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Stealth Peptides Leading Mitochondrial Therapeutics
Slide 2 Stealth Peptides
Mitochondria primer
Origins of mitochondria
oProkaryotic cells including bacteria
oEukaryotic cells
Mitochondria Origin
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
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
Slide 5 Stealth Peptides
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
Slide 6 Stealth Peptides
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
Slide 7 Stealth Peptides
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
Slide 8 Stealth Peptides
Bendavia Therapeutic Potential
Heart failure Skeletal muscle disorders
Renal disease
Dysfunctional Mitochondria
Cardiovascular disease Ophthalmology
Metabolic and diabetic diseases
Atherosclerosis
Neurodegeneration
Orphan mitochondrial diseases
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
Slide 10 Stealth Peptides
Chronic Kidney Disease Restores Renal Function in Animal Model
Eirin et al. ASN 2011
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
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
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
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
Slide 15 Stealth Peptides
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