Retinostat (OXB-201) / Oxford Biomedica - LARVOL DELTA

[VIRTUAL] Generation of a Lentiviral Based Gene Therapy Vector for the Treatment of Neovascular Age-Related Macular Degeneration (nAMD) (ASGCT 2021) - P1 | "Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that is known to have a key role in the development of nAMD and anti-VEGF treatments such as Aflibercept, Ranibizumab and Bevacizumab are the current standard of care for this disease...As such, we have developed an EIAV (OXB-203E) and HIV (OXB-203H) lentiviral vector encoding Aflibercept for the treatment of nAMD.Clinical data from RetinoStat®/OXB-201, a predecessor EIAV (equine infectious anaemia virus) gene therapy vector for the treatment of nAMD, expressing endostatin and angiostatin, demonstrated that following a single subretinal injection of this vector in patients, there was stable, long term expression of the transgenes in the aqueous humour out to 6 years, providing proof-of-principle for this type of single-injection gene therapy approach (NCT01301443 (Phase I GEM study) and NCT01678872 (follow-up study)).OXB-203 is the successor to our nAMD programme...In a preclinical study using..."

Age-related Macular Degeneration • Anemia • Complement-mediated Rare Disorders • Gene Therapies • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

OXB-204: A Lentiviral Vector-based Gene Therapy Approach to Treat Leber Congenital Amaurosis 10 Due to Mutations in CEP290 (ARVO 2020) - "Building on our clinical data from OXB-201, (Campochiaro et al, 2017) which demonstrated long term transgene expression out to 6 years following a single subretinal administration to patients, CEP290 was cloned into the same clinical vector backbone driven by a constitutive CMV promoter.Results Lentiviral vectors were generated and shown to express the full length CEP290 protein. To demonstrate CEP290-dependent cilia defects, endogenous expression of CEP290 in ARPE-19 was knocked down using CEP290-specific shRNA. Rescue of the cilia defects obtained in the ARPE-19 CEP290-knock down cells with OXB-204 was achieved.Conclusions OXB-204, a lentiviral vector encoding a full-length copy of human CEP290 was capable of rescuing CEP290-knock down cilia defects in vitro."

OXB-203, a lentiviral vector expressing aflibercept as a single dose, long-term treatment for wet Age-Related Macular Degeneration (ARVO 2020) - "A number of anti-VEGF therapeutic strategies have been developed and are the current standard of care, including aflibercept, ranibizumab and bevacizumab. However, development of new treatments are necessary as current anti-VEGF treatments are only effective for 1-2 months and as such require frequent injections for an extended period of time causing a significant burden to patients and are associated with side effects such as inflammation, haemorrhage and retinal detachment.Methods Clinical data from OXB-201, our first-generation treatment for wet AMD (equine infectious anemia virus (EIAV)-endostatin and angiostatin) program (Campochiaro et al, 2017) demonstrated that following a single subretinal injection of the vector in patients, there is stable long term expression of the transgenes out to 6 years providing proof-of-principle for this type of single-injection gene therapy approach...In vitro angiogenesis assays demonstrated that both cell proliferation and tubule..."

OXB-203, a Lentiviral Vector Expressing Aflibercept as a Single Dose, Long-Term Treatment for Wet Age-Related Macular Degeneration (ASGCT 2019) - "...A number of anti-VEGF therapeutic strategies have been developed and are the current standard of care for wet AMD, including aflibercept, ranibizumab and bevacizumab...Clinical data from our Retinostat® (EIAV-endostatin and angiostatin) program (Campochiaro, 2017) following a single subretinal injection in three US clinical sites has demonstrated stable long term expression of the transgenes out to 6 years (so far) providing proof-of-principle for this type of single injection gene therapy approach...In vitro angiogenesis assays in HUVEC cells demonstrated that both cell proliferation and matrigel tubule formation were significantly inhibited with vector derived aflibercept similar to that of recombinant aflibercept. Preclinical studies using a rat choroidal neovascularization model following a subretinal administration of EIAV-aflibercept vector are ongoing."