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Nanoscope Reports Positive Topline Results from Phase 2b Trial of MCO-010 for the Treatment of Retinitis Pigmentosa

March 31, 2023

Rare Daily Staff

Nanoscope Therapeutics reported topline results from the Phase 2b RESTORE clinical trial of MCO-010, an optogenetic therapy for vision restoration in advanced retinitis pigmentosa, irrespective of gene mutation.

Retinosis 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.

Current gene therapies are aimed to treat patients with specific gene mutation in outer retinal cells, while ambient-light activatable MCO optogenetic monotherapy targeting abundant inner retinal neurons has the potential to restore vision lost due to advanced RP, with degenerated outer retinal cells. MCO-010 is the only broadband, fast, and most-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.

In the multicenter, randomized, double-masked, sham-controlled RESTORE trial, 18 patients with severe vision impairment due to RP received a single intravitreal injection of MCO-010 while 9 received a sham intravitreal injection procedure. Results showed vision function improvements after treatment with MCO-010 consistent with previous studies as well as a favorable safety profile. The primary outcome measure was mean change in Multi-Luminance Y-Mobility Test (MLYMT, vision-guided mobility) score vs. placebo. Other key efficacy assessments included the Multi-Luminance Shape Discrimination Test (MLSDT, near object recognition) and Best-Corrected Visual Acuity (BCVA). For the MLYMT and MLSDT, a 2 or more luminance level change is considered clinically meaningful. For BCVA, a 0.3 LogMAR change is considered clinically meaningful, with negative change indicating improved visual acuity.

Key efficacy outcomes at 12-month were: 16 of 18 (88.9 percent) of MCO-010 treated patients demonstrated a 2 or more luminance level improvement in MLYMT or MLSDT at 12 months compared to 4 of 9 (44.4 percent) receiving placebo; 12 of 18 MCO-010 treated patients improved by 2 or more luminance levels in the MLYMT compared to 3 of 9 receiving placebo; 10 of 18 MCO-010 treated patients improved by 2 or more luminance levels in the MLSDT compared to 2 of 9 receiving placebo; 7 of 18 MCO-010 treated patients improved by -0.3 LogMAR or more in BCVA compared to 1 of 9 receiving placebo; and change in MLYMT score (primary outcome), difference vs. placebo was +1.0.

In addition to the evidence of a clinically meaningful effect, MCO-010 was well-tolerated with no serious or severe ocular or systemic adverse events reported. One SAE occurred in a placebo treated patient. There was a comparable incidence of treatment emergent adverse events (TEAEs) across study arms. The most common ocular TEAEs reported across treatment arms were anterior chamber cells, ocular hypertension, and conjunctival hemorrhage.

“This is a pivotal moment for the field of mutation-agnostic gene therapy and establishes optogenetics as a therapeutic modality that can restore functional vision in ambient light in patients with severe retinal degeneration,” said Samarendra Mohanty, co-founder, president, and chief scientific officer of Nanoscope.

The RESTORE results are consistent with those observed in the earlier phase 1/2 trial, demonstrating improvements in functional vision in the majority of patients treated with MCO-010 together with a favorable safety profile. People with severe vision loss due to RP currently have no available treatments to improve vision. MCO-010 has received both orphan drug and fast track designations from the U.S. Food and Drug Administration.

“These results suggest that MCO-010 provides substantial benefit to patients with severe vision loss due to advanced RP, a condition for which there are currently no available treatments,” said Sulagna Bhattacharya, co-founder and CEO of Nanoscope. “We are looking forward to engaging with the FDA and other regulatory agencies on the future of MCO-010, with the goal of expeditiously getting this novel therapy to patients.”

The Company expects to present the RESTORE top-line results at upcoming medical conferences.

Photo: Sulagna Bhattacharya, co-founder and CEO of Nanoscope

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