Sarepta Therapeutics, Inc. · NASDAQ:SRPT
Sarepta Therapeutics — Corporate Update (October 2015)
46 slides from Sarepta Therapeutics's corporate update, Oct 1, 2015
Slide 1: Sarepta Therapeutics October 1, 2015 Investor Update
Exhibit 99.1 Sarepta Therapeutics October 1, 2015 Investor Update
Slide 2: Presenter
Edward Presenter 2SVP, Chief Kaye, Medical MD Officer Interim Chief Executive Officer Sarepta Therapeutics Cambridge, Massachusetts, USA
Slide 3: Forward-Looking Statements
Forward-Looking This “intends,” their Muscular the Each or including product not Sarepta’s and Any 3forward-looking demonstrate presentation be uncertainties Sarepta’s of presentation, implications, forward-looking able the candidates Annual Dystrophy, a“potential,” foregoing to negative other compl
Slide 4: Panelists
AnneOhio Panelists Professor, Jerry The Nationwide Columbus, Eugenio 4Professor RConnolly, Mendell, Mercuri, of State Neurology Ohio, Children’s Pediatric University MD MD USA MD,and Neurology Hospital PhD Pediatrics CollegeUniversità ofNeuromuscular Medicine CattolicaDivision del Sacro Washington C
Slide 5: Panelists (cont'd)
Panelists Perry Associate David Steve Foundation Professor 5All panel Shieh, Wilton, Geffen (cont’d) members Professor, Chair MD, PhD, School in PhD either BSc Molecular Department of Medicine, adviseTherapy or ofUniversity consult Neurology Centre forof Sarepta Director, for California, Comparative
Slide 6: Summary – Eteplirsen Accomplishments
Summary –Confirmed Reverse-transcription–polymerase Dystrophin % Western Expanded 6Eteplirsen 4th dystrophin-positive biopsy blot of clinical safety New clinical production intensity Accomplishments Drug database program activity Application fibers confirmed of eteplirsen (NDA) by chain each in reac
Slide 7: Key Data Included in NDA Filing
Key –ITT Pulmonary 4th 7Rescore Safety Intermediate biopsy analysis DataofIncluded %function ofdystrophin-positive clinical 6MWTin NDA endpoint or Study Filing upon 201/202 fibers which vs external the eteplirsen control NDA filed with FDA
Slide 8: ITT Analysis of 6MWT for Study 201/202 vs External Control
8ITT Analysis of 6MWT for Study 201/202 vs External Control
Slide 9: Establishing External Control Cohort
Establishing Only –Prospectively Leuven Italian 96MWT, Age, Genetic Equivalent External two DMD steroid Neuromuscular 6-minute Duchenne mutation control an care Telethon defined use, Appropriate walk standards patients and data muscular filters Center mutation test; Research would including NSAA, Ex
Slide 10: Italian and Leuven Investigator-initiated Registries
Italian Investigator-initiated Registries Patients –Enrolled 6MWT Published 10 Attending Steroid Genetically No cognitive Telethon administered treated all use data patients a recorded confirmed participating in impairment according &peer-reviewed Leuven who by studies, trained diagnosis met to NMRC
Slide 11: Derivation of Prospectively Defined External Control Groups
Derivation Prospectively N=186 DMD N=116 type) Baseline 6MWT N=25 Age N=41 Not N=37 Amenable N 11 indicates Amenable <7N=13 N=91 N=50 Raw •external Available Age Non-biased &toof Data ?1 participants All ?7 Amenable External defined Post-baseline tocontrols Mutations Amenable • Requested (recognized
Slide 12: Impact on 6MWT in Any Genotype Patients
Impact Any PATIENTS –Patients It 450 (m) Distance 400 N=91 350 6MWT 300 Mean 250 ?7 Baseline 200 †Difference 12 54-meter isYears, N=25 +54 -93 <7 challenging Genotype **p<0.01; Dof Years, Age: m <7 = mMonth ** Any Baseline +25 167 p<0.001 increase initially <7 ?7 *** in9.4 Any Genotype SHOW mean m m
Slide 13: Impact on 6MWT in Exon Skip Amenable Patients
Impact SIMILAR Patients 450 +14 N=17 Distance N=50 350 300 6MWT Mean 250 -111 <7 ?7 -180 Baseline 150 †Difference 13 Years, Years, *** -44 m m*p<0.05; *** of p<0.001 m <7 Month Age: Amenable Amenable Baseline 400 TREND Dinitially in=9.7 Age: mean 194 ***p<0.001 12†Age Month m OBSERVED improve 6.0 to
Slide 14: External Control Declines More Rapidly
Exon (m) 300 400 External 0B 14aseline Distance 51 Declines Control—All Control—Any Month 200126MWT More Month Mutations, Exon, Rapidly Mean 24 Month ?7100 Than Years ?7 Years 36Other OldOld External Genotypes Control—Exon 51, ?7 Years Old
Slide 15: Patient Characteristics at Baseline
Patient Parameter Study Age, 9.4 6MWT 363.2 Mean Deletion 15 (1.18) years (42.19) (SD) 201/202 Characteristics distance, mutations 9.5 Pivotal (1.45) 357.6 Exon mStudy 45–50, (66.75) 9.7 51atAny (1.52) 6MWT Baseline: 48–50, 355.7 Exon External (87.28) 45–50, Number Eteplirsen Control 48–50, of and p
Slide 16: 151-Meter ITT Analysis for Eteplirsen-Treated Patients
151-Meter ITT External N=12 (m) 350 SEM Distance 250 6MWT Mean 150 Eteplirsen-treated, 100 Baseline 250 †Difference 16patients N=13 ANALYSIS, 300 Age: **p<0.01 p<0.01 controls Month 200 ±in Age: Difference 9.4 in the D=151 mean 9.5 historical 12N=12 were Amenable Month **change m† Between steroid-tr
Slide 17: Slower Rate of Decline vs Multiple Controls
Analysis (m) 400 Eteplirsen 6MWT 200 Eteplirsen-treated Mean 0External †Sample ‡Difference 17Month 300 100 N=50†, Control—All 12 size Shows N=13†, Treated N=12† Month atat36 Ä=79 baseline. Slower months Distance (Exon Patients Ä=151 24 m‡ Month Mutations, Rate 51) in m‡ Compared N=91†, mean of 366 M
Slide 18: Individual Patient Data: Rate of Decline
Individual DIFFERENCE Distance 400 (m) 0B Baseline EC External 18aseline Etep EC control—Exon control Month 12 300 Patient Months Etep 6MWT IN 12 (age EC Data RATE Month 24 200 ?7, Etep Months for 51 on OF Mean 24 EC Eteplirsen (N=13) steroids, DECLINE Month Etep 36 100Months Eteplirsen-treated %36
Slide 19: Lower Rate of Loss of Ambulation Than External Control
Eteplirsen-treated 6/13 2/12 Eteplirsen-treated—Amenable 50 45 Percent 30 35 40 16.7% 20 10 5215 19 Months /12 Historical 7.7% (46%) (17%; 1/13 16.7% 252/12 23.1% all untreated Control—Amenable 16.7% in 3/13 year Patients 2/12 external 1) eteplirsen 6/13 (N=12) 0controls to0–12 Exon to Showed patien
Slide 20: Eteplirsen Maintains Benefit Through Week 192
Eteplirsen-treated 10/12 0~160 Eteplirsen -10 (m) -40 -60 Mean External Baseline -100 N=8 treatment 20Week -16% -42% change -19% atWEEKS -80 ETEPLIRSEN-TREATED month 192 Control, -30 Month -22% -43% included -31% Eteplirsen-treated, 6MWT 48 SINCE -20 from 12 as Amenable Cohort above. -70 Month the -
Slide 21: Pulmonary Function
Pulmonary Function 21
Slide 22: Pulmonary Function Remains Relatively Stable
Pulmonary Age 125 Median 92 87 % 77 75 72 BL 50 NATURAL WEEKS FVC CINRG MEP, *Wilson 22 82 92 90 84 79 78 75 66 12 Mean at% 84 maximum 94 89 85 81 77 74 24 Baseline Predicted 9.7 2013 84 et 92 93 79 78 36 9.3 al. Function: MEP 88 HISTORY 91 76 48CINRG Mean 1984 86 62 (yrs): expiratory % MIP 90 74 eq
Slide 23: Efficacy Summary
Efficacy SLOWER –Slowed Relative 23 At Decrease 3 years disease stability Summary RATE in6MWT proportion progression in OF%ÄDMD predicted = 151 losing PROGRESSION atm, 3 ambulation years p< MIP 0.01 and compared MEP (17% ATover to 3vsYEARS external 346%) yearsOBSERVED controls compared amenable to I
Slide 24: Fourth Biopsy
FOURTH BIOPSY 24
Slide 25: Fourth Biopsy Background and Measurements
Background –11/12 Measurements 25 All Western RT-PCR Percent Dystrophin protocols patients dystrophin-positive blot on signal volunteered of were designed Fourth mechanism dystrophin intensity blinded, Biopsy in for collaboration expression randomized, of fibers surgical action biopsy with and FDA a
Slide 26: Demonstration of Exon Skipping by RT-PCR
Demonstration 4th In-frame 100% *1 26 boy Biopsy: ofopted patients mRNA All out of (100%) transcripts of dosed Exon the voluntary with patients Skipping aseteplirsen a (N=11*) result by surgical RT-PCR of inexon demonstrated completed biopsy. and 51 skipping Confirmed clinical exonconfirmed studies
Slide 27: Dystrophin-positive Fibers in Eteplirsen-Treated Biopsies
Dystrophin-positive DYSTROPHIN Eteplirsen-Treated PT One DMD 27 #1(1)#9 #3 #4 #2 #3 #4 PTeteplirsen DMD subject #5 PT#8 #7 #8 #6 #7 DETECTED #9 #11 declined Week PT DMD Fibers #2 180 PT #1 the Visibly #6 DMD Untreated IN optional PT 10/11 Present #5 #104th BIOPSIES Exon surgical in Eteplirsen-treate
Slide 28: Patient 11 Biopsy Images
Patient SUBJECT Eteplirsen-Treated PT 28 #11 #11: PT 11: #11 AllEVERY PT 4th#11 Week Biopsy PT IMAGE 180: #11 Images Untreated DMD OFCompared 4TH #1 PT Every BIOPSY #11toBiopsy PT Exon SHOWN #1151 Image PTDMD #11 BELOW Patient PT Skip #11#11 Amenable TODMD DMD SHOW #251 Controls PT MULTIPLE Controls
Slide 29: Statistically Significant Increase in Dystrophin-positive Fibers
Statistically 4PROTOCOL Flagship Increase 1453% 60 p<0.001 Treated Fibers Positive % 0(+SD) 29BLINDED Pathol. *** ***50 30 641% Untreated 40 *** in Nationwide 1*** Pathol. Detected *** Significant PATHOLOGISTS REVIEWED Treated Dystrophin 2 Pathol. Dystrophin vsIncrease Untreated 20 BY3Mean Pathol. F
Slide 30: Increase in Dystrophin Fluorescence Intensity
Mean Increase 140% 40 (+SD) 0T 30 reated ***p<0.001 Fluorescence Treated Intensity Untreated in Detected vs30 Untreated Fluorescent Intensity Dystrophin Demonstrated 20 Relative 10 a Statistically Mean Significant Increase in Treated vs Controls
Slide 31: Role of Western Blot
Role –Primary Nine One DMD, 31 Absence Presence out of untreated Duchenne Western 11 of diagnostic of eteplirsen-treated 9ofcontrols band band DMD Blot muscular confirmed confirmed tool controls had prior andystrophy; observable patients to DMD BMD amenable the introduction had BMD, band toanskippin
Slide 32: Western Blot Patient A
WesternABlot WESTERN Patient Dystrophin Consistent 32 Baseline 50 Band BLOT Results µg total (DYS1): (Untreated) vsprotein Baseline Absent per Patient Patient lane Dystrophin A loaded Week A Exposure Band 180 (Treated) (DYS1): time 30 Present minutes per gel
Slide 33: Western Blot Patient B
WesternBBlot WESTERN Patient Dystrophin Consistent 33 Baseline 50 Band BLOT Results µg total (DYS1): (Untreated) vsprotein Baseline Absent per Patient Patient lane Dystrophin B loaded Week B Exposure Band 180 (Treated) (DYS1): time 30 Present minutes per gel
Slide 34: Fourth Biopsy Summary
Fourth RT-PCR—Exon Eteplirsen-treated Dystrophin % –Western 34 Automated 4Dystrophin-positive Presence blinded Biopsy Blot of pathologists Intensity quantification dystrophin Summary: skipping vs Untreated (p<0.001) Fibers independently protein in Following of 100% (p<0.001) dystrophin Exon confirme
Slide 35: Rescore of Percent Dystrophin-positive Fibers in Study 201
Rescore of Percent Dystrophin-positive Fibers in Study 201 35
Slide 36: Rescore Background
Background Original –Met Re-assessment Scored 36Statistically primary byassessment 3one independent on endpoint significant blinded of Rescore dystrophin-positive of pathologist dystrophin-positive blinded increasepathologists, in %fibers dystrophin-positive fibers in plus Study inblinded Study 4658
Slide 37: Rescore Results by 3 Independent Pathologists
3 Independent 30 50 Placebo: Patient Dystrophin Week -10 Inter-rater 37 mg/kg: 12, 12 onNo Week which 30 reliability Statistically No Baseline significant mg/kg significant Pathologists 24 demonstrates at (ICC 10Week significant change inchange = from Confirmed 0.793) 24 a from Change delay from inc
Slide 38: Safety
38 Safety
Slide 39: Eteplirsen Clinical Safety Database
Eteplirsen 0.09, Proof-of-concept IV† Dose Study 30, Double-blind, 30 Studies Recently ALL 46 †Dose 39 IV† patients 50 12 ETEPLIRSEN 0.9 ranging & 33 28 201/202 IV† administered weeks 12-24 301 Description IM initiated 0.5, Safety ~3 (46 &Single 1, 4, weeks 19 years 204 patient-years) 2, 10, Databas
Slide 40: Enhanced NDA Safety Database
Enhanced NDA Most –Adverse No *AESI, 4012drug 114 Nodrug-related elevated clinically thrombocytopenia, patients evidence common submitted patients adverse related drug Safety GGT, treated significant reactions to of adverse alopecia event with serious be Database drug-related glomerular included for
Slide 41: Week 192 Safety Update
Week Total Majority No Most Adverse 41 missed eteplirsen-related intermittent drug hospitalizations doses common 192holidays, drug ofSafety doses administered missed reactions AEs dosing due Update: no doses were due serious to dose needed to to eteplirsen-related mild >2300 due No Eteplirsen drug-r
Slide 42: Cardiac Health: Ejection Fraction
Age60atAll Median 70 Week 30 NATURAL Mean eteplirsen 42 50 Baseline Ejection 9.3 ± Change Baseline 9.7 SEM 40 Groups Ejection treatment Median HISTORY (N=12) From Fraction 1(yrs): 12 1.49% Fraction 13.4 24 Baseline Age SHOWS 36 Through 48 at(%) WK to 62Over Week CARDIAC 74 192 192 84Weeks 192 192 (y
Slide 43: Summary of Efficacy and Safety
Summary 151-meter Pulmonary 4th Biochemical (Supportive Efficacy –Rescore Drug No 43RT-PCR: Dystrophin 30 injection-site hospitalizations decrease Biopsy mg/kg: continues ofof advantage Weeks (Voluntary: 100% stability –Statistically in Key intensity: %ejection todystrophin-positive reactions, Resul
Slide 44: Sarepta's Mission and Exon-Skipping Programs
Sarepta’s OUR We Four Exons –Our Evaluating PMO, 44 Working Eteplirsen Meeting Clinical are goal clinical MISSION phosphorodiamidate 53 committed is Vision & trials with collaboratively internally approaches to45 for trials develop EMA underway exon ISto ongoing, TOon developing 51 and treatments be
Slide 45: Panel Discussion
Panel Discussion 45
Slide 46: Thank you / Open Line for Questions
Thankopen Line 46 youfor questions
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