Nanoscope Therapeutics Announces Positive Top-line Results from Randomized Controlled Trial of MCO-010 for Retinitis Pigmentosa

• MCO-010 achieved its primary and key secondary endpoints with statistical significance and no serious adverse events
• Data from the Phase 2b RESTORE trial demonstrate clinically meaningful vision improvement in legally blind individuals with progressive and permanent neurodegeneration of the retina
• RESTORE is the first randomized, controlled trial of a mutation-agnostic gene therapy for a genetic disease
• Nanoscope anticipates submitting a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the second half of 2024

DALLAS, March 26, 2024 -- Nanoscope Therapeutics Inc., a late-stage clinical biotechnology company developing gene therapies for inherited retinal diseases and age-related macular degenerations (AMD), today announced positive top-line results after the completion of the 2-year Phase 2b RESTORE randomized, controlled clinical trial of its lead program, MCO-010, a mutation-agnostic gene therapy for patients with permanent and severe vision loss from advanced retinitis pigmentosa (RP).

The trial met its primary endpoint, demonstrating a statistically significant improvement of best-corrected visual acuity (BCVA) at week 52 in both the high-dose (0.337 LogMAR; p=0.021) and low-dose (0.382 LogMAR; p=0.029) treatment groups compared to the sham control group (0.050 LogMAR). The Phase 2b RESTORE trial represents the only randomized controlled trial in retinal degenerative disease to demonstrate improvement beyond the clinically important BCVA > 0.3 LogMAR threshold in a statistically significant manner.

Improvements in visual function persisted or increased following week 52 in the study, demonstrating the durable effect of a single intravitreal injection of MCO-010. BCVA improvement at week 76, a key secondary endpoint, was statistically significant in the high-dose treatment group compared to the control group (0.539 LogMAR; p=0.001). At week 76, the improvement in BCVA in the low-dose treatment group was not statistically significant compared to control (0.374 LogMAR; p=0.065). These results are consistent with what has been previously observed in the earlier Phase 1/2a open-label study. The high-dose MCO-010 (1.2E11gc/eye) is planned to be the commercial dose.

In another pre-specified secondary endpoint, the composite functional endpoint of novel multi-luminance shape discrimination and y-mobility testing showed an 89% response rate in both the high-dose and low-dose treatment groups at week 52, offering further support of vision improvement following MCO-010 administration. Additional data from this clinical trial will be presented in a series of scientific meetings in the coming months, beginning with a presentation at the Annual Scientific Meeting of the Association for Research in Vision and Ophthalmology on May 6, 2024, in Seattle, Washington, by Allen Ho, MD, Director of Retina Research and Co-Director of the Retina Service at Wills Eye Hospital.

MCO-010 was generally well tolerated with no treatment-related serious or severe adverse events reported, consistent with prior studies. The most common adverse events were mild or moderate anterior chamber cell and ocular hypertension. No adverse events of special interest related to intraocular inflammation, such as endophthalmitis, retinitis, retinal vasculitis, retinal occlusive vasculitis, or hypotony, were reported in the treatment groups.

"We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind," said David Boyer, MD an investigator in the trial and Adjunct Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine. "Many patients treated with MCO-010 derived a clinically meaningful benefit measurable on the primary visual function test, and this effect was confirmed by a parallel improvement in functional vision assessments. If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition."

Based on these results, Nanoscope intends to submit a BLA to the U.S. FDA in the second half of 2024 as the first step in executing its global regulatory and commercialization strategy.

"I am thrilled to see that MCO-010 has the potential to improve vision in patients with advanced RP," said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates and Clinical Professor at the University of Nevada, Reno School of Medicine. "This is a pivotal moment for the field of ocular gene therapy to have a potential intravitreal mutation-agnostic treatment for RP, a disease that has no available treatment currently and leads to permanent vision loss."

"Nanoscope is at the forefront of advancing optogenetics into a tangible therapeutic solution for patients with RP," said Sulagna Bhattacharya, co-founder and Chief Executive Officer of Nanoscope. "The compelling data from the most recent analyses of the RESTORE trial at week 76 provide additional validation of Nanoscope's versatile MCO platform, which is driving our expanding pipeline of programs in both Stargardt disease and geographic atrophy (GA) due to age-related macular degeneration (AMD). We extend our heartfelt appreciation to the trial participants and their families, as well as to the investigators and all those who contributed to this groundbreaking trial and its successful completion." 

These results represent the first evidence of effectiveness of a mutation-agnostic gene therapy for a genetic disease. These results reflect more than a decade of innovation across all aspects of the MCO-010 program, including vector design, manufacturing, and clinical trial design, as well as the development of novel functional vision endpoints for this population with severe vision loss.

"These results are the culmination of more than a decade of work by numerous dedicated individuals, underscoring the potential of our unique broadband, highly photosensitive, and rapid MCO-010 platform," said Samarendra Mohanty, PhD, co-founder, President, and Chief Scientific Officer of Nanoscope. "This achievement marks a significant milestone in the field of mutation-agnostic gene therapy, firmly establishing the promise of optogenetics as a therapeutic modality. We extend our sincere gratitude to the National Eye Institute-NIH and collaborators for their invaluable contributions in realizing the therapeutic potential of MCO therapy, offering hope for vision restoration to patients regardless of their underlying genetic mutation."

RESTORE Trial Detail

The multicenter, Phase 2b trial randomized 28 subjects with severe vision loss and confirmed clinical diagnosis of RP. One randomized subject, who withdrew consent before baseline measurements and study intervention, was not included in the mITT population. Reported results are from the mITT population that included all randomized subjects who received the intervention in the study eye (MCO-010 or control): 18 subjects in the MCO-010 groups and 9 subjects in the control group. For the primary and key secondary endpoints, subjects were evaluated at multiple time points over two years to assess BCVA, measured by the Freiburg visual acuity test.

• A linear mixed-effects model for repeated measures (MMRM) was performed on the primary and key secondary endpoints, where the visual acuity data from all post-baseline visits was included in the model, with baseline visual acuity as a covariate.
• Comparisons between the treatment groups were performed using a Hochberg procedure to adjust for multiple comparisons against the control. Using the results obtained from the MMRM model, the p-values from the two comparisons of the MCO-010 groups versus the control were ordered from largest to smallest.
• Primary and key secondary visual acuity endpoint results being reported are based on regulatory discussions, as previously announced on January 18, 2024, and align the study endpoints with the originally intended study objectives. A revised statistical analysis plan (SAP) was finalized and submitted to regulators before the completion of week 76 and later time points of the study.
• The functional vision was assessed by evaluating subject performance in object recognition or navigating a mobility course under a variety of light levels encountered in activities of daily living.

A summary of top-line efficacy results follows:

About Retinitis Pigmentosa

Retinitis Pigmentosa (RP) encompasses a group of rare genetic disorders in which the retina's photoreceptor cells degrade over time, leading to impaired vision and eventual blindness. These disorders are believed to be linked to over 100 different gene mutations. Approximately 100,000 people in the U.S. and an estimated 2 million people worldwide suffer from RP, making it the leading cause of inheritable blindness.

About MCO-010

Current gene therapies aim to treat patients with specific genetic mutations and are further limited in advanced diseases with degenerated outer retina cells. Ambient-light activatable MCO optogenetic monotherapy targets abundant inner retinal neurons and has the potential to restore vision permanently lost due to advanced RP. MCO-010 (sonpiretigene isteparvovec, suspension for intravitreal injection) is the only broadband, fast, and highly light-sensitive opsin currently in clinical trials. With bipolar cell targeting via mGluR6 promoter-enhancer, the MCO-010 expression cassette is designed for restoring high-quality vision in real-world environments. The proprietary AAV2 vector allows robust transduction of MCO-010 in bipolar cells upon intravitreal injection. The Phase 1/2a study of MCO-010 in advanced RP patients demonstrated favorable safety and dose-dependent improvement in visual acuity.

About Nanoscope Therapeutics Inc.

Nanoscope Therapeutics is developing gene-agnostic, sight-restoring optogenetic therapies for the millions of patients blinded by inherited retinal diseases, for which no cure exists. The company's lead asset, MCO-010, recently completed the RESTORE Phase 2b multicenter, randomized, double-masked, sham-controlled clinical trial in the U.S. for retinitis pigmentosa (NCT04945772). The company has also recently completed the Phase 2 STARLIGHT trial of MCO-010 therapy in patients with Stargardt disease (NCT05417126 ). MCO-010 has received FDA fast-track designations and FDA orphan drug designations for both RP and Stargardt disease. Preclinical assets include non-viral laser-delivered MCO-020 gene therapy for GA due to AMD.

Investor Contact:

Argot Partners

212-600-1902

Nanoscope@argotpartners.com

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