ONL1204 / ONL Therap - LARVOL DELTA

ONL1204 for the Treatment of Geographic Atrophy: Phase Ib Study Evaluating Safety, Tolerability, and Efficacy. (PubMed, Ophthalmol Sci) - "These results support further evaluation of ONL1204 in patients with GA. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Clinical • Journal • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD (clinicaltrials.gov) - P2 | N=324 | Recruiting | Sponsor: ONL Therapeutics | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2027 ➔ Nov 2028

Enrollment open • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

In Vivo Characterization of ONL1204, a Small Peptide Inhibitor of the Fas Receptor, as a Potential Neuroprotective Therapy for Geographic Atrophy and Dry Age-Related Macular Degeneration. (PubMed, Biomedicines) - "In the chronic mouse model, two administrations of ONL1204 preserved RPE morphology, reduced caspase-8 activity, and decreased inflammation. These data represent key characteristics of ONL1204, highlighting its clinical potential as a therapeutic for chronic retinal diseases, including GA."

Journal • Preclinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • CASP8

Neuroprotection of photoreceptors by combined inhibition of both Fas and autophagy pathways in P23H mice. (PubMed, Cell Death Dis) - "Our previous data have shown that both the Fas (CD95) death receptor and hyperactivation of autophagy contribute to photoreceptor (PR) death in a mouse model of P23H-RHO adRP...Hydroxychloroquine (HCQ) was given in the drinking water at P21 to reduce autophagy flux...These results were recapitulated in HCQ-treated P23H mice receiving intravitreal injections of ONL1204. Our data suggest that in the mouse model of P23H adRD, inhibition of both the Fas pathway and autophagy pathways results in a greater protective effect, demonstrating the potential multipronged therapeutic approach to reduce PR death and improve retinal function in patients with P23H."

Journal • Preclinical • Genetic Disorders • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CDKN1A • FAS

AI analysis of OCT images from a Phase 1b study of ONL1204 Fas inhibition treatment for geographic atrophy secondary to age-related macular degeneration (ARVO 2025) - P1 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

ONL Therapeutics Announces Multiple Presentations at Leading Ophthalmology Meetings (GlobeNewswire) - "ONL Therapeutics, Inc...today announced that the company will present clinical data and scientific research at the following first quarter meetings: 48th Annual Meeting of the Macula Society, February 12-15, 2025, at the Sunseeker Resort in Charlotte Harbor, Florida; Glaucoma Innovation Summit at the American Glaucoma Society (AGS) 2025 Annual Meeting, February 26 - March 2, 2025, at the Omni Shoreham Hotel in Washington, D.C; 9th Military Vision Symposium on Novel Technology and Vision Restoration hosted by Harvard Medical School Department of Ophthalmology and Mass Eye and Ear, February 27-28, 2025, at the Starr Center and Wyndham Boston Beacon Hill Hotel in Boston, Massachusetts."

Clinical data • Glaucoma

Phase 2 Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD (clinicaltrials.gov) - P2 | N=324 | Not yet recruiting | Sponsor: ONL Therapeutics

New P2 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Phase 1b Study of ONL1204 Ophthalmic Solution in Patients with Progressing Open Angle Glaucoma (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: ONL Therapeutics | Active, not recruiting ➔ Completed | Phase classification: P1b ➔ P1 | Trial completion date: Oct 2024 ➔ Apr 2024

Phase classification • Trial completion • Trial completion date • Glaucoma • Ophthalmology

Intravitreal Fas inhibitor ONL1204 for Macula-off Rhegmatogenous Retinal Detachment: Phase 2 Clinical Trial Results (AAO 2024) - No abstract available

Clinical • Late-breaking abstract • P2 data • Ophthalmology • Retinal Disorders

Preservation of retinal structure and function in two mouse models of inherited retinal degeneration by ONL1204, an inhibitor of the Fas receptor. (PubMed, Cell Death Dis) - "Treatment with ONL1204 also reduced immune cell activation in the retinas of both rd10 and P23H mice. The protective effect of pharmacologic inhibition of Fas by ONL1204 in two distinct mouse models of retinal degeneration suggests that targeting this common pathophysiologic mechanism of cell death and inflammation represents a potential therapeutic approach to preserve the retina in patients with IRD, regardless of the genetic underpinning."

Journal • Preclinical • Inflammation • Ophthalmology • CASP8

Neuroprotection of photoreceptors by combined inhibition of both Fas and autophagy pathways in P23H mice. (ARVO 2024) - "In the adRP model of P23H mice, inhibition of Fas pathway or autophagy alone is protective, and inhibiting both pathways showed greater protective effects. Our results suggest that the combined treatment of inhibiting autophagy by HCQ, and suppressing Fas pathway by ONL1204 represents a potential combined therapeutic approach in patients with P23H."

Preclinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CASP8 • CDKN1A • FAS

Preservation of retinal structure and function in two mouse models of inherited retinal degeneration by ONL1204, an inhibitor of the Fas receptor (ARVO 2024) - "Protective effect of pharmacologic Fas inhibition by ONL1204 in two distinct mouse models of retinal degeneration suggests that targeting this common pathophysiologic mechanism of cell death and inflammation represents a potential mutation-independent therapeutic approach to preserve the retina in patients with IRD."

Preclinical • Ophthalmology • CASP8

ONL1204 Ophthalmic Solution in Patients With Geographic Atrophy Associated With Age-related Macular Degeneration (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: ONL Therapeutics | Active, not recruiting ➔ Completed | Phase classification: P1b ➔ P1 | Trial completion date: Sep 2024 ➔ Feb 2024

Phase classification • Trial completion • Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

A Phase 2 Study to Assess the Safety and Efficacy of Intravitreal ONL1204 Ophthalmic Solution in Subjects With Mac-off Retinal Detachment (clinicaltrials.gov) - P2 | N=136 | Completed | Sponsor: ONL Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Feb 2024 | Trial primary completion date: Feb 2025 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date • Ophthalmology • Retinal Disorders

A Phase 2 Study to Assess the Safety and Efficacy of Intravitreal ONL1204 Ophthalmic Solution in Subjects With Mac-off Retinal Detachment (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: ONL Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Retinal Disorders

A Phase 1b Study of ONL1204 Ophthalmic Solution in Patients With Progressing Open Angle Glaucoma (clinicaltrials.gov) - P1b | N=25 | Active, not recruiting | Sponsor: ONL Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ Oct 2024 | Trial primary completion date: Jun 2023 ➔ Apr 2024

Enrollment closed • Trial completion date • Trial primary completion date • Glaucoma • Ophthalmology

ONL1204 Ophthalmic Solution in Patients With Geographic Atrophy Associated With Age-related Macular Degeneration (clinicaltrials.gov) - P1b | N=28 | Active, not recruiting | Sponsor: ONL Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2023 ➔ Sep 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2024

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ONL Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of First-in-Class Fas-Inhibitor in Patients with Macula-Off Rhegmatogenous Retinal Detachment (GlobeNewswire) - "ONL Therapeutics...today announced that the first patient has been dosed in its Phase 2 clinical trial of ONL1204 Ophthalmic Solution in patients with macula-off rhegmatogenous retinal detachment (RRD)....the company will continue its focus on generating interim data and completing its ongoing Phase 1b studies in the chronic indications of geographic atrophy associated with age-related macular degeneration and progressing open-angle glaucoma that are being conducted at sites in Australia and New Zealand."

Trial status • Ophthalmology • Retinal Disorders

A Phase 2 Study to Assess the Safety and Efficacy of Intravitreal ONL1204 Ophthalmic Solution in Subjects With Mac-off Retinal Detachment (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: ONL Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology • Retinal Disorders

Safety and tolerability of intravitreal ONL1204 in patients with macula-off rhegmatogenous retinal detachment (ARVO 2023) - P1 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders

Protective effect of pharmacological Fas inhibition in two mouse models of inherited retinal degeneration (ARVO 2023) - "The purpose of this study was to examine the effects of pharmacologic inhibition of Fas in these two models by intravitreal injection with a small peptide inhibitor of the Fas receptor, ONL1204...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Preclinical • Ophthalmology • CASP8

ONL Therapeutics Receives U.S. FDA Clearance of Investigational New Drug Application for ONL1204 Ophthalmic Solution (GlobeNewswire) - “ONL Therapeutics, Inc…announced the U.S. Food and Drug Administration (FDA) has authorized the company to proceed with the Investigational New Drug (IND) application for ONL1204 Ophthalmic Solution, a first-in-class small molecule Fas inhibitor designed as a neuroprotectant for key retinal cells. The company intends to initiate a Phase 2 clinical study of ONL1204 Ophthalmic Solution in patients suffering from macula-off rhegmatogenous retinal detachment (RRD) at sites in the U.S. in the second quarter of 2023.”

IND • New P2 trial • Ophthalmology • Retinal Disorders

A Phase 2 Study to Assess the Safety and Efficacy of Intravitreal ONL1204 Ophthalmic Solution in Subjects With Mac-off Retinal Detachment (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: ONL Therapeutics

New P2 trial • Ophthalmology • Retinal Disorders

Fas Inhibition with ONL1204 for the Treatment of Geographic Atrophy: First-Time Interim Results from a Phase 1 Open-Label Dose Escalation Study (Macula 2023) - P1b | "A single injection of ONL1204 was safe and well-tolerated in patients with GA secondary to AMD. This study is ongoing and will continue to assess the safety of additional injections, with additional efficacy endpoints being evaluated."

Clinical • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Vasculitis

A Phase 1b Study of ONL1204 Ophthalmic Solution in Patients With Progressing Open Angle Glaucoma (clinicaltrials.gov) - P1b | N=25 | Recruiting | Sponsor: ONL Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2022 ➔ May 2022

Enrollment open • Trial initiation date • Glaucoma • Ophthalmology