O X Y - 17 ® F O R MU L AT IO N S

Oxy-17® Fusion: a pat-

ented formula delivering Oxy -17® Gas to target tissue

intravenously in the form of

a proprietary perfluorocar-

bon emulsion.

O X Y - 17 ® A V A IL AB IL IT Y

Oxy-17® Gas is approved for human use in the United States and European Union, and has been commercially available for more than 20

years. Oxy-17® Gas is sold in 5L, 10L and lar- ger volumes.

Oxy-17® Fusion is in regulatory marketing

approval studies for human use in Germany (EU) and the United States. However, it is

available in a 50mL vial for research use in ani- mal models and approved investigator studies.

Smaller volume prefilled syringes are in devel-

opment.

Oxy-17® Gas: an enriched form of the naturally available

Oxygen-17 gas.

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Oxy-17® is a patented technology developed by Rockland Technimed Ltd. (RTL), pioneers in real-time metabolic magnetic resonance imaging. Oxy-17® Fusion, RTL’s lead preclinical candidate, is the first, ready-to-use intrave- nous formulation of Oxygen-17 and will be commercialized by RTL and Nukem Isotopes GmbH, a global leader in providing isotopes in form of ultra-pure substances.

R E F E R E N C E S / C R E D I T S

1. Derdeyn CP, Videen TO, Yundt KD, et al. Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemody-

namic impairment revisited. Brain. 2002;125(Pt 3):595-607. 2. McCommis KS, He X, Abendschein DR, Gupte PM, Gropler RJ, Zheng J. Cardiac 17O MRI: toward direct quantification of myocar-

dial oxygen consumption. Magn Reson Med. 2010 Jun;63(6):1442-7. 2011;701:215-22 3. Oxy-17® MRI of Human Brain Tissue Mass; Reprinted with permission from: Atkinson IC, Thulborn KR Feasibility of mapping the tissue

mass corrected bioscale of cerebral metabolic rate of oxygen consumption using 17-oxygen and 23-sodium MR imaging in a hu- man brain at 9.4 T. Neuroimage. 2010 Jun;51(2):723-33. DeLaPaz R, Gupte P. Potential Application of 17O MRI to Human Ischemic Stroke. Adv Exp Med Biol.

4. Direct 17O MRI with partial volume correction: first experiences in a glioblastoma patient, Magn Reson Mater Phy, published online April 1, 2014

PIONEERS IN MRI TISSUE VIABILITY IMAGING

ON E I N TERN A TI ON A L BL V D . SU I TE 4 0 0 , MA H W A H , N J 0 7 4 9 5

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© Rockland Technimed Ltd

http://www.ncbi.nlm.nih.gov/pubmed?term=cerebral%20metabolic%20rate%20oxygen-17mailto:staff@technimed.comhttp://www.oxy-17.com/

Oxy-17® MRI can enable physicians to rapidly assess tissue viability and make better in-formed, “personalized” treatment decisions by targeting tissue at highest risk of injury. Unlike gadolinium or iron oxide-based MRI contrast agents, Oxy-17® can cross an intact blood brain barrier to image normal and ischemic cerebral oxygen metabolism (CMRO2). In addi-tion, an Oxy-17® MRI can measure myocardial oxygen metabolism (MRO2).

Oxy-17® is the only non-radioactive imaging medium to measure real-

time oxygen metabolism, oxygen extraction fraction and molecular oxygen

consumption using an unaltered clinical magnetic resonance imaging

scanner.

Oxygen-17 is a stable, naturally occurring, non-radioactive isotope of

oxygen with identical chemical properties to Oxygen-16, the predominant

oxygen isotope in the air. Because Oxygen-17 is a normal component of

the oxygen we breathe, it naturally participates in all normal cellular

metabolic processes. However, unlike Oxygen-16, Oxygen-17 has a unique net 5/2 spin property to its

nucleus which interacts with the proton (H) when converted to metabolic water (H217O) via oxidative respi-

ration. This interaction can be detected using standard, unmodified MRI proton coils and software (T2W

or T1p pulse sequences) enabling clinicians and researchers to measure cellular oxygen metabolism

at 1mm spatial resolution (using proton MRI). The only other method for imaging oxygen metabolism

is 15O PET, which uses the radioactive isotope Oxygen-15 and yields a 6mm spatial resolution. Oxy-17®

offers higher resolution imaging and can be used in repeat tests without the dose limitations associated

with radioactive imaging methods, such as 15O PET.

A Nove l M e t abo l i c M ag ne t i c Res o nan ce Ima g i ng M ed ium E l e v a t i n g M R I t o a R e a l - t i m e M o n i t o r o f C e l l H e a l t h

Oxy-17®: Versatile Metabolic MRI Medium with Vast Clinical Potential

ONCOLOGY

EPILEPSY DRUG DISCOVERY

CEREBRAL & CARDIAC ISCHEMIA

An Oxy-17® MRI can pin-point the seizure focus

based on reduced inter-ictal oxygen metabolism, enabling physicians to

plan surgical resection more accurately.

DISCOVER OXY-17®

TISSUE VIABILITY ASSESSMENT WITH OXY-17®

Different levels of cell injury

have corresponding rates of

oxygen uptake from the blood

(oxygen extraction fraction,

OEF) in order to maintain viable

levels of oxygen respiratory me-

tabol ism: Oxygen-starved

ischemic or hypoxic tissue ex-

tracts a larger percentage of

oxygen than normal tissue while

nonviable (necrotic) tissue does

not take up any 17O2 gas and

hence does not produce detect-

able water (H217O). Conven-

tional MRI used with Oxy-17®

can distinguish hypoxic but

viable regions from those in

which cell death has occurred

due to necrosis and apoptosis.

Oxy-17® can be used as a consistent non-invasive biomarker for an investigative com-

pound’s mechanism of action at the cellular level and provide a surrogate end point for clinical trials starting from drug discovery thru

clinical use. Oxy-17® can also serve as a com-panion diagnostic to personalize treatment by more specifically targeting treatable tissue.

Molecular oxygen levels in neoplastic (cancerous) tissues fluctuate based on the tumor grade and

level of oxidative vs. anaerobic metabolism. An Oxy-17® MRI can safely track oxygen metabo-lism changes in tumor tissue before and

throughout the course of treatment without ex-posing the patient to additional radiation.

More than 38% contrast observed after a bolus

venous injection of the Oxy-17® Fusion versus

normal control image

Cerebral Oxygen Metabolism Imaged with Oxy-17®

Visualization of Tumor Hypoxia

Quantification of Cardiac Ischemia

Reference 2

Reference 3

Reference 4

Oxygen Extraction Fraction

0

50

100

-50

-100

Cerebral Blood Flow

Patient displays symptoms, but is not at risk of tissue failure Risk of tissue failure

dramatically increases

Necrosis and

apoptotic cell death cascade

commences

Time-window for tissue treatment is open Time-window for

tissue treatment is closing

Oxy-17® is the only non-

radioactive

imaging me-dium that can visualize this

point in the evolution of

ischemia

Perc

enta

ge C

hange

Oxy-17®: A Real-time Monitor of the Evolution of Ischemia

Time-window

for tissue treat-ment is closed

Auto-regulation A B Failing Infarction C

Reference 1

Send correspondence to:

Perfluorocarbon Oxygen Carriers and COVID-19 Robert L DeLaPaz, MD*

Pradeep M Gupte,MSBME**

Perfluorocarbon emulsions

Pefluorocarbons (PFC) were first developed as insulating oils during creation of the atomic bomb.

The capacity of perfluorocarbon to carry high concentrations of molecular oxygen (O2) was first

demonstrated in 1966 when mice were able to survive while completely immersed in a clear liquid

PFC solution and received adequate O2 for survival while “breathing” the solution into their lungs. 1

PFC’s are synthetic molecules composed of various length chains of carbon and fluorine atoms

with very high affinity for O2 and outstanding biological stability. (Figure 1) They are chemically

very stable, non-reactive with biological tissue and not metabolized by enzymes. These properties

arise from the strong carbon-fluorine (C-F) bonds and a dense electron “sheath” that surrounds

the fluorine chain. 2, 4 This results in very low solubility in water or lipids (high hydrophobic and

high lipophobic properties). The hydrophobic property means that they do not significantly interact

with other water-soluble molecules and are not metabolized by enzymes. The lipophobic property

means that they do not cross cell membranes and are not stored in body fat. Although PFC’s are

liquid at room temperature, the hydrophobic property prevents them from being directly injected

into blood. They need to be formulated in a colloid emulsion (PFCe) in order to be carried by the

blood. PFCe’s can carry high concentrations of both O2 and CO2, as much as 50 times blood

plasma). 3, 4 PFCe’s are cleared from the body by two routes, exhalation through the lungs and

clearance of emulsion particles by the reticuloendothial system (RES) macrophages in the liver

and spleen. Exhalation through the lungs occurs when the PFC in the blood at body temperature

and pulmonary arterial pressure becomes volatile as it passes through the alveolar capillaries

and changes phase to a gas as the high concentration in the blood diffuses to the low

concentration and low pressure in the alveolar air. 2 Clearance by the RES macrophages

depends on emulsion particle size and is minimized with emulsions particles of 0.2 microns (0.2

um = 200 nanometers, nm) or less.

Oxygen Delivery

1

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Oxygen delivery to tissue is regulated by the balance between O2 supply (O2 in air inhaled by the

lungs, the blood O2 carrying capacity and blood flow) and O2 demand (tissue O2 metabolic

consumption). Oxygen delivery by the blood to tissues consists of convection delivery (bulk flow of

O2 bound to hemoglobin (Hb) in red blood cells (RBC’s) from the lungs to the tissue vascular

network and capillaries) and diffusion delivery (O2 diffusion from the RBC’s through the blood

plasma and cellular cytoplasm to the mitochondria, where oxidative metabolism takes place).

Cells can only use the O2 that has first been released by Hb, dissolved in the plasma and then

diffused into the cells to the mitochondria. 3 The first and last stages in O2 delivery are the stages

where a perfluorocarbon emulsion (PFCe) enhances this process. In the lungs, PFCe in the

blood plasma enhances the uptake of O2 from inspired air, supplementing Hb O2 uptake by

increasing the O2 solubility (carrying capacity) in blood plasma. PFCe adsorbs O2 passively and

linearly, according to Henry’s Law, much more efficiently than blood plasma, depending on the O2

saturation in air (e.g. 21% or 160mm Hg in room air at sea level) but less efficiently than Hb which

binds O2 chemically. 4 (Figure 2) Increasing the inspired air O2 saturation further enhances the O2

dissolved in plasma in the presence of PFCe. At the other end of the process, more total O2 is

delivered by the blood to the tissue capillaries and PFCe in the plasma also facilitates the

diffusion of O2 through the plasma from the RBC’s to the tissue. This “plasma gap” normally acts

as a relative barrier to O2 diffusion and PFCe affinity for O2 overcomes this barrier by forming an

“oxygen bridge”. 5 (Figure 3) PFCe also facilitates the absorption of CO2 produced by cellular

metabolism into blood and its elimination by the lungs.

Figure 1. Perfluorocarbons (PFC) are synthetic molecules composed of various length chains of

2

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carbon and fluorine atoms with very high affinity for O2 and outstanding biological stability. 4

Figure 2. The linear oxygen absorption curves of PFC’s (Oxygent and Perftoran) compared to

plasma and the nonlinear, chemical oxygen binding of hemoglobin in blood. 4

3

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Figure 3. PFC emulsion (200 nm particles) dispersed through the plasma, shown in the diagram

and photomicrograph, enhance the oxygen carrying capacity of the plasma and also form an

“oxygen bridge” through the plasma that facilitates the diffusion of oxygen from hemoglobin in red

blood cells to the mitochondria in cells for utilization in oxidative metabolism. 3, 4

Perfluorocarbons and COVID-19

The beneficial effects PFCe for improved O2 distribution throughout the body applies to many

disease processes, as described below, but especially to COVID-19. There are multiple points

along the pathway from O2 uptake in the lungs to delivery of O2 to cells and during the progressive

stages of the COVID-19 disease where PFCe is likely to have a beneficial effect.

COVID-9 is a respiratory tract and lung tissue SARS-CoV-2 viral disease in the early stages that

produces profound hypoxia and later progresses with spread of the virus and the immune

inflammatory response from the lungs to other organs, including the heart, brain and kidneys.

The early lung disease is produced by direct invasion of the cells in the small air sacs (alveoli) by

the SARS CoV2 virus, producing initial damage to the thin membrane that allows O2 to pass from

the air in the alveoli to the small capillaries that surround the alveoli and then to the hemoglobin

molecules and blood plasma that carry the O2 throughout the body for release to tissues. 6, 7

Following this initial invasion and damage, there is production and release of cytokines into the

blood that stimulate and target the immune system to attack the same alveolar membrane cells

that have already been damaged by the SARS CoV2 virus, in an effort to eliminate the virus. The

4

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result is that these membranes become thickened by reactive fibrosis, inflammatory cells and

proteinaceous exudate accompanied by accumulation of inflammatory macrophages and

monocytes and fluid within the alveolar air spaces. 7 (Figure 4) These changes result in severe

barriers to diffusion of O2 from the air in the alveoli to the capillaries. This not only limits the

uptake of O2 by capillary hemoglobin but also inhibits the diffusion of CO2, produced by oxidative

energy metabolism in the entire body, away from the hemoglobin into the alveolar air. A third

mechanism of lung injury involves the renin-angiotensin system because the cellular membrane

receptor for SARS-CoV-2 virus is the angiotensin converting enzyme II (ACE2) which is inhibited,

resulting in increased angiotensin II that produces lung vasoconstriction, inflammation and

fibrosis, further worsening the diffusion of O2 into the blood. 9 A fourth process that directly

reduces the O2 uptake and CO2 release is the reduction of capillary blood flow around the alveoli

caused by microthrombi induced by SARS-CoV-2 and angiotensin II. 10 It is clear that the

presence of PFCe in the alveolar capillary blood is likely to have a beneficial effect in this situation

by enhancing the uptake of O2 in the plasma even at low partial pressure gradients of O2 (the

difference between the higher O2 concentration in the alveolar air and the low concentration in the

capillary blood) as well as the release of CO2 in the opposite direction from high blood to low air

CO2 concentrations.

There is also a special circumstance that has been recently observed in COVID-19 called “silent

hypoxia” where PFCe is likely to have an especially significant benefit. This is a little harder to

visualize than the inflammatory barriers to O2 and CO2 diffusion in the lungs described above.

Although the cause of this phenomenon is not completely understood at this stage of the

pandemic, it appears to be very similar to respiratory failure in air with low O2 concentration at

high altitude. 11, 12 The characteristic clinical picture is a patient without respiratory “distress” but

with rapid respirations (greater that the normal 12-16/min, as high as 30-40/min) and severe

hyoxemia (low hemoglobin saturation, SaO2, of less than 80%, as low as 50% in some cases).

The physiological effect of this rapid respiration is to disproportionately clear CO2 from the blood

more rapidly than O2 (CO2 diffuses about 20 times more rapidly through tissue than O2) producing

alkalosis of the blood (increased PH) which, in turn, causes a “left shift” of the hemoglobin oxygen

affinity curve making it more likely to take up O2 and also less likely to release the O2. The PFD

5

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“oxygen bridge” that facilitates O2 diffusion through the blood plasma from hemoglobin tissue

would be beneficial in these “silent hypoxia” cases by reducing the plasma barrier and increasing

the delivery of O2 to tissue from this “left shifted” hemoglobin. Hemoglobin otherwise remains

normal with normal oxygen carrying capacity in COVID-19. There is no evidence that reduced

oxygen carrying capacity of Hb is produced by direct binding of SARS-CoV-2 components as has

been suggested by some. 8, 13

Figure 4. In the alveoli of the lungs the initial invasion and damage to the thin membrane wall by

6

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the SARS-CoV-2 virus is followed by an immune response that causes the membrane to become

thickened by reactive fibrosis, inflammatory cells and proteinaceous exudate accompanied by

accumulation of inflammatory macrophages and monocytes and fluid within the alveolar air

spaces. These changes result in severe barriers to diffusion of O2 from the air in the alveoli to

the capillaries and of CO2 from the capillaries into the alveolar air. 7, 8

Other Clinical Applications

The ability of PFCe’s to enhance blood O2 uptake and carrying capacity with the facilitation

of O2 delivery to tissue has applications in a wide range of disease states. Pathologies that

produce obstructive airway disease or alveolar damage such as COPD or pneumonia, are

obvious applications, similar to COVID-19. Reduced pulmonary blood flow, as with pulmonary

embolus, is another application. At the O2 delivery stage, the increased O2 content of blood and

the improved O2 diffusion into tissue is especially beneficial in situations of generalized reduced

blood flow (blood loss or shock) or focal vascular obstruction such as cerebral or cardiac

thrombosis where small PFCe particles (0.2 microns or less) can circulate with plasma past the

obstruction into collapsed or compressed capillaries beyond the reach of the 35 times larger

RBC’s (7.0 micron) (Figure 5).

The use of PFCe’s to improve brain oxygen delivery and reduce injury with arterial

thrombosis in acute ischemic stroke has already been demonstrated in humans. 14 Acute

cerebral ischemia has also been recently identified complication of COVID-19. 15, 16 Use of PFCe

to improve oxygen delivery to the brain or heart during catheter treatment of arterial thrombosis or

stenosis has also been demonstrated. 17, 18 Improving oxygen delivery to skeletal muscle with

PFCe’s has a potential role in limb preservation with peripheral vascular disease, muscle

conditioning in rehabilitation and exercise physiology. PFCe’s have also been demonstrated

improved organ preservation and transport for transplantation.

Before the COVID-19 pandemic, OxyFusionTM, (Rockland Technimed, Ltd.) a nano-emulsion

of 17O and perfluorodecalin (PFD), an FDA-approved PFD, MRI medium was developed for the

7

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evaluation of cerebral ischemia using MRI. OxyFusionTM has been focused on potential to

become the primary MRI medium for diagnosing stroke for a number of reasons. First, the carried

17O-labeled oxygen metabolizes to water in the tissue in 10 minutes so thus has the potential to

be used with standard MRI technology to rapidly determine CMRO2, CBF and OEF, which allows

for the identification of the penumbra. The quantification of CMRO2 is simple and reliable owing to

the fact that 17O MRI only detects and images the 17O signal that has been metabolized into water

(H217O), whereas PET detects both, which complicates the PET imaging processing and

quantification. 17O also is non-radioactive, thus enabling its repeated use in individual patients and

eliminating the need for an expensive cyclotron, radioactive chemistry lab or PET scanner.

OxyFusionTM is stable, with a “ready-to-use” shelf-life of more than 18 months. Perhaps most

importantly, the 17O of OxyFusionTM exhibits preferential uptake by hypoxic tissue, thus delivering

extra oxygen to the hypoxic penumbra and treating the ischemic stroke. The goal of all current

acute stroke therapies is to improve the delivery of O2 to ischemic tissue in order to limit the

volume and severity of ischemic injury. This is most commonly done by improving blood flow by

removing flow obstruction (e.g., rtPA thrombolysis, catheter thrombectomy), improving collateral

blood flow (e.g., hypertension) or enhancing blood oxygen content (e.g., hyperbaric O2).

Nevertheless, the risk of reperfusion injury secondary to oxygen free radical production is

common to all of these therapies. A potential advantage of enhancing O2 delivery with

OxyFusionTM is reduction of oxygen free radical by improved aerobic metabolism, as well as the

property of PFD emulsions to scavenge oxygen free radicals. This is expected to mitigate the

direct membrane toxicity and reduce the mitochondrial triggering of apoptosis by oxygen free

radicals.18 By working as a dual-functional diagnostic and therapeutic agent, OxyFusionTM is a

theranostic, which is an emerging cutting edge medical field.

8

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Oxy-17Fusion™ Expands critical rescue opportunity

Expands treatable population from 4% to over 40%, reducing disabilities and costs in Stroke alone

Approximately 92.1 million Americans are living with some form

of cardiovascular disease or after effects of stroke. The total

direct and indirect cost of cardiovascular diseases and stroke in

the US is estimated at US $316 billion 4

Fig-5: The use of PFCe’s to improve brain oxygen delivery and reduce injury with arterial

thrombosis in acute ischemic stroke has already been demonstrated in humans. Exploration of a

similar application cardiac ischemia is being investigated.

History of Perfluorocarbon Emulsions

Following the demonstration of PFC oxygen carrying capacity adequate for animal respiration in

the 1960’s development of PFC emulsions (PFCe) for human intravascular use as “blood

substitutes” was begun in Japan with Fluosol-DA (Green Cross Corp.) Fluosol-DA was approved

by the US FDA in 1989 for use in small volumes with cardiac angioplasty to improve oxygen

delivery while unblocking heart arteries but was later supplanted by improvements in catheters

and blood flow recirculation techniques and discontinued. As a first generation agent, Fluosol-DA

was also not sable at room temperature and the emulsifying agent induced adverse reactions.17, 18

Second generation PFCe agents, developed in the early 1990’s, were stable at room temperature,

used new emulsifying agents and had higher PFC concentrations and oxygen carrying capacity.

In 1993 the US FDA approved a PFCe for use as an imaging contrast agent for CT, MRI and

9

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ultrasound (Oxygent, Alliance Pharmaceuticals Corp.). 17 Large volume intravascular Oxygent

was also studied through phase 3 in a cardiac surgery study but was suspended due to

complications from extreme hemodilution (greater than 50% reduction in blood volume). 17 In the

mid 1990’s an emulsion of perfluorodecalin and perfluoromethylcyclopiperidine in a nonionic

surfactant (Proxanol 268) was developed (Perftoran, Scientific Productive Company) with a small

particle size (70 nm) intended to reduce reactions seen with earlier PFCe’s with larger particle

sizes (greater than 200nm). 19 However, Perftoran needed to be stored frozen and carefully

thawed, after which is was stable for only 2 weeks. In 1996 Perftoran was licensed for treatment

of hemorrhagic anemia in Russia, Ukraine and Kazakhstan and later in 2005, in Mexico (Perftech,

KEM Laboratories) but production was suspended in 2011. Perftoran remains licensed by a

Florida company as Vidaphor (FluorO2 Therapeutics) but has not undergone U.S. clinical trials

and is not approved by the US FDA.

In the early 2010’s, another second generation agent, Oxycyte (Synthetic Blood International, Inc.,

Tenax Therapeutics, Inc.) underwent a human trial of increasing O2 delivery to the brain with

traumatic brain injury (TBI) but was suspended for lack of enrollment. A phase 1/2 trial of Oxycyte

and hyperbaric oxygen for human cerebral ischemia (stroke) therapy was approved in 2018 but

has not yet recruited subjects (NCT03463551).

More recently, a PFCe originally US FDA approved as an ultrasound contrast agent (EchoGen,

Sonos Pharmaceruticals, inc.) was repurposed as generic DDFPe (dodecafluoropentane, Nuvox

Pharma, Inc.) and used in a phase 1b/2 trial for treatment of human cerebral ischemia which

showed no dose-limiting toxicity and improved acute and chronic outcomes versus saline infusion

controls. 14 However, DDFPe is a relatively small PFC and therefore more volatile than other

PFC’s with rapid elimination as a gas through the lungs. DDFP is elimination by this route has a

half-life (t1/2) of about 2 minutes with 99% elimination in 2 hours. 20 This short therapeutic effect

requires repeated injections every 90 minutes which limits its use in clinical applications with

longer time frames than the respiratory disease associated with COVID-19. Longer chain PFC’s

are less volatile and are eliminated more slowly through the lungs with a t1/2 of about 8-24 hours,

resulting in 99% elimination in several days, depending on their specific formulation. 2

10

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The PFCe agent that we have developed (PFD, perfluorodecalin, Oxy-17-PFD, namely

Oxy17Fusion™ Rockland Technimed, Ltd) is a larger, more stable, PFC than DDFP which is also

eliminated as a gas through the lungs but with a much longer therapeutic effect and improves O2

uptake in the lungs over 1-2 days under normal pulmonary conditions, more appropriate for most

clinical applications. It is anticipated that the inflammatory changes that inhibit O2 uptake in the

lungs with COVID-19 will also reduce the pulmonary elimination of longer chain perfluorocarbons

and prolong their recirculation, resulting in improved blood O2 carrying capacity for several

additional days after a single dose. The precise total time for elimination of the longer chain

PFC’s is more difficult to determine than for the short chain PFC’s because as the larger emulsion

particles recirculate they are also subject to detection as foreign particles by the by the

reticuloendothelial system and phagocytosis by macrophages in the liver and spleen. The degree

of this response varies according to the specific formulation, emulsifying agent, particle size and

characteristics of the individual patients but is generally minimized at emulsion particles of sizes of

0.2 microns (200 nanometers) or less. Oxy-17-PFD emulsion has the advantage of small particle

size (95%

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REFERENCES

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https://medium.com/@amdahl/covid-19-debunking-the-hemogoobin-story-ce27773d1096 14. Culp WC, et.al., Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial, J Vasc Interv Radiol 2019; 30:1244–1250. 15. Oxley TJ, et.al., Large Vessel Stroke as a Presenting Feature of Covid-19 in the Young, N Engl J Med 382;17 Nejm.Org April 28, 2020.

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20. Johnson JLH, Dolezal MC, Kerschen A, Matsunaga O and Unger EC, In Vitro Comparison of Dodecafluoropentane (DDFP), Perfluorodecalin (PFD) and Perfluoroctylbromide (PFOB) in the Facilitation of Oxygen Exchange, Artificial Cells, Blood Substitutes and Biotechnology, 37:156-162, 2009.

Authors Affiliations:

*Robert L DeLaPaz, MD, Professor Emeritus Columbia University, Board Member and Medical Director of Rockland Technimed Limited Contact Email: robert.delapaz@oxy-17.com **Pradeep M Gupte, MSBME, Founder & CEO Rockland Technimed Limited Contact Email: pgupte@oxy-17.com

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