Bologna, June
John Campbell, Senior Director, Clinical and Regulatory Affairs
MitoCon Presentation
Slide 2
StealthIntroduction
● Clinical-stage biopharmaceutical company leading mitochondrial medicine
● Bendavia and Ocuvia represent a novel class of mitochondrial targeted compounds‒ Currently studied in several exploratory Phase 2 clinical trials‒ Phase 3 clinical trials are planned for 2016
● Bendavia and Ocuvia focus on opportunities in rare and common diseases‒ Demonstrated clinical benefit in cardiac and renal patients‒ Well-tolerated in trials of more than 500 patients and volunteers
● Broad mitochondrial platform beyond Bendavia and Ocuvia‒ Deep capabilities in mitochondrial biology and chemistry‒ Robust patent portfolio with more than 200 granted patents
● Founded in 2007 by life science investors, Morningside Group
Mitochondrion
Slide 3
Cell DysfunctionAnd Death
Healthy Mitochondria
Disease ContinuumMitochondrial Structure and Function
Aging, Muscle Wasting & Diabetes
HealthyPhysiology
Chronic Diseases
(CHF, CKD & DME)
Rare Genetic Diseases
Acute Ischemia,Inflammation &
Death
ROSROS
ATP ATPATP
ROS
Slide 4
Mitochondrial Therapeutic ChallengesBendavia and Ocuvia: A Novel Class
Cardiolipin● Bendavia and Ocuvia overcome the challenges of developing mitochondrial targeted compounds ‒ Diffusing across cellular and mitochondrial membranes,
targeting cardiolipin, a lipid present only in mitochondria‒ No effect on healthy mitochondria
● Ocuvia is a topical ophthalmologic product and Bendavia is an oral, subcutaneous or intravenous product‒ Modifying disease without changing conventional surrogates such as glucose,
heat rate or blood pressure ‒ Complementary to standard-of-care
● Different than conventional mitochondrial approaches and nonspecific targets
Slide 5
Healthy Mitochondrial Structure
Diseased Mitochondrial Structure
Normal ATP Increased ROS
Healthy Cardiolipin
DiseasedCardiolipin
● Cardiolipin shapes mitochondrial structure‒ Foundation of electron transport chain (ETC)‒ Maintains healthy ATP levels and minimal
ROS production
● Disease alters and compromises cardiolipin ‒ Disrupts ATP generation and increases ROS‒ Changes mitochondrial structure and
function, progressing disease
● Bendavia and Ocuvia reestablish healthy mitochondrial structure and function in disease‒ Selective interaction with cardiolipin,
maintaining ETC‒ Restoring healthy ATP and ROS levels ‒ Modifying disease
ETC
Restores normal ATP levels and decreases ROS
in disease
Bendavia
Bendavia and OcuviaImprove Mitochondrial Structure and Function
Slide 6
Bendavia and OcuviaClinical Studies
Rare Diseases (White) & Broad Indications (Black) Phase 1 Phase 2 Phase 3
Ocular Diseases
Ocuvia
Diabetic Macular Edema (DME)
ReVIEW
Leber's Hereditary Optic Neuropathy
ReSIGHT
Muscle DiseasesBendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal DiseasesBendavia
Heart Failure (CHF)
PREVIEW
Acute Kidney Injury (AKI)
EVOLVE
Acute Coronary Syndrome (ACS)
EMBRACE
Current Status Expected Progress
Fully-Enrolled with Data H2 2015
Study Initiating H2 2015
Study Recruiting Patients Data H2 2015
Study Recruiting Patients Data H1 2016
Study Topline Data H1 2015
Study Interim Data H1 2015
Study Topline Data H1 2015
Mitochondrial Platform with Novel Candidates Planned for Clinical Studies in H2 2015
Slide 7
Rare Diseases (White) & Broad Indications (Black) Phase 1 Phase 2 Phase 3
Ocular Diseases
Ocuvia
Diabetic Macular Edema (DME)
ReVIEW
Leber's Hereditary Optic Neuropathy
ReSIGHT
Muscle DiseasesBendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal DiseasesBendavia
Heart Failure (CHF)
PREVIEW
Acute Kidney Injury (AKI)
EVOLVE
Acute Coronary Syndrome (ACS)
EMBRACE
OcuviaOcular Clinical Studies
Current Status Expected Progress
Fully-Enrolled with Data H2 2015
Study Initiating H2 2015
Study Recruiting Patients Data H2 2015
Study Recruiting Patients Data H1 2016
Study Topline Data H1 2015
Study Interim Data H1 2015
Study Topline Data H1 2015
Mitochondrial Platform with Novel Candidates Planned for Clinical Studies in H2 2015
Slide 8
Leber's Hereditary Optic NeuropathyIntroduction
● Leber's Hereditary Optic Neuropathy (LHON)‒ Mitochondrial optic neuropathy causing optic nerve atrophy
and blindness‒ Due to three distinct mitochondrial DNA point mutations with
G11778A comprising more than 90% of LHON patients
● Nearly 40,000 patients worldwide‒ Thousands more carry G11778A mutation‒ Most common inherited mitochondrial optic neuropathy
● Tragic disease presentation‒ Sudden blindness ‒ Predominately males older than 20 years of age
● LHON is entirely mitochondrial ATP and ROS mediated‒ Ocuvia holds promise for LHON patients by restoring ATP and
reducing ROS production
● More than 20 rare mitochondrial optic neuropathies with no FDA approved therapies
Electron Microscopy
Retinal Mitochondria in LHON
LHON Vision
Slide 9
Ocuvia in LHONReSIGHT Clinical Study
● ReSIGHT exploratory design‒ Randomized study ‒ Evaluating safety, tolerability and efficacy of Ocuvia in
patients with LHON (G11778A mutation) ‒ Endpoints: Humphrey's visual field testing, best corrected
visual acuity and retinal nerve fiber thickness by OCT
● Investigators and steering committee are the leading LHON clinicians in the U.S. and Europe
● Progressing FDA and EMEA discussions on clinical study design‒ Strong support from LHON patient advocacy group
● ReSIGHT study recruitment planned for H2 2015
Humphrey's Visual Field Testing
Slide 10
BendaviaMuscle Clinical Studies
Rare Diseases (White) & Broad Indications (Black) Phase 1 Phase 2 Phase 3
Ocular Diseases
Ocuvia
Diabetic Macular Edema (DME)
ReVIEW
Leber's Hereditary Optic Neuropathy
ReSIGHT
Muscle DiseasesBendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal DiseasesBendavia
Heart Failure (CHF)
PREVIEW
Acute Kidney Injury (AKI)
EVOLVE
Acute Coronary Syndrome (ACS)
EMBRACE
Current Status Expected Progress
Fully-Enrolled with Data H2 2015
Study Initiating H2 2015
Study Recruiting Patients Data H2 2015
Study Recruiting Patients Data H1 2016
Study Topline Data H1 2015
Study Interim Data H1 2015
Study Topline Data H1 2015
Mitochondrial Platform with Novel Candidates Planned for Clinical Studies in H2 2015
Slide 11
Bendavia in Muscle DiseasesRestores ATP and Muscle Function
Bendavia Improves Muscle Function with Age
p<0.05
● Age-related skeletal muscle dysfunction in mice 5 and 27 months of age‒ Maximal ATP production assessed by in vivo metabolic spectroscopy (nmole ATP/gs) ‒ Endurance capacity evaluated by treadmill time (seconds)
Single 3mg/kg dose of Bendavia assessed after one-hour
7-days of 3mg/kg Bendavia dosing in mice 27 months of age
Marcinek et al. Aging Cell 2013
Impaired ATP Production with Age
p<0.05
Control
Bendavia
Slide 12
Bendavia in Muscle Diseases MOTION Clinical Study
● MOTION exploratory design‒ Randomized, double-blind placebo-controlled study ‒ Evaluating safety, tolerability and efficacy of Bendavia in patients older than 65 years of
age‒ Endpoints: ATP production by in vivo metabolic spectroscopy and skeletal muscle
function ‒ 40 patients receiving placebo or a single intravenous dose of Bendavia
● Single-site clinical study‒ University of Washington‒ National Institute of Aging center of excellence
● MOTION data H2 2015
Slide 13
Bendavia in Mitochondrial MyopathyMMPOWER Clinical Study
● MMPOWER exploratory design‒ Randomized, multiple ascending dose, double-blind placebo-controlled study ‒ Evaluating safety, tolerability and efficacy of Bendavia in patients with MM‒ Endpoints: Standard 6-minute walk test (6-MWT) and cardiopulmonary exercise
capacity‒ 36 patients dosed once a day for five-days
● Investigators and steering committee include leading mitochondrial clinicians at Massachusetts General Hospital, Cleveland Clinic, Mayo Clinic, University of California at San Diego and University of Pittsburgh
● FDA and patient advocacy ‒ Identified Phase 3 registration endpoints for MM patients including 6-MWT and
cardiopulmonary exercise capacity‒ Strong support from patient advocacy groups including United Mitochondrial Disease
Foundation (UMDF) and MitoAction
● MMPOWER currently recruiting patients with topline data expected H1 2016
Slide 14
Treatments to PATIENTS
Faster
Trial Design & Endpoints
Broad Coalition of Partners
Biomarkers
Clinical Data Sets & Registries
Collaborate & Educate
MM Clinical DevelopmentPatient Focus and Collaboration in Rare Disease
Thank You!
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