Multi-Characteristic Opsin Optogenetic Therapy Meets Phase 2 Endpoint in Retinitis Pigmentosa

MCO-010 (Nanoscope Therapeutics) gene therapy yielded clinically meaningful vision improvements in 88.9% (n = 16) of patients with retinitis pigmentosa (RP) treated in the phase 2 RESTORE clinical trial (NCT04945772).

"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," investigator Victor H. Gonzalez, MD, founder, Valley Retina Institute, McAllen, Texas, said in a statement. "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."

The RESTORE trial treated 18 participants with severe RP with a single intravitreal injection of MCO-010 and another 9 that received a sham injection. Sixteen of 18 patients (88.9%) had at least a 2-luminance level clinically meaningful improvement on Multi-Luminance Y-Mobility Test (MLYMT)or Multi-Luminance Shape Discrimination Test (MLSDT) scores compared to 4 participants in the placebo group (P <.05) at 12 months. Specifically, 12 participants improved by at least 2 levels on MYLMT scores compared to 3 in the placebo group and 10 participants improved by at least 2 levels on MLSDT scores compared to 2 in the placebo group at 12 months. Seven of 18 treated participants also improved by at least –0.3 LogMAR or more in best-corrected visual acuity compared to 1 in the placebo group at 12 months. Altogether, the study has met its primary outcome, with a +1.0 (95% CI [0.0-3.0]) difference in change in MYMT score compared to placebo.

Investigators found that MCO-010 was well-tolerated with no serious ocular or systemic adverse events (AEs) reported. One serious AE occurred in a patient treated with placebo. Rates of treatment-emergent (TE) AEs were comparable across study arms and common ocular TEAEs included anterior chamber cells, ocular hypertension, and conjunctival hemorrhage.

READ MORE: NIH Awards Grant for Engineered Mechanosensitive Channel Glaucoma Gene Therapy

"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. 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," Samarendra Mohanty, Co-founder, President and Chief Scientific Officer, Nanoscope, added to the statement.

MCO-010 is a gene-agnostic, ambient-light-activated Multi-Characteristic Opsin (MCO) optogenetic therapy being evaluated in clinical trials in both RP and Stargardt disease, with additional preclinical indications including Usher syndrome. It uses bipolar cell targeting via mGluR6 promoter-enhancer to restore damaged retinal cells.

"We are thrilled to see such encouraging results from the RESTORE trial," Sulagna Bhattacharya, Co-founder and Chief Executive Officer, Nanoscope, added. "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. 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. We sincerely thank the trial participants and families as well as the investigators and all who contributed to this groundbreaking trial. We would also like to thank our investors, the NIH and collaborators for diligently supporting us over many years in realizing the potential of MCO therapy in vision restoration for patients regardless of underlying genetic mutation."

REFERENCE

Nanoscope Therapeutics Announces Positive Topline Results from Phase 2b RESTORE Trial of MCO-010 for the Treatment of Retinitis Pigmentosa. News release. Nanoscope Therapeutics. March 30, 2023. https://www.prnewswire.com/news-releases/nanoscope-therapeutics-announces-positive-topline-results-from-phase-2b-restore-trial-of-mco-010-for-the-treatment-of-retinitis-pigmentosa-301785351.html