JNJ-1887 / J&J - LARVOL DELTA

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=305 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jul 2025 ➔ Feb 2026

Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Gene Therapy in Age-related Macular Degeneration. (PubMed, Int Ophthalmol Clin) - "Current trials in wet AMD include ADVM-022 and RGX-314. Current trials in dry AMD include GT-005 and JNJ-1887."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future. (PubMed, Rom J Ophthalmol) - "Advances include molecularly targeted therapies (Pegcetacoplan, Avacincaptad Pegol) that reduce inflammation, gene therapy (HMR59) protecting RPE cells, and mitochondria-targeted drugs (SS-31) mitigating oxidative stress...However, further clinical trials are needed to optimize these strategies, assess long-term outcomes, and expand patient access to effective treatments. These advancements have the potential to significantly improve the quality of life for individuals affected by dry AMD."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Infectious Disease • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Transplantation

A Long-term Extension Study of JNJ-81201887 (AAVCAGsCD59) Parent Studies in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=311 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2029 ➔ Jun 2030

Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=305 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Long-term Extension Study of JNJ-81201887 (AAVCAGsCD59) Parent Studies in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=311 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Aug 2029 ➔ Dec 2029

Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Long-term Extension Study of JNJ-81201887 (AAVCAGsCD59) Parent Studies in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=311 | Recruiting | Sponsor: Janssen Research & Development, LLC

New P2 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond. (PubMed, Genes (Basel)) - "This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials...Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases."

Gene therapy • Journal • Review • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC

Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-related Macular Degeneration. (PubMed, Ophthalmology) - "All 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted."

Gene therapy • Journal • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2026 ➔ Jan 2026

Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jan 2026 ➔ Jun 2026

Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC | Phase classification: P2b ➔ P2

Phase classification • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Janssen to Highlight Innovation in Retinal Pipeline at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting (PRNewswire) - "The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that five company-sponsored presentations will be featured during the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting in New Orleans from April 23-27, 2023. Janssen presentations will include updates from the Phase 1/2 MGT009 trial for investigational gene therapy botaretigene sparoparvovec (bota-vec, formerly AAV-RPGR) in patients with the inherited retinal disease (IRD) X-linked retinitis pigmentosa (XLRP) associated with the retinitis pigmentosa GTPase regulator (RPGR) gene, and pooled safety analysis data from two Phase 1 trials of the investigational gene therapy JNJ-81201887 (JNJ-1887); one trial in patients with geographic atrophy (GA), a late-stage and severe form of age-related macular degeneration (AMD) and one trial in wet AMD (Abstracts #5446 and #732-C0314)."

P1/2 data • P2 data • Age-related Macular Degeneration • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

A Study to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P2b | N=300 | Recruiting | Sponsor: Janssen Research & Development, LLC

New P2b trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Pooled safety analysis of a single intravitreal injection of JNJ-1887 (gene therapy, AAVCAGsCD59) in patients with age-related macular degeneration (AMD) (ARVO 2023) - "In both studies, the side effects observed were generally mild or moderate in severity and resolved spontaneously or with steroid treatment. Together, these studies show that JNJ-1887 is generally safe, with side effects that can be managed in patients with GA and wet AMD."

Clinical • Gene therapy • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • CD59

Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy (GA) Due to Age-related Macular Degeneration (AMD) (Macula 2023) - "At 24 months, all 3 doses of JNJ-1887 were tolerated with a manageable safety profile. Further investigation of JNJ-1887 for the treatment of GA secondary to dry AMD is warranted."

Gene therapy • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Immunology • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • CD59

Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway. (PubMed, Immunol Rev) - "This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Gene Therapies • Hematological Disorders • Inflammation • Macular Degeneration • Ophthalmology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Retinal Disorders

AAVCAGsCD59 for the Treatment of Wet AMD (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Review of gene therapies for age-related macular degeneration. (PubMed, Eye (Lond)) - "Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders

Geographic Atrophy: Targeting the Complement Pathway (Retina Today) - "To date, no treatments are approved to reverse, prevent, or reduce the rate of geographic atrophy (GA) progression-an area of urgent unmet medical need as the population ages. A leading contributor to the pathogenesis of GA is complement system-mediated inflammation and retinal cell degeneration. Genome-wide association studies identified polymorphisms in a number of complement proteins among patients with AMD. In addition, patients with GA had alterations in complement cascade components both systemically and within the eye. Active research is underway to find a treatment for GA, and most studies focus on the complement cascade."

Intravitreal AAVCAGsCD59 for Advanced Dry Age-related Macular Degeneration (AMD) With Geographic Atrophy (GA) (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Hemera Biosciences; N=132 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders

Intravitreal AAVCAGsCD59 for Advanced Dry Age-related Macular Degeneration (AMD) With Geographic Atrophy (GA) (clinicaltrials.gov) - P2; N=132; Not yet recruiting; Sponsor: Hemera Biosciences; Initiation date: Jul 2020 ➔ Jul 2021

Clinical • Trial initiation date • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders

AAVCAGsCD59 for the Treatment of Wet AMD (clinicaltrials.gov) - P1; N=25; Active, not recruiting; Sponsor: Hemera Biosciences; Trial completion date: Feb 2021 ➔ Jan 2022

Trial completion date • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Complement inhibition as a therapeutic strategy in retinal disorders. (PubMed, Expert Opin Biol Ther) - "The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies...The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies...Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. Expert opinion: While complement inhibition has not yet demonstrated ability to halt GA progression in a phase 3 trial, further study is warranted."

Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Gene Therapies • Genetic Disorders • Immunology • Macular Degeneration • Ophthalmology • Rare Diseases • Retinal Disorders

Intravitreal AAVCAGsCD59 Compared With Sham for Eyes With Advanced Dry Age-related Macular Degeneration (AMD) With Geographic Atrophy (GA) (clinicaltrials.gov) - P2; N=132; Not yet recruiting; Sponsor: Hemera Biosciences

Clinical • New P2 trial • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Gene Therapies • Genetic Disorders • Macular Degeneration • Ophthalmology • Rare Diseases • Retinal Disorders