Spark Therapeutics
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Spark Therapeutics is developing gene therapies for genetic disorders including SPK-RPE65 for retinal diseases. SPK-RPE65 achieved highly statistically significant results in a pivotal Phase 3 trial, demonstrating long-lasting benefits on vision tests over 3 years. If approved, it could be the first gene therapy approved in the US for a genetic disease. Spark is applying its validated AAV gene therapy platform to expand its pipeline to additional retinal diseases and indications.
![8 Private and Confidential
BL D30 D90 D180 Y1
Study visit
Phase 3 trial results of SPK-RPE65: MT and FST
(mITT/safety population, n=29)
65% of intervention subjects (no controls) passed at 1
lux, demonstrating maximum improvement possible
100-fold improvement in light sensitivity in subjects
receiving SPK-RPE65
0
1
2
3
4
5
6
BL D30 D90 D180 Y1
Luxscore,bilateral
Study visit
Intervention Control
Mean MT lux score/level, bilateral (mITT)
N (Intervention)=20
N (Control)=9
P-value=0.004
Abbreviations: BL=baseline
Intervals are +/- one standard error
Maximum Improvement
1 lux
4 lux
10 lux
50 lux
125 lux
250 lux
400 lux -4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
Whitelight,botheyes[(log10(cd.s/m2)]
Intervention Control
Mean FST: white light, averaged over both eyes (mITT)
N (Intervention)=20
N (Control)=9
P-value=0.001
Abbreviations: BL=baseline, FST=Full-field light threshold sensitivity testing
Intervals are +/- one standard error](https://image.slidesharecdn.com/sparkcompressed-160218160658/85/Spark-Therapeutics-8-320.jpg)
![10 Private and Confidential
Durability of effect of SPK-RPE65: FST over 3 years
BL D30 D90 D180 Y1
Study visit
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
Whitelight,botheyes[(log10(cd.s/m2)]
Intervention Control
Mean FST: white light, averaged over both eyes (mITT)
N (Intervention)=20
N (Control)=9
P-value=0.001
Mean FST: white light, 102-injected eye
-30
-20
-10
0
10
BL W4 W8D90 D180 Y1 Y2 Y3
MeanFST,102-injectedeyeAbbreviation: BL: Baseline, FST=Full-field light threshold sensitivity testing
Intervals are +/- one standard error, N=8
Year 3: N=5 due to pending monitoring
Durability of benefit demonstrated out 3 years post-injection by FST in entire cohort of 102 trial
subjects which would have qualified for Phase 3
Study visit
Abbreviations: BL=baseline, FST=Full-field light threshold sensitivity testing
Intervals are +/- one standard error](https://image.slidesharecdn.com/sparkcompressed-160218160658/85/Spark-Therapeutics-10-320.jpg)
Spark Therapeutics
- 1. 1 Private and Confidential Spark Therapeutics, Inc. OIS@AAO November 12, 2015
- 2. 2 Private and Confidential Forward-looking statements This presentation includes ‘‘forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, expectations regarding the clinical development of our product candidates, future operations, future financial position, future revenue, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘potential,’’ ‘‘will,’’ ‘‘would,’’ ‘‘could,’’ ‘‘should,’’ ‘‘continue’’ 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. 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 a variety of risks and uncertainties, including those described in the ‘‘Risk Factors’’ section of our public filings with the Securities and Exchange Commission. We do not assume any obligation to update any forward- looking statements, whether as a result of new information, future events or otherwise, except as required by law.
- 3. 3 Private and Confidential Fully integrated company with R&D, manufacturing, commercial Lead program, SPK-RPE65, clinically de-risked with highly statistically significant results in pivotal, Phase 3 of RPE65-mediated blindness Durability data at 3 years and counting for comparable Phase 1 cohort Pre-commercial activities underway with BLA filing expected in 2016 Validated platform being applied across deep, growing product development pipeline across multiple tissues and target indications First follow-on eye program, SPK-CHM, in Phase 1/2 trial of choroideremia Factor IX partnership with Pfizer, an industry leader in hemophilia Neurodegenerative programs to be announced in 2015 and 2016 Founded on know-how accumulated over 20 years at CHOP, including manufacturing platform applied safely across >150 administrations Cash at June 30, 2015: $223 million Spark is a gene therapy company developing one-time, life-altering treatments for debilitating genetic disorders
- 4. 4 Private and Confidential Validated platform being applied across deep, growing pipeline of AAV gene therapy candidates REPLACE WITH JEFF’S VERSION Worldwide rights Worldwide rights Worldwide rights Worldwide rights SPK-RPE65: RPE65-mediated IRDs Positive results in pivotal, Phase 3 SPK-CHM: Choroideremia Phase 1/2 second dose cohort initiated Genable RhoNova: RHO-adRP Preclinical SPK-FIX: Hemophilia B Phase 1/2 trial initiated Hemophilia A IND-enabling study to start in 2016 Undisclosed IND-enabling study to start in 2015 Preclinical Status Commercial rightsIND-enabling Phase 1/2 Phase 3Program Collaboration Inherited retinal dystrophies (IRDs) Hematologic disorders Neurodegenerative diseases Worldwide rightsUndisclosed IND-enabling study to start in 2016
- 5. 5 Private and Confidential Phase 3 trial design (n=31 ITT, n=29 mITT/safety) Mobility test (MT) change score at 1 year, bilateral Primary Full-field light threshold sensitivity testing (FST), averaged over both eyes MT change score, first injected eye Visual acuity (VA), averaged over both eyes Secondary Endpoint reached at 1 year Eligibility screening 2nd injection (12 ± 6 days) Control group n=10 ITT (9 mITT/safety) ≤ 12 months (± 30 days) First injection (≤ 90 days of baseline) Intervention group n=21 ITT (20 mITT/safety) Baseline testing Randomization (2:1 intervention to control) Assignment (balanced for age and baseline MT performance) All followed control subjects (n=9) have crossed over and received SPK-RPE65 Study fully enrolled in 2013; randomization completed in 2014 Dosing regimen: 1.5e11 vg/eye in 300 µL Crossover to intervention group Trial endpoints
- 6. 6 Private and Confidential SPK-RPE65: Measuring functional vision through a validated mobility test Mobility course layout (1 of 12) The ability to design trials and clinically meaningful endpoints is a critical component of developing a gene therapeutic for IRDs 1 Styrofoam object or cone. 2 Foam is a raised foam block. 3 Waist-high object. Lux levels Foam2 Foam2 Door Raised Grass Grass Hole STY1 StopHole Step Start Raised Hole STY1 Waste 3 Moonless summer night or indoor nightlight 1 400 Office setting 4 Outdoor parking lot at night or Christmas tree lights 10 An hour following sunset in a city setting or a bus stop at night 125 Half-an-hour before sunrise or the interior of a shopping mall or train or bus at night 250 Interior of an elevator or office hallway Outdoor train station at night or the inside of a stairwell 50
- 7. 7 Private and Confidential Highly statistically significant Phase 3 data reported in October 2015 (ITT efficacy population, n=31) Primary endpoint Endpoint Statistical significance (p-value) Mobility test change score, bilateral p = .001 Secondary endpoint Endpoint Statistical significance (p-value) FST, averaged over both eyes p < .001 MT change score, first injected eye p = .001 VA, averaged over both eyes p = .17 No serious adverse events related to SPK-RPE65 No deleterious immune responses observed in the trial Procedure-related adverse events consistent with prior trials Adverse events
- 8. 8 Private and Confidential BL D30 D90 D180 Y1 Study visit Phase 3 trial results of SPK-RPE65: MT and FST (mITT/safety population, n=29) 65% of intervention subjects (no controls) passed at 1 lux, demonstrating maximum improvement possible 100-fold improvement in light sensitivity in subjects receiving SPK-RPE65 0 1 2 3 4 5 6 BL D30 D90 D180 Y1 Luxscore,bilateral Study visit Intervention Control Mean MT lux score/level, bilateral (mITT) N (Intervention)=20 N (Control)=9 P-value=0.004 Abbreviations: BL=baseline Intervals are +/- one standard error Maximum Improvement 1 lux 4 lux 10 lux 50 lux 125 lux 250 lux 400 lux -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 Whitelight,botheyes[(log10(cd.s/m2)] Intervention Control Mean FST: white light, averaged over both eyes (mITT) N (Intervention)=20 N (Control)=9 P-value=0.001 Abbreviations: BL=baseline, FST=Full-field light threshold sensitivity testing Intervals are +/- one standard error
- 9. 9 Private and Confidential Durability of effect of SPK-RPE65: MT change score over 3 years Durability of benefit demonstrated out 3 years post-injection on MT in entire cohort of 102 trial subjects which would have qualified for Phase 3 Mean MT lux score/level, 102-injected eye Abbreviation: BL=baseline Intervals are +/- one standard error, N=8 Day 30: N=7 due to incomplete follow-up 0 1 2 3 4 5 6 BL D30 D90 D180 Y1 Luxscore,bilateral Study visit Intervention Control Mean MT lux score/level, bilateral (mITT) N (Intervention)=20 N (Control)=9 P-value=0.004 0 1 2 3 4 5 6 BL D30 D90 D180 Y1 Y2 Y3 Luxscore,102-injectedeye 1 lux 4 lux 10 lux 50 lux 125 lux 250 lux 400 lux Maximum Improvement Study visit Maximum Improvement Abbreviations: BL=baseline Intervals are +/- one standard error
- 10. 10 Private and Confidential Durability of effect of SPK-RPE65: FST over 3 years BL D30 D90 D180 Y1 Study visit -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 Whitelight,botheyes[(log10(cd.s/m2)] Intervention Control Mean FST: white light, averaged over both eyes (mITT) N (Intervention)=20 N (Control)=9 P-value=0.001 Mean FST: white light, 102-injected eye -30 -20 -10 0 10 BL W4 W8D90 D180 Y1 Y2 Y3 MeanFST,102-injectedeyeAbbreviation: BL: Baseline, FST=Full-field light threshold sensitivity testing Intervals are +/- one standard error, N=8 Year 3: N=5 due to pending monitoring Durability of benefit demonstrated out 3 years post-injection by FST in entire cohort of 102 trial subjects which would have qualified for Phase 3 Study visit Abbreviations: BL=baseline, FST=Full-field light threshold sensitivity testing Intervals are +/- one standard error
- 11. 11 Private and Confidential SPK-RPE65: Market opportunity and commercialization model An estimated 3,500 patients in US and EU5 – ~6% to 11% of LCA patients (LCA2)1 – ~1% to 3% of RP patients (RP20) Received Orphan Product Designation in US and EU for LCA and RP due to RPE65 mutations – Currently seeking expansion of designation to all RPE65- mediated IRDs 100% of worldwide rights retained by Spark Commercialization through patient-centric approach and Centers of Excellence (COE) for treating IRDs Payor dialogue underway and BLA submission anticipated in 2016 SPK-RPE65 has the potential to be the first gene therapy approved in the US for the treatment of a genetic disease and the first approved pharmacologic treatment for any IRD 0 1,000 2,000 3,000 4,000 5,000 6,000 US and EU5 Estimated Prevalence of RPE65-mediated IRDs RP20 LCA2 Source: Spark calculations based on incidence/prevalence from Genetics Home Reference and commissioned market research. 1 Note: All clinical trials of SPK-RPE65 have included only subjects diagnosed with LCA2.
- 12. 12 Private and Confidential SPK-RPE65 creates a platform for addressing additional IRDs Product candidate Gene Vector capsid Expression cassette Route of administration Target cells in retina Manufacturing process Commercialization model SPK-RPE65 RPE65 AAV2 CBA Sub-retinal RPE Scaled COE SPK-CHM CHM AAV2 eCBA Sub-retinal RPE Scaled COE RhoNova RHO-r RHO-s AAV5 Undisclosed Sub-retinal Photoreceptors Scaled COE SPK-CHM: Choroideremia affects an estimated 12,500 males in the US and EU5; 3.5x the SPK-RPE65 population – Currently enrolling in Phase 1/2 trial; first dose cohort complete with no product-related SAEs RhoNova: Addresses RHO-adRP and utilizes a novel dual-vector gene therapy strategy: (i) suppress the mutant rhodopsin gene and (ii) replace with normal gene resistant to suppressor – License, supply and development consultancy agreements with tiered, mid-single-digit royalties Evaluating additional IRD targets (over 220 genes implicated in IRDs) and new technologies (i.e., Clearside suprachoroidal space microinjector) to expand and enhance platform
- 13. 13 Private and Confidential Proven track record of moving the concept of gene therapy toward a therapeutic reality for patients 2013 2016 est. • SPK-RPE65: Submit BLA in US • SPK-FIX: Phase 1/2 proof-of-concept results • Hemophilia A: Initiate IND-enabling study • Follow-on CNS: Initiate IND-enabling study 2015 est. $185 million IPO SPK-CHM: Phase 1/2 trial initiated Clearside Biomedical microinjector option SPK-FIX: Phase 1/2 trial initiated SPK-RPE65: Positive Phase 3 results • Lead CNS: Preclinical POC data published • Lead CNS program: IND-enabling study initiated 2014 Collaboration with Genable on RhoNova $73 million Series B SPK-RPE65: FDA granted breakthrough Opened facility supporting corporate, R&D, manufacturing SPK-FIX: Executed Pfizer collaboration Recruited industry executives including CCO and CFO Acquired rights to IP and programs from CHOP,Penn, Iowa $10 million Series A Recruited gene therapy pioneers from CHOP SPK-RPE65: Phase 3 fully recruited Hemophilia B human POC with predecessor vector