Gensight Biologics Sa · EURONEXT:SIGHT
Gensight Biologics Sa — Investor Presentation (July 2019)
41 slides from Gensight Biologics Sa's investor presentation, July 2019
Slide 1: Corporate Presentation
Corporate Presentation July 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 Genetic mutations • Immune-p
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) & Oct (72w) 2018 and in May 2019 (96w). GS010 RESCUE: P
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 to produce working mRNA, with MTS technology
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: Visual Acuity: REVERSE 96-week
Visual Acuity: REVERSE 96-week Visual Acuity bilaterally improved by +15 and +13 ETDRS letters equivalent from baseline to Week 96 in GS010- and sham-treated eyes, respectively, sustaining the gain at Week 72 Mean visual acuity (BCVA) among GS010-treated eyes and sham-treated eyes evolved with simil
Slide 12: Contrast Sensitivity: REVERSE 96-week
Contrast Sensitivity: REVERSE 96-week Like BCVA, contrast sensitivity (Pelli-Robson) showed a bilateral trend, improving from baseline to Week 96 in both GS010-treated and sham eyes Mean contrast sensitivity for GS010-treated eyes showed a more robust improvement versus baseline over the course of t
Slide 13: Responder Analysis: REVERSE 96-week
Responder Analysis: REVERSE 96-week • 65% of GS010-treated and 46% of sham-treated eyes achieved a clinically meaningful BCVA improvement from baseline (-0.2 LogMAR or +10 ETDRS letters) at Week 96 (p = 0.0348, statistically significant difference) • Based on a generalized estimating equation (GEE)
Slide 14: Responder Analysis: Subjects Mapping in REVERSE at 96 weeks
Responder Analysis: Subjects Mapping in REVERSE at 96 weeks Visual Acuity Change of Sham eyes was correlated with that of GS010 eyes in most REVERSE subjects Subjects are well concentrated around the mean REVERSE – Scatterplot of Change from Baseline at Week 96 Pearson Corr Coeff = 0.776; p – 1.677e
Slide 15: Natural History: REVERSE 96-week
Natural History: REVERSE 96-week Comparison to natural history based on a study by Santhera(1) • In a natural history study conducted by Santhera(1), 15% of subjects with the ND4 (11778A) mutation achieved the following definition of “clinically relevant recovery” (CRR) from baseline in at least one
Slide 16: Quality of Life: REVERSE 96-week
Quality of Life: REVERSE 96-week 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 versus baseline at Week 48, Week 72 and Week 96 • Magnitudes of mean score improv
Slide 17: Visual Acuity: RESCUE 72-week
Visual Acuity: RESCUE 72-week Visual Acuity bilaterally improved by +21 and +22 ETDRS letters from nadir to week 72 in GS010- and sham-treated eyes, respectively, although VA was still below baseline for both groups of eyes at week 72 (-10 and -11 ETDRS letters, respectively) Mean visual acuity (BCV
Slide 18: Contrast Sensitivity: RESCUE 72-week
Contrast Sensitivity: RESCUE 72-week Bilateral contrast sensitivity evolved similarly to BCVA: while values for GS010-treated eyes and sham-treated eyes remained below baseline, CS also recovered so that the difference with baseline diminished at Week 72 compared to Week 48. 18 May 2019 – Non-Confid
Slide 19: Responder Analysis: RESCUE 72-week
Responder Analysis: RESCUE 72-week • 40% of eyes, both GS010-treated and sham-treated, achieved a clinically meaningful BCVA improvement from nadir (-0.3 LogMAR or +15 ETDRS letters) at Week 72. • 58% of GS010-treated and 50% of sham-treated eyes achieved a clinically meaningful BCVA improvement fro
Slide 20: Visual Acuity: Improvement from Baseline
Visual Acuity: Improvement from Baseline REVERSE: Continuous bilateral improvement of Visual Acuity up to Week 96 RESCUE: Worsening VA compared to baseline reflects brutal progression of LHON Change from BASELINE Week 72 Week 96 ETDRS Letter ETDRS Letter LS Mean (SE) a n LogMAR Equivalent n LogMAR E
Slide 21: Visual Acuity: Recovery from Nadir
Visual Acuity: Recovery from Nadir Visual Acuity deteriorates to a low point before recovering significantly in both eyes Change from NADIR a Week 72 Week 96 ETDRS Letter ETDRS Letter Mean (SD) b n LogMAR Equivalent n LogMAR Equivalent GS010 Eyes 37 -0.548 (0.435) +27 37 -0.561 (0.439) +28 Sham Eyes
Slide 22: Visual Acuity: Time Course in LogMAR values
Visual Acuity: Time Course in LogMAR values Bilateral improvement post Nadir On-Chart On-Chart Off-Chart Off-Chart Weeks after administration Weeks after administration LogMAR All eyes GS010 Sham All LogMAR All eyes GS010 Sham All Baseline 1.67 (0.50) 1.55 (0.42) 1.61 (0.46) Baseline 1.31 (0.52) 1.2
Slide 23: Safety: REVERSE & RESCUE
Safety: REVERSE & RESCUE Favorable safety and tolerability profile • No serious adverse events in GS010-treated eyes • No discontinuation in the trial • Most common ocular AEs were considered related to injection procedure, except for intraocular inflammation (accompanied by elevated intraocular pre
Slide 24: Efficacy key findings: REVERSE & RESCUE
Efficacy key findings: REVERSE & RESCUE REVERSE: 96-Week RESCUE: 72-Week • Sustained bilateral improvement in visual acuity • GS010 and Sham eye groups track together at (BCVA) at Week 96 Week 72 ○ Versus baseline: +15 ETDRS letters equivalent in GS010 eyes and +13 ETDRS letters equivalent in sham e
Slide 25: 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 26: Engagement with EMA
Engagement with EMA Preparing for submission 5 months 6 weeks Pre-submission Request pre- Pre- Finalized Submission process submission submission document for meeting meeting e-submission Indicative timings Q4 19 Early Q1 20 Q3 20 Q3 20 Topics to be prepared Outcomes • Draft overviews for clinical,
Slide 27: Engagement with FDA
Engagement with FDA Type B 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 Q2 19 Q3 19 Q3 19 Clinical updates CMC updates • Objective: provide updates relevant to • Objec
Slide 28: GS010 Path to Market
GS010 Path to Market Launch readiness and commercial platform Pre-Launch 2018 2019 2020 April February September Q3 REVERSE RESCUE RESCUE REFLECT Week 48 Week 48 Week 96 Week 52 October April / May H2 REVERSE RESCUE BLA filing Week 72 Week 72 & REVERSE Q3 Week 96 MAA filing 28 May 2019 – Non-Confide
Slide 29: GS030 Second lead product candidate
GS030 Second lead product candidate targeting photoreceptor degenerative diseases (RP/AMD)
Slide 30: GS030 aim: treat 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 31: 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 Na+ + The product of Step 1 Step 2 Step 3 research collaboration with Gene therapy Stimulation with Retinal output sent transfer of the gene optoelectronic to brain for image that encodes light- d
Slide 32: 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 33: 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 34: 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 Highest Best- Tolerated Dose Data Safety Monitoring Prior to Dose Escalation 4 weeks post-injection of 3rd (last) patient of
Slide 35: 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 36: 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 Completion Designation in PIONEER of patient US and EU FIM enrollment Early findings from PIONEER first patients in Preliminary PIONEER Results 36 May 2019 – Non-Confidential
Slide 37: Building high strategic value
Building high strategic value
Slide 38: 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 39: 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 40: 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 41: 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 Jun 30, 2019) • July 2016 – Euronext IPO – €45m • June 2017 – PIPE – €22m • February 2019 – PIPE – €8m €14.3m Listed on Euronext Paris (SIGHT)
GenSight Biologics — Investor Presentation (July 2019) on 6ix