Jjohn campbell- Stealth, Convegno Mitocon 2015

Bologna, June

John Campbell, Senior Director, Clinical and Regulatory Affairs

MitoCon Presentation

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

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

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

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

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 Topline Data H1 2015

Study Interim Data H1 2015


Mitochondrial Platform with Novel Candidates Planned for Clinical Studies in H2 2015


Ocular Diseases

Ocuvia


ReVIEW


ReSIGHT




MMPOWER


Heart Failure (CHF)

PREVIEW


EVOLVE


EMBRACE

OcuviaOcular Clinical Studies










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

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

BendaviaMuscle Clinical Studies


Ocular Diseases

Ocuvia


ReVIEW


ReSIGHT




MMPOWER


Heart Failure (CHF)

PREVIEW


EVOLVE


EMBRACE










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

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

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

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!

Jjohn campbell- Stealth, Convegno Mitocon 2015

Health & Medicine

Transcript of Jjohn campbell- Stealth, Convegno Mitocon 2015