Stealth Peptides Leading Mitochondrial Therapeutics Mitochondria - PowerPoint PPT Presentation

Stealth Peptides Leading Mitochondrial Therapeutics

Mitochondria Origin  Mitochondria primer  Origins of mitochondria o Prokaryotic cells including bacteria o Eukaryotic cells Slide 2 Stealth Peptides

Mitochondria Function  Mitochondria o The 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 Slide 3 Stealth Peptides

Continuum of Mitochondrial Dysfunction Disease Progression Progression ATP ROS of Disease Healthy Aging or Risk Factors ATP ROS (Smoking and Obesity) Chronic ATP ROS Diseases (CHF and CKD) ATP Genetic ROS Diseases Cell Dysfunction and Death Acute Mitochondria Ischemia, Apoptosis Inflammation, No ATP and Death Nucleus Slide 4 Stealth Peptides

Mitochondria Role in Disease  Diseased mitochondria produce excess ROS and lack ATP stores o Vicious cycle of disease progression  Heart failure  Autism  Orphan mitochondrial diseases  Inflammation and sepsis  Neurodegeneration  Diabetes  Ophthalmology  Kidney disease Slide 5 Stealth Peptides

Mitochondria Therapeutic Hurdles  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 Slide 6 Stealth Peptides

Bendavia First-in-Class Mitochondrial Targeted Compound  Targets cardiolipin, found exclusively in the inner mitochondrial membrane o Restores ATP o Prevents the formation of ROS  No apparent effect in healthy mitochondria  Ongoing and planned Phase 2 clinical trials o ACS study, led by Dr. Michael Gibson o CKD study, led by Dr. Stephen Textor o DME study, led by Dr. Jeffrey Heier Slide 7 Stealth Peptides

Bendavia Therapeutic Potential Orphan mitochondrial diseases Renal disease Heart failure Skeletal muscle disorders Dysfunctional Mitochondria Atherosclerosis Metabolic and diabetic diseases Cardiovascular disease Neurodegeneration Ophthalmology Slide 8 Stealth Peptides

Bendavia Therapeutic Potential Mitochondrial diseases Renal disease Heart failure Skeletal muscle disorders Dysfunctional Mitochondria Atherosclerosis Metabolic and diabetic diseases Cardiovascular disease Neurodegeneration Ophthalmology Slide 9 Stealth Peptides

Chronic Kidney Disease Restores Renal Function in Animal Model Eirin et al. ASN 2011 Slide 10 Stealth Peptides

Bendavia Therapeutic Potential Mitochondrial diseases Renal disease Heart failure Skeletal muscle disorders Dysfunctional Mitochondria Atherosclerosis Metabolic and diabetic diseases Cardiovascular disease Neurodegeneration Ophthalmology Slide 11 Stealth Peptides

Aging Restores Muscle Function in Animal Model Improves Maximal ATP Production Improves Endurance in Age In Age 1200 p <0.05 1200 Control Endurance Capacity Maximal ATP Production Bendavia 1000 1000 800 800 p <0.05 600 600 400 400 200 200 0 0 5 months 27 months Control Bendavia Treatment Age No apparent effect of Bendavia on normal muscle function Marcinek et al. Aging Cell 2013 Slide 12 Stealth Peptides

Bendavia Therapeutic Potential Mitochondrial diseases Renal disease Heart failure Skeletal muscle disorders Dysfunctional Mitochondria Atherosclerosis Metabolic and diabetic diseases Cardiovascular disease Neurodegeneration Ophthalmology & Diabetes Slide 13 Stealth Peptides

Diabetic Vision Loss Reversed with Bendavia in Animal Model Normal Diet Diabetic Diet Plus Streptozotocin (STZ) 0.45 0.45 Spatial Frequency (c/d) Spatial Frequency (c/d) 0.40 0.40 0.35 0.35 p<0.05 Normal Diet + Vehicle 0.30 0.30 Normal Diet + Vehicle Normal Diet + Bendavia Diabetic diet/STZ+ Vehicle Diabetic diet/STZ+ Bendavia 0.25 0.25 STZ Study Drug Study Drug 0.00 0.00 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 Week Week No apparent effect of Bendavia on blood glucose or body weight Alam et al. ADA 2012 Slide 14 Stealth Peptides

Summary Mitochondria and Bendavia  Everyone has mitochondrial disease o The 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 o More than 100-peer reviewed papers and abstracts o More than 300 patients and volunteers of clinical experience with Bendavia  No apparent effect in normal, healthy mitochondria Stealth Peptides Slide 15 Stealth Peptides