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FDA and EU Regulators provide consistent advice that visual acuity may serve as primary endpoint to evaluate the effectiveness of MCO-010 in the treatment of low-vision retinitis pigmentosa (RP) patients Regulatory feedback provides clarity for potential path to approval in the US and in Europe for MCO-010 in RP; Nanoscope preparing for immediate execution DALLAS, Jan. 18, 2024 /PRNewswire/ -- Nanoscope Therapeutics Inc., a late-stage clinical biotechnology company developing gene therapies for inherited retinal diseases and age-related macular degenerations (AMD), 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. In connection with the productive Type B End-of-Phase 2 discussion with the FDA, Nanoscope received feedback on its MCO-010 optogenetic gene therapy program in patients with severe vision loss from advanced RP. The FDA stated that change from baseline in a measure of visual acuity in low vision patients could be an appropriate primary efficacy assessment in an adequate and well-controlled study to provide substantial evidence of benefit to support BLA approval. MCO-010 has received both orphan drug and fast track designations from the FDA. Nanoscope also received positive feedback from a Scientific Advice meeting with the IMA as part of the approval path for MCO-010 in Europe. The IMA endorsed visual acuity as the appropriate primary endpoint to evaluate low-vision RP patients after MCO-010 treatment. The IMA also endorsed 0.3 logMAR change as being clinically meaningful for the severe vision loss RP patients. The IMA suggested Nanoscope explore conditional approval for MCO-010 in Europe based on the existing data. 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. "Consistent input from both the FDA and IMA on the potential for visual acuity to serve as the primary endpoint for the clinical program is a major milestone for Nanoscope and provides MCO-010 with a clear regulatory path in the US and in Europe," said Sulagna Bhattacharya, Co-founder, and CEO of Nanoscope. 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 gene mutations, and are further limited in advanced disease 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 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. The Phase 1/2 study of MCO-010 in advanced RP patients demonstrated favorable safety and dose-dependent improvement in visual acuity. Nominally significant visual acuity improvements in MCO-010 treated patients were observed in comparison to control in Phase 2b RESTORE trial. There were also nominally significant functional vision improvements as assessed by multi-luminance vision-guided mobility and shape discrimination, along with a favorable safety profile. 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 reported topline results from 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 retinitis pigmentosa and Stargardt disease. Preclinical assets include non-viral laser-delivered MCO-020 gene therapy for geographic atrophy. Investor Contact: Argot Partners 212-600-1902 PR@nanostherapeutics.com

100% (18/18) MCO-010 patients experienced a clinically meaningful improvement in vision-guided mobility (MLYMT), near-field object recognition (MLSDT) or visual acuity (BCVA) (p=0.007 vs sham) 94.4% (17/18) MCO-010 patients showed vision improvement in the MLYMT or BCVA (p=0.008 vs sham) 88.9% (16/18) of MCO-010 patients experienced a clinically meaningful 2 or more luminance level improvement in MLYMT or MLSDT (p=0.02 vs sham) Favorable safety profile for MCO-010 with no serious or severe adverse events DALLAS, April 27, 2023 /PRNewswire/ -- Nanoscope Therapeutics Inc., a clinical-stage biotechnology company developing gene therapies for retinal degenerative diseases, today announced the presentation of key data from its Phase 2b multicenter, randomized, double-masked, sham-controlled RESTORE clinical trial (NCT04945772) of MCO-010 at the ARVO annual meeting. MCO-010 is an ambient-light activatable Multi-Characteristic Opsin (MCO) optogenetic therapy for vision restoration in advanced retinitis pigmentosa (RP), irrespective of gene mutation. Composite efficacy data validate MCO-010 as a potential treatment for RP. MCO-010 has received both orphan drug and fast track designations from the U.S. Food and Drug Administration (FDA). In the 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. Results showed vision function improvements after treatment with MCO-010 consistent with previous studies as well as a favorable safety profile. Key efficacy measures included Multi-Luminance Y-Mobility Test (MLYMT, vision-guided mobility), Multi-Luminance Shape Discrimination Test (MLSDT, near-field object recognition), and Best-Corrected Visual Acuity (BCVA) scores. 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. Composite outcomes in key efficacy measures at 12-months were: 18 of 18 (100%) MCO-010 treated patients showed vision improvement in the MLYMT, MLSDT or BCVA compared to 5 of 9 (55.6%) receiving placebo (p=0.007); 17 of 18 (94.4%) MCO-010 treated patients showed vision improvement in the MLYMT or BCVA compared to 4 of 9 (44.4%) receiving placebo (p=0.008); 16 of 18 (88.9%) MCO-010 treated patients demonstrated a 2 or more luminance level improvement in the MLYMT or MLSDT compared to 4 of 9 (44.4%) receiving placebo (p=0.02); and 14 of 18 (77.8%) MCO-010 treated patients showed vision improvement in the MLSDT or BCVA compared to 3 of 9 (33.3%) receiving placebo (p=0.04). 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. 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. These RESTORE results are consistent with those observed in the earlier Phase 1/2 trial (NCT04919473) in which 9 of 11 (82%) of subjects demonstrated 2 luminance level improvements in vision-guided mobility or 0.3 logMAR in visual acuity. In this Phase 1/2 study, a favorable safety profile was observed, with no serious or severe adverse events. People with severe vision loss due to RP currently have no available treatments that can improve their vision. "I am honored to present the RESTORE trial results at ARVO. I have had the privilege of treating severely blind patients, enrolled in MCO-010 clinical trials, and have observed some improvement in their visual function. The fact that we see any gains in vision after a single intravitreal injection is remarkable," said David Boyer, MD, Retina-Vitreous Associates Medical Group in Beverly Hills, CA and Nanoscope Clinical Advisory Board member. "Some participants who were living with severe vision impairment due to RP have noticed improvement in visual function. In addition, MCO-010 had a favorable safety profile. It is an honor to have been a part of the first randomized controlled trial to show a visual improvement in a profoundly visually impaired population." "RP patients with severe vision loss are a heterogeneous population with different genotypes and phenotypic manifestations of degeneration in their macula and peripheral retina. For this reason, we strongly believe that no single assessment can adequately capture clinically important changes in vision across this broad population. Composite endpoints can be used to evaluate overall vision function changes in a single measurement when the individual tests assess different aspects of vision performance, such as vision-guided mobility, object recognition and visual acuity. Across composite endpoints in the RESTORE study, significantly more MCO-010 treated patients experienced clinically significant vision improvements. This randomized controlled trial provides compelling evidence that MCO-010 optogenetic therapy, as a mutation-agnostic treatment, can improve vision in patients with advanced RP," said Samarendra Mohanty, Co-founder, President and Chief Scientific Officer of Nanoscope. "The treatment landscape for severe vision loss due to RP is one of no approved therapies and lacking a pre-defined single endpoint for approval. The improvements we are seeing in MCO-010 treated patients across the key composite measures of efficacy make it a promising candidate for the treatment of patients with severe vision loss due to RP," added Sulagna Bhattacharya, Co-founder and Chief Executive Officer of Nanoscope. "We look forward to our upcoming conversations with the FDA on the totality of this data regarding an expeditious path to market for this exciting therapy. It truly brings us joy to see the impact and difference MCO-010 is making in the lives of patients, and we are grateful to all participants and investigators for being a part of the success of the RESTORE trial." About Retinitis Pigmentosa In normal eyes, opsins are expressed by photoreceptor cells and intrinsically photosensitive Retinal Ganglion Cells in the retina, and when activated by light they trigger the physiological process of vision. 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 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 (sonpiretigene isteparvovec, suspension for intravitreal injection) 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. The Phase 1/2 trial of MCO-010 in advanced RP patients demonstrated improvement in vision-guided mobility, shape discrimination and visual acuity. A significant proportion of patients treated with MCO-010 in Phase 2b RESTORE trial exhibited improvements in functional vision assessed by vision-guided mobility, shape discrimination and visual acuity, along with a favorable safety profile. About Nanoscope Therapeutics Inc. Nanoscope Therapeutics is developing gene-agnostic, sight restoring optogenetic therapies for the millions of patients blinded by retinal degenerative diseases, for which no cure exists. The company's lead asset, MCO-010, recently reported topline results from the RESTORE Phase 2b multicenter, randomized, double-masked, sham-controlled clinical trial in the U.S. for retinitis pigmentosa (NCT04945772). The company has also fully enrolled a Phase 2 STARLIGHT trial of MCO-010 therapy in Stargardt patients (NCT05417126). MCO-010 has received FDA Fast Track designations and FDA orphan drug designations for both RP and Stargardt. Preclinical assets include non-viral laser delivered MCO-020 gene therapy for geographic atrophy. Investor Contact: Argot Partners 212-600-1902 [email protected] SOURCE Nanoscope Therapeutics

88.9% (16/18) of MCO-010 treated patients experienced a clinically meaningful 2 or more luminance level improvement in vision-guided mobility or object recognition Clinically meaningful visual acuity gains observed in several MCO-010 treated patients Favorable safety profile for MCO-010 with no serious or severe adverse events DALLAS, March 30, 2023 /PRNewswire/ -- Nanoscope Therapeutics Inc., today announced topline results from the Phase 2b multicenter, randomized, double-masked, sham-controlled RESTORE clinical trial (NCT04945772) 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 U.S. Food and Drug Administration (FDA). In the 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%) 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," said Victor H. Gonzalez, MD, founder of Valley Retina Institute, McAllen, Texas and RESTORE investigator. "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. 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," added Samarendra Mohanty, Co-founder, President and Chief Scientific Officer of Nanoscope. "We are thrilled to see such encouraging results from the RESTORE trial," said Sulagna Bhattacharya, Co-founder and Chief Executive Officer of Nanoscope. "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." The Company expects to present the RESTORE top-line results at upcoming medical conferences. About Retinitis Pigmentosa In normal eyes, opsins are expressed by photoreceptor cells and intrinsically photosensitive Retinal Ganglion Cells in the retina, and when activated by light they trigger the physiological process of vision. 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 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 (sonpiretigene isteparvovec, suspension for intravitreal injection) 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. The Phase 1/2 trial of MCO-010 in advanced RP patients demonstrated improvement in vision-guided mobility, shape discrimination and visual acuity. A significant proportion of patients treated with MCO-010 in Phase 2b RESTORE trial exhibited improvements in functional vision assessed by vision-guided mobility, shape discrimination and visual acuity, along with a favorable safety profile. About Nanoscope Therapeutics Inc. Nanoscope Therapeutics is developing gene-agnostic, sight restoring optogenetic therapies for the millions of patients blinded by retinal degenerative diseases, for which no cure exists. The company's lead asset, MCO-010, recently reported topline results from the RESTORE Phase 2b multicenter, randomized, double-masked, sham-controlled clinical trial in the U.S. for retinitis pigmentosa (NCT04945772). The company has also fully enrolled a Phase 2 STARLIGHT trial of MCO-010 therapy in Stargardt patients (NCT05417126). MCO-010 has received FDA Fast Track designations and FDA orphan drug designations for both RP and Stargardt. Preclinical assets include non-viral laser delivered MCO-020 gene therapy for geographic atrophy. Investor Contact: Argot Partners 212-600-1902 [email protected] SOURCE Nanoscope Therapeutics