cotoretigene toliparvovec (BIIB112) / Biogen - LARVOL DELTA

Modelling RPE65 and RPGR retinal gene therapy in non-human primates: (I) RPE changes following subretinal viral vector administration (ARVO 2024) - "Purpose: Dose-related retinal inflammation has been observed in patients receiving voretigene neparvovec (Luxturna) for RPE65 Leber congenital amaurosis and cotoretigene toliparvovec for RPGR X-linked retinitis pigmentosa...Left eyes also received intravitreal anti-TNFα (1.5mg adalimumab) at time of surgery and 4 weekly thereafter... Subretinal injection of AAV2 or AAV8 with ubiquitous or photoreceptor-specific promoter at current recommended clinical dose in NHPs can cause RPE changes and subretinal infiltration within bleb areas. Their distribution is suggestive of localised retinal inflammation at sites of maximal vector particle deposition related to the retinotomy, gravity and pattern of subretinal fluid resorption by RPE pump. Further investigation will explore the mechanism of retinal inflammation and effects of anti-TNFα treatment."

Gene therapy • Viral vector • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • Uveitis

Assessment of Visual Function With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study. (PubMed, Ophthalmology) - P1/2 | "The primary microperimetry endpoint was not met. Significant improvements in LLVA and mean microperimetry and fewer serious adverse events were observed with low-dose cotoretigene toliparvovec."

Journal • P2/3 data • Gene Therapies • Genetic Disorders • Infectious Disease • Inherited Retinal Dystrophy • Novel Coronavirus Disease • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P3 | N=330 | Enrolling by invitation | Sponsor: NightstaRx Ltd, a Biogen Company | Trial completion date: Mar 2027 ➔ Jun 2026 | Trial primary completion date: Mar 2027 ➔ Jun 2026

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Changes in Retinal Sensitivity Associated With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa With RPGR Gene Variations. (PubMed, JAMA Ophthalmol) - P=N/A, P1/2 | "Results suggest that early and sustained improvements in retinal sensitivity and low-luminance visual acuity in some participants through 12 months support consideration of additional clinical trials. ClinicalTrials.gov Identifier: XIRIUS: NCT03116113; XOLARIS: NCT04926129."

Journal • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

XOLARIS: Natural History of the Progression of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P=N/A | N=201 | Completed | Sponsor: NightstaRx Ltd, a Biogen Company | Active, not recruiting ➔ Completed | N=300 ➔ 201

Enrollment change • Trial completion • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

XOLARIS: Natural History of the Progression of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P=N/A; N=300; Active, not recruiting; Sponsor: NightstaRx Ltd, a Biogen Company; Recruiting ➔ Active, not recruiting; Trial completion date: Sep 2024 ➔ Dec 2022; Trial primary completion date: Sep 2024 ➔ Dec 2022

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P3; N=440; Enrolling by invitation; Sponsor: NightstaRx Ltd, a Biogen Company; Phase classification: P=N/A ➔ P3

Clinical • Phase classification • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Visual function improvements with BIIB112 (NSR-RPGR) in X-linked retinitis pigmentosa: XIRIUS (dose- expansion) and XOLARIS (natural disease progression) studies (ARVO 2021) - P1/2 | "Treatment with BIIB112 was well tolerated and, in cohorts 3-6, led to early and durable improvements in 2 measures of visual function."

Diabetic Retinopathy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P=N/A; N=440; Enrolling by invitation; Sponsor: NightstaRx Ltd, a Biogen Company; N=100 ➔ 440; Trial completion date: Apr 2024 ➔ Mar 2027; Trial primary completion date: Apr 2024 ➔ Mar 2027

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

XIRIUS: A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 (clinicaltrials.gov) - P1/2; N=50; Completed; Sponsor: NightstaRx Ltd, a Biogen Company; Recruiting ➔ Completed; Phase classification: P2/3 ➔ P1/2; Trial completion date: Mar 2021 ➔ Nov 2020; Trial primary completion date: Mar 2021 ➔ Nov 2020

Clinical • Phase classification • Trial completion • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] PA054: X-Linked RP: Natural Progression and Improvements With BIIB112 (NSR-RPGR) Subretinal Gene Therapy (AAO 2020) - P2/3 | "In contrast, spontaneous increases in central retinal sensitivity were observed in 1.7% (n = 1) of untreated XOLARIS pts who met the inclusion criteria for XIRIUS (n = 60). Conclusion Treatment with BIIB112 (NSR-RPGR) was generally well tolerated and led to improvements in retinal function."

Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa