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| 8-K - Cytosorbents Corp | v204295_8k.htm |
| EX-99.1 - Cytosorbents Corp | v204295_ex99-1.htm |
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CYTOSORBENTS CORPORATION
(OTCBB: CTSO) is a critical-care focused therapeutic device company in
clinical trials with a powerful purification technology based on
biocompatible, highly porous polymer beads designed to actively remove
disease-causing substances from blood and physiologic fluids. CytoSorb™,
the company’s flagship product, is an efficient cytokine filter intended
to reduce deadly inflammation caused by “cytokine storm” in critically-ill
patients. With frequently fatal diseases commonly seen in
medical and surgical intensive care units, such as sepsis, advanced
influenza, severe lung injury, serious burn injury, trauma and
pancreatitis, this cytokine storm-driven inflammation often leads to
multiple organ failure that is a major cause of death in these patients.
Current standard of care therapies are mainly supportive and do little to
hasten disease recovery. CytoSorb represents a new generation of “active”
therapies, designed to reverse the underlying cause of organ failure,
potentially helping patients heal and recover faster, leading to reduced
overall costs of treatment.
CytoSorb’s
blood compatible polymer beads are highly porous, capturing appropriately
sized substances in its pores, while letting larger or smaller substances
pass around or through. As blood is circulated through a
cartridge of these beads using standard blood pumps such as dialysis
equipment, cytokines and other toxins are captured by the beads and
removed from blood. The “purified” blood is then returned to
the patient. Based on all data from a single, major academic
site (6 treated, 6 control patients) that was part of a human sepsis pilot
study, CytoSorb demonstrated substantial improvements in a number of key
secondary clinical endpoints, including mortality, ventilator-free days
and vasopressor use. CytoSorbents has now enrolled 90 patients
out of a targeted 100 patient randomized, controlled European Sepsis Trial
comparing standard of care therapy with standard of care therapy plus
CytoSorb in the treatment of patients with severe infection and sepsis in
the setting of respiratory failure. CytoSorbents recently achieved ISO
13485:2003 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 European Union (E.U.)
CytoSorbents plans to seek CE Mark approval for its flagship device,
CytoSorb™, in the E.U. as a “cytokine filter” which would mark an
important transition from a development stage to a commercial stage
company.
CYTOSORBENTS IS A CRITICAL
CARE PURE
PLAY. Critical care medicine includes the treatment of
patients with life-threatening diseases who require comprehensive care in
the intensive care unit (ICU), with highly-skilled physicians and nurses
and advanced technologies to support critical organ function to keep them
alive. Some of these diseases have definitive treatment, but the standard
of care treatment in many other diseases, particularly those due to
massive inflammation, is mainly supportive care that is designed to keep
the patient from dying while using acute management to tip the balance
towards gradual recovery over time (“watchful waiting”). This
is generally true for the treatment of many of the diseases mentioned
above with high expected mortality. The lack of “active”
therapies that can reverse the underlying cause of these diseases means
that patients linger in the intensive care unit and are subject to
secondary infections and other serious complications that greatly increase
their risk of death. The treatment of these critical care
patients is often so variable, that the costs often exceed the standard
DRG (diagnosis related group) reimbursement that provides a lump sum
reimbursement for that particular disease state, forcing already
financially challenged hospitals to absorb these massive
losses. As an example, a burn patient with more than 30% of his
total body surface area burned can cost as much as $200,000 to treat.1 CytoSorbents
is a critical care pure play that hopes to change this dynamic with its
flagship product, CytoSorb™, and a robust pipeline designed to actively
treat a number of critical care
illnesses.
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CRITICAL CARE MEDICINE IS A STRONG MARKET.
Critical care medicine remains a strong market for innovative therapies
that can heal patients faster and reduce the costs of treatment, particularly in
the current environment of healthcare reform. For instance, effective
treatments for ICU patients who face life or death with serious diseases such as
sepsis, acute respiratory distress syndrome (ARDS), burn injury, and others, are
“need to have” therapies that can command significant price
premiums. Depending on patient outcome, these therapies are often
inexpensive in comparison to the overall cost of treatment. Also,
intensivists faced with watching their patients die due to the lack of effective
therapies, are much more likely to try new therapies, particularly where few
alternatives exist. The relative lack of competition in critical care
therapies allows approved products to rapidly gain market
penetration. And the concentrated focus of large ICUs in major
referral center hospitals makes a targeted sales and marketing effort for
critical care therapies much more cost effective.
CYTOSORB™ IS THE CORNERSTONE OF OUR
CRITICAL CARE
STRATEGY. CytoSorb™ is a unique, biocompatible cytokine filter
that has the potential to broadly reduce cytokine storm without compromising the
integrity of the immune system. Cytokines are small proteins that, in
moderation, help to stimulate and regulate the immune system and are required
for proper immune system function. However, in excess, cytokines can
cause or exacerbate disease, such as in autoimmune diseases like rheumatoid
arthritis, psoriasis and inflammatory bowel disease. This has led to
the blockbuster category of targeted anti-cytokine therapies such Remicade ®,
Enbrel ®, and Humira ®, that collectively have more than $14 billion in
worldwide sales and have validated the anti-cytokine
approach. However, in vast excess, often called “cytokine storm”,
cytokines can cause organ damage and failure and, in many cases,
death. Cytokine storm is a major cause of organ failure in severe
sepsis, burn injury, trauma, ARDS, pancreatitis and a number of other diseases
where no or few effective therapies exist. Targeted anti-cytokine
therapies have not historically been effective in treating these
diseases. In these cases, the ability of CytoSorb to broadly remove
many different cytokines is needed.
CYTOSORBENTS IS INITIALLY FOCUSED ON
TREATING SEVERE SEPSIS, or the body’s immune response to “overwhelming
infection”. The incidence of serious infection and sepsis is rising
due to the spread of antibiotic resistant bacteria like MRSA, an aging
population, an increase in co-morbid conditions like cancer and diabetes, and an
increasing use of implantable devices like artificial hips and knees that are
prone to infection. Severe sepsis afflicts more than one million
patients in the US annually, 1.5 million in Europe, and an estimated 18 million
people worldwide, killing one in every three, despite the best standard of care
treatment that includes antibiotics. Septic shock, a more dangerous
form of severe sepsis with persistent low blood pressure, kills more than one in
every two patients. More die from severe sepsis and septic shock in
the U.S. than from either heart attacks, strokes or any single form of
cancer. The recent H1N1 swine influenza pandemic highlighted the
serious lack of effective therapies for critically-ill septic
patients. Only one product, Xigris® by Eli Lilly, has been approved
to treat severe sepsis, but is not widely used due to concerns of cost and
efficacy.
SEPSIS IS COSTLY. In addition
to the human toll, sepsis is one of the most expensive acute care diseases to
treat. Severe sepsis patients account for up to 20% of all intensive
care unit (ICU) admissions and require expensive and highly variable treatment
and diagnostic procedures. For example, a septic patient in the ICU
typically has multi-organ dysfunction requiring constant skilled nursing care
and the use of expensive, supportive therapies such as mechanical ventilation,
dialysis, and the administration of blood products, vasopressors, and costly
drugs and antibiotics. These patients also undergo a wide range of
other procedures including diagnostic imaging (X-rays, CT, MRI, ultrasound),
blood tests, arterial blood gases, placement of blood and urine catheters,
amongst others. In many cases, patients require some kind of surgical
exploration, resection and debridement of necrotic tissues or
fluid. The treatment of most sepsis patients in the ICU is also
multi-disciplinary, often requiring the expertise of consultants in infectious
disease, nephrology, surgery, nutrition and other fields. It is
therefore not surprising that in 2001, the average cost per day in the ICU for a
sepsis patient was nearly $3,000 a day, with an overall average total hospital
cost and length of stay of $40,000 and 19 days, respectively. On the high end,
septic patients in the ICU could cost twice this amount.2 Another
2001 study concluded similar costs and estimated the total annual U.S. burden of
sepsis at $16.7 billion, leading to substantial losses for the healthcare
system.3 These
expenses have significantly increased over the past decade due to rising
healthcare costs, an increase in sepsis incidence, and a continued lack of
effective “active” therapies to reverse the underlying cause of sepsis and organ
failure.
SEVERE SEPSIS IS THE RESULT OF TWO
PROCESSES. The first is the infectious trigger, typically from either a
bacterial infection like pneumonia or a viral infection like
influenza. This can often be treated with antibiotics or antiviral
medications. The second, and often more devastating, is the body’s
abnormal immune response to the infection, in the form of a massive production
of cytokines termed “cytokine storm”. Cytokine storm is directly
toxic to cells, tissues and organs. In fact, it is widely accepted
that cytokine storm and the ensuing severe inflammation, rather than the initial
infection itself, is responsible for much of the organ failure, immune
dysfunction, morbidity and death seen in sepsis. Cytokine storm has
also been implicated as a major contributor of mortality with certain virulent
strains of influenza such as avian (H5N1) and the 1918 H1N1
flu. Until recently, there have been no practical technologies that
could actively reduce cytokine storm effectively – the holy grail of the
industry for the past three decades. CytoSorb™ is a leader in this
field and as a highly efficient cytokine filter, is being evaluated in clinical
trials as a potential treatment for reducing cytokine storm.
CYTOSORB HAS SHOWN HUMAN PROOF-OF-CONCEPT.
Based on all data from a single, major academic site (6 treated, 6
control patients) that was part of a randomized, controlled human sepsis pilot
study, CytoSorb™ demonstrated encouraging improvements in key clinical endpoints
including ventilator-free days, vasopressor use, all-cause mortality, organ
failure scores, and days in the ICU. An encouraging finding was a
more rapid pace of ventilator weaning in the treatment arm. Since
respiratory failure requiring mechanical ventilation is a major reason why
sepsis patients need to remain in the ICU, the ability to reverse lung injury
and help patients get off the ventilator and out of the ICU, at $3,000 per day,
could lead to substantial savings.
2
CYTOSORBENTS IS CURRENTLY CONDUCTING
ITS EUROPEAN SEPSIS TRIAL, a 14-site, randomized, controlled clinical
trial in Germany using CytoSorb™ to treat 100 patients with severe sepsis
in the setting of respiratory failure. Patients are treated daily for
up to seven days. Endpoints include cytokine reduction, 28- and
60-day all-cause mortality, ventilator status, organ failure scores, hemodynamic
stability, immune system function and others. In the Sepsis trial to
date, the treatment has been well-tolerated with no serious device-related
adverse events in approximately 300 human treatments. Overall,
CytoSorb™ has been used safely in a number of different human studies in
approximately 650 treatments to date. CytoSorb plans to seek CE Mark
approval in Europe.
CYTOSORB COMMERCIALIZATION STRATEGY.
CytoSorbents has achieved ISO 13485:2003 Full Quality Systems
certification. ISO
13485 is 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 European Union (E.U.). It is a regulatory requirement of the E.U.'s
Medical Device Directive and an important step toward attaining European CE Mark
approval. If CytoSorb also receives CE Mark approval, the company intends
to begin marketing CytoSorb™ in Germany, the third largest medical device market
in the world, and the largest, by far, in the European Union. The
German Sepsis Society estimates more than 145,000 cases of sepsis each year in
Germany alone. CytoSorbents is currently working with major thought leaders in
the area of critical care and sepsis research at leading medical centers in
Germany as part of the European Sepsis Trial. This will be helpful in
marketing CytoSorb and in fostering scientific discourse. CytoSorb
reimbursement is anticipated to fall under the German “diagnosis related group”
(DRG) acute care reimbursement. Under this system, hospitals would
purchase CytoSorb and subtract the cost from a pre-determined lump-sum payment
made by insurance to the hospital based on the patient’s
diagnosis. No specific reimbursement code would be required for the
CytoSorb device. If approved, CytoSorb could be used in Germany for
the treatment of cytokine storm in other critical care diseases, and still be
reimbursed. Following an initial launch in Germany, other countries
such as the United Kingdom, Italy, France and Spain would also be
targeted.
CYTOSORBENTS PLANS TO SEEK
US STUDY. In 2007,
CytoSorbents received FDA allowance of its IDE application to begin a small
sepsis study in the US. The company elected to pursue a much larger
trial in Germany, but still incorporated many of the requests of the FDA into
this trial. The Company intends to present the European Sepsis Trial
data to the FDA and work to negotiate the commencement of a randomized,
controlled study in the US. CytoSorbents seeks to be a leading
therapy in the US and Europe for the treatment of sepsis, cytokine storm, and
other critical care illnesses.
CYTOSORBENTS COLLABORATES with
investigators at the University of Pittsburgh Medical Center (UPMC) Department
of Critical Care, one of the largest funded and most active centers for critical
care research. In animal sepsis studies carried out at UPMC,
CytoSorb™ significantly improved survival to 65% in CytoSorb™ treated animals
from only 12.5% in sham controls. In addition, CytoSorb™ prevented
shock and lowered cytokine levels in these animals as
expected. CytoSorbents also collaborates with UPMC on a $7M
multi-year NIH grant based on the usage of polymer technology in the treatment
of sepsis.
CYTOSORBENTS’ BROAD-SPECTRUM APPROACH
IS VERY DIFFERENT from all previous
attempts to treat sepsis with drugs or biologics. With the exception
of Xigris® (Eli Lilly), which has not been widely embraced by physicians due to
high cost, questions of efficacy and potentially dangerous side effects, none
have been successful. Most have tried to remove or interfere with
only a single cytokine or inflammatory mediator. In sepsis, however,
there are too many cytokines and too much redundancy in the immune system for
the removal of just one cytokine to have much effect. CytoSorb™, as a
medical device, has the potential to broadly and simultaneously reduce multiple
cytokines, toxins and other important factors in sepsis that a single drug or
antibody cannot. By reducing the direct toxic effects of cytokines
and either preventing or mitigating organ failure, CytoSorb™ may have a
beneficial “multiplier effect” that could increase
survival. Potential examples include reduction of organ ischemia due
to hypotensive shock, faster weaning from mechanical ventilation with decreased
risk of ventilator acquired pneumonias, reduction in acute kidney injury leading
to improved fluid balance, toxin removal and acid-base control, reduced
permeability of the gut epithelium potentially decreasing endotoxemia, and fewer
days in the intensive care unit with fewer interventions and
complications.
CYTOSORBENTS’ PATENT PORTFOLIO IS
STRONG AND GROWING with 27 issued patents,
2 notices of allowance and multiple applications pending. These
patents establish CytoSorbents as one of the leaders in extracorporeal blood
purification to remove toxins and cytokines from blood and physiologic fluids.
The patents, all of which have substantial patent life, cover a broad platform
technology that has many therapeutic applications outside of
sepsis.
3
CYTOSORB™
ADVANTAGES
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Razor / razor-blade disposable
– Works with standard hospital dialysis equipment, and is the high
margin “razor-blade” in the “razor/razor-blade” business
model
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Broad spectrum device –
Specifically designed to remove
a broad range of cytokines and toxins making this the most logical
strategy to treat cytokine storm
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Efficient cytokine
removal – Capable of removing up to 90% of
certain cytokines from blood in a single in vitro
treatment
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Strong animal data
– Significantly improved short and long-term survival,
hemodynamic stability and cytokine removal 4,5
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Easy to use – Minimal
learning curve, uncomplicated set up and high ease of
use
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Hemocompatible – Polymer
beads can directly contact blood without material negative
effects
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Massive capacity – A
single cartridge has more than seven football fields of surface area to
bind cytokines
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Long shelf life – No
biologic components such as antibodies or cells means excellent storage
and shelf life
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Extensive testing and safety
history – Passed extensive animal safety with 160 canine treatments
and ISO 10993 biocompatibility testing. No serious
device-related adverse events in approximately 650 human treatments with
good tolerability and safety
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Low manufacturing risk –
CytoSorbents manufactures and packages its own polymer bead cartridges and
has achieved ISO 13485 Full Quality Systems certification. CytoSorbents’
current manufacturing facilities are sufficient to supply anticipated
initial demand for approximately 1-2
years
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Limited competition – In
the U.S. and Europe, only Xigris (Eli Lilly) has been approved to treat
sepsis, but is expensive and has questionable efficacy and
safety
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Reimbursement friendly –
Falls under the favorable diagnosis related group (DRG) hospital
reimbursement and not individual product reimbursement. An
ability to demonstrate improved patient outcome with reduced ICU care
should drive adoption
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PIPELINE
CytoSorbents’
valuable patented polymer technology can be modified to remove substances as
small as drugs to substances as large as antibodies from blood and physiologic
fluids. This technology platform is the basis of a robust pipeline of
potential products in development.
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PRODUCT
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INDICATION
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DESCRIPTION
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STATUS
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CytoSorb™
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Severe
sepsis and septic shock
ARDS
/ acute lung injury
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Highly
efficient cytokine filter that is designed to treat cytokine
storm
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Current
European Sepsis Trial intended for CE Mark approval
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CytoSorb™
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Cardiac Surgery
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Organ Preservation
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Influenza
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ARDS/ALI
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Burns & Inhalation injury
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Severe Pancreatitis
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Trauma
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Highly
efficient cytokine filter to reduce cytokine-induced organ
injury
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-Observational
human study
-Human
pilot study completed
-Pre-clinical
-Pre-clinical
-Pre-clinical
-Pre-clinical
-Pre-clinical
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BetaSorb™
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Improvement
of hemodialysis in end-stage renal disease
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Removal
of mid-molecular weight toxins that are inefficiently removed by standard
dialysis
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Four
human pilot studies
completed
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CST
101
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Drug
overdose, chemical exposure or intoxication
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Efficient
single pass removal of a number of drugs from blood
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Pre-clinical
proof of concept completed
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CST
201
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Adjunct
cancer treatment: Chemotherapy removal during high dose regional
chemotherapy
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Efficient
single pass removal of certain chemotherapy agents from
blood
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Pre-clinical
proof of concept completed
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CST
301
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Trauma
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Removal
of myoglobin from blood caused by muscle breakdown and rhabdomyolysis in
trauma
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Pre-clinical
proof of concept completed
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4
BUSINESS DEVELOPMENT
STRATEGY CytoSorbents has an active business development program,
seeking potential strategic partners to license various potential applications
of our technology, help fund clinical development and assist in the sales,
marketing and distribution of CytoSorb™ in various geographic
territories. The economics of a high margin disposable device
in an under-served multi-billion dollar market with strategically important
technology should be attractive to a number of potential partners in the medical
device, dialysis, material science, filtration and critical care
spaces. CytoSorbents also seeks to out-license a number of
non-core applications of its resin to better commercially develop its platform
technology. Whether through strategic partnerships or taken to the
market directly, the technology represents a promising adjunctive treatment for
severe sepsis and other critical care disease states.
In
addition, CytoSorbents actively seeks non-dilutive grants, funding
opportunities, and partnership collaborations within the government, National
Institutes of Health, and the military to expand its clinical
applications. For military applications, CytoSorb has the potential
to address the major reasons why soldiers die, including penetrating wound
injury and sepsis, trauma and burn injury. CytoSorbents received
positive feedback on their technology when it exhibited at the Force Health
Protection Conference and the Advanced Technology Applications for Combat
Casualty Care (ATACCC) conference in August. Earlier this month,
CytoSorbents was awarded a non-dilutive cash grant of up to $488,958 from the
Federal Qualifying Therapeutic Discovery Project Program.
EXPERIENCED
AND ACCOMPLISHED MANAGEMENT TEAM
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Phillip Chan, MD, PhD – Chief
Executive Officer – is a Board-certified internal medicine
physician trained at Harvard and Yale Medical School, a former Partner at
NJTC Venture Fund focused on healthcare and life science investments, and
a co-founder of the privately-held medical device firm, Andrew
Technologies.
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Robert Bartlett, MD - Chief
Medical Officer - is world-renowned as the pioneer in
extracorporeal membrane oxygenation therapy (ECMO) and the former Director
of the Surgical Intensive Care Unit at University of Michigan, with
extensive experience in critical care medicine including the treatment of
sepsis and respiratory disease.
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Vincent Capponi, MS - Chief
Operating Officer - has more than 20 years experience in the
medical device, pharmaceutical and imaging fields at Upjohn, Sims Deltec
and Sabratek with strengths in operations and manufacturing.
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David Lamadrid, MBA
– Chief Financial Officer – has over 18 years of business
experience in finance and management, previously at Chase Manhattan
Bank.
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SUMMARY
CytoSorbents
is a critical care-focused therapeutic device company using blood purification
to treat major critical care diseases that currently have few “active”
therapies. Our flagship product is CytoSorb™, a highly efficient cytokine filter
designed to treat potentially deadly inflammation caused by “cytokine storm”.
CytoSorbents plans to seek CE Mark approval for CytoSorb™ and begin marketing
the device in the European Union. If approved as a cytokine filter,
in addition to sepsis, the device could be used in Europe for many other
critical care diseases such as burn injury, acute respiratory distress syndrome,
trauma and others. This would mark a major milestone in the history of the
Company, transitioning it from a development stage company to a commercial stage
company. The Company has leading, patented technology backed by strong science
and a highly profitable business model. We believe CytoSorb™ has the
potential to be a blockbuster therapy that can be sold throughout the world as a
treatment for sepsis and other diseases exacerbated by cytokine
storm. If successful, these characteristics position the Company well
for growth and future value creation for shareholders. Also, we
continue to unlock the value of our underlying polymer platform technology
through the ability to modify it for other medical applications, further
broadening our pipeline and potential for out-licensing
opportunities. If interested in learning more about CytoSorbents,
please contact Dr. Phillip Chan, CEO at pchan@cytosorbents.com
REFERENCES
1 Saffle,
JR, et al. “Recent outcomes in the treatment of burn injury in the United
States; a report from the American Burn Association Patient Registry”, J Burn
Care Rehabil (1995); 16(3 Part 1); 219-232.
2 Teres,
D, et al. “Cost fo care associated with early sepsis (first 24 hours of
admission) in a United States medical center”, Critical Care (2001), 5(Suppl
1):258
3 Angus,
D, et al. “Epidemiology of severe sepsis in the United States: Analysis of
incidence, outcome and associated costs of care”, Crit Care Med (2001),
29(7):1303-1310.
4 Kellum,
JA, et al “Hemoadsorption removes TNF, IL-6, and IL-10, reduces NF-KB DNA
binding, and improves short-term survival in lethal endotoxemia”, Crit Care Med
(2004), 32(2): 801-805
5 Peng,
ZY, Carter, MJ, Kellum, JA “Effects of hemoadsorption on cytokine removal and
short term survival in rats”, Crit Care Med (2008), 36(5): 1573-7
Remicade®,
Enbrel®, Humira® and Xigris® are registered trademarks of Johnson&Johnson,
Amgen, Abbott Laboratories, and Eli Lilly and Company, respectively
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Statements in this
summary regarding CytoSorbents Corporation 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. Readers are referred to a
discussion of important risk factors detailed in the Company’s Form 10-K
filed with the Securities and Exchange Commission on April 9, 2010 and
other reports and documents filed from time to time by us, which are
available online at www.sec.gov.
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