MeiraGTx : Ph1/2 AAV5-RPGR (Botaretigene Sparoparvovec) Gene Therapy Trial in RPGR-associated X-linked Retinitis Pigmentosa (XLRP) Presentation

Ph1/2 AAV5-RPGR (Botaretigene

Sparoparvovec) Gene Therapy Trial

in RPGR-associatedX-linked

Retinitis Pigmentosa (XLRP)

Michel Michaelides,1,* Cagri G. Besirli,2,† Yesa Yang,1 Sui Chien Wong,3 Jose Sahel,4 Syed Mahmood Shah,4 Neruban Kumaran,1 Rachel Huckfeldt,5 Jason Comander,5 Anastasios Georgiadis,6 Stuart Naylor,6 Jialin Xu,7 Michael Clark,7 Eddy Anglade,7 Peggy Wong,7 Penny Fleck,7 Alexander Smith,1 Caterina Ripamonti,8

Robin Ali,1 Alexandria Forbes,6 James Bainbridge1

1UCL Institute of Ophthalmology, London, UK; 2Kellogg Eye Center, Ann Arbor, MI, USA; 3Moorfields Eye Hospital, London, UK;

4University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Harvard Medical School, Boston, MA, USA; 6MeiraGTx, New York, NY, USA; 7Janssen Pharmaceuticals, Raritan, NJ, USA; 8Cambridge Research Systems, Rochester, UK.

*Presenter.

† Current affiliation: Janssen Pharmaceuticals, Raritan, NJ, USA.

Presented at the American Academy of Ophthalmology (AAO) Retina Subspecialty Day; October 1, 2022.

Financial Disclosures

Michel Michaelides, MD (presenter)

• Consultant: Acucela, Stargazer Pharmaceuticals, 2C Tech, MeiraGTx, Janssen Pharmaceuticals
• PI: Acucela, ProQR, MeiraGTx
• Equity ownership: MeiraGTx

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MGT009: Phase 1/2 Trial of AAV5-RPGR

Open-label study of an AAV5-RPGR gene therapy (NCT03252847) conducted at 5 sites in the US and UK

Dose-escalation phase

Dose

Expansion cohort

confirmation

Adults

Children

Adults and children

Followed for 12 months

Low

Intermediate

dose

Intermediate

dose

Low dose (n = 8)

(n = 3)

dose

(n = 3)

High

Intermediate dose (n = 11)

(n = 4)

dose

(n = 3)

R†

Control participants

6 months

followed for 6 months

Primary endpoint: Safety

after AAV5-RPGR

Randomized

N = 32

Low dose

Key inclusion criteria:

concurrent

• Males aged ≥5 years

control group

Intermediate

(n = 13)

dose

•

With RP caused by disease-causing variants in RPGR

•

SD-OCT evidence of relative preservation of retinal

R = randomized by:

structure at the macula

group (immediate treatment or control),

•

Able to undertake age-appropriate clinical assessments

dose (low or intermediate), and

eye (right or left).

† 1:1:1 randomization.

RPGR, retinitis pigmentosa GTPase regulator; RP, retinitis pigmentosa; SD-OCT, spectral domain optical coherence tomography.

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Clinical Safety in MGT009

• Doses for the expansion cohort were selected based upon the balance of safety and activity observed in the dose- escalation phase of the study
• AAV5-RPGR gene therapy demonstrated an AE profile that is anticipated and manageable
• Most AEs were related to the surgical delivery procedure, transient, and resolved without intervention
• Dose-escalationphase SAEs (previously reported)1:
• • 1 retinal detachment: related to study procedure and resolved with treatment, with no sequelae
  • 1 panuveitis (low dose)
• Dose-expansionphase SAE
• • 1 increased intraocular pressure, resolved on treatment
• No dose-limiting events
• Following the implementation of a modified prophylactic steroid regimen for the expansion phase, there was a reduction in inflammation-related AEs in the expansion phase of the study

Number of participants with ocular

inflammation-related AEs by severity of AE

participantsof	inflammationocular	20		16
		15
Number	experiencing	10						8	7
5									3
		0							0	0
					Mild		Moderate	Severe
									Severity of AE
						Without Triamcinolone			With Triamcinolone

AE, adverse event; RPGR, retinitis pigmentosa GTPase regulator; SAE, serious adverse event.

1. Michaelides M, et al. Presented at the American Academy of Ophthalmology (AAO) Annual Meeting; November 13-15, 2020; Virtual.

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Improvement in MRS in Pooled Low and Intermediate Doses Across All Adult Cohorts at 6 Months Observed:

Static Perimetry and Microperimetry

			Dose escalation + expansion§		Sensitivity analysis
				applying phase 3 criteria†,#
Parameter	Dose			LS mean	Treated - concurrent		LS mean	Treated - concurrent
		N		control difference	N	control difference
			change	change
				(±95% CI)‡		(±95% CI)‡
	Pooled low +	24		2.41		22	2.56
Static perimetry	intermediate
			1.96 (0.59, 3.34)*			2.42 (0.91,3.93)***
MRS10°	Concurrent	13		0.45
		11	0.14
	control
	Pooled low +	15		0.88		15	0.88
Microperimetry	intermediate
			1.06 (0.05, 2.07)*			1.06 (0.05, 2.07)*
MRS-Scotopic Red	Concurrent	7		-0.15	7	-0.15
	control

§Full analysis set population (observed data). Includes participants randomized to intermediate and given high dose.

† Participants excluded when applying phase 3 criteria.

#Sensitivity analysis dataset is the same dataset as for the full analysis. Microperimetry was not available at all sites.

‡Adjusted for baseline, 2-sided nominal P value. *Nominal P value <0.05.

***Nominal P value <0.001.

CI, confidence interval; LS, least squares; MRS, mean retinal sensitivity.

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