OPGx-LCA5 / Opus Genetics - LARVOL DELTA

Opus Genetics…announced that the last patient has been enrolled in its registrational Phase 3 clinical trial evaluating OPGx-LCA5, the Company’s investigational gene therapy for LCA5-associated inherited retinal disease (GlobeNewswire) - "The Phase 3 study was designed in collaboration with the FDA to support a potential Biologics License Application (BLA) for what could become the first approved therapy for patients living with LCA5-associated inherited retinal disease....Participants are currently completing the run-in period, and the Company expects to initiate dosing of OPGx-LCA5 in the fourth quarter of 2026, with topline data expected by the end of 2027."

P3 data: top line • Trial status • Inherited Retinal Dystrophy

Opus Genetics…announced that it has reached alignment with the U.S. Food and Drug Administration (FDA) in a Type B Rare Disease Evidence Principles (RDEP) meeting on the design of its registrational Phase 3 clinical trial evaluating OPGx-LCA5 for LCA5-associated IRD, an early-onset severe inherited retinal dystrophy (GlobeNewswire) - "Opus Genetics has received the meeting minutes from the Type B meeting confirming several key elements of the trial. The Phase 3 study is expected to enroll eight participants who are able to complete microperimetry testing with both eyes treated. The study is also expected to include a six-month run-in period, allowing each participant to serve as their own natural history control prior to receiving treatment....The Company expects to initiate dosing in the fourth quarter of 2026."

FDA event • New P3 trial • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

OPGx-LCA5 (The Manila Times) - "In the ongoing Phase 1/2 clinical trial, visual acuity was improved and maintained in the adult cohort over 24 months and improved in the pediatric cohort over 6 months....Recruitment is ongoing in the run-in period for the pivotal Phase 3 trial....Dosing with OPGx-LCA5 is expected to start in the fourth quarter of 2026."

Enrollment status • P1/2 data • Retinal Disorders

Opus Genetics Announces FDA Acceptance of OPGx-LCA5 into Rare Disease Evidence Principles (RDEP) Program (GlobeNewswire) - "As part of the RDEP program, the FDA will work closely with Opus Genetics to guide the ongoing development of OPGx-LCA5, including considerations for clinical trial design, approaches to generating efficacy in a small patient population, and strategies to support demonstration of clinical benefit. The program also provides a framework for evaluating substantial evidence of effectiveness, including the potential use of a single adequate and well-controlled study supported by confirmatory evidence."

FDA event • Rare Diseases • Retinal Disorders

Restoration of Cone-Mediated Vision After Gene Augmentation in Children with LCA5 (ARVO 2026) - P1/2 | "Purpose To assess the safety and efficacy of subretinal delivery of a recombinant adeno-associated virus serotype 8 (AAV8) vector carrying the native human LCA5 cDNA (OPGx-001) in adolescents with Leber congenital amaurosis associated with pathogenic variants in LCA5 (LCA5-LCA)...There were subjective and objective signs of efficacy detectable by one month post-treatment. The favorable outcomes pave the path for enrolling milder phenotypes at this dose level.(ClinicalTrials.gov: NCT05616793)"

Clinical • Inherited Retinal Dystrophy • Ophthalmology

Opus Genetics Presents Clinical and Preclinical Data at ARVO 2026 Demonstrating Continued Pipeline Advancement in Inherited Retinal Diseases (GlobeNewswire) - "The data highlight emerging evidence that Opus Genetics’ gene therapy OPGx-LCA5 may restore daytime vision mediated by cones in pediatric patients with severe, early-onset disease, while also advancing Opus Genetics’ broader pipeline across BEST1 and RHO programs....Six-Month Clinical Data Demonstrate Restoration of Cone-Mediated Vision in Pediatric LCA5 Patients, with Sensitivity Improvements Reaching Normal Ranges....Preclinical RHO Programs Demonstrate Durable Retinal Preservation and Support Clinical Translation."

Clinical data • Preclinical • Ophthalmology • Retinal Disorders

OPGx-LCA5 – Gene Therapy for Leber Congenital Amaurosis (LCA) (Opus Medicus) - "Multiple regulatory designations granted including Rare Pediatric Disease, Orphan Drug, and Regenerative Medicine Advanced Therapy (RMAT) with potential eligibility for Priority Review Voucher upon approval; Positive Phase 1/2 safety and efficacy data reported in adults and pediatric participants; Enrollment ongoing in run-in period for planned, adaptive pivotal Phase 3 trial; Dosing with OPGx-LCA5 in the Phase 3 trial expected in the second half of 2026."

New P3 trial • P1/2 data • Regulatory • Retinal Disorders

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: Opus Genetics, Inc | N=15 ➔ 22

Enrollment change • Ophthalmology

Opus Genetics, Inc…announced the successful completion of a Type B Regenerative Medicine Advanced Therapy (RMAT) meeting with the U.S. Food and Drug Administration (FDA) regarding OPGx-LCA5, its gene therapy candidate for Leber congenital amaurosis (LCA) caused by mutations in the LCA5 gene. (The Manila Times) - "Opus will incorporate the FDA’s feedback into its updated clinical development and CMC plans for the Phase 3 portion of the study to include enrolling as few as 8 participants in a single arm, 12-month study utilizing an adaptive design, which provides flexibility on endpoints and number of participants, reflective of LCA5 as a rare condition with an urgent medical need....Following availability of validated clinical drug supply manufactured with the intended commercial processes, dosing with OPGx-LCA5 is anticipated in the second half of 2026, with topline clinical data expected approximately one year later."

FDA event • New P3 trial • P3 data: top line • Ophthalmology

OPGx-LCA5 - Gene Therapy for Leber Congenital Amaurosis (LCA) (The Manila Times) - "Initial pediatric data at one-month post-treatment showed vision improvement with no drug-related adverse events; three-month pediatric data is expected to be reported in Q3 2025."

P1/2 data • Inherited Retinal Dystrophy

Recovery of Cone-Mediated Vision in Lebercilin-Associated Severe Retinal Ciliopathy (LCA5) after Gene Therapy: One Year Results of a Phase Ib/IIa Trial. (PubMed, Mol Ther) - P1/2 | "We assessed the preliminary safety of a recombinant adeno-associated virus serotype 8 vector carrying the native human LCA5 cDNA (OPGx-001) in LCA5-associated Leber congenital amaurosis (LCA5-LCA), a congenital blindness...Visual acuity returned to baseline or improved in the treated eyes of all participants. The favorable safety profile and efficacy outcomes pave the path for enrolling milder phenotypes with careful dose escalation."

Journal • P1/2 data • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Opus Genetics, Inc | Trial completion date: Jan 2028 ➔ Jun 2028 | Trial primary completion date: Dec 2024 ➔ Jun 2028

Trial completion date • Trial primary completion date • Ophthalmology

Expected Growth Drivers in 2025 and Beyond (GlobeNewswire) - "Initial data from three pediatric patients treated with OPGx-LCA5 anticipated in Q3 2025; IND filing and initiation of a Phase 1/2 clinical trial for OPGx-BEST1 is planned for 2025, with preliminary data expected in Q1 2026; Topline data from the LYNX-2 pivotal Phase 3 trial evaluating Phentolamine Ophthalmic Solution 0.75% for visual loss in low light conditions associated with keratorefractive surgery are expected mid-year 2025; Topline data from the VEGA-3 pivotal Phase 3 clinical trial evaluating Phentolamine Ophthalmic Solution 0.75% for the treatment of presbyopia are expected in the first half of 2025."

Clinical data • IND • New P1/2 trial • Ophthalmology • Retinal Disorders

Opus Genetics Granted FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for OPGx-LCA5 Gene Therapy Candidate (GlobeNewswire) - "Opus Genetics, Inc...announced today that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to OPGx-LCA5, its investigational gene therapy for the treatment of Leber Congenital Amaurosis (LCA) due to genetic variations in the LCA5 gene....The RMAT designation for OPGx-LCA5 is based on early clinical evidence from Opus’s ongoing Phase 1/2 open-label, dose-escalation trial, which is evaluating the safety and potential efficacy of OPGx-LCA5 in patients with severe vision loss due to confirmed mutations in the LCA5 gene."

FDA event • Ophthalmology

Recovery of Cone-Mediated Vision in a Severe Ciliopathy after Gene Augmentation: One Year Results of a Phase I/II Trial for LCA5-LCA (ARVO 2025) - "Purpose To assess the safety and efficacy of an investigational subretinal delivery of a recombinant adeno-associated virus serotype 8 (AAV8) vector carrying the native human LCA5 cDNA (OPGx-001) in LCA5-LCA...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

P1/2 data • Ophthalmology

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Opus Genetics, Inc | Trial completion date: Sep 2027 ➔ Jan 2028 | Trial primary completion date: Aug 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Ophthalmology

AAV8-hLCA5 Subretinal Delivery to the Macula in LCA5-associated Leber Congenital Amaurosis (LCA5-LCA): Preliminary Safety and Efficacy Results of an Ongoing Phase I/II Gene Therapy Trial (ARVO 2024) - "Administration of OPGx-001 by SR injection appears to be safe and well tolerated. There were subjective and objective signs of biologic efficacy even in these severely affected patients. Efficacy at lowest dose warrants careful dose escalation."

Clinical • Gene therapy • P1/2 data • Inherited Retinal Dystrophy • Ophthalmology

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) (clinicaltrials.gov) - P1/2 | N=9 | Recruiting | Sponsor: Opus Genetics, Inc | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2023 ➔ Jun 2023

Enrollment open • Trial initiation date • Ophthalmology

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) (clinicaltrials.gov) - P1/2 | N=9 | Not yet recruiting | Sponsor: Opus Genetics, Inc | Trial completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Ophthalmology

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) (clinicaltrials.gov) - P1/2 | N=6 | Not yet recruiting | Sponsor: Opus Genetics, Inc

New P1/2 trial • Ophthalmology