads, pressure monitoring gauges, and a blood pump to maintain blood flow.
+Added: The extracorporeal circuit consists of plastic blood tubing, our blood filtration cartridges containing adsorbent polymer beads, pressure monitoring gauges, and a blood pump to maintain blood flow.
The patient’s blood is accessed through a catheter inserted into his or her veins.
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A major cause of death is multiple organ failure, where vital organs such as the lungs, kidneys, heart and liver are damaged and no longer function properly.
−Removed: These patients are kept alive with supportive care therapy, or “life support”, such as mechanical ventilation, dialysis and vasopressor treatment, that is designed to keep the patient from dying while using careful patient management to tip the balance towards gradual recovery over time.
+Added: These patients are kept alive with supportive care therapy, or “life support”, such as mechanical ventilation, dialysis, extracorporeal liver support, and vasopressor treatment, that is designed to keep the patient from dying while using careful patient management to tip the balance towards gradual recovery over time.
Unfortunately, most supportive care therapies only help to keep patients alive by supporting organ function but do not help reverse the underlying causes of organ failure and do not help patients recover more quickly.
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The main driver of sepsis incidence is the aging demographic, specifically patients who are older than age 65 who are more prone to infection and now account for two-thirds of patients hospitalized for sepsis and the majority of sepsis deaths.
−Removed: Other factors contributing to the increase in sepsis incidence include the spread of antibiotic resistant bacteria like methicillin-resistant Staphylococcus aureus (“MRSA”), an increase in co-morbid conditions like HIV, cancer, obesity, and diabetes that increases the risk of infection, an increasing use of implantable devices like artificial hips and knees that are prone to colonization by bacteria, and the appearance of new highly virulent or contagious strains of common pathogens such as H3N2 or H1N1 influenza, COVID-19 coronavirus, and others.
+Added: Other factors contributing to the increase in sepsis incidence include the spread of antibiotic resistant bacteria like methicillin-resistant Staphylococcus aureus (“MRSA”), an increase in co-morbid conditions like HIV, cancer, obesity, and diabetes that increases the risk of infection, an increasing use of implantable devices like artificial hips, knees and heart valves that are prone to colonization by bacteria, and the appearance of new highly virulent or contagious strains of common pathogens such as H3N2 or H1N1 influenza, COVID-19 coronavirus, and others.
There are generally three categories of sepsis, including mild to moderate sepsis, severe sepsis and septic shock.
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Because of this, we believe that cost savings to hospitals and/or clinical efficacy, rather than the cost of treatment itself, will be the determining factor in the adoption of CytoSorb in the treatment of sepsis.
−Removed: CytoSorb is approved in the EU and is being sold directly in Germany, Austria, Switzerland, Belgium, Luxembourg, Poland, Norway, Denmark, Sweden, and the Netherlands with our own direct sales force.
+Added: CytoSorb is approved in the EU and is being sold directly in Germany, Austria, Switzerland, Belgium, Luxembourg, Poland, Norway, Denmark, Sweden, the United Kingdom and the Netherlands with our own direct sales force.
In December 2016, we announced the achievement of a dedicated reimbursement procedure code for CytoSorb therapy in Germany, providing for specific and enhanced reimbursement in the largest medical device market in Europe.
−Removed: We have established strategic partnerships with Fresenius Medical Care, the world’s largest dialysis company, for exclusive distribution of CytoSorb for critical care applications in France, Finland, the Czech Republic, Mexico, and Korea, and Terumo Cardiovascular, the largest cardiac surgery disposables company, for exclusive distribution of the CytoSorb Cardiopulmonary Bypass Kit in France, Finland and Iceland.
+Added: We have established strategic partnerships with Fresenius Medical Care, the world’s largest dialysis company, for distribution of CytoSorb for critical care applications in France, Finland, the Czech Republic, Colombia, Ecuador, Mexico, and Korea, and Terumo Cardiovascular, the largest cardiac surgery disposables company, for exclusive distribution of the CytoSorb Cardiopulmonary Bypass Kit in France.
We are also partnered with Biocon Biologics Limited, India’s largest biopharmaceutical company, for exclusive distribution of CytoSorb in India, Sri Lanka, and other select emerging markets.
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We have ongoing discussions with potential corporate partners and independent distributors to market CytoSorb in other select EU countries and in other countries outside the EU that accept CE Mark approval.
−Removed: We have established direct sales or distribution of CytoSorb in more than 70 countries worldwide.
+Added: We have established direct sales or distribution of CytoSorb in approximately 75 countries worldwide.
We estimate that the market potential in Europe for CytoSorb is larger than that in the U.S.
For example, in the U.S.
−Removed: there are an estimated 1.6 million cases of sepsis, while the European Sepsis Alliance estimates 3.4 million individuals in Europe become septic each year.
+Added: there are an estimated 1.6 million cases of sepsis each year, while the European Sepsis Alliance estimates 3.4 million individuals in Europe become septic each year.
In Germany alone, according to the Center of Sepsis Control and Care, there are approximately 175,000 cases of severe sepsis each year.
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This scenario is most common in patients presenting with an acute coronary syndrome (ACS).
−Removed: In the US alone there are approximately 1.1 million ACS hospital admissions annually.
−Removed: CytoSorb is able to very efficiently remove ticagrelor and DOACs from blood, and is approved in the E.U.
−Removed: for the removal of both ticagrelor and rivaroxaban during cardiothoracic surgery requiring cardiopulmonary bypass.
+Added: alone there are approximately 1.1 million ACS hospital admissions annually.
+Added: CytoSorb is able to very efficiently remove ticagrelor and DOACs from blood and is approved in the EU for the removal of both ticagrelor and rivaroxaban during cardiothoracic surgery requiring cardiopulmonary bypass.
The use of CytoSorb during emergency coronary artery bypass surgery (CABG) in patients on ticagrelor or rivaroxaban significantly reduced periooperative bleeding complications in a landmark observational study and had projected cost savings of approximately $5,000 per patient, including the cost of the device.
−Removed: In the U.S., the Company is conducting two pivotal, randomized, controlled trials, the STAR-T and STAR-D trials, to evaluate the potential ability of the DrugSorb-ATR antithrombotic removal system, which uses an equivalent polymer technology to CytoSorb, to reduce perioperative bleeding risk in patients undergoing cardiothoracic surgery in the presence of ticagrelor, or the direct oral anticoagulants, apixaban and rivaroxaban, respectively.
−Removed: Each study, if successful, is intended to independently support U.S.
+Added: and Canada, the Company is currently conducting the pivotal, randomized, controlled STAR-T trial to evaluate the potential ability of the DrugSorb-ATR antithrombotic removal system, which uses an equivalent polymer technology to CytoSorb, to reduce perioperative bleeding risk in patients undergoing cardiothoracic surgery in the presence of ticagrelor.
+Added: The Company expects to resume the STAR-D trial, targeting a reduction in perioperative bleeding risk in cardiothoracic surgery through the removal of the direct oral anticoagulants, apixaban and rivaroxaban, upon completion of the STAR-T trial.
+Added: The STAR-T trial and STAR-D trial (if resumed), if successful, are each intended to independently support U.S.
+Added: FDA marketing approval for DrugSorb-ATR for this indication., or the direct oral anticoagulants, apixaban and rivaroxaban, respectively.
+Added: The Company expects to resume the STAR-D trial upon completion of the STAR-T trial.
+Added: The STAR-T trial and STAR-D trial (if resumed), are each intended to independently support U.S.
FDA marketing approval for DrugSorb-ATR for this indication.
The initial annual addressable market in the U.S.
−Removed: to remove these drugs during cardiothoracic surgery is estimated between $500-750 million.
+Added: to remove these drugs during cardiothoracic surgery is estimated between $500 million to $750 million.
Acute Respiratory Distress Syndrome
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Patients with ALI and ARDS typically require mechanical ventilation, and sometimes extracorporeal membrane oxygenation (ECMO) therapy if the lungs become so diseased that mechanical ventilation fails, to help achieve adequate oxygenation of the blood.
−Removed: Patients on mechanical ventilation are at high risk of ongoing
−Removed: ventilator-induced lung injury, oxygen toxicity, barotrauma, ventilator-acquired pneumonias, and other hospital acquired infections, and outcome is significantly dependent on the presence of other organ dysfunction as well as co-morbid conditions such as pre-existing lung disease (e.g., emphysema or chronic obstructive pulmonary disease) and age.
+Added: Patients on mechanical ventilation are at high risk of ongoing ventilator-induced lung injury, oxygen toxicity, barotrauma, ventilator-acquired pneumonias, and other hospital acquired infections, and outcome is significantly dependent on the presence of other organ dysfunction as well as co-morbid conditions such as pre-existing lung disease (e.g., emphysema or chronic obstructive pulmonary disease) and age.
Because of this, mortality has been high (16-33%) even with modern medicine and ventilation techniques.
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CytoSorb treatment of patients with either ALI or ARDS in the setting of sepsis was the subject of our European Sepsis Trial where in a post-hoc analysis in patients with very high cytokine levels, we observed faster ventilator weaning in CytoSorb treated patients that showed a statistical trend towards benefit.
−Removed: Published results from our CytoSorb Therapy in COVID-19 (CTC) registry in the medical journal, Frontiers in Medicine, in December 2021, demonstrated that in 52 consecutive patients from 5 U.S.
−Removed: ECMO centers, 90-day survival was 73% in critically ill COVID-19 patients who failed mechanical ventilation and were treated with ECMO and CytoSorb under FDA Emergency Use Authorization, For context, 90-day survival was 50% (as of December 2021) among more than 6,400 adult patients in the North American cohort of the Extracorporeal Life Support Organization (ELSO) COVID-19 ECMO Registry.
+Added: Published results from our U.S.
+Added: CytoSorb Therapy in COVID-19 (CTC) registry in the medical journal, Frontiers in Medicine, in December 2021, demonstrated that in 52 consecutive patients from 5 U.S.
+Added: ECMO centers, 90-day survival was 73% in critically ill COVID-19 patients who failed mechanical ventilation and were treated with ECMO and CytoSorb under FDA Emergency Use Authorization.
+Added: The CTC Registry completed enrollment at 100 patients, confirming 90-day survival of 74%.
+Added: For context, 90-day survival was 53% (as of December 2022) among more than 7,300 adult patients in the North American cohort of the Extracorporeal Life Support Organization (ELSO) COVID-19 ECMO Registry.
Future, prospectively defined, larger studies are required to confirm these findings.
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For example, in critically ill COVID-19 patients on mechanical ventilation, the RECOVERY study demonstrated use of once daily dexamethasone led to a reduction in mortality from 41.4% control to 29.3% treatment.
−Removed: However, techniques to improve ventilation and reduce ongoing lung injury are being used.
+Added: In general, patients studied in the RECOVERY study were not as severely ill as those treated for refractory respiratory failure with CytoSorb and ECMO in the CTC Registry.
+Added: Techniques to improve ventilation and reduce ongoing lung injury are also being used.
For example, low tidal volume ventilation has been demonstrated to improve mortality (31.0% as compared to 39.8% control) in this patient population in the ARDSNet Trial.
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According to the National Center for Health Statistics, in the U.S., there are more than 31 million visits to hospital emergency rooms, with 1.9 million hospitalizations, and 167,000 deaths every year due to injury.
−Removed: The leading causes of injury are trauma from
−Removed: motor vehicle accidents, being struck by an object or other person, and falls.
+Added: The leading causes of injury are trauma from motor vehicle accidents, being struck by an object or other person, and falls.
Trauma is a well-known trigger of the immune response and a surge in cytokine production or cytokine storm.
24 unchanged sentences
CytoSorb represents a potentially superior liver dialysis therapy, as it can remove both liver toxins such as bilirubin and bile salts, as well as cytokines.
−Removed: In May 2018, the approved indications for use of CytoSorb in the E.U.
−Removed: were expanded to include the removal of bilirubin in liver disease.
+Added: In May 2018, the approved indications for use of CytoSorb in theEU were expanded to include the removal of bilirubin in liver disease.
The total addressable market for CytoSorb for the treatment of acute-on-chronic liver disease, acute hepatitis, and acute liver failure is estimated to bed more than $15 billion worldwide.
13 unchanged sentences
Cancer cachexia is a systemic inflammatory condition, driven by excessive pro-inflammatory cytokines and other factors, that cripples the patient’s physical and immunologic reserve to fight cancer.
−Removed: afflicting millions of patients worldwide each year, there are no effective approved treatments for cancer cachexia, with only symptomatic treatments available.
+Added: Despite afflicting millions of patients worldwide each year, there are no effective approved treatments for cancer cachexia, with only symptomatic treatments available.
CytoSorb blood purification may stop or reverse cancer cachexia through broad reduction of cytokines and other inflammatory mediators, when treated over time.
26 unchanged sentences
This represents a U.S.
−Removed: and European total addressable market for the ECOS-300CY device of approximately $400-600 million.
+Added: and European total addressable market for the ECOS-300CY device of approximately $400 million to $600 million.
Blood Transfusions
13 unchanged sentences
Other early transfusion reactions such as transfusion-associated dyspnea, fever and allergic reactions occur in 3% to 5% of all transfusions and can vary in severity depending on the patient’s condition.
−Removed: These are caused by cytokines, bioactive lipids, free hemoglobin, toxins, foreign antigens, and a number of other inflammatory mediators that accumulate in transfused
−Removed: blood products during storage.
+Added: These are caused by cytokines, bioactive lipids, free hemoglobin, toxins, foreign antigens, and a number of other inflammatory mediators that accumulate in transfused blood products during storage.
Leukoreduction can remove the majority of white cells that can produce new cytokines but cannot eliminate those cytokines already in blood, and cannot otherwise remove other causative agents such as free hemoglobin and antibodies.
10 unchanged sentences
Radiocontrast Removal
−Removed: ContrastSorb is a development-stage blood purification technology that is being optimized for the removal of IV contrast from blood in order to prevent contrast -induced nephropathy ("CIN").
+Added: ContrastSorb is a development-stage blood purification technology that is being optimized for the removal of IV contrast from blood in order to prevent contrast -induced nephropathy (“CIN”).
CIN is the acute loss of renal function within the first 48 hours following IV contrast administration.
36 unchanged sentences
However, there can be no assurance that we will ever obtain regulatory approval for any other device, or that the CytoSorb device will be able to generate significant sales.
−Removed: We manufacture the CytoSorb device at our facility located in Monmouth Junction, New Jersey.
+Added: We manufacture the CytoSorb device at our facility located in Princeton, New Jersey.
We purchase our raw materials from multiple vendors located primarily in the United States.
28 unchanged sentences
With the exception of Xigris ® from Eli Lilly, no other products have been approved in either the U.S.
−Removed: or Europe for
−Removed: the treatment of sepsis.
+Added: or Europe for the treatment of sepsis.
In 2011, after completing a follow up study required by the FDA, it was subsequently determined that Xigris® did not have a statistically significant mortality benefit, and Eli Lilly withdrew Xigris® from all markets worldwide.
11 unchanged sentences
In 2011, the CytoSorb adsorber received EU regulatory approval under the CE Mark as an extracorporeal cytokine adsorber to be used in clinical situations where cytokines are elevated.
−Removed: Our manufacturing facility has also achieved ISO 13485:2003 Full Quality Systems certification, an internationally recognized quality standard designed to ensure that medical device manufacturers have the necessary comprehensive management systems in place to safely design, develop, manufacture and distribute medical devices in the EU.
+Added: manufacturing facility has also achieved ISO 13485:2003 Full Quality Systems certification, an internationally recognized quality standard designed to ensure that medical device manufacturers have the necessary comprehensive management systems in place to safely design, develop, manufacture and distribute medical devices in the EU.
We are currently manufacturing our CytoSorb device for commercial sale in the EU.
−Removed: We are currently selling CytoSorb in Germany, Austria, Switzerland, Belgium, Luxembourg, Poland, Norway, Sweden, Denmark, and the Netherlands with a direct sales force.
+Added: We are currently selling CytoSorb in Germany, Austria, Switzerland, Belgium, Luxembourg, Poland, Norway, Finland, Sweden, Denmark, the United Kingdom and the Netherlands with a direct sales force.
Based on its CE Mark approval, CytoSorb can also be sold throughout all 27 countries of the EU, the United Kingdom and countries outside the EU that will accept European regulatory approval with registration.
19 unchanged sentences
Background and Rationale:
−Removed: A shared feature of many life-threatening conditions seen in the ICU is severe inflammation (either sepsis or systemic inflammatory response syndrome) due to an over-reactive immune system and high levels of cytokines that can cause
−Removed: or contribute to organ dysfunction, organ failure and patient death.
+Added: A shared feature of many life-threatening conditions seen in the ICU is severe inflammation (either sepsis or systemic inflammatory response syndrome) due to an over-reactive immune system and high levels of cytokines that can cause or contribute to organ dysfunction, organ failure and patient death.
Examples of such conditions include severe burn injury, trauma, acute respiratory distress syndrome and severe acute pancreatitis.
9 unchanged sentences
Our goal is to stimulate investigator-initiated clinical studies with our device for these applications.
−Removed: Currently, we have more than 45 investigator-initiated or company-sponsored studies being planned, enrolling, or completed.
+Added: Currently, we have many investigator-initiated or company-sponsored studies being planned, enrolling, or completed.
We have been moving forward in parallel with a program to further understand the potential benefit of CytoSorb hemoadsorption in these conditions through additional investigational animal studies and potential human pilot studies in the U.S.
11 unchanged sentences
● reduce the total cost of patient care;and
−Removed: reduce the risk of perioperative bleeding complications such as need for blood and platelet transfusions, rethoracotomy, and death.
+Added: ● reduce the risk of perioperative bleeding complications such as need for blood and platelet transfusions, re-thoracotomy, and death.
Background and Rationale:
4 unchanged sentences
If our products are able to prevent or reduce the accumulation of cytokines or free hemoglobin in a patient’s blood stream, we may be able to prevent or mitigate post-operative complications caused by an excessive or protracted inflammatory response to the surgery.
−Removed: Intraoperative use of CytoSorb on high-risk cardiac surgery patients, where the risk of post-operative complications is the highest, is one of our main markets.
+Added: Intraoperative use of CytoSorb on high-risk cardiac surgery patients, such as those with infective endocarditis, aortic dissection, or heart or lung transplantation, where the risk of post-operative complications is the highest, is one of our main markets.
The use of CytoSorb in the post-operative period to treat postoperative SIRS is another application of the technology.
12 unchanged sentences
This application is also the focus of number of planned and enrolling company-sponsored and investigator-initiated studies of DrugSorb-ATR in the United States and CytoSorb in Europe.
−Removed: In July 2021, we received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study for up to 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval - T icagrelor ( STAR-T ),” in the United States to support FDA marketing approval.
−Removed: This was done under the previously announced FDA Breakthrough Designation granted for the removal of ticagrelor in a cardiopulmonary bypass circuit to reduce the likelihood of serious perioperative bleeding during urgent cardiac surgery.
−Removed: In October 2021, the first patient was enrolled and the STAR-T study is now actively recruiting at multiple sites.
−Removed: Pending any COVID-19 related delays we expect that the study will complete enrollment in the next 12 to 18 months.
+Added: In July 2021, we received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study in 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval – T icagrelor ( STAR-T ),” in the United States to support FDA marketing approval.
+Added: This was done under the previously announced FDA Breakthrough Device Designation granted for the removal of ticagrelor in a cardiopulmonary bypass circuit to reduce the likelihood of serious perioperative bleeding during urgent cardiac surgery.
+Added: In October 2021, the first patient was enrolled and the STAR-T study is now actively recruiting at multiple U.S.
+Added: In November 2022, the first milestone was completed with the first one-third of patients enrolled, triggering the first Data Safety Monitoring Board (DSMB) meeting.
+Added: The DSMB recommended to continue the study as planned without any modifications.
+Added: In 2022, we also received FDA approval to expand the study to Canada and subsequently received Health Canada approval allowing inclusion of Canadian sites into the STAR-T trial in January 2023.
+Added: Enrollment is expected to be complete during summer of 2023.
In October 2021, we also received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study for up to 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval – D irect Oral Anticoagulants ( STAR-D ),” in the United States to support FDA marketing approval.
−Removed: This was done under the previously announced 2 nd FDA Breakthrough Designation granted for our DrugSorb-ATR Antithrombotic Removal System.
+Added: This was done under the previously announced 2 nd FDA Breakthrough Device Designation granted for our DrugSorb-ATR Antithrombotic Removal System.
This Breakthrough Device designation covers the removal of the Direct Oral Anticoagulants (DOACs) apixaban and rivaroxaban in a cardiopulmonary bypass circuit to reduce the likelihood of serious perioperative bleeding during urgent cardiac surgery.
−Removed: First sites have been activated and we expect the first patient to be enrolled in the first quarter of 2022 with target enrollment completion in 12-18 months after the first patient enrolled.
−Removed: For further detailed information regarding our clinical trial strategy, see the section entitled "Clinical Studies"
−Removed: of this Item 1 of this Report.
−Removed: APPLICATION :
+Added: The study was placed on temporary enrollment hold in November of 2022 for business reasons and is scheduled to resume enrollment upon completion of the STAR-T trial.
+Added: For further detailed information regarding our clinical trial strategy, see the section entitled “Clinical Studies” of this Item 1 of this Report.
Maintaining or improving the quality of solid organs harvested from donors for organ transplant
30 unchanged sentences
VetResQ is compatible with standard hemodialysis, continuous renal replacement therapy (“CRRT”), and hemoperfusion blood pumps.
−Removed: Like CytoSorb, VetResQ is designed to help treat (via hemoadsorption of cytokines, bacterial toxins and other inflammatory mediators) deadly inflammation and toxic injury in animals with critical illnesses such as septic shock, toxic shock syndrome, toxin-mediated diseases, pancreatitis, trauma, liver failure, drug intoxication, and lung injury.
+Added: Like CytoSorb, VetResQ is designed to help treat (via hemoadsorption of cytokines, bacterial toxins and other inflammatory mediators) deadly inflammation and toxic injury in animals with critical illnesses such as septic shock, toxic shock syndrome, toxin-mediated diseases, pancreatitis, trauma, liver failure, drug intoxication, heat stroke and lung injury.
Critical illness in animals is similar to that in humans.
15 unchanged sentences
It is expected to follow a similar path to E.U.
−Removed: approval as CytoSorb, expected within 4-5 years.
+Added: approval as CytoSorb, expected within 4 to 5 years.
The HemoDefend Blood Purification Technology Platform (Acute and Critical Care)
14 unchanged sentences
A number of retrospective studies have also suggested that administration of older blood leads to increased adverse events and even increased mortality, compared with blood recently harvested.
−Removed: Biological studies have demonstrated the accumulation of erythrocyte storage lesions that compromise the function and structural integrity of packed red blood cells and have also demonstrated the accumulation of substances during blood storage that can lead to transfusion reactions.
+Added: Biological studies have demonstrated the accumulation of erythrocyte storage lesions that compromise the function and structural integrity of packed red blood cells and have also demonstrated the accumulation of substances such as free hemoglobin, bioactive lipids, potassium, and others during blood storage that can lead to transfusion reactions.
Three adult, prospective, randomized, controlled studies were designed to evaluate the morbidity and mortality in cardiovascular surgery patients (RECESS) and critically ill patients (ABLE and TRANSFUSE), treated with either “new or fresh” or “older” blood.
18 unchanged sentences
The base polymer is ISO 10993 biocompatible, meeting standards for biocompatibility, hemocompatibility, cytotoxicity, genotoxicity, acute sensitivity and complement activation.
−Removed: HemoDefend has demonstrated the in vitro removal of many different substances from blood such as antibodies, free hemoglobin, cytokines and bioactive lipids.
+Added: HemoDefend has demonstrated the in vitro removal of many different substances from blood such as antibodies, free hemoglobin, potassium, cytokines and bioactive lipids.
We have also prototyped a number of different implementations of the HemoDefend technology, including the “Beads in a Bag” blood treatment blood storage bag, and standard in-line blood filters.
−Removed: The technology has been supported by the NHLBI, a division of the National Institute of Health, under a Phase I SBIR, an awarded $1.5M Phase II SBIR contract (funded by NHLBI and U.S.
−Removed: Special Operations Command (USSOCOM)), and more recently
−Removed: under a $3M multi-year Phase IIB bridge contract funded by NHLBI.
−Removed: Barring additional delays due to the COVID-19 pandemic, including nationwide blood shortages, we expect to advance the in-line filter to human testing in 2022.
+Added: The technology has been supported by the NHLBI, a division of the National Institute of Health, under a Phase I SBIR, an awarded $1.5 million Phase II SBIR contract (funded by NHLBI and U.S.
+Added: Special Operations Command (USSOCOM)), and more recently under a $3 million multi-year Phase IIB bridge contract funded by NHLBI.
+Added: Barring additional delays due to the COVID-19 pandemic, including nationwide blood shortages, we expect to advance the in-line filter to human testing in the next 12 - 18 months.
Removal of anti-A and anti-B blood group antibodies from fresh whole blood and plasma
18 unchanged sentences
Work is continuing to advance these prototypes to clinical study-ready devices.
−Removed: This work has received cumulatively approximately $9.6 million in Phase I and II Small Business Technology Transfer (STTR) funding by the U.S.
+Added: This work has received cumulative funding of approximately $15.9 million in Phase I and II Small Business Technology Transfer (STTR) funding by the U.S.
Army Medical Research Acquisition Activity (USAMRAA), U.S.
−Removed: Army Medical Research and Materiel Command (USAMRMC), Defense Health Agency, and CDMRP.
+Added: Army Medical Research and Materiel Command (USAMRMC), Defense Health Agency, CDMRP, DMRDP, and JWMRP.
K + ontrol (Acute and Critical Care)
13 unchanged sentences
Orally administered potassium sorbents such as Kayexalate® (Sanofi-Aventis) and Veltassa® (Relypsa) are only recommended for the non-emergent lowering of mild to moderate hyperkalemia, while the use of insulin and glucose to drive potassium into cells in severe hyperkalemia is only a temporary strategy.
−Removed: Dialysis has been the definitive treatment of severe hyperkalemia, but requires a large dialysis machine, electricity, bags of dialysate, a skilled technician, and prolonged treatment times that are not practical in certain situations such as in remote locations, during prolonged field care in combat, in areas that lack modern medical facilities, or in situations where the
−Removed: numbers of victims outstrip available dialysis equipment and supplies.
+Added: Dialysis has been the definitive treatment of severe hyperkalemia, but requires a large dialysis machine, electricity, bags of dialysate, a skilled technician, and prolonged treatment times that are not practical in certain situations such as in remote locations, during prolonged field care in combat, in areas that lack modern medical facilities, or in situations where the numbers of victims outstrip available dialysis equipment and supplies.
Because of this, there is a major need for simple, but effective ways to rapidly treat severe hyperkalemia.
57 unchanged sentences
In total, we have sponsored clinical studies utilizing our BetaSorb device on 20 patients involving approximately 345 total treatments.
−Removed: Each study was conducted by a clinic or hospital personnel with us providing technical assistance as requested.
+Added: Each study was conducted by clinic or hospital personnel with us providing technical assistance as requested.
As discussed above, due to practical and economic considerations, we are focusing our efforts and resources on commercializing our CytoSorb device for critical care and cardiac surgery applications.
7 unchanged sentences
Under the terms of the expanded partnership, the term of the distribution agreement was extended to December 2022.
+Added: We are currently negotiating an additional extension to this agreement.
On May 27, 2020, Biocon announced that CytoSorb has received approval from the Drugs Controller General of India to treat COVID-19 patients in certain instances.
18 unchanged sentences
Under the terms of these agreements, Fresenius has exclusive rights to distribute CytoSorb for acute care and other hospital applications in South Korea and Mexico.
−Removed: Commercial sales of CytoSorb are underway in both countries after securing market registration clearance from the South Korean and Mexican health authorities in 2021 and 2020, respectively.
+Added: Registration clearance was obtained from the South Korean and Mexican health authorities in 2021 and 2020, respectively.
These multi-year agreements include an initial stocking order and are subject to annual minimum purchases of CytoSorb to maintain exclusivity.
−Removed: These agreements, which commenced on January 1, 2019, have an initial term of three years and will automatically renew for an additional two years unless terminated by either party.
−Removed: In 2020, we entered into agreements to expand the partnership with Fresenius into Columbia and Equador.
+Added: These agreements, which commenced on January 1, 2019, have an initial term of three years and automatically renew for an additional two years unless terminated by either party.
+Added: In 2020, we entered into agreements to expand the partnership with Fresenius into Colombia and Ecuador.
+Added: In August 2022, the Company entered into a Marketing Agreement (the “Marketing Agreement”) with Fresenius, which expanded the Company’s current strategic partnership with Fresenius by establishing a multi-stage global collaboration to combat life-threatening diseases in critical care.
+Added: The Marketing Agreement provides for the combined marketing and promotion of CytoSorb with Fresenius’ critical care products by Fresenius’ marketing organization worldwide, excluding the United States.
+Added: The Marketing Agreement has an initial term of three years, with an automatic renewal for an additional two years at the end of such initial term, subject to earlier termination by either of the parties (the “Term”).
+Added: Compared to the prior co-marketing agreement between the parties, the Marketing Agreement intends to increase the commitments from both parties and to ensure an ongoing and consistent level of marketing and promotional activity specifically focused around CytoSorb, where Fresenius will actively market and promote CytoSorb as the featured blood purification therapy for removal of cytokines, bilirubin, and myoglobin on its critical care platforms.
+Added: Specifically, the Marketing Agreement provides that various Fresenius-led in-person, virtual, social media, and web-based marketing programs and events will feature the CytoSorb therapy and highlight the cooperation between the two companies in the field of critical care during the Term.
+Added: To help support the increased marketing and promotional efforts of the expanded collaboration, CytoSorbents has agreed to subsidize a portion of the marketing costs through a royalty payment to Fresenius Medical Care based on CytoSorb sales in the intensive care unit on Fresenius Medical Care platforms, excluding the United States.
+Added: In addition to strengthening and expanding the global marketing of CytoSorb, the Company and Fresenius also plan to work together to bring new innovative solutions to the market.
+Added: The Marketing Agreement also includes the certification of compatibility of CytoSorb for usage on Fresenius’ current critical care platforms.
+Added: Certain initial activities have been completed with the formal launch of this program expected to occur sometime in 2023.
Aferetica s.r.l.
8 unchanged sentences
At the same time, CytoSorbents announced CE Mark approval of the ECOS-300CY cartridge for the removal of inflammatory mediators during ex vivo perfusion, which has been designated, PerSorb™, a trade name exclusive to the PerLife system.
−Removed: In August 2021, we announced that commercialization of PerSorb(TM) and Aferetica's PerLife(TM) ex vivo organ perfusion system commenced in Italy.
+Added: In August 2021, we announced that commercialization of PerSorb(TM) and Aferetica’s PerLife(TM) ex vivo organ perfusion system commenced in various European countries.
Terumo Cardiovascular Group
6 unchanged sentences
Financial terms of this agreement have not been disclosed.
−Removed: This agreement expires on March 31, 2022.
+Added: This agreement expired on March 31, 2022.
+Added: On January 1, 2023, we amended and restated the original distribution agreement from October 2016.
+Added: Under the terms of the amended and restated agreement, Terumo will have non-exclusive distribution rights in France to promote and sell the CytoSorb CPB procedure pack for intra-operative use during cardiac surgery at specifically named hospitals in France.
+Added: The amended and restated agreement allows the Company to sell directly to other hospital customers in France for the cardiac surgery application.
+Added: Financial terms of this agreement have not been disclosed.
+Added: The agreement terminates on December 31, 2023.
In August 2020, we announced an initial collaboration with Terumo to exclusively sell CytoSorb to hospitals in ten U.S.
9 unchanged sentences
Braun will supply the market with the OMNI ® and OMNIset ® Plus while CytoSorbents and its network of direct sales, strategic partners, and distributors will continue to supply the market with CytoSorb ® .
−Removed: CytoSorb ® is CE Mark certified and distributed in 67 countries worldwide.
−Removed: This global co-marketing agreement applies to the countries where both products are registered (US market is specifically excluded).
+Added: This global co-marketing agreement applies to the countries where both products are registered (U.S.
+Added: market is specifically excluded).
Financial terms of this agreement have not been disclosed.
+Added: Nikkiso Europe GmbH
+Added: In June 2022, the Company announced that, following a successful pilot program in three countries, the Company signed an expanded non-exclusive agreement with Nikkiso Europe GmbH (“Nikkiso”) to distribute Nikkiso’s PureADJUST stand-alone hemoperfusion pump and accessories in a total of 14 countries.
+Added: In addition to securing the rights to sell Nikkiso’s stand-alone pump and accessories in Germany, Austria, and Luxembourg, the Company entered into an expanded multi-country reseller agreement with Nikkiso covering the following countries:
+Added: Belgium, Bosnia and Herzegovina, Croatia, Finland, France, Iceland, Lichtenstein, Poland, Serbia, Slovenia and Switzerland.
+Added: The Company will also be able to provide field support services in these countries.
University of Pittsburgh Medical Center
7 unchanged sentences
However, we are not currently focusing our efforts on the commercialization of CytoSorb for application in organ donors.
−Removed: In September 2005, the University of Pittsburgh Medical Center was awarded a grant of approximately $7 million from NIH entitled “Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS)” to study the use of adsorbent polymer technology in the treatment of severe sepsis.
+Added: In September 2005, the University of Pittsburgh Medical Center was awarded a grant of approximately $7 million from NIH entitled “Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS)” to study the use of our adsorbent polymer technology in the treatment of severe sepsis.
The study, which lasted for a total of five years, commenced in September 2005.
16 unchanged sentences
In February 2017, all rights, title and interest to the Royalty was assigned to The Robert Shipley Living Trust.
+Added: In November 2022, all rights, title and interest to the Royalty was assigned to ROKK, LLC.
For the year ended December 31, 2022 we have recorded royalty costs of approximately $849,000.
+Added: On August 1, 2022, the Company entered into the Marketing Agreement with Fresenius, which expands the Company’s strategic partnership with Fresenius by establishing a multi-stage global collaboration to combat life-threatening diseases in critical care.
+Added: The Marketing Agreement has an initial term of three years, with an automatic renewal for an additional two years at the end of such initial term, subject to earlier termination by either of the parties (the “Term”) To help support the increased marketing and promotional efforts of the expanded collaboration, the Company has agreed to subsidize a portion of the marketing costs through royalty payments to Fresenius.
+Added: Initially, the Marketing Agreement provides for royalty payments equal to 0.9% of the Company’s net sales of CytoSorb products made during the Term (excluding net sales in the United States).
+Added: This initial royalty rate was determined based on certain assumptions regarding the percentage of the Company’s sale of CytoSorb products that are used with the Fresenius critical care platforms in the intensive care unit outside of the United States but is subject to adjustment if the Company determines that the underlying assumptions have changed significantly.
+Added: For the year ended December 31, 2022, the Company did not record any expense related to this agreement as Fresenius did not commence any marketing activities as defined by the agreement.
License Agreement
27 unchanged sentences
In the United Kingdom, market access and reimbursement of drugs, medical devices and diagnostics is heavily dependent on the guidance published by the National Institute for Health and Care Excellence (NICE).
−Removed: In 2021, NICE published its report on CytoSorb for the removal of ticagrelor in urgent and emergent cardiac surgery patients in a MedTech Innovation Briefing (MIB) called “CytoSorb for reducing risk of bleeding during cardiac surgery".
+Added: In 2021, NICE published its report on CytoSorb for the removal of ticagrelor in urgent and emergent cardiac surgery patients in a MedTech Innovation Briefing (MIB) called “CytoSorb for reducing risk of bleeding during cardiac surgery”.
The MIB highlights the safety and efficacy of CytoSorb in this indication, as well its innovative nature and the substantial cost savings CytoSorb generates and has aided adoption in the UK.
4 unchanged sentences
Across all countries, we are mitigating financial barriers though use of health economics, local data generation and targeted KOL management.
+Added: In August 2022, we disclosed that the Israeli Ministry of Health (MoH) had approved national reimbursement for CytoSorb in certain cardiac surgery indications, including the intraoperative treatment for urgent or emergency cardiac surgery in patients treated with ticagrelor or rivaroxaban, the intraoperative treatment during cardiac surgery in patients with acute infective endocarditis, and the intraoperative treatment during surgery for correction of aortic dissection.
+Added: In the same month, we announced that the Turkish Ministry of Health had approved national reimbursement for CytoSorb, which is now a reimbursed catalog product in the State Supply Office of Turkey (DMO) portal and can be purchased directly by hospitals and physicians without restrictions.
United States
9 unchanged sentences
If CytoSorb can improve outcomes and reduce the costs of ICU treatment and hospital length of stay, it could potentially save hospitals a significant amount of money.
−Removed: In January 2021, the Centers for the Centers for Medicare & Medicaid Services (CMS) announced the Medicare Coverage of Innovative Technology pathway that will provide national Medicare coverage as early as the same day as FDA market authorization for Breakthrough Designated medical devices, where coverage would last 4 years.
+Added: In January 2021, the Centers for the Centers for Medicare & Medicaid Services (CMS) announced the Medicare Coverage of Innovative Technology (MCIT) pathway that will provide national Medicare coverage as early as the same day as FDA market authorization for Breakthrough Designated medical devices, where coverage would last 4 years.
Although this program was rescinded by CMS in November 2021, a legislative version of the program is currently contained within the CARES 2.0 bill, though not yet approved.
−Removed: If passed, this program may be applicable to DrugSorb-ATR, if it can achieve U.S.
+Added: In addition, CMS has announced a new initiative called “Transitional Coverage for Emerging Technologies” (TCET) as a potential replacement for MCIT, with more detail planned for April 2023.
+Added: If passed, either of these programs may be applicable to DrugSorb-ATR, if it can achieve U.S.
approval for the removal of ticagrelor and Direct Oral Anticoagulants (DOACs) apixaban and rivaroxaban during emergent or urgent cardiothoracic surgery.
−Removed: These applications were granted FDA Breakthrough Designation in April 2020 and August 2021, respectively.
+Added: These indications were granted FDA Breakthrough Designation in April 2020 and August 2021, respectively.
Our core adsorbent porous polymer bead technology is used in our marketed products, such as the CytoSorb, ECOS-300CY, and VetResQ cartridges, and other products under advanced development, such as CytoSorb XL and DrugSorb-ATR.
41 unchanged sentences
A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding.
−Removed: There was no difference in 28-day mortality of 15% in each group, and the study did not reach significant improvement in the primary endpoint in the
−Removed: pre-defined mITT population.
+Added: There was no difference in 28-day mortality of 15% in each group, and the study did not reach significant improvement in the primary endpoint in the pre-defined mITT population.
However, in the PP analysis that excluded 17 patients, the company claims clinical composite endpoint success of 54.3% treatment vs 40.3% control.
12 unchanged sentences
The TIGRIS study will be in US sites only, randomized (2:1), open label trial, with an additional 150 new patients (100 treated, 50 control) to be added.
−Removed: As of February 11, 2022, 30 patients of the targeted 150 patients have been enrolled.
+Added: As of January 12, 2023, 50 patients of the targeted 150 patients have been enrolled, with an expansion of trial sites to a total of 25, with 15 currently active.
Enlivex has developed an investigational cell-based therapy called Allocetra that is an infusion of donor mononuclear cells that have been chemically induced to be apoptotic.
1 unchanged sentence
In September 2021, Enlivex announced the start of a Phase IIb study using Allocetra in severe and critical COVID-19 patients with acute respiratory distress syndrome (ARDS).
−Removed: In November 2021, Enlivex reported that Allocetra is being evaluated in a randomized, controlled, multi-center trial in patients with pneumonia-associated sepsis.
+Added: In November 2021, Enlivex reported that Allocetra is being evaluated in a randomized, controlled, Phase II multi-center trial in patients with pneumonia-associated sepsis.
It is expected to enroll 120-160 patients across 4 cohorts of varying doses of Allocetra or placebo.
The primary endpoints of the trial are safety and change in SOFA score from baseline at 28 days.
+Added: As of February 2023, enrollment has not been disclosed.
In 2017, a single center, retrospective, non-randomized, unblinded before-after clinical study evaluating the effect of hydrocortisone, intravenous Vitamin C, and thiamine in a total of 94 patients with severe sepsis and septic shock was published suggesting a significant decrease in hospital mortality of 8.5% (4 of 47 treated) versus mortality of 40.4% (19 of 47 control), p<0.001.
23 unchanged sentences
Mortality was 66.6% in patients receiving oXiris treatment after 14 days from admission, and a mortality of 47.4% mortality when used earlier.
−Removed: In addition, Baxter also launched the Theranova mid-
−Removed: molecular weight cutoff or high retention onset (HRO) hemodialysis membrane to improve the efficiency of hemodialysis, claiming improved mid-molecular weight substance removal.
+Added: In addition, Baxter also launched the Theranova mid-molecular weight cutoff or high retention onset (HRO) hemodialysis membrane outside the U.S.
+Added: to improve the efficiency of hemodialysis, claiming improved mid-molecular weight substance removal.
Neither oXiris nor Theranova are approved in the U.S.
+Added: for treatment of sepsis or respiratory failure.
Each of the following technologies claims to remove inflammatory mediators such as cytokines, or to treat sepsis, and represents a potential competitive alternative to CytoSorb.
14 unchanged sentences
We believe that CytoSorb, which can treat whole blood directly, and which works with standard hemodialysis pumps already found in hospitals worldwide, has significant competitive advantages compared to these multi-cartridge sorbent systems.
−Removed: Kaneka Corporation currently markets Lixelle™, a modified porous cellulosic bead, for the removal of beta 2 –microglobulin during hemodialysis in Japan To our knowledge, no large, randomized, controlled trials have been conducted with Lixelle as a treatment for sepsis.
+Added: Kaneka Corporation currently markets Lixelle™, a modified porous cellulosic bead, for the removal of beta 2 –microglobulin during hemodialysis in Japan.
+Added: To our knowledge, no large, randomized, controlled trials have been conducted with Lixelle as a treatment for sepsis.
Kaneka obtained U.S.
3 unchanged sentences
Jafron Biomedical is an integrated dialysis public company in China selling dialysis machines and hemodialysis and hemoperfusion cartridges containing a neutral microporous adsorption resin to purify blood of toxins in liver failure, critical illness, poisoning, and autoimmune diseases.
−Removed: According to clinicaltrials.gov, there are 5 investigator-initiated studies evaluating Jafron's technology in sepsis, and cardiac and respiratory failure.
+Added: According to clinicaltrials.gov, there are 5 investigator-initiated studies evaluating Jafron’s technology in sepsis, cardiac and respiratory failure and liver disease.
Jafron is currently recruiting a 144 patient efficacy and safety study in China using its CA330 cartridge to reduce IL-6 in septic patients.
−Removed: The estimated study completion date was October 2020.
+Added: The status of the trial has not been updated since February 2019.
+Added: Another investigator-initiated RCT evaluating the HA-330 device in 200 patients with norepinephrine-resistant septic shock (CLEANSE) began in Thailand in November 2021 and is still enrolling.
Foshan Biosun Medical Technology Co, Ltd, and Baihe Medical Technology Co, market hemoperfusion cartridges under the BioSky brand name, including the MG series claiming cytokine reduction, and the DX series for bilirubin reduction.
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Cardiopulmonary Bypass Surgery
−Removed: There is currently a pre-existing market for the use of leukocyte reduction filters sold by Pall Corporation, Terumo Medical Corporation and others in the cardiopulmonary bypass circuit.
−Removed: The purpose of these devices is to reduce cytokine-producing white blood cells from blood.
−Removed: They do not remove cytokines, free hemoglobin, or activated complement directly and are not considered by many to be an effective solution for the reduction of these substances.
+Added: Previously, leukocyte reduction filters sold by Pall Corporation, Terumo Medical Corporation and others were used in the cardiopulmonary bypass circuit to reduce cytokine-producing white blood cells from blood.
+Added: They did not remove cytokines, free hemoglobin, or activated complement directly and were not considered by many to be an effective solution for the reduction of these substances.
Other than blood compatible sorbent technologies, we are not aware of any practical competitive approaches for removing cytokines, free hemoglobin, activated complement, and a broad range of other inflammatory mediators in patients undergoing cardiopulmonary bypass during cardiac surgery.
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Alternative therapies such as “off-pump” surgeries are available but “post-bypass” syndrome and cytokine production still remain a problem in this less invasive, but more technically challenging procedure.
−Removed: If successful, CytoSorb is expected to be useful in both on-pump and off-pump procedures.
+Added: CytoSorb has been used in both on-pump and off-pump procedures.
CytoSorb is also being used with a dialysis machine to treat the development of a post-cardiac surgery systemic inflammatory response syndrome, a deadly complication of open-heart surgery that if left untreated, can lead to multiple organ dysfunction syndrome, multiple organ failure, and potentially death.
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RenalGuard encourages excretion of IV contrast and a reduction of CIN, by administering IV hydration that matches urine output in patients receiving a loop diuretic.
−Removed: Hemodialysis can remove IV contrast, but is relatively slow (46% at 1
−Removed: hour, 65% at 2 hours, and 75% at 3 hours) in chronic renal failure patients who lack normal renal clearance.
+Added: Hemodialysis can remove IV contrast, but is relatively slow (46% at 1 hour, 65% at 2 hours, and 75% at 3 hours) in chronic renal failure patients who lack normal renal clearance.
In high risk patients, the rapid and direct removal of IV contrast from the blood with ContrastSorb to prevent CIN represents a potentially more effective alternative.
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Each method has its own limitations, many of which are associated with the timing of administration following overdose.
−Removed: Blood purification with high flux dialyzers or with activated charcoal cartridges by Gambro, Fresenius, Nephros and others are typically efficient at removing hydrophilic drugs that are not protein bound.
+Added: Blood purification with therapeutic plasma exchange, high flux dialyzers or with activated charcoal cartridges by Gambro, Fresenius, Nephros and others are typically efficient at removing hydrophilic drugs that are not protein bound.
However, they are inefficient at removing drugs that have a large volume of distribution, or drugs that are hydrophobic or lipophilic.
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We are not aware of any directly competitive products to address the application of our technology for the mitigation of organ dysfunction and failure resulting from severe inflammation following brain-death, or in the removal of inflammatory mediators during ex vivo organ perfusion
−Removed: Removal of Anti-thrombotics such as Ticagrelor and Direct Oral Anticoagulants in Cardiac Patients During Surgery Requiring Cardiopulmonary Bypass
+Added: Removal of Antithrombotics such as Ticagrelor and Direct Oral Anticoagulants in Cardiac Patients During Surgery Requiring Cardiopulmonary Bypass
There are more than $20 billion in annual worldwide sales of anti-thrombotic drugs such as the P2Y 12 platelet inhibitors (e.g.
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during cardiopulmonary bypass in urgent or emergent cardiopulmonary bypass.
−Removed: The only recommended alternative is to wait for 3-5 days to allow natural drug elimination and washout prior to surgery.
+Added: The only recommended alternative is to wait for 3 to 5 days to allow natural drug elimination and washout prior to surgery.
CytoSorb has already demonstrated the ability to remove ticagrelor rapidly and efficiently from human blood in vitro .
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In the U.S., we are currently executing the U.S.
−Removed: STAR-T and STAR-D (Safe and Timely Antithrombotic Removal of Ticagrelor, or DOACs, respectively) pivotal randomized, controlled clinical trials designed to support U.S.
+Added: STAR-T (Safe and Timely Antithrombotic Removal of Ticagrelor, ) pivotal randomized, controlled clinical trials designed to support U.S.
FDA Marketing approval of the DrugSorb-ATR antithrombotic removal system, which uses an equivalent polymer technology to CytoSorb.The use of platelet transfusions, Kcentra ® (CSL Behring;
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reversal agent for dabigatran) and other interventions have either not demonstrated consistent benefit, or are not used because of potential safety concerns, in the reversal of antithrombotics in the setting of cardiopulmonary bypass.
−Removed: PhaseBio, a clinical-stage biopharmaceutical company, has licensed an intravenously administered monoclonal antibody fragment with high affinity for ticagrelor called bentracimab (PB2452) from Medimmune, a division of AstraZeneca.
−Removed: The company paid AstraZeneca $100,000 upfront, with $68 million in potential future milestones.
−Removed: AstraZeneca owns approximately 5% of PhaseBio’s stock.
−Removed: PB2452 is a novel reversal agent for the antiplatelet drug ticagrelor, which was developed for the treatment of patients on ticagrelor who are experiencing a major bleeding event or those who require urgent surgery.
+Added: We anticipate resuming the STAR-D (Safe and Timely Antithrombotic Removal of DOACs) trial upon completion of the STAR-T trial.
+Added: PhaseBio, a now defunct clinical-stage biopharmaceutical company, had licensed an intravenously administered monoclonal antibody fragment with high affinity reversal agent for ticagrelor called bentracimab (PB2452) from Medimmune, a division of AstraZeneca.
+Added: PhaseBio paid AstraZeneca $100,000 upfront, with $68 million in potential future milestones.
+Added: AstraZeneca owned approximately 5% of PhaseBio’s stock.
The FDA granted Breakthrough Therapy designation for PB2452 in April 2019.
−Removed: PhaseBio is seeking US FDA approval of PB2452 in the United States through an accelerated approval process.
−Removed: PhaseBio is currently conducting its U.S.
+Added: PhaseBio was conducting its U.S.
REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial) study, a Phase 3, prospective, multi-center, open-label, single-arm trial designed to study reversal of the antiplatelet effects of ticagrelor with bentracimab to treat patients who present with uncontrolled major or life-threatening bleeding or when used prophylactically in patients who require urgent surgery or an invasive procedure to prevent bleeding.
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two with septic shock, and two with cardiogenic shock.
−Removed: Of 150 patients, 8 patients (5.3%) had thrombotic events, including 2 ischemic strokes, 1 transient ischemic attack, 3 myocardial infarctions, and two with arterial thromboembolisms in the right lower extremity.
+Added: Of 150 patients, eight patients (5.3%) had thrombotic events, including two ischemic strokes, one transient ischemic attack, three myocardial infarctions, and two with arterial thromboembolisms in the right lower extremity.
The FDA had recommended an interim analysis of approximately 100 patients, comprising approximately 50 patients in each arm, in order to support the submission of a Biologics License Application (BLA) for accelerated approval of bentracimab.
In November 2021, PhaseBio announced that it continues to enroll more patients into the uncontrolled major or life-threatening bleeding arm of the study and intends to submit a BLA for both subgroups by Summer 2022.
−Removed: Bentracimab is not yet approved in any market.
+Added: However, in October 2022, PhaseBio filed for Chapter 11 bankruptcy.
+Added: The bentracimab asset was transferred to PhaseBio’s creditor, SFJ Pharmaceuticals in December 2022, that expects to file the BLA in mid-2023.
Meanwhile, Andexxa is a Factor Xa analog that competes for binding to Factor Xa inhibitors.
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There are only a few directly competitive approved products to address the removal of substances from blood and blood products that can cause transfusion reactions.
−Removed: Leukoreduction (Haemonetics, Terumo-BCT, Hemerus Corporation, others) is widely
−Removed: used in transfusion medicine and can remove the majority of white cells that can produce new cytokines but cannot eliminate those cytokines already in blood, and cannot otherwise remove other causative agents.
+Added: Leukoreduction (Haemonetics, Terumo-BCT, Hemerus Corporation, others) is widely used in transfusion medicine and can remove the majority of white cells that can produce new cytokines but cannot eliminate those cytokines already in blood, and cannot otherwise remove other causative agents.
Automated washing of pRBC is very effective at cleansing contaminants from blood, but is impractical due to the time, cost, materials, and logistics of washing each unit of blood and is not widely used.
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FDA Emergency Use Authorization for the treatment of adult critically ill COVID-19 patients with confirmed or imminent respiratory failure.
−Removed: The C ytoSorb T herapy in C OVID-19 ( CTC ) Registry was launched to capture outcomes and device utilization patterns from multiple U.S.
+Added: C ytoSorb T herapy in C OVID-19 ( CTC ) Registry was launched to capture outcomes and device utilization patterns from multiple U.S.
participating centers.
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centers showed high survival rates (73%) compared with the international benchmark Extracorporeal Life Support Organization (ELSO) Registry.
−Removed: The initial CTC results were presented at the International Symposium of Intensive Care Medicine conference in August 2021 in Brussels, Belgium, and published in the peer reviewed journal Frontiers in Medicine.
−Removed: The CTC has completed enrollment and the final results will also be submitted for publication.
+Added: The initial CTC results on the first 52 critically ill patients from five U.S.
+Added: ECMO centers were presented at the International Symposium of Intensive Care Medicine conference in August 2021 in Brussels, Belgium, and published in the peer reviewed journal Frontiers in Medicine.
+Added: The CTC registry completed enrollment with 100 patients from five centers, and the final results mirror the high survival (74%) seen in the previous analysis, and have been submitted for publication.
The German PROCYSS multicenter, randomized controlled trial evaluating the ability of CytoSorb to restore hemodynamic stability in patients with refractory septic shock is now actively enrolling.
−Removed: The speed of enrollment remains uncertain due to COVID-19, however we currently estimate that the next important milestone of the interim analysis after 50% enrollment will occur in 2023.
−Removed: The German multicenter Hep-On-Fire single-arm trial evaluating CytoSorb in patients suffering from acute liver failure due to alcoholic hepatitis received Ethics Committee approval in October 2021 and study start-up activities are ongoing.
−Removed: We expect that the study will begin enrollment in the first half of 2022 and that the next important milestone of the interim analysis after 50% enrollment will occur in 2023.
+Added: The speed of enrollment remains uncertain due to COVID-19 related institutional research staff shortages, however we anticipate conditions to improve in the second half of 2023 which should help recruitment toward the next milestone of the interim analysis after 50% enrollment.
The international COSMOS Registry was designed to capture real world outcomes and device utilization patterns across multiple critical care indications including but not limited to sepsis, acute respiratory failure, postoperative vasoplegia, acute liver failure, and acute pancreatitis.
−Removed: The Registry is undergoing start-up activities and scheduled to begin enrollment in the first half of 2022 with the goal of being active in multiple countries in 2023.
+Added: The Registry is actively enrolling in Spain and Germany with plans to expand in more countries in 2023.
The intent of the Registry is to report outcomes at international conferences and submit the results for publication on a rolling basis as enrollment progresses.
Cardiac Surgery
−Removed: In February 2015, the U.S.
−Removed: Food and Drug Administration (the “FDA”) approved our Investigational Device Exemption (“IDE”) application to commence a planned U.S.
−Removed: cardiac surgery feasibility randomized controlled study called REFRESH I.
−Removed: The study was designed to evaluate the safety and feasibility of two CytoSorb devices used intra-operatively with a heart-lung machine to reduce plasma free hemoglobin (pfHb) and cytokines in patients undergoing complex cardiac surgery.
−Removed: On October 5, 2016, we announced that the independent Data Safety Monitoring Board (“DSMB”) found no serious device related adverse events with CytoSorb, achieving the primary safety endpoint of the study and demonstrating the safety of intra-operative use in patients undergoing high risk cardiac surgery.
−Removed: The study was published in the peer reviewed journal Seminars in Thoracic and Cardiovascular Surgery.
−Removed: In December 2017, the FDA approved our IDE application for the randomized, controlled, multi-center REFRESH 2-AKI study designed to evaluate intraoperative use of two CytoSorb devices as a therapy to reduce the incidence and severity of acute kidney
−Removed: Postoperative AKI following cardiac surgery is common and is associated with higher mortality, and is a risk factor for developing chronic kidney disease requiring hemodialysis in the future.
−Removed: The study was scheduled to enroll up to 400 patients and completed the first scheduled Data Monitoring Committee (DMC) safety review after the first 153 patients enrolled on July 24, 2020 with no safety concerns.
−Removed: The decision was made to stop the REFRESH 2-AKI study in January 2022 for business reasons to shift resource allocation to the prioritized U.S.
−Removed: STAR-T and STAR-D trials discussed below.
−Removed: Importantly, there were no safety issues in the REFRESH 2-AKI trial.
In January 2020, CytoSorb received European Union CE Mark label expansion to include the removal of ticagrelor during cardiopulmonary bypass in patients undergoing cardiothoracic surgery.
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The international S afe and T imely A ntithrombotic R emoval ( STAR ) Registry is designed to capture real world clinical and health economic outcomes with intraoperative antithrombotic drug removal.
−Removed: The Registry is actively enrolling in the U.K.
−Removed: and Germany and is planned to expand to additional EU countries before the end of 2022.
−Removed: The intent of the Registry is to report outcomes at international conferences and submit the results for publication on a rolling basis as enrollment progresses.
−Removed: In July 2021, we received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study for up to 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval – T icagrelor ( STAR-T ),” in the United States to support FDA marketing approval.
+Added: The Registry is actively recruiting in the U.K., Germany, Austria and Sweden and is planned to expand to additional countries in 2023.
+Added: The intent of the Registry is to report outcomes at international conferences and submit the results for publication on a rolling basis as enrollment progresses with estimated first data readouts in 2023.
+Added: In July 2021, we received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study in 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval – T icagrelor ( STAR-T ),” in the United States to support FDA marketing approval.
This was done under the previously announced FDA Breakthrough Device Designation granted for the removal of ticagrelor in a cardiopulmonary bypass circuit to reduce the likelihood of serious perioperative bleeding during urgent cardiac surgery.
−Removed: In October 2021, the first patient was enrolled and the STAR-T study is now actively recruiting at multiple sites.
−Removed: We expect the study to reach its first scheduled milestone of the first Data Safety Monitoring Board (DSMB) meeting after 33% of patients are enrolled this summer.
−Removed: Enrollment is expected to be complete within 12 months from today.
+Added: In October 2021, the first patient was enrolled, and the STAR-T study is now actively recruiting at multiple U.S.
+Added: In November 2022, the first milestone was completed with the first one-third of patients enrolled, triggering the first Data Safety Monitoring Board (DSMB) meeting.
+Added: The DSMB recommended to continue the study as planned without any modifications.
+Added: In 2022, we also received FDA approval to expand the study to Canada and subsequently received Health Canada approval allowing inclusion of Canadian sites into the STAR-T trial in January 2023.
+Added: In early 2023, the study exceeded 50% enrollment and is expected to reach the 2 nd milestone of 67% enrollment in the spring of 2023 triggering another DSMB safety review.
+Added: The study is expected to reach 100% enrollment sometime in the summer of 2023.
+Added: Based on the accelerated enrollment rate and expected evaluation period associated with an interim analysis, we are considering foregoing the interim analysis and proceeding to study completion and final analysis.
+Added: Should we choose to forego the interim analysis, we would be required to notify the FDA.
In October 2021, we also received full FDA approval of an Investigational Device Exemption (IDE) application to conduct a double-blind, randomized, controlled clinical study for up to 120 patients entitled, “ S afe and T imely A ntithrombotic R emoval – D irect Oral Anticoagulants ( STAR-D ),” in the United States to support FDA marketing approval.
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This Breakthrough Device designation covers the removal of the Direct Oral Anticoagulants (DOACs) apixaban and rivaroxaban in a cardiopulmonary bypass circuit to reduce the likelihood of serious perioperative bleeding during urgent cardiac surgery.
−Removed: First sites have been activated and we expect the first patient to be enrolled in the first quarter of 2022 with target study enrollment completion in 12-18 months following the first patient enrolled.
−Removed: The single arm TISORB study executed in the U.K.
−Removed: and the single arm CYTATION study in Germany evaluating ticagrelor removal during cardiac surgery were both stopped in 2021.
−Removed: The decision was made since the larger, far more rigorous double blind RCT STAR-T will generate much higher quality data on ticagrelor removal and is powered to also report clinical outcomes rendering these two single arm studies redundant.
−Removed: Once again, it is important to emphasize that this was a business decision to enhance the focus and resource allocation to the STAR programs and that there were no safety concerns in either of the two stopped studies as confirmed by the independent DSMBs of each study.
−Removed: Update on the REMOVE Investigator Initiated Study
−Removed: The German government funded, investigator initiated, REMOVE clinical study reported topline results at the European Association of Cardiothoracic Surgery in October 2021.
−Removed: The primary efficacy endpoint was not met;
−Removed: however, the intraoperative use of CytoSorb was well tolerated and safe without any excess in adverse events compared to controls and the mechanism of action for the reduction of cytokines was validated.
−Removed: We are awaiting publication of the results and plan to review the results carefully in close collaboration with the investigators to determine the potential for a company-sponsored study in infective endocarditis.
+Added: Study enrollment was paused in November of 2022 for business reasons and is scheduled to resume after completion of the STAR-T trial.
COVID-19 Business Update
−Removed: COVID-19 patients develop life-threatening complications such as acute respiratory distress syndrome (ARDS), shock (i.e.
−Removed: a potentially fatal drop in blood pressure), kidney failure, acute cardiac injury, thromboses and emboli, and secondary bacterial infections.
+Added: COVID-19 patients develop life-threatening complications such as acute respiratory distress syndrome (ARDS), shock (i.e., a potentially fatal drop in blood pressure), kidney failure, acute cardiac injury, thromboses and emboli, and secondary bacterial infections.
The underlying cause for these complications is often 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.
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The EUA will be effective until a declaration is made that the circumstances justifying the EUA have terminated or until revoked by the FDA.
−Removed: The CTC (CytoSorb Therapy in COVID-19) Registry was launched to capture outcomes and device utilization patterns from multiple U.S.
+Added: CTC (CytoSorb Therapy in COVID-19) Registry was launched to capture outcomes and device utilization patterns from multiple U.S.
participating centers.
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In December 2021, we announced the publication of these results in the peer-reviewed journal Frontiers in Medicine .
+Added: The CTC Registry has completed enrollment and the final results confirming high survival (74%) were presented at the European Society of Intensive Care Medicine conference in October 2022 and also have been submitted for publication.
Government Research Grants
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This program was funded by the Joint Program Executive Office - Chemical and Biological Defense (“CBD”) SBIR program.
−Removed: We received approximately $999,996 in funding under this contract and no further funding remains under this contract.
+Added: We received $999,996 in funding under this contract and no further funding remains under this contract.
Our performance under this contract has been completed.
2 unchanged sentences
This contract provides for maximum funding of $719,000 over four years.
−Removed: As of December 31, 2021, we received approximately $696,000 and have approximately $23,000 remaining under this contract.
+Added: As of December 31, 2022, we received $719,000 and have no further funding remaining under this contract.
In September 2017, the Company was awarded a Phase II SBIR contract for its development program entitled “Investigation of a sorbent-based potassium adsorber for the treatment of hyperkalemia induced by traumatic injury and acute kidney injury”.
The purpose of this contract is to continue development of two novel and distinct treatment options for life-threatening hyperkalemia.
−Removed: This work is being funded by the USAMRAA under contract W81XWH-17-C-0142 and provides for maximum funding of approximately $999,871.
−Removed: As of December 31, 2021, we received approximately $999,871 and no further funding remains under this contract.
+Added: This work is being funded by the USAMRAA under contract W81XWH-17-C-0142 and provides for maximum funding of $999,871.
+Added: As of December 31, 2022, we received $999,871 and no further funding remains under this contract.
In August 2018, the Company was awarded a Phase IIB Bridge SBIR contract by the NHLBI to facilitate and accelerate the commercialization of our HemoDefend blood purification technology for the purification of pRBC transfusions.
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On April 19, 2021, the Company received notification that it received a U.S.
−Removed: Army Medical Research Acquisition Activity Award (the “USAMRAAA”) entitled "Investigation of a potassium adsorber for the treatment of hyperkalemia induced by traumatic injury and acute kidney injury in austere medicine."
−Removed: The USAMRAAA Phase II Sequential Award, for up to $1,499,987, was granted to the Company to continue development of two novel and distinct treatment options for life-threatening hyperkalemia.
+Added: Army Medical Research Acquisition Activity Award (the “USAMRAAA”) entitled “Investigation of a potassium adsorber for the treatment of hyperkalemia induced by traumatic injury and acute kidney injury in austere medicine.” The USAMRAAA Phase II Sequential Award, for up to $1,499,987, was granted to the Company to continue development of two novel and distinct treatment options for life-threatening hyperkalemia.
This award is being funded by the USAMRAAA under Contract No.
1 unchanged sentence
As of December 31, 2022, we have received $871,000 funding under the contract and have approximately $629,000 remaining under the contract.
+Added: On May 9, 2022, the Company received a U.S.
+Added: Army Medical Research Acquisition Activity Award (the “USAMRAAA”) entitled “Demonstration of the Safety and Efficacy of Field-Ready Blood Group Antibody (BGA) Adsorber in the Porcine Universal Transfusion Model.” The Department of Defense (DoD) Defense Medical Research and Development Program (DMRDP) Joint Program Committee 6 (JPC-6) Combat Casualty Care Research Program (CCCRP) Battlefield Resuscitation for the Immediate Stabilization of Combat Casualties Award, for up to $1,977,024, was granted to the Company to validate the safety and efficacy of the BGA device in a preclinical study in pigs.
+Added: This award is being funded by the USAMRAAA under Contract No.
+Added: W81XWH-22-1-0235.
+Added: As of December 31, 2022, we have received $124,000 funding under the contract and have approximately $1,853,000 remaining under the contract.
+Added: On August 22, 2022, the Company received a U.S.
+Added: Army Medical Research Acquisition Activity Award (the “USAMRAAA”) entitled “Integrating Isoagglutinin Reduction for a Universal Dried Plasma Product for Battlefield and First Responder Use.” This three-year Phase III contract, which is valued at $4,292,641, is to be used to customize the design of the HemoDefend-BGA™ filter for sterile integration into collections systems for freeze-dried plasma processing to generate freeze-dried universal plasma.
+Added: Without the need for blood typing, widespread availability of universal plasma could help save lives via faster emergency treatment in both civilian and military settings.
+Added: This award is being funded by the USAMRAAA under Contract No.
+Added: W81XWH-22-C0046.
+Added: As of December 31, 2022, we have received $35,000 funding under the contract and have approximately $4,257,000 remaining under the contract.
+Added: On August 29.
+Added: 2022, the Company was granted a Phase I Small Business Innovation Research (SBIR) award entitled “Novel Extracorporeal Therapy for the Reversal of Septic Shock and Restoring Hemodynamic Stability” by the National Institute of General Medical Sciences (NIGMS), a division of the U.S.
+Added: National Institutes of Health.
+Added: This eight-month award, which is valued at $281,835, will allow CytoSorbents to test the ability of its novel and existing polymers to remove cytokines and lipopolysaccharide (LPS) endotoxin, a well-known potent and deadly trigger of sepsis and septic shock, from septic porcine plasma.
+Added: As of December 31, 2022, we have received $29,000 funding under the contract and have approximately $253,000 remaining under the contract.
+Added: On December 1, 2022, the Company was granted a Phase I Small Business Innovation Research (SBIR) award by AFWERX, a United States Air Force program with the goal of fostering a culture of innovation within the service.
+Added: This three-month award, which is valued at $74,955, will allow CytoSorbents to perform customer discovery within the Department of the Air Force (DAF) and to better understand DAF end-user needs and help define product requirements for our solution to prevent and treat certain infectious diseases that threaten warfighters.
+Added: As of December 31, 2022, we have received $18,000 funding under the contract and have approximately $57,000 remaining under the contract.
Our business could be adversely impacted by automatic cuts in Federal spending.
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These agencies require manufacturers of medical devices to comply with applicable laws and regulations governing the development, testing, manufacturing, labeling, marketing and distribution of medical devices.
−Removed: are generally subject to varying levels of regulatory control, the most comprehensive of which requires that a clinical evaluation be conducted before a device receives approval for commercial distribution.
+Added: Devices are generally subject to varying levels of regulatory control, the most comprehensive of which require that a clinical evaluation be conducted before a device receives approval for commercial distribution.
In the EU, medical devices that we manufacture are required to comply with the Medical Devices Directive 93/42/EC (“MDD”) and obtain CE Mark certification in order to market medical devices.
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As of May 27, 2021, devices that have not received CE Mark renewal under the MDD or where existing device or processes are substantially amended, certification would be required in accordance with the new European Union Medical Device Regulation (“MDR”).
−Removed: However, devices already certified under the MDD can continue to use the CE Mark under the MDD until the expiry of those MDD CE certificates and in August of 2019, we announced that CytoSorb received renewal of its E.U.
−Removed: CE Mark through May 2024.
+Added: However, devices already certified under the MDD can continue to use the CE Mark under the MDD until the expiry of those MDD CE certificates and in August of 2019, we announced that CytoSorb received renewal of its EU CE Mark through May 2024.
In March 2011, we successfully completed our technical file review with our notified body and received approval to apply the CE Mark to the CytoSorb device as an extracorporeal cytokine adsorber.
We also achieved ISO 13485:2003 Full Quality Systems certification, an internationally recognized quality standard designed to ensure that medical device manufacturers have the necessary comprehensive management systems in place to safely design, develop, manufacture and distribute medical devices in the EU.
−Removed: In February 2015, we extended the coverage of our ISO 13485 Certificate with the inclusion of Canadian Quality Systems requirements.
−Removed: This additional level of certification will allow us to apply for product approvals in Canada in the future.
−Removed: In June 2016, we successfully completed an ISO 13485:2003 annual surveillance audit maintaining our good standing with our notified body.
−Removed: In September 2016, we were granted a two-year renewal for the CytoSorb CE Mark.
−Removed: In June 2018, we received clearance from our notified body to begin production in our new manufacturing facility.
−Removed: In July 2018, we successfully completed an audit upgrade from an ISO 13485:2003 certification to an ISO 13485:2016 certification, which is valid through September 2022.
+Added: In February 2015, we extended the coverage of our ISO 13485 Certificate with the inclusion of Canadian Quality Systems requirements, however, Canada has replaced this earlier program with the Medical Device Single Audit Program (“MDSAP”) and the Company is now evaluating the requirements for this certification.
+Added: Since 2011, CytoSorbents has maintained a valid ISO13485 certificate.
+Added: In July 2018, we successfully completed an audit upgrade from an ISO 13485:2003 certification to an ISO 13485:2016 certification, valid through 2019.
+Added: Subsequent surveillance and recertification audits have been successfully completed to maintain the certification.
+Added: In April 2022, we successfully completed an annual ISO 13485:2016 surveillance audit that encompassed both the Deer Park manufacturing site and the new manufacturing facility at 305 College Road East, Princeton, NJ.
+Added: In September 2022, we received ISO 13485 Certification of this new facility, clearing the way for full manufacturing of CytoSorb, DrugSorb-ATR, and ECOS-300C from this site.
In the EU, as in other geographies, there are limits to the claims we are allowed to make, associated with the use of our devices.
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The FDA may require additional information, including clinical data, to make a determination regarding substantial equivalence.
−Removed: After an applicant has obtained clearance, changes to the device (which do not significantly affect safety or effectiveness) which do not significantly affect safety or effectiveness can generally be made without additional 510(k) Submissions, but evaluation of whether a new 510(k) is needed is a complex regulatory issue, and changes must be evaluated on an ongoing basis to determine whether a proposed change triggers the need for a new 510(k), or even PMA .The 510(k) clearance pathway is not available for all devices:
+Added: After an applicant has obtained clearance, changes to the device which do not significantly affect safety or effectiveness can generally be made without additional 510(k) Submissions, but evaluation of whether a new 510(k) is needed is a complex regulatory issue, and changes must be evaluated on an ongoing basis to determine whether a proposed change triggers the need for a new 510(k), or even PMA.The 510(k) clearance pathway is not available for all devices:
whether it is a suitable path to market depends on several factors, including regulatory classifications, the intended use of the device, and technical and risk-related issues for the device.
−Removed: Should a suitable predicate device not be available, the second pathway is the de novo request pathway.
−Removed: The de novo pathway is available for novel device technologies, including novel device changes, that have not been previously classified by FDA and for which there is no suitable predicate device.
+Added: Should a suitable predicate device not be available, the second pathway is the 510(k) De Novo request.
+Added: The de novo pathway is available for medium risk novel device technologies, including novel device changes, that have not been previously classified by FDA and for which there is no suitable predicate device.
To obtain marketing authorization via the de novo pathway, the applicant must show that the subject device can be reclassified as Class I or Class II.
−Removed: The de novo request pathway typically requires additional testing data, which may include clinical data.
+Added: The de novo request pathway typically requires additional testing data, which includes clinical data.
The third, more rigorous, process requires that an application for PMA be made to the FDA to demonstrate that the device is safe and effective for its intended use as manufactured.
This approval process applies to most Class III devices.
−Removed: A PMA submission is the most burdensome FDA premarket submission type for devices and includes data regarding design, materials, bench and animal testing, and human clinical data for the medical device.
+Added: A PMA submission is the most rigorous FDA premarket submission type for devices and includes data regarding design, materials, bench and animal testing, and human clinical data for the medical device.
Again, clinical trials are subject to extensive FDA regulation.
24 unchanged sentences
On April 10, 2020 the FDA granted CytoSorbents Emergency Use Authorization of CytoSorb to treat patients 18 years of age or older, with confirmed COVID-19 admitted to the ICU with confirmed or imminent respiratory failure.
−Removed: Per the FDA, "The Emergency Use Authorization (EUA) authority allows the FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures needed during public health emergencies.
−Removed: Under Section 564 of the Federal Food, Drug, and Cosmetic Act (the "Act"), the FDA commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives."
−Removed: EUA is an approval limited in scope and, subject to FDA discretion regarding duration of the approval.
+Added: Per the FDA, “The Emergency Use Authorization (EUA) authority allows the FDA to help strengthen the nation’s public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures needed during public health emergencies.
+Added: Under Section 564 of the Federal Food, Drug, and Cosmetic Act (the “Act”), the FDA commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives.”
+Added: EUA is an authorization limited in scope and, subject to FDA discretion regarding EUA duration.
Devices with EUA are neither formally cleared nor approved for the indication to treat patients with COVID-19 infection.
1 unchanged sentence
The FDA can at its discretion cancel the EUA approval when there is no longer a threat to public health.
−Removed: The delivery of our devices in the U.S.
+Added: The placement of our devices in the U.S.
market would be subject to regulation by the U.S.
Department of Health and Human Services and comparable state agencies responsible for reimbursement and regulation of health care items and services.
−Removed: regulations are imposed primarily in connection with the Medicare and Medicaid programs, as well as the government’s interest in regulating the quality and cost of health care.
+Added: laws and regulations are imposed primarily in connection with the Medicare and Medicaid programs, as well as the government’s interest in regulating the quality and cost of health care.
Federal health care laws apply when we or customers submit claims for items or services that are reimbursed under Medicare, Medicaid, or other federally-funded health care programs.
13 unchanged sentences
The process of obtaining clearance or approval to market products is costly and time-consuming in virtually all of the major markets in which we expect to sell products and may delay the marketing and sale of our products.
−Removed: Countries around the world have recently adopted more stringent regulatory requirements, which are expected to add to the delays and uncertainties associated with new product releases, as well as the clinical and regulatory costs of supporting those releases.
+Added: Countries around the world have recently adopted more stringent regulatory requirements, which are expected to add to the delays and uncertainties associated with new product releases, as well as the pre-clinical, clinical and regulatory costs of supporting those releases.
No assurance can be given that any of our other medical devices will be approved on a timely basis, if at all, or that our CytoSorb® device will be approved for CE Mark labeling under the MDR in other potential medical applications or that it will be approved for cytokine adsorption in markets not covered by the CE Mark on a timely basis, or at all.
3 unchanged sentences
Pertaining to our VetResQ™ device (offered for veterinary use only), in the U.S., the FDA does not require submission of a 510(k), PMA, or any other pre-market review application for devices used in veterinary medicine.
−Removed: Device manufacturers who exclusively manufacture or distribute veterinary devices are not required to register their establishments and list veterinary devices and are exempt from post-marketing reporting.
−Removed: FDA does have regulatory oversight over veterinary devices and can take appropriate regulatory action if a veterinary device is misbranded or adulterated.
+Added: Device manufacturers who exclusively manufacture or distribute veterinary devices are not required to register their establishments and list veterinary devices and are exempt from some post-marketing reporting.
+Added: FDA does have regulatory oversight over veterinary devices and can take appropriate regulatory action.
It is the responsibility of the manufacturer and/or distributor of these articles to assure that these animal devices are safe, effective, and properly labeled.
15 unchanged sentences
In 2021, we expanded direct sales to include all applications in Sweden, Denmark and Norway.
−Removed: As part of this effort, the Company established
−Removed: CytoSorbents Poland Sp.
−Removed: z.o.o., a wholly-owned subsidiary of CytoSorbents Europe GmbH.
−Removed: From the beginning of the controlled market release in the fourth quarter of 2011 through December 31, 2021, we achieved cumulative sales of CytoSorb of approximately $152,356,000.
+Added: As part of this effort, the Company established CytoSorbents Poland Sp.
+Added: and in 2022 we established CytoSorbents France SAS as wholly-owned subsidiaries of CytoSorbents Europe GmbH.
+Added: From the beginning of the controlled market release in the fourth quarter of 2011 through December 31, 2022, we achieved cumulative sales of CytoSorb of approximately $181.7 million.
During this time period, the CytoSorb device represented substantially all of our product sales.
7 unchanged sentences
In addition to our direct and distributor commercial channels, we have a number of strategic partners to market and distribute CytoSorb.
−Removed: These partners include Biocon Biologics Limited, Fresenius Medical Care AG, Aferetica s.r.l.
+Added: These partners include Biocon Biologics Limited, Fresenius Medical Care AG, B.
+Added: Braun Avitum AG, Aferetica s.r.l.
and Terumo Cardiovascular Group.
−Removed: In March 2021, we added B.
−Removed: Braun Avitum AG as a global co-marketing partner.
+Added: In August 2022, we expanded our partnership with Fresenius Medical Care to a global marketing collaboration.
For detailed information regarding these partnerships, see the section entitled “Commercial and Research Partners” in item 1 of this report.
15 unchanged sentences
We rely on a combination of patents, trademarks, trade secrets and non-disclosure agreements to protect our intellectual property.
−Removed: As of February 28, 2021, our patent portfolio includes 21 issued United States patents as well as multiple issued foreign patents and pending patent applications both in the U.S.
+Added: As of March 9, 2023, our patent portfolio includes 18 issued United States patents as well as multiple issued foreign patents and pending patent applications both in the U.S.
and internationally, directed to various compositions and methods of use related to our blood purification technologies, which are expected to expire between 2023 and 2038 absent any patent term extensions.
2 unchanged sentences
Description/Indications
−Removed: Hemocompatible Coated Polymer and Related One-Step Methods
−Removed: Hemocompatible Coated Polymer and Related Methods
−Removed: Hemocompatible Coated Polymer and Related One-Step Methods
Hemocompatible Polymer Systems and Related Devices
3 unchanged sentences
Method of Treating Inflammation
−Removed: Polymer Modification
−Removed: Method of Treating Acute Radiation Syndrome
Method of Treating Inflammation
−Removed: Method of Removal of Impurities from Whole Blood
−Removed: Use of Gastrointestinally Administered Porous Sorbent Polymers
−Removed: Use of Polymeric Sorbent Polymers
Method of Treating Inflammation
Method of Treating Inflammation
+Added: Method of Treating Inflammation
+Added: Polymer Modification
+Added: Method of Removal of Impurities from Whole Blood
+Added: Use of Polymeric Sorbent Polymers
Hemocompatible Modifiers
+Added: Method of Treating Acute Radiation Syndrome
+Added: Use of Gastrointestinally Administered Porous Sorbent Polymers
Hemocompatible Porous Beads
−Removed: Method of Treating Inflammation
Removal of Endotoxemia
20 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.