rAAV2tYF-CB-hRS1 / Beacon Therapeutics - LARVOL DELTA

Safey and Efficacy of ATSN-201 Dose Escalation in Patients with X-linked Retinoschisis (XLRS) (ASGCT 2025) - "The presence of schisis cavities in the central retina poses a challenge to safe and effective delivery of AAV-RS1 to XLRS patients. In conclusion, ATSN-201 is a promising treatment approach for patients with XLRS, a disease for which no treatments currently exist. Disease Focus of Abstract:Ophthalmic Diseases"

Clinical • Age-related Macular Degeneration • Gene Therapies • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: VegaVect, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Oct 2024 | Trial primary completion date: Jul 2025 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

IND‐enabling studies to support the clinical development of ATSN‐201, a subretinally delivered, laterally spreading gene replacement therapy for X‐Linked Retinoschisis (XLRS) (ESGCT 2023) - "A single, subretinal injection of ATSN-201 significantly improved retinal structure and function, supporting the clinical use of ATSN-201 for the treatment of XLRS. The ability of the novel AAV.SPR capsid to effectively deliver the RS1 to the central retina of primates following extrafoveal SRI represents a safer and potentially more effective treatment option for XLRS patients."

Clinical • Age-related Macular Degeneration • CNS Disorders • Inflammation • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • SPR

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis. (PubMed, Front Med (Lausanne)) - "Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials."

Gene therapy • Journal • Preclinical • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders

Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: National Eye Institute (NEI) | Trial primary completion date: Jun 2021 ➔ Jul 2025

Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Safety and Efficacy Study of Novel Gene Therapy ZM-01 for X-linked Retinoschisis Patients (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Zhongmou Therapeutics

Gene therapy • New P1 trial • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Safety and Efficacy of rAAV-hRS1 in Patients With X-linked Retinoschisis (XLRS) (clinicaltrials.gov) - P1/2 | N=27 | Completed | Sponsor: Applied Genetic Technologies Corp | Active, not recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ May 2023

Trial completion • Trial completion date • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Intravitreal Delivery of rAAV2tYF-CB-hRS1 Vector for Gene Augmentation Therapy in X-linked Retinoschisis - 1 Year Clinical Results. (PubMed, Ophthalmol Retina) - "Gene augmentation therapy with rAAV2tYF-CB-hRS1 for XLRS was generally safe and well-tolerated but failed to demonstrate a measurable treatment effect. The clinical trial is ongoing through 5-year follow-up to assess long-term safety."

Journal • Immunology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis

Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: National Eye Institute (NEI) | Trial primary completion date: Jul 2025 ➔ Jun 2021

Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Laterally Spreading AAV.SPR-hRS1 Vector for Treatment of XLRS (ASGCT 2022) - "Purpose: The presence of schisis cavities in the central retina has hampered safe and effective delivery of AAV-RS1 to XLRS patients...Efficacy of AAV.SPR and AAV5 vectors carrying the photoreceptor specific human rhodopsin kinase promoter (hGRK1) driving human RS1 (hRS1) were evaluated in Rs1 knock-out (RS1KO) mice... A novel AAV vector has been developed for the treatment of XLRS. AAV.SPR-hGRK1-hRS1 leads to therapeutic levels of RS1 in subretinally injected RS1KO mice, resulting in improvements in both retinal structure and function. In addition, AAV.SPR safely and efficiently mediated RS1 expression in the central retina of primate eyes following peripheral SRI."

CNS Disorders • Immunology • Inflammation • Ocular Inflammation • Ophthalmology

AAV-RS1 Trials for X-linked Retinoschisis: Disease Condition, Trial Parameters, and Immune Status (ASGCT 2022) - No abstract available

Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Laterally Spreading AAV.SPR-hRS1 Vector for Treatment of XLRS (ARVO 2022) - "Purpose: The presence of schisis cavities in the central retina has hampered safe and effective delivery of AAV-RS1 to XLRS patients... A novel AAV vector has been developed for the treatment of XLRS. AAV.SPR delivered therapeutic levels of hRS1 to subretinally injected RS1KO mice, resulting in improvements in both retinal structure and function. In addition, AAV.SPR safely and efficiently mediated hRS1 expression in the central retina of primate eyes following peripheral subretinal injection."

Ophthalmology • MYC

Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: National Eye Institute (NEI) | N=24 ➔ 12 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

[VIRTUAL] Retinal structural and functional rescue by subretinal delivery of RS1 gene in mouse models of X-linked juvenile retinoschisis (ARVO 2021) - "Subretinal delivery of AAV RS1 is effective in all three Rs1 mutant mouse models, providing partial retinal structural and functional restoration. Gene supplementation shows promise for XLRS gene therapy. Less invasive delivery method and robust photoreceptor promoters for more efficient treatment are being explored."

Preclinical • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: National Eye Institute (NEI); Trial completion date: Jul 2023 ➔ Jul 2025; Trial primary completion date: Jul 2023 ➔ Jul 2025

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

Safety and Efficacy of rAAV-hRS1 in Patients With X-linked Retinoschisis (XLRS) (clinicaltrials.gov) - P1/2; N=27; Recruiting; Sponsor: Applied Genetic Technologies Corp; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar

AAV RS1: “Safety data through month 12+ post-injection shows study drug generally well tolerated” (AGTC) - Macula Society Annual Meeting

P1/2 data • Inherited Retinal Dystrophy • Ophthalmology

XLRS gene therapy: Top-line interim 6-month data from P1/2 trial (NCT02416622) for X-linked retinoschisis by the end of 2018 (AGTC) - Investor Presentation

P1/2 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

XLRS gene therapy: Patent protection related to methods to manufacture AAV vectors until 2025 (AGTC) - Annual Report 2017: Patent protection until 2034

Patent • Ophthalmology

AGTC announces topline interim six-month data from phase 1/2 X-linked retinoschisis clinical study; Termination of Biogen collaboration (agtc Press Release) - P1/2, N=27; NCT02416622; Sponsor: Applied Genetic Technologies Corp; "Applied Genetic Technologies Corporation...today reported topline interim six-month data from its Phase 1/2 clinical trial of rAAV2tYF-CB-hRS1...Results from the study show that rAAV2tYF-CB-hRS1 is generally safe and well-tolerated, but no signs of clinical activity were observed at six-months. As per the study protocol, AGTC will continue to monitor enrolled patients at scheduled visits through the end of the study...AGTC also announced that the company will regain full rights to the XLRS...programs and the three other partnered discovery programs following Biogen’s termination of the collaboration agreement, which will be effective on March 8, 2019."

Enrollment status • Licensing / partnership • P1/2 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

AGTC announces preclinical data evaluating cone-specific promoters for use in gene therapy of achromatopsia and other retinal diseases (agtc Press Release) - "Applied Genetic Technologies Corporation...today announced preclinical data evaluating cone-specific promoters for use in gene therapy of achromatopsia (ACHM) and other retinal diseases. Results were published online in the peer-reviewed journal Human Gene Therapy and will appear in the January print issue."

Preclinical • Ophthalmology

AGTC Announces topline safety data for X-linked retinoschisis phase 1/2 study (agtc Press Release) - P1/2, N=12; "Applied Genetic Technologies Corporation...announced topline safety data for the dose escalation phase of the company's Phase 1/2 X-linked retinoschisis (XLRS) clinical trial...Mild to moderate ocular inflammation was observed in the treated eye for the majority of patients and resolved or was controlled either without further intervention or after treatment with topical or oral corticosteroids."

P1/2 data • Inherited Retinal Dystrophy • Ophthalmology

"$BIIB fresh new pipeline? New programs MS:BTK inh SMA: BIIB078/110/100 Pain: BIIB095 Ophtalmology: BIIB111/112 Neurocognitive disorders: BIIB104 Out MS: BIIB098 Ophthalmolog: BIIB087 Acute neurology: Natalizumab AD: Elembecestast Switch Parkinson to AD & Dementia: BIIB092 https://t.co/Vr96h9huu9" (@BursatilBiotech)

Alzheimer's Disease • CNS Disorders • Dementia • Gene Therapies • Genetic Disorders • Movement Disorders • Pain • Parkinson's Disease • Tauopathies And Synucleinopathies

AGTC announces financial results and business update for the quarter ended September 30, 2019 (agtc Press Release) - "Research and development expenses were $8.6 million for the three months ended September 30, 2019, compared to $10.1 million for the three months ended September 30, 2018. The decrease of $1.5 million for the quarter was primarily due to...decreased discovery spending associated with the company’s pre-clinical ophthalmology programs, and decreased XLRS spending associated with completing enrollment of the XLRS Phase 1/2 trial in April 2018."

Commercial

AGTC announces financial results and business update for the fourth quarter and fiscal year ended June 30, 2019 (agtc Press Release) - P1/2, N=NA; "The company also provided topline six-month data from the dose escalation groups of the Phase 1/2 XLRP program as planned...Both data sets demonstrated a favorable safety profile with stability of visual function in peripherally dosed patients and improvement of visual function in 50% of centrally dosed patients. AGTC also provided an early look at data from the achromatopsia B3 and A3 trials showing signs of clinically meaningful improvements in light discomfort...To date, 27 patients have been dosed across the B3 and A3 Phase 1/2 trials....Data Safety Monitoring Committee (DSMC) has supported continued dose escalation and dosing of pediatric patients."

DSMB • P1/2 data • Trial status