Slide 1: Investor Presentation June 2012
Cyto Sorbents Investor Presentation June 2012 OTCBB: CTSO Cyto Sorbents Corporation Working to Save Lives Through Blood Purification
Slide 2: Safe Harbor Statement
Cyto Sorbents 2 Safe Harbor Statement Statements in this presentation regarding CytoSorbents Corporation and its operating subsidiary CytoSorbents, Inc that are not historical facts are forward - looking statements and are subject to risks and uncertainties that could cause actual future events or r
Slide 3: CytoSorbents Overview
Cyto Sorbents 3 Cyto Sorbents Overview Cyto Sorbents is a publicly - traded, critical care - focused device company using blood purification to treat disease, with its first European Union approved product, Cyto Sorb ® The goal of Cyto Sorb ® is to modulate the immune response to prevent or treat or
Slide 4: CytoSorb approved in the EU: key highlights
Cyto Sorbents 4 • CytoSorb ® is is now approved for use in the European Union as a first - in - class cytokine filter, clinically proven to reduce “cytokine storm” in patients with septic shock, one of the biggest killers in the intensive care unit • This reduction in “cytokine storm” led to a stati
Slide 5: Management Team
Cyto Sorbents 5 Management Team • Phillip Chan, MD, PhD – Chief Executive Officer and President Board - certified internal medicine physician. MD/PhD from Yale School of Medicine. Internal Medicine residency at the Beth Israel Deaconess Medical Center at Harvard. Former Partner at NJTC Venture Fund
Slide 6: Medical Advisory Board
Cyto Sorbents 6 Medical Advisory Board John Kellum, MD Professor of Critical Care Medicine & Anesthesiology University of Pittsburgh Medical Center Chair of the Sepsis Advisory Board Emil Paganini, MD Former Section Head of Dialysis and Extracorporeal Therapy Cleveland Clinic Foundation Joseph Parri
Slide 7: Technology Overview
Cyto Sorbents 7 Technology Overview The heart of the technology is a biocompatible, highly porous, polymer bead that can remove a wide range of toxic substances from blood and fluids based on pore capture and surface adsorption
Slide 8: Beads Can Be Used In Many Forms
Cyto Sorbents 8 Beads Can Be Used In Many Forms Hemoperfusion “Beads in a Bag” In - line Filter
Slide 9: CytoSorb: Modulating the Immune System to Prevent or Treat Organ Failure
Cyto Sorbents Cyto Sorb ® Modulating the Immune System to Prevent or Treat Organ Failure
Slide 10: Critical Care Is a Big Market in Need
Cyto Sorbents 10 Critical Care Is a Big Market in Need • Intensive care unit (ICU) expenses account for ~20% of a hospital’s budget • ICU care is the highest level of medical care and costs ~$2,000 per patient daily • In 2005, $82 billion was spent treating critically ill patients in the US or 0.7%
Slide 11: Organ Failure is the Top Cause of Death
Cyto Sorbents 11 Organ Failure is the Top Cause of Death Organ Failure occurs when vital organs stop working. It is the leading cause of death in the intensive care unit.
Slide 12: Little to Prevent or Treat Organ Failure
Cyto Sorbents 12 Little to Prevent or Treat Organ Failure • Multiple Organ Dysfunction Syndrome (MODS) and Multi - organ Failure are common in the ICU • Most of the therapies in the ICU are supportive care therapies that help keep a patient alive, but do not prevent or treat organ failure • Mechanic
Slide 13: CytoSorb Is Our Answer to the Problem
Cyto Sorbents 13 Cyto Sorb ® Is Our Answer to the Problem Cyto Sorb ® is the cornerstone of our critical care strategy. It is now approved for sale in the European Union as an Extracorporeal Cytokine Filter to be used whenever cytokines are elevated
Slide 14: Clinically Proven to Reduce Cytokine Storm
Cyto Sorbents 14 Clinically Proven to Reduce Cytokine Storm Cyto Sorb ® is clinically proven to safely reduce the excessive production of cytokines, or “cytokine storm”, triggered by critical illnesses that could otherwise lead to a systemic inflammatory response (SIRS) • Left unchecked, this worsen
Slide 15: CytoSorb is Elegant and Easy to Use
Cyto Sorbents 15 • Obtain venous access with temporary dialysis catheter • Pump blood through the cartridge using standard dialysis machines found in most hospitals • The polymer beads remove cytokines • “Purified” blood is pumped back into the patient • Can treat 20 - 30 total blood volumes per 6 h
Slide 16: CytoSorb Is Active in Cytokine Sweet Spot
Cyto Sorbents Cyto Sorb Is Active in Cytokine Sweet Spot Hemodialysis 0 kDa 10 20 30 40 50 60 70 IL - 1 b, IL - 1 a TNF - α monomer IFN - γ monomer IL - 1Ra IL - 10 TNF - α trimer IFN - γ dimer HMGB1 TGF - β IL - 6 sFas ligand MCP - 1 IL - 13 MCP - 1 glycosylated Albumin IL - 8 MIP - 1α IL - 18 sTNF
Slide 17: CytoSorb Broadly Reduces Cytokines
Cyto Sorbents Cyto Sorb Broadly Reduces Cytokines IL - 6 TNF - a IL - 10 IL - 1 a IL - 1ra IL - 8 Cytokine reduction over time during in vitro perfusion with serum (or buffer) Valenti, I “Characterization of a Novel Sorbent Polymer for the Treatment of Sepsis” 2008 17
Slide 18: Why is the Reduction of Cytokines by a Cytokine Filter Important?
Cyto Sorbents Why is the Reduction of Cytokines by a Cytokine Filter Important?
Slide 19: Cytokines: A Dual-Edged Sword
Cyto Sorbents 19 Cytokines: A Dual - Edged Sword • Cytokines are small proteins that, in moderation, normally help stimulate and regulate the immune system. They are required for proper immune system function • However, in mild to moderate excess, cytokines can cause or exacerbate disease (e.g. auto
Slide 20: You Have Had a Mini Cytokine Storm
Cyto Sorbents 20 You Have Had a “Mini Cytokine Storm” Influenza is a simple example of an infection that triggers the body’s immune system and induces a mild cytokine storm causing a systemic inflammatory response syndrome (SIRS) Common symptoms: • High fever • Overwhelming fatigue and weakness • Se
Slide 21: Cytokine Storm Is Common in the ICU
Cyto Sorbents 21 Cytokine Storm Is Common in the ICU Cytokine Storm Infection ARDS Burns Trauma Surgery Pancreatitis Influenza The difference is that this cytokine storm is severe and deadly
Slide 22: Cytokine Storm Causes Direct Organ Injury
Cyto Sorbents 22 Shock Clotting Cytokine Storm Causes Direct Organ Injury Cytokine Storm Inflammation, Organ Failure and Infection Lung Injury Cell Death Renal Failure Immune Paralysis
Slide 23: Cytokine Storm Also Causes Immune Confusion
Cyto Sorbents 23 Cytokine Storm Also Causes “Immune Confusion” An injury or infection usually leads to the local production of cytokines. Normally, these cytokines allow white blood cells to home in on the infection and migrate from the blood stream into the affected area. Blood Vessel (blood flow )
Slide 24: But Cytokine Storm Masks the Injury Site
Cyto Sorbents 24 But Cytokine Storm Masks the Injury Site Cytokine Storm Cytokine Storm makes the entire body looks inflamed, injured and infected
Slide 25: Result: Cytokine and Cell-Mediated Organ Injury
Cyto Sorbents 25 Result: Cytokine and Cell - Mediated Organ Injury This leads to “Immune Confusion” and widespread inflammation with white blood cells infiltrating and damaging innocent bystander organs causing organ damage/failure
Slide 26: Cytokine Storm in Action
Cyto Sorbents 26 Cytokine Storm in Action TeGenero Anti - CD28 monoclonal antibody Phase I Trial • Designed to stimulate the immune system to treat cancer • Phase I safety trial (2006) – 6 healthy adult males • 90 minutes: All had a systemic inflammatory response Headache, nausea, muscle pain, diarr
Slide 27: Treating Cytokine Storm – The Holy Grail
Cyto Sorbents 27 Treating Cytokine Storm – The Holy Grail Reduction in Cytokine Storm has been the target of the industry for three decades • Unfortunately, most drugs and biologics can only reduce a single cytokine or inflammatory mediator • Too much redundancy in the immune system for this strateg
Slide 28: CytoSorb: Sepsis and Infection
Cyto Sorbents Cyto Sorb ® Sepsis and Infection: A Classic Example of Cytokine Injury and Multiple Organ Failure
Slide 29: Sepsis is a Worldwide Crisis
Cyto Sorbents Sepsis is a Worldwide Crisis Sepsis is the result of an overzealous immune response to infection driven by “cytokine storm” • Top 10 killer afflicting 18 million people worldwide every year • Incidence of sepsis doubled in the past 10 years and is increasing • Severe sepsis kills 1 in
Slide 30: Costs of Treatment Are Enormous
Cyto Sorbents Costs of Treatment Are Enormous Without adequate therapies, the treatment of sepsis is costly • 10 - 20% of all admissions to the ICU are for sepsis • Average cost of treating a septic patient in the ICU is ~$2000 - 3000 per day in both the United States and European Union • Average le
Slide 31: Standard of Care is Inadequate
Cyto Sorbents Standard of Care is Inadequate Standard of care therapy • Antibiotics • Fluids • Nutrition • Medications • Supportive care therapies • Vasopressors for hemodynamic instability • Oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) for respiratory failure • Rena
Slide 32: Sepsis has two facets but only one is treated
Cyto Sorbents Time (days to weeks) Sepsis has two facets but only one is treated Pro - Inflammatory Anti - inflammatory Organ Failure Death Recovery TOXIC Cytokine Storm The infectious insult can be treated with antibiotics/antivirals, but there are currently no therapies to treat the immune respons
Slide 33: CytoSorb Can Fight Cytokine Storm
Cyto Sorbents Antibiotics Cyto Sorb Can Fight Cytokine Storm TOXIC Organ Damage Time Recovery Cyto Sorb 33
Slide 34: CytoSorb Pre-Clinical Animal Data
Cyto Sorbents Cyto Sorb ® Pre - Clinical Animal Data
Slide 35: CytoSorb Has Strong Animal Data
Cyto Sorbents Cyto Sorb Has Strong Animal Data Cyto Sorb animal models simulating sepsis from a ruptured appendix* with no antibiotics and only a single 3 - hour treatment … Increased survival to 65% (treated) from 12.5% (sham), p<0.01 * Cecal ligation puncture (CLP): 20 hours after CLP, rats were t
Slide 36: ...and reduction of cytokines
Cyto Sorbents … and reduction of cytokines 20 hours after CLP, rats were treated for 3 hours with either CytoSorb or sham. Treatment was discontinued and cytokine values were taken again 6 hours after the end of treatment, p<0.05 Peng, ZY, Carter, MJ, Kellum, JA “Effects of hemoadsorption on cytokin
Slide 37: ...with prevention of shock
Cyto Sorbents … with prevention of shock Peng, ZY, Carter, MJ, Kellum, JA “Effects of hemoadsorptionon cytokine removal and short term survival in rats” Crit Care Med (2008) 36(5): 1573 - 7 Effects of hemoadsorption on mean arterial pressure (MAP) (Mean +/ - SEM, mm Hg) in the CLP rat sepsis model.
Slide 38: CytoSorb May Also Decrease Cytokine Production
Cyto Sorbents Cyto Sorb May Also Decrease Production Endotoxin Challenge Model NF - k B activity in the livers of CytoSorb or sham - treated animals following 4 hours of treatment as determined by nuclear extract and electrophoretic mobility shift assay. Mean data from 12 animals (p<0.05). CytoSorb
Slide 39: CytoSorb Also Reduces Immune Confusion
Cyto Sorbents 39 Cyto Sorb Also Reduces “Immune Confusion” Cyto Sorb Cyto Sorb treatment also helps to “unmask” the true site of infection, allowing better white blood cell targeting and improved bacterial clearance at the site of infection, while preventing indiscriminate cell - mediated organ inju
Slide 40: CytoSorb Human Clinical Data
Cyto Sorbents Cyto Sorb ® Human Clinical Data
Slide 41: CytoSorb European Sepsis Trial
Cyto Sorbents 41 Cyto Sorb European Sepsis Trial Randomized, controlled clinical trial in 43 patients with predominantly septic shock and respiratory failure • Compared Standard of Care (SOC) therapy alone versus SOC therapy plus Cyto Sorb treatment • Patients had a very high risk of death • All had
Slide 42: Treatment was Safe
Cyto Sorbents 42 Treatment was Safe • No serious device related adverse events in more 300 treatments in septic patients in the trial, increasing the total number of safely administered human Cyto Sorb treatments to more than 650 • Treatment was well - tolerated by patients First Do No Harm Cyto Sor
Slide 43: CytoSorb Broadly Reduces Cytokines
Cyto Sorbents Achieved statistically significant 30 - 50% reduction in key cytokines across the 7 - day treatment period. 49.1% reduction p=0.01* 49.5% reduction p=0.002 36.5% reduction p=0.001 30.2% reduction p=0.002 Cyto Sorb ® Broadly Reduces Cytokines N = 43 (18 treatment; 25 control) *interim a
Slide 44: Who Benefits Most from Cytokine Reduction?
Cyto Sorbents Who Benefits Most from Cytokine Reduction? 44 There were two sub - groups that were of great interest • Patients with very high cytokine levels • Based on literature and our hypothesis, those with very high cytokines have very severe disease and are at highest risk of multi - organ fai
Slide 45: Patients with Very High Cytokine Levels
Cyto Sorbents Patients with Very High Cytokine Levels
Slide 46: Treatment Reduced Need for Ventilation in Patients with High Cytokine Levels
Cyto Sorbents Treatment Reduced Need for Ventilation in Patients with High Cytokine Levels 46 Patients on mechanical ventilation at 28 - days: (33% vs 88% control, p=0.09, N = 14; 6 treated, 8 control) * IL - 6 (>1,000 pg/mL) or IL - 1ra (>16,000 pg/mL) *
Slide 47: Treatment Improved Mortality in Patients with High Cytokine Levels
Cyto Sorbents Treatment Improved Mortality in Patients with High Cytokines Levels Statistically significant 28 - day mortality benefit with small number of patients (0% vs 63% control, p=0.03, n=14) 60 - day mortality (17% vs 63% control, p=0.14, n=14) 47 * IL - 6 >1,000 pg/mL or IL - 1ra >16,000 pg
Slide 48: Patients 65 Years and Older
Cyto Sorbents Patients 65 Years and Older
Slide 49: Statistically Significant Reduction in 14-Day Mortality (Age ≥ 65)
Cyto Sorbents Statistically Significant Reduction in 14 - Day Mortality (Age ≥ 65) CytoSorb use is correlated with a potential protective effect for up to 14 days (0% vs 36% mortality in control, p=0.04, n=21 (10 treated, 11 control) in patients ≥ 65 years of age 49 14-Day Survival (Age > 65) 50% 60
Slide 50: Longer Treatment Could Extend Benefit
Cyto Sorbents Longer Treatment Could Extend Benefit • 28 - day mortality shows gradual loss of treatment effect on mortality (40% vs 45% control, p=0.6; n=21) • CytoSorb treatment was limited to only 7 days by protocol to ensure patient safety, regardless of how patients were doing. In this sick pop
Slide 51: Improvement in Organ Dysfunction (Age ≥ 65)
Cyto Sorbents Improvement in Organ Dysfunction (Age ≥ 65) 51 -30% -25% -20% -15% -10% -5% 0% % Reduction in MODS Score on Day 7 (versus Day 1) Control Treatment • The Multiple Organ Dysfunction Score (MODS) is used to measure the level of organ injury over time (high score is worse) • Cyto Sorb trea
Slide 52: The Pieces are in Place for Potential Commercial Success
Cyto Sorbents The Pieces are in Place for Potential Commercial Success
Slide 53: CytoSorb Is Part of a Growing ICU Trend
Cyto Sorbents Cyto Sorb ® Is Part of a Growing ICU Trend Critical care therapies that purify or treat blood out of the body are commonplace and becoming more prevalent • Hemodialysis and hemofiltration - The most popular forms of extracorporeal blood purification and used worldwide • ECMO (Extracorp
Slide 54: Major Unmet Need & Little Competition
Cyto Sorbents Major Unmet Need & Little Competition No Approved Therapies in the EU or US to Prevent or Treat Organ Failure • Severe sepsis and septic shock • Acute respiratory distress syndrome • Trauma • Burn injury • Severe Acute Pancreatitis • Cardiopulmonary bypass and complications of surgery
Slide 55: CytoSorb is State of the Art Technology
Cyto Sorbents 55 Cyto Sorb ® is State of the Art Technology • CE Mark approved • Clinically proven as an effective cytokine filter with encouraging clinical data • Biocompatible and hemocompatible – ISO 10993 • Good safety track record – 160 canine, >650 human treatments • Massive capacity • Easier
Slide 56: CytoSorb Is Reimbursable In Germany
Cyto Sorbents 56 CytoSorb is reimbursable in Germany at more than $ 500 per cartridge or ~$ 3,500 for 7 days of treatment • This is in excess of the standard DRG payment • It reduces the risk of a major barrier to adoption Cyto Sorb Is Reimbursable In Germany
Slide 57: CytoSorb Has Big Market Potential
Cyto Sorbents • CytoSorb hemoperfusion ~ $ 500/device • CytoSorbents treatment (7 days) ~ 7 devices • Average patient treatment revenue ~ $ 3,500 • Annual sepsis patients in US and EU ~ 2.5 million Sepsis Alone $ 6 - 10 Billion US* and EU Market $ 500 - 800M Germany only All Critical Care Applicatio
Slide 58: CytoSorb is Manufactured Profitably
Cyto Sorbents Cyto Sorb is Manufactured Profitably CytoSorbents manufactures its own polymer and devices at its New Jersey facility Manufacturing is a Mature Process • ISO 13485:2003 Full Quality Systems certification • Manufacturing plant • Polymer production, device fill, packaging, QA/QC testing
Slide 59: Infrastructure Is Nearly Complete
Cyto Sorbents Infrastructure Is Nearly Complete • Established CytoSorbents Europe GmbH subsidiary • Berlin office forms the center of our activities in Europe • New key hires including VP Sales and Marketing and sales team in process • Cyto Sorb ® is now a registered trademark in the E.U. and U.S. •
Slide 60: Initial Launch of CytoSorb In Germany
Cyto Sorbents • Initial focus is on direct sales in Germany * Sepsis * Acute Respiratory Distress Syndrome * Trauma * Burn and smoke inhalation injury * Pancreatitis * Surgical complications • Orders from early adopters led to early modest revenue during a controlled market release of Cyto Sorb in s
Slide 61: Drive CytoSorb Adoption in Key Accounts
Cyto Sorbents • The focus is on key opinion leaders (KOLs) who are early technology adopters while leveraging contacts from the sales team • Provide good customer support to ensure optimal outcomes • Establish deep contacts at hospitals and encourage repeat usage • Provide data to support utilizatio
Slide 62: CytoSorb Gaining Government Support
Cyto Sorbents • We were awarded a Phase I SBIR grant from the US Army Medical Research and Materiel Command to develop and evaluate Cyto Sorb and our next generation technologies as a treatment for trauma and rhabdomyolysis • DARPA (Defense Advanced Research Projects Agency) selected our research pr
Slide 63: CytoSorbents Has a Robust Pipeline
Cyto Sorbents With strong development capabilities Cyto Sorbents Has a Robust Pipeline NAME INDICATION DESCRIPTION STATUS CytoSorb ® Severe sepsis and septic shock ARDS/ acute lung injury Burn and smoke inhalation injury Trauma Severe acute pancreatitis Complications of influenza Autoimmune disease
Slide 64: HemoDefend: Protection for Blood Transfusions
Cyto Sorbents Hemo Defend Protection for Blood Transfusions • 100M+ blood transfusions worldwide annually • Hundreds of thousands of people develop transfusion reactions due to contaminants in blood products • HemoDefend beads are designed to go into the blood storage bag and remove these contaminan
Slide 65: Removes A Broad Range of Substances
Cyto Sorbents Removes A Broad Range of Substances Antibodies Bioactive Lipids Hemoglobin Cytokines 65
Slide 66: Strong IP Position
Cyto Sorbents 66 Strong IP Position • Strong patent portfolio with 29 issued patents • IP covers composition of matter, resin characteristics, manufacturing techniques, methods and clinical applications • Oldest patents still have 6 years of patent life remaining • Multiple applications pending for
Slide 67: CytoSorbents Seeks Strategic Alliances
Cyto Sorbents 67 Cyto Sorbents has an active business development program seeking partners for its growth technology portfolio Cyto Sorb ® Hemo Defend Others Potential partners include companies involved in: • Dialysis and renal therapies • Pharmaceuticals • Critical care • Advanced materials • Bloo
Slide 68: CytoSorbents Is a Major Potential Growth Story
Cyto Sorbents • Cyto Sorb targets some of the most costly and unmet medical needs in medicine today by trying to prevent or treat multi - organ failure - the root cause of why almost half of patients die in the ICU • Critical care is a tremendous opportunity with a total addressable market that exce
Slide 69: Goals for 2012-2013
Cyto Sorbents • Drive market awareness, adoption, and sales of Cyto Sorb ® in Germany via direct sales force, leveraging partners or distributors in rest of Europe • Conduct new clinical trials and generate more clinical data • Publish the results of the European Sepsis Trial • Advance discussions w
Slide 70: Contact: Phillip P. Chan, CEO and President
Cyto Sorbents Phillip P. Chan, MD, PhD CEO and President 7 Deer Park Drive, Suite K Monmouth Junction, NJ 08852 (732) 329 - 8885 ext *823 pchan@cytosorbents.com Cyto Sorbents Corporation Working to Save Lives Through Blood Purification OTCBB: CTSO Cyto Sorbents Corporation