Hemoglobin Oxygen Therapeutics LLC

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Mission Statement
To develop and commercialize the first and best in class technology platform for oxygen-carrying solutions addressing critical unmet medical needs in human and veterinary indications.

Company at a Glance
Delaware registered in 2014, technology is going back to 1990s with $1 billion invested
$20 million in equity financing to date
Acquired and developed the intellectual property for two Hemoglobin-Based Oxygen Carrier (HBOC) products :
Hemopure (HBOC-201) for human use
Oxyglobin (HBOC-301) for veterinary use
Existing collaborations in veterinary and human markets
Groundbreaking HBOC organ perfusion technology
Currently 12 employees
Production facility in Souderton, Pennsylvania

Brian Dawson
Senior Director, Process Development
25 years experience in development & commercialization of HbO2’s products from pre-clinical research to product approval & marketing.
Igor Serov
Co-Founder & CFO
Over 20 years of investment banking experience
Greg Dube, PhD
VP, Research & Development
30 years experience in drug R&D in large pharma and biotech firms.
Arkadiy Pitman
Senior Director, Statistics & Data Management
20 years of pharmaceutical & healthcare US experience with strong background in mathematics, statistics & logistics.
Melissa Zafirelis
Director, Regulatory & Clinical Operations
Over 22 years multinational regulatory & clinical operations experience.
Joseph Rappold, MD
Chief Medical Officer
30 years of active service (US Navy) with 6 combat deployments commanding a variety of medical facilities. Professor of Surgery at Tufts University. Chief of Acute Care Surgery and Trauma Medical Director at Maine Medical Center.
Highly experienced team
Fantao Meng
Director of Research and Development
Hemoglobin specialist with 20 years of research experience in developing hemoglobin-based oxygen carriers (HBOCs)
Zaf Zafirelis
Co-Founder & CEO
30 years of Biotech, Pharma, and Medical Device industries
More than 20 years CEO experience
Raised more than $100 million with successful exits

Hemopure and Oxyglobin
HBOCs with unique efficacy and safety profiles…

Worldwide blood shortage
COVID-19 pandemic highlights the need for a product that can successfully substitute blood’s oxygen carrying capacity in time of need
Shortages of blood donations, not reaching the critical threshold of 30 per 1000 population in many countries
Russia and South Africa alone cumulate a 3 millions blood units shortfall.
Blood shortage represents a $1 billion worldwide market per year.
Global Status Report on Blood Safety and Availability 2016
Hemopure has received marketing authorizations for acute anemia in South Africa & Russia

Strategic National Stockpiles
Out-of-hospital / Ambulance services
Remote locations / Military battlefield use
Prehospital trauma (military & civilian) and disaster preparedness in the US markets
represent $500 million in revenue per year.
Prehospital Trauma & Medical Readiness

Blood Is Not An Option
Blood disorders including Sickle Cell disease, Hemolytic Anemia, etc.
Rare blood types
Religious objectors (refuse blood transfusion).
BNO
160,000 patients with blood disorders need transfusions per year in US and Europe, which represents $400 million in revenue per year. Religious objectors represent another $149 million in annual revenue in the United States alone.

Blood shortage, a similar issue in
veterinary markets
2 million canine transfusions are needed annually in US and in Europe
Veterinary product is approved in US and EU
30 different species has been successfully treated with Oxyglobin
The US and European canine markets represent $550 million in revenue.
Only up to 25% of veterinary transfusion blood supplies are covered by blood banks
84% of US veterinarians are dissatisfied with current options

ZK1
Nutrients
There is a constant demand for donated organs
Organ eligibility criteria are extremely severe
The ability to extend the life of organs ex-vivo and to assess their compatibility and health can dramatically improve the supply for transplantations
The perfusion process allows doctors to assess reconditioning and viability of organs, limbs and tissues prior to transplantation both at room temperature and body temperature (37oC)
The transplantation market amounts to $137 million per year.
Organ Transplantation:
Another Worldwide Shortage

Additional indications include…
Ischemia indications including
Minimization of infarct size (STEMI - ST-Elevation myocardial infarction)
Resuscitation from sudden cardiac arrest
Minimization of tissue loss in Limb ischemia / PAD claudication
Antidote for carbon-monoxide and cyanide poisoning
Oncology with solid tumors
Burn victims and plastic surgery
Perfusion of
Limbs prior to transplantation
Brain cells for diagnostic purposes
The average potential US market size in each of these new indications is $500m.

Robust Pipeline

Strong value creating recent progress
US Department of Defense signed and sponsored Hemopure trial for pre-hospital trauma
Groningen liver transplantation trial finalized with 100% success
Patent filed for HBOC/Freeze Dried Plasma combination
Collaboration signed with Department of Defense and Teleflex on Hemopure use as a reconstitution agent for FDP
Yale University brain perfusion study with Hemopure published in Nature
Publication of high dose Hemopure case series
Patent filed for smoke inhalation antidote
Publication of an article supporting use of Hemopure in emergency preparedness including pandemics such as COVID-19

Strong value creating milestones
FDA submission for Hemopure Phase 3 pivotal BNO clinical trial
Start of hand transplant study
Submission of the IDE for the kidney perfusion trial
Oncology collaboration for the treatment of refractory solid tumors
Completion of production facility
Filing of CE Mark for perfusion solution
cGMP facility validation by US & EU regulators
Oxyglobin market launch
Hemopure market launch in South Africa

Major academic & health centers collaborations

Expanded access program hospitals

Over 300 peer-reviewed publications

Characteristics of Hemopure
Hb concentration 13 g/dL
Plasma half-life ~ 19 hours
Size = ~ 1 million < RBC
Stable for 3 years at 2-30 °C
Iso-osmotic, iso-oncotic
P50 = 40 mm Hg
Colloid (COP ~ to 6% albumin)
Viscosity = 2.1 cP (~4 cP for RBC)

Relative Efficacy to Increase Total Hb
Impact of 250 mL : PRBCs > whole blood, > Hemopure, > hetastarch

Vital Organ Blood Flow
MAP responds to Hemopure; ↑ 10 – 20 mmHg
Vital organ blood flow maintained
Mongan et al, J. Trauma 67:51-60, 2009

Tissue Oxygenation
Vital Organ Oxygenation Maintained
Hemodilution carried out in 3 stages: 10%, 30%, 50%
Organ-specific tissue PO2 determination via EPR imaging
Model
Results
Muir et al Shock v35, 597-603, 2011

Expanded Access Real World Clinical Experience
Representative Cases
Three sickle cell patients in crisis: RBCs refused/unavailable
Hb nadirs 3.5 - 4.0 g/dL
Febrile, MOF, neurologic dysfunction.
Hemopure administered: 6, 23, and 27 Units
Full recoveries
Kidney – Pancreas transplant: RBCs refused
Hb Nadir 2.0 g/dL
Tachycardia, tachypnea.
Hemopure administered: 12 units.
Full recovery
Autoimmune Hemolytic Anemia: RBCs refused
Hb nadir 4.6 g/dL
Elevated lactate
Hemopure administered: 27 units.
Full recovery
Davis et al, Transfusion, v58, 132-137, 2017
Gomez et al, Am J Transplant, v17, 1941-1944, 2017
Epperla et al, Transfusion, v56, 1801-1806, 2016

Ex-situ Perfusion prior to Transplantation
Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: a prospective clinical trial
DHOPE = dual hypothermic oxygenated machine perfusion (4°C - 12°C).
COR = controlled oxygenated rewarming.
NMP = normothermic machine perfusion (37°C)
Declined livers (ECD = high-risk)
Post-operative results
12-mo Graft survival: 100% (≥ std DCD & DBD)
Peak ALT & AST: << std DBD & DCD
DHOP-COR-NMP: ↑ donor livers 20% vs. std DCD & DBD
Van Leeuwen et al, Ann Surg, 2019
de Vries Y, et al. BMJ Open 2019

Manufacturing capacities
Facility building is fully constructed
Stage I is in place and operational ($20m replacement value)
Stage II – all equipment is acquired and waiting for installation ($70m replacement value)
Production facility fully operational in 9 months
Expansion capacity is secured on an adjacent plot
The manufacturing process involves two stages:
Certification from US and EU regulators is expected in 18 months
Stage I
Stage II
Hemopure
Oxyglobin

Cash positive in 2023 with $50m investment
$20m commitment secured