GS030 / GenSight - LARVOL DELTA

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: GenSight Biologics

First-in-human • New P1/2 trial • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: GenSight Biologics | Initiation date: Jan 2018 ➔ May 2018

First-in-human • Trial initiation date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: GenSight Biologics | Not yet recruiting ➔ Recruiting | Trial completion date: May 2024 ➔ Jan 2025 | Initiation date: May 2018 ➔ Sep 2018 | Trial primary completion date: Jun 2020 ➔ Sep 2020

Enrollment open • First-in-human • Trial completion date • Trial initiation date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: GenSight Biologics | Recruiting ➔ Active, not recruiting | N=15 ➔ 10 | Trial completion date: Dec 2025 ➔ Oct 2027 | Trial primary completion date: Dec 2022 ➔ Oct 2027

Enrollment change • Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: GenSight Biologics | Trial primary completion date: Dec 2021 ➔ Dec 2022

First-in-human • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

PIONEER: Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: GenSight Biologics | Trial completion date: Jan 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2020 ➔ Dec 2021

First-in-human • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Bridging the blue: narrative review of neurosurgical access, aeromedical retrieval, and telehealth in Fiji and the pacific. (PubMed, J Clin Neurosci) - "Fiji's emerging role as a regional stabilization and tele-neurosurgery hub highlights a feasible model for strengthening neurosurgical access across the Pacific. A tiered network linking national hospitals to tertiary centers in Australia, New Zealand, India and France could reduce inequity if supported by regional policy frameworks, workforce upskilling, and outcome monitoring."

Journal • Review • Cardiovascular • CNS Disorders • Vascular Neurology

Bringing gene-independent strategies to the clinic: focus on Optogenetics (ARVO 2023) - P1/2 | "Initial results of the clinical trial NCT03326336 evaluating the safety and tolerability of the combination product “GS030-Drug Product and GS030-Medical Device (engineered goggles)” showed that the optogenetic therapy partially restored vision to a 58-year-old man who had been diagnosed with Retinitis Pigmentosa 14 years earlier and whose vision was limited to rudimentary light perception...As a mutation-independent therapeutic strategy, optogenetics carries a great potential for treatment of a broad spectrum of retinal dystrophies with photoreceptor degeneration. It complements other gene-independent approaches e.g. neuroprotection by Rod-derived Cone Viability Factor potentially applicable at earlier stages."

Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Current and Future Treatment of Retinitis Pigmentosa. (PubMed, Clin Ophthalmol) - "Amongst the 15 cell and gene therapies in late-stage development, 5 leading candidates have been selected to profile based on the development stage, drug target and geography: gene therapies AGN-151597, GS-030 and VMCO-1 and human stem cell therapies jCell and ReN-003. Gene therapies may be attractive as their fundamental goal is to restore vision; however, cell therapies will likely have a broader application and do not rely on genetic testing, which can delay treatment. Ensuring effective therapeutic options for RP patients across disease stages requires the continued diversification and advancement of the development pipeline, and sustained efforts to promote early patient identification and timely diagnosis."

Journal • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Optogenetics in the Clinic: Safety and Efficacy Updates on the Phase ½ Clinical Trial PIONEER (AAO 2022) - "The good safety profile of GS030 was demonstrated up to 2.5 years after vector administration."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Optogenetics in the clinic: safety and efficacy updates on the phase 1/2 clinical trial PIONEER (Macula 2022) - "The good safety profile of GS030 was demonstrated up to 2.5 years after vector administration, and preliminary efficacy assessment showed partial functional recovery in 2 subjects."

Clinical • P1/2 data • CNS Disorders • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Optogenetics in the clinic: safety and efficacy updates on the phase 1/2 clinical trial PIONEER (ARVO 2022) - "GS030 demonstrates a good safety profile up to 2.5 years after vector administration, and preliminary efficacy assessment shows partial functional recovery in two patients."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

"gensight qui utilise un brevet de Novartis pour GS030. tkt que Novartis la suis de pret" (@VialleJean)

"GenSight Biologics Reports Second Patient Case Showing Significant Visual Recovery after GS030 Optogenetic Treatment https://t.co/eOKLTgLUQw" (@NewsFromBW)

Clinical • Gene Therapies

[VIRTUAL] Optogenetic GS030 Therapy in Subjects with Retinitis Pigmentosa: Safety and Tolerability Up to Two Years After Treatment Administration in the Phase 1/2a PIONEER Study (ARVO 2021) - "The PIONEER study is the first clinical trial combining a gene therapy and a medical device using an optogenetic approach. The treatment was well tolerated up to two years after gene therapy administration."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Optogenetic GS030 Therapy in Subjects with Retinitis Pigmentosa: Safety and Tolerability Up to Two Years After Treatment Administration in the Phase 1/2a PIONEER Study (Macula 2021) - No abstract available

Clinical • P1/2 data • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] PA056: Optogenetics in the Clinic: PIONEER, a Phase 1/2 Gene Therapy Program for Nonsyndromic RP (AAO 2020) - "Purpose To evaluate the safety and tolerability of GS030, an optogenetic treatment combining a gene therapy (GS030-DP) and a medical device (GS030-MD) in subjects with end-stage nonsyndromic retinitis pigmentosa (RP)...Conclusions PIONEER uses a unique vision restoration optogenetic approach. Therapy is well tolerated in all six subjects to date."

P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Optogenetics in the clinic: PIONEER, a phase 1/2a, open-label, non-randomized, dose-escalation study to evaluate safety and tolerability of GS030 in subjects with retinitis pigmentosa (EURETINA 2020) - "At advanced stages of RP, although both rod and cone photoreceptors have degenerated, RGCs are preserved and can be converted into photosensitive cells via optogenetics approach. PIONEER is the first clinical trial combining a gene therapy independent of underlying genetic defects and a light-stimulating medical device in the treatment of RP, and as such offers great promise in the treatment of inherited retinal diseases."

Clinical • P1/2 data • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Signs of Functional Vision Recovery in an Advanced Stage RP Patient After Optogenetic Therapy (RS-LONDON 2020) - "GS030 is an investigational treatment combining a gene therapy and a medical device currently in clinical development to treat RP... This is the first reported case of functional recovery in a neurodegenerative disease after optogenetic therapy."

Clinical • CNS Disorders • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Organophosphate hydrolase interacts with ferric-enterobactin and promotes iron uptake in association with TonB dependent transport system. (PubMed, Biochem J) - "The E. coli GS030 cells having SfTonBDT system with OPH showed increased iron uptake. Such an increase was not seen in E. coli GS029, cells having SfTonBDT system generated either by omitting OPH or by including its variants, OPHD301A, OPHD301N suggesting a role for OPH in enhanced iron uptake."

Journal

Optogenetics in the Clinic: PIONEER, a Phase 1/2a Gene Therapy Program for Non-Syndromic Retinitis Pigmentosa (ARVO 2020) - "GS030 is an optogenetic treatment using a drug product (GS030-DP) with a medical device (GS030-MD) in clinical development to potentially restore vision function in RP patients independent of their underlying mutation...Optogenetics therapy is a vision restoration approach in clinical development to potentially restore vision function in RP patients independent of their underlying causative genetic mutation. PIONEER is the first clinical trial for RP combining the simultaneous action of a gene therapy targeting the inner retinal cells to encode a light-sensitive protein and a medical device encoding images of the visual scene to modulate an amplifying light source projected onto the genetically engineered retina."

P1/2 data