Market/Novel Tech – Euretina Brief

A new gene therapy candidate – “OPGxBEST1” – has received FDA clearance from Opus Genetics for an investigational new drug application (IND) for the treatment of bestrophin-1-related IRD.

Dr. Gearóid Tuohy — Mon, 01 Sep 2025 11:25:15 +0000

Opus Genetics (Nasdaq: IRD) have announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for OPGx-BEST1, a gene therapy for the treatment of bestrophin-1 (BEST1)-related IRD. The experimental treatment is being developed for bestrophin-1 (BEST1)-related inherited retinal diseases, a form of macular degeneration found primarily in adults, estimated to affect approximately 9,000 people in the U.S. Bestrophinopathy is characterized by retinal lesions, with symptoms including dimness of vision, metamorphopsia or scotoma. The gene therapy treatment will use an adeno-associated virus (AAV) vector to deliver a functional copy of the BEST1 gene to the retina to allow bestrophin-1 protein to be produced in retinal pigment epithelial (RPE) cells. The approach aims to restore normal function of the RPE cells such that they may provide proper support to photoreceptors.

Opus Genetics is a public company, supported by the Retinal Degeneration Fund (RD Fund), the venture arm of the Foundation Fighting Blindness, aimed at rapidly driving research toward preventions, treatments and cures for the entire spectrum of retinal degenerative diseases. The Company’s pipeline features AAV-based gene therapies targeting inherited retinal diseases including Leber congenital amaurosis (LCA), bestrophinopathy, and retinitis pigmentosa. The company is also advancing Phentolamine Ophthalmic Solution 0.75%, a partnered therapy currently approved in one indication and being studied in two Phase 3 programs for presbyopia and reduced low light vision and nighttime visual disturbances. The Company is based in Research Triangle Park, North Carolina.

Best disease, also known as vitelliform macular dystrophy, is caused by mutations in the BEST1 (VMD2) gene, inherited in an autosomal dominant fashion although there is variable penetrance in the pathology. The prevalence of the disease is estimated at between 1 and 9/100,000 and the gene product (bestrophin-1)is a transmembrane protein expressed on the basolateral aspect of the RPE cells. The protein functions to facilitate chloride conductance across the RPE and mutations of the gene can affect fluid transport across the RPE leading to an accumulation of debris between the photoreceptors and RPE.

Figure 1. BEST1 disease is an inherited retinal disease that causes macular degeneration. The BEST1 gene encodes for bestrophin-1, a protein that functions as a retinal pigment epithelial (RPE) cell membrane channel. The BEST1 channel, when activated by calcium (Ca2+) ions, controls chloride (Cl-) ion transfer into and out of the RPE cell. This function is crucial to maintaining homeostasis between rod and cone photoreceptors and RPE cells. Mutations in BEST1 disrupt this homeostasis and result in the breakdown of the rod and cone interphotoreceptor matrix (cIPM) and microvilli (cMV) connection with the RPE. Retinal lesions form containing vitelliform material (“egg-yolk” like) between the RPE and Bruch’s membrane (BM)/choroid (CH). These vitelliform lesions disrupt and cause atrophy of the RPE. Without support from the RPE, photoreceptor cells critical for normal vision die, resulting in progressive vision loss. (Available at https://opusgtx.com/pipeline-programs/ird-programs/)

According to the company, George Magrath, M.D., Chief Executive Officer stated that, “the FDA’s clearance of our BEST1 IND is a significant step forward for the IRD community and for our mission at Opus Genetics focused on restoring vision for patients. BEST-related IRDs have no approved treatments today, leaving patients and families with uncertainty about the future of their vision. The OPGx-BEST1 trial will be our third ongoing clinical program, reflecting the depth of our pipeline and our commitment to advancing multiple therapies in parallel for patients with urgent, unmet needs.”

60-week results from 4D-150 “SPECTRA” treatment for DME Phase 3 data reports sustained visual acuity gains.

Dr. Gearóid Tuohy — Fri, 15 Aug 2025 08:48:10 +0000

4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT), based in Emeryville, California, have announced 60-week summary data from their “SPECTRA” diabetic macular edema (DME) Phase III clinical trial. 4D-150 is an intravitreal gene therapy treatment expressing both aflibercept and a VEGF-C inhibitory RNAi, proposing a dual-transgene to inhibit four members of the VEGF angiogenic family targeting DME (VEGF A, B, C and PlGF). According to the company, 4D-150 appears to be well tolerated with no intraocular inflammation with sustained gains in visual acuity and anatomic control. The Phase 3 dose (3×10^-1 vg/eye) have reported a 78% reduction in treatment burden vs. projected on-label aflibercept 2mg Q8W.

4D-150 is an investigational agent designed to provide sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) utilizing thecompany’s customized intravitreal vector, R100. 4D-150 is being developed for wet AMD and DME for the purpose of avoidpatients from burdensome injections while preserving vision. The company’s product candidates are in clinical or preclinical development, not yet been approved for marketing by regulatory authorities. The company is aimed to align a single Phase 3 clinical trial for both the FDA and EMA, based on data generated for 4D-150 from two planned Phase 3 clinical trials in ta “4FRONT” wet age-related macular degeneration (wet AMD) program, potentially acceptable as the basis for a marketing authorization application (MAA) submission for 4D-150 in DME.

In the SPECTRA (DME) study, the company reported efficacy results through 60 Weeks from a Phase 3 dose showing a sustained gain of best corrected visual acuity (BCVA) of +9.7 letters and a sustained improvement in anatomic control, with reduction of CST, as measured by optical coherence tomography (OCT), of -174 µm. Following the announcement, David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT stated that, “the consistency of dose response, safety and efficacy data we’ve seen with 4D-150 across all patients evaluated in both DME and wet AMD reinforces our belief that 4D-150 has the potential to become a true backbone therapy, and may significantly improve the lives of millions of patients living with retinal vascular disease. With alignment from both FDA and EMA for a single Phase 3 DME trial to complement the 4FRONT wet AMD program, we believe we have a clear streamlined path to bring 4D-150 to patients with high unmet need”.

Beacon Therapeutics announce the completion of enrolment for the Phase 2/3 trial for “laru-zova”, for the treatment of XLRP.

Dr. Gearóid Tuohy — Mon, 04 Aug 2025 10:10:20 +0000

Beacon Therapeutics Holdings Limited, based in London, UK and Cambridge, Massachusetts, have announced the completion of enrolment in its registrational Phase 2/3 VISTA trial evaluating “laru-zova” for the treatment of X-linked retinitis pigmentosa (XLRP). The study has enrolled eligible male patients aged 12 to 50 across sites in North America, the United Kingdom, and Australia. Twelve month topline data from this trial are expected in the second half of 2026. The VISTA trial (#NCT04850118) is a randomized, controlled, masked, multi-center Phase 2/3 study, designed to evaluate the efficacy, safety, and tolerability of laru-zova in male patients with XLRP caused by mutations in the RPGR gene. The primary outcome of the trial is the proportion of participants with a ≥15 letter increase from baseline in LLVA (Low Luminance Visual Acuity) within 12 months. The trial is assessing two dose levels of laru-zova compared to an untreated control group, evaluating the proportion of participants with improvement in LLVA and mean sensitivity as observed by microperimetry, among other measures of visual function.

Figure 1. Presented by Beacon Therapeutics, published available online on https://www.beacontx.com/publications-and-presentations/

“laru-zova”,[AGTC-501] is a gene therapy treatment of XLRP, also referenced to “AGTC-501”, and previously named as rAAV2tYF-GRK1-RPGR. XLRP is one of the most common forms of retinitis pigmentosa with mutations in the RP GTPase regulator gene (RPGR gene), thought to account for approximately 75% of XLRP recorded cases. The gene encodes a ciliary protein that regulates trafficking of proteins to the outer segment of photoreceptors. Males are more severely affected by the X-linked pathology with night blindness generally occurring within the first decade of life, followed by restriction of the visual field and loss of visual acuity leading to legal blindness in most patients by the fourth to fifth decade of life. AGTC-501/laru-zova correctly expresses the full length RPGR protein, thereby addressing the entirety of photoreceptor damage caused by XLRP, including both rod and cone loss.

Previously, Beacon Therapeutics acquired Applied Genetic Technologies Corporation, (previously Nasdaq: AGTC) for €112 million in summer 2023, with AGCT’s clinical-stage adeno-associated virus (AAV)-based gene therapy assets. Beacon now plans to use the data from the VISTA trial, alongside long-term data from ongoing Phase 2 DAWN trial, the Phase 1/2 HORIZON and Phase 2 SKYLINE studies to support regulatory submissions in the United States and Europe. Following the current announcement of the Phase 2/3 enrolment milestone, Dr. Daniel Chung, D.O., M.A., Chief Medical Officer of Beacon Therapeutics, stated that: “the VISTA study has been carefully designed to provide the clinical evidence needed to demonstrate laru-zova’s potential to improve functional vision in patients with XLRP. We are applying our deep understanding of both ocular disease and gene therapy by using a highly efficient AAV capsid and a stabilized gene cassette that expresses the full-length RPGR protein, to support better vision outcomes. We are cautiously optimistic about the potential for laru-zova to treat a condition that has long been considered untreatable.”

Beacon Therapeutics’ team is led by CEO Lance Baldo, MD, previously at Freenome, Adaptive Biotechnologies, Roche Group and Genentech, andl; Daniel Chung, Chief Medical Officer, previously at Sparing Vision, Spark Therapeutics plc., and FM Kirby Center for Molecular Ophthalmology at the University of Pennsylvania Perelman School of Medicine.

Publicly available at https://www.beacontx.com/about-us/

Astena Therapeutics has announced an expansion of a Phase 1 / 2 study into a continuous Phase 1 / 2 / 3 trial, agreed by U.S. Food and Drug Administration (FDA).

Dr. Gearóid Tuohy — Mon, 21 Jul 2025 12:16:15 +0000

Atsena Therapeutics, based in Durham, North Carolina, has announced that the U.S. Food and Drug Administration (FDA) has agreed to the expansion of the company’s ongoing Phase 1 / 2 (“LIGHTHOUSE study”), of ATSN-201, into a continuous Phase 1 / 2 / 3 trial, enabling it to serve as a pivotal trial to support a Biologics License Application (BLA) for the treatment of X-linked retinoschisis (XLRS). There are no approved treatments for XLRS, which is typically diagnosed in early childhood and affects ~30,000 males in the U.S. and the EU. The ATSN-201 treatment uses a novel “spreading capsid” technique to achieve therapeutic levels of gene expression in photoreceptors of the central retina, while avoiding the surgical risks of foveal detachment. Previously, the company received “Fast Track” designation, granted by the FDA for treatments intended to address serious or life-threatening diseases that have demonstrated the potential to meet an unmet medical need. The company has additionally received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designations from the FDA. ASTN-201 (rAAV.SPR-hGRK1-hRS1syn) is a subretinal gene therapy product being developed to introduce the functional human retinoschisin (hRS1) gene to photoreceptors.

X-linked retinoschisis (XLRS) is an uncommon inherited retinal degeneration (IRD), with a prevalent estimate ranging from 1 to 5,000 to 1 in 25,000 cases, mainly affected in males however, a number of female carriers may exhibit the phenotype due to altered X-inactivation. XLRS is caused by mutations in the RS1 gene, encoding a retinal protein, retinoschisin, which plays a key role in maintaining the retinal structure. The protein is expressed and localized in the surface of photoreceptor and bipolar cells, functioning in cell-to-cell adhesion, maintaining tissue integrity and homeostasis, and regulates apoptosis signalling. The deficiency or absence of retinoschisin in XLRS leads to photoreceptor degeneration due to cell apoptosis and disruption of the retinal layers. The disorder causes schisis (or splitting) of the neural retina leading to reduced visual acuity and disturbances in central vision, strabismus or nystagmus, affecting from an early age impacting daily function, including difficulty with reading and obtaining a driver’s license. Mutations of the RS1 gene comprise >200 alterations, most of which are missense and the majority occur in exon 4-6, corresponding to the discoidin domain of the protein. The disease can be highly variable make it challenging to correlate genotype-to-phenotype for patients.

Figure 1. Highlighted at Atsena Therapeutics’ website*, the company shows to schisis (or splitting) of the neural retina leading to reduced visual acuity caused by mutations in the RS1 gene, and; delivery optimization of AAV.-RS1.SPR (spread) allowing for subretinal injection in the peripheral retina, avoiding foveal detachment and potential trauma and efficiently transduces the vector to foveal photoreceptors covering a larger area resulting in wider area of retinal transduction.(* https://atsenatx.com/wp-content/uploads/2023/12/ESGCT2023_INDXLRS-1.pdf).

Following the announcement, Patrick Ritschel, Chief Executive Officer of Atsena Therapeutics commented that, “this regulatory milestone marks another significant step toward delivering a potentially first- and best-in-class gene therapy for patients living with XLRS. The agency’s agreement will expedite the clinical development of ATSN-201 by at least 1.5 years, compared to a separate Phase 3 clinical trial. If approved, this would be the first available treatment for XLRS, offering hope to patients and families affected by this inherited retinal disease. We’re grateful for the FDA’s continued guidance as we continue to advance this trial and prepare for filing a BLA in early 2028.”

Potential paradigm shift of anti-VEGF treatment with sub-cutaneous injections at home, following Phase II summary results.

Dr. Gearóid Tuohy — Mon, 07 Jul 2025 14:25:04 +0000

Clinical trial research on the treatment of sub-cutaneous (subQ) migaldendranib (MGB), sponsored by Ashvattha Therapeutics, has announced interim results from an ongoing Phase II study for the treatment of diabetic macular oedema (DME) and wet age-related macular degeneration (AMD). The results were presented at the MaculArt Meeting, June 29–July 1, 2025 in Paris, providing “a first-in-class subcutaneously administered candidate being developed for convenient, at-home monthly treatment of DME and wet AMD, aiming to reduce treatment burden while avoiding systemic side effects.” If approved by regulators, the treatment may provide a paradigm shift of medical care for patients by reducing the burden of intravitreal injections at clinical hospital or consultant offices.

Migaldendranib (MGB) is a potent anti-angiogenic nanomedicine (“dendranib”) that crosses the blood-retinal barrier and selectively targets activated microglia, macrophages and retinal pigment epithelial cells in the eye. If approved, the treatment may offer an at-home dosing option by a subcutaneous route of administration, rather than delivery via intravitreal injection. The sponsor’s study, entitled “ Subcutaneous Migaldendranib (MGB) for the Treatment of Neovascular Age-Related Macular Degenerations and Diabetic Macular Edema: Interim Results of Chronic Dosing Phase 2 Study”, showed promising safety and tolerability in both DME and wet AMD patients in the first 24 weeks of treatment.

Figure 1 [a] and [b]).Previously presented by Michael Singer, MD, a board-certified vitreoretinal specialist and director of clinical research at Medical Center Ophthalmology Associates in San Antonio, Texas, and clinical professor of ophthalmology at the University of Texas Health Science Center in San Antonio. Dr. Singer is principal investigator for Ashvattha’s Phase 2 clinical trial evaluating migaldendranib, and is on the company’s advisory board.

The summary results showed that wet AMD patients had a central subfield thickness (CST) and a stable mean best corrected visual acuity (BCVA) for 24 weeks, with 45.5µm and +3 letters, respectively, and a comparable 79.9% reduction in treatment burden. DME patients exhibited a decreased central subfield thickness (CST) of -69.1 µm and an increased BCVA of +4.5 letters, with an observed reduction in treatment burden by 80%. In addition, the sponsor noted that fellow eye results also showed substantial treatment burden reduction of approximately 75%, compared to pre-treatment, demonstrating the potential bilateral benefits of subcutaneous administration. Finally, safety findings included injection site reactions in 8.6% of injections administered, which were reported to be localized, transient and mostly mild. According to Dr. Singer, Principal Investigator of the trial, he commented that, “this medicine is a subcutaneous injection that will treat both eyes with a single shot, and presumably we do it at home. It’s a tyrosine kinase inhibitor (TKI) like other TKIs, that blocks other forms of vascular endothelial growth factor (VEGF). What’s interesting is that it’s cleared in the kidney, so there’s no systemic or liver toxicity. It’s uptake is only by the retinal pigment epithelial (RPE) cells and macrophages in actively inflammatory lesions. It’s retained in the cells for 30 days and then cleared from the body in 2 days.”

VeonGen Therapeutics GmbH announce re-branding of the company (previously ViGeneron) and the progression of treatments for Stargardt’s disease and retinitis pigmentosa.

Dr. Gearóid Tuohy — Mon, 23 Jun 2025 14:10:31 +0000

VeonGen Therapeutics GmbH, based in Munich, Germany, have announced the progression of two proprietary gene therapies to the clinic based on a novel gene therapy platform, and the re-branding of the company, formerly known as ViGeneron. The re-branding was aimed to re-position their company from a pre-clinical to a clinical-stage company for patients with high unmet medical needs, and progressing lead programmes of “VG801”, for Stargardt’s disease, and “VG901” for retinitis pigmentosa. VG801 is a novel dual AAV gene therapy for Stargardt disease and other ABCA4 related retinal disorders, and VG901 is an intravitreally delivered AAV gene therapy for retinitis pigmentosa caused by CNGA1 mutations. Commenting on their announcement, Dr. Caroline Man Xu, Co-founder & Chief Executive Officer of VeonGen Therapeutics stated that, “this rebranding reflects our journey – from a platform innovator to a clinical -stage company with two gene therapies in the clinic. With VG801 and VG901 progressing in clinical trials and our platforms demonstrating robust translational potential, we are well positioned to expand the frontier of genetic medicine in ophthalmology and beyond.”

VeonGen presents three differentiated technology platforms: (1) engineered AAV capsids with enhanced transduction efficiency and the ability to overcome biological barriers, enabling less invasive delivery routes such as intravitreal and systemic administration; (2) a trans-splicing platform – “vgRNA REVeRT (Reconstitution via mRNA Trans-splicing)” – designed to enable the delivery and reconstitution “of large genes exceeding the 4.7 kb AAV cargo limit at the mRNA level in tissues targeted by a selected AAV capsid, and finally; (3) a third platform, “AAV Transactivation”, using CRISPR/Cas technology enabling the activation or repression of disease relevant genes using gene supplementation or applying novel applications in genetic diagnostics.

Figure 1. The company’s pipeline is presented online, available at https://veongen.com/pipeline/

According to the company, VG801 is a novel mRNA trans-splicing gene therapy using dual adeno-associated virus (AAV) vectors to deliver the full-length human native ABCA4 gene. Their gene supplementation treatment aims to address biallelic ABCA4 mutation-associated Stargardt disease, and other ABCA4-linked retinal dystrophies. VG801 has previously demonstrated in vivo functionality and expression of the full-length ABCA4 gene in an animal model of Stargardt disease, as well as efficient, expression and safety in non-human primate retinas. The company’s lead program VG801, has received FDA Rare Pediatric Disease Designation and is now progressing in a first-in-human Phase 1/2 trial for Stargardt disease, with functional endpoint development underway through the FDA’s RDEA program. Finally, VG901, to treat patients with retinitis pigmentosa (RP) caused by mutations in the CNGA1 gene have received FDA Rare Pediatric Disease Designation (RPDD) to VG901, and the company’s independent Data Safety Monitoring Board (DSMB) has previously approved a dose escalation study in an ongoing Phase 1b clinical trial. Mutations in the CNGA1 gene, encoding a subunit of CNG channels in rod photoreceptors, are reported to cause approximately 2% – 8% of autosomal recessive retinitis pigmentosa (arRP).

The company’s key personnel are available at the VeonGen’s website and can provide further details below (https://veongen.com/about/#our-core-team ):

First predictive AI tool for retinal therapy planning receives a European CE-mark (Class IIa) by deepeye Medical (Munich).

Dr. Gearóid Tuohy — Mon, 09 Jun 2025 14:05:51 +0000

An innovative biomedical company, deepeye Medical GmbH, based in Munich Germany, has received a regulatory CE mark (Class IIa) service for a novel AI tool to provide retinal therapy planning of intravitreal injections (IVI) to support ophthalmologists managing treatments for anti-VEGF therapy for nAMD patients. The AI initiative, regulating the EU Medical Device Regulation (MDR 2017/745), received certification by the Notified Body Kiwa Assurance. According to the company, the “deepeye® TPS (Therapy Planning Support)” tool provides “a major regulatory milestone for medical AI – not just in ophthalmology – and paves the way for rollout across Europe.”

deepeye Medical outlines that while anti-VEGF therapy for retinal diseases have made an enormous benefit for the treatment of neovascular age-related macular degeneration (nAMD), “real-world outcomes often lag behind trial data”. According to the company, “many patients discontinue therapy prematurely, leading to irreversible vision loss. deepeye® TPS is designed to close this gap by enhancing both the efficiency and potentially the effectiveness of intravitreal injection (IVI) therapy planning in daily practice.”

See https://www.deepeye-medical.com/deepeye-tps

A busy clinic may be able to send spectral domain OCT scans to the company and their AI tool will automatically analyse pseudonymised OCT and generate a report providing an assessment of disease for each individualised patient. The data can then advise and support decision making, biomarker visualisation and an AI recommendation. The company engages with the ophthalmologists “to optimize your IVI therapy planning”, presenting the world’s first AI assistant to support the ophthalmologist with a second reading of every OCT. deepeye Medical worked with the Eye Center at St. Franziskus-Hospital Münster, showed that “double reading of OCT imaging has tripled visual acuity gains and doubled therapy adherence compared to other real-world studies.” The company stated that the AI tool “was trained on thousands of patient cases from more than 200 retina centres” and “clinically validated, for instance in collaboration projects with Novartis, Bayer, and Roche.”

The announcement of the CE mark provides the first predictive AI tool for therapy planning for nAMD patients and the CEO of the company, Manuel Opitz, stated that, “this regulatory milestone of the first predictive AI assistant for therapy management shows that Europe can be innovative. We are happy to offer ophthalmologists across Europe our AI assistant, supported by our partners, in their daily work of driving clinical outcomes and therapy adherence.” deepeye® TPS is available via Heidelberg Heyex2 AppWay, with upcoming connections for Topcon Harmony, ZEISS FORUM, and other OCT imaging platforms.

Scientific advisors of the technology include, Prof. Dr. med Albrect Lommatzsch, Univ. Prof. Dr. med. Siegfried Priglinger and Prof. Dr. Adam Dubis:

Ashvattha Therapeutics has announced positive Phase 2 results for subcutaneous migaldendranib, delivered via a hydroxyl dendrimer for retinal vascular disease.

Dr. Gearóid Tuohy — Mon, 26 May 2025 13:30:29 +0000

Ashvattha Therapeutics, based in Redwood City, California, have announced positive interim Phase 2 results for migaldendranib (MGB) and hydroxyl dendrimer, aimed to treat retinal vascular diseases. The company are focused on a new class of clinical-stage nanomedicine therapeutics targeting regions of inflammation. MGB is a VEGF receptor tyrosine kinase inhibitor delivered via a hydroxyl dendrimer platform, aimed to selectively targets activated cells in the retina, thereby reducing VEGF expression and fluid production in both eyes simultaneously. Results for their experimental drug treating AMD and DME, presented data at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, (May 4 – May 8, 2025, in Salt Lake City, UT).

The migaldendranib and dendrimer is aimed to block forms of vascular endothelial growth factor (VEGF), expected to clear the kidney and liver avoiding toxicity. The delivery uptake is only targeted to the retinal pigment epithelial (RPE) cells and macrophages in actively inflammatory lesions and is retained in the cells for 30 days and then cleared from the body in ~2 days.

A graphical abstract of the innovation, using a triamcinolone acetonide (TA) conjugate, shows a systemic hydroxyl-terminated polyamidoamine dendrimer-TA conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. [Authored by Kambhampati, Siva P. et al., Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration. Journal of Controlled Release, Volume 335, 10 July 2021, Pages 527-540, also listed at Ashvattha Therapeutics website, https://avttx.com/resources/?_sft_resource_type=publications].

Following a Phase 2 open-label study of subcutaneous (subQ) MGB, 27 subjects (16 with wet AMD [age-related macular degeneration] and 11 with DME [diabetic macular edema]) were previously treated with anti-VEGF intravitreal injections (IVT). Subjects received a single anti-VEGF IVT and subQ MGB at baseline, followed by subQ MGB every 2 or 4 weeks for 40 weeks. The interim analysis focuses on 24-week data from 8 wet AMD and 6 DME subjects. Following of completing 24 weeks of treatment, summary results presented at ARVO showed:

9% reduction in wet AMD subjects and 80.0% reduction in DME subjects compared to the 24 weeks prior to Day 1, representing a 5.0-fold decrease in anti-VEGF treatment burden for both indications
Bilateral treatment effect with 66.7% reduction in fellow eye IVT injections for wet AMD subjects and 85.8% reduction for DME subjects
Mean best corrected visual acuity improved by 3 letters in study eye of wet AMD subjects (from baseline to week 24) and improved by 4.5 letters in study eye of DME subjects (from baseline to week 24)
Mean central subfield thickness improved by 45.5 microns in wet AMD subjects and by 69.1 microns in DME subjects
No serious adverse events or ocular adverse events related to MGB were reported. Injection site reactions were reported in 5 subjects (3 wet AMD, 2 DME), with only 26 reactions across 302 total subcutaneous injections (8.6%), mostly Grade 1 (mild)

Following their presentation at ARVO, Jeff Cleland, Ph.D., CEO of Ashvattha Therapeutics, stated that, “these updated Phase 2 results demonstrate MGB’s potential to address a significant unmet need in retinal vascular diseases. A monthly subcutaneous injection that effectively treats both eyes simultaneously while improving vision and reducing retinal fluid addresses a significant unmet need. We look forward to advancing this promising therapy into late-stage clinical development.”

Opus Genetics Inc., has announced 12-month summary results for OPGx-LCA5 – an experimental gene therapy treatment of LCA5 retinal disease.

Dr. Gearóid Tuohy — Mon, 12 May 2025 14:32:58 +0000

Opus Genetics Inc., (NASDAQ: IRD), based in Raleigh, North Carolina, has announced the one-year summary results from adult patients treated in an ongoing Phase 1/2 study of the gene therapy candidate: OPGx-LCA5, an experimental treatment for Leber congenital amaurosis (LCA). OPGx-LCA5 is an adeno-associated virus 8 (AAV8) vector designed to deliver a functional LCA5 gene to the outer retina in patients. Following a presentation at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), in Salt Lake City, Utah, Dr. Aleman, of the Scheie Eye Institute, University of Pennsylvania, stated that, “the preliminary data emerging from this Phase 1/2 study of OPGx-LCA5 are very encouraging. We are pleased to see evidence of durable efficacy, with the treatment benefits observed at six months being sustained out to one year. Unquestionable gains in cone-mediated vision (daytime) confirmed one year after treatment have been associated with improvements in patients’ reading vision and ability to recognize objects, which are meaningful to these patients with severely impaired visual function. These findings support continued development of this gene therapy, which offers potentially ground breaking opportunities, as we look forward to enrolling additional patients into the study.”

Previously defined as a juvenile form of RP (retinitis pigmentosa), LCA is a severe congenital or early infant-onset form of non-syndromic retinal disease, characterised by severe retinal dystrophy, vision loss, nystagmus, an absence of a normal pupil response and an almost non-recordable ERG. To date, there are now 25 genes causative for LCA, one of which, lebercilin (LCA5), now accounts ~ 2% of LCA cases with a particularly severe form of the disease. The LCA5 gene, located in chromosome 6q14.1, encodes an 80kDa protein expressed in the connecting cilium of photoreceptors. In a Phase 1 / 2 clinical study, the trial was designed to evaluate the safety and preliminary efficacy of OPGx-LCA5 in patients, diagnosed with inherited retinal degeneration due to biallelic mutations in LCA5. Efficacy endpoints include measurement of functional vision using: 1) the Multi-Luminance orientation and Mobility Test (MLoMT), similar to a primary endpoint that was approved by the FDA in 2017 for the treatment of LCA2 (voretigene neparvovec (Luxturna)); 2) Full-Field Stimulus Testing (FST); and 3) microperimetry, details available on NCT05616793 cliniclatrials.gov.

Figure 1. MLoMT assay, developed by Opus Genetics Inc., provides a virtual reality-based test designed to measure changes in functional vision; the MLoMT assay provides a “second generation” mobility test, the “MLMT” which was used as a primary endpoint approved by the FDA for voretigene neparvovec in Dec. 2027. Summary data of the MLoMT is available at the public Opus Genetics Inc., website, Corporate Presentation of May 5^th 2025: https://d1io3yog0oux5.cloudfront.net/_7d861fc3e29b54997eb3d39d2d8ff0fe/ocuphire/db/453/5871/pdf/Opus+Corporate+Deck+May+2025+FINAL+%28002%29.pdf

Following the 1-year results of OPGx-LCA5, summary data reported that the MLoMT assay, a virtual reality-based test designed to measure changes in functional vision, showed that two out of the three participants had a clinically meaningful improvement, while one of the participants were unable to complete the MLoMT course. Visual acuity improvements averaged 0.35 logMAR, equivalent to a 3.5 line improvement across three participants. FST measurements showed improvements in sensitivity from baseline, with a 0.86 log improvement being observed at 12 months vs 0.16 log units for the control eyes. Finally, in microperimetry, capable for correlating functional information (visual field testing) with structural/anatomical data (retinal imaging), indicated that one patient saw substantial improvements in macular sensitivity, suggesting improved central vision with improved fixation. However, data of the other two participants could not be collected due to poor fixation at the baseline visit. Safety was well tolerated with no reports of dose-limiting toxicities or serious adverse events out to 12 months. Commenting on the announcement, George Magrath, M.D., Chief Executive Officer of Opus Genetics, stated that, “the new data, while in a limited number of adults patients, give us even more conviction that our initial success with OPGx-LCA5 has the potential to translate to the rest of our pipeline, which contains gene therapy treatments for six additional inherited retinal diseases, as we plan to enter Phase 1/2 with our BEST-1 program later this year.”

LumiThera Inc., obtains FDA authorisation in the US on a photo-biomodulation (PBT) medical device – “Valeda” – for the treatment of dry AMD.

Dr. Gearóid Tuohy — Mon, 28 Apr 2025 14:16:37 +0000

LumiThera Inc., based in Seattle, Washington, USA, has recently received the U.S. Food & Drug Administration (FDA) authorisation, marketing for “Valeda Light Delivery System” for treatment of patients with dry age-related macular degeneration (AMD). According to the company, their Valeda therapy is the first ever authorized treatment by the FDA for vision loss in dry AMD patients, providing “an improvement in best corrected visual acuity (BCVA) over 24 months of >5 letters or equivalent to a line on the eye chart. In the pivotal U.S. LIGHTSITE III trial, the Valeda treatment met its primary endpoint and was shown to be safe and effective in increasing and maintaining improved visual acuity.” Valeda is CE Marked in the EU and is available in select countries in Latin America.

The “LIGHTSITE III” study was conducted by a multi-centre clinical trial in dry age-related macular degeneration (AMD). The photo-biomodulation (PBM) device is aimed to activate mitochondrial respiratory chain components resulting “in stabilization of metabolic function and initiation of a signalling cascade, which promotes cellular proliferation and cytoprotection”, according to the company. Previously, in the EU, the medical device developed a CE mark to use wavelengths of light in the far red to near infrared spectrum (590, 660 and 850 nm) to modulate biologic function through direct and indirect cellular effects on mitochondrial respiratory chain components. PBM activation “of photo-acceptors in the mitochondria improves generation of adenosine triphosphate (ATP), modulates the production of intracellular signalling molecules such as reactive-oxygen species (ROS) and nitric oxide (NO), and triggers secondary effects that produce sustained changes in cell function and viability”.

Non-invasive painless treatment for DRY AMD – According to Progressive Vision, treatment options for Dry AMD have been limited to dietary supplements and lifestyle interventions. However, the new and only available treatment for Dry AMD is here, using a safe, non-invasive and painless therapy – photobiomodulation. The Valeda Light Delivery System (LDS) provides a direct treatment for Dry Age – Related Macular Degeneration (https://www.progressivevision.ie/valeda/)

According the US authorisation, LumiThera submitted the US LIGHTSITE III clinical data as part of a technical package to the FDA under a “De Novo” request with special controls. Lori Holder, Vice President, Regulatory Affairs, LumiThera, Inc. stated that, “the De Novo authorization established Valeda as the first device for treatment of dry AMD patients with vision loss and creates a threshold for this novel class of PBM devices that must show similar clinical and nonclinical performance controls equivalent to the Valeda Light Delivery System.” In addition, David Boyer, MD, Retina Vitreous Associates Medical Group, Beverly Hills, CA commented that, “the RCT results demonstrated clinical benefits in early to intermediate dry AMD patients out to 24 months and an excellent safety profile. Patients will now be able to try a non-invasive treatment that can help improve their vision earlier in the disease process.” The Duke Reading Center also reported that the PBM treatment had a beneficial effect on multiple anatomic biomarkers finding that, “that incident geographic atrophy (GA) was reduced in the PBM-treated eyes compared to the sham treated eyes respectively, 6.8% versus 24%. Although incident GA was not a prespecified clinical endpoint, the results supported overall safety benefits of treating earlier in dry AMD disease.”