AGTC-402 / AGTC - LARVOL DELTA

Genome-wide identification of heavy-metal ATPases genes in Areca catechu: investigating their functionality under heavy metal exposure. (PubMed, BMC Plant Biol) - "Results showed that the expression levels of AcHMA1 and AcHMA3 genes were significantly up-regulated under Cd2 + and Zn2 + stress. Similarly, in response to Cu2+, the AcHMA5 and AcHMA8 revealed the highest expression in roots and leaves, respectively. In conclusion, this study will offer a foundation for exploring the role of the HMAs gene family in dealing with heavy metal stress conditions in A. catechu."

Journal • CD2

Photoreceptor structure following gene therapy in CNGA3-mediated Achromatopsia: adaptive optics imaging results from a Phase 1/2 dose escalation clinical trial for AGTC-402 (rAAV2tYF-PR1.7-hCNGA3) (ARVO 2024) - "The foveal cone loss observed following subretinal injection of AGTC-402 may be a consequence of the surgical procedure and/or a short-term response to the study agent. The emergence of waveguiding cones in a subset of pediatric participants suggests younger individuals may be more amenable to treatment. Further investigation is needed to evaluate whether the appearance of waveguiding cones alters visual function."

Clinical • Gene therapy • P1/2 data • Achromatopsia • Ophthalmology

Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial) (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Applied Genetic Technologies Corp | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Aug 2026 | Trial primary completion date: Sep 2021 ➔ Aug 2022

Enrollment closed • Trial completion date • Trial primary completion date • Achromatopsia • Gene Therapies • Ophthalmology

Findings on visual photosensitivity in two phase 1/2 clinical trials of subretinal gene therapy with AGTC-401 and AGTC-402 for CNGB3 and CNGA3 achromatopsia (ARVO 2022) - "Subretinal gene therapy with AGTC-401 resulted in clinically-meaningful and sustained improvement in light discomfort in some participants with CNGB3 ACHM. Fewer individuals showed a response after treatment with AGTC-402 in the CNGA3 trial. Further study is needed to understand the bilateral nature of the LDT improvement."

Clinical • P1/2 data • Achromatopsia • Ophthalmology • Retinal Disorders

Interim Safety Results in Two Phase 1/2 Open-label, Dose-escalation Clinical Trials of Subretinal Gene Therapy with AGTC-401 (rAAV2tYF-PR1.7-hCNGB3) and AGTC-402 (rAAV2tYF-PR1.7-hCNGA3) in Subjects with Achromatopsia (ACHM) (ARVO 2022) - "AGTC-401/AGTC-402 gene therapy to potentially treat ACHM was safe and well-tolerated in children up to and including second highest dose (1.1e12vg/mL), and in adults up to and including the highest dose (3.2e12vg/mL), which was assessed to be a DLT level in children due to intraocular inflammation that responded to adjusted steroid regimens. Imaging studies were very important in characterizing the SAEs. Layman Abstract: Subretinal gene therapy for achromatopsia with study agents AGTC-401/AGTC-402 to date has exhibited an overall favorable safety profile."

Clinical • P1/2 data • Achromatopsia • Glaucoma • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis

Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia. (PubMed, Int J Mol Sci) - "This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families."

Clinical • Journal • Achromatopsia • Ophthalmology • Retinal Disorders • ATF6

[VIRTUAL] Twelve-month Findings from Two Phase 1/2 Clinical Studies of Subretinal Gene Therapy Drugs for Achromatopsia (ARVO 2021) - "Safety results suggest AGTC-401 and AGTC-402 are safe and well tolerated in ACHM patients. There were no indications of significant immunological responses to the vector or capsid. Data across both studies show encouraging signs of biologic activity."

Clinical • P1/2 data • Achromatopsia • Ocular Inflammation • Ophthalmology • Retinal Disorders

Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: Applied Genetic Technologies Corp; Trial completion date: Jun 2023 ➔ Sep 2025

Clinical • Trial completion date • Achromatopsia • Ophthalmology