Corporate Presentation - Jefferies · Mitochondrial Structure and Function Aging, Muscle Wasting & Diabetes Healthy Physiology Chronic Diseases (CHF, CKD & DME) Rare Genetic ... for

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 Topline Data H1 2015

Study Interim 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


Ocular

Diseases

Ocuvia


ReVIEW


ReSIGHT

Muscle

Diseases

Bendavia



MMPOWER

Cardio-Renal

Diseases

Bendavia

Heart Failure(CHF)

PREVIEW


EVOLVE


EMBRACE










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


Ocular

Diseases

Ocuvia


ReVIEW


ReSIGHT

Muscle

Diseases

Bendavia



MMPOWER

Cardio-Renal

Diseases

Bendavia

Heart Failure(CHF)

PREVIEW


EVOLVE


EMBRACE

Bendavia Cardio-Renal Clinical Studies










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


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


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


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


● 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


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


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

Corporate Presentation

Beth DelGiaccoStern Investor Relations(212) 362-1200 [email protected]

Documents

Corporate Presentation - Jefferies · Mitochondrial Structure and Function Aging, Muscle Wasting & Diabetes Healthy Physiology Chronic Diseases (CHF, CKD & DME) Rare Genetic ... for