A Phase 2 Open-label Study to Evaluate the Safety of Laruparetigene Zovaparvovec Administered Bilaterally in Male Participants With X-Linked Retinitis Pigmentosa

Inclusion Criteria:

General inclusion criteria

• Provide written informed consent or assent (per local regulation) prior to theconduct of any study-related procedures. Participants who provide assent must have aparent, guardian, or legal representative provide written informed consent.

• Be between 12 and 50 years of age (inclusive) at the time of providing informedconsent and assent (as applicable)

• Be male (XY chromosome) and have at least 1 documented pathogenic or likelypathogenic variant in the RPGR gene, within exons 1-14 and/or ORF15, from anappropriately certified or accredited laboratory

• Have a clinical diagnosis of XLRP

• Be in good general health to withstand subretinal surgery and perioperativemedications based on a complete physical examination and results from hematology,chemistry, and coagulation analyses performed at screening

• Be able and willing, as assessed by the Investigator, to follow study instructions,complete study assessments, comply with the protocol, and attend all study visits

• If the participant has a parent or caregiver, the parent or caregiver must be ableto follow study instructions, comply with the protocol, and attend study visits withthe participant, as required

Ocular inclusion criteria (both eyes)

• Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200) in each eye based on an ETDRS chart at eachscreening visit. The ETDRS letter score is the main visual acuity inclusioncriterion for participants. Participants unable to read the ETDRS letters may use atumbling "E" chart for the BCVA assessments

• Have an LLVA ≤ 64 letters (approximately Snellen, 20/50) in both eyes based on anETDRS chart at each screening visit. Participants unable to read the ETDRS lettersmay use a tumbling "E" chart for the LLVA assessments

• Have an LLD of >10 letters

• Be able to perform all tests of visual and retinal function and structure in botheyes based on the participant's reliability and fixation, per the Investigator'sdiscretion

• Have a detectable mean macular sensitivity by MAIA microperimetry at baselinebetween 1 and 12 dB in both eyes, as determined by the Investigator and confirmed bythe central reading center (CRC), with a fixation loss ≤ 20% at each screening visit

• Have a detectable sub-foveal EZ line as assessed by SD-OCT in both eyes as confirmedby the CRC

Exclusion Criteria:

General Exclusion Criteria

• Have other known disease-causing mutations documented in the participant's medicalhistory or identified through a retinal dystrophy gene panel that, in the opinion ofthe Investigator, would interfere with the potential therapeutic effect of the studydrug or the quality of the assessments

• For participants with herpes simplex virus (HSV):

1. Have a history of oral or genital herpes and be unable and/or unwilling to usea prophylactic antiviral medication.

2. Have a history of ocular herpes.

3. Have active oral or genital herpes or are currently receiving treatment foractive HSV infection

• Have complicating systemic diseases (e.g., medical conditions causingimmunosuppression, autoimmunity, active systemic infection) that would preclude thegene transfer or ocular surgery if not adequately managed or treated

• Have a known sensitivity or allergy to systemic corticosteroids or otherimmunosuppressive medications

• Have used anticoagulant agents that may alter coagulation (e.g., warfarin, heparin,apixaban, or high-dose docosahexaenoic acid [fish oil]) within 7 days prior to studydrug administration (ibuprofen, aspirin, or similar agents are acceptable

• Have received any vaccination/immunization within 60 days prior to Day 1 and/orduring screening with the exception of the influenza vaccine, which is onlyexclusionary if received within 28 days prior to Day 1

• Have used systemic corticosteroids or other immunosuppressive medications within 3months prior to study drug administration. Corticosteroids used on an as-neededbasis administered by insufflation, inhalation, or local administration to the skinand mucosa such as Symbicort® (budesonide/formoterol), Flonase® (fluticasonepropionate), and skin creams and ointments containing corticosteroids shall not beexclusionary

• If sexually active or planning to become sexually active, are unwilling to usebarrier contraception for 3 months following study drug administration

• Have any other condition or reason that, in the opinion of the Investigator, wouldprevent the participant from completing all study assessments

• Have any other condition or reason that, in the opinion of the Investigator, makesthe participant unsuitable for the study

• Are currently participating or recently participated in any other research protocolinvolving investigational agents or therapies that, in the opinion of theInvestigator, would make the participant unsuitable for the study. Recentparticipation is defined as participation within 90 days of initial screening forthis study OR within 10 half-lives of the investigational drug, whichever is longer

• Have previously received any adeno-associated virus (AAV) gene therapy product, stemcell therapy, cell-based therapy, or similar biologics

Ocular exclusion criteria (either eye)

• Have pre-existing eye conditions in either eye that would preclude the plannedsurgery, interfere with the interpretation of study endpoints, or increase the riskof surgical complications (e.g., corneal opacities, diabetic retinopathy, retinalvasculitis, glaucoma, active cystoid macular edema)

• Have significant media opacity impacting evaluation of the retina or vitreous ineither eye. This includes cataracts considered to be a major contributor to reducingvisual acuity and/or if the participant is likely to require cataract extractionwithin 3 months of study drug administration

• Had intraocular surgery in either eye within the 90 days prior to the plannedadministration of study drug

• Have any active ocular/intraocular infection or inflammation (e.g., severeblepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis,idiopathic or autoimmune-associated uveitis, or herpetic lesions) in either eye

• Have a history of corticosteroid-induced raised intraocular pressure (IOP) of > 25mmHg following corticosteroid exposure in either eye, despite topical IOP-loweringpharmacologic therapy

• Have any artificial retinal implant or prosthesis in either eye

• Have an absence of clear ocular media and/or inadequate pupil dilation to facilitategood quality SD-OCT images in either eye.

• Have any history of rhegmatogenous retinal detachment in either eye

• Have myopia (spherical equivalent) exceeding -10 diopters Investigator or thepresence of pathologic myopia in either eye.