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|1 |1 NASDAQ: CTSO Investor Presentation December 2024
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|2 Safe Harbor Statement Statements in this presentation regarding CytoSorbents Corporation and its operating subsidiaries CytoSorbents Medical, Inc and CytoSorbents Europe GmbH that are not historical facts are forward-looking statements and are subject to risks and uncertainties that could cause actual future events or results to differ materially from such statements. Any such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. It is routine for our internal projections and expectations to change. Although these expectations may change, we are under no obligation to inform you if they do. Actual events or results may differ materially from those contained in the projections or forward-looking statements. The following factors, among others, could cause our actual results to differ materially from those described in a forward-looking statement: our history of losses; potential fluctuations in our quarterly and annual results; competition, inability to achieve regulatory approval for our device, technology systems beyond our control and technology-related defects that could affect the companies’ products or reputation; risks related to adverse business conditions; our dependence on key employees; competition for qualified personnel; the possible unavailability of financing as and if needed; and risks related to protecting our intellectual property rights or potential infringement of the intellectual property rights of third parties. This list is intended to identify only certain of the principal factors that could cause actual results to differ from those discussed in the forward- looking statements. Readers are referred to a discussion of important risk factors detailed in the Company’s 2022 Form 10-K filed with the Securities and Exchange Commission on March 14, 2024, and other reports and documents filed from time to time by us, which are available online at www.sec.gov.
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CytoSorbents at a Glance • Platform blood purification technology for removing toxins and harmful substances from the blood • High margin “razorblade” that is “plug and play” into existing hospital blood pumps • Two main products leveraging the underlying porous polymer technology o CytoSorb • Treatment of life-threatening conditions in the ICU and cardiac surgery • Core business with ~$34 million in trailing 12-month product sales (~100% OUS)* • E.U. Approved with >250,000 CytoSorb devices utilized cumulatively to date in 76 countries o • Investigational device to remove “blood thinners” / antithrombotic drugs during urgent cardiovascular surgery • Two FDA Breakthrough Device Designations • Submitted to FDA in September 2024 and Health Canada in November 2024 with regulatory decisions expected in 2025 • If approved/cleared, we expect to begin commercialization rapidly, targeting a significant unmet need in large U.S. and Canada addressable markets *As of 9/30/24 |3
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|4 |4 The Power of the Bead Hemocompatible, highly porous polymer bead platform technology that act like tiny sponges to remove harmful substances from blood by pore capture, adsorption, and concentration • Excellent removal of a broad range of substances from whole blood and plasma • Solid state porous polymer chemistry that does not use ligands, antibodies, cells, or biologics • 22 issued U.S. patents and multiple patents issued and pending worldwide • Beneficiary of ~$50M in grants and non-dilutive funding from NIH, DARPA, DOD, others
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|5 Products are “Plug and Play” Compatible Compatible with Existing Blood Pump Infrastructure In Hospitals Today ECMO (Extracorporeal Membrane Oxygenation) CPB (Cardiopulmonary Bypass) Dialysis or CRRT (Continuous Renal Replacement Therapy) CytoSorbents Confidential Hemoperfusion (Standalone Treatment) CytoSorbents launched its PuriFi pump, an easy-to-use hemoperfusion pump, to excellent reviews in June 2024 PuriFi gives hospitals the ability to administer CytoSorb therapy earlier and without the need for dialysis. This is particularly important in countries that do not have a well-established dialysis infrastructure CytoSorbents PuriFi Pump Launched Q2 2024
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|6 We are Expanding the Dimension of Blood Purification® by removing a broad range of toxins that dialysis does not remove well Dialysis works like the kidney Small Molecules and Water soluble substances Urea, Ammonia Electrolytes Water Water-soluble drugs CytoSorb works like the liver Large Molecules and Fat soluble substances Cytokines Inflammatory mediators Bacterial toxins Liver toxins Proteins and peptides Fat-soluble drugs Looks Like Dialysis, but Key Differences CytoSorb has 7 football fields of surface area to bind toxins compared to ¾ of a ping pong table for a dialyzer
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|7 The Opportunity of * The DrugSorb-ATR system is an investigational device that is not yet cleared/approved by FDA, Health Canada, or by any other Global Regulatory Agency and is not commercially available for sale
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|8 There is no approved reversal agent for these specific drugs in the U.S. or Canada for cardiac surgery. CytoSorb is approved for this indication in the E.U. and is the only option for cardiac surgery ROW Large Unmet Need for Blood Thinner Reversal Eliquis® (apixaban) (Pfizer, BMS) A-Fib, Peripheral Vascular Disease, DVT/PE, Others • Cardiac surgeons are frequently faced with patients on antithrombotics needing urgent surgery • Guidelines recommend that such patients wait for 3-5 days for these drugs to “washout” to avoid bleeding complications • Frequently the surgery cannot wait, and patients are operated at a very high risk for major bleeding complications • Delaying surgery for washout is also not optimal o Exposes patients to risk for complications while waiting o Hospital efficiency is reduced when beds are occupied with patients waiting Brilinta® (ticagrelor) (AstraZeneca) Acute Coronary Syndrome, Stents, Prosthetic Heart Valves Xarelto® (rivaroxaban) (Bayer, Jansenn/J&J) Atrial Fibrillation (lifelong therapy) Millions of people worldwide are on Anti-thrombotic blood thinners to reduce risk of heart attack and stroke Direct Oral Anticoagulants (DOAC)Anti-platelets (P2Y12 platelet inhibitor)
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|9 |9 DrugSorb-ATR is an FDA Breakthrough Device • DrugSorb-ATR is an investigational device that uses an equivalent polymer technology to CytoSorb and installs easily into a cardiopulmonary bypass machine * • As whole blood is pumped through the cartridge, it is designed to remove free drug during surgery from blood to reverse its antithrombotic effect • FDA has granted 2 Breakthrough Device Designations (BDD) for DrugSorb-ATR highlighting the major unmet medical need and lack of effective therapies, and provides for priority review of marketing submissions • 2020: Removal of Brilinta® in emergent or urgent cardiothoracic surgery • 2021: Removal of DOACs, Eliquis® and Xarelto® for same * The DrugSorb-ATR system is an investigational device that is not yet cleared/approved by FDA, Health Canada, or by any other Global Regulatory Agency and is not commercially available for sale Brilinta is our initial focus for the U.S. and Canadian market
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|10 |10 Brilinta® and the Use Case for 5 - 10% will need open heart surgery X X X X X The ultimate goal of DrugSorb-ATR is to allow patients to get the critical surgery they need without delay, while reducing or preventing bleeding complications
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|11 Al-Attar et. al., J Cardiothoracic Surg (2019)14:64. Spahn et al Hemotherapy 46 (2019) 282–93. Christensen et. al., J Card Vasc Anesth (2012) 26:46-5. Bleeding at baseline varies according to type of cardiothoracic surgery without the use of antithrombotic drugs In-hospital bleeding complications and reoperation rates in 7774 cardiac surgery patients (3963 CABG; 2363 valve replacement/ repair; 160 aortic procedures; 1288 multiple procedures, primarily CABG+valve). Cardiac Surgery and Bleeding Risk Factors associated with bleeding: • Type of Surgery • Surgical duration • Duration of cardiopulmonary bypass (CPB) • Body temperature • Use of cardiac assist devices • Intraoperative complications Isolated CABG without blood thinners: ~5% Major Bleeding Re-operation 1/300 What happens when blood thinners are added to the mix?
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|12 12 Holm M, et. al. Ann Thorac Surg. 2019 Jun;107(6):1690-1698. The rate of severe or massive bleeding is >3X higher in patients undergoing CABG within 2 days of last dose of Brilinta®, compared with a 4-5 day washout • In this E-CABG registry study, the incidence of severe or massive bleeding in patients on Plavix® (clopidogrel) or Brilinta® (ticagrelor) was assessed based on last dose of the drug and timing of CABG surgery • Used the Universal Definition of Perioperative Bleeding (UDPB) – a bleeding scale developed specifically for cardiac surgery – where UDPB ≥ 3 represents severe, massive, or fatal bleeding The European Multicenter Study on CABG (E-CABG) Registry is one of the largest real-world data registries evaluating outcomes in CABG patients – the most common cardiac surgery Brilinta Increases Bleeding Risk in Isolated CABG Surgery Dyke, C., et al. “Universal Definition of Perioperative Bleeding in Adult Cardiac Surgery”, J Thorac Cardiovasc Surg (2014); 147(5):1458-1463.
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|13 A Pivotal Randomized, Sham-Controlled Trial Examining the Safety and Efficacy of Intraoperative Removal of Ticagrelor in Patients Undergoing Urgent Cardiac Surgery Topline Results of the STAR - T Trial Michael Mack, MD Richard Whitlock, MD C. Michael Gibson, MD for the STAR-T Investigators April 28, 2024 13
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|14 Adverse Events STAR-T RCT: Safe & Timely Antithrombotic Removal of Ticagrelor • Evaluate the safety of intraoperative use of DrugSorb-ATR • Evaluate DrugSorb-ATR efficacy in reducing perioperative bleeding Randomized 1:1 DrugSorb-ATR Sham Device 140 patients enrolled in ~30 centers in US and Canada undergoing cardiac surgery within 2 days of last dose of Brilinta Study Objectives: Intraoperative Period CPB Duration Post-Op Day #1 Post-Op Day #2 Study Follow-up to Post-Op Day #30 Standard of Care Standard of Care Fatal Bleeding UDPB Events 24-hour Chest Tube Drainage Prespecified Study Endpoints: • Safety: Adverse event rates assessed by independent Data Safety Monitoring Board (DSMB) • Efficacy: Perioperative bleeding based on UDPB grade and 24-Hr Chest Tube Drainage (CTD) • Composite #1: fatal, moderate/severe (UDPB≥2) bleeding and 24-hr CTD (Primary) • Composite #2: fatal, severe (UDPB≥3) bleeding and 24-hr CTD Composite endpoints analyzed with a hierarchical WIN Ratio of the 3 components
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|15 |15 STAR-T Results Presented by Dr. Michael Mack
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|16 |16 STAR-T Key Takeaways & Next Steps • No safety concerns - Primary safety endpoint met • Imbalances in the number of high-risk non-CABG surgeries and other factors in the treatment arm led to missing the primary efficacy endpoint in overall surgery population (92% CABG + 8% other) • However, the severe bleeding endpoint was met in the pre-specified CABG per protocol population • Overall, in patients undergoing CABG, DrugSorb-ATR was associated with: • Reduced bleeding severity by either UDPB grade or CTD volume • NNT (Number Needed to Treat) of 6 to prevent a major bleed (UDPB 3 event or CTD >1 Liter) • Favorable benefit-to-risk profile • Corroborated with real world data in 102 CABG patients on ticagrelor from European STAR Registry with CytoSorb • U.S. FDA De Novo marketing application submitted 9/27/24 and accepted by FDA in October 2024, now under substantive review. FDA Breakthrough Device status = priority review • Health Canada Medical Device License application submitted 11/1/24 with MDSAP certification • FDA and Health Canada decisions expected in 2025 * The DrugSorb-ATR system is an investigational device that is not yet cleared/approved by FDA, Health Canada, or by any other Global Regulatory Agency and is not commercially available for sale
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|17 |17 (1) Cleveland Clinic 2023 Patient Price Information List DrugSorb-ATR is a Potential Win for All Stakeholders Patients ✓ Minimize delays to definitive surgery ✓ Reduce serious bleeding risk, which is associated with longer hospital stays and increased morbidity and mortality Surgeons ✓ No change in workflow, seamless integration into CPB machine ✓ Reduce serious perioperative bleeding ✓ Protect surgeon’s reputation and quality rating ✓ Faster disposition of patients, increased throughput of new patients, reduces expensive and time-consuming re-exploratory surgery Hospital Administrators ✓ Reduces hospital resource utilization ✓ Avoiding costs of 3 - 5 day washout: ~$18-30K in the ICU, ~$6-10K in a cardiac bed ✓ Reduced adverse events protects hospital’s CMS STAR rating
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|18 |18 Strong Value Proposition for Hospitals Average Washout Duration: US: 4 days CAN: 3.7 days Washout Location ICU Stepdown ICU General Ward US 13% 79% 8% CANADA 24% 26% 50% Survey of Select STAR-T US Pivotal Trial Sites* Cost savings calculated based on washout duration and hospital location. Hospital bed costs as reported in literature. Illustrative Hospital Savings with DrugSorb-ATR Waiting in the hospital for multiple days for the drug to “washout” is highly problematic: $3,704 $3,018 $8,890 $6,338 USA Canada Per Day Per STAR-T ($USD) ($CAD) Surgery at 1.6 days with DrugSorb-ATRGuidelines recommend Ticagrelor washout for 3-5 days * CytoSorbents data on file • Exposes patients to added risk due to the delay of having the needed operation • Increases hospital costs and reduces efficiency by blocking beds and reducing throughput
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|19 |19 US & Canada TAM for Brilinta Removal ~60,000 patients on Brilinta needing emergent/urgent CABG surgery annually in U.S. and Canada x ~ $5,000 per device (USD and Canadian) ~$300M (USD) Initial US & Canada Total Addressable Market Brilinta market share expected to grow • DrugSorb-ATR would make Brilinta the only reversible platelet inhibitor • Brilinta goes off patent in 2024 leading to a likely drop in prices Targeting label expansion to include DOACs >$600M US & Canada Total Addressable Market Potential at Premium Expected Product Gross Margins
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|20 |20 >$300M Initial Opportunity • U.S. & CAN Ticagrelor Removal in CABG >$200M >$450M Future Opportunity $1-2 Billion • U.S. & CAN Ticagrelor Removal in CABG • DOAC Removal in CABG • DOAC Removal in Hospital-Wide Applications >$150M >$450M Near-Term Opportunity >$600M • Expansion of U.S. & CAN Ticagrelor Removal in CABG • DOAC Removal in CABG Large Total Addressable Market
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|21 CytoSorb Our Core Business
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|22 |22 CytoSorb Targets Massive Inflammation - the Heart of Critical Illness • Acute inflammation is the body’s mechanism to fight injury and infection • However, severe inflammation, driven by cytokine storm, can cause a chain reaction of problems that can end in organ failure and death • Severe inflammation is the common thread amongst most critical illnesses and is directly correlated to increased severity of illness, organ failure, and mortality CytoSorb controls deadly inflammation and has demonstrated the reversal or prevention of many of these complications SHOCK CAPILLARY LEAK IMMUNE DYSFUNCTION DIRECT TISSUE DAMAGE MICROVASCULAR DYSFUNCTIONHYPERCOAGULABILITY CELL-MEDIATED INJURY
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|23 |23 Targets Deadly Conditions That Afflict Millions of People Lung Injury Burn Injury Sepsis COVID-19 Influenza Cytokine Release Syndrome Surgical Complications Liver Failure Trauma Critical Care Cardiothoracic Surgery Removes the “fuel to the fire” of massive uncontrolled inflammation that is often associated with organ failure and death Reduces inflammation and blood thinners, targeting reduction in complications of cardiac surgery like sepsis, bleeding, shock, and others Life-threatening bleeding due to anti-thrombotic “blood thinners” Infective Endocarditis High Risk Procedures Pancreatitis
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|24 100% This is Why CytoSorb Continues To Grow in ICU applications 80%60%40%20% Dialysis/CRRT for Kidney Failure CytoSorbents Sepsis, Septic Shock, Other Shock Infectious diseases (flu, COVID-19, other) Burn injury Drug overdose Blood thinner toxicity Trauma, Rhabdomyolysis Cytokine storm/ Cytokine release syndrome Liver failure Acute Respiratory Distress Syndrome (ARDS) High risk surgical procedures, aortic surgery, Infective endocarditis Post-surgical complications Organ transplant Pancreatitis Neuroinflammation Percentage of Applicable Patients in the ICU CytoSorb helps to treat critical illnesses where massive inflammation plays a dangerous role in 40-60% of patients in the ICU. Compare this to the only 10-15% of patients who require dialysis in the ICU
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|25 CytoSorb Key Facts • E.U. approved and used in 76 countries worldwide with more than a quarter million treatments used cumulatively • By treating deadly inflammation, CytoSorb helps to prevent or treat organ failure – the cause of nearly half of all deaths in the ICU. Because of this, we believe we are very strategically and uniquely positioned to help solve many of the most difficult to treat life-threatening illnesses that are estimated to account for 40-60% of patients in the ICU • CytoSorb is expanding the dimension of blood purification well beyond kidney dialysis by acting like the other major detoxification organ…the liver. We believe CytoSorb is the best-in-class technology for this application • Manufactured in the U.S. at our new state-of-the-art facility (peak capacity $400M sales) at high blended product gross margins (>70%) that mix higher margin direct sales ($1,000+ ASP) with lower margin distributor sales • Partnered with some of the leading multinational corporations in the world in critical care and cardiac surgery * The DrugSorb-ATR system is an investigational device that is not yet cleared/approved by FDA, Health Canada, or by any other Global Regulatory Agency and is not commercially available for sale
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|26 |26 Financial Performance
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|27 CytoSorbents sells through Direct Sales in 15 countries and Distributors in 60+ others * 2022 and 2023 Core Product Sales were impacted by fall of the Euro to dollar compared to 2021. ** TTM sales as of 9/30/24 $4.0 $8.2 $13.4 $20.3 $22.8 $30.1 $33.8 $31.1 $9.4 $6.3 $0.0 $5.0 $10.0 $15.0 $20.0 $25.0 $30.0 $35.0 $40.0 $45.0 2015 2016 2017 2018 2019 2020 2021 2022 2023 TTM $ IN MILLONS Annual Product Sales Core Non-COVID-19 Product Sales COVID-19 Sales $39.5M $40.1M $29.4M* $29.1 $31.1M* 2024: Continued Growth • $33.7M Trailing 12-month sales** • Q1-Q3 Product Sales of $26.4M +11% yoy • Product gross margins of 70% YTD $33.7M** $33.7 $29.1 Annual Product Sales
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|28 Solid Financial Performance in Q3 2024 Metric Performance Product revenue $8.6M, 11% year-over-year growth Gross margin 61% (planned slowdown and short-term manufacturing issue that was resolved in the quarter) compared to 75% in Q2 2024. 70% YTD Operating expenses 25% year-over-year decrease Operating loss 40% year-over-year improvement Adjusted EBITDA $3.6 million vs $5.6 million Q324 Cash burn $2.7 million, down from $5 million in 2Q24
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|29 |29 Cash Conservation – A Top Corporate Priority Cash burn was approximately $2.7 million during the quarter versus approximately $5.0 million in Q2 2024 Reduced cash burn during the quarter $12.2 million in cash Includes $6.5 million of restricted cash and $5.7 million in unrestricted cash Cash balance as of September 30, 2024 Secured a $20 million loan facility in June 2024, with $10 million immediately accessible and $5 million held as restricted cash, contingent on FDA acceptance of our DrugSorb-ATR marketing application which was recently received, and receipt of $3-5 million in equity proceeds by March 31, 2025. A remaining tranche of $5 million is available at the Company’s option between July and December 2025, conditioned on FDA marketing approval of DrugSorb-ATR Optionality with current loan and security agreement
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|30 A Simple and Compelling Value Proposition • We continue to demonstrate solid top line performance of our core international CytoSorb business in critical care and cardiac surgery • Delivering improved operating efficiencies, margin expansion to drive core business toward cash flow break even in 2H 2025 • We expect key regulatory decisions for DrugSorb-ATR in the U.S. and Canada in 2025 • First entry to the important North American market, focused on blood thinner removal for CABG surgery • Higher margin business expected to be catalytic to growth, profitability and future expansion • We are developing and investing in real-world clinical evidence to support our therapies • We continue to cultivate multiple potential drivers of growth
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Company Contact: Dr. Phillip Chan pchan@cytosorbents.com 908-307-0367 www.cytosorbents.com NASDAQ: CTSO 31 CytoSorbents Corporation