Nanoscope Therapeutics Announces Positive Topline Results from Phase 2b Trial of Optogenetic Therapy for RP

Nanoscope Therapeutics announced topline results from the phase 2b RESTORE clinical trial of MCO-010, an ambient-light activatable Multi-Characteristic Opsin (MCO) optogenetic therapy for vision restoration in advanced retinitis pigmentosa (RP), irrespective of gene mutation. MCO-010 has received both orphan drug and fast track designations from the FDA.

In the RESTORE trial (NCT04945772), 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%) 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%) receiving placebo (P<0.05);
• 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: +1.0 (95% CI 0.0, 3.0).

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.

Today’s 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.

“I have had the privilege of observing substantial improvements in visual function in several patients who have enrolled in MCO-010 clinical trials over the past year. The fact that we see sustained and sometimes transformative gains in vision function, allowing them to walk in the clinic with more certainty, after a single treatment is remarkable and unprecedented,” Victor H. Gonzalez, MD, founder of Valley Retina Institute, McAllen, Texas and RESTORE investigator, said in a company news release. “These participants who were living with severe vision impairment due to RP now have an improved quality of life, very different from before receiving MCO-010. In addition, MCO-010’s favorable safety profile further strengthens my confidence in this ground-breaking treatment that I expect to become an important treatment option for people with advanced RP.”

“These results are gratifying, as they demonstrate the potential of MCO-010 to restore vision and represent more than a decade of work by many dedicated individuals involved in the discovery and development of this unique fast, broadband, and highly sensitive platform," said Samarendra Mohanty, Co-founder, President and Chief Scientific Officer of Nanoscope. "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. The RESTORE trial data further validate Nanoscope’s MCO platform that is being applied across a growing pipeline of programs. Our approach demonstrates potential across a range of diseases and therapeutic areas and Nanoscope is uniquely poised to advance optogenetics to be a therapeutic reality for patients."

The company expects to present the RESTORE topline results at upcoming medical conferences.