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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

  • 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

  • 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

    Stealth Peptides MitochondriaOriginMitochondriaFunctionContinuum of Mitochondrial DysfunctionDisease ProgressionMitochondriaRole in DiseaseMitochondriaTherapeutic HurdlesBendaviaFirst-in-Class Mitochondrial Targeted CompoundBendaviaTherapeutic PotentialBendaviaTherapeutic PotentialChronic Kidney DiseaseRestores Renal Function in Animal ModelBendaviaTherapeutic PotentialAgingRestores Muscle Function in Animal ModelBendaviaTherapeutic PotentialDiabetic Vision LossReversed with Bendavia in Animal ModelSummaryMitochondria and Bendavia