Opus Genetics Reports Positive Pediatric Data from OPGx-LCA5 Phase 1/2 Trial in Leber Congenital Amaurosis Type 5 (LCA5)
Opus Genetics (NASDAQ:IRD) announced positive three-month data from the pediatric cohort of its Phase 1/2 clinical trial for OPGx-LCA5, a gene therapy targeting Leber congenital amaurosis type 5 (LCA5). The trial showed significant improvements in three pediatric participants aged 16-17, demonstrating enhanced cone-mediated vision and visual acuity.
Key results include an average 0.3 logMAR improvement in visual acuity among pediatric participants, with individual improvements ranging from 0.2 to 0.7 logMAR. All participants showed greater than one log unit improvement in cone sensitivity and better object identification in mobility tests. Adult participants maintained improvements through 18 months, suggesting treatment durability. The therapy has been well-tolerated with no serious adverse events.
Opus Genetics (NASDAQ:IRD) ha comunicato dati positivi di tre mesi dalla coorte pediatrica del suo trial di Fase 1/2 per OPGx-LCA5, terapia genica mirata alla Leber congenital amaurosis di tipo 5 (LCA5). L trial ha mostrato notevoli miglioramenti in tre partecipanti pediatrici di età 16-17 anni, con un incremento della visione mediata dai coni e dell’acuità visiva.
I risultati chiave includono in media un miglioramento di 0,3 logMAR nell’acuità visiva tra i partecipanti pediatrici, con miglioramenti individuali da 0,2 a 0,7 logMAR. Tutti i partecipanti hanno mostrato più di un’unità logaritmica di miglioramento della sensibilità ai coni e un miglioramento nell’individuazione degli oggetti nei test di mobilità. I partecipanti adulti hanno mantenuto i miglioramenti per 18 mesi, suggerendo una durata del trattamento. La terapia è stata ben tollerata senza eventi avversi seri.
Opus Genetics (NASDAQ:IRD) anunció datos positivos a tres meses de la cohorte pediátrica de su ensayo de fase 1/2 para OPGx-LCA5, una terapia génica dirigida a la amaurosis congénita de Leber tipo 5 (LCA5). El ensayo mostró mejoras significativas en tres participantes pediátricos de 16-17 años, con mayor visión mediada por conos y agudeza visual.
Resultados clave incluyen una media de 0,3 logMAR de mejora en la agudeza visual entre los participantes pediátricos, con mejoras individuales entre 0,2 y 0,7 logMAR. Todos los participantes presentaron una mejora de más de una unidad logarítmica en la sensibilidad de los conos y una mejor identificación de objetos en las pruebas de movilidad. Los participantes adultos mantuvieron las mejoras durante 18 meses, lo que sugiere durabilidad del tratamiento. La terapia se toleró bien y no se reportaron eventos adversos graves.
Opus Genetics (NASDAQ:IRD)는 LCA5를 표적으로 하는 유전자 치료제 OPGx-LCA5의 1상/2상 임상시험의 소아 코호트에서 3개월 데이터가 긍정적이라고 발표했다. 연구는 16-17세의 세 명의 소아 참가자에서 cones를 매개로 한 시력과 시력 선명도 개선을 보여주었다.
주요 결과로는 소아 참가자들 사이에서 평균 시력 logMAR 0.3 개선이 나타났고, 개별 개선은 0.2에서 0.7 logMAR에 이르렀다. 모든 참가자는 cone 감도에서 1 log 단위 이상 개선과 이동성 테스트에서 물체 인식이 향상되었다. 성인 참가자들은 18개월까지 개선을 유지하며 치료의 지속 가능성을 시사한다. 이 치료는 잘 견디고 심각한 이상 반응은 없었다.
Opus Genetics (NASDAQ:IRD) a annoncé des données positives à trois mois provenant de la cohorte pédiatrique de son essai de phase 1/2 pour OPGx-LCA5, une thérapie génique ciblant la rétinite pigmentaire congénitale de Leber type 5 (LCA5). L’essai a montré des améliorations significatives chez trois participants pédiatriques âgés de 16 à 17 ans, avec une vision centrée sur les cônes et une acuité visuelle améliorées.
Les résultats clés incluent en moyenne une amélioration de 0,3 logMAR de l’acuité visuelle chez les participants pédiatriques, avec des améliorations individuelles allant de 0,2 à 0,7 logMAR. Tous les participants ont présenté plus d’un ordre de grandeur d’amélioration de la sensibilité des cônes et une meilleure identification des objets dans les tests de mobilité. Les participants adultes ont conservé les améliorations pendant 18 mois, suggérant une durabilité du traitement. La thérapie est bien tolérée, sans événements indésirables graves.
Opus Genetics (NASDAQ:IRD) hat positive Drei-Monats-Daten aus der pädiatrischen Kohorte der Phase-1/2-Studie zu OPGx-LCA5, einer Gentherapie zur Behandlung der Leberer Congenital Amauose Typ 5 (LCA5), bekannt gegeben. Die Studie zeigte bei drei pädiatrischen Teilnehmern im Alter von 16-17 Jahren signifikante Verbesserungen der konenvermittelten Sicht und der Sehschärfe.
Wichtige Ergebnisse umfassen im Durchschnitt eine Verbesserung der Sehschärfe um 0,3 logMAR bei den pädiatrischen Teilnehmern, mit individuellen Verbesserungen von 0,2 bis 0,7 logMAR. Alle Teilnehmer zeigten eine Steigerung der Cone-Sensitivität um mehr als eine log-Unit und eine bessere Objekterkennung in Mobilitätstests. Erwachsensteilnehmer behielten die Verbesserungen über 18 Monate bei, was auf eine Therapiedauer hinweist. Die Therapie wurde gut vertragen und es traten keine schweren unerwünschten Ereignisse auf.
Opus Genetics (NASDAQ:IRD) أعلنت عن بيانات إيجابية لمدة ثلاثة أشهر من Cohorte الأطفال في تجربتها السريرية من المرحلة 1/2 لـ OPGx-LCA5، وهي علاج جيني يستهدف ضمور البصر الخلقي في ليبير من النوع 5 (LCA5). أظهرت التجربة تحسنا ملحوظا لدى ثلاثة مشاركين أطفال تتراوح أعمارهم بين 16 و17 عاما، مع تحسين في الرؤية المعتمدة على المخاريط وبصر حاد.
تشمل النتائج الأساسية متوسط تحسن بمقدار 0.3 logMAR في حدة البصر بين المشاركين الأطفال، مع تحسينات فردية من 0.2 إلى 0.7 logMAR. أظهر جميع المشاركين تحسنا يزيد عن وحدتين لوجاريتيتين في حساسيتهم للمخاريط وتحسنا في التعرف على الأشياء في اختبارات التنقل. حافظ المشاركون البالغون على التحسن حتى 18 شهرا، ما يوحي بدوام العلاج. كما أن العلاج تحمّله بشكل جيد ولم يسجل أحداث سلبية خطيرة.
Opus Genetics (NASDAQ:IRD) 宣布其针对 OPGx-LCA5 的1/2期临床试验儿科人群的三个月数据呈现积极结果，该治疗是一种针对 Leber 先天性黑矇性疾病5型 (LCA5) 的基因治疗。试验在< b>16-17岁的三名儿科参与者中显示出以圆锥细胞为介导的视力显著改善及视力敏锐度提升。
关键结果包括儿科参与者的平均< b>视力以logMAR表示提升0.3，个体改善范围为0.2到0.7 logMAR。所有参与者都显示出< b>圆锥敏感度提升超过一log单位，在移动性测试中的对象识别也有所提高。成人参与者在< b>18个月内维持改善，提示治疗持久性。治疗耐受良好，未出现严重不良事件。
- None.
- One pediatric participant experienced worsening of pre-existing cataract
- Two of three pediatric participants could not conduct microperimetry test due to poor visual acuity and nystagmus
Insights
Opus reports strong vision improvements in pediatric LCA5 patients with durable 18-month benefits in adults and good safety profile.
The Phase 1/2 trial data for OPGx-LCA5 in Leber congenital amaurosis type 5 represents a significant breakthrough in the gene therapy landscape for inherited retinal diseases. The pediatric cohort demonstrated remarkable cone-mediated vision improvement - particularly notable since these teenagers had already experienced profound vision loss. The average 0.3 logMAR visual acuity improvement in the pediatric group exceeded the adult cohort's response, with one patient showing an impressive 0.7 logMAR improvement maintained through three months.
What's mechanistically compelling is the greater than one log unit improvement in cone sensitivity to both red and blue light across all pediatric participants, providing objective evidence of functional retinal recovery. This sensitivity enhancement aligns with the therapy's mechanism of action - gene augmentation addressing the underlying LCA5 genetic defect in photoreceptor cells.
The durability data from adults extending to 18 months is perhaps equally significant, suggesting the treatment effect persists long-term - critical for gene therapies where single-administration durability is essential for clinical and commercial viability. The clean safety profile with no ocular serious adverse events, dose-limiting toxicities, or drug-related adverse events is reassuring for an interventional subretinal injection procedure.
The improvements in the Multi-Luminance Orientation and Mobility Test translate these clinical metrics into functional benefits - patients identifying more objects represents meaningful improvement in daily visual function. With an FDA meeting scheduled for Q4 2025, these positive results position OPGx-LCA5 strongly for potential accelerated development pathways given the ultra-rare disease designation and unmet need in LCA5.
The reported data represents a particularly robust signal of efficacy in a challenging patient population. The pediatric cohort's response profile is especially promising given the early intervention hypothesis for genetic disorders - treating younger patients before irreversible photoreceptor degeneration occurs.
Several methodological strengths stand out: First, the use of multiple complementary endpoints (visual acuity, FST, microperimetry, and MLoMT) provides convergent evidence of therapeutic effect across different visual domains. Second, the treated vs. untreated eye comparison creates an internal control that mitigates placebo effect and individual variability concerns. The MLoMT test showing greater improvement in the treated eye versus control eye in two of three participants reinforces the biological plausibility of the treatment effect.
The magnitude of improvement is clinically meaningful - particularly the 0.7 logMAR improvement maintained through three months in one participant, which represents multiple line gains on a standard eye chart. The greater than one log unit enhancement in cone sensitivity to both red and blue light suggests restoration of photoreceptor function across the cone spectral range.
While promising, several important considerations remain: (1) the small sample size (three pediatric participants) means results must be interpreted cautiously; (2) longer follow-up in the pediatric cohort will be essential to confirm if they mirror the adult 18-month durability profile; and (3) the cataract progression in one participant, while attributed to the surgical procedure rather than the therapy itself, highlights the inherent risks of subretinal delivery that will require monitoring in larger studies.
- Pediatric participants demonstrated large gains in cone-mediated vision; therapy remains well tolerated with no ocular serious adverse events or dose-limiting toxicities
- Lasting, durable responses observed out to 18 months in adult participants
- Expected FDA Meeting in Q4 2025
- Management to Host Webcast and Conference Call Today at 8:30 A.M. ET
RESEARCH TRIANGLE PARK, N.C., Sept. 30, 2025 (GLOBE NEWSWIRE) -- Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage biopharmaceutical company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and small molecule therapies for other ophthalmic disorders, today announced positive three-month data from the pediatric cohort of its ongoing Phase 1/2 clinical trial (OPGx-LCA5-1001) evaluating OPGx-LCA5, an investigational gene augmentation therapy for Leber congenital amaurosis type 5 (LCA5).
“These pediatric results are particularly exciting, as they provide evidence that OPGx-LCA5 can potentially restore cone-mediated vision in teenagers who had already experienced profound vision loss,” said George Magrath, M.D., Chief Executive Officer, Opus Genetics. “These outcomes, alongside observed durable improvements observed in adults out to 18 months, give us confidence in the potential for OPGx-LCA5 to deliver meaningful and lasting benefit to patients. We expect to meet with the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year to discuss these results and the next steps for our LCA5 program targeting this ultra-rare disease.”
Three pediatric participants aged 16-17 with severe baseline vision impairment received a single subretinal injection of OPGx-LCA5. All three participants had improvements across multiple measures of visual function, as described below:
- Visual Acuity (VA):
For the pediatric cohort, early data showed a group average of a 0.3 logMAR improvement which is greater than was observed in the adult cohort.- Participant 01-05 had a baseline visual acuity of 2.2 logMAR with an improvement of 0.5 logMAR reported at one month.
- Participant 01-06 had a baseline visual acuity of 0.96 logMAR with an improvement of 0.2 logMAR reported at three months. They reported perceiving a clear difference in brightness between their treated and untreated eyes.
- Participant 01-07 had a baseline visual acuity of 2.3 logMAR with an improvement of 0.7 logMAR reported at one month, which was maintained through three months.
- Full-Field Stimulus Testing (FST):
All three participants showed improvements in the treated eyes from one month. Participants showed greater than one (>1) log unit improvement in cone sensitivity to both red and blue light. These changes provide evidence of recovery in retinal sensitivity. - Multi-Luminance Orientation and Mobility Test (MLoMT):
All participants identified more objects through three-months compared to baseline. Two out of the three participants had greater improvement in the treated eye compared to the control eye. - Microperimetry:
Two of the three pediatric participants could not conduct a microperimetry test due to their poor visual acuity and nystagmus at screening. However, microperimetry data was obtained on one participant, for whom early signs of improved fixation stability were observed, consistent with functional retinal recovery.
In addition, combined adult data support that improvements in visual acuity were sustained through 18 months, both in terms of mean change from baseline and mean interocular difference, underscoring the potential durability of the treatment response.
OPGx-LCA5 has been well-tolerated in all six participants treated to date (three adults and three pediatric participants). No ocular serious adverse events or dose-limiting toxicities have been observed. All ocular adverse events were mild in severity and were anticipated. No events were related to the study drug. One pediatric participant had a pre-existing cataract that worsened at three months, which was attributed to the surgical procedure itself and did not obscure improvements in retinal sensitivity.
“Seeing pediatric participants achieve measurable improvements in visual acuity, retinal sensitivity, and real-world navigation tasks within three months and adult participants maintaining those improvements is a remarkable step forward,” said Tomas S. Aleman, M.D., of the Scheie Eye Institute, University of Pennsylvania and principal investigator of the study. “This is important evidence supporting that gene augmentation therapy can potentially restore cone function in patients with LCA5.”
Conference Call & Webcast Details
Opus Genetics management will host a webcast and conference call today at 8:30 a.m. Eastern Time to discuss the OPGx-LCA5 clinical trial data. The live and archived webcast may be accessed on the Opus Genetics website under the Investors section: Events. The live call can be accessed by dialing 888-506-0062 (domestic) or 973-528-0011 (international) and entering conference code: 906168. Opus Genetics suggests participants join 15 minutes in advance of the event.
About the OPGx-LCA5-1001 Phase 1/2 Clinical Trial
The OPGx-LCA5-1001 trial is a Phase 1/2 open-label, ascending-dose study evaluating the safety and preliminary efficacy of OPGx-LCA5 administered via subretinal injection in participants with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. The trial has enrolled a total of six participants: three adults and three pediatric participants. Efficacy evaluations include measurements of visual acuity; Full-Field Stimulus Testing (FST), which measures the retina's sensitivity to light; performance outcomes on the Multi-Luminance orientation and Mobility Test (MLoMT); and microperimetry, which measures point-wise sensitivity to light. For more information, visit clinicaltrials.gov (NCT05616793).
About OPGx-LCA5
OPGx-LCA5 is designed to address a form of Leber congenital amaurosis (LCA) due to biallelic mutations in the LCA5 gene (LCA5), which encodes the lebercilin protein. LCA5-associated inherited retinal disease is an early-onset severe inherited retinal dystrophy. Studies in patients with this mutation have reported evidence for the dissociation of retinal architecture and visual function in this disease, suggesting an opportunity for therapeutic intervention through gene augmentation. OPGx-LCA5 uses an adeno-associated virus 8 (AAV8) vector to precisely deliver a functional LCA5 gene to the outer retina. OPGx-LCA5 is currently being evaluated in a Phase 1/2 clinical trial at the University of Pennsylvania. Data from pediatric participants demonstrated large gains in cone-mediated vision, and the therapy remains well tolerated with no ocular serious adverse events or dose-limiting toxicities. The adult cohort showed durable improvements in cone sensitivity and visual function out to 18 months. OPGx-LCA5 has received Rare Pediatric Disease, Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA.
About Leber Congenital Amaurosis (LCA) and LCA5
Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by severe impaired vision or blindness at birth. Some retinal experts consider LCA to be a severe form of retinitis pigmentosa (RP). The condition is caused by degeneration and/or dysfunction of photoreceptors, the cells in the retina that make vision possible. Mutations in one of more than two dozen genes can cause LCA.
LCA5 is an ultra-rare disease caused by mutations in the LCA5 gene, which encodes lebercilin, a protein essential for photoreceptor structure and function. LCA5 accounts for roughly
About Opus Genetics
Opus Genetics is a clinical-stage biopharmaceutical company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and small molecule therapies for other ophthalmic disorders. The Company’s pipeline features AAV-based gene therapies targeting inherited retinal diseases including Leber congenital amaurosis (LCA), bestrophinopathy, and retinitis pigmentosa. Its lead gene therapy candidates are OPGx-LCA5, which is in an ongoing Phase 1/2 trial for LCA5-related mutations, and OPGx-BEST1, a gene therapy targeting BEST1-related retinal degeneration. Opus Genetics is also advancing Phentolamine Ophthalmic Solution
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to the clinical development of, and clinical results and future plans for, OPGx-LCA5, potential meetings with the FDA regarding our OPGx-LCA5 program, and expectations regarding us, our business prospects, and our results of operations and are subject to certain risks and uncertainties posed by many factors and events that could cause our actual business, prospects and results of operations to differ materially from those anticipated by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those described under the heading “Risk Factors” included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 , our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2025 and June 30, 2025, and in our other filings with the U.S. Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. These forward-looking statements are based upon our current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “aim,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. We undertake no obligation to revise any forward-looking statements in order to reflect events or circumstances that might subsequently arise.
Contacts
Investors
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Remy Bernarda
IR Advisory Solutions
ir@opusgtx.com
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KKH Advisors
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kimberly.ha@kkhadvisors.com
Source: Opus Genetics, Inc.
FAQ
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