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Stealth Peptides Leading Mitochondrial Therapeutics

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Page 1: Stealth Peptides

Stealth Peptides Leading Mitochondrial Therapeutics

Page 2: Stealth Peptides

Slide 2 Stealth Peptides

Mitochondria primer

Origins of mitochondria

oProkaryotic cells including bacteria

oEukaryotic cells

Mitochondria Origin

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Slide 3 Stealth Peptides

Mitochondria

oThe organelle that produces energy in cells, often termed the “powerhouse of cells”

Mitochondria produce energy or ATP using energy from food

Primary source of ROS, initiates apoptosis or cellular death

Mitochondria Function

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Slide 4 Stealth Peptides

ATP ROS

Mitochondria

No ATP Nucleus

Apoptosis

ATP ROS

ATP ROS

ATP ROS

Healthy

Aging or Risk Factors

(Smoking and Obesity)

Chronic Diseases (CHF and

CKD)

Cell Dysfunction and Death

Genetic Diseases

Acute Ischemia,

Inflammation, and Death

Progression of Disease

Continuum of Mitochondrial Dysfunction Disease Progression

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Mitochondria Role in Disease

Diseased mitochondria produce excess ROS and lack ATP stores

oVicious cycle of disease progression

Heart failure

Autism

Orphan mitochondrial diseases

Inflammation and sepsis

Neurodegeneration

Diabetes

Ophthalmology

Kidney disease

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Challenges to treating mitochondria

o Cellular and outer mitochondrial membrane penetration

o Reduced membrane potential in disease

o Mitochondrial toxicity

Critical need for therapies to overcome these hurdles

Mitochondria Therapeutic Hurdles

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Bendavia First-in-Class Mitochondrial Targeted Compound

Targets cardiolipin, found exclusively in the inner mitochondrial membrane

oRestores ATP

oPrevents the formation of ROS

No apparent effect in healthy mitochondria

Ongoing and planned Phase 2 clinical trials

oACS study, led by Dr. Michael Gibson

oCKD study, led by Dr. Stephen Textor

oDME study, led by Dr. Jeffrey Heier

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Bendavia Therapeutic Potential

Heart failure Skeletal muscle disorders

Renal disease

Dysfunctional Mitochondria

Cardiovascular disease Ophthalmology

Metabolic and diabetic diseases

Atherosclerosis

Neurodegeneration

Orphan mitochondrial diseases

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Slide 9 Stealth Peptides

Bendavia Therapeutic Potential

Heart failure Skeletal muscle disorders

Renal disease

Dysfunctional Mitochondria

Cardiovascular disease Ophthalmology

Metabolic and diabetic diseases

Atherosclerosis

Neurodegeneration

Mitochondrial diseases

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Slide 10 Stealth Peptides

Chronic Kidney Disease Restores Renal Function in Animal Model

Eirin et al. ASN 2011

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Slide 11 Stealth Peptides

Bendavia Therapeutic Potential

Heart failure Skeletal muscle disorders

Renal disease

Dysfunctional Mitochondria

Cardiovascular disease Ophthalmology

Metabolic and diabetic diseases

Atherosclerosis

Neurodegeneration

Mitochondrial diseases

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Slide 12 Stealth Peptides

Aging Restores Muscle Function in Animal Model

p <0.05

Age5 months 27 months

Max

imal

ATP

Pro

duct

ion

0

200

400

600

800

1000

1200ControlBendavia

Improves Maximal ATP Production In Age

Marcinek et al. Aging Cell 2013

TreatmentControl Bendavia

End

uran

ce C

apac

ity0

200

400

600

800

1000

1200 p <0.05

Improves Endurance in Age

No apparent effect of Bendavia on normal muscle

function

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Slide 13 Stealth Peptides

Bendavia Therapeutic Potential

Heart failure Skeletal muscle disorders

Renal disease

Dysfunctional Mitochondria

Cardiovascular disease Ophthalmology &

Diabetes

Metabolic and diabetic diseases

Atherosclerosis

Neurodegeneration

Mitochondrial diseases

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Slide 14 Stealth Peptides

Diabetic Vision Loss Reversed with Bendavia in Animal Model

Normal Diet + VehicleNormal Diet + Bendavia

Week0 4 8 12 16 20 24 28

Spat

ial F

requ

ency

(c/d

)

0.00

0.25

0.30

0.35

0.40

0.45Normal Diet

Study Drug

Normal Diet + VehicleDiabetic diet/STZ+ VehicleDiabetic diet/STZ+ Bendavia

Week0 4 8 12 16 20 24 28

Spat

ial F

requ

ency

(c/d

)

0.00

0.25

0.30

0.35

0.40

0.45Diabetic Diet Plus Streptozotocin (STZ)

Study DrugSTZ

Alam et al. ADA 2012

p<0.05

No apparent effect of Bendavia on blood glucose or body weight

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Summary Mitochondria and Bendavia

Stealth Peptides

Everyone has mitochondrial disease

oThe continuum from aging to genetic mitochondrial diseases

The continuum of mitochondrial dysfunction features increased ROS and decreased ATP

Bendavia appears to restore ATP levels and prevents ROS formation, without affecting healthy mitochondria

oMore than 100-peer reviewed papers and abstracts

oMore than 300 patients and volunteers of clinical experience with Bendavia

No apparent effect in normal, healthy mitochondria