Perftoran / Vidaphor

1. Perftoran/Vidaphor Introduction into Western Medicine

2. My Background/Prospective/Disclosures • Background in Diving Medicine, Hyperbaric Oxygen Therapy as well as Anesthesiology and interest in Neurosurgery and Trauma • Long standing interest in Vascular Gas Embolus • First involved as Navy proponent for PFC research in Decompression Sickness (~1998) • Lobbied Alliance Pharmaceutical to provide Oxygent for DCS studies (~1999) • Advised/advocated for research by NMRC in DCS • Served on Scientific Advisory Board for Synthetic Blood, Oxygen Biotherapeutics, Inc. • Recently served as consultant for FluorO2 Therapeutics • Active Neurosurgical Anesthesiologist – no involvement between Texas A&M or Baylor Scott and White with my role in PFC

3. Perftoran/Perftec, now “Vidaphor”

4. Perftoran - Composition • 2 PFC compounds, 20% w/v solution • Submicron Emulsion, stabilized by surfactant Proxanol268 (Kolliphor– BASF) • Balanced Electrolyte solution • Enhanced Solubility of gases, including oxygen, carbon dioxide, nitrogen

7. Perftoran– Key Characteristics • Different from “2nd Generation” PFC’s like Oxygent and Oxycyte • Not egg phospholipid emulsion • Much smaller particle size • Stored Frozen, but quick thaw, can be refrozen • *Smaller particle size – possibly enhancing effects and decreasing some side effects

9. Advantages of VIDAPHOR Fewer Side Effects Far More Exposures Longer Half Life 30,000+ exposures with good results in 88% of cases; 8% of recipients saw no measurable improvement Smallest particle size of any of the PFC emulsions in development; ~ one-third smaller than the particle size of either Oxygent, Oxycyte or DDFP Blood T1/2 varies inversely with particle size, and is 3 to 4 times longer for emulsions with a mean particle size < 0.2 microns. Smaller emulsion particles more effectively evade the reticuloendothelial system, which results in longer intravascular retention, less macrophage activity, and reduced febrile responses.

10. Compared size of Perftoran particles and erythrocytes

11. Electron microscopepicture of erythrocyte and emulsion of Perftoran

13. While oxygen delivery capacity may be less than Oxygent, total surface area of Particles is greater which may facilitate oxygen transport.

14. Side effects: • allergic reactions (urticaria, pruritis, integument reddening), (Apparently manageable) • increase of heart rate • Reduction of arterial pressure • Elevation oftemperature • headache, retrosternal pain and lumbago • difficult breathing, anaphylactoid reactions. • Frequency of side effects is 1.8 - 6% • Note – often used in awake patients who can report side effects, in contrast to experience with other PFCs

15. Clinical application : • Effective anti-shock and anti-ischemic medicine • Acute or chronic hypovolemia or anemia as result of trauma,hemorrhage,burn;cardiogenic shock; endotoxical shock • Cranial trauma, brain and spine injury • Disturbance of brain microcirculation, acute ischemic stroke, fat embolism • Internal transplantation (ischemia protective perfusion of donor organs ) • Cardiology, cardiac surgery • Ophthalmology • Obliterating vessel diseases (Limb Ischemia) • Local applications (lavage of peritoneum and bronchialtree,intra-articular infusion, lavage of septicwounds and atrophic ulcers).

16. Perftoran– Clinical Applications • Major Indications: (over 50% of administrations) • Hemorrhagic Anemia/shock • Regional Ischemia – particularly limb • Cardiac Surgery • Brain Trauma • Spinal trauma

17. Characteristics of patients with grave polytrauma and massive loss of blood.

18. Complicationsof patients with grave polytrauma;treatment by Perftoran (1group) or saline solution (group 2).

19. Clinical Need • Mexico, Latin America and other nations do not have the medical infrastructure comparable to US and Europe • Significant limitations in blood availability • Donors, blood banking • Prevalence of blood borne disease, Zika, etc. • Limited availability for vascular intervention • Less robust trauma, Neuro ICU support

21. FluorO2 Therapeutics • Incorporated in US (Florida) • Management Team In Place • Has manufacturing plan developed for production in US with GMP standards • Mexican Health Ministry will re-issue approval when production certified • Reciprocal approval by other Latin American countries anticipated • Capital Investment needed • POC Deb Thompson

22. The percentage of patients treated with Perftoran, by indication. Total number of patients = 3528

23. Results Reportedly, 88% beneficial response, 8% neutral, 4% some adverse event Cardiac Surgery trial in Mexico, Chavez et.al. Reduced use of RBCs, no significant adverse outcomes.

24. Effect of Perftoran infusion; termovision imaging of patient suffered from occlusion vessel disease. (by Ivanitcky G.A.et al.2004) Two hours after Perftoran infusion (200 ml) Before treatment

25. PERFLUOROCARBON-BASED OXYGEN CARRIER IN TREATMENT OF ACUTE SPINAL CORD INJURY. Katunyan P., KlushnikT.*,Scherbakova I*., Peyker A.,Merenkov D. Department of Traumatology, Laboratory of molecular biochemistry*. Moscow Medical Academy,Moscow, Russia

26. Hematomyelia after experimental SCI: treatment by SMS-(right); supplemental oxygenation by Pf (center); normal (left).

28. Burn treatment

29. Before treatment

30. Final Remarks • Perftoran/Vidaphor has a very favorable benefit/risk • Greatest experience in actual human use of any PFC • Meets several critical needs in many countries • FTO2 is prepared to manufacture with GMP in USA • Experience and research with Perftoran is highly relevant to other PFC products – Oxygen is really the key • Many Research opportunities when product available • US FDA approval for human use would likely require extensive research, replication of at least some key studies. • Approval for use in many other countries could be gained relatively quickly through reciprocal agreements

31. Additional Information and References • Reference package available • Contact Deb Thompson • Deb.thompson@fluoro2therapeutics.com • Gary Latson, M.D. • garylatson@aol.com