Core Viewpoint - CytoSorbents Corporation has filed a request for supervisory review with the FDA regarding the De Novo Denial Letter for its DrugSorb-ATR Device, which aims to reduce bleeding severity in CABG surgery patients on Brilinta® [1][2][7] Group 1: Company Overview - CytoSorbents Corporation specializes in blood purification technologies for treating life-threatening conditions in intensive care and cardiac surgery [5] - The company's proprietary technologies utilize biocompatible polymer beads to remove toxic substances from blood, applicable in various medical scenarios including sepsis and organ failure [5][6] - CytoSorbents' lead product, CytoSorb®, is CE Marked in the EU and has been used over 270,000 times globally [6] Group 2: Regulatory Developments - The FDA issued a De Novo Denial Letter on April 25, 2025, citing deficiencies that must be resolved before the DrugSorb-ATR can be authorized for U.S. commercialization [2][7] - The company has engaged with the FDA to clarify these deficiencies and believes that the supervisory review process will effectively address the concerns [2][4] - The appeals process typically results in a final decision approximately 60 days after filing, with the company optimistic about receiving a regulatory decision in 2025 [3][7] Group 3: Market Context - DrugSorb-ATR is designed to mitigate perioperative bleeding in patients undergoing high-risk surgeries while on antithrombotic medications [7] - The application for DrugSorb-ATR is also under advanced review by Health Canada, with the agency committed to issuing a decision despite current delays [4][7]

Company Overview - CytoSorbents has a platform blood purification technology for removing toxins, with two main products: CytoSorb and DrugSorb-ATR[8] - CytoSorb is approved in the E U with over 250,000 devices used in 76 countries, generating approximately $34 million in trailing 12-month product sales[8] - DrugSorb-ATR, an investigational device for removing blood thinners, has been submitted to the FDA and Health Canada, with regulatory decisions expected in 2025[8] DrugSorb-ATR Opportunity - The initial U S and Canada total addressable market for Brilinta removal is estimated at ~$300 million[67] - The total addressable market potential for DrugSorb-ATR, including DOAC removal, is >$600 million in the U S and Canada[67] - In patients undergoing CABG, DrugSorb-ATR was associated with a Number Needed to Treat (NNT) of 6 to prevent a major bleed (UDPB 3 event or CTD >1 Liter)[56] CytoSorb Core Business - CytoSorb targets massive inflammation, which affects 40-60% of patients in the ICU[79] - The company's manufacturing facility has a peak capacity of $400 million in sales, with blended product gross margins >70%[83] Financial Performance - The company reported $33.7 million in trailing 12-month sales[88] - Q1-Q3 product sales reached $26.4 million, an 11% year-over-year increase[88] - The company's cash burn was reduced to approximately $2.7 million in Q3 2024, compared to $5 million in Q2 2024[90]

Financial Performance - Total revenue for Q3 2023 was $881 million, an increase of approximately 86% compared to $811 million for Q3 2022[27] - Product sales for Q3 2023 were approximately $775 million, a 20% increase compared to $646 million in Q3 2022[27] - Product gross margins for Q3 2023 were 72%, compared to 55% for Q3 2022[27] - Total YTD revenue as of September 30, 2023, was $2768 million, a 94% increase compared to $2530 million for the same period in 2022[28] - YTD product sales as of September 30, 2023, were approximately $2374 million, a 93% increase over $2172 million for the same period a year ago[28] Operational Highlights & DrugSorb-ATR - The STAR-T RCT completed in August, with follow-up on 100% of patients, at 30 centers in the US and Canada[12] - The company expects DrugSorb-ATR to have a higher ASP and product gross margin than CytoSorb and would open an expected US and Canadian TAM of $600-650 million for Brilinta alone[40] - Over 221000 cumulative human treatments delivered across 75 countries worldwide[7] Cash Flow - Cash balance as of 9/30/2023 was approximately $10 million, which included restricted cash of approximately $17 million[33] - The quarterly cash burn during the nine months in 2023 averaged approximately $46 million, down significantly from the average quarterly cash burn in the nine months of 2022 of approximately $99 million[33] Strategic Partnership - Fresenius has begun marketing CytoSorb as the "featured technology for cytokine, bilirubin, and myoglobin removal" on its critical care platforms worldwide (excluding the US)[23] - CytoSorbents benefits from the global endorsement and push on Fresenius' sales and marketing platform and has agreed to subsidize this effort with a 09% royalty to FMC on ex-US CytoSorb sales[23]

Financial Performance - Total revenue for 2023 was $36.3 million, a 5% increase compared to $34.7 million in 2022[39] - CytoSorb product sales were $31.0 million in 2023, a 9% increase from $28.6 million in 2022[39] - Q4 2023 total revenue decreased by 8% to $8.7 million compared to $9.4 million in Q4 2022[42] - Q4 2023 CytoSorb sales decreased slightly by 1% to $7.3 million compared to $7.4 million in Q4 2022[42] - The company has $15.6 million in cash as of December 31, 2023, which is expected to fund operations into the fourth quarter of 2024[43] Operational Highlights - Over 228,000 cumulative CytoSorb treatments have been delivered as of the end of 2023, a 17% increase from the end of 2022[9] - International Direct sales experienced strong growth of 27% to $6 million (19% product sales)[23] - The company expects to launch its new PuriFi pump later this year, following the expiration of the distribution agreement with Nikkiso Europe GmbH in September 2023[12] DrugSorb-ATR and STAR-T Trial - The pivotal STAR-T RCT was selected for a Breakout Presentation at the American Association of Thoracic Surgery (AATS) Annual Meeting[13, 17] - The company plans to submit for regulatory approval of DrugSorb-ATR to the U S FDA and Health Canada in the second half of 2024[13, 17] - The initial U S & Canada Total Addressable Market for Brilinta removal is estimated at $325 million, with a potential of $650 million[18, 19] Product Pipeline and Expansion - The company has received ~$50 million in grants, contracts, and other non-dilutive funds since 2003 for its technology[24] - VetResQ, bringing CytoSorb to veterinary medicine, had a limited but successful launch in 2023, with plans for an integrated all-in-one solution in 2024[33] - HemoDefend-BGA aims to create "universal plasma" and has received over $17 million in funding from the U S Department of Defense[37]

Financial Performance - Q1 2024 product sales reached approximately $9.0 million, a 14% increase from $7.9 million in Q1 2023[12, 20] - Q1 2024 product sales increased 22% sequentially from $7.3 million in Q4 2023[12] - Product gross margins for Q1 2024 were 76%, up 800 basis points from 68% in Q1 2023, excluding a one-time inventory adjustment[12, 20] - Grant revenue was $797,000 in Q1 2024, compared to $1.5 million in Q1 2023, a decrease of 48%[20] - Total revenue for Q1 2024, including product sales and grant income, was $9.8 million, compared to $9.4 million for Q1 2023, a 4% increase[20] Operational Highlights - Cumulative CytoSorb treatments exceeded 237,000 as of March 31, 2024, and are expected to reach a quarter million this year[15] - The company expects to launch the PuriFi hemoperfusion pump in select international countries in Q2 2024[15] - The company is on track to submit marketing applications for the DrugSorb-ATR system to the FDA and Health Canada in Q3 2024[12] DrugSorb-ATR and Regulatory Path - The FDA has granted two Breakthrough Device Designations for DrugSorb-ATR[30] - Regulatory experts recommend FDA submission for DrugSorb-ATR use in CABG surgery under the De Novo pathway[40] - The company is targeting parallel De Novo submission to FDA and Health Canada in Q3 2024, with FDA review potentially taking 6-12 months following submission[39, 40] STAR-T Trial - In the Isolated CABG Per Protocol group, the Severe endpoint showed a WIN Ratio of 1.59 with a p-value of 0.041[32] - Exploratory analysis of Major Bleeding showed a reduction from 22% in the control group to 6% in the DrugSorb group, with p=0.028[34]

Financial Performance - Total revenue in Q2 2024 increased by 5% to $9.9 million compared to $9.4 million in Q2 2023[10, 20] - Product sales in Q2 2024 increased by 10% to $8.8 million compared to $8.1 million in Q2 2023[10, 20] - Operating loss in Q2 2024 decreased by 48% to $3.4 million from $6.6 million[10] - For the first half of 2024, total revenue increased by 4% to $19.7 million compared to $18.9 million in the first half of 2023[21] - Product sales for the first half of 2024 increased by 12% to approximately $17.8 million compared to $16.0 million in the same period last year[21] - The company's cash balance at the end of Q2 2024 was $14.9 million, including $8.5 million in unrestricted cash and $6.5 million in restricted cash[10] Operational Highlights - Over a quarter million CytoSorb devices have been cumulatively delivered to date[10] - The company completed additional cutbacks, expected to save an additional $5 million in expenses going forward, and decreased the workforce by 17% over the past 5 months[10] - The company secured an additional $20 million credit facility with Avenue Capital Group[10] Regulatory and Clinical Developments - The company is on track to submit marketing applications for the investigational DrugSorb-ATR system to FDA as a De Novo application and Health Canada in Q3 2024[15] - Data from the STAR Registry was presented at EuroPCR 2024 and was selected as a top 5 finalist in the best scientific abstract competition[15] - Real-world data from the STAR Registry showed a 44% lower rate of severe bleeding (UDPB 3) with CytoSorb compared with the E-CABG Registry when TLD is less than 24 hours, and an 80% lower rate when TLD is between 24-72 hours[37]

Financial Performance - CytoSorbents' product revenue in Q3 2024 reached $8.6 million, showing an 11% year-over-year growth[16] - The company's operating expenses decreased by 25% year-over-year in Q3 2024[16,51] - The operating loss was reduced by 40% year-over-year[16,51] - Cash burn was reduced to $2.7 million in Q3 2024, down from $5 million in Q2 2024[16,54] - As of September 30, 2024, the company had $12.2 million in cash, including $6.5 million of restricted cash and $5.7 million in unrestricted cash[57] DrugSorb-ATR Regulatory and Clinical Updates - DrugSorb-ATR, an investigational device, has been submitted to the FDA and Health Canada, with regulatory decisions expected in 2025[12,21] - The company submitted a De Novo medical device marketing application to the FDA on September 27, 2024, which was accepted in October 2024[22] - In isolated CABG patients, the intraoperative use of DrugSorb-ATR was associated with reduced bleeding severity[20] - Real-world evidence from an additional 102 CABG patients on Brilinta suggests that the guideline-recommended washout period of a minimum of 72 hours may be substantially shortened with CytoSorb and DrugSorb-ATR[23] Market Opportunity - The company estimates an initial market opportunity of over $300 million for Ticagrelor removal in CABG in the U S and Canada[31]

Financial Performance - Q1 2025 product sales were $8.7 million, a 3% year-over-year decrease, but flat on a constant currency basis[18] - Product gross margin was 71% in Q1 2025, consistent with the average from 2024[18] - Total operating expenses decreased by 12% year-over-year, from $11.5 million to $10.1 million[50] - Net loss improved by 17% year-over-year, from $6.1 million ($0.11/share) to $1.5 million ($0.02/share)[50] DrugSorb-ATR Regulatory Update - The company submitted a De Novo submission to the FDA and a Medical Device License application to Health Canada, but received a denial letter from the FDA on April 25, 2025[36] - The company plans to file a formal appeal within 60 days of the FDA letter[36] - Health Canada submission is in advanced review, with a decision expected in 2025[36] DrugSorb-ATR Market Opportunity - DrugSorb-ATR addresses a $300+ million initial market opportunity, which could exceed $1 billion as Brilinta becomes generic and DrugSorb-ATR expands to additional indications[33] CytoSorb Core Business - Core product sales reached a record $35.6 million in 2024[14] - The company aims to return Germany to growth in the second half of 2025 after flat sales for two consecutive years[18] - The company is managing its total core business toward near breakeven in the second half of 2025[18] Balance Sheet - The company received $6.8 million from a successful Rights Offering[51] - The company released $5.0 million of restricted cash[51] - The company had $13.1 million in cash, cash equivalents, and restricted cash at March 31, 2025[51]

Summary of CytoSorbents Conference Call Company Overview - **Company**: CytoSorbents - **Industry**: Medical Supplies and Devices - **Key Products**: - **CytoSorb**: Blood purification technology for critical care and cardiac surgery - **DrugSorb ATR**: Investigational product for reducing perioperative bleeding during CABG surgery Core Points and Arguments 1. **CytoSorb Product Performance**: - Achieved record core non-COVID product sales of $35.6 million in 2024, growing 15% year-over-year [3] - Over 270,000 human treatments in more than 70 countries [3] - High gross margins of 71% [27] 2. **DrugSorb ATR Development**: - Designed to address bleeding complications in patients on blood thinners during surgery [11] - Received two FDA breakthrough device designations [14] - Aimed at a significant unmet medical need in the US and Canadian markets [3] 3. **Technology and Mechanism**: - Utilizes a patented polymer bead technology that effectively removes a broad range of harmful substances from blood [4] - CytoSorb targets severe inflammation, which affects up to 60% of ICU patients [7] 4. **Clinical Research and Efficacy**: - Recent studies show significant reductions in mortality and shock reversal in patients treated with CytoSorb [8][10] - Meta-analysis indicated a 50% reduction in 28-day all-cause mortality in patients treated with CytoSorb [10] 5. **Regulatory Updates**: - FDA denial letter received on April 25, 2025, but the company plans to file a formal appeal [23][24] - Health Canada submission is under advanced review, with expectations for decisions in 2023 [25] 6. **Market Potential**: - Total addressable market estimated at $300 million initially, potentially growing to over $1 billion with additional indications [26] 7. **Financial Position**: - Cash position of $13.1 million at the end of Q1, with a quarterly burn rate of $2.5 million to $3 million [46] - Aiming for cash flow breakeven by the second half of 2025 [28] 8. **Sales Strategy**: - Plans for a controlled market release in clinical trial centers post-approval, followed by a broader launch in 2026 [36] - Predominantly direct sales force in the US, complemented by perfusionist distributors [37] 9. **Challenges in Germany**: - Germany accounts for about 40% of revenue but has seen flat growth due to macroeconomic factors [52] - Organizational changes are being made to drive deeper into accounts and improve sales effectiveness [53] Additional Important Information - **Cost Savings for Hospitals**: - Using DrugSorb can save hospitals $18,000 to $30,000 per patient by reducing the need for prolonged ICU stays to wash out blood thinners [43] - **Clinical Trial Insights**: - The STAR T trial showed that DrugSorb ATR significantly reduced bleeding severity in CABG patients [19] - **Market Preparation**: - The company is actively preparing for market entry while awaiting regulatory decisions [31] This summary encapsulates the key points discussed during the conference call, highlighting the company's product performance, regulatory challenges, market potential, and strategic direction.

Core Insights - CytoSorbents Corporation presented a real-world data analysis showing that its blood purification technology significantly reduces severe bleeding and transfusion needs in urgent CABG patients on ticagrelor [1][6] Study Details - The analysis compared two groups: 150 patients using CytoSorbents' device from the STAR Registry and 644 control patients who did not use the device [3][12] - The primary outcome measured was the incidence of severe bleeding as defined by the BARC-4 criteria, which includes intracranial bleeding, re-operation for bleeding, and large transfusion events [12] Results - The use of the device resulted in a reduction of BARC-4 severe bleeding rates to 10.7% compared to 33% in the control group, with a p-value of <0.001 [7][12] - Large transfusion events (≥5 units of blood) were reduced to 6% in the device group versus 27% in the control group, p<0.001 [7][12] - The need for re-operations to control bleeding was 4% in the device group compared to 9.6% in the control group, p=0.02 [7][12] Safety and Efficacy - No device-related adverse events or deficiencies were reported, indicating the device's safety and ease of use in clinical practice [4][12] - The findings support the routine use of CytoSorbents' device in urgent CABG surgeries for patients on blood thinners like ticagrelor [5][12] Company Overview - CytoSorbents Corporation specializes in blood purification technologies aimed at treating life-threatening conditions in intensive care and cardiac surgery [9] - The company's lead product, CytoSorb®, is approved in the EU and distributed in over 70 countries, with over 250,000 devices used to date [10] - CytoSorbents is also developing the DrugSorb™-ATR system for antithrombotic removal, which has received FDA Breakthrough Device Designations [11][13]