CytoSorbents Corporation · NASDAQ:CTSO
CytoSorbents — Technical Presentation (July 2020)
91 slides from CytoSorbents's technical presentation, Jul 13, 2020
Slide 1: CytoSorb Antithrombotic Removal
WORKING TO SAVE LIVES yi ae CytoSorb Antithrombotic Removal ” July 13, 2020
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains “forward-looking statements” pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, without limitation, any statement that may predict, forecast, indicate, or imply future re
Slide 3: Opening Remarks
Opening Remarks Dr. Phillip Chan, MD, PhD Chief Executive Officer CytoSorbents Corporation 3
Slide 4: CytoSorbents At a Glance (NASDAQ: CTSO)
CytoSorbents At a Glance (NASDAQ: CTSO) • CytoSorbents is a U.S. NASDAQ-traded medical device company that specializes in treating life-threatening conditions with its blood purification technology • CytoSorb® is E.U. approved, manufactured in the U.S. by CytoSorbents, and commercialized in 65 count
Slide 5: CytoSorb is "Plug and Play" Compatible
CytoSorb is “Plug and Play” Compatible Compatible with Existing Blood Pump Infrastructure In Hospitals Today Dialysis or CRRT ECMO (Continuous Renal Replacement Therapy) (Extracorporeal Membrane Oxygenation) Hemoperfusion CPB (Standalone Treatment) (Cardiopulmonary Bypass) 5
Slide 6: CytoSorb Commercialization Focus
CytoSorb Commercialization Focus By Market By Geography Other Critical Care – 17% • ARDS 20 – 30% Distributor / Partner • Reversal of Shock • Trauma 17% • Austria Critical Care 67% 10 – 15% Other Direct • Acute Liver / Pancreatic • Switzerland • Many Others • 7 other Sepsis countries and Cardiac Car
Slide 7: CytoSorb Adoption Continues to Grow
CytoSorb Adoption Continues to Grow Product Sales(ttm) and Blended Product Gross Margin Growth $30,000,000 77% $26,345,244 75% $25,000,000 73% $20,395,666 $20,000,000 71% $15,219,016 69% $15,000,000 67% $9,204,720 $10,000,000 65% $4,937,610 63% $5,000,000 $3,269,802 61% $0 59% Q1 2015 Q1 2016 Q1 201
Slide 8: Growth Driven By Many Macro Trends in Healthcare
Growth Driven By Many Macro Trends in Healthcare 8
Slide 9: Introduction of Agenda & Speakers
Introduction of Agenda & Speakers Efthymios N. Deliargyris, MD, FACC, FESC, FSCAI Chief Medical Officer CytoSorbents Corporation 9
Slide 10: Antithrombotic Removal
cd cytoSorh 3 cy So Antithrombotic Removal a 9 >. ( a — CytoSorbents.
Slide 11: CytoSorb Drug Adsorption: Mechanism of Action
CytoSorb Drug Adsorption: Mechanism of Action Device : adsorption on divinylbenzene polymer surface • favors hydrophobic binding • pore size = selective access to 60 kDa • dependent on drug concentration • dependent on time of blood exposure Drug: • Hydrophobic molecular functional groups (aromati
Slide 12: CytoSorb Integrates Easily Into Cardiopulmonary Bypass
CytoSorb Integrates Easily Into Cardiopulmonary Bypass • CytoSorb installs within minutes and is placed in a parallel circuit: post-pump, back to the venous reservoir • High blood flow, low resistance up to 700 mL/min • Fully-compatible with heparin anti-coagulation • Used safely in thousands of car
Slide 13: Antithrombotic Removal - Overview
Antithrombotic Removal - Overview P2Y12 NOAC Evidence TICAGRELOR RIVAROXABAN APIXABAN DABIGATRAN EDOXABAN Antithrombotic Drug Removal: Status Benchtop | In vitro >90% >90% -- >90% >90% Human PK/PD + + -- -- -- Clinical Evidence √ √ -- -- -- EU | US √ | BD √ | -- -- | -- -- | -- -- | --
Slide 14: Today's Agenda & Speakers
Today’s Agenda & Speakers Speaker Title Time Phillip Chan Welcome & Opening Remarks 5 min Makis Deliargyris Introduction of Agenda & Speakers 5 min Robert Storey Ticagrelor and CytoSorb 15 min Intraoperative removal of Ticagrelor and Rivaroxaban Michael Schmoeckel 15 min during Emergency Cardiac Ope
Slide 15: Antithrombotic Removal
Antithrombotic Removal - Unmet clinical need - Clinical evidence with CytoSorb - Size of the addressable market
Slide 16: Ticagrelor and CytoSorb
Ticagrelor and CytoSorb Professor Robert Storey, BSc, BM, DM, FRCP, FESC Professor of Cardiology and Cardiovascular Disease Theme Lead, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield and Academic Director and Honorary Consultant Cardiologist, Cardiology and Car
Slide 17: Ticagrelor: first oral reversibly-binding P2Y12 antagonist
Ticagrelor: the first oral reversibly-binding P2Y12 receptor antagonist belonging to the class CPTP (cyclo-pentyl-triazolo-pyrimidine) HO Chiral N N N HO H N F O N N F S OH van Giezen JJJ, Humphries RG. Semin Thromb Hemost. 2005;31:195-204.
Slide 18: ONSET/OFFSET Study: inhibition of platelet aggregation
ONSET/OFFSET Study: inhibition of platelet aggregation 100 Ticagrelor 180mg LD / Ticagrelor 90 mg bd (n=54) 90 * * * * * † Clopidogrel 600mg LD / 75 mg od (n=50) * * 80 70 * 60 Clopidogrel IPA % 50 * 40 ‡ 30 † 20 10 0 0 0.5 1 2 4 8 24 6 weeks 0 2 4 8 24 48 72 120 168 240 Onset Maintenance O
Slide 19: PLATO Platelet: VerifyNow P2Y12 Assay
PLATO PLATELET: VerifyNow P2Y12 Assay Comparing Maintenance Therapy with Clopidogrel vs Ticagrelor in ACS 500 **** **** Platelet Reaction Units 400 300 235 PRU 200 100 0 Clopidogrel Ticagrelor Clopidogrel Ticagrelor Trough Peak ***P<0.0001; PRU = Platelet reaction units. Storey RF, et al. J Am Coll
Slide 20: PLATO Secondary efficacy endpoints
PLATO Secondary efficacy endpoints Myocardial infarction Cardiovascular death 7 6.9 7 Clopidogrel Cumulative incidence (%) Cumulative incidence (%) 6 6 5.8 5 5 Clopidogrel 5.1 Ticagrelor 90mg bd 4 4 4.0 3 3 Ticagrelor 90mg bd 2 2 1 1 HR 0.84 (95% CI 0.75–0.95), p=0.005 HR 0.79 (95% CI 0.69–0.91), p=
Slide 21: UK networks for ACS and revascularisation
UK networks for ACS and revascularisation South Yorkshire Cardiothoracic Centre Provides a PCI and CABG surgery service including 24/7 primary PCI to the South Yorkshire and North Derbyshire regions of England – a population of 1.8 million people
Slide 22: Sheffield observational study
Sheffield observational study 10,793 consecutive invasively-managed ACS patients NSTE-ACS Clopidogrel Ticagrelor (90mg) Prasugrel STEMI Ticagrelor (90mg) Prasugrel Clopidogrel 2009 2010 2011 2012 2013 2014 2015 Iqbal J et al. Presented at AHA 2014; Gosling R et al. Platelets 2017 online
Slide 23: Sheffield observational study
Sheffield observational study Adjusted definite stent thrombosis rates Gosling R et al. Platelets 2017
Slide 24: BCIS National Audit Adult Interventional Procedures
TI '*TC SS JIU LAD BCIS National Audit Adult Interventional Procedures 1st April 2018 to 31st March 2019
Slide 25: PCI by Indication and Clinical Syndrome
25-10-2019 80 70 60 50 % PCI Performed by 40 Indication 30 20 10 Clinical Syndrome 2nnTte. SDOUINn& 2018-19 data J 67 -e-Stable | 33,2 Acute 2 OG bh BD O WNW DV Aw ne G6 B OB SHS HHK HSS HP HS PS He
Slide 26: Ticagrelor Use by Indication for PCI
2018-19 data Ticagrelor Use by Indication for PCI 49.1 m2012 62013 m2014 m2015 = 2016 @2017-18 42018-19 % of Procedures F il Stable NSTEMI/UA_ PCI for STEMI
Slide 27: Isolated CABG surgery: elective vs. urgent
Isolated CABG surgery: elective vs. urgent Mean time waiting for urgent CABG in 2017/18 was 10 days in the UK (no change from 2016/17) Proportion treated within 7 days = 34% Only 4 hospitals managed to treat >50% within 7 days
Slide 28: PLATO: chest tube drainage according to time after drug intake
PLATO: chest tube drainage according to time after drug intake Held C et al. J Am Coll Cardiol 2011
Slide 29: PLATO: fall in hemoglobin according to time after drug intake
PLATO: fall in hemoglobin >50g/L according to time after drug intake Held C et al. J Am Coll Cardiol 2011
Slide 30: Offset of ticagrelor's effects in ACS patients
Offset of ticagrelor’s effects in ACS patients Ow K, Storey RF et al. Platelets 2020
Slide 31: Expert position paper on antiplatelet therapy in CABG surgery
@ European Heart Journal CURRENT OPINION doi:10,1093/eurheartehut 58 Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery Miguel Sousa-Uva"?, Robert Storey?, Kurt Huber‘, Volkmar Falk, Adeline Leite-Moreira®’, Julien Amour®, Naww
Slide 32: Angheloiu GO et al. JACC Basic Trans Sci 2017
Angheloiu GO et al. JACC Basic Trans Sci 2017
Slide 33: Ticagrelor removal by CytoSorb reduces morbidity: economic model
Ticagrelor removal by CytoSorb® is associated with reduced morbidity in patients who require emergent or urgent cardiac surgery: An economic model with implications for hospital resource utilisation in the UK M. Javanbakht1, K. Rahimi2, F. Degener3, D. Adam3, F. Preissing3, J. Scheier4, SF. Cook5, E
Slide 34: Methods
Methods • A de novo decision analytic model was developed to estimate resource utilisation in each strategy (CytoSorb vs. usual care) over a 30-day time horizon • Primary clinical inputs were those that might have significant impact on hospital care resource utilisation, including: – bleeding compli
Slide 35: Results: Emergent Cardiac Surgery (Cohort 1)
Results: Emergent Cardiac Surgery (Cohort 1) • CytoSorb use resulted in fewer blood product transfusions, fewer re-thoracotomies, shorter operation time, and shorter ICU/hospital length of stay • Patients treated with CytoSorb incurred lower total cost (-£3,982) and had better health-related quality
Slide 36: Results: Urgent Cardiac Surgery (Cohort 2)
Results: Urgent Cardiac Surgery (Cohort 2) • In urgent CABG, CytoSorb was less costly (-£55) and more effective when compared to waiting for 5 days to allow for physiological washout of ticagrelor to reduce bleeding risk • In all 3 comparators, waiting alone, waiting plus short acting antiplatelet a
Slide 37: Ticagrelor CytoSorb Hemoadsorption (TISORB) study
Ticagrelor CytoSorb Hemoadsorption (TISORB) study UK prospective, multi-center study in patients undergoing cardiac surgery <48 hours since last dose of ticagrelor 8 Sites
Slide 38: TISORB patient journey
TISORB patient journey: Surgery 48 hrs after last ticagrelor dose Study Enrollment completion Screening Pre-CPB Operation Post-CBP Follow up Post-Operation Phase Phase Phase Phase Phase Visit Bounded by the Period within Period of the Period from the end From admission to the ICU Patients will hav
Slide 39: TISORB primary effectiveness endpoint
TISORB primary effectiveness endpoint intra-op ticagrelor removal from blood by CytoSorb [ticagrelor]Blood pre-op [ticagrelor]Blood post-op Pharmacodynamic compare Pharmacodynamic end point: end point: ADPtest on MEA ADPtest on MEA HYPOTHESIS : < 22 U > 22 U
Slide 40: Summary
Summary • Acute coronary syndromes (ACS) have become the dominant reason for revascularization over the last decade • Dual antiplatelet therapy with aspirin and ticagrelor is first-line therapy for ACS patients and has dramatically cut stent thrombosis rates in PCI patients • Level of platelet P2Y12
Slide 41: Intraoperative removal of Ticagrelor and Rivaroxaban during Emergency Cardiac Operations
Intraoperative removal of Ticagrelor and Rivaroxaban during Emergency Cardiac Operations Prof. Dr. med. Michael Schmoeckel Head Dept. of Cardiac Surgery AK St. Georg, Hamburg, Germany
Slide 42: Perioperative management of NOACs
Perioperative management of NOACs • Apixaban (Eliquis) discontinue apixaban 24 to 48 hours prior to surgery depending on the bleeding risk. • Dabigatran (Pradaxa) high bleeding risk procedures or surgeries: to be discontinued 48–72 hours before. in renal impairment: 72–96 hours before. • Rivaroxaban
Slide 43: Drainage volume (ml)
Drainage volume (ml) : 400 * 300 - 0 2 4 6 8 10 12 Withdrawal period of NOAC (days) wny unuciem Upcimieant vperauuns at yur uutuuU between July 2014 and June 2016. All patients presented for surgery while on NOAC therapy: 37 received rivar- oxaban (45.7%), 35 apixaban (43.2%), and 9 dabigatran (11.1
Slide 44: Evolution of PCI in Germany
Evolution of PCI in Germany DGK/DGTHG, Deutscher Herzbericht 2017
Slide 45: Evolution of antiplatelet therapy after PCI
Evolution of antiplatelet therapy after PCI ESC Guidelines 2017
Slide 46: 2017 ESC Guidelines for STEMI patients
2017 ESC Guidelines for STEMI patients Eur Heart J 2018; 39:119-77
Slide 47: CABG-related bleeding complications with ticagrelor or clopidogrel
European Heart Journal (2016) 37, 189-197 FASTTRACK caroreay — doi:10.1093/eurheart/ehv381 ESC Clinical Registry s ae g Zz Coronary artery bypass grafting-related bleeding Sexy 139° complications in patients treated with ticagrelor or clopidogrel: a nationwide study Emma C. Hansson’, Lena Jidéus?, B
Slide 48: Ticagrelor removal over time and recirculation
…after 10 hours, and 94% after 3-4 hours recirculation MIT Cambridge, MA, USA & Astra Zeneca
Slide 49: Hypothesis
Hypothesis Platelet transfusion is not a definitive solution because of circulating Ticagrelor binding to transfused platelets. Using adsorber technology may reduce bleeding complications in patients treated with Ticagrelor. Similar effects may be expected in patients treated with NOACs
Slide 50: Study design (n = 55)
Study design (n = 55) Single centre prospective cohort study Patients who underwent emergency cardiac surgery at our institution between June 2016 and June 2018 with preoperative treatment of ticagrelor (n = 43) or rivaroxaban (n = 12). Since April 2017 (JACC paper) we routinely installed stan
Slide 51: Intraoperative setting
Intraoperative setting Hassan K et al. Ann Thorac Surg 2019;108:45-51
Slide 52: Single center prospective cohort study
Single center prospective cohort study Emergency open-heart surgery June 2016 – June 2018; n=217 n=55 (25.3%) n=162 (74.7%) Operations under Ticagrelor (n=43) Operations without previous Ticagrelor or Rivaroxaban (n=12) or Rivaroxaban therapy since 04/2017 until 04/2017 Cytosorb adsorption Cytosorb
Slide 53: Preoperative data I
Preoperative data I Cytosorb Cytosorb Control Control Ticagrelor Rivaroxaban Ticagrelor Rivaroxaban Demography (n=32) (n=7) (n=11) (n=5) p value age (y) 66 77 69 72 .33 female (%) 19 57 18 20 .22 BMI (kg/m2) 27 26 27 27 .79 NYHA class (%) II 56 57 36 60 III 38 43 64 40 IV 6 0 0 0 Comorbidities (%) h
Slide 54: Preoperative data II
Preoperative data II Cytosorb Cytosorb Control Control Ticagrelor Rivaroxaban Ticagrelor Rivaroxaban (n=32) (n=7) (n=11) (n=5) p value LVEF (%) .73 good (>50%) 47 57 36 40 moderate (31-50%) 47 14 64 40 poor (<30%) 6 29 0 20 Pathology (%) coronary artery dis. 100 100 100 100 aortic valve disease 9 -
Slide 55: Results
Results Cytosorb Cytosorb Control Control Ticagrelor Rivaroxaban Ticagrelor Rivaroxaban (n=32) (n=7) (n=11) (n=5) p value Surgical procedure CABG 84 100 91 100 CABG + AVR 9 CABG + MVR 3 9 Aortic replacement 3 Concomitant surgery Afib ablation 9 43 9 40 LAA occlusion 6 14 9 40 Time-related outcome CP
Slide 56: Bleeding / Length of stay
Bleeding / Length of stay Cytosorb Cytosorb Control Control Ticagrelor Rivaroxaban Ticagrelor Rivaroxaban (n=32) (n=7) (n=11) (n=5) p value Rethoracotomy 0 0 36 40 .0003 Drainage volume (24hrs) 350 390 890 600 .004 Days in ICU 2 2 3 6 .01 Total length of stay (days) 11 11 14 18 .02 Hassan K et al. A
Slide 57: Postoperative drainage volume
Postoperative drainage volume p = 0.004 Hassan K et al. Ann Thorac Surg 2019;108:45-51
Slide 58: Summary
Summary Serr 198 Emergency open-heart surgery June 2016 —June 2018; n=217 n=162 (74.7%) n=55 (25.3%) y U | Cytosorb adsorption | Cytosorb adsorption No Cytosorb adsorption of Rivaroxaban n=5 No Cytosorb adsorption of Ticagrelor n=11 of Ticagrelor n=32 of Rivaroxaban n=7 L L ----0.0037 ---- Drainage
Slide 59: Conclusions
Conclusions Both medical and economic benefits of using Cytosorb in Ticagrelor- and Rivaroxaban-loaded patients: reduced operation time decreased use of blood products saves costs by faster discharge of patients from ICU The data show that the strategy is a safe and effective method to reduc
Slide 60: The story continues…
The story continues… Cytosorb Cytosorb Ticagrelor Ticagrelor (n=32) (n=61) Rethoracotomy 0 1 (1.6%) Drainage volume/ 24hrs 420 ± 246 487 ± 222 Days in intensive care 3±2 2±3 Total length of stay 12 ± 7 12 ± 5 30-days-mortality, n (%) 0 1 (1.6%) Transfusion of platelets 11 (34.4%) 20 (32.8%) Transfus
Slide 61: Alternatives: Ticagrelor / NOAC antidots
Alternatives: Ticagrelor / NOAC antidots PB2452 for Ticagrelor (PhaseBio Pharma. Inc.) monoclonal ab, phase I (2019) Idarucizumab (Praxbind) for Dabigatran 5g (100ml) US$ 8,385.20 Andexanet alfa (Ondexxya) for Apixaban, Rivaroxaban US$ 2,873.38/ 100 mg vial low dose: 400 mg bolus + 480 mg iv total U
Slide 62: Clinical perspective
Clinical perspective Standard procedure: Cytosorb adsorption in all ticagrelor and/or NOAC-loaded patients during emergency cardiac surgery
Slide 63: Thank you for your attention!
Thank you for your attention ! [email protected]
Slide 64: NOACs and CytoSorb
NOACs and CytoSorb C. Michael Gibson, M.S., M.D. Interventional Cardiologist Professor of Medicine Harvard Medical School President & CEO of Non-Profit Baim Institute Founder, Editor-In-Chief www.wikidoc.org Baim Harvard Medical Institute School
Slide 65: Disclosure
Disclosure • Dr. Gibson has received research grant support and consulting fees in the past from all major manufacturers of antiplatelets and antithrombins • This is an educational lecture and is not intended to be an inducement to use any drug or drug in a fashion that is inconsistent with the drug
Slide 66: Disclosures
Disclosures Present Research/Grant Funding Consultant Angel Medical Corporation Janssen/Johnson & Johnson (with monies paid to hospital) CSL Behring Bayer Corporation SCAD Alliance Baim Institute Janssen Pharmaceuticals Patents and Stocks: None Spouse: Employee of Boston Clinical Research Institute
Slide 67: Indications for NOAC
Indications for NOAC • Atrial fibrillation • Surgical VTE prophylaxis (knee and hip surgery) • Medically ill VTE prophylaxis • VTE treatment (DVT and PE) • Acute coronary syndrome (Ex US)
Slide 68: Atrial Fibrillation Prevalence Continues to Grow
Atrial Fibrillation Prevalence Continues to Grow • Atrial fibrillation prevalence is substantial and expected to grow. 18 15.9 16 Continued increase in incidence 14.3 14 Patients With AF (Millions) 11.7 12 No further increase in incidence 12.1 10 8.9 11.1 8 9.4 6.7 7.5 6 5.1 6.1 5.1 4 2 0 2000 2010
Slide 69: Atrial Fibrillation Prevalence Increases with Age
Atrial Fibrillation Prevalence Increases with Age • Atrial fibrillation prevalence increases with age. 80 70 68.9 Patients With AF (% per 1000 PTY) 60 53.5 50 40 38.3 30 28.8 20 18.8 12.9 10 0 67- 69 70- 74 75-79 80- 84 85- 89 ≥90 Age Slides by C. Michael Gibson Circ Cardiovasc Qual Outcomes. 2012;5
Slide 70: NOAC in Atrial Fibrillation
NOAC in Atrial Fibrillation Risk Ratio (95% CI) Ischemic Stroke 0.92 (0.83 - 1.02) p=0.10 Hemorrhagic Stroke 0.49 (0.38 - 0.64) p<0.0001 Myocardial Infarction 0.97 (0.78 - 1.20) p=0.77 All-Cause Mortality 0.90 (0.85 - 0.95) p=0.0003 0.2 0.5 1 2 Favors NOAC Favors Warfarin Heterogeneity p=NS for all
Slide 71: NOAC in Atrial Fibrillation: Major Bleeding
NOAC in Atrial Fibrillation Major Bleeding Risk Ratio (95% CI) RE-LY 0.94 (0.82 - 1.07) [150 mg] ROCKET AF 1.03 (0.90 - 1.18) ARISTOTLE 0.71 (0.61 - 0.81) ENGAGE AF-TIMI 48 0.80 (0.71 - 0.90) [60 mg] Combined 0.86 (0.73 - 1.00) [Random Effects Model] p=0.06 N=58,498 0.5 Favors NOAC 1 Favors Warfarin
Slide 72: NOAC Are the Standard of Care For VTE and Atrial Fibrillation
NOAC Are the Standard of Care For Venous Thromboembolism and Atrial Fibrillation 1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-52. 2. Ansell J. Universal, class-specific and drug-specific reversal ag
Slide 73: Anticoagulants market forecast
https://www.prnewswire.com/news-releases/anticoagulants-market-to-be-worth-us-40-158-4-million-by-2026--says-tmr-300843446.html
Slide 74: ED Visits for ADEs By Drug Class (2005-2014)
ED Visits for ADEs By Drug Class (2005-2014) ED Visits National Estimate, % (95% CI) Drug Class 2005-2006 2007-2008 2009-2010 2011-2012 2013-2014 Antibiotics 19.2 (17.7-20.7) 18.6 (16.8-20.4) 18.6 (16.7-20.6) 17.9 (16.6-19.3) 16.1 (14.4-17.8) Anticoagulants 7.3 (4.6-9.9) 9.9 (7.6-12.2) 11.2 (8.2-14.
Slide 75: Increased Morbidity and Mortality in Patients Admitted on a NOAC
Increased Morbidity and Mortality in Patients Admitted on a NOAC As Compared to Non-Anticoagulated Patients 5 4.5 Cost of Major Bleeding: 4 - Top 15% > $100K to treat3 3.5 - Mean ~$50,0004 4X 3 Higher 2.5 2 1.5 2X 1 Higher 1.25X 0.5 Longer 0 Mortality Readmissions LOS 1. Truven, MarketScan Commercia
Slide 76: Management for Patients on NOAC Today
Management for Patients on NOAC Today Treatment for Life-Threatening NOAC Bleeding Pradaxa® Praxbind (dabigatran) (idarucizumab) Xarelto® (rivaroxaban) Eliquis® Andexxa (apixaban) (andexanet alfa) Savaysa® (edoxaban) 1. Praxbind® prescribing information. Ridgefield, CT. Boehringer Ingelheim Pharmace
Slide 77: Andexanet Limitations
Andexanet Limitations • Approved for reversal of ongoing life threatening bleeding • NOT approved for reversal in a patient with no bleeding who is to undergo surgery • Numeric excess of thrombotic events following reversal • Cost
Slide 78: Management for Patients on NOAC in the Future
Management for Patients on NOAC in the Future Treatment for NOAC Prevention of Bleeding Life-Threatening Bleeding Pradaxa® Praxbind (dabigatran) (idarucizumab) Xarelto® (rivaroxaban) CytoSorb® Eliquis® Andexxa (apixaban) (andexanet alfa) Savaysa® (edoxaban)
Slide 79: Preventing Bleeding in Cardiac Surgery
Preventing Bleeding in Cardiac Surgery Hassan K et al. Ann Thorac Surg 2019;108:45-51
Slide 80: Cardiac Surgery vs. Non-Cardiac Surgery
Cardiac Surgery vs. Non-Cardiac Surgery 40 NCS EP CS 31.7 30 27.3 22.3 % of 16.3 20 patients 9.1 10 5.1 1.6 3.8 4.3 4.7 3.3 2.2 2.7 1.3 3.4 3.7 4.0 2.1 2.6 3.1 0 0.8 0.1 6 12 24 36 48 60 Months Saia F., et al. Surgery after Stent. Circulation CV Qual Outcomes 2016.
Slide 81: In-vitro Removal of Rivaroxaban by CytoSorb
In-vitro Removal of Rivaroxaban by CytoSorb “Within 1 hour 91.6% of circulating rivaroxaban was removed.” “For normal therapeutic concentrations below 300 μg/L, we expect plasma concentration to be reduced below the critical threshold in 30 to 60 minutes.” Koertge A et al. Extracorporeal Hemoperfusi
Slide 82: Ticagrelor + Rivaroxaban Removal off-pump
Ticagrelor + Rivaroxaban Removal off-pump 58 y/o male, high bleeding risk, undergoing urgent OPCAB • PCI - dissected LAD. On aspirin, ticagrelor, rivaroxaban (Afib) • Ongoing chest pain, (+) TnI • Urgent OPCAB recommended • Cytosorb started 1 hour prior to surgery and continued for 1.5 h into CABG •
Slide 83: In-vitro Removal of Dabigatran by CytoSorb
In-vitro Removal of Dabigatran by CytoSorb 1 0.98 Removal rate (%) 0.96 “Dabigatran is robustly removed by a sorbent hemadsorption 0.94 method already proven successful for ticagrelor. Dabigatran removal 0.92 restores the aPTT, suggesting reversal of the anticoagulant effect 0.9 10 mL 20 mL 40 mL of
Slide 84: In-vitro Removal of Edoxaban by CytoSorb
In-vitro Removal of Edoxaban by CytoSorb 600 99.5% (30 min) Edoxaban concentration (ng/mL 500 400 “Sorbent-mediated technology 300 may represent a viable 200 pathway for edoxaban removal from human plasma.” 100 0 Before After Angheloiu AA et al. Drugs in R&D 2020 May 15. doi: 10.1007/s40268-020-0030
Slide 85: Hospital-wide Applications
Hospital-wide Applications • Off-pump cardiac surgery • Cardiac electrophysiology procedures • Neurosurgical procedures Reduce risk of life-threatening bleeding Avoid surgery (subdural hematomas) • Acute stroke (NOAC = contraindication for t-PA) • Urgent orthopedic procedures • Urgent GI or onco
Slide 86: Summary: NOAC and CytoSorb
Summary: NOAC and CytoSorb • NOAC are the standard of care for chronic anticoagulation (Afib, VTE, etc.) • Aging of the population will only increase use • Patients on NOAC present unique challenges in the hospital setting due to bleeding risk • CytoSorb® is the only strategy that can prevent bleedi
Slide 87: Closing Remarks
Closing Remarks Efthymios N. Deliargyris, MD, FACC, FESC, FSCAI Chief Medical Officer CytoSorbents Corporation 87
Slide 88: Regulatory Status & Clinical Activities
Regulatory Status & Clinical Activities European Union • CytoSorb is CE Mark label approved for ticagrelor and rivaroxaban removal USA • Ticagrelor removal granted FDA Breakthrough Designation • Ongoing discussions with FDA to set regulatory pathway Study Design Region Start TISORB Q3 ’20 Prospectiv
Slide 89: Total Addressable Market For Ticagrelor Removal
Total Addressable Market For Ticagrelor Removal United States US Addressable Market Today Ticagrelor ~50,000 Surgeries Pre-treated Patients ($ 250M TAM)* (~50%) P2Y12 Pre-treated ~100,000 Surgeries ($500M TAM)* Patients (~65%) (92,000 CABG and 8,000 AA) Urgent/Emergent Surgeries (~40%) ~154,000 Surg
Slide 90: US Market – Sequential Growth
US Market – Sequential Growth TICAGRELOR + NOAC All surgery $1.5B TICAGRELOR + NOAC Cardiac surgery $500M TICAGRELOR Cardiac surgery $250M (Today)
Slide 91: Final Thoughts
Final Thoughts • Antithrombotic drug removal with CytoSorb is a novel solution to a very large unmet hospital need • Currently no available therapies to prevent bleeding • Andexxa® or PB2452 (not yet approved) intended only for use after life-threatening bleeding • CytoSorb antithrombotic removal in