Targeting the powerhouse of the cell - to treat rare genetic and age-related diseases - Stealth BioTherapeutics Inc.

Targeting the powerhouse of the cell
 to treat rare genetic and age-related diseases

 September 2020

Our forward-looking statements and disclaimers

 This presentation and various remarks we make during this presentation contain forward-looking statements within the meaning of The Private Securities Litigation
 Reform Act of 1995. Such forward-looking statements include those regarding Stealth BioTherapeutics’ plans, strategies and expectations for its preclinical and
 clinical advancement of its drug development programs including elamipretide, SBT-20, SBT-272, SBT-259 and SBT-550; the potential benefits of Stealth
 BioTherapeutics’ product candidates; its key milestones for 2020; its plans regarding future data presentations; and its financial guidance regarding the period in
 which it will have capital available to fund its operations. The words “anticipate,” “expect,” “hope,” “plan,” “potential,” “possible,” “will,” “believe,” “estimate,”
 “intend,” “may,” “predict,” “project,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking
 statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and
 you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations
 disclosed in the forward-looking statements we make as a result of known and unknown risks, uncertainties and other important factors, including: our ability to
 obtain additional funding; the ability to successfully demonstrate the efficacy and safety of Stealth BioTherapeutics’ product candidates and future product
 candidates; the preclinical and clinical results for Stealth BioTherapeutics’ product candidates, which may not support further development and marketing
 approval; the potential advantages of Stealth BioTherapeutics’ product candidates; the content and timing of decisions made by the U.S. FDA, the EMA or other
 regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, which may affect the initiation, timing and progress of
 preclinical studies and clinical trials of Stealth BioTherapeutics product candidates; Stealth BioTherapeutics’ ability to obtain and maintain requisite regulatory
 approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Stealth BioTherapeutics’ ability to
 obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; and general economic and market
 conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in the Stealth BioTherapeutics’ Annual Report on Form
 20-F for the year ended December 31, 2019 filed with the Securities and Exchange Commission on April 1, 2020 and any future filings with the Securities and
 Exchange Commission. Any forward-looking statements contained in this presentation and various remarks we make during this presentation speak only as of the
 date hereof, and Stealth BioTherapeutics expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information,
 future events or otherwise, except as required by law.

2 © 2020 Stealth BioTherapeutics.

Pioneering mitochondrial medicine

 Platform potential Improved organ function Patient-focused
 rare and common diseases with long-term therapy targeting unmet needs

 Barth, Geographic
 Duchenne, atrophy,
 Becker, LHON
 Friedreich’s

 ALS, MSA

 Elamipretide: TAZPOWER (Barth
 ReCLAIM (drysyndrome)
 AMD) Across rare and common
 rare cardiomyopathies, geographic Geographic
 ↑ left ventricular atrophy
 stroke volumegrowth
 (BL torate
 Week 72 patient populations
 atrophy, LHON measured
 OLE slope of ∆ p

Elamipretide normalizes dysfunctional mitochondrial morphology across diseases

 Improved mitochondrial function observed
 across multiple models, including::
 Dry age-related macular
 degeneration, glaucoma,
 diabetic macular edema,
 diabetic retinopathy, Leber’s
 hereditary optic neuropathy
 Heart failure (reduced and
 preserved, ischemic and
 nonischemic, congenital
 (Barth, Becker) and
 acquired), acute and chronic
 kidney disease
 Age-related skeletal muscle
 dysfunction, mitochondrial
 Mouse model of diabetic retinopathy myopathy, Friedreich’s ataxia

4 © 2020 Stealth BioTherapeutics. Szeto, Birk, Am J Physiol 2014 Szeto HH, Birk AV. Clin Pharmacol Ther. 2014

Our pipeline

 Category Product Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Next
 Candidate Milestone
 Complete
 Geographic atrophy enrollment YE
 2020
 Elamipretide P2 to commence
 Friedreich’s ataxia Enrolling H2 2020
 H2 2020
 Leber’s hereditary
 P3 initiation
 optic neuropathy
 Phase 2/3 completed
 2020 regulatory
 Barth syndrome
 interactions
 Elamipretide
 Duchenne, other rare Protocol
 Planning
 cardiomyopathies submission 2021
 POLG and replisome- MMPOWER-3 Protocol
 Elamipretide Planning
 related disorders subgroup submission 2021
 Amyotrophic lateral
 ongoing
 ongoing ongoing
 ongoing** Complete Phase 1
 SBT-272 sclerosis/multiple
 *in healthy volunteers trial
 system atrophy
 Charcot-Marie-Tooth Progress to clinical
 SBT-259 ongoing
 T2/other trials
 Leigh’s Preclinical
 SBT-550 ongoing
 syndrome/other studies

5 © 2020 Stealth BioTherapeutics.

Over 10 decades of drug development expertise

 Reenie McCarthy, Chief Executive Officer

 Brian Blakey, PharmD, Chief Business Officer

 Jim Carr, PharmD, Chief Clinical Development Officer

 Marty Redmon, PhD, Executive VP, Discovery,
 Development and Technical Operations

 Rob Weiskopf, Chief Financial Officer

6 © 2020 Stealth BioTherapeutics.

Elamipretide mechanism

7

Elamipretide aggregates and stabilizes cardiolipin

 Normal mitochondria Diseased mitochondria

 ATP (energy)

 Cardiolipin Oxidative stress/free radicals ROS

 Protein importation

 Super-complex formation
 Elamipretide (ELAM) associates with
 cardiolipinFission,
 (CL) in fusion,
 a 1ELAM:mitophagy
 2CL molar ratio,
 improving mitochondrial structure and
 function across numerous disease models
 Cardiolipin

 Cristae

 Electron transport chain (ETC) complexes

 e Electrons

 Reactive oxygen species (ROS)
8 © 2020 Stealth BioTherapeutics

Elamipretide normalizes mitochondrial networking

 Healthy Cardiomyopathy Cardiomyopathy + ELAM

 Fibroblasts from a cardiomyopathy patient

9 © 2019 Stealth BioTherapeutics. C O N F I D E N T I A L Machiraju et al., biorchiv 2019

Elamipretide restores healthy mitochondrial function

 ↑ ATP production ↓ Oxidative stress/free radicals ↑ Protein transcription/importation

 Healthy elderly patients (n=40) with Increased mitochondrial ROS in Improvements observed in protein importation observed in BTHS, FRDA and HF
 muscle mitochondrial dysfunction cardiomyopathy fibroblasts models; may explain differential signals in mtDNA vs nDNA mutations in PMM
 P3 trial
 MOTION P2 trial

 p=0.055* Elamipretide improves frataxin expression in
 Plac
 Elam FRDA patient-derived lymphoblasts (GM15850)

 *after exclusion of 1 outlier Machiraju et al., Frontiers Cardiovascular Medicine 2019 Zhao, Sci Rep, 2017; UMDF Virtual Symposium 2020 (see slide 40)
 Conley et al., HFSA 2016

10 © 2020 Stealth BioTherapeutics

Elamipretide safety

11

Elamipretide - safety and tolerability

 Exposure Duration Side effects Injection site
 of exposure in >5% exposed subjects reactions

 ~900 subjects >2 years Eosinophil increase (mild/moderate + Transient mild to moderate
 systemically, (systemic and topical) no associated signs/symptoms), URI, ISRs in majority of subjects
 ~53 subjects topical increased blood IgE (no associated receiving elamipretide by SC
 ophthalmic drops signs/symptoms), dizziness, administration
 headache, UTI + viral gastroenteritis

 IgE – immunoglobin E; ISR – injection site reaction; SC – subcutaneous; URI – upper respiratory tract infection; UTI – urinary tract infection

12 © 2020 Stealth BioTherapeutics

Ophthalmic indications

13

Dry AMD development program

 Route of Preclinical Natural Clinical Current &
 administration models history data next steps

 1 mg/kg SC elamipretide Improved mitochondrial High risk drusen + Phase 1 ReCLAIM trial showed ReCLAIM-2 Phase 2b
 reaches retina in higher function and vision in intermediate geographic improvement in visual function trial of SC elamipretide
 concentrations than 1.0% animal models. atrophy (GA) patients lose in patients with GA and drusen in patients with GA
 topical ophthalmic drops + Improvements in dry up to 5 letters of visual and apparent slowing of GA ongoing; data 2021.
 is more quickly efficacious. AMD donor eyes. acuity every progression after 6 mos. once IVT development
 6-12 months. daily SC elamipretide. ongoing.
 Stealth, data on file; Alam, Cousins, Retina Today, Holkamp, Angiogenesis, Angiogenesis, 2019,
 Dis. Mod. Mech. 2015 2016, Angiogenesis, 2017, 2018; Ladd, data on file. ARVO, 2019, ASRS 2019
 Kapphahn, ARVO, 2017
14 © 2020 Stealth BioTherapeutics

Preclinical reversal of AMD pathophysiology & improvement of vision
 Normal Diet High Fat + Vehicle High Fat + Elamipretide High Fat + Vehicle High Fat + Elamipretide

Oxidative stress
 Flavoprotein
Fluorescent green

 Cell integrity
 RPE nuclei blue *
 Cytoskeleton red
 *
 Deposits

 300
 #818090-1 (Normal diet) Right eye, Steps 1-9
 300
 #945945-2 (HFC diet) Left eye, Steps 1-9
 300
 #787562-2 (MTP-131 Tx) Left eye, Steps 1-9
 Electron microscopy
 Vision
 200 200
 200 Chan 1 (Result (uV))
 Chan 1 (Result (uV))
 Chan 2 (Result (uV))

 100 100 100

pattern electrogram
 0 0 0

 -100 -100 -100

 -200 -200 -200

 -300 -300 -300
 -100 0 100 200 300 400 500 -100 0 100 200 300 400 500 -100 0 100 200 300 400 500
 Step 1 (Time (ms)) Step 1 (Time (ms)) Step 1 (Time (ms))

 S. Cousins, Duke Eye Center, Angiogenesis, Exudative, and Degeneration, February 2016, Miami, FL
 15 © 2020 Stealth BioTherapeutics

ReCLAIM Phase 1 high-risk drusen and geographic atrophy

 Screening BL W1 W4 W8 W12 W16 W20 W24 W28: Washout

 >5 letters Endpoints
 High-risk drusen low luminance
 deficit Primary Endpoint: Safety
 Adverse event attributed to drug

 Exploratory Endpoints: Efficacy
 BCVA ≥ 55
 n=21 Low luminance visual acuity (LLVA)
 letters
 Elamipretide 40 mg (s.c.) Best corrected visual acuity (BCVA)

 Once daily Low luminance reading acuity (LLRA)
 Low Luminance Questionnaire (LLQ)
 >5 letters No placebo control NEI Visual Function Questionnaire (VFQ)
 Noncentral GA low luminance
 Dark adaptation (DA)
 deficit
 Drusen volume
 Fundus hyperautofluorescence
 BCVA ≥ 55 letters n=19 Cone light sensitivity (microperimetry)

Stealth Biotherapeutics [data on file].

 16 © 2020 Stealth BioTherapeutics

Phase 1 improvement in low luminance visual acuity
 Drusen: Mean Change in LLVA n=19 Quiescent Neovascular
 Quiescent Non-Study
 neovascular AMD
 Eyes: Mean Change
 non-study eyes in LLVA

 p=0.006

 GA: Mean Change
 GA: Mean change inin LLVA n=15
 LLVA

 Mean:+6.1 letters
 p=0.0012
 n=14

 p=0.025

17 © 2020 Stealth BioTherapeutics

Phase 1 improvement in visual acuity

 Drusen: Mean Change in BCVA n=19 Quiescent Neovascular
 Quiescent Non-Study
 neovascular AMD
 non-study eyes
 p=0.025 Eyes: Mean Change in BCVA

 GA: Mean Change
 GA: Mean change inin BCVA n=15
 LLVA
 p=0.003

18 © 2020 Stealth BioTherapeutics

Phase 1 improvement in low light reading acuity

 Drusen: Mean Change in Low-Luminance Smallest Line Read Correctly
 p=0.0001

 3-line gain

 GA:GA:Mean Change
 Mean change in Low-Luminance
 in Low-Luminance Smallest Line ReadSmallest
 Correctly Line Read Correctly

 p=0.017

 5-line gain

19 © 2020 Stealth BioTherapeutics

Phase 1 geographic atrophy growth rate trails natural history

 Elamipretide may be slowing disease progression at 6 months

 10 Studies
 0.91mm2 5 Studies 0.19 mm 5 Studies 0.18 mm
 0.14 mm 0.13 mm^^

 0.50 mm2

 Other Studies2 X Stealth Study

 1 6 Month change in GA Area by OCT is 0.45 mm2
 2 Fleckenstein, Ophthalmology. 2018 Mar;125(3):369-390, “Filly”, Mac. Soc. Feb. 2018; “Chroma” and “Spectri”, JAMA Opth. Jun. 2018; “Proxima A”, Angiogenesis 2018 (all assuming linear growth)

20 © 2020 Stealth BioTherapeutics

ReCLAIM 2B for geographic atrophy currently enrolling

 Projecting full enrollment H2 2020

 Screening BL W4 W8 W12 W24 W36 W48 W52: Washout

 Elamipretide 40 mg SC or placebo once daily, 2:1 randomization
 GA area ≥0.05mm2/ Efficacy endpoints
 5 letters low Best corrected visual acuity (BCVA)
 luminance deficit
 Geographic atrophy by fundus autofluorescence (FA)
 Geographic atrophy by optical coherence tomography (OCT)
 NEI Visual Function Questionnaire (VFQ)
 Inclusion criteria mimic Phase 1
 ReCLAIM GA cohort (BCVA ≥ 55 letters, Low Luminance Questionnaire (LLQ)
 >5 letters low luminance deficit) Conversion to choroidal neovascularization (wet AMD)

21 © 2020 Stealth BioTherapeutics

Friedreich’s ataxia development program

 Nonclinical Natural Clinical
 Data history plan

 Elamipretide improves Friedreich’s Ataxia Collaborative Phase 2 52-week open-label
 frataxin expression and Clinical Research Network has clinical study at CHOP to assess
 mitochondrial function in assessed visual acuity in >500 safety and efficacy and inform
 FRDA patient-derived patients longitudinally over 5+ Phase 2/3 endpoint selection.
 lymphoblasts (GM15850) years. Cardiac natural history is Interim data analysis planned at
 also well-established. 36-weeks to inform extension to
 Zhao, et al., Scientific Reports, 2017. Balcer, Visual Function in FRDA; Pousset et al., JAMA Neurol. 2015
 104-weeks.

22 © 2020 Stealth BioTherapeutics

Vision loss and cardiomyopathy in Friedreich’s ataxia – an unmet need

 Pressing unmet need Natural history Nonclinical data
 Mean Change in Overall Vision Acuity from BL
 “Without vision you have 0 1 2 3 4 5 6 Control FRDA FRDA + Elam
 nothing - isolation from the 6.00
 4.00
 world is complete.” 2.00 1.13
 0
 0.00
 -2.00 -1.38

 Mean Change
 - FRDA Voice of the Patient Report -4.00
 -6.00 -3.98
 -8.00 -7.36

 most experience -10.00
 -12.00
 -10.97
 -12.58
 visual dysfunction -14.00
 -13.33
 -16.00
 Years from Baseline

 >90% develop Total Cohort Age 40 @ BL

 cardiomyopathic symptoms
 Collaborative Clinical Research Network FRDA
 37.5 natural history cohort; n=~900, >500 with 5+ years
 Elamipretide improves mitochondrial morphology
 in FRDA patient-derived lymphoblasts (GM15850)
 average age of death longitudinal data

 Hanson, et.al., World J Cardiol., Jan. 2019; FRDA Voice of the Patient Report, 2017. Zhao, et al., Scientific Reports, 2017.

23 © 2020 Stealth BioTherapeutics

Phase 2 study commencing H2 2020*

 Screening BL W1 W4 W16 W36 W52 Optional 52-week extension

 Interim analysis
 Genetically
 confirmed FRDA n=10 Safety Endpoints
 Elamipretide ≥40 mg (s.c.) Adverse event attributed to drug
 Ophthalmic Efficacy Endpoints
Primarily visually High contrast visual acuity or low vision alternative
compromised: Primarily affected by Low contrast visual acuity
 cardiac dysfunction: Once daily Low luminance visual acuity (LLVA)
Visual acuity worse Optical coherence tomography
than 20/40 • Ejection fraction Visual function questionnaire

LHON development program

 Route of Preclinical Natural Clinical Open-label Current &
 administration Models history data data next steps

 1.0% topical ophthalmic Improved mitochondrial For patients >12 mos. ReSIGHT Phase 2 did not Improvements from P2 Phase 3 protocol
 drops reach the retina in function in murine-derived post vision-loss, visual show improvement in BCVA baseline in visual acuity, submitted to FDA
therapeutic concentrations retinal ganglion cell (RGC) field and acuity are not after 48-weeks of visual field, color, contrast + year-end 2019.
 + demonstrate efficacy. line. Improved RGC survival + expected to improve elamipretide 0.1% topical visual quality of life Phase 3 initiation
 Higher concentrations visual outcomes in murine over 2 yr. period. ophthalmic drops. observed at week 28. post-2020.
 reach retina via SC acute traumatic optic Improved visual field and
 delivery. neuropathy model. visual quality of life.

Stealth, data on file; Alam, Dis. Chen 2017; Pelaez, Tse (ongoing) Lam, JAMA Ophthamology, ARVO, 2019, EUNOS, 2019, ARVO, 2019, EUNOS, 2019,
 Mod. Mech. 2015 2014 UMDF, 2019. UMDF 2019
25 © 2020 Stealth BioTherapeutics

Early improvement in central visual field; long-term improvement across endpoints

 Double-masked, fellow-eye control trial Open-label extension (at 6 months)

 Visual Field OLE BCVA OLE
In double-masked, fellow-eye control trial, improvements p=0.025 p=0.051
observed in Humphrey’s visual field (p

Rare cardiomyopathies
 Barth; potential for DMD

27

Metabolic cardiomyopathies

Failing heart: an engine out of fuel Progressive remodeling Significant US unmet need

 Barth 3m*
 * Pipeline partnering potential
 cardiac death cardiac death, blood clots,
 edema, heart failure
 BSF Voice of the Patient Report, 2019; Hanson, et.al., World J Cardiol., Jan. 2019; Payne, R.M., Prog. Pediatr. Cardiol., 2011; Giugliano, GR et al., Tex Heart Inst J, 2007; Machiraju et al., Front Cardiovasc Med 2019; Vasan et al., JACC: Cardiovascular Imaging 2018.
 28 © 2020 Stealth BioTherapeutics

Barth development program

 Our Barth development initiative was prompted by requests from advocacy (Barth Syndrome Foundation) and KOLs.

 Preclinical Clinical Open-label Natural history Current &
 models data data comparative control next steps

 BTHS derived No changes in 6MWT or Improvement from Phase 2/3 SPIBA-001 observational Rare pediatric designation.
 cardiomyocytes + BTHSA-Total Fatigue during baseline on multiple pre- study established the NDA and protocol
 lymphoblastoid cells; TAZ 12-week treatment in specified endpoints (cardiac effectiveness of elamipretide submissions planned.
 KD mouse model; lipid bi- TAZPOWER Phase 2/3 function, 6MWT, BTHSA-Total compared to natural history
 layer modeling systems; crossover trial. Responders Fatigue, Muscle Strength, PGI control with statistically
 DCMA fibroblasts observed in pre-specified Symptoms) in 8 patients at significant improvement on
 Pu, BSF, 2016; Vernon, sub-group. Improvements in week 36 of OLE. 6MWT (p=0.0005) primary
 ongoing; Mitchell, 2019; metabolic biomarkers; trends endpoint and other
 Allen, 2019, pub. pend., toward improved cardiac MDA, 2019, UMDF 2019 secondary endpoints.
 Machiraju, 2019
 function.
 MDA, 2019, UMDF, 2019
29 © 2020 Stealth BioTherapeutics Saric et al., Frontiers Genetics, 2016

Barth syndrome – an unmet need

 Pressing unmet need Nonclinical data Supportive clinical data

 “On April 23rd in 2000, I suffered my first
 cardiac arrest at age 11, and I had my first
 defibrillator implanted. On April 17th,
 2018, I suffered my eighth cardiac arrest
 and was saved by the shock of my fourth
 defibrillator.”

 - BTHS Voice of the Patient Report

TAZPOWER: changes in biomarkers of cardiovascular health and metabolism

 Medium-chain (C6-C12) Acylcarnitines (AC) Reduced by Elamipretide

 • Elevated ACs reflect impaired or
 Plasma T.E. = -34%
 50 T.E. = -16% incomplete mitochondrial fatty acid
 50 Urine
 oxidation (FAO) and are linked to cardio-
 ∆ C6-C12 Acylcarnitine

 *P = 0.012

 ∆ C6-C12 Acylcarnitine
 n = 10 - 11 subjects per point

 ***P = 0.0003 metabolic diseases, including Barth.

 n = 10 -11 subjects per point
 paired t test
 � P.2)/2

 � P.2)/2
 25 paired t test
 0 • Elamipretide may improve mitochondrial
 +12% AC transport by stabilizing cardiolipin
 � P.1 + % 

 � P.1 + % 
 -16% C8crn
 0 C10crn
 C6crn - 32% • Elam-mediated decreased plasma
 C12crn
 medium chain ACs are consistent with
 (% 

 -50

 P n E v bsln% C6-C12 -101003 paired
 SPIBA_201 AA all.2c-101003:u Acylcrn
 C8crn - 22%

 (% 
 -25 C6crn
 C10crn
 C12crn improved mitochondrial FAO
 ** * • Improved mitochondrial FAO starting in
 -50 P = 0.328 0.0335
 vs. 0 **P = 0.0051vs. 0 P = 0.1713vs. 0 *P = 0.0404vs. 0 TAZPOWER Part 1 may have contributed
 SPIBA_201 AA all.2c-101003:b Acylcrn
 -100 to improved cardiac function with
 P n E v bsln% C6-C12 OK paired
 PCBO ELAM PCBO ELAM
 longer-term therapy in Part 2 OLE

31 © 2020 Stealth BioTherapeutics Fatima et al., Metabolites, 2019; Kuka et al., Sci Rprts, 2017; Oates Poster BTHS SMS 2020.

TAZPOWER: increased left ventricular volumes

 SV is a key component of CO and EF. All forms of HF are associated with deteriorating SV and CO; EF has been well-correlated with survival.
 SPIBA-201 patients under-perfused at BL
 3D LV Stroke Volume (Indexed)
 mean BL CI = 2.3L/min/m2 (~3,300 L/day)
 40.00
 Double-blind cross-over Open-label extension
 38.00

 35.33 35.31
 36.00

 5.0 L Healthy teenager 34.00 33.38 34.46
 ~4.13L/min/m2
 (6,000-7,500 L/day ) 32.00 32.46
 28.69 30.49
 30.00
 3.0 L Congestive heart failure
 ~2.3L/min/m2 28.00
 28.48
 28.52
 28.17
 Cardiogenic shock 26.00

TAZPOWER: longer therapy during OLE improved multiple endpoints

 6MWT (n=8) BTHS-SA fatigue (n=8) Muscle strength (n=8) SWAY balance (n=8) 5X SST (n=8) CGI Symptoms (n=8) PGI Symptoms (n=8)
 500 489 9 200 85 84 14 2.0 2.0
 478 188 1.75
 480 Worst feeling of fatigue (3 - 15 points)
 7.95
 8 180 175
 460
 Meters walked in 6 minutes

 12.9 1.5
 80 13 1.5 1.38
 440 1.25
 7 160
 1.13
 420 6.25

 Seconds
 Newtons
 76
 5.88 1.0
 400 6 140 132 75 12 1.0
 382
 380 0.75
 11.3
 5 120 71
 360 0.5
 11 10.8 0.50
 340 70 0.5
 4 100
 320
 0.0
 300 3 80 10
 BL W36 W72 BL W36 W72 BL W36 W72 65 BL W36 W72 0.0 BL W36 W72
 OLE OLE OLE OLE OLE OLE BL W36 OLE W72 OLE OLE OLE BL W36 OLE W72 OLE OLE OLE

 Wk 36 OLE p=0.02 Wk 36 OLE p=0.03 Wk 36 OLE p=0.02 Wk 36 OLE p=0.20 Wk 36 OLE p=0.22 Wk 36 OLE p=0.10 Wk 36 OLE p=0.05
 Wk 72 OLE p=0.01 Wk 72 OLE p=0.07 Wk 72 OLE p=0.008 Wk 72 OLE p=0.01 Wk 72 OLE p=0.10 Wk 72 OLE p=0.0006 Wk 72 OLE p=0.10

 • Correlations between cardiac and functional endpoints (resting SV & 6MWT) strengthening with long-term OLE therapy (OLE Week 72 r=0.52)
 • Borg scale showed no observed increase in effort from Part 1 baseline through OLE Week 72 (∴improvement not due to expectation/hope bias)
 • Safety: no deaths, transplants or cardiac events over >72-weeks; compares to 9% death in 12-19-year-olds and 27% death in ≥20-year-old US patients
 (12% of all transplants in 12 to 19-year-old US patients, 4% of all transplants in in ≥20-year-old US patients).

33 © 2020 Stealth BioTherapeutics McCurdy, K., Letter to FDA, 5/26/2020.
 .

SPIBA-001 natural history comparative control study

 Week 72 OLE compared to prognostically matched natural history controls (NHC)*
 Primary endpoint Secondary endpoints Cardiac function

 6MWT Δ from baseline Muscle strength by 5XSST Δ from SWAY balance Δ from LVSV ∆ from BL
 140 HHD Δ from baseline baseline baseline 3
 70 0 1.92
 14 2
 116.92 62.07
 120 12.16
 60 -0.5 -0.37
 12
 Meters walked in 6 minutes

 1
 100 -1
 50 10 0

 Seconds
 80 -1.5 Elamipretide

 LVSV (mL)
 40 8 -1
 Newtons

 NHC Elamipretide
 60 -2 -2
 30 6 NHC
 40 -2.5 -3
 20 4
 -3 -4
 20 2
 10
 1.73 3.89 0.24 -5
 -3.5 -4.8
 0 0
 0 -3.60
 Elamipretide NHC Elamipretide NHC -6
 Elamipretide NHC -4

 Week 72 OLE: p=0.0003 Week 72 OLE: p=0.0002 Week 72 OLE: p=0.008 Week 72 OLE: p=0.03 Week 72 OLE: LSM 6.72, p=0.002

 Week 36 OLE: Elam 80.30, NHC 0.60, Week 36 OLE: Elam 41.79, NHC Week 36 OLE: Elam -2.36, NHC Week 36 OLE: Elam 7.40, NHC
 p=0.0004 1.04, p=0.0002 -0.002, p=0.042 0.86, p=0.13
 Week 48 OLE: Elam 91.86, NHC 0.89, Week 48 OLE: Elam Δ 48.67, NHC Week 48 OLE: Elam Δ -2.83, NHC Week 48 OLE: Elam 8.81, NHC
 p=0.0005 Δ 1.97, p=0.0005 Δ -0.003, p=0.034 1.08, p=0.12

 *Week 72 analysis conducted post-hoc at FDA request
34 © 2020 Stealth BioTherapeutics.

Cardiomyopathy in Duchenne’s muscular dystrophy – an unmet need

 Pressing unmet need Natural history Nonclinical data

“Heart issues don’t just affect some people
with Duchenne; they affect ALL people with
Duchenne. While advances in respiratory
care have improved respiratory outcomes,
heart muscle disease…and heart failure
remain the leading cause of death in
Duchenne.” www.parentprojectmd.org/why-the-heart-matters

 virtually all
 develop cardiomyopathy by age 18
 heart failure
 is a leading cause of death
 Regression line for mitochondrial disease
 19.6 Regression line for DMD

 average age of death for Indexed stroke volume is low in DMD patients Elamipretide improves mitochondrial respiration in
 patients with cardiomyopathy explanted cardiac tissue from Becker muscular
 dystrophy patient
 Meyers, Townsend, Int J Mol Sci. 2019; Nigro, Acta Myol. 2012; Payne, R.M., Prog.
 Pediatr. Cardiol., 2011; Giugliano, GR et al., Tex Heart Inst J, 2007; Machiraju et al.,
 Front Cardiovasc Med 2019. Lee et al., Korean J Pediatr 2014. Stauffer, et al., unpublished, 2020.
 .
 35 © 2020 Stealth BioTherapeutics

Duchenne cardiomyopathy – protocol development underway

 Leading scientific advisory board Clinical trial planning – discussing protocol with KOLs, FDA interactions anticipated H1 2021
Stefan Anker, MD, PhD, Charité; Michael Bristow, MD, PhD,
CU; Javed Butler, MD, Ole Miss; Katie Chatfield, MD, PhD, Subject demographics:
CU; Linda Cripe, MD, N.C.H.; Brian Feingold, MD, UPMC; • Evidence of left ventricular hypertrophy by echocardiography/cardiac MRI
Gerasimos Filipatos, MD, UCY; Gregg Fonarow, MD, UCLA;
Pat Furlong, PPMD; Kan Hor, MD, N.C.H., John Jefferies, • Prior to severe fibrosis and dilation (i.e. pre-pubescent through mid-teens)
MD, UT; Tony Sabbah, PhD, HFH; Eve Slater, MD (Co-chair),
Columbia; Lee Sweeney, PhD, UF; Carolyn Taylor, MD, • Normal ejection fraction
MUSC; Jeffrey Towbin, MD, SJCRH; Jim Udelson, MD, Tufts
 • n = ~100+
 Strong advocacy support Duration:
 6-month run-in followed by randomization of responders to 1-year randomized withdrawal trial
 “Now that we have drugs to Endpoints:
 hopefully help the skeletal • left ventricular volume index
 muscle in our boys, are their • stroke volume
 hearts built to last?” • diastolic function (E/e’, LAVI, E/A ratio)
 • diaphragm function (MED scale, ultrasound)
 - Leading patient advocate, in discussion with FDA • myocardial fibrosis
 • global longitudinal strain

 36 © 2020 Stealth BioTherapeutics

Beyond rare – HFpEF pipeline partnering potential
 Heart failure with preserved ejection fraction (HFpEF)
 a disease in which the heart is not relaxing properly, leading to low cardiac volumes & reduced perfusion, particularly during maximum stress
 P2, 1-month elamipretide or placebo, n=46, assessed function during stress and at rest

 Cardiac function during maximum stress favored elamipretide across numerous endpoints

 Δ in end diastolic Δ in end systolic Δ in ejection Δ in stroke volume Δ in cardiac output Δ in cardiac index Δ in septal E/è Δ in left atrial
 ∆volume
 EDV(ml) n=26
 (ml) ∆volume
 ESV(ml) n=26
 (ml) ∆fraction
 EF (%) (%) n=26 ∆(ml)
 SVn=26
 (ml) ∆(L/min)
 CO n=26
 (L/min) ∆(L/min/m
 2) n=262
 CI (L/min/m ) ∆n=45
 Sep E/e' ∆volume
 LAV(ml) (ml)
 10 12 1.0 0.4 0.5 5
 20 10 Control Control Control Control
 Control
 Control Control
 Control Control Control Control Control
 8 8 MTP-131 9 Elam
 MTP-131 0.8 Elam
 MTP-131 Elam
 15 MTP-131
 Elam
 MTP-131
 Elam Elam 0.3 MTP-131
 0.0 0
 6 6 0.6
 10 6 0.2 -5
 4 4 0.4
 -0.5
 5 2 3 0.2 0.1
 2 -10
 0 0 0 0 0.0 0.0 -1.0
 -2 -2 -0.2 -15
 -5 -3 -0.1
 -4 -4 -0.4 -1.5
 -10 -6 -20
 -6 -0.6 -0.2
 -6
 -15 -9 -2.0 -25
 -8 -8 -0.8 -0.3 Control
 Control Control
 Control
 -20 -10 -10 -12 -1.0 Elam
 MTP-131 Elam
 MTP-131
 -0.4 -2.5 -30
 Diastolic volumes are Systolic volumes are Ejection fraction is Stroke volume is Cardiac output is Elevated in HFpEF, Left atrial
 reduced in HFpEF reduced in HFpEF normal in HFpEF reduced in HFpEF reduced in HFpEF particularly during enlargement
 stress common in HFpEF
 Graphs reflect assessment of raw data conducted by Dr. Hani Sabbah, Henry Ford Institute, for Stealth BT.

 • Did not hit primary endpoint for change in E/E’ at rest.
 • Trends toward improvement E/E’ and global longitudinal strain during maximal exertion
 • Trends toward improvement across multiple echocardiographic parameters
 Fang, Curr Opin Card, Feb 2014; Nanayakkara, et.al., JAHA, Sep. 2017; Obokata, Circulation, Feb. 2017
37 © 2020 Stealth BioTherapeutics

Rare neurological diseases

38

POLG and replisome related disorders – an unmet need

 Pressing unmet need mtDNA maintenance proteins are encoded by nDNA Nonclinical data

“[My son] is 11 now but has the functional
abilities of a toddler. His mobility is limited,
and he primarily uses a wheelchair to get
around. His life is not easy, but he is a
fighter and my personal hero. He is an
inspiration and brings so much joy to my
life and to so many others.
 UMDF Voice of the Patient Report, 2019.

 most common • Cardiolipin mediates importation of nuclear Elamipretide improves mitochondrial
mitochondrial genetic mutation(POLG) proteins via the translocase outer membrane (TOM) respiration in POLG-patient fibroblasts
 complex and tethers mtDNA nucleoids to the IMM
 • Replisome defects usually lead to deletion/depletion

POLG and replisome related disorders – protocol development underway

 Preferential response in nDNA subgroup (MMPOWER-3) Replisome-related mutations (post-hoc) Clinical trial planning underway
 Subgroup: Nuclear
 MMPOWER-3 DNA Mutation
 Subgroup: – per
 Nuclear DNA protocol (n=55)
 Mutations (n=51)
 Elamipretide 40 mg
 35 35
 LSM (SE) of Change from Baseline

 16.4 (-18.5, 51.2)
 Elamipretide
 Placebo 40 mg
Least Squares Mean (SE) of Change from

 30 p = 0.35 27.8
 30 Placebo
 25
 in 6MWT (meters)
 Baseline in 6MWT (meters)

 25 20
 LSM∆ 24.1 (-0.1, 48.3)
 20 15
 p = 0.05
 Elamipretide (n=24)
 15 10 16.0
 Placebo (n=24)
 5 3.7
 10 P=0.04 (ANOVA;
 0
 treatment effect)
 5 -5
 0 -10 -0.4
 -5 0 4 8 12 16 20 24
 0 4 8 Weeks
 12 16 20 24
 Weeks

• Intent-to-treat (n=55) LSM∆ 16.4 meters (-18.5, 51.2), p=0.35
• nDNA patients on placebo did not improve on 6MWT • Includes POLG, TWINKLE, and other • PMM investigators recommend further
 functional assessment – possibly suggesting limited replisome-related nDNA mutations clinical studies
 mitochondrial reserve capacity • Protocol development ongoing
• Most nDNA patients had POLG-related or other replisome
 related disorders – i.e. defects in nuclear genes encoding for • FDA regulatory interactions expected
 proteins important for mtDNA replication H1 2021
• PK/PD data shows relationship (p=0.03) between increasing • Trial initiation expected H2 2021
 exposure and 6MWT improvement
 40 © 2020 Stealth BioTherapeutics. C O N F I D E N T I A L

Pipeline compounds

 100+ SBT-272 SBT-259 SBT-550
 proprietary Clinical stage (Phase 1) ↑ mitochondrial uptake in 550 series may protect cells
 differentiated peripheral tissue (>3X)^ from ferroptosis, a form of
 ↑ mitochondrial uptake (>6X)^
 compounds under assessment for cell death implicated in
 Cmax (~3X), AUC (>25X) in rat brain^ several neurodegenerative
 multiple families peripheral neuropathy/CMT
 ↑ survival in male cohort of ALS SOD-1 diseases
 model; correlated NfL reduction

 ^in each case relative to elamipretide; Cmax = maximum concentration; AUC = area under the drug concentration-time curve; NfL = neurofilament light chain
 Stealth BT data on file; Keefe et al., NEALS 2019; Wu, et.al., J Mol Neurosci., Oct 2018

41 © 2020 Stealth BioTherapeutics

SBT-272: potential neuronal protective therapeutic agent

 Improved blood-brain-barrier penetration Improved survival correlates with NfL in ALS SOD-1 model

 Pearson r 0.8
 120 SBT-0272 NfL Δ p25X higher AUC in brain relative to plasma concentrations and morbidity across various diseases.
 elamipretide • SBT-272 has also demonstrated neuroprotective benefit in a murine stroke
 • Phase 1 single ascending dose ongoing; data H2 2020 (safety, model (p=0.006)(measuring respiratory control ratio in brain mitochondria
 tolerability, plasma PK) post ischemia reperfusion).
 Stealth BT data on file; showing brain accumulation in Sprague Dawley after 5mg/kg • Preclinical studies ongoing in TDP-43 ALS and proteinopathy models
 SBT-272 or elamipretide (n=4 per time-point). ALS=amyotrophic lateral sclerosis; MSA=multiple system atrophy; SOD-1=copper zinc
 superoxide dismutase 1; TDP-43=(transitive response DNA/RNA-binding protein 43 kDa
42 © 2020 Stealth BioTherapeutics
 Keefe, et al. NEALS 2019

At a glance

 Leading Significant First in class Multi-asset Experienced
 mitochondrial unmet need therapies platform team
 medicine

 Orphan diseases: Life-limiting cardiomyopathy: 10 decades drug
 Barth, LHON (clinical) US Barth patients; potential for Barth, LHON, AMD w/GA 100+ pipeline compounds development experience
FRDA, ALS, CMT (preclinical) Friedreich’s ataxia (FRDA) Orphan drug: Mito targeting platform Dedicated to improving
 Age-related diseases: Visual impairment: Barth, LHON >600 patents issued + pending the lives of patients
 dry AMD ~10m US AMD + ~10k LHON patients No US approved therapies
 Orphan neurodegeneration
 Orphan peripheral neuropathy

43 © 2020 Stealth BioTherapeutics

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