Complementary Collaboration Aims to Advance Cell Therapy Study

■ Lineage Cell Therapeutics, Inc, and its subsidiary, Cell Cure Neurosciences Ltd., have entered into an agreement with Roche and Genentech for the development and commercialization of Opregen, a retinal pigment epithelium cell therapy for the treatment of ocular disorders, including advanced dry age-related macular degeneration (AMD) with geographic atrophy (GA). Opregen is currently being evaluated in a phase 1/2a open-label, dose-escalation clinical safety and efficacy study in patients with advanced dry AMD with GA.

Under terms of the agreement, Genentech will pay Lineage a $50 million upfront payment and Lineage is eligible to receive up to $620 million in additional development, approval, and sales milestone payments, in addition to tiered double-digit royalties. Genentech will assume responsibility for further clinical development and commercialization of Lineage’s OpRegen program, and Lineage will perform manufacturing initiatives, as well as activities related to the ongoing clinical study.

“Genentech’s desire to combine our cell therapy technology with their ophthalmology expertise and capabilities will help advance the Opregen program more rapidly, and we believe successfully, to patients with serious ocular disorders, such as dry AMD,” Lineage CEO Brian M. Culley said in a news release.

Clearside Announces Positive Safety Results From OASIS CLS-AX Trial

■ Clearside Biomedical, Inc., announced positive safety results from OASIS, its ongoing phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension), administered by suprachoroidal injection via Clearside’s SCS Microinjector. OASIS is evaluating CLS-AX for the treatment of neovascular age-related macular degeneration (wet AMD).

Clearside reported on results from cohort 2, as well as combined data from cohorts 1 and 2, and the OASIS safety monitoring committee has approved advancing to cohort 3, with a dose of 0.5 mg of CLS-AX. The primary endpoints were achieved in cohort 2. The 0.1 mg dose of CLS-AX was well tolerated with no serious adverse events; there were no treatment-emergent adverse events related to aflibercept, CLS-AX, or the suprachoroidal injection procedure. There was no dispersion of drug into the vitreous. In addition, there were no adverse events related to intraocular pressure, inflammation, or vasculitis.

“We believe the absence of any dose-limiting toxicities in the first 2 cohorts of the OASIS trial, combined with our preclinical toxicology data, supports our plan to escalate to the higher CLS-AX dose of 0.5 mg in cohort 3 rather than the previous 0.3 mg dose,” said Clearside Chief Medical Officer Thomas Ciulla, in a news release.

Mark R. Barakat, MD, director of research at Retinal Consultants of Arizona and an investigator in the OASIS clinical trial said in a news release, “The suprachoroidal injection procedure has been easy to perform, reliable, and well tolerated by patients during this study. The consistent safety data from cohorts 1 and 2 support escalation to higher dosing, which we anticipate will provide further insights related to safety, visual acuity, ocular anatomy, and durability.”

First Patients Dosed in Milestone Trial of RNA Therapy for Retinitis Pigmentosa

■ The first patients have been dosed in the phase 2/3 Sirius and Celeste clinical trials investigating QR-421a (Ultevursen) in patients with USH2A-mediated retinitis pigmentosa (RP) and Usher syndrome, according to an announcement by ProQR Therapeutics, a company dedicated to the development of RNA therapies for genetic eye diseases. Sirius and Celeste are double-masked, randomized, sham controlled, 24-month, multiple dose studies to evaluate whether QR-421a is effective at stopping vision loss and whether it is safe and well-tolerated. “Our goal is that the Sirius and Celeste studies further validate QR-421a’s ability to stabilize vision loss in people with USH2A-mediated RP and Usher syndrome,” Aniz Girach, MD, chief medical officer of ProQR, said in a news release.

QR-421a is a first-in-class investigational RNA therapy designed to address the underlying cause of vision loss in USH2A-mediated RP and Usher syndrome due to mutations in exon 13 of the USH2A gene. It has been granted orphan drug designation in the United States and the European Union and received fast-track and rare pediatric disease designations from the FDA.

Unity Biotechnology Announces Positive Data From Phase 1 of UBX1325

■ Unity Biotechnology Inc. announced 24-week data from its ongoing phase 1 safety study of UBX1325 in patients with advanced diabetic macular edema (DME) and wet AMD. A majority of patients with DME across all doses had rapid improvements in vision, and patients in the higher dose cohorts showed a mean gain of 9.5 ETDRS letters in best-corrected visual acuity (BCVA) at 24 weeks following a single injection of UBX1325. In most patients, central subfield thickness (CST) remained stable through the study period.

“A treatment that reduces the frequency of injections while showing meaningful and sustained improvements in BCVA would be of huge value for patients and physicians,” Arshad Khanani, MD, MA, managing partner of Sierra Eye Associates, said in a news release.

UNITY’s phase 2 study of UBX1325 in DME is under way, with 12-week safety and efficacy data anticipated in the first half of 2022. A phase 2 study in wet AMD is planned for the first half of 2022, with 12-week data expected in the second half of the year.

Positive Results From Phase 3 KESTREL DME Study Announced

■ Novartis announced second-year results from the phase 3 KESTREL study comparing the safety and efficacy of Beovu (brolucizumab) 6 mg and aflibercept, in the treatment of patients with visual impairment due to DME. Results from the final year of the 2-year study were consistent with those seen at year 1, including maintenance of best-corrected visual acuity (BCVA) and sustained reductions in CST. Additionally, fewer Beovu patients had intraocular fluid and/or subretinal fluid (IRF/SRF) than patients treated with aflibercept. More than 40% of Beovu patients were maintained on 12-week dosing intervals, and 70% of patients who completed the first 12-week cycle after loading remained on 12-week dosing through year 2, which reveals the potential for Beovu to offer fluid resolution in more DME patients with fewer injections vs aflibercept.

“The extended dosing and fluid resolution observed in year 2 of the KESTREL clinical trial suggest Beovu has the potential to help appropriate patients more conveniently and effectively manage their disease with dosing intervals every 12 weeks, after an initial loading phase,” David M. Brown, MD, director of research at Retina Consultants of Texas, said in a news release.

Study Illustrates Efficacy of Diabetic Retinopathy Self Testing

■ In a prospective, multicenter, cross-sectional diagnostic study, researchers found that Eyenuk, Inc.’s EyeArt artificial intelligence (AI) system safely and accurately detected both mild diabetic retinopathy (mtmDR) and vision-threatening diabetic retinopathy (vtDR) without physician assistance. Their findings were published in JAMA Network Open. The EyeArt clinical trial included 942 individuals with diabetes from 15 US primary care and eye care facilities.

The EyeArt AI system analyzed 2 undilated images per eye and results were then evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale using 10 fundus images per eye captured after dilation. The accuracy of the EyeArt system was high in detecting mtmDR (sensitivity 96% and specificity 88%) and vtDR (sensitivity 97% and specificity 90%). The EyeArt system gave mtmDR and vtDR detection results for more than 97% of the eyes, with most (88%) not requiring dilation.

The study demonstrates the ability of EyeArt system to accurately detect mtmDR and vtDR without physician oversight or the need for dilation in most individuals, thereby enabling diabetic eye exams at nonspecialist facilities and enabling accelerated referral of vision-threatening DR. In addition to FDA 510(k) clearance, the EyeArt AI System has CE marking as a class 2a medical device in the European Union and a Health Canada license. The EyeArt System is reimbursable by government and private payors in the United States under CPT code 92229.

Opus Genetics to Advance Gene Therapy for Blinding Conditions

■ The Retinal Degeneration Fund, the venture arm of the Foundation Fighting Blindness, has launched Opus Genetics, a patient-focused gene therapy company aimed at developing therapies for orphan inherited retinal diseases. The initiative’s $19 million in seed financing was led by the Retinal Degeneration Fund, with participation from the Manning Family Foundation and Bios Partners.

Opus Genetics’ lead programs will focus on treatments to address mutations in genes that cause different forms of Leber congenital amaurosis (LCA), rare inherited retinal diseases that typically present in infancy and are characterized by degeneration of photoreceptors. Opus’s lead program, OPGx-001, is designed to address mutations in the LCA5 gene, one of the most severe forms of LCA, which affects approximately 1 in 1.7 million people.

The company’s second program, OPGx-002, will focus on restoring protein expression and halting functional deterioration in patients with retinal dystrophy caused by mutations in the retinal dehydrogenase (RDH12) gene LCA13, which affects one in 288,000 people. Opus expects to file an Investigational New Drug application for its OPGx-001 program in early 2022 and enter the clinic in mid-2022.

More Positive Data Reported From RGX-314 Wet AMD and DR Trials

■ Regenxbio Inc. announced additional positive data from its ongoing phase 2 AAVIATE trial as well as its ongoing phase 2 ALTITUDE trial of RGX-314 using in-office suprachoroidal delivery for the treatment of wet AMD and diabetic retinopathy (DR) without center-involved diabetic macular edema (CI-DME), respectively. “The initial data from cohort 2 of the AAVIATE trial provides encouraging evidence of the emerging clinical profile of RGX-314 for the treatment of wet AMD using suprachoroidal delivery,” principal investigator Robert L. Avery, MD, founder of California Retina Consultants and Research Foundation, said in a news release.

In cohort 2, patients dosed with RGX-314 demonstrated stable BCVA and central retinal thickness (CRT) at 6 months. These patients also demonstrated stable CRT, with a mean change of -33 µm at 6 months from day 1. There was a meaningful reduction in anti-VEGF treatment burden in patients following administration of RGX-314 compared to the mean annualized injection rate during the 12 months prior to administration.

Patients in cohort 2 received a mean of 1.3 injections over 6 months following administration of RGX-314, which represents a 71.8% reduction in anti-VEGF treatment burden. The most recent data from cohort 1 of the ALTITUDE trial revealed that at 3 months, 15 patients dosed with 2.5x10 GC/eye of RGX-314 demonstrated stable BCVA of +2.6 letters, while 5 patients in the observational control arm demonstrated stable BCVA of -0.4 letters.

Updated Classification Aims for Improved ROP Standardization

■ The International Classification of Retinopathy of Prematurity (ICROP) has been revised, and the third edition, ICROP3, was published in Ophthalmology in October 2021. The ICROP3 aims to improve quality and standardization of ROP care worldwide and provide a foundation to improve research and clinical care.

The authors report that the update comes in response to “concerns about subjectivity in critical elements of disease classification; innovations in ophthalmic imaging; novel pharmacologic therapies (eg, anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.” In an editorial that accompanied the latest update, Michael X. Repka, MD, professor of ophthalmology and a professor of pediatrics at the Johns Hopkins University School of Medicine said, “The ICROP3 begins the transition from describing a binary yes/no decision to a continuous condition of retinal vascularity in the newborn eye.”

Major updates in the ICROP3 include refined classification metrics (eg, posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. Retinopathy of prematurity regression and reactivation are described in detail, with additional description of long-term sequelae.

Study Supports Causal Effect of Smoking and Alcohol Intake on AMD

■ Researchers analyzed whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD and found that genetically predicted smoking and lifetime smoking are associated with elevated risk of AMD, and genetically predicted alcohol intake is associated with increased risk of GA. Their analysis included genetic data for more than 16,000 people with AMD, including about 3,300 with GA.

The study, led by Valerie Kuan, PhD, University College London, Institute of Health Informatics, concluded, “We found genetic evidence that increased alcohol consumption has a potential causal association with risk of GA. We also present genetic evidence that smoking initiation and lifetime smoking behavior may be casually associated with risk of advanced AMD, while smoking cessation results in a lower risk of advanced AMD than persistent smoking. These associations were stronger for neovascular AMD than for GA. To reduce the prevalence of advanced AMD in aging populations, public health campaigns and programs to support smoking abstention, smoking cessation, and reduced alcohol intake should incorporate the evidence that these activities can lead to blindness.”

Weekly Dose of Deep Red Light Improves Declining Vision

■ Three minutes of exposure to deep red light once a week, when delivered in the morning, can significantly improve declining eyesight, according to findings published by researchers from University College London. The study builds on the team’s earlier work that showed daily 3-minute exposure to longwave deep red light “switched on” energy producing mitochondria cells in the retina, helping boost naturally declining vision.

In their latest study, the researchers found there was, on average, a 17% improvement in participants’ color contrast vision when they were exposed to 3 minutes of 670 nm in the morning, and the effects of this single exposure lasted for at least a week. However, when the same test was conducted in the afternoon, no improvement was seen. Lead author, Professor Glen Jeffery, UCL Institute of Ophthalmology, said in a news release, “Morning exposure is absolutely key to achieving improvements in declining vision. As we have previously seen in flies, mitochondria have shifting work patterns and do not respond in the same way to light in the afternoon — this study confirms this.”

M&S Technologies Introduces New Enhancements to Its Clinical Trial Suite

■ M&S Technologies announced that its Clinical Trial Suite (CTS) visual testing software has a new dedicated product, the DVA-5000, that specifically addresses the needs of glaucoma and retina trial sponsors and researchers. The DVA-5000 is an automated ETDRS tool that guides technicians through the testing algorithm eliminating technician bias, and errors. Its standardized, calibrated background luminance is set to 85 cd/m² as recommended by the FDA/ISO and can be customized to fit any luminance levels. “With CTS, biotechnicians are no longer concerned about erroneous data generated from the investigator sites due to human error during paper documentation and related calculation errors,” Joe Marino, founder and global head of M&S Technologies, said in a news release.

CTS test results are automatically calculated and ready for review as letter score, logMAR, decimal score, and Snellen equivalent. Reports are immediately available in XML or CSV format for export to any EDC, reading center, or other location.

Acquisition Signals Synergistic Light-Based Capabilities Platform

■ Lumithera, maker of the Valeda Light Delivery System for dry AMD, announced that it will acquire Diopsys, maker of a diagnostic test that measures electrical activity in the retina. Diopsys’ electroretinography (ERG) technology could provide a complementary diagnosis and monitoring platform for the Valeda photobiomodulation (PBM) system. “The synergy of these technologies makes sense on many levels and could optimize Valeda treatments,” Clark E. Tedford, PhD, president and CEO of Lumithera, said in a news release.

Last year, Lumithera and Diopsys announced positive top-line data from the ELECTROLIGHT pilot study in intermediate dry AMD patients. A total of 23 eyes from 15 subjects with dry AMD were enrolled into the prospective clinical study and treated with PBM using the Valeda system (3 times per week for 3 weeks) and ERG function was evaluated with the Diopsys NOVA ERG system. Multiluminance ERG improved by 14.4% from baseline after 1 month.

Kodiak Completes Enrollment in Phase 3 Anti-VEGF RVO Trial

■ Kodiak Sciences Inc. announced that it has completed enrollment in its BEACON phase 3 clinical trial of KSI-301, its anti-VEGF antibody biopolymer conjugate, in patients with macular edema due to retinal vein occlusion (RVO). KSI-301 is an investigational anti-VEGF therapy designed to maintain potent and effective drug levels in ocular tissues for longer than existing available agents. The phase 3 BEACON study is a global, multicenter, randomized study designed to evaluate the durability, efficacy, and safety of KSI-301 in patients with treatment-naïve macular edema due to RVO, including both branch and central subtypes. “Current FDA approved anti-VEGF therapies are labeled only for monthly dosing in RVO. In BEACON, we are studying KSI-301’s potential to be a longer-lasting treatment for patients,” said Jason Ehrlich, MD, PhD, Kodiak’s chief medical and development officer, in a news release.

AGTC Exceeds Enrollment Target for XLRP SKYLINE Trial

■ Applied Genetic Technologies Corporation announced that it exceeded its enrollment target in its SKYLINE trial of AGTC-501, a recombinant AAV vector-based gene therapy developed for the treatment of X-linked retinitis pigmentosa (XLRP). A total of 14 patients have been enrolled across the high-dose and low-dose groups, exceeding the planned target enrollment of 12. Sue Washer, president and chief executive officer of AGTC, said in a news release that this milestone in the clinical development of AGTC-501 positions the company to announce interim 3-month trial results in the second quarter of 2022.

Early in 2022, AGTC released updated data from the ongoing phase 1/2 clinical trial of AGTC-501, which demonstrated that at 12 months, 50% of patients in the high-dose groups were considered responders to treatment based on visual sensitivity and that treatment resulted in a statistically significant improvement in best-corrected visual acuity (BCVA) across all treatment groups in patients where the macula was treated. RP