GenSight Biologics : Corporate presentation, November 2019

Corporate Presentation

November 2019

A LEADING GENE THERAPY BIOTECHNOLOGY COMPANY

GENSIGHT-BIOLOGICS.COM

Disclaimer

This document contains forward-looking statements and estimates made by the GenSight Biologics S.A. (the "Company"), including with respect to the anticipated future performance of the Company, its subsidiaries and affiliates, and the market in which they operate. They include all matters that are not historical facts. These forward-looking statements can be identified by the use of forward-looking terminology including the terms "developments," "estimates," "expects," "intends," "may," "milestones," "potential," "value," "time to market," "targeting," "on track," "planned," "will," "move to," or other variations or comparable terminology, or by discussions of strategy and funding, as well as the Company's, its subsidiaries' and affiliates' technology, and are based on financial and non-financial information, including projections as to the future regulatory situation and other information and assumptions. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may

depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of the Company, its subsidiaries and affiliates or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Forward- looking statements, forecasts and estimates only speak as of the date of this forward-looking statement, and no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. The Company, its subsidiaries and affiliates disclaim any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in the Company's expectations with regard thereto, or any events, or changes in conditions or circumstances on which any such statement, forecast or estimate is based.

2 November 2019 - Non-Confidential

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

• Mitochondrial targeting sequence (MTS)
• Optogenetics

Lead projects target:

• GS010 - Leber Hereditary Optic Neuropathy (Phase III)
• GS030 - Retinitis pigmentosa and dry-AMD (Phase I/II)

Listed on Euronext Paris (SIGHT)

• Established in 2012, IPO in July 2016 (EUR45m)
• GenSight Biologics Inc incorporated in the US in May 2017

3 November 2019 - Non-Confidential

Executive Team

Bernard Gilly

Chief Executive Officer

PIXIUM VISION (Since 2011) Chairman of the Board, Founder

FOVEA PHARMA (2005-2009)Chairman & CEO - sold to Sanofi

SOFINNOVA PARTNERS (2000-2005)Managing Partner

TRANSGENE (1992-2000) Chairman & CEO

Ph.D. in biology and bio-economics

4 November 2019 - Non-Confidential

Thomas Gidoin

Chief Financial Officer

DBV TECHNOLOGIES (2012-2015)

VP of Finance

IPSEN (2008-2011)

UK Operations Controller (London)

Senior Financial Analyst (Paris)

ERNST & YOUNG (2007-2008)

Auditor

Magali Taiel

Chief Medical Officer

ProQR THERAPEUTICS (2016-2018)VP of Clinical Development

ELI LILLY (2004-2016) Medical Department Lead

PFIZER (2001-2004) Medical Advisor

SERVIER (1999-2001)

R&D International Project Manager MD, Board-certified ophthalmologist

Our target: degenerative retinal diseases with underlying genetic causes

 Unmet need: high

LEBER HEREDITARY OPTIC

NEUROPATHY (LHON)

1. Degeneration of RGCs

1

• Inexorable progression to blindness for most patients
• No approved treatments*

Genetic mutations	 The eye: an ideal laboratory
•	Intravitreal injections to introduce of genetic
	•	Immune-privileged, closed system
Aging	•	material close to target cells
	Slow turnover of retinal cells support long-
		term expression of transduced genes

	2. Degeneration of photoreceptors	2	 AAV: proven vector for gene therapy
RETINITIS PIGMENTOSA (RP)	•	Proven safety and proof of effect in humans
			•	Efficient transduction of retinal cells
GEOGRAPHIC ATROPHY		•	No need to screen patients for Nab before
(Late stage form ofAge-Related		•	treatment
Macular Degeneration - AMD)		Validated manufacturing process

	Source: Company
5 November 2019 - Non-Confidential	*Except for exceptional circumstances for idebenone in Europe

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

GS010

(FDA & EMA LHON ND4

Orphan Drug

Designation)

MTS platform

REVERSE: Phase III top-line data reported in Apr (48w) & Oct (72w) 2018 and in May 2019 (96w)

RESCUE: Phase III top-line data reported in Feb (48w), Apr (72w) and Sep (96w) 2019

REFLECT*: Phase III recruitment completed in July 2019, top-line data expected in Q3 2020

	GS011	LHON ND1			Initiate preclinical studies following
			GS010 Phase III clinical data
	Undisclosed
	Mitochondrial	Undisclosed
	Target
	GS030				PIONEER: Second cohort ongoing in
	(FDA & EMA	RP			PIONEER Phase I/II clinical trial.
	Orphan Drug			Report interim data one year after last
Optogenetics Designation)				subject treated
		Dry AMD &
	GS030	Geographic
		Atrophy
					*Conducting this trial under a special protocol assessment with the FDA

Lead candidate, GS010, is expected to file for MAA in Europe in the coming year

6 November 2019 - Non-Confidential

GS010

Fully enrolled Phase III trials for our lead product candidate dedicated to Leber Hereditary Optic Neuropathy (LHON)

GS010 aim: treat LHON, the most common mitochondrial disease causing bilateral blindness in the prime of life

Evolution of vision from onset

ONSET	3M	6	12
		M	M
1stEYE	2ndEYE
VISION			Blindness
		occurs
		sequentially
		within
			12 months
			of onset
			TIME

Image source: illustrated from Newamn NJ et al., Am J Ophthalmom. 141(6), 1061-1067,2006

Retinal nerve fiber layer thickness average change

30

20

10

0

-10	baseline
-20
	vs.
-30	change%

-40

-50	PRE-ONSET	ONSET	3M	6M	9M TIME

Image source: illustrated from Barboni et al Natural History

of Leber's Hereditary Optic Neuropathy: An OCT Study

		• Orphan maternally inherited mitochondrial disease
Incidence	0.15/100,000
• Painless sudden loss of central vision in the 1st eye with 2nd eye sequentially impaired:
Prevalence	1/31k-40k	•	symmetric disease with poor visual recovery
		Thinning of the Ganglion Cell Layer occurs after the onset of vision loss and stabilizes at
Blindness	15-35y
	approximately 6 months

• 97% of patients have bilateral involvement < 1 year / 25% of cases are simultaneous

• Targets ND4 which accounts for ~75% of LHON in North America & Europe

8 November 2019 - Non-Confidential

Solution: Gene therapy to produce working mRNA, with MTS* technology to shuttle mRNA directly to affected mitochondria

MTS in action for GS010:

The product of

research

collaboration with

Gene

encapsulated

in AAV

Step 1		Step 2		Step 3		Step 4
Retinal cell transduced		Wild-type		Wild-type mRNA		Finally, the wild-type
with vector containing		mitochondrial gene		delivered by MTS		mitochondrial protein is
wild-type mitochondrial		transcribed in the		directly to polysomes		translocated inside the
gene		nucleus		located at the		mitochondrion, where it
				mitochondrial surface,		restores energy
				where protein synthesis		production
				occurs

Gene therapy	MTS*
9 November 2019 - Non-Confidential	*MTS = mitochondrial targeting sequence

RESCUE & REVERSE Phase III trials

Time-based strategy to assess GS010 efficacy

Different patient inclusion criteria

REVERSE	•	Onset of disease
	•	6 months to ≤ 1 year
	37 patients enrolled
	•	Fully enrolled Feb 2017

RESCUE	•	Onset of disease
	•	≤ 6 months
	39 patients enrolled
	•	Fully enrolled July 2017

Source: Company

10 November 2019 - Non-Confidential

Same design

• Double-masked,multi- center
• One eye randomized to GS010; other eye received sham injection

Group 1

GS010	SHAM
in right eye	in left
	eye
	Group 2

SHAM	GS010
in right eye	in left
	eye

Same endpoints

at Week 48

Primary

• Mean difference change from baseline, ETDRS letters, drug treated eyes vs. sham treated eyes (LogMAR used for statistical analysis) at Week 48

Secondary

• SD-OCT,visual field, color and contrast vision
• Responders analysis:
  o Gain from baseline of 15 or more ETDRS letters
  o Snellen acuity > 20/200
• Treated vs. sham eyes' BCVA for best-seeingand worst- seeing eyes
• Quality of life assessments

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-treatedeyes, respectively, sustaining the gain at Week 72

Mean visual acuity (BCVA) among GS010-treated eyes and sham-treated eyes evolved with similar trajectories, worsening to a post-treatment low point, or nadir, before recovering at Week 96 by +28 and +24 ETDRS letters equivalent, respectively

11 November 2019 - Non-Confidential

Contrast Sensitivity: REVERSE 96-week

Like BCVA, contrast sensitivity (Pelli-Robson) showed a bilateral trend, improving from baseline to Week 96 in both GS010-treatedand sham eyes

Mean contrast sensitivity for GS010-treated eyes showed a more robust improvement versus baseline over the course of the trial comparing to sham-treated eyes

12 November 2019 - Non-Confidential

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-08 / Spearman Corr Coeff = 0.727; p = 3.492e-07

Quadrant superior right: Subjects get BCVA improvement from baseline in both eyes

13 November 2019 - Non-Confidential

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 baselinein at least one eye:
• • Improved by at least 10 ETDRS letters from their on-chart visual acuity, or
  • Improved from an off-chart level of visual acuity to being able to read at least 5 ETDRS letters (on-chart)

By comparison …

• 68% of REVERSE subjects achieved this definition of CRR at Week 96, with GS010-treated eyes significantly more likely to achieve this than sham-treated eyes (62% vs. 43%, p = 0.0348, statistically significant difference).

"The data show that both the treated and the sham eye improved in both high and low contrast, defying the accepted natural history of this disease and improving upon it, based upon the clinical experiences of generations of neuro-ophthalmologists."

Dr. Robert C. Sergott

Director, Wills Eye Hospital, Neuro-Ophthalmology and Director, William

H. Annesley, Jr, EyeBrain Center, Thomas Jefferson University,

Philadelphia, PA

REVERSE subjects experienced a significantly higher rate of "clinically relevant recovery" than natural history

1. Silva et al (2019), "Natural History of Leber's Hereditary Optic Neuropathy (LHON): Findings from a Large Patient Cohort", Poster presented at NANOS March 16-21, 2019; Poster Session II: Scientific Advancements; Poster: 163

14 November 2019 - Non-Confidential

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 improvement observed with GS010 correlate with clinically meaningful improvements in best-correctedvisual acuity (BCVA)

NEI VFQ-25 Results from REVERSE

Mean change from baseline (absolute score and percent)

	Composite	Near	Distance	Dependency	Role	General	Mental
	Score**	Activities	Activities	Difficulties	Vision	Health
Week 48	+7.2	+10.4	+9.6	+12.4	+14.5	+10.3	+11.2
+23.2%	+65.1%	+49.8%	+100.6%	+65.0%	+50.9%	+81.9%
Week 72	+8.1	+9.5	+8.2	+18.9	+15.2	+11.9	+15.2
+25.2%	+58.1%	+42.5%	+130.2%	+70.9%	+54.1%	+105.6%
Week 96	+9.5	+13.3	+10.7	+18.5	+15.9	+6.5	+16.1
+28.8%	+78.1%	+47.4%	130.2%	+78.9%	+32.4%	+108.2%
Clinically	+3.90 to	+4.67 to	+5.15 to	+4.72 to	+3.31 to	+4.38 to	+4.70 to
relevant
+4.34	+6.06	+5.38	+4.98	+4.70	+4.82	+4.88
difference*

*Suñer et al. (2009): clinically relevant score differences based on a clinically significant 15-letter BCVA improvement at 12 months. **The composite score is an average of the vision-targetedsub-scale scores, excluding the general health rating question.

15 November 2019 - Non-Confidential

Visual Acuity: RESCUE 96-week

Visual Acuity bilaterally improved by +26 and +23 ETDRS letters from nadir to week 96 in GS010- and sham-treatedeyes, respectively. Mean visual acuity has transitioned from off-chart to on-chart.

Time Course of Best-Corrected Visual Acuity (BCVA) in LogMAR

Least-Squares Mean ± 1 Std. Error

Off-ChartOn-Chart

Study Week

Mean visual acuity (BCVA) among GS010-treated eyes and sham-treated eyes evolved with similar trajectories, worsening to a lowest point, or nadir, before significantly improving to week 96 - coherent with REVERSE

16 November 2019 - Non-Confidential

Natural History: RESCUE 96-week

Comparison to LHON Natural History

• In a natural history study conducted by Santhera(1), 28% of subjects with the ND4 (11778A) mutation achieved the following definition of "clinically relevant recovery" (CRR) from nadirin at least one eye:

»Improved by at least 10 ETDRS letters from their visual acuity, or

»Improved from an off-chart level of visual acuity to being able to read at least 5 ETDRS letters

• 63% of RESCUE subjects achieved this definition of CRR at Week 96, with GS010-treated eyes as likely to achieve this as sham-treated eyes (58% vs. 45%, p = 0.0956).

"Patients in RESCUE were treated before the nadir so, as expected, they continued to worsen early on. But then from week 48 until week 96 they experienced a recovery from the nadir. That is much better than the natural history in any prior studies."

RESCUE subjects experienced a significantly higher rate of "clinically relevant recovery" than natural history

Dr. Mark L. Moster

Neuro-Ophthalmology, Wills Eye Hospital, Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, PA, and Principal Investigator in the REVERSE and RESCUE trials

1. Silva et al (2019), "Natural History of Leber's Hereditary Optic Neuropathy (LHON): Findings from a Large Patient Cohort", Poster presented at NANOS March 16-21, 2019; Poster Session II: Scientific Advancements; Poster: 163

17 November 2019 - Non-Confidential

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
LS Mean (SE) a	n	LogMAR	ETDRS Letters	n	LogMAR	ETDRS Letters
Equivalent	Equivalent
GS010 Eyes	37	-0.294 (0.063)	+15	37	-0.308 (0.068)	+15
Sham Eyes	37	-0.246 (0.063)	+12	37	-0.259 (0.068)	+13

		Week 72			Week 96
LS Mean (SE) a	n	LogMAR	ETDRS Letters	n	LogMAR	ETDRS Letters
Equivalent	Equivalent
GS010 Eyes	34	+0.192 (0.104)	-10	34	+0.168 (0.132)	-8
Sham Eyes	33	+0.216 (0.104)	-11	34	+0.238 (0.132)	-12

1. Efficacy Endpoint was assessed using a mixed model of analysis of covariance (ANCOVA), with change from baseline at week of interest as the response, and subject, eyes of the subject as random factor, treatment and the baseline LogMAR value as covariates.
   Missing data were not imputed.

18 November 2019 - Non-Confidential

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
	Mean (SD) b	n	LogMAR	ETDRS Letters		n	LogMAR	ETDRS Letters
	Equivalent		Equivalent
	GS010 Eyes	37	-0.553 (0.444)	+27.6		37	-0.566 (0.450)	+28.3
	Sham Eyes	37	-0.478 (0.498)	+23.9		37	-0.490 (0.480)	+24.5
			Week 72				Week 96
	Mean (SD) b	n	LogMAR	ETDRS Letters		n	LogMAR	ETDRS Letters
	Equivalent		Equivalent
	GS010 Eyes	34	-0.509 (0.496)	+25.4	34	-0.526 (0.479)	+26.3
	Sham Eyes	33	-0.452 (0.495)	+22.6	34	-0.457 (0.485)	+22.8

1. NADIR: Nadir was defined as the lowest Visual Acuity value from baseline up to Week of interest. LP/NLP vision was assigned a LogMAR value of 4.0 and 4.5 respectively.
2. Mean change from nadir was calculated using observed values (no data were imputed).

19 November 2019 - Non-Confidential

Visual Acuity: Time Course in LogMAR values in REVERSE and RESCUE

REVERSE and RESCUE show coherent pattern of meaningful and durable bilateral visual recovery from nadir

Time Course of Best-Corrected Visual Acuity (BCVA) in LogMAR,

REVERSE and RESCUE

LogMAR All eyes	GS010	Sham	All
Baseline	1.67 (0.50)	1.55 (0.42)	1.61 (0.46)

LogMAR All eyes	GS010	Sham	All
Baseline	1.31 (0.52)	1.27 (0.62)	1.29 (0.57)

20 November 2019 - Non-Confidential

Safety: REVERSE & RESCUE

Favorable safety and tolerability profile

• GS010 was well tolerated throughout both studies
• No serious adverse events in GS010-treated eyes, and no discontinuation due to ocular events
• Most frequently seen ocular adverse events in the therapy group were mainly related to the injection procedure
• Except for the occurrence of intraocular inflammation:
• • likely related to GS010
  • accompanied by elevation of intraocular pressure in some patients
  • responsive to conventional treatment and without sequelae
• No systemic serious adverse events or discontinuations that were related to study treatment or study procedure.

GS010 was well-tolerated through 96 weeks after injection

21 November 2019 - Non-Confidential

Efficacy key findings: REVERSE & RESCUE

REVERSE: 96-WeekFollow-Up

• Sustained bilateral improvement in visual acuity (BCVA) at Week 96
• • Versus baseline: +15 ETDRS letters equivalent in GS010 eyes and +13 ETDRS letters equivalent in sham eyes
  • Versus nadir: +28 ETDRS letters equivalent in GS010 eyes and +24 ETDRS letters equivalent in sham eyes
• 68% of REVERSE subjects attained Clinically Relevant Recovery (CRR) from baseline in at least one eye, compared to 15% in a natural history study
• 78% of REVERSE subjects attained Clinically Relevant Recovery (CRR) from nadir in at least one eye, compared to 28% in a natural history study
• Patients' quality of life scores continue to increase, especially in ability to carry out vision-relatedactivities
• Preservation of anatomy for both eyes, as observed for retinal layers of interest: GCL, Temporal and PMB RNFL

22 November 2019 - Non-Confidential

RESCUE: 96-WeekFollow-Up

• Sustained bilateral improvement in BCVA from Week 48 to Week 96
• • From Week 48 to Week 96:+10 ETDRS letters equivalent in GS010 eyes and +9 ETDRS letters equivalent in sham eyes
• Compelling bilateral improvement in BCVA from Nadir
• • Versus nadir:+26 ETDRS letters equivalent in GS010 eyes and +23 ETDRS letters equivalent in sham eyes
• Clinically Relevant Recovery (CRR) from Nadir1
• • 63% RESCUE subjects attained CRR
  • compared to 28% in a natural history study
• Preservation of anatomy for both eyes, as observed for retinal layers of interest: GCL, Temporal and PMB RNFL

1 "Nadir" here is defined as the worst observed BCVA from baseline to the week of interest, including baseline. When the baseline is excluded from consideration, the proportion of RESCUE subjects achieving CRR is 58%.

GS010 Local Biodistribution: Evidence from Non-Clinical Primate Study

Viral vector DNA detected in uninjected eye  potential mechanism for bilateral effect in REVERSE and RESCUE

• Three test monkeys injected in oneeye using dose equivalent of treatment in REVERSE and RESCUE trials

• Highly sensitive validated test for presence of GS010 DNA used on tissue samples from primates in study

• Key finding:

○ GS010 viral vector DNA was detected/quantified in many tissue samples from contralateral (uninjected) eye

"The presence of viral vector DNA in the optic chiasm and optic nerve of the contralateral uninjected eye points towards a possible diffusion pathway."

Dr. Patrick Yu-Wai-Man, Senior Lecturer & Honorary Consultant Ophthalmologist at the University of Cambridge, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, London, UK

23 November 2019 - Non-Confidential

Notes: One control monkey was injected in one eye with saline solution. Three test monkeys were injected with GS010 in one eye using dose allometrically equivalent to that used in REVERSE and RESCUE. Tissue samples were taken at 3 months after injection and tested using a protocol that specifically targeted the CMV promoter of the GS010 DNA. The sensitivity, specificity and accuracy of the test were validated in a dedicated study.

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 52

• 98 patients with vision loss
  ≤ 1 year
• Initiation: 4Q 2017 (1st patient treated in March 2018)
• Recruitment completed in July 2019

Group 1

GS010	GS010
in first	in second
affected eye	affected eye
First affected eye	Second affected
eye randomized
always treated
between GS010
with GS010
and placebo

GS010	Placebo
in first	in second
affected eye	affected eye

Primary

• Difference in change of vision compared to baseline between GS010 Treatment vs. Placebo in second affected/not yet affected eyes
  (LogMAR visual acuity used for statistical analysis)

Secondary

• Best Corrected Visual Acuity at 2 years
• Spectral domain OCT biomarkers
• Humphrey visual field analysis
• Pelli Robson Low Vision Contrast Sensitivity
• Quality of life assessments

Group 2

24 November 2019 - Non-Confidential

Source: Company

Engagement with EMA

Preparing for submission

		6 weeks
Pre-submission	Request pre-		Pre-
process	submission		submission
	meeting		meeting
Indicative timings	Early Q1 20		Q1 20

Topics to be prepared

• Draft overviews for clinical, non-clinical and CMC data
• Draft SmPC, patient information leaflet, packaging
• Pediatric updates
• Information related to Conditional Marketing Authorisation and orphan market exclusivity
• Pharmacovigilance and other risk management aspects

25 November 2019 - Non-Confidential

5 months

FinalizedSubmission document for

e-submission

Q3 20

Q3 20

Outcomes

• Assigned rapporteur
• Administrative guidance for dossier

Engagement with FDA

Type B meeting to provide updates

	Request	75 days	EoP2		~30 days
End of Phase 2
		EoP2 official
process	meeting / send	meeting	minutes
	draft protocol +
	briefing package
Indicative timings	Q4 19	Dec 19		Jan 20

Clinical updates

• Objective: provide updates relevant to clinical strategy
• Topics
• • REVERSE and RESCUE results to date
  • Implications for REFLECT
  • Investigations into contralateral effect
  • Potential new study with a more robust control arm

CMC updates

• Objective: provide updates on CMC
• Topics
• • Comparability protocol
  • Update on potency assay
  • Align on data to be available at time of submission
  • Discuss further data needs

26 November 2019 - Non-Confidential

GS010 Path to Market

Launch readiness and commercial platform

Pre-Launch

2018		2019

April		February		September
REVERSE		RESCUE		RESCUE
Week 48		Week 48		Week 96
	October			April / May
	REVERSE			RESCUE
	Week 72			Week 72
					&
					REVERSE
					Week 96

2020

Q3

REFLECT

Week 52

H2

BLA filing

Q3

MAA filing

27 November 2019 - Non-Confidential

GS030

Second lead product candidate targeting photoreceptor degenerative diseases (RP/AMD)

GS030 aim: treat degenerative diseases of photoreceptors that lead toblindness

Retinitis Pigmentosa	Geographic Atrophy (GA) in AMD
	(Age-Related Macular Degeneration)

• Blinding genetic disease caused by mutations in over 100 different genes
• Sequential photoreceptor degeneration leads to slow & irreversible progression to blindness, usually at age 40-45
• 15-20,000new patients each year in the US and EU

29 November 2019 - Non-Confidential

• Early (dry-form) AMD evolves with age into late AMD, one of whose forms is GA
• AMD strikes 350-400,000 new patients a year, most of them at 55-60 years of age
• Prevalence of GA increases with age, from 3.5% among 75-year-olds to 22% among those over 90
• Late AMD patients with GA account for 10-20% of blind patients in their age group

Optogenetics using GS030: gene therapy-based approach to restore light sensitivity

AAV2.7m8 + ChrimsonR

Na+	+

The product of

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-		device to transform		processing
sensitive protein		external light stimuli
Expression in retinal		into signal that can
ganglion cells (RGCs)		activate the RGCs

30 November 2019 - Non-Confidential

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
		Full field 590 nm light from ~ 4.7x1015 to 1.1x1017 photons/cm2/sec
	In vivo in NHP assessment 6 months after IVT injection

Dose-ranging response to firing relationship in NHP

Active dose range : 5x1010 and 5x1011 VG/eye

MEA assessment 6 months after IVT injection in NHP

31 November 2019 - Non-Confidential

GS030: well-tolerated and safe in pre-clinical studies

Toxicity study of GS030 product in

non-human primates (n=32)

Bilateral IVT administration with vehicle vs 7.21x1010 VG/eye (low dose) vs 7.84x1011 VG/eye (high dose) in 100 µL

Ophthalmology

• Dose-dependentocular inflammation in the anterior

segment and vitreous, improving/resolving from Month 2 up to Month 6

• Not associated with any retinal tissue destruction or functional changes
• No or very slight residual inflammation in all animals at 6 months (self-resolution,no treatment before or after injection)

Histology

• Dose-dependentminimal mononuclear cell infiltration in eye tissues
• No histological findings in other tissues

Immunogenicity (anti-AAV2 NAb)

• Expected humoral immune response in serum starting at Day 15; tended to decrease at Week 13 then sustained up to Month 6
• Dose-dependentlocal immune response in aqueous humor and vitreous

Local tolerance of GS030 product with light

exposure in rd1 blind mice (n=36)

Bilateral IVT administration with vehicle vs 7.84x109 VG/eye in 1 µL; 590 nm LED light at 1.4×1016 vs 1.7×1017 photons/cm2/s vs ambient room light

Local tolerance

• No ophthalmic findings related to gene therapy (GS030- DP) or to LED light
• No microscopic findings in the retina related to GS030- DP or to LED light
• Transient corneal edema & lens opacity linked to anesthesia procedure

ChrimsonR-tdTomato expression

• Good expression of ChrimsonR-tdTomato in retinas and optic nerves

32 November 2019 - Non-Confidential

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 each cohort

• First-in-man,dose-escalation safety study, multi-center (France, UK, US)
• Study population: end-stagenon-syndromic RP (vision < Counting Fingers)
• Primary analysis: Safety at 1 year
• Single intra-vitreal injection in the worst affected eye
• Decision to increase the dose taken by a DSMB

1st DSMB recommended to continue with cohort 2 without modification on April 30, 2019

33 November 2019 - Non-Confidential

GS030: CMC progress & Regulatory interactions

CMC

• Manufacturing process developed up to 25L
• • Toxicology batch produced at 25L scale
  • Drug Substance titers (> 2E13 vg/ml) and characteristics in line with expectations
  • Scale up to 100L batch successful
• Manufacturing process successfully transferred to GMP
• • GMP clinical supply ready
  • 100L GMP batches manufactured
• Potency assay
• • Development completed
  • Transfer in progress

Regulatory

• Orphan Drug Designation granted in the US and in Europe
• Active strategy & interactions with US and EU Agencies to obtain advice on preclinical package to support FIM and exploit the existing process of expedited programs
• CTA approved in the UK and in France
• IND released by FDA in the US

34 November 2019 - Non-Confidential

GS030 Key Milestones

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

35 November 2019 - Non-Confidential

Building high strategic value

Curing blindness represents major market opportunity

285m people visually impaired

39m

totally blind

6M BLIND

PEOPLE IN

NORTH AMERICA

AND EU

Source: WHO, IAPB-VISION2020,NORC-Univ. of Chicago / The Economic Burden of Vision Loss and Eye Disorders in the United States, 2014.

Favorable reimbursement conditions:

• Gene therapy in ophthalmology for rare diseases could be considered similar to organ transplants for payers
• Blindness imposes a high burden on health systems
• • Total blindness costs exceed tens of billions USD per annum
• Absence of curative treatments
• • Increasing pressure from patients and patients associations

Geographical Split - Blind people in major markets

Europe

North 3.0m Asia

America

3.2m16m

37 November 2019 - Non-Confidential

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 RPE65 mutation-associated retinal dystrophy
• List price: $425,000 per eye
• Early commercial agreements with select health plans
• • Pay-for-performance
  • Staggered payments
  • Special procurement process using specialty pharmacies
  • CMS policy (Medicare coverage) to be published in 2019

• Approved May 2016 for treatment of ADA-SCID
• List price: 594,000€ per patient
• Positive HTA assessments in UK and IT; covered by EU Directive 2011/24*
• • Treatment administered only at the designated treatment center in Milan

Note: Luxturna received Marketing Authorization for Europe in November 2018.

So far, NHS England reached £613,410 per patient at full price ($744,000, -12% of US price).

A full list price has not yet been published.

• Openness to alternative pay-for-performance /risk-sharing options among individual plans
• Industry consultation into legislative initiatives covering new payment models for regenerative therapies

• Ongoing cross-border initiatives in the EU, e.g., European reference networks (ERN EYE for ophthalmology)
• HTA-industryconsultations on refining cost effectiveness models for curative treatments

*The directive sets out the conditions under which a patient may travel to another EU country to receive medical care and reimbursement. It covers healthcare costs, as well as the prescription and delivery of medications and medical devices.

38 November 2019 - Non-Confidential

Potential applications of GenSight technology platforms

Current focus

Potential applications

MTSLHON

PLATFORM

SENSORIAL

Other LHON

Dominant Optic Atrophy

NON-SENSORIAL

NARP Leigh Syndrome

Amyotrophic

Lateral Sclerosis

Parkinson's

RP

OPTOGENETICS

PLATFORMGA

Dry-AMD		Vagus Nerve Stimulation

Congenital Deafness

Abilityto leveragetechnologyplatformsand significantexpertiseto expand the pipelinein ophthalmologyand otherneurodegenerativedisorders

39 November 2019 - Non-Confidential

GenSight Biologics

Key financial information

Financing history

• March 2013 - Series A round - €20m
• June 2015 - Series B round - €32m
• July 2016 - Euronext IPO - €45m
• June 2017 - PIPE - €22m
• February 2019 - PIPE - €8m

Listed on Euronext Paris (SIGHT)

• Established in 2012, IPO in July 2016

Recognition from Blue-Chip specialist investors

• Perceptive, Fidelity, Abingworth, Versant, Sofinnova, JP Morgan AM and others

Analyst coverage

• Oddo & Cie - Martial Descoutures (FR)
• Gilbert Dupont - Jamila El Bougrini (FR)
• Chardan - Gbola Amusa (US)
• NIBC - Dylan van Haaften (NL)

40 November 2019 - Non-Confidential

Cash position

(as of Jun 30, 2019)

€14.3m

Number of

outstanding shares

29.0m