VMCO-I / Nanoscope Therap - LARVOL DELTA

Development of Orthogonal Potency Assays for Multi-Characteristic Opsin Gene Therapy: Gene Expression and Light-Stimulated Activity (ASGCT 2025) - "The successful implementation of these potency assays supports product release and stability testing and establishes standards for optogenetic gene therapy products. Disease Focus of Abstract:Rare Diseases"

Gene therapy • Gene Therapies • Rare Diseases

Forced Degradation Studies of Multi-Characteristic Opsin Gene Therapy Drug Product (ASGCT 2025) - "These findings support the use of these validated assays for quality control and stability monitoring during MCO-010 drug product storage and handling for future clinical use. Disease Focus of Abstract:Ophthalmic Diseases"

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

Perspectives and open questions in vision restoration with vMCO-010. (PubMed, Mol Ther) - No abstract available

Journal

A Long-Term Follow-Up Study in Subjects Who Received vMCO-I Administered Via Intravitreal Injection (clinicaltrials.gov) - P=N/A | N=11 | Enrolling by invitation | Sponsor: Nanoscope Therapeutics Inc. | Trial completion date: Dec 2024 ➔ May 2025 | Trial primary completion date: Dec 2024 ➔ May 2025

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

126-Week Visual Acuity Outcomes Following Mutation-Agnostic Optogenetic Therapy, MCO-010, for Retinitis Pigmentosa (RP) (ARVO 2025) - "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."

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

Analysis of Patient-Reported Outcomes of MCO-010 Mutation Agnostic Optogenetic Therapy for Retinitis Pigmentosa: 12-Month Results from a Phase 2b Randomized, Sham-Controlled, Patient- and Assessor-Masked Clinical Trial (RESTORE) (ISPOR 2025) - "RESTORE data demonstrate improved patient-reported outcomes on vision-related quality of life at week 52 in MCO-010 treated patients."

Clinical • P2b data • Patient reported outcomes • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

SUSTAIN: Non-interventional Long Term Follow-up Study of Participants Previously Enrolled in the STARLIGHT Study (clinicaltrials.gov) - P=N/A | N=6 | Active, not recruiting | Sponsor: Nanoscope Therapeutics Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

REMAIN: Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study (clinicaltrials.gov) - P=N/A | N=18 | Active, not recruiting | Sponsor: Nanoscope Therapeutics Inc. | Enrolling by invitation ➔ Active, not recruiting

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

Verana Health and Nanoscope Therapeutics Announce Collaboration to Accelerate Retinitis Pigmentosa Research (GlobeNewswire) - "Verana Health....and Nanoscope Therapeutics...today announced a partnership to accelerate research for retinitis pigmentosa (RP), a rare inherited retinal disease that affects approximately 100,000 people in the U.S....Through this collaboration, Nanoscope Therapeutics will utilize Verana Health’s Qdata Retinitis Pigmentosa, which is a research-ready, real-world dataset that can be used to analyze patients with RP and track their clinical outcomes....Such insights will support the development and commercialization of MCO-010, Nanoscope Therapeutics’ optogenetic gene therapy that is designed to restore vision and potentially slow neurodegeneration."

Commercial • Retinitis Pigmentosa

Nanoscope Therapeutics Announces Presentations at Upcoming Medical Meetings (PRNewswire) - "Nanoscope Therapeutics Inc....today announced presentations at two upcoming medical meetings....Nanoscope is developing restorative treatments. As part of this, Dr. Ho will discuss 126-week data from Nanoscope's REMAIN long-term follow-up study of advanced retinitis pigmentosa patients dosed in the RESTORE randomized controlled trial....Dr. Gonzalez will present and discuss long-term follow-up efficacy and safety data of Nanoscope's MCO-010 optogenetic therapy for vision restoration in patients with severe vision loss due to retinitis pigmentosa."

Observational data • Ophthalmology • Retinitis Pigmentosa

Efficacy of Intravitreal Multi-Characteristic Opsin (MCO-010) Optogenetic Gene Therapy in a Mouse Model of Leber Congenital Amaurosis. (PubMed, J Ocul Pharmacol Ther) - "It also significantly improved the vision in rd12 mice relative to control AAV2-injected mice. MCO-010 therefore represents a novel and efficacious optogenetic therapeutic to treat LCA and other IRDs irrespective of the genetic defect(s)."

Gene therapy • Journal • Preclinical • CNS Disorders • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Nanoscope Publishes Breakthrough Showing MCO-010 Treatment Arrests Neurodegeneration (PRNewswire) - "Nanoscope Therapeutics...announced a breakthrough discovery in Translational Vision Science & Technology (TVST, an ARVO journal) demonstrating that MCO-010 optogenetic treatment of the inner retina arrests further retinal degeneration in an animal model of retinitis pigmentosa (RP), as assessed by optical coherence tomography and immunohistochemical analysis. Following intravitreal MCO-010 treatment (sonpiretigene isteparvovec), approximately 80% of bipolar cells were transduced in the retina, and no alterations in retinal thickness were observed, unlike the control group. The results described in the publication provide evidence that the expression of MCO-010 in the retinas of mice experiencing photoreceptor degeneration halts further loss and prevents further disorganization of the retinal cell layers."

Preclinical • Ophthalmology • Retinitis Pigmentosa

Multi-Characteristic Opsin Therapy to Functionalize Retina, Attenuate Retinal Degeneration, and Restore Vision in Mouse Models of Retinitis Pigmentosa. (PubMed, Transl Vis Sci Technol) - "Intravitreal MCO-010 was well tolerated in rd1 and rd10 mice models of RP, and it appeared to attenuate retinal photoreceptor degeneration based on retinal structure and functional outcome measures. As reported here, optogenetic treatment of the inner retina attenuates further retinal degeneration in addition to photosensitizing higher order neurons, and this disease-modifying aspect should be evaluated in optogenetic clinical trials."

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

Nanoscope Therapeutics Announces End-of-Phase 2 Meeting with U.S. FDA and Plan to Initiate a Phase 3 Clinical Trial of MCO-010 to Treat Stargardt Macular Degeneration (PRNewswire) - "The FDA provided clear input on the proposed Phase 3 registrational trial in patients with SMD intended to support safety and effectiveness of MCO-010. The proposed study design will consist of a single MCO-010 intravitreal dose group, randomized 1:1 to a control cohort receiving a sham injection; The FDA provided valuable input on statistical methods for the proposed primary and secondary endpoints that will inform further engagement with FDA to align on statistical analyses; The FDA offered continued discussion and assistance to plan further evaluation of the multi-luminance shape discrimination test to support use as a key secondary endpoint; The FDA agreed on the sufficiency of the current nonclinical package to support a future BLA submission."

FDA event • New P3 trial • Macular Degeneration • Ophthalmology

Safety of intravitreally delivered AAV2 vector-mediated multi-characteristic opsin genetic construct in wild type beagle dogs. (PubMed, J Gene Med) - "In summary, MCO-010 demonstrated a favorable safety profile when administered to the eyes of adult Beagle dogs of both sexes at dose levels up to 2.2 × 1011 gc per eye, with no adverse effects observed. This dose was identified as the No Observed Adverse Effect Level (i.e. NOAEL) and guided selection of safe doses for human clinical trials."

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

Longitudinal Analysis of BCVA and Near-Field Object Recognition in Low- or High-Dose MCO-010 Mutation Agnostic Optogenetic Therapy for Retinitis Pigmentosa: 12-Month Results from a Phase 2b/3 Randomized, Sham-Controlled, Patient- and Assessor-Masked Clinical Trial (RESTORE) (ASGCT 2024) - "MCO-010 patients had mean baseline BCVA scores of 2.207 ± 0.105 and 2.250 ± 0.00 logMAR (low- and high-dose, respectively), and the sham patients had a mean baseline BCVA of 2.172 ± 0.1342 logMAR. The following BCVA results are reported from weeks 16, 24, 36, and 52. Compared to sham, low-dose MCO-010 patients had a mean improvement of 0.160, 0.192, 0.431, and 0.336 logMAR (P = 0.2780, 0.1958, 0.0060 and 0.0300 respectively)."

Clinical • P2/3 data • P2b data • CNS Disorders • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Characterization of a broadband ambient light activatable multi-characteristic opsin supporting its superior performance in restoring vision (ARVO 2024) - "The unique structure and functioning of MCO-010 represent key characteristics needed to restore vision in subjects with degenerative retinal conditions. Broadband light sensitivity with high dynamic range of MCO has opened new vistas in restoring vision at ambient lighting environments, without the need for a light stimulation device."

Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • HSPA5

In vivo efficacy of a novel multi-characteristic opsin (MCO-010) in a mouse model of Leber congenital amaurosis (ARVO 2024) - "The MCO-010 treatment was well tolerated by LCA-harboring mice. Furthermore, this gene therapy significantly attenuated retinal cell loss in the RPE65 mice and restored their vision as judged by structural and functional activity parameters described above. MCO-010 therefore represents a useful therapeutic modality for improving visual outcomes in this LCA animal model."

Preclinical • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Multi-characteristic opsin gene therapy attenuates retinal degeneration and restore vision in mouse models of retinitis pigmentosa (ARVO 2024) - "Intravitreal MCO-010 treatment enabled durable restoration of visual behavior in ambient light in mouse models of RP. Notably, attenuation of progressive structural retinal degeneration was observed on OCT and IHC analysis. This structural preservation combined with functional gains supports disease-modifying potential for MCO-based optogenetic therapies in advanced retinal degeneration."

Gene therapy • Preclinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • PRKCA

Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE] (clinicaltrials.gov) - P2 | N=27 | Completed | Sponsor: Nanoscope Therapeutics Inc. | Active, not recruiting ➔ Completed

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

Nanoscope Therapeutics Provides Regulatory Update on MCO-010 for the Treatment of Retinitis Pigmentosa (PRNewswire) - "Nanoscope Therapeutics Inc...today provided an update following recent regulatory discussions with the U.S. Food and Drug Administration ('FDA') and from the Scientific Advice meeting with the Icelandic Medicines Agency ('IMA'), regarding the regulatory path of MCO-010 for the treatment of RP....Based on regulatory discussions, Nanoscope has reverted to visual acuity as the primary endpoint in the ongoing randomized, double-masked, multicenter Phase 2b study (RESTORE). The end-of-study, 100-week data are expected to be reported in H1 2024."

FDA event • P2b data • Retinitis Pigmentosa

Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE] (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Nanoscope Therapeutics Inc. | Phase classification: P2b ➔ P2

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

REMAIN: Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study (clinicaltrials.gov) - P=N/A | N=18 | Enrolling by invitation | Sponsor: Nanoscope Therapeutics Inc.

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

STARLIGHT: Safety and Effects of a Single Intravitreal Injection of vMCO-010 Optogenetic Therapy in Subjects With Stargardt Disease (clinicaltrials.gov) - P2a | N=6 | Completed | Sponsor: Nanoscope Therapeutics Inc. | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • PROM1

Economic Burden and Changing Treatment Landscape in Stargardt Disease: A Literature and Database Review (ISPOR-EU 2023) - "Seven trials investigated 5 drug interventions (emixustat, tinlarebant, STG-001, avacincaptad pegol, ALK-001) with the eighth trial investigating a gene therapy (GT) (vMCO-010). The current healthcare costs associated with SD are not well established. With uncertainty around the current economic burden of SD, it will be difficult to determine the economic impact of new treatment options when making access decisions. Future analysis of analogues from other ocular degeneration disorders may prove useful in determining the current economic burden of SD."

HEOR • Review • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • ALK