Jefferies Healthcare Conference 2015 Corporate 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 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 Delivery
Novel Peptoids
Small Molecules
Novel Peptides
Mitochondrial Pipeline
Novel Peptidomimetics
StealthMitochondrial Platform
Mitochondrial Biology Innovative Chemistry
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
‒ Electrostatic 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
StealthHighlights
● Bendavia and Ocuvia are "stealth" no longer
‒ Prominent clinical and scientific opinion leaders studied Bendavia and Ocuvia
‒ Demonstrating breakthrough therapeutic potential at premier conferences including
AHA, ESC, ASN, ARVO, ACC and ADA
● More than 100 peer-reviewed publications, abstracts and symposia
‒ Featured in IOVS, Circulation and JACC
‒ ASN top presentation
‒ ADA late-breaking presentation
‒ ESC ACS & heart failure symposia
‒ Cover of JASN
‒ Cover of Hypertension
Bendavia Bendavia
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
Diseases
Bendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal
Diseases
Bendavia
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
Ocuvia in Diabetic Eye DiseasesRestores Visual Function
p<0.05
‒ Dose-dependently reduces VEGF
expression and inflammation, restoring
visual acuity
‒ No effect on diabetic surrogates
including glucose or weight across
doses: 0.1, 1 and 3% eye drops
OcuviaDiabetesNormal
Industry and
academic
standard for
studying
visual acuity
Once a day
topical ocular
dosing with
Ocuvia (1%)
versus placebo
in diabetic mice
Electron Microscopy of Retinal Mitochondria
Normal Diabetes 0.1% 1% 3%
Alam et al. ADA 2012
Slide 9
Ocuvia in Diabetic Macular EdemaReVIEW Clinical Study
● Mitochondrial dysfunction
is an established and major
contributor to retinal inflammation,
edema and vascular permeability
● ReVIEW exploratory design
‒ Multiple ascending dose study
‒ Evaluating safety, tolerability and efficacy of
Ocuvia in patients with DME
‒ Endpoints: Imaging central subfield thickness
by optical coherence tomography (OCT) and
best corrected visual acuity
‒ 21 patients to be dosed twice a day for one-month
● Investigators and steering committee include
ophthalmologists that led registration trials
for Eylea® and Lucentis®
● ReVIEW data H2 2015
Imaging by OCT
Journal
Slide 10
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 11
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 12
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
Diseases
Bendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal
Diseases
Bendavia
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 13
Bendavia in Muscle DiseasesRole of Mitochondria
● Mitochondrial dysfunction is an established and major contributor
to skeletal muscle disorders
‒ Aging and sarcopenia
‒ Rare genetic mitochondrial diseases
‒ Wide-ranging skeletal muscle disorders including muscular dystrophy, cachexia
and Huntington's disease
Journal
Journal
Slide 14
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 15
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 16
Mitochondrial MyopathyA Mitochondrial Disease
Each rare genetic
mitochondrial
disease features
a reduced energetic
state
Bendavia improves mitochondrial energetics and
is the first-in-class therapy for MM
Mitochondrial myopathy (MM) comprises more than 200 rare genetic
mitochondrial diseases and 40,000 patients worldwide
MERRF
MELAS
POLG
KSS
Leigh's
MNGIENARP
Most common
complaint from genetic
mitochondrial disease
patients is skeletal
muscle fatigue
Slide 17
Bendavia in Rare Mitochondrial DiseasesPOLG: A Genetic Disorder
● Bendavia patient fibroblast study
of rare genetic POLG disorder
with MM
‒ Acute: Single 1mM ex vivo dose of
Bendavia
‒ Chronic: 7-days of 1mM Bendavia
dosing ex vivo
● No effect on normal healthy
patient fibroblasts (Control)
Journal
Bamberger et al. UMDF 2013
Saline
Acute
Chronic
p<0.05
Slide 18
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 19
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
Diseases
Bendavia
Skeletal Muscle DisordersMOTION
Mitochondrial Myopathy
MMPOWER
Cardio-Renal
Diseases
Bendavia
Heart Failure(CHF)
PREVIEW
Acute Kidney Injury (AKI)
EVOLVE
Acute Coronary Syndrome (ACS)
EMBRACE
Bendavia Cardio-Renal 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 20
Bendavia in Heart FailureImproves Cardiac Structure and Function
‒ Industry standard model pioneered by Dr. Hani
Sabbah and involved in the development of
every commercial heart failure drug
‒ Benefit comparable to best commercial drugs
without effecting heart failure surrogates
including heart rate or blood pressure
‒ More than 80 genetic pathways altered by heart
failure restored to normal with Bendavia
Supply ofEnergy
Demands forEnergy
Bendavia Heart
FailureCurrent
Therapies
BendaviaPlacebo
Electron Microscopy of Cardiac
Mitochondria in Heart Failure
Journal
Rabinovitch et al. Circulation 2013
Placebo
Bendavia
Eje
cti
on
Fra
cti
on
p<0.001
30%
35%
25%
Canine model
of heart failure
dosed once a day
with 0.5mg/kg
Bendavia for
3-months
Slide 21
Bendavia in Heart FailurePREVIEW Clinical Study
● PREVIEW exploratory design
‒ Randomized, single and multiple ascending dose,
double-blind placebo-controlled study
‒ Evaluating safety, tolerability and efficacy of Bendavia
in New York Heart Association Class II-III heart failure
patients
‒ Endpoints: Cardiac function, including ejection fraction,
by echocardiography and biomarkers of heart failure
‒ 36 patients receiving placebo or a single intravenous
dose of Bendavia
‒ Multiple ascending dose cohorts administered Bendavia
once a day for five-days
● Investigators and steering committee include
renowned cardiologists
‒ Duke University, Cleveland Clinic, Brigham and Women's
Hospital, Mayo Clinic, Ohio State University, University of
Glasgow, Charité, INSERM and Imperial College London
● PREVIEW data H1 2015
Cardiac Echocardiography
Slide 22
Bendavia in Heart FailurePREVIEW Clinical Study
Me
an
Pa
tie
nt LV
ES
V (
mL
)
● PREVIEW results
‒ Improves end systolic volume without changing heart rate or blood pressure
‒ End systolic volume is a major predictor of heart failure patient mortality
Anker et al. ESC Heart Failure 2015
160
120
100
80
0
180
140
60
Δ -46.0
40
20
Left Ventricular End Systolic Volume (LV ESV)
Placebo Bendavia
End-dose
12 hours post-dose
Canine Treatment Effect
Δ LV ESV (mL)
Placebo Bendavia
4
2
0
-2
-4
-6
Slide 23
Bendavia in Heart FailurePREVIEW Clinical Study
Me
an
Pa
tie
nt LV
ED
V (
mL
)
● PREVIEW results
‒ Improves end diastolic volume without changing heart rate or blood pressure
‒ Correlates with ejection fraction and cardiac output benefits for heart failure patients
Anker et al. ESC Heart Failure 2015
240
180
150
120
0
270
210
90
Δ -35.9
60
30
Left Ventricular End Diastolic Volume (LV EDV)
Placebo Bendavia
End-dose
12 hours post-dose
Canine Treatment Effect
Δ LV EDV (mL)
Placebo Bendavia
4
2
0
-2
-4
-6
Slide 24
Bendavia in Kidney DiseaseImproves Kidney Structure by Computed Tomography
X80,000
Electron Microscopy of Kidney
MitochondriaEirin et al. Cardio. Research 2013
Normal CKD with AKI Bendavia
Slide 25
Bendavia in Kidney DiseaseImproves Perfusion and Blood Flow by BOLD MRI
BOLD MRI: Blood oxygen level
detection (BOLD)
Eirin et al. Cardio. Research 2013
Normal CKD with AKI Bendavia
Slide 26
Bendavia in Acute Kidney InjuryEVOLVE Clinical Study
Renal Artery Stenosis
● EVOLVE exploratory design
‒ Randomized, double-blind placebo-controlled study at Mayo Clinic
‒ Evaluating safety, tolerability and efficacy of Bendavia in chronic kidney disease (CKD)
patients undergoing renal revascularization (AKI) to reduce blood pressure
‒ Endpoints: Parameters of renal function, including perfusion, by various imaging
modalities, GFR and biomarkers of kidney disease
‒ 28 patients receiving placebo or a single intravenous dose of Bendavia during AKI
● EVOLVE interim analysis featured at NIH symposium in February 2015
Slide 27
BendaviaEVOLVE Clinical Study
Chronic
Kidney
Disease
(CKD)
Patient
Before AKI
Increasing
Renal
Hypoxia
&
Decreasing
Perfusion
AKI &
Treatment
Placebo
Patient
Textor et al. NIH 2015
Bendavia
Patient
● BOLD MRI
‒ Significant serum creatinine decrease (p<0.05)
Slide 28
BendaviaEVOLVE Clinical Study
Bendavia
● Cortical perfusion by MDCT (mL/min)
‒ Multidetector computed tomography (MDCT)
Placebo
Textor et al. NIH 2015
p<0.05
*
Slide 29
Bendavia in Acute Coronary SyndromeReduces Infarct Size and Preserves Cardiac Microvasculature
Cardiovascular Disease BendaviaBendavia
Normal ACS
● Porcine model of ACS and ischemia reperfusion injury
‒ Single 0.05mg/kg/hr dose of Bendavia administered during revascularization
‒ Cardiac images by computed tomography 8-weeks after dosing
Eirin et al. J. Hypertension 2013
Slide 30
Bendavia in Acute Coronary SyndromeEMBRACE Clinical Study
● EMBRACE exploratory design
‒ Randomized, double-blind placebo-controlled study
‒ Evaluating safety, tolerability and efficacy of Bendavia in patients undergoing
primary angioplasty and stenting during STEMI
‒ Endpoints: Cardiac enzymes and imaging infarct volume by cardiac MRI
‒ Fully-enrolled with 297 patients
● EMBRACE Late-Breaking Clinical Trial (LBCT) presentation during
ACC 2015
Journal
Slide 31
Bendavia in Acute Coronary SyndromeEMBRACE Clinical Study
20
0
30
10Hea
rt F
ailu
re P
rob
ab
ility
(%
)
Placebo
Bendavia
0 4 8 12 16 20 24
25%
13.8%
Hours
Left Ventricular Ejection
Fraction (LVEF)
41.9 ± 10.4
(n=55)
44.0 ± 11.0
(n=52)p=0.16
Gibson et al. ACC 2015
● Clinical outcomes and heart failure
‒ Bendavia reduces (p=0.16) the incidence of heart failure during the initial day after ACS
by ~50% in the primary analysis population (n=118)
‒ No differences in clinical safety and patient tolerability
Slide 32
Bendavia in Acute Coronary SyndromeEMBRACE Clinical Study
● 297 patients in EMBRACE
‒ Bendavia significantly improves renal function in ACS patients (p=0.04, covariate
analysis)
4000
3000
2500
2000
0
Placebo
(n=145)
3732mmol∙h/L
3500
1500
Urina
ry C
rea
tin
ine fro
m 0
-48
Ho
urs
1000
500
Bendavia
(n=148)
3519mmol∙h/L
Gibson et al. ACC 2015
Slide 33
StealthOpportunity
Dystrophies
Skeletal Muscle & Movement Disorders
Coronary Syndromes & Atherosclerosis
Neurodegeneration
Renal Diseases
Neurologic Disorders & Autism
Bendavia
Rare Mitochondrial Diseases
Critical Care
Metabolic & Diabetic Disorders
Pulmonary & Respiratory Disorders
Ophthalmology
Heart Failure
Slide 34
Mitochondrial PipelineSBT 020 Preferential Distribution
Brain
SBT-020
140
120
0
100
80
2
4
6
0.5 hours 6 hours 16 hours
Bendavia
Tis
su
e/P
las
ma R
ati
o
Heart
SBT-020
6
4
0
2
Bendavia
Tis
su
e/P
las
ma R
ati
o
Lin et al. SBT 2014
● SBT 020 clinical studies planned for H2 2015
‒ Rare neurologic disorders including inherited mitochondrial diseases
‒ Neurodegeneration
Slide 35
Normal Placebo
SBT-020
8
6
4
0
2
Sta
ine
d N
eu
ron
al C
ell
s (×
10
00
)
12
10
#
SBT 020 in Parkinson DiseaseNeuroprotection
p<0.05
Normal Placebo SBT-020
Bamberger et al. SBT 2015
Slide 36
StealthMilestones
Indication Anticipated Milestones Timing
Diabetic Macular Edema(DME)Ocuvia
Initiate ReVIEW open-label study
Report topline data
H2 2014
H2 2015
Leber's Hereditary Optic Neuropathy
OcuviaInitiate ReSIGHT placebo-controlled study H2 2015
Skeletal Muscle DisordersBendavia
Initiate MOTION placebo-controlled study
Report topline data
H2 2014
H2 2015
Mitochondrial MyopathyBendavia
Initiate MMPOWER placebo-controlled study
Report topline data
H2 2014
H1 2016
Heart Failure(CHF)
BendaviaPREVIEW topline data H1 2015
Acute Kidney Injury(AKI)
BendaviaEVOLVE interim data H1 2015
Acute Coronary Syndrome (ACS)
BendaviaEMBRACE topline data H1 2015
Slide 37
StealthManagement Team
• Morningside Group: Chimerix (NASDAQ), Genocea (NASDAQ), BioVex (acquired by Amgen) and Argos (NASDAQ)
• More than a decade of biotechnology and venture investing experience
Travis Wilson — Chief Executive Officer
• Former CFO of AtheroGenics (NASDAQ) and Transgenomic (NASDAQ)
• More than 30 years of pharmaceutical and biotechnology experience including Schering-Plough
Mark Colonnese — Chief Financial Officer
• Former Director of Pfizer Cardiovascular and Metabolic Disease Research
• More than 20 years experience in drug discovery and early clinical development of blockbuster drug classes including statins and inhibitors of PCSK9 and CETP
Mark Bamberger, PhD — Chief Scientific Officer
• Former CEO of Neuron Systems (NASDAQ), founder and President of Vidus Ocular (acquired by OPKO Health) and founder and CEO of Peptimmune (acquired by Genzyme)
• More than 25 years of biotechnology and venture investing experience including BioSurface Technology (acquired by Genzyme)
Ben Bronstein, MD — Chief Medical Officer
• Commercial leadership roles with GlaxoSmithKline and Novo Nordisk, heading the commercial launch of multiple blockbuster drug classes
• More than 20 years pharmaceutical and biotechnology experience including Corgentech (NASDAQ)
Brian Blakey, PharmD — Chief Business Officer
Slide 38
StealthFinancials and Partnership Opportunities
● More than $225 million in raised capital
‒ Funding to initiate Phase 3 clinical development of Bendavia and Ocuvia
‒ Additional clinical candidates in H2 2015 and expansion of mitochondrial platform
‒ More than $90 million in available capital as of Q2 2015
● Planning for commercial launch in orphan mitochondrial diseases
by 2018
● Robust patent portfolio with compositions for Bendavia and Ocuvia
‒ More than 500 granted patents and pending applications worldwide
‒ Patent portfolio includes carrier compounds and liposomes delivering payloads to
mitochondria
● Collaboration opportunities with mitochondrial platform technologies
● Opportunities to partner during later-stage development
‒ Broad indications including cardio-renal diseases
‒ Potential geographic strategy with codevelopment and copromotion rights
Slide 39
StealthSummary
● Bendavia and Ocuvia represent a novel class of mitochondrial
targeted compounds
‒ Cardiolipin is a novel mitochondrial target
‒ Fundamental to maintaining healthy ATP and ROS production
● Clinical benefit in cardiac and renal disease patients from several
exploratory studies
‒ Well-tolerated in clinical trials of more than 500 patients and volunteers
● Broad mitochondrial platform with additional candidates planned
for clinical studies in H2 2015
‒ Innovative biology and chemistries enabling development of mitochondrial
targeted compounds
● Experienced leadership
‒ Deep capabilities in rare genetic mitochondrial diseases
‒ Core competencies in broad indications including ocular, muscle and cardio-renal
diseases
● Leading mitochondrial medicine