GenSight Biologics SA · EURONEXT:SIGHT
GenSight Biologics SA — Investor Presentation (February 2019)
39 slides from GenSight Biologics SA's investor presentation, February 2019
Slide 1: Corporate Presentation
Corporate Presentation February 2019 A LEADING GENE THERAPY BIOTECHNOLOGY COMPANY GENSIGHT-BIOLOGICS.COM
Slide 2: Disclaimer
Disclaimer This document contains forward-looking depend upon factors that are beyond the statements and estimates made by the GenSight Company’s control. Therefore, actual results, the Biologics S.A. (the “Company”), including with financial condition, performance or achievements respect to the ant
Slide 3: Corporate Overview
Corporate Overview Clinical-stage gene therapy company • Focused on severe retinal degenerative pathologies leading to blindness as well as CNS diseases • Well positioned to advance disruptive gene therapy technologies in ophthalmology to commercialization Two disruptive technology platforms • Mitoc
Slide 4: Executive Team
Executive Team Bernard Gilly Thomas Gidoin Barrett Katz Chief Executive Officer Chief Financial Officer Chief Medical Officer PIXIUM VISION (Since 2011) DBV TECHNOLOGIES (2012-2015) MONTEFIORE MED CENTER & A. Chairman of the Board, Founder VP of Finance EINSTEIN COLLEGE OF MEDICINE, NY, USA (2011-20
Slide 5: Our target: degenerative retinal diseases with underlying genetic causes
Our target: degenerative retinal diseases with underlying genetic causes Unmet need: high LEBER HEREDITARY OPTIC • Inexorable progression to blindness for most NEUROPATHY (LHON) patients • No approved treatments* 1. Degeneration of RGCs 1 The eye: an ideal laboratory • Immune-privileged, closed
Slide 6: Pipeline: solid and advanced product portfolio in ophthalmic gene therapy
Pipeline: solid and advanced product portfolio in ophthalmic gene therapy Product Technology Candidate Indication Research Preclinical Phase I/II Phase III Registration Next Expected Events REVERSE: Phase III top-line data reported in Apr (48w) and Oct (72w) 2018. 96w expected in May 2019. GS010 RES
Slide 7: Fully enrolled Phase III trials for GS010
GS010 Fully enrolled Phase III trials for our lead product candidate dedicated to Leber Hereditary Optic Neuropathy (LHON)
Slide 8: GS010 LHON, the most common mitochondrial disease causing bilateral blindness
GS010 aim: treat LHON, the most common mitochondrial disease causing bilateral blindness in the prime of life Evolution of vision from onset Retinal nerve fiber layer thickness average change 30 ONSET 3M 6 12 M M 20 1st EYE 2nd EYE 10 0 Blindness % change vs. baseline VISION occurs -10 sequentially
Slide 9: Solution: Gene therapy with MTS technology to shuttle mRNA to mitochondria
Solution: Gene therapy to produce working mRNA, with MTS* technology to shuttle mRNA directly to affected mitochondria The product of research collaboration with MTS in action for GS010: Gene encapsulated in AAV Step 1 Step 2 Step 3 Step 4 Retinal cell transduced Wild-type Wild-type mRNA Finally, th
Slide 10: RESCUE & REVERSE Phase III trials
RESCUE & REVERSE Phase III trials Time-based strategy to assess GS010 efficacy Different patient Same endpoints Same design inclusion criteria at Week 48 • Double-masked, multi- Primary center • One eye randomized to • Mean difference change from GS010; other eye received baseline, ETDRS letters, dr
Slide 11: REVERSE Data at 72 Weeks: Improvement of central Visual Acuity
REVERSE Data at 72 Weeks: Improvement of central Visual Acuity Sustained improvement of best-corrected visual acuity (BCVA), to clinically meaningful levels at Week 72 • A clinically meaningful improvement of +15 ETDRS letters reported in treated eyes • A continuous bilateral improvement from Baseli
Slide 12: REVERSE Data at 72 Weeks: Additional visual function outcomes
REVERSE Data at 72 Weeks: Additional visual function outcomes Improvement of Contrast Sensitivity • Contrast sensitivity as determined by Pelli-Robson low contrast testing increased in both eyes from baseline to week 72: Treated eyes: +0.21 LogCS Untreated eyes: +0.15 LogCS • Proportion of treated e
Slide 13: REVERSE Data at 72 Weeks: Anatomic targets successfully engaged
REVERSE Data at 72 Weeks: Anatomic targets successfully engaged • SD-OCT demonstrated statistically significant preservation of retinal ganglion cells and preservation of retinal fiber layer in treated eyes vs. untreated eyes ○ Change from baseline in retinal ganglion cell macular volume measured: T
Slide 14: REVERSE Results at W72 – NEI VFQ-25
REVERSE Results at W72 – NEI VFQ-25 Sustained Quality of Life Improvement • Composite score and relevant sub-scores in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ- 25) showed sustained improvements at Week 48 and Week 72 • Magnitudes of score improvement observed with GS010
Slide 15: RESCUE 48-week Topline Data: Similar trajectories with nadir for visual acuity
RESCUE 48-week Topline Data: Similar trajectories with nadir for visual acuity Visual Acuity deteriorates to a low point before beginning to improve: mean improvement from nadir to Week 48 of +13 and +11 ETDRS letter equivalent in GS010- and sham-treated eyes, respectively Change from BASELINE to We
Slide 16: RESCUE 48-week Topline Data
RESCUE 48-week Topline Data Responder analyses show outcomes in favor of GS010-treated eyes in subset of patients • GS010-treated eyes were significantly more likely to have 20/200 or better vision, the threshold for legal blindness (statistically significant with p=0.0347; odds ratio = 2.9), than s
Slide 17: RESCUE & REVERSE safety data
RESCUE & REVERSE safety data Favorable safety and tolerability profile for GS010 • GS010 reported to be well-tolerated • Ocular adverse events most frequently reported in the therapy group were mainly related to the injection procedure • Occurrence of intraocular inflammation (accompanied by elevati
Slide 18: REFLECT Phase III trial: assess efficacy and safety of bilateral injection
REFLECT Phase III trial: assess efficacy and safety of bilateral injection Double-masked, confirmatory study under Special Protocol Assessment from FDA Patient inclusion criteria Design Endpoints at Week 48 Group 1 Primary • Difference in change of vision compared to baseline between GS010 Treatment
Slide 19: Engagement with EMA
Engagement with EMA Preparing for submission 6 months 6 weeks Pre-submission Request pre- Pre- Finalized Submission process submission submission document for meeting meeting e-submission Indicative timings May June Oct Dec Topics to be prepared Outcomes • Overviews for clinical, non-clinical and CM
Slide 20: Engagement with FDA
Engagement with FDA End of Phase 2 (EOP2) meeting to provide updates 75 days ~30 days End of Phase 2 Request EoP2 EoP2 official process meeting / send meeting minutes draft protocol + briefing package Indicative timings Q1 Q2 Q2 Clinical updates CMC updates • Objective: provide updates relevant to •
Slide 21: GS010 Path to Market
GS010 Path to Market Launch readiness and commercial platform Pre-Launch 2018 2019 2020 April Early Q1 Q2 REVERSE RESCUE REFLECT Week 48 Week 48 Week 52 October Q2 H2 REVERSE RESCUE BLA filing Week 72 Week 72 & REVERSE End Q4 2020 Week 96 CMA filing Expected approval 21 February 2019 – Non-Confident
Slide 22: GS030 Second lead product candidate targeting photoreceptor degenerative diseases
GS030 Second lead product candidate targeting photoreceptor degenerative diseases (RP/AMD)
Slide 23: GS030 degenerative diseases of photoreceptors that lead to blindness
GS030 aim: treat degenerative diseases of photoreceptors that lead to blindness Retinitis Pigmentosa Geographic Atrophy (GA) in AMD (Age-Related Macular Degeneration) • Blinding genetic disease caused by mutations • Early (dry-form) AMD evolves with age into late in over 100 different genes AMD, one
Slide 24: Optogenetics using GS030: gene therapy-based approach to restore light sensitivity
Optogenetics using GS030: gene therapy-based approach to restore light sensitivity AAV2.7m8 + ChrimsonR The product of Na+ + research collaboration with Step 1 Step 2 Step 3 Gene therapy Stimulation with Retinal output sent transfer of the gene optoelectronic to brain for image that encodes light- d
Slide 25: GS030: activated RGCs provide visual information to the higher visual centers
GS030: activated RGCs provide visual information to the higher visual centers Localization of light-sensitive protein in NHP retina Restoration of a functional vision in P23H rats Expression of ChrR-tdT in midget cells of Light-induced visual evoked cortical responses monkey perifovea In vivo in NHP
Slide 26: GS030: well-tolerated and safe in pre-clinical studies
GS030: well-tolerated and safe in pre-clinical studies Toxicity study of GS030 product in Local tolerance of GS030 product with light non-human primates (n=32) exposure in rd1 blind mice (n=36) Bilateral IVT administration with vehicle vs 7.21x1010 VG/eye (low dose) vs Bilateral IVT administration w
Slide 27: PIONEER Phase I/II clinical trial: A First-in-Man study
PIONEER Phase I/II clinical trial: A First-in-Man study Study design Cohort 1 (N = 3) Cohort 2 (N = 3) Cohort 3 (N = 3) Extension Cohort 5E10 vg/eye 1.5E11 vg/eye 5E11 vg/eye 5E11 vg/eye Data Safety Monitoring Prior to Dose Escalation 4 weeks post-injection of 3rd (last) patient of each cohort • Fir
Slide 28: GS030: CMC progress & Regulatory interactions
GS030: CMC progress & Regulatory interactions CMC Regulatory • Manufacturing process developed up to • Orphan Drug Designation granted in the 25L US and in Europe ○ Toxicology batch produced at 25L scale ○ Drug Substance titers (> 2E13 vg/ml) and • Active strategy & interactions with US characterist
Slide 29: GS030 Key Milestones
GS030 Key Milestones Pivotal trial expected to be initiated in 2020 2016-2017 2018 2019 2020 CTA CTA IND Orphan Drug October Early data Designation in PIONEER from all US and EU FIM patients in PIONEER Early data from PIONEER first cohort in Week 48 PIONEER 29 February 2019 – Non-Confidential
Slide 30: Building high strategic value
Building high strategic value
Slide 31: Curing blindness represents major market opportunity
Curing blindness represents major market opportunity Favorable reimbursement conditions: • Gene therapy in ophthalmology for rare diseases could 285m people visually impaired be considered similar to organ transplants for payers • Blindness imposes a high burden on health systems 39m ○ Total blindne
Slide 32: Pricing and reimbursement environments are evolving for cell and gene therapies
Pricing and reimbursement environments are evolving to accommodate curative potential of innovative cell and gene therapies Early entrants are setting pricing and contracting benchmarks, and authorities signal flexibility to new thinking • Approved December 2017 for treatment of biallelic • Approved
Slide 33: Potential applications of GenSight technology platforms
Potential applications of GenSight technology platforms Current focus Potential applications SENSORIAL NON-SENSORIAL NARP Leigh Syndrome Other LHON MTS LHON Amyotrophic PLATFORM Dominant Optic Atrophy Lateral Sclerosis Parkinson’s RP Dry-AMD Vagus Nerve Stimulation OPTOGENETICS PLATFORM GA Congenita
Slide 34: GenSight Biologics: Key financial information
GenSight Biologics Key financial information Financing history • March 2013 – Series A round – €20m • June 2015 – Series B round – €32m Cash position (as of Dec 31, 2018) • July 2016 – Euronext IPO – €45m • June 2017 – PIPE – €22m €26.2m Listed on Euronext Paris (SIGHT) • Established in 2012, IPO in
Slide 35: Back-up Slides
Sele tle) Slides
Slide 36: REVERSE 72-week Topline Data
REVERSE 72-week Topline Data Visual Acuity improved by +15 and +12 ETDRS letter equivalent from BASELINE to Week 72 in GS010- and sham- treated eyes, respectively Change from BASELINE to Week 48 LS Mean (SE) a LogMAR ETDRS Letter Equivalent GS010 Eyes -0.218 (0.055) +11 Sham Eyes -0.211 (0.055) +11
Slide 37: Visual Acuity
Broad coherence of RESCUE & REVERSE Topline Data Visual acuity evolved bilaterally, with improvement seen once the disease passed a nadir point Evolution of Visual Acuity RESCUE Study: -50 GS010-treated eyes in RESCUE and REVERSE Subjects Sham-treated eyes REVERSE Study: Visual Acuity GS010-treated
Slide 38: RESCUE 48-week Topline Data
RESCUE 48-week Topline Data Anatomic outcomes pointing to the right direction • The difference between GS010-treated and sham-treated eyes in change from baseline of temporal retinal nerve fiber layer missed statistical significance (p=0.0513). • The change from baseline in GS010-treated eyes of pap
Slide 39: Pricing and prevalence: organ transplant / gene therapy
Pricing and prevalence: organ transplant / gene therapy Orphan Therapy Annual Transplant cost per patient Cost per Patient ($) to 180 days $600 000 INTESTINE $1 500 000 $550 000 $1 350 000 CARBAGLU $500 000 HEART $1 200 000 $450 000 ELAPRASE $1 050 000 $400 000 CINRYSZ SOLIRIS LUNG ALLOGENEIC BONE M
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