−Removed: We are a leader in the treatment of life-threatening conditions in the intensive care (“ICU”) and cardiac surgery using blood purification via our proprietary polymer adsorption technology.
+Added: We are a leader in the treatment of life-threatening conditions in intensive care (“ICU”) and cardiac surgery using blood purification via our proprietary polymer adsorption technology.
We have a number of products commercialized and in development based on this technology platform.
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FDA marketing approval.
−Removed: The first clinical trial, STAR-T, is underway and currently enrolling patients.
−Removed: 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.
+Added: The first clinical trial, STAR-T, completed enrollment in July of 2023.
+Added: Final database lock in December 2023 triggered the initial data analysis on efficacy and the final Data Safety Monitoring Board (“DSMB”) safety review of the full unblinded data on all 140 patients in the STAR-T trial.
+Added: In late December 2023, we reported that the DSMB found no safety concerns with the device in the study, thereby meeting the primary safety endpoint of the trial.
+Added: Based on the initial analysis of the STAR-T data, the study did not meet the primary effectiveness endpoint in the overall patient population that underwent different types of cardiac surgeries.
+Added: However, the study did demonstrate evidence of reduced bleeding complications, including serious bleeding events, in patients in the pre-specified isolated coronary artery bypass graft (“CABG”) surgery population.
+Added: We believe that the safety and efficacy results of the STAR-T study will support regulatory submissions for marketing approval to U.S.
+Added: FDA and Health Canada.
+Added: The second clinical trial, STAR-D, has been terminated early for business reasons.
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.
9 unchanged sentences
Organ failure is the leading cause of death in the ICU, and remains a major unmet medical need, with little more than supportive care therapy (e.g., mechanical ventilation, dialysis, vasopressors, fluid support, etc.) as treatment options.
−Removed: By potentially preventing or treating organ failure, CytoSorb may improve clinical outcome, including survival, while reducing the need for costly ICU treatment, thereby potentially saving significant healthcare costs.
+Added: By potentially preventing or treating organ failure, CytoSorb may improve clinical outcomes, including survival, while reducing the need for costly ICU treatment, thereby potentially saving significant healthcare costs.
Our CE Mark enables CytoSorb to be sold throughout the European Union and member states of the European Economic Area.
−Removed: In addition, many countries outside the EU accept the CE Mark for medical devices but may also require registration with or without additional clinical studies.
+Added: In addition, many countries outside the EU accept the CE Mark for medical devices but may also require registration with or without
+Added: additional clinical studies.
The broad indication for which CytoSorb is CE marked allows it to be used “on-label” in diseases where cytokines are elevated including, but not limited to, critical illnesses such as those mentioned above, autoimmune disease flares, cancer cachexia, and many other conditions where cytokine-induced inflammation plays a detrimental role.
19 unchanged sentences
In 2017, we further expanded our direct sales efforts into Belgium and Luxembourg.
−Removed: In May 2018, the approved uses of CytoSorb in the E.U.
−Removed: were expanded to include the removal of bilirubin in liver disease, and the removal of myoglobin in trauma.
+Added: In May 2018, the approved uses of CytoSorb in the EU were expanded to include the removal of bilirubin in liver disease, and the removal of myoglobin in trauma.
On March 5, 2019, the Company announced the expansion of direct sales of CytoSorb for all applications to Poland and the Netherlands, and critical care applications to Sweden, Denmark and Norway.
11 unchanged sentences
The Breakthrough Devices Program provides for more effective treatment of life-threatening or irreversibly debilitating disease or conditions, in this case the need to reverse the effects of ticagrelor in emergent or urgent cardiac surgery that can otherwise cause a high risk of serious or life-threatening bleeding.
−Removed: Through Breakthrough Designation, the FDA intends to work with CytoSorbents to expedite the development, assessment, and regulatory review of the Company’s proprietary polymer adsorption technology for the removal of ticagrelor, while maintaining statutory standards of regulatory approval (e.g., 510(k), de novo 510(k) or premarket approval) consistent with the FDA’s mission to protect and promote public health.
+Added: Through Breakthrough Device Designation, the FDA intends to work with CytoSorbents to expedite the development, assessment, and regulatory review of the Company’s proprietary polymer adsorption technology for the removal of ticagrelor, while maintaining statutory standards of regulatory approval (e.g., 510(k), de novo 510(k) or premarket approval) consistent with the FDA’s mission to protect and promote public health.
In July 2021, the Company received full approval of its Investigational Device Exemption (“IDE”) by the FDA to conduct the pivotal STAR-T (Safe and Timely Antithrombotic Removal – Ticagrelor) double-blind, randomized control trial (“RCT”) for up to 120 patients in the United States to support FDA marketing approval of DrugSorb-ATR, which is based on the same proprietary polymer technology as CytoSorb.
+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: The study completed enrollment in July of 2023.
+Added: Final database lock in December 2023 triggered the initial data analysis on efficacy and the final DSMB safety review of the full unblinded data on all 140 patients in the STAR-T trial.
+Added: In late December 2023, we reported that the DSMB found no safety concerns with the device in the study, thereby meeting the primary safety endpoint of the trial.
+Added: Based on the initial analysis of the STAR-T data, the study did not meet the primary effectiveness endpoint in the overall patient population that underwent different types of cardiac surgeries.
+Added: However, the study did demonstrate evidence of reduced bleeding complications, including serious bleeding events, in patients in the pre-specified isolated coronary artery bypass graft (“CABG”) surgery population.
+Added: Patients undergoing CABG surgery represented more than 90% of the overall study population.
+Added: Analysis of the efficacy results is ongoing with the intent of presenting them at an international cardiovascular conference in 2024.
+Added: We believe that the safety and efficacy results of the STAR-T study will support regulatory submissions for marketing approval to U.S.
+Added: FDA and Health Canada.
In May 2020, we received CE-Mark label expansion approving the use of CytoSorb for the removal of rivaroxaban, a widely-used Factor Xa inhibitor and novel oral anticoagulant, during cardiothoracic surgery requiring cardiopulmonary bypass.
−Removed: With this announcement, and the E.U.
−Removed: approval in January 2020 to remove ticagrelor, for the same indication, CytoSorb is providing cardiac surgeons and perfusionists an easy-to-use and rapid new treatment option to help reduce the risk of serious and potentially fatal perioperative bleeding complications caused by these two drugs, in separate categories of blood thinners.
+Added: With this announcement, and the EU approval in January 2020 to remove ticagrelor, for the same indication, CytoSorb is providing cardiac surgeons and perfusionists an easy-to-use and rapid new treatment option to help reduce the risk of serious and potentially fatal perioperative bleeding complications caused by these two drugs, in separate categories of blood thinners.
In October 2020, we announced the E.U.
approval of the ECOS-300CY cartridge for the removal of inflammatory mediators during ex vivo organ perfusion under CE Mark designation, with the goal of helping to preserve or improve the health and quality of solid organs to be transplanted.
−Removed: CytoSorbents also announced a partnership with Aferetica srl to provide the ECOS-300CY cartridge under the exclusive trade name, PerSorb™, that is compatible with Aferetica’s PerLife™ ex vivo organ perfusion system, recently approved in the E.U.
+Added: CytoSorbents also announced a partnership with Aferetica srl to provide the ECOS-300CY cartridge under the exclusive trade name, PerSorb™, that is compatible with Aferetica’s PerLife™ ex vivo organ perfusion system, recently approved in the EU as well.
In 2021, commercialization of PerSorb™ and Aferetica’s PerLife™ ex vivo organ perfusion system commenced in Italy.
1 unchanged sentence
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: The new production facility successfully passed its E.U.
−Removed: notified body audit in early 2022, and received ISO 13485 certification from its E.U.
−Removed: notified body in September 2022, clearing the way for full manufacturing of CytoSorb, DrugSorb-ATR, ECOS-300CY from this site.
+Added: The new production facility successfully passed its EU notified body audit in early 2022 and received ISO 13485 certification from its EU 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.
1 unchanged sentence
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 cardiothoracic surgery.
−Removed: 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.
−Removed: This trial is currently paused until the anticipated completion of the STAR-T trial.
+Added: 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
+Added: and Timely Antithrombotic Removal – Direct Oral Anticoagulants (STAR-D),” in the United States to support FDA marketing approval.
+Added: In 2023, this study was terminated early for business reasons.
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.
−Removed: The DrugSorb-ATR Antithrombotic Removal System is based on the same polymer technology as CytoSorb.
+Added: The DrugSorb-ATR Antithrombotic Removal System is based on the equivalent polymer technology as CytoSorb.
+Added: In March 2022, the Company formed CytoSorbents Medical UK Limited to provide marketing and direct sales services in the United Kingdom and the Republic of Ireland.
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.
13 unchanged sentences
The Marketing Agreement also includes the certification of compatibility of CytoSorb for usage on Fresenius’ current critical care platforms.
−Removed: Certain initial activities have been completed with the formal of this program expected to occur sometime in 2023.
+Added: Certain initial activities have been completed with the formal launch of this program expected to occur sometime in 2024.
+Added: In October 2022, the Company formed CytoSorbents France SAS to provide marketing and direct sales services in France.
+Added: In May 2023, the Company formed CytoSorbents India Private Limited to provide marketing and direct sales services in India.
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.
18 unchanged sentences
In addition to our direct and distributor commercial channels, we have a number of strategic partners to market and/or distribute CytoSorb.
−Removed: These partners include Biocon Biologics Limited, Fresenius Medical Care AG, B.
+Added: These partners include Fresenius Medical Care AG, B.
Braun Avitum AG, Aferetica s.r.l., and Terumo Cardiovascular Group.
26 unchanged sentences
Direct Anticoagulants Removal During Cardiac Surgery
−Removed: Temporarily paused
United States
16 unchanged sentences
See the section entitled “Government Research Grants” of this Item 1 of this Report for information regarding the specific grants.
−Removed: In 2023, our goal is to successfully complete the STAR-T trial, finalize our data analysis, and file for U.S.
+Added: In 2024, our goal is to finalize our data analysis of the STAR-T trial, and file for U.S.
FDA and Health Canada regulatory approvals.
We are preparing for commercialization of DrugSorb-ATR in the U.S.
−Removed: In addition, we are seeing improvements in market conditions, and we are focused on a return to sales growth in our existing markets.
+Added: In addition, we are also seeing improvements in market conditions, and we are focused on a return to sales growth in our existing markets.
Corporate History
28 unchanged sentences
Our most recent financing transactions are discussed below.
−Removed: 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”).
−Removed: 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.
−Removed: The Company received gross proceeds of approximately $57.5 million from the Offering and after deducting the underwriting discounts and commissions and fees and expenses payable by the Company in connection with the Offering, the Company received net proceeds of approximately $53.8 million.
+Added: December 13, 2023 Offering
+Added: On December 13, 2023, the Company closed on a registered direct offering for the sale, directly to investors, of 7,733,090 registered shares of common stock and warrants to purchase up to 2,706,561 shares of common stock (the “Offering”).
+Added: Each share of common stock and accompanying warrant to purchase up to 0.35 shares of common stock, were sold together for a combined purchase price of $1.33, for an aggregate purchase price of approximately $10,285,000.
+Added: After deducting transaction fees and expenses payable by the Company in connection with the Offering, the Company received net proceeds of approximately $9,785,000, excluding any proceeds that may be received upon the exercise of the warrants.
+Added: Each warrant is immediately cash exercisable at an exercise price of $2.00 per share and will expire on the fifth anniversary of the issue date.
+Added: The Company’s executive officers, directors, and certain non-executive officer employees of the Company also participated in the Offering with a combined investment of $435,000.
Shelf Registration
3 unchanged sentences
On December 30, 2021, the Company entered into an Open Market Sale Agreement (the “Sale Agreement”) with Jefferies LLC (the “Agent”), 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 Agent, as the Company’s sales agent.
−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 2021 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.
+Added: 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
+Added: Company’s 2021 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.
Subject to the terms of the Sales Agreement, the Agent is 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).
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 years ended December 31, 2022 and 2021.
+Added: There were no sales pursuant to the Amended Sale Agreement during the year ended December 31, 2022.
+Added: During the year ended December 31, 2023, the Company sold 2,656,464 shares pursuant to the Sale Agreement, at an average selling price of $1.76 per share, generating net proceeds of approximately $4,532,000.
Research and Development
15 unchanged sentences
It is widely understood by the medical community that dialysis has inherent limitations in that its ability to remove toxic substances from blood drops precipitously as the size of toxins increases.
−Removed: Our hemocompatible adsorbent technology helps to address this shortcoming by removing toxins and toxic compounds largely untouched by dialysis technology.
+Added: Our hemocompatible adsorbent technology helps to address this shortcoming by removing toxins and toxic compounds poorly removed by dialysis technology.
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.
39 unchanged sentences
Data released by the Healthcare Cost and Utilization Project (H-CUP) identified approximately 1.6 million cases of sepsis each year in the U.S.
−Removed: According to the CDC, the incidence of serious infection and sepsis has doubled in the U.S.
+Added: to the CDC, the incidence of serious infection and sepsis has doubled in the U.S.
in the past 10 years.
22 unchanged sentences
In a post-hoc analysis, this was associated with improvements in clinical outcome in two high-risk patient populations – those with very high cytokine levels and patients 65 years of age and older.
−Removed: We have completed a follow-up dosing study at several clinical trial sites in Germany, supporting the safety of continuous treatment, exchanging a new device daily for up to 7 days.
+Added: We have completed a follow-up dosing study at several clinical trial sites in Germany, supporting the safety of continuous treatment, exchanging a new device daily for up to seven days.
The only treatment that had been approved to treat sepsis in the U.S.
or EU was Xigris from Eli Lilly.
−Removed: Because of concerns of cost, limited efficacy, and potentially dangerous side effects including the increased risk of fatal bleeding events such as intracranial bleeding for those at risk, and also because of problems with reimbursement, worldwide sales of Xigris decreased from $160M in 2009 to $104M in 2010.
+Added: Because of concerns of cost, limited efficacy, and potentially dangerous side effects including the increased risk of fatal bleeding events such as intracranial bleeding for those at risk, and also because of problems with reimbursement, worldwide sales of Xigris decreased from $160 million in 2009 to $104 million in 2010.
In October 2011, following its PROWESS SHOCK trial that demonstrated no benefit in mortality in septic shock patients, Lilly voluntarily withdrew Xigris from all markets worldwide, and is no longer available as a treatment.
6 unchanged sentences
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.
−Removed: 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.
+Added: We were 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.
+Added: In November 2023, Eris Lifesciences (“Eris”), a publicly-listed Indian
+Added: pharmaceutical company and a leading player in the domestic branded formulation market, entered into a definitive agreement to acquire Biocon Biologics’ dermatology and nephrology branded formulations business units in India, and with it, Biocon’s key leadership and field force of these businesses, including the personnel commercializing CytoSorb in India.
+Added: In connection with this proposed transfer, the Company and Eris entered into a temporary agreement for the distribution of CytoSorb products in India.
+Added: This temporary agreement has the same terms as the Company’s existing distribution agreement with Biocon except for the expiration date of the agreement, which has been updated from September 13, 2026, under the existing Biocon distribution agreement to December 31, 2025, under the temporary agreement.
+Added: Both the Company and Eris have agreed that they will use their best efforts to negotiate and finalize a new distribution agreement that will be commercially attractive to both parties.
+Added: As a result, Eris would act the Company’s exclusive distributor of CytoSorb ® products in India.
+Added: If a new distribution agreement with Eris is not executed by December 31, 2025, this temporary agreement will become null and void.
In March 2021, we announced a strategic partnership with B.
36 unchanged sentences
In the acute management of these patients, especially when they need interventional procedures such as stent placement therapy is escalated using two antiplatelet drugs (dual antiplatelet therapy - DAPT).
−Removed: Ticagrelor (Astra Zeneca - Brilinta ® , Brilique ® ) is considered best in class and is one of the most commonly used anti-platelet drugs to reduce the risk of cardiac death, heart attacks, and strokes in patients with either a history of a heart attack, or those actively undergoing percutaneous coronary intervention (PCI) with stent placement for acute coronary syndrome or heart attack.
+Added: Ticagrelor (Astra Zeneca - Brilinta ® , Brilique ® ) is considered best in class and is one of the most commonly used anti-platelet drugs to reduce the risk of cardiac death, heart
+Added: attacks, and strokes in patients with either a history of a heart attack, or those actively undergoing percutaneous coronary intervention (PCI) with stent placement for acute coronary syndrome or heart attack.
On the other hand, patients with atrial fibrillation or venous thrombosis require chronic anticoagulation.
A new category of drugs called Direct Oral Anticoagulants (DOAC) is now the new standard of care with tens of millions of patients relying on them for lifelong protection.
−Removed: The two leaders in the category, apixaban (Bristol Myers Squibb - Eliquis ® ) and rivaroxaban (Janssen and Bayer - Xarelto ® ) are estimated to reach 40 billion USD in sales by 2026.
+Added: The two leaders in the category, apixaban (Bristol Myers Squibb - Eliquis ® ) and rivaroxaban (Janssen and Bayer - Xarelto ® ) are estimated to reach $40 billion in sales by 2026.
There is a clear and large unmet medical need when patients on these antithrombotic agents need to undergo surgery due to the very high risk of bleeding.
2 unchanged sentences
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 EU for the removal of both ticagrelor and rivaroxaban during cardiothoracic surgery requiring cardiopulmonary bypass.
+Added: CytoSorb is able to 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: 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.
−Removed: 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.
−Removed: The STAR-T trial and STAR-D trial (if resumed), if successful, are each intended to independently support U.S.
−Removed: FDA marketing approval for DrugSorb-ATR for this indication., or the direct oral anticoagulants, apixaban and rivaroxaban, respectively.
−Removed: The Company expects to resume the STAR-D trial upon completion of the STAR-T trial.
−Removed: The STAR-T trial and STAR-D trial (if resumed), are each intended to independently support U.S.
−Removed: FDA marketing approval for DrugSorb-ATR for this indication.
+Added: and Canada, the Company has completed 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: As described above, the STAR-T trial met the primary safety endpoint but missed the primary efficacy endpoint in the overall population that included different types of surgeries.
+Added: However, in the pre-specified isolated coronary artery bypass graft (“CABG”) surgery population, the study demonstrated evidence of reduced bleeding complications, including serious bleeding events, in patients.
+Added: Analysis of the efficacy results is ongoing with the intent of presenting them at an international cardiovascular conference in 2024.
+Added: We believe that the safety and efficacy results of the STAR-T trial will support regulatory submissions for marketing approval by the FDA and Health Canada.
+Added: If FDA marketing approval is obtained, the device will be marketed as DrugSorb-ATR in the United States and Canada.
The initial annual addressable market in the U.S.
15 unchanged sentences
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.
−Removed: The CTC Registry completed enrollment at 100 patients, confirming 90-day survival of 74%.
−Removed: 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.
−Removed: Future, prospectively defined, larger studies are required to confirm these findings.
+Added: The CTC Registry completed enrollment at 100 patients.
+Added: As published in the peer reviewed journal, Critical Care, in June 2023, the data on these 100 patients confirmed 90-day survival of 74% and demonstrated that earlier intervention with CytoSorb and ECMO was associated with shorter need for mechanical ventilation, ECMO, and ICU stay.
+Added: These results lend support to our concept of “enhanced lung rest,” where ECMO helps the lungs rest by oxygenating blood extracorporeally and reducing the need for mechanical ventilation that can cause ventilator-induced lung injury, while CytoSorb reduces the circulating inflammatory mediators that cause continued capillary leak syndrome in the lungs.
+Added: Together, the goal of this dual-therapy strategy is to give the lungs a chance to recover and heal, a pre-requisite for weaning off of mechanical ventilation and ECMO.
+Added: For context, when ECMO was used alone, 90-day survival was 53% (as of December 2022) among more than 7,300 adult patients with refractory ARDS on ECMO in the North American cohort of the Extracorporeal Life Support Organization (ELSO) COVID-19 ECMO Registry.
+Added: We believe early intervention of enhanced lung rest with CytoSorb and ECMO represents one of the newest and most promising strategies to treat severe ARDS.
Although a number of therapies have been tried such as nitric oxide, surfactant therapy, and others, only corticosteroids, such a dexamethasone or methylprednisolone, have demonstrated mortality benefit in patients with ARDS.
4 unchanged sentences
Prone positioning, or placing a patient chest-side down, in severe ARDS patients in order to redistribute gravity-dependent pulmonary edema and allow ventilation of collapsed or atelectatic alveoli, is also used, following studies that suggest benefit including the PROSEVA trial (16% vs 32.8% in the control).
−Removed: However, even with these interventions, we believe mortality is still unacceptably high.
+Added: A combination of some or all of these approaches may yield even greater improvements in the survival of ARDS patients.
The total addressable market for CytoSorb to treat ARDS and ALI in the EU is estimated to be between $500 million to $1.25 billion, and approximately $2 billion for the U.S.
26 unchanged sentences
Renal failure in trauma is associated with a significant increase in expected mortality.
+Added: Myoglobin is poorly removed by standard dialysis or continuous renal replacement therapy.
Cytokine and myoglobin reduction by CytoSorb and related technologies may have benefit in trauma, potentially improving clinical outcome.
−Removed: In May 2018, the approved indications for use of CytoSorb in the EU were expanded to include the removal of myoglobin in trauma.
+Added: In May 2018, the approved indications for use of CytoSorb in the EU were expanded to include
+Added: the removal of myoglobin in trauma.
The total addressable market for CytoSorb for the treatment of trauma is estimated to be $1.5 billion to $2.0 billion in the U.S.
13 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 theEU were expanded to include the removal of bilirubin in liver disease.
−Removed: 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.
+Added: In May 2018, the approved indications for use of CytoSorb in the EU were expanded to include the removal of bilirubin in liver disease.
+Added: The total addressable market for CytoSorb for the treatment of acute-on-chronic liver disease, acute hepatitis, and acute liver failure is estimated to be more than $15 billion worldwide.
Severe Acute Pancreatitis
21 unchanged sentences
In March 2017, the pioneer of CAR T-cell immunotherapy, Dr.
−Removed: Carl June at University of Pennsylvania, joined our scientific advisory board.
+Added: Carl June at University of Pennsylvania,
+Added: joined our scientific advisory board.
In 2017, both Kymriah from University of Pennsylvania and Novartis, and Yescarta from Kite Pharma and Gilead Sciences, received FDA approval for the treatment of certain hematologic cancers.
12 unchanged sentences
In addition, CytoSorb treatment in a porcine animal model of brain death demonstrated a reduction in cytokines as well as a preservation of cardiac function compared to untreated controls.
−Removed: In October 2020, CytoSorbents announced the EU approval of the ECOS-300CY cartridge for the removal of inflammatory mediators during ex vivo organ perfusion, with the goal of either preserving organ function in healthy organs, or rehabilitating dysfunctional organs that would otherwise have been discarded.
−Removed: We believe the ECOS-300CY cartridge has the potential to expand the organ donor pool.
+Added: In October 2020, CytoSorbents announced the EU approval of the ECOS-300CY cartridge for the removal of inflammatory mediators during ex vivo organ perfusion (EVOP), with the goal of either preserving organ function in healthy organs or rehabilitating dysfunctional organs that would otherwise have been discarded.
+Added: We believe the ECOS-300CY cartridge has the potential to expand the organ donor pool and improve clinical outcomes For example, recent published research in porcine and human lung transplant suggests that when used during EVOP as well as intraoperatively during transplant, our technology can improve lung function prior to transplant, and can reduce the incidence of primary graft dysfunction – a major problem in lung transplant, and may have a benefit in reducing acute rejection..
According to Eurotransplant, there were approximately 6,400 transplants from deceased donors and roughly 14,000 patients on waiting list for organs in Europe last year.
24 unchanged sentences
Today, plasma and whole blood products must be carefully blood-type matched to prevent potentially fatal hemolytic transfusion reactions in the recipient, caused by the accidental administration of mismatched blood products.
−Removed: The reduction of anti-A and anti-B antibodies could potentially reduce or eliminate this risk, allowing for a broader range of available donors and simplifying the transfusion process.
+Added: The reduction of anti-A and anti-B antibodies could potentially reduce or eliminate this risk, allowing for a broader range of available donors
+Added: and simplifying the transfusion process.
According to the American Red Cross, nearly 10,000 units of plasma are needed daily in the United States, or more than 3.5 million units a year.
37 unchanged sentences
In 2011, we completed our European Sepsis Trial of our CytoSorb device.
−Removed: The study was a randomized, open label, controlled clinical study in 14 sites in Germany of 100 critically ill patients with predominantly septic shock and respiratory failure.
+Added: The study was a randomized, open label,
+Added: controlled clinical study in 14 sites in Germany of 100 critically ill patients with predominantly septic shock and respiratory failure.
The trial successfully demonstrated the ability of CytoSorb to reduce levels of key cytokines from whole blood in treated patients, and that treatment was safe in these critically-ill patients with multiple organ failure.
78 unchanged sentences
Prolonged illness, malnutrition, age, multiple interventional procedures, and exposure to antibiotic resistant pathogens are just some of the many risk factors for functional immune suppression and infection.
−Removed: In sepsis and SIRS, the overexpression of pro-inflammatory cytokines can also cause a depletion of immune effector cells through apoptosis and other means, and anti-inflammatory cytokines can cause profound immune suppression, both major risk factors for infection.
+Added: In sepsis and SIRS, the overexpression of pro-
+Added: inflammatory cytokines can also cause a depletion of immune effector cells through apoptosis and other means, and anti-inflammatory cytokines can cause profound immune suppression, both major risk factors for infection.
Projected Timeline:
25 unchanged sentences
The use of CytoSorb in the post-operative period to treat postoperative SIRS is another application of the technology.
−Removed: In 2020, CytoSorb was approved to remove the anti-platelet agent, ticagrelor, during cardiac surgery involving cardiopulmonary bypass via label expansion of its CE Mark.
+Added: In 2020, CytoSorb was EU approved to remove the anti-platelet agent, ticagrelor, during cardiac surgery involving cardiopulmonary bypass via label expansion of its CE Mark.
Ticagrelor (Brilinta®, Astra Zeneca) is a widely used anti-platelet agent used to decrease cardiovascular risk and risk of stroke in patients with a known history of heart disease or heart attack.
4 unchanged sentences
Georg in Hamburg, Germany on the investigational use of CytoSorb to reverse the effects of ticagrelor during emergency cardiac surgery demonstrated a greatly reduced risk of bleeding complications and the need for repeat surgery to explore the source of bleeding, with extrapolations showing projected cost savings of £3,982, or approximately $5,000 USD, per patient in a U.K.
−Removed: CytoSorb was also approved for the removal of rivaroxaban, a widely used Factor Xa inhibitor and novel oral anticoagulant, during cardiothoracic surgery requiring cardiopulmonary bypass via label expansion of its CE Mark.
−Removed: This new category of drugs called Direct Oral Anticoagulants (DOAC) is now the new standard of care with tens of millions of patients relying on them for chronic, often lifelong protection.
+Added: CytoSorb was also EU approved for the removal of rivaroxaban, a widely used Factor Xa inhibitor and novel oral anticoagulant, during cardiothoracic surgery requiring cardiopulmonary bypass via label expansion of its CE Mark.
+Added: This new category of drugs called Direct Oral Anticoagulants (DOAC) is now the new standard of care with tens of millions of patients relying on them for chronic, often
+Added: lifelong protection.
The two leaders in the category are apixaban (Bristol Myers Squibb - Eliquis ® ) and rivaroxaban (Janssen and Bayer - Xarelto ® ).
1 unchanged sentence
Cardiac surgeons, cardiac perfusionists, and cardiothoracic ICU intensivists in Germany, Austria, and other countries have now used CytoSorb intra-operatively and post-operatively in more than 70,000 treatments in cardiac surgery patients.
−Removed: 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.
+Added: This application is also the focus of number of completed, planned and enrolling company-sponsored and investigator-initiated studies of DrugSorb-ATR in the United States and CytoSorb in Europe.
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 U.S.
+Added: In October 2021, the first patient was enrolled and the STAR-T study was actively recruiting at multiple U.S.
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.
1 unchanged sentence
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.
−Removed: Enrollment is expected to be complete during summer of 2023.
+Added: The study completed enrollment in July of 2023.
+Added: As described above, the STAR-T trial met the primary safety endpoint but missed the primary efficacy endpoint in the overall population that included different types of surgeries.
+Added: However, in the pre-specified isolated coronary artery bypass graft (“CABG”) surgery population, the study demonstrated evidence of reduced bleeding complications, including serious bleeding events, in patients.
+Added: Analysis of the efficacy results is ongoing with the intent of presenting them at an international cardiovascular conference in 2024.
+Added: We believe that the safety and efficacy results of the STAR-T study will support regulatory submissions for marketing approval by the FDA and Health Canada.
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.
1 unchanged sentence
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: 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: The study was terminated in 2023 for business reasons.
For further detailed information regarding our clinical trial strategy, see the section entitled “Clinical Studies” of this Item 1 of this Report.
33 unchanged sentences
Critical illness in animals is similar to that in humans.
−Removed: Based upon cumulative studies, VetResQ is capable of reducing a broad range of excessive inflammatory mediators and toxins that could otherwise cause direct tissue injury or serious systemic inflammation that can rapidly lead to instability, organ failure, and death.
+Added: Based upon cumulative studies, VetResQ is capable of reducing a broad range of excessive hydrophobic drugs, inflammatory mediators and toxins that could otherwise cause direct tissue injury or serious systemic inflammation that can rapidly lead to instability, organ failure, and death.
VetResQ is available in the U.S.
13 unchanged sentences
It is expected to follow a similar path to E.U.
−Removed: approval as CytoSorb, expected within 4 to 5 years.
+Added: approval as CytoSorb, expected within four to five years.
The HemoDefend Blood Purification Technology Platform (Acute and Critical Care)
2 unchanged sentences
The HemoDefend RBC blood purification technology platform is designed to reduce contaminants in the blood supply that can cause transfusion reactions or disease.
−Removed: It is a development stage technology that is not yet approved in any markets, but is comprised of our highly advanced, biocompatible, polymer bead technology.
+Added: It is a development stage technology that is not yet approved in any markets,
+Added: but is comprised of our highly advanced, biocompatible, polymer bead technology.
If this technology is successfully developed and then incorporated into a regulatory approved product, it could have a number of important benefits, including:
34 unchanged sentences
Special Operations Command (USSOCOM)), and more recently under a $3 million 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 the next 12 - 18 months.
+Added: We seek to out-license this technology platform to a potential strategic partner.
Removal of anti-A and anti-B blood group antibodies from fresh whole blood and plasma
1 unchanged sentence
The HemoDefend-BGA blood purification technology platform is designed to reduce anti-A and anti-B antibodies in plasma and whole blood.
−Removed: The goal is to either enable the production of universal plasma or enable fresh warm whole blood transfusions.
+Added: The goal is to either enable the production of universal plasma or enable fresh warm whole blood
+Added: transfusions.
If this technology is successfully developed and then incorporated into a regulatory approved product, it could have a number of important benefits, including:
13 unchanged sentences
Prototype filtration devices have been evaluated by a government agency, resulting in excellent depletion of both anti-A and anti-B antibodies.
−Removed: Work is continuing to advance these prototypes to clinical study-ready devices.
+Added: Work is continuing to advance these prototypes to clinical study-ready devices and have had preliminary discussions with the U.S.
+Added: FDA on the regulatory path forward.
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.
20 unchanged sentences
It has also been recognized as a serious complication of combat injury since World War II, when hyperkalemia and acute kidney injury was associated with a mortality rate of 90%, and was a leading cause of post-traumatic death in the Korean War, until the advent of dialysis therapy.
−Removed: In the wars in Iraq and Afghanistan, an estimated 5.8% of all combat casualties developed hyperkalemia within 48 hours of injury.
+Added: In the wars in Iraq and Afghanistan, an estimated 5.8% of all combat casualties developed hyperkalemia within 48
+Added: hours of injury.
Even in non-crush traumatic injury, severe hyperkalemia (>6 mmol/L) occurred in approximately 20% of patients.
4 unchanged sentences
Air Force Materiel Command.
−Removed: We are currently discussing the potential clinical development plan of K + ontrol with the FDA.
+Added: We seek to outlicense this technology platform to a potential strategic partner.
ContrastSorb (Radiology and Interventional Radiology)
20 unchanged sentences
Assuming successful optimization of the ContrastSorb polymer, safety and efficacy of IV contrast removal will need to be established in human clinical studies.
−Removed: We seek to out-license this technology to a potential strategic partner.
+Added: We seek to out-license this technology platform to a potential strategic partner.
The BetaSorb Device (Chronic Care)
28 unchanged sentences
Biocon Biologics Limited
−Removed: In September 2013, we entered into a distribution agreement with Biocon Biologics Limited, (“Biocon”), India’s largest biopharmaceuticals company, under which Biocon was granted exclusive commercialization rights to the CytoSorb therapy in India and select emerging markets, initially focused on sepsis.
−Removed: Biocon committed to annual minimum purchases to maintain exclusivity.
−Removed: In October 2014, the Biocon partnership was expanded to include all critical care applications and cardiac surgery.
−Removed: In addition, Biocon committed to higher annual minimum purchases of CytoSorb to maintain distribution exclusivity and committed to conduct and publish results from multiple investigator-initiated studies and patient case studies.
−Removed: Under the terms of the expanded partnership, the term of the distribution agreement was extended to December 2022.
−Removed: We are currently negotiating an additional extension to this agreement.
−Removed: 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.
+Added: On November 8, 2023, Biocon Biologics (“Biocon”) announced that it entered into a definitive agreement with Eris Lifesciences (“Eris”) for the divestiture of its Dermatology and Nephrology branded formulations business units in India.
+Added: This transaction closed in November 2023.
+Added: In connection with this proposed transfer, the Company and Eris have entered into a temporary agreement for the distribution of CytoSorb ® products in India.
+Added: This temporary agreement has the same terms as the Company’s existing distribution agreement with Biocon except for the expiration date of the agreement, which has been updated from September 13, 2026, under the existing Biocon distribution agreement to December 31, 2025, under the temporary agreement.
+Added: Both the Company and Eris have agreed that they will use their best efforts to negotiate and finalize a new distribution agreement that will be commercially attractive to both parties.
+Added: As a result, Eris would act the Company’s exclusive distributor of CytoSorb ® products in India.
+Added: If a new distribution agreement with Eris is not executed by December 31, 2025, this temporary agreement will become null and void.
Fresenius Medical Care AG
11 unchanged sentences
Fresenius further provides written endorsements of CytoSorb for use with their multiFiltrate and multiFiltratePRO acute care dialysis machines that can be used by us and our distribution partners to promote CytoSorb worldwide.
−Removed: Training and preparation for this co-marketing program began in five initial countries in 2017 and is continuing, with implementation of the co-marketing program in additional countries planned for the future.
In December 2018, the Fresenius agreement signed in December 2014 was amended, to grant Fresenius exclusive distribution rights for the Czech Republic and Finland and all critical care medicine and ICU applications on dialysis or ECMO machines for France.
15 unchanged sentences
The Marketing Agreement also includes the certification of compatibility of CytoSorb for usage on Fresenius’ current critical care platforms.
−Removed: Certain initial activities have been completed with the formal launch of this program expected to occur sometime in 2023.
+Added: Certain initial activities have been completed with the formal launch of this program expected to occur in 2024.
Aferetica s.r.l.
38 unchanged sentences
Nikkiso Europe GmbH
−Removed: 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.
−Removed: 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:
−Removed: Belgium, Bosnia and Herzegovina, Croatia, Finland, France, Iceland, Lichtenstein, Poland, Serbia, Slovenia and Switzerland.
−Removed: The Company will also be able to provide field support services in these countries.
+Added: The Nikkiso agreement to distribute its PureAdjust ® hemoperfusion pump in selected countries expired in September 2023.
+Added: The Company is actively working with a new supplier to provide a stand-alone hemoperfusion pump.
University of Pittsburgh Medical Center
5 unchanged sentences
The observational and dosing phases of the study, involving 30 viable donors and eight non-viable donors, respectively, have been completed.
−Removed: The next phase of this study, the treatment phase, was planned to involve viable donors.
+Added: The next phase of this
+Added: study, the treatment phase, was planned to involve viable donors.
However, we are not currently focusing our efforts on the commercialization of CytoSorb for application in organ donors.
24 unchanged sentences
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.
−Removed: 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.
+Added: For the years ended December 31, 2023 and 2022, the Company did not record any expense related to this agreement as the launch of this program is expected to occur in 2024.
License Agreement
4 unchanged sentences
Under the terms of the Settlement Agreement, we have agreed to pay Purolite royalties of 2.5% to 5% on the sale of those of our products, if and when those products are sold commercially, that are used in direct contact with blood or, in certain cases, in direct contact with a physiological fluid other than blood.
−Removed: The royalty payments provided for under the Settlement Agreement would apply to our currently envisioned CytoSorb, VetResQ, and BetaSorb products.
+Added: The royalty payments provided for under the Settlement Agreement would apply to
+Added: our currently envisioned CytoSorb, VetResQ, and BetaSorb products.
For the year ended December 31, 2023 per the terms of the license agreement we have recorded royalty costs of approximately $1,233,000.
−Removed: Following the expiration of the 18-year term of the Settlement Agreement, the patents and patent applications that are the subject of the Settlement Agreement should have expired under current patent laws, and the technology claimed in them will be available to the public.
−Removed: However, we have additional issued patents separate from those in this Settlement Agreement, and patents pending worldwide that may extend patent protection of our core technology.
−Removed: We will also continue to exclusively own any confidential and proprietary know how.
Product Payment & Reimbursement
−Removed: Effective January 1, 2017, we achieved a dedicated reimbursement code in Germany that provides for specific and enhanced reimbursement for our CytoSorb device.
−Removed: We believe in most cases that this dedicated reimbursement code provides our customers in Germany with reimbursement that not only covers the cost of the device, but the procedural costs as well.
−Removed: Reimbursement can also be covered by the standard “diagnosis related group” (“DRG”) acute care reimbursement.
−Removed: Under this system, hospitals would purchase CytoSorb and subtract the cost from a pre-determined lump-sum payment made by the payor to the hospital based on the patient’s diagnosis.
−Removed: In 2019, CytoSorb was assigned a procedure code from the Swiss Federal Statistical Office, a division of the Federal Department of Home Affairs in Switzerland under the category “Adsorption of Cytokines and Interleukin”.
−Removed: During 2020, this code category was replaced by a new category entitled “Extracorporeal Adsorption of Specific Substances”.
−Removed: Use of this code gives Swiss hospitals the ability to collect cost data related to CytoSorb treatments.
−Removed: In 2021, SwissDRG performed the first cost analysis of CytoSorb.
+Added: Effective January 1, 2024, the coding (“OPS”) for plasmapheresis, adsorption (previously:
+Added: immunoadsorption) and related treatments has been extensively restructured to enable a more precise and rational classification.
+Added: Therefore, the coding for hemoadsorption therapy (including CytoSorb device) has been updated to the new procedure code “8-821.30 hemoperfusion [whole blood adsorption]:
+Added: selective, removal of hydrophobic substances (low and/or middle-sized molecules)”.
+Added: This coding keeps on triggering the previous supplementary reimbursement that each hospital negotiates on an annual basis with the health insurers (valid in 2024:
+Added: “ZE2023-09” as this code is being updated annually).
+Added: A dedicated coding as well as reimbursement for hemoadsorption was effective since January 1, 2017 (procedure code “8-821.2 adsorption of hydrophobic, small and middle-sized molecular substances”).
+Added: According to the hospital’s budget negotiations, the reimbursement rate not only covers the cost of the device, but the procedural costs as well.
+Added: Since 2020, the most specific procedure code (“CHOP”) for any treatment with CytoSorb has been installed:
+Added: “99.76.31 Adsorption of hydrophobic, small and middle-sized molecular substances”.
+Added: Before, in 2018 CytoSorb had to be coded via the pre-existing CHOP code 99.76.99 “Extracorporeal immunoadsorption, other” and in 2019 CytoSorb was assigned the first dedicated procedure code from the Swiss Federal Statistical Office, a division of the Federal Department of Home Affairs in Switzerland under the category “99.76.12 Adsorption of Cytokines and Interleukin”.
+Added: Use of these specific codes since 2019 gave Swiss hospitals the ability to collect cost data related to CytoSorb treatments.
+Added: In 2021, SwissDRG performed the first cost analysis of all procedures coded with 99.76.31.
This analysis showed that there were no additional treatment costs associated with use of CytoSorb against the relevant DRGs, suggesting CytoSorb may be cost neutral or even cost-saving across all indications.
−Removed: The Company is working with these Swiss hospitals to publish the analysis.
Europe (excluding Germany and Switzerland)
5 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).
+Added: In 2020, NICE published a Report on “Cytokine adsorption devices for treating respiratory failure in people with COVID-19”.
+Added: The report showed that cytokine adsorption devices reduce levels of cytokines in the blood in people with COVID-19.
+Added: This may help improve lung function.
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”.
5 unchanged sentences
Across all countries, we are mitigating financial barriers though use of health economics, local data generation and targeted KOL management.
+Added: Effective in 2018, in all hospitals in Moscow and St Petersburg the CytoSorb therapy is being fully reimbursed (polymer-based system for cytokine adsorption/extracorporeal haemocorrection, pos.
+Added: In hospitals in Ekaterinburg the therapy costs are being covered by 50%.
+Added: Since commercialization of CytoSorb in Turkey it could be coded under the apheresis code “sepsis column” with a reimbursement rate of approximately 5,400 TL (≈ 800 €).
+Added: However, this code was only applicable to septic patients in the ICU, and three signatures were needed to obtain reimbursement (hematologist, anesthesiologist and infection control doctor).
+Added: In 2022, the Turkish Ministry of Health has approved national reimbursement for CytoSorb® in the public sector, 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.
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.
−Removed: 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
11 unchanged sentences
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: 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: In addition, in June 2023, CMS has announced a new initiative called “Transitional Coverage for Emerging Technologies” (TCET) as a potential replacement for MCIT, that would provide coverage to FDA Breakthrough Devices for 3 to 5 years.
+Added: There has been significant industry feedback to CMS on the new program, which has not been finalized.
If passed, either of these programs may be applicable to DrugSorb-ATR, if it can achieve U.S.
2 unchanged sentences
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.
−Removed: We believe these products represent a unique approach to disease states and health complications associated with the presence of larger toxins (often referred to as middle molecular weight toxins) and poorly dialyzable drugs in the bloodstream, including sepsis, acute respiratory distress syndrome, trauma, severe burn injury, pancreatitis, post-operative complications of cardiac surgery, damage to organs donated for transplant prior to organ harvest, renal disease and drug intoxication.
+Added: We believe these products represent a unique approach to disease states and health complications associated with the presence of larger toxins (often referred to as middle molecular weight toxins) and poorly dialyzable drugs in the bloodstream, including sepsis, acute respiratory distress syndrome, trauma, severe burn injury, pancreatitis, post-operative complications of cardiac surgery, damage to organs donated for
+Added: transplant prior to organ harvest, renal disease and drug intoxication.
For example, researchers have explored the potential of using standard membrane-based dialysis technology to treat patients suffering from sepsis.
31 unchanged sentences
In 2019, the results of the study were published in JAMA, demonstrating no benefit in 28-day all-cause mortality.
−Removed: The 800 patient Phase III SCARLET-2 randomized, controlled trial, evaluating Recomodulin in patients with sepsis and coagulopathy, was scheduled to begin in July 2019, but was withdrawn to be amended following the results of the SCARLET trial.
−Removed: The status of the trial is unknown.
+Added: The 800 patient Phase III SCARLET-2 randomized, controlled trial, evaluating Recomodulin in patients with sepsis and coagulopathy, was scheduled to begin in July 2019, but was withdrawn to be amended following the results of the SCARLET trial and now has been terminated.
Atox Bio, a development stage company in clinical studies with peptide therapeutics that are designed to prevent superactivation of the immune response by certain toxins such as toxic shock syndrome toxin.
19 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 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.
+Added: As of February 28, 2024, 93 patients of the targeted 150 patients have been enrolled, with an expansion of trial sites to a total of 25, with 21 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, Phase II multi-center trial in patients with pneumonia-associated sepsis.
−Removed: It is expected to enroll 120-160 patients across 4 cohorts of varying doses of Allocetra or placebo.
+Added: In November 2021, Enlivex reported that Allocetra is being evaluated in a blinded, randomized, controlled, Phase II multi-center trial in patients with moderate to severe sepsis related to pneumonia, biliary, urinary tract, or peritoneal infections.
+Added: As of February 21, 2024, it enrolled all 120 patients 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.
−Removed: As of February 2023, enrollment has not been disclosed.
+Added: Topline data is expected by the end of March 2024.
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.
14 unchanged sentences
Spectral is now pursuing an amendment to the EUPHRATES trial, called TIGRIS.
−Removed: There have been now several large scale studies failing to demonstrate a benefit of Toraymyxin on 28-day mortality in sepsis.
+Added: There have been now several large
+Added: scale studies failing to demonstrate a benefit of Toraymyxin on 28-day mortality in sepsis.
Toraymyxin represents a competitive, although potentially complementary, therapeutic approach to CytoSorb.
5 unchanged sentences
In October 2020, results from 4 hospitals on 37 patients from its OxirisNet Registry in the journal, Critical Care.
−Removed: 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-molecular weight cutoff or high retention onset (HRO) hemodialysis membrane outside the U.S.
+Added: Mortality was 66.6% in patients receiving oXiris treatment after 14 days from admission, and a mortality of 47.4% when used earlier.
+Added: In addition, Baxter also launched the Theranova mid-molecular weight cutoff or high retention onset (HRO) hemodialysis membrane internationally, including in the U.S.
to improve the efficiency of hemodialysis, claiming improved mid-molecular weight substance removal.
22 unchanged sentences
To our knowledge, none of the following technologies are approved in the U.S.
−Removed: and none are approved for cytokine reduction or as a therapy to treat sepsis in the EU.
+Added: and no large scale pivotal randomized controlled trials are being conducted in sepsis.
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.
1 unchanged sentence
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 status of the trial has not been updated since February 2019.
−Removed: 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.
+Added: The status of the trial has not been updated since February 2019 on clinicaltrials.gov.
+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, with no update on clinicaltrials.gov since November 2021.
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.
5 unchanged sentences
It received EU CE-Mark approval in July 2019, and established distribution in Germany, Italy and Benelux.
−Removed: In 2020, Seraph received FDA Emergency Use Authorization for use in adult critically ill COVID-19 patients to reduce pathogens and inflammatory mediators from the bloodstream.
+Added: In 2020, Seraph received FDA Emergency Use Authorization for use in adult critically ill COVID-19 patients to reduce pathogens and inflammatory mediators
+Added: from the bloodstream.
In 2021 and 2022, Exthera expanded distribution to market Seraph in select European countries and Mexico with Fresenius to remove certain bacterial and viral pathogens during dialysis.
96 unchanged sentences
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: We anticipate resuming the STAR-D (Safe and Timely Antithrombotic Removal of DOACs) trial upon completion of the STAR-T trial.
+Added: Due to business reasons, we have terminated the STAR-D (Safe and Timely Antithrombotic Removal of DOACs) trial but may revisit this study in the future.
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.
16 unchanged sentences
However, in October 2022, PhaseBio filed for Chapter 11 bankruptcy.
−Removed: The bentracimab asset was transferred to PhaseBio’s creditor, SFJ Pharmaceuticals in December 2022, that expects to file the BLA in mid-2023.
+Added: The bentracimab asset was transferred to PhaseBio’s creditor, SFJ Pharmaceuticals in December 2022.
+Added: Serb Pharma acquired exclusive US rights for bentracimab from SFJ Pharmaceuticals in May 2023, and expected to file the BLA by end of 2023.
+Added: There have been no public updates on the status of this submission.
Meanwhile, Andexxa is a Factor Xa analog that competes for binding to Factor Xa inhibitors.
9 unchanged sentences
The HemoDefend platform represents a potentially superior alternative to these methods, as it can provide comprehensive removal of a wide variety of contaminants that can trigger transfusion reactions without washing blood, requires no additional equipment, energy source, or manipulation, and can be incorporated directly into the blood storage bag or used as an in-line blood filter.
+Added: In terms of HemoDefend - BGA, to our knowledge there are no commercially ready or available solutions to produce universal plasma in the U.S.
Clinical Studies
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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.
−Removed: 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.
+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 published in the peer reviewed journal Critical Care.
+Added: The data further demonstrate that earlier intervention with CytoSorb and ECMO was associated with shorter need for mechanical ventilation, ECMO, and ICU stay.
+Added: These results lend support to our concept of “enhanced lung rest,” where ECMO helps the lungs rest by oxygenating blood extracorporeally and reducing the need for mechanical ventilation that can cause ventilator-induced lung injury, while CytoSorb reduces the circulating inflammatory mediators that cause continued capillary leak syndrome in the lungs.
+Added: Together, the goal of this dual-therapy strategy is to give the lungs a chance to recover and heal, a pre-requisite for weaning off of mechanical ventilation and ECMO.
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 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.
+Added: The speed of enrollment remains uncertain due to COVID-19 related institutional research staff shortages, however we anticipate conditions to gradually improve that together with a recently completed protocol amendment should help recruitment going forward.
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 actively enrolling in Spain and Germany with plans to expand in more countries in 2023.
+Added: The Registry is actively enrolling in Spain, Germany and Italy with plans to expand in more countries in 2024.
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.
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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 recruiting in the U.K., Germany, Austria and Sweden and is planned to expand to additional countries in 2023.
+Added: The Registry is actively recruiting in the U.K., Germany, Austria, Belgium and Sweden and is planned to expand to additional countries in 2024.
+Added: Data outputs from the STAR Registry have already been reported at the EuroPCR 2023 conference in Paris in May 2023 and at the European Association of Cardiothoracic Surgery conference in Vienna in October 2023.
+Added: The Registry will continue to report analyses at international conferences in 2024 and submit the results for publication on a rolling basis as enrollment progresses.
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.
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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.
−Removed: 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.
−Removed: The study is expected to reach 100% enrollment sometime in the summer of 2023.
−Removed: 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.
−Removed: Should we choose to forego the interim analysis, we would be required to notify the FDA.
+Added: In early 2023, the study exceeded 50% enrollment
+Added: and reached the 2 nd milestone of 67% enrollment in the spring of 2023, triggering another DSMB safety review, which found no safety concerns and recommended completion of the trial.
+Added: The study completed enrollment in July of 2023 triggering the final DSMB safety review following database lock in December 2023, which reported no safety concerns thereby meeting the primary safety endpoint of the study.
+Added: Based on the initial analysis of the STAR-T data, the study did not meet the primary effectiveness endpoint in the overall patient population that underwent different types of cardiac surgeries.
+Added: However, the study did demonstrate evidence of reduced bleeding complications, including serious bleeding events, in patients in the pre-specified isolated coronary artery bypass graft (“CABG”) surgery population.
+Added: Patients undergoing CABG surgery represented more than 90% of the overall study population.
+Added: Analysis of the efficacy results is ongoing with the intent of presenting them at an international cardiovascular conference in 2024.
+Added: We believe that the safety and efficacy results of the STAR-T study will support regulatory submissions for marketing approval by the FDA and Health Canada.
+Added: March 13, 2024, we were notified that the 140-patient, double-blinded, multicenter, pivotal STAR-T randomized, controlled trial was selected for a Breakout Presentation at the American Association of Thoracic Surgery (AATS) Annual Meeting being held April 27-30, 2024 in Toronto, Canada.
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: Study enrollment was paused in November of 2022 for business reasons and is scheduled to resume after completion of the STAR-T trial.
+Added: The study has been terminated early for business reasons.
COVID-19 Business Update
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Under the EUA, CytoSorbents can make CytoSorb available, through commercial sales, to all hospitals in the U.S.
−Removed: for use in patients, 18 years of age or older, with confirmed COVID-19 infection who are admitted to the intensive care unit with confirmed or imminent respiratory failure and who have early acute lung injury or ARDS, severe disease, or life-threatening illness resulting in respiratory failure, septic shock, and/or multiple organ dysfunction or failure.
−Removed: The CytoSorb device has been authorized by FDA under an EUA.
+Added: for use in patients, 18 years of age or older, with confirmed COVID-19 infection who are admitted to the intensive care unit with confirmed or imminent respiratory failure.
It has neither been cleared nor approved for the indication to treat patients with COVID-19 infection.
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In December 2021, we announced the publication of these results in the peer-reviewed journal Frontiers in Medicine .
−Removed: 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.
+Added: The CTC Registry has completed enrollment at 100 patients and the final results confirming high survival (74%) were presented at the European Society of Intensive Care Medicine conference in October 2022.
+Added: As published in the peer reviewed journal, Critical Care, in June 2023, the data on these 100 patients further demonstrated that earlier intervention with CytoSorb and ECMO was associated with shorter need for mechanical ventilation, ECMO, and ICU stay.
+Added: These results lend support to our concept of “enhanced lung rest,” where ECMO helps the lungs rest by oxygenating blood extracorporeally and reducing the need for mechanical ventilation that can cause ventilator-induced lung injury, while CytoSorb reduces the circulating inflammatory mediators that cause continued capillary leak syndrome in the lungs.
+Added: Together, the goal of this dual-therapy strategy is to give the lungs a chance to recover and heal, a pre-requisite for weaning off of mechanical ventilation and ECMO.
+Added: For context, when ECMO was used alone, 90-day survival was 53% (as of December 2022) among more than 7,300 adult patients with refractory ARDS on ECMO in the North American cohort of the Extracorporeal Life Support Organization (ELSO) COVID-19 ECMO Registry.
Government Research Grants
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The contract, entitled “pRBCs Contaminant Removal with Hemocompatible Porous Polymer Beads” (award number 2R44HL141928-03), provides for maximum funding of approximately $2,971,000 over a three-year period.
−Removed: As of December 31, 2022, we received approximately $2,386,000 in funding under this contract and have approximately $585,000 remaining under this contract.
−Removed: Under the terms of this contract, we must make a matching contribution equal to the funds awarded thereunder.
+Added: As of December 31, 2023, we received approximately $2,570,000 in funding under this contract and no further funding will be received under this contract.
In September 2019, the Company was awarded a Rapid Innovation Fund contract by the USAF/AFMC to develop a simple, easy-to-use renal support system to treat severe hyperkalemia.
The contract, entitled “K+ontrol Renal Support System for Reduction of Hyperkalemia” (award number FA8650-19-C-6065), provides for maximum funding of approximately $2,960,000 over a two-year period.
−Removed: As of December 31, 2022, we received approximately $2,396,000 funding under this contract and have approximately $564,000 remaining under this contract.
+Added: As of December 31, 2023, we received approximately $2,851,000 in funding under this contract and no further funding will be received under this contract.
In June 2020, the Company was awarded a two-year Defense Health Agency Small Business Technology transfer (STTR) Phase III contract to advance its HemoDefend-BGA plasma and whole blood adsorber to human clinical trials.
(award number W81XWH20C0050 ), provides for maximum funding of approximately $2,897,000 over a two-year period.
−Removed: As of December 31, 2022, we received approximately $2,472,000 funding under this contract and have approximately $425,000 remaining under this contract.
+Added: As of December 31, 2023, we received approximately $2,897,000 funding under this contract and no further funding remaining under this contract.
In July 2020, the Company was a three-year contract awarded by the Assistant Secretary of Defense for Health Affairs, endorsed by the Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP), as part of a Peer Reviewed Medical Research Program Technology/ Therapeutic Development Award to complete preclinical development of the HemoDefend™-BGA plasma and whole blood adsorber (award number W81XWH2010712).
25 unchanged sentences
This eight-month award, which is valued at $288,335, 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.
−Removed: As of December 31, 2022, we have received $29,000 funding under the contract and have approximately $253,000 remaining under the contract.
+Added: As of December 31, 2023, we have received $288,335 in funding under the contract and no further funding remaining under the contract.
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.
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.
−Removed: As of December 31, 2022, we have received $18,000 funding under the contract and have approximately $57,000 remaining under the contract.
+Added: As of December 31, 2023, we have received $74,955 of funding under the contract and no further funding remains under the contract.
+Added: On June 1, 2023, the Company was granted a Phase I Small Business Innovation Research (SBIR) award by AFWERX Joint Injury, 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 $74,918, 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 related to Joint Injuries.
+Added: As of December 31, 2023, we have received $74,918 of funding under the contract and no further funding remains under the contract.
Our business could be adversely impacted by automatic cuts in Federal spending.
11 unchanged sentences
The CE Mark certification, granted following approval from an independent notified body, is an EU-wide international symbol evidencing adherence to quality assurance standards and compliance with the MDD or other applicable European Medical Devices Directives.
−Removed: Distributors of medical devices may also be required to comply with other foreign regulations, such as Ministry of Health Labor and Welfare approval in Japan.
+Added: Distributors of medical devices may also be required to comply with other foreign regulations.
The time required to obtain these foreign approvals to market our products may be longer or shorter than that required in the U.S., and requirements for those approvals may differ from those required by the FDA.
−Removed: In Europe, our devices are classified as Class IIb, and conform to the MDD.
+Added: In Europe, our devices are classified as Class IIb, and currently conform to the MDD.
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”).
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.
−Removed: 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.
+Added: In March 2023, the EU Parliament and Council extended the MDR transition period for CytoSorbents’ CytoSorb device (Class IIb) to December 2028 and it will stay CE Marked under MDD until the end of transition period (subject to Notified Body surveillance) or until the full transition to MDR certification before the end of the transition period.
+Added: 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 for multiple indications for use.
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.
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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.
+Added: This certification is currently maintained.
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.
−Removed: Specifically, claims that are made are required to be included in our Clinical Evaluation Report, which is part of the conformity assessment process conducted by the Notified Body.
−Removed: If our claims exceed the assessed claims, either regarding performance or intended uses, we may be subject to regulatory actions, which could include customer notifications or even product or literature (i.e.
−Removed: labeling) recalls.
+Added: Specifically, claims that are made are required to be in applicable CE Certificate and based on our Clinical Evaluation Report, which is part of the conformity assessment process conducted by the Notified Body.
+Added: If our claims exceed the assessed claims, either regarding performance or intended uses, we may be subject to regulatory actions, which could include customer notifications or even product recalls.
+Added: We are currently tracking a proposal for healthcare reform of Germany’s hospital system.
+Added: In July 2023, Germany’s federal and state governments issued a consensus white paper that could result in new laws that change how hospitals are funded.
+Added: Government payments to hospitals would de-emphasize the DRG (diagnosis-related group) “lump sum” payment system that incentivizes revenue generation through more patients treated and procedures performed, and instead emphasize base payments focused on quality measures and appropriate patient care.
+Added: This is expected to favor a shift of routine operations and procedures to outpatient centers, consolidation of smaller hospitals into larger ones, and importantly, an increased focus of remaining hospitals on sicker patients, more complex operations such as cardiothoracic surgery and organ transplant, and on therapies that help reduce the severity of illness and help patients recover faster.
+Added: Given that the goal of our therapies is to improve clinical outcomes while reducing the costs of critical care and cardiac surgery by controlling deadly inflammation and other life-threatening conditions, while reducing the need for expensive life support measures that keep patients in the hospital, we believe such reform may favor our business in the longer-term.
+Added: Hospital administrators expect such change will take careful planning and time, potentially years, to implement.
+Added: However, given there is no formal law enacted to our knowledge, the overall impact to our business cannot yet be determined.
In the U.S., specific permission from FDA to distribute a new device is usually required (that is, other than in the case of very low risk devices), and we expect that some form of marketing authorization will be necessary for our devices.
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Also, during the review period, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA.
−Removed: In addition, the FDA will conduct a pre-approval inspection of the manufacturing facilities to evaluate compliance with the FDA’s Quality System Regulation (“OSR”), which requires manufacturers to implement and follow design, testing, control, documentation and other quality assurance and good manufacturing practice procedures.
−Removed: Following review of a PMA, the FDA will authorize commercial distribution if it determines there is reasonable assurance that the medical device is safe and effective for its intended purpose.
+Added: In addition, the FDA will conduct a pre-approval inspection of the manufacturing facilities to evaluate compliance with the FDA’s Quality System Regulation (“QSR”), which requires manufacturers to implement and follow design, testing, control, documentation and other quality assurance and good manufacturing practice procedures.
+Added: Following approval of a PMA, the FDA will authorize commercial distribution if it determines there is reasonable assurance that the medical device is safe and effective for its intended purpose.
This determination is based on the benefit outweighing the risk for the population intended to be treated with the device.
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As part of this effort, the Company established CytoSorbents Poland Sp.
−Removed: and in 2022 we established CytoSorbents France SAS as wholly-owned subsidiaries of CytoSorbents Europe GmbH.
+Added: In March 2022, the Company formed CytoSorbents Medical UK Limited to provide marketing and direct sales services in the United Kingdom and the Republic of Ireland.
+Added: In October 2022, the Company formed CytoSorbents France SAS to provide marketing and direct sales services in France.
+Added: In May 2023, the Company formed CytoSorbents India Private Limited to provide marketing and direct sales services in India.
From the beginning of the controlled market release in the fourth quarter of 2011 through December 31, 2023, we achieved cumulative sales of CytoSorb of approximately $212.8 million.
8 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, B.
−Removed: Braun Avitum AG, Aferetica s.r.l.
+Added: These partners include Fresenius Medical Care AG, B.
+Added: Braun Avitum AG, Eris LifeSciences, Aferetica s.r.l.
and Terumo Cardiovascular Group.
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Description/Indications
−Removed: Hemocompatible Polymer Systems and Related Devices
Size-Selective Hemoperfusion Polymeric Adsorbents
10 unchanged sentences
Hemocompatible Modifiers
+Added: Methods of Reducing Contamination in a Biological Substance
+Added: Removing Protein Based Toxins and Potassium from Biological Fluids
Method of Treating Acute Radiation Syndrome
23 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.