OCU400 / Ocugen - LARVOL DELTA

Preclinical biodistribution and toxicology assessment of an AAV5-based subretinal modifier gene therapy for retinitis pigmentosa. (PubMed, Front Med (Lausanne)) - "In this study, we evaluated the safety and biodistribution (delivery and expression) of a gene therapy candidate, OCU400 (AAV5-hNR2E3), in Göttingen minipigs delivered via the subretinal route...AAV5-hNR2E3 vector was preferentially localized to the target retinal tissues with minimal to no exposure to systemic organs and tissues after subretinal administration. This localized delivery efficiently transduced retinal cells, where the delivered transgene produced the NR2E3 protein."

Journal • Preclinical • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3

[Musunuri] announced an exclusive licensing agreement with Kwangdong Pharmaceutical Company Limited for OCU400 in South Korea, with the potential for up to $7.5 million in upfront and development milestone payments and a 25% royalty on net sales. (MSN News)

Commercial • Retinitis Pigmentosa

Musunuri emphasized that the OCU400 Phase 3 liMeLiGhT clinical trial remains on track for BLA and MAA submissions in 2026, describing it as "the only broad retinitis pigmentosa RP gene-agnostic trial to address multiple genetic mutations with a single therapeutic approach." (MSN News)

EMA filing • FDA filing • Retinitis Pigmentosa

Genetic Therapies for Retinitis Pigmentosa: Current Breakthroughs and Future Directions. (PubMed, J Clin Med) - "Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes...Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod-cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a..."

Journal • Review • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3 • PRPF31 • USH2A

liMeliGhT: A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Ocugen | Trial primary completion date: Jun 2025 ➔ Dec 2026

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

Safety and Efficacy of OCU400 Gene Therapy for Retinitis Pigmentosa: Two-Year Follow-Up of Phase 1/2 Clinical Trial (SOE 2025) - P1/2, P3 | "OCU400 shows a favorable long-term safety and tolerability profile. Treatment effect in subjects with different genetic backgrounds indicates a gene-agnostic mechanism of action. A Phase 3 trial is ongoing (NCT06388200)."

Clinical • Gene therapy • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3

Preclinical safety evaluation of AAV5-hNR2E3 (OCU400), a mutation agnostic gene therapy candidate for retinitis pigmentosa and leber congenital amarousis (ASGCT 2025) - "We observed that OCU400 is specifically delivered to the target tissues and efficiently transduces retinal cells where it is translated to produce NR2E3 protein. Administration of OCU400 at all dose levels was well tolerated and resulted in ocular changes that were minor and mostly related to the dosing procedure with no significant signs of toxicity. Disease Focus of Abstract:Ophthalmic Diseases"

Gene therapy • Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3

Ocugen Provides Business Update with First Quarter 2025 Financial Results (GlobeNewswire) - "OCU400 for RP – The EMA provided a positive opinion for ATMP classification for OCU400 and granted eligibility to submit the OCU400 MAA via the centralized procedure as an ATMP based on the current study design and statistical analysis plan. Actively recruiting patients in the U.S. and Canada in the Phase 3 liMeliGhT clinical trial and on track to meet BLA/MAA filing targets in mid-2026; OCU410ST for Stargardt Disease – Received FDA alignment to move forward with Phase 2/3 pivotal confirmatory clinical trial, which can be the basis of a BLA submission. ATMP classification granted by the EMA; OCU410 for GA – Announced that dosing was complete, ahead of schedule, in the Phase 2 portion of the Phase 1/2 ArMaDa clinical trial for OCU410. Received ATMP classification from the EMA."

EMA filing • FDA filing • New P2/3 trial • Trial status • Genetic Disorders • Ophthalmology • Retinitis Pigmentosa

Ocugen to Present on Modifier Gene Therapy Platform at Association for Research in Vision and Ophthalmology 2025 Annual Meeting and Retina World Congress (GlobeNewswire) - "Ocugen, Inc...today announced that the Company will present on its innovative modifier gene therapy platform, including OCU400 for the treatment of retinitis pigmentosa (Phase 3 LiMeliGhT clinical trial), OCU410ST for the treatment of Stargardt disease (Phase 2/3 pivotal confirmatory clinical trial), and OCU410 for the treatment of geographic atrophy (Phase 2 ArMaDa clinical trial), at The Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting at the Calvin L. Rampton Salt Palace Convention Center in Salt Lake City, Utah from May 4-8, 2025, and Retina World Congress at the Marriott Harbor Beach Resort in Ft. Lauderdale, Florida from May 8-11, 2025."

Clinical data • Retinitis Pigmentosa

Ocugen Provides Business Update with Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "OCU400 –The European Commission (EC) provided a positive opinion from the EMA’s CAT for OCU400 ATMP classification. Actively enrolling patients in the U.S. and Canada in the Phase 3 liMeliGhT clinical trial for the treatment of RP and are on track to complete enrollment in the first half of 2025..."

Enrollment status • Retinitis Pigmentosa

OCU400-101: Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis (clinicaltrials.gov) - P1/2 | N=22 | Active, not recruiting | Sponsor: Ocugen | Trial completion date: Dec 2024 ➔ Mar 2027 | Trial primary completion date: Dec 2024 ➔ Mar 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290 • NR2E3

Ocugen Announces Positive Opinion of European Medicines Agency’s Committee for Advanced Therapies for Advanced Therapy Medicinal Product Classification for Modifier Gene Therapy Candidate OCU400 for Retinitis Pigmentosa (GlobeNewswire) - "Ocugen, Inc...today announced that the European Commission has provided a positive opinion from the European Medicines Agency’s (EMA) Committee for Advanced Therapies (CAT) for OCU400 Advanced Therapy Medicinal Product (ATMP) classification. OCU400 is the first gene therapy to enter Phase 3 with a broad retinitis pigmentosa (RP) indication...'This designation makes it possible to stay on track with our clinical and commercial strategy and potentially provide this novel modifier gene therapy candidate to all RP patients in the United States (U.S.) and Europe by 2027.'...Additionally, this classification allows Ocugen to interact with EMA more frequently for scientific advice and protocol assistance as the Company pursues Marketing Authorization Application (MAA) filing in 2026."

EMA filing • European regulatory • Launch Europe • Launch US • Retinitis Pigmentosa

Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa (GlobeNewswire) - P1/2 | N=22 | NCT05203939 | Sponosr: Ocugen | "100% (9/9) of treated evaluable subjects demonstrated improvement or preservation in visual function compared to untreated eyes at both one and two years; 100% (9/9) of treated evaluable subjects demonstrated improvement or stabilization in mobility testing, which was only performed up to one year; Improvement in visual function was statistically significant (p=0.01, treated vs untreated eyes), regardless of mutation at two years; Favorable long-term safety and tolerability profile with no serious adverse events related to OCU400...OCU400 demonstrated meaningful improvement of 2-line gain (10 letters on ETDRS chart) in low-luminance visual acuity (LLVA) in treated eyes when compared to untreated fellow eyes...The Phase 3 OCU400 liMeliGhT clinical trial is currently ongoing and on target for BLA submission in the first half of 2026."

Filing • P1/2 data • Retinitis Pigmentosa

Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis (clinicaltrials.gov) - P1/2 | N=22 | Active, not recruiting | Sponsor: Ocugen | Recruiting ➔ Active, not recruiting | N=124 ➔ 22

Enrollment change • Enrollment closed • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290 • NR2E3

Safey and Efficacy of OCU400 Gene Modifier Therapy for Retinitis Pigmentosa: Phase 1/2 Study Updates (AAO 2024) - "Improvements from baseline in visual acuity and multiluminance mobility test scores were observed in 75% of RP subjects, who demonstrated either stabilization or improvement in the treated eye. Conclusion OCU400 demonstrates clinical benefit, supporting gene agnostic mechanism of action."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290 • NR2E3

Expanded Access Program for RP in Adults (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Ocugen

New trial • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

liMeliGhT: A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Ocugen

Gene therapy • New P3 trial • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

OCU400 Nuclear Hormone Receptor-Based Gene Modifier Therapy: Safety and Efficacy from Phase 1/2 Clinical Trial for Retinitis Pigmentosa Associated with NR2E3 and RHO Mutations (ARVO 2024) - P1/2 | "OCU400 demonstrated relative safety in low and medium doses and showed potential efficacy for AR-NR2E3 and AD-RHO cases but not for AD-NR2E3 cases. Further efficacy testing of this therapy is warranted."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • NR2E3

Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Ocugen | Trial completion date: Feb 2024 ➔ Dec 2024 | Trial primary completion date: Feb 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290

The Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Ocugen | N=24 ➔ 124

Enrollment change • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290

"@Ocugen @OcugenPE is ready to go on command! #OCU500 #OCU400 #OCU200 💪🏼 @US_FDA @BARDA" (@nrbarile)

The Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis (clinicaltrials.gov) - P1/2 | N=21 | Recruiting | Sponsor: Ocugen | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Apr 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CEP290

"$OCGN Ocugen Announces Completion of Dosing in OCU400 Phase 1/2 Cohort 2 https://t.co/HZejvP6keV" (@stock_titan)

The Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Ocugen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

The Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa (clinicaltrials.gov) - P1/2; N=18; Not yet recruiting; Sponsor: Ocugen

New P1/2 trial • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa