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Forward-Looking Statements
includes forward-looking statements about our business prospects, financial position, and development of vepoloxamer and AIR001 for therapeutic use in humans. Any statement that is not a statement of historical fact should be considered a
forward-looking statement. Because forward-looking statements relate to the future, they are subject to inherent risks, uncertainties and changes in circumstances that are difficult to predict. Actual events or performance may differ materially from
our expectations indicated by these forward-looking statements due to a number of factors, including, but not limited to, results of our pending and future clinical studies, the timeline for clinical and manufacturing activities and regulatory
approval; our dependency on third parties to conduct our clinical studies and manufacture our clinical trial material; our ability to raise additional capital, as needed; our ability to establish and protect proprietary rights related to our product
candidates; and other risks and uncertainties more fully described in our press releases and our filings with the SEC, including our annual report on Form 10-K filed with the SEC on March 26, 2014.
We caution you not toplace undue reliance on any of these forward-looking statements, which speak only as of the date of
this presentation. Wedonot intendtoupdate anyforward-looking statement included in this presentation to reflect events or circumstances arising after the date of the presentation, except as may be required by law.
biopharmaceutical company based in San Diego
? Developing vepoloxamer (MST-188) for:
? Rare ( orphan ) diseases:
? Sickle Cell Disease ? Acute Limb Ischemia
Large market opportunities:
? Heart Failure? Stroke
? Developing AIR001 for:
? Heart failure with preserved ejection fraction? Commercially complementary to vepoloxamer
Product Candidate Pipeline
Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease
Heart Failure Planned
Preclinical Phase 1 Phase 2 Phase 3
Heart Failure ( HFpEF ) Enrolling
Vepoloxamer: A Biophysical Agent
Poiseuille s Law describes Newtonian flow
? Want lower viscosity?
? Reduce friction by
lowering adhesion and improving the deformability of cells
? Reduce surface tension with vepoloxamer
Vepoloxamer Overview
(CH2CHO)30 (CH2CH2O)79 H
API Structure: | CH3
Large, synthesized polymer with extraction process to CMC: remove undesirable (toxic) components
Composition of matter claims pending Administration: IV infusion
Rapidly and predominantly cleared by kidneys (4-8h) ADME:
Ether linkages cannot be cleaved; no drug metabolites
Vepoloxamer Mechanism of Action
adheres to hydrophobic domains on a cell surface, such as damaged membranes and adhesive proteins.
for Healthy Cell Membranes
But Adheres to Damaged Cell Membranes
Vepoloxamer Pharmacodynamics
Lowers adhesion Cell
integrity maintained Improves flow Ca2+ influx reduced
Vepoloxamer adheres to hydrophobic domains on cells and
lowers surface tensions
Intracellular Ca2+ Level
2.5 5 10 20 40 80 0 Low Dose High Dose
Vepoloxamer Pharmacodynamics
to hydrophobic domains on cells and lowers surface tensions
Viscosity is reduced
Improves flow Membranes are sealed
Ca2+ influx reduced Sickle Cell Disease: Less cell adhesion, reduced hemolysis
Acute Limb Ischemia: Faster thrombolysis, less reperfusion injury
Heart Failure: Lower viscosity, more membrane repair
Objective Improve blood flow
and shorten the duration of crisis
Overview of Sickle Cell Disease
genetic disorder and rare (orphan) disease
? Affects 90,000 to 100,000 people in the US . .
? Characterized by severe deformation (i.e., sickling ) of red blood cells
? Hallmark of disease is a vaso-occlusive crisis
? Exceedingly painful condition? Leading cause of hospitalization
? Significant unmet need
? No approved agents to shorten duration or severity of crisis
? Standard of care (hydration and analgesics) unchanged for >10 years
? Vaso-occlusion is associated with early death
Obstructed blood flow -> hypoxia -> tissue death -> organ failure? Average age at death; 42 years (males), 48 years (females)
Role of Vepoloxamer in Sickle Cell Disease
Vaso-Occlusive Crisis:
? Adhesion of poorly-deformable, sticky cells to endothelium and to each other leads to vessel obstruction? Occluded RBC s cannot deliver oxygen, leading to ischemia,
? Lowers viscosity, reduces adhesion of cells to endothelium, lowers RBC aggregation, improves RBC deformability and restores blood flow
Vepoloxamer Reduces RBC Aggregation (normal volunteers)
Dose-dependent effect on red blood cell aggregation
1 gation Aggregate extent
Aggre 0.6 Aggregate strength
0.25 0.5 1 2 5 Poloxamer 188* (mg/mL)
? The effect of five concentrations of poloxamer 188* on RBC aggregation was determined using a Myrenne aggregometer.
? Results represent the mean of samples from 20 healthy volunteers relative to PBS controls. (Meiselman, et. al.)
*Vepoloxamer is purified poloxamer 188
Vepoloxamer Reduces RBC Aggregation (sickle cell patients)
Dose-dependent effect on sickle cell red blood cell aggregation
Aggregate extent tion 0.8
Aggrega 0.6 Aggregate strength
0 0.25 0.5 1 Poloxamer 188* (mg/mL)
? The effect of poloxamer 188 on sickle cell RBC aggregation determined by a Myrenne aggregometer? Results represent the mean from 11 patients relative to PBS controls (Meiselman, et al.)
*Vepoloxamer is purified poloxamer 188
Vepoloxamer Decreases Blood Viscosity Under Low Shear Rates
Poloxamer 188* decreased viscosity of sickle cell whole blood
Poloxamer 188 concentration (mg/mL)
188 added to whole blood (40% hematocrit) and viscosity measured using a Contraves viscometer at 3 shear rates.
? Results represent the mean of samples from 11 SCD patients relative to PBS controls. (Meiselman, et al.)
*Vepoloxamer is purified poloxamer 188
Vepoloxamer Effect on Sickle Cells
tension improves flow and deformability (video)
Before vepoloxamer After vepoloxamer
Vepoloxamer Improves Blood Flow
improved microvascular blood flow in SCD patients during vaso-occlusive crisis
1.8 Vepoloxamer 1.6 Placebo
0.8 Red cell velocity (mm/s) Veloci 0.6 measured by video microscopy in nine sickle cell patients with
02. vaso-occlusive crisis.
Before Infusion 2-Hours 7-Hours
(Crisis Baseline) After Loading After Loading