Oxford BioMedica
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A novel gene-based treatment for neovascular "wet" age-related macular degeneration (AMD).

Phase 1 trial complete.

"Wet" AMD

Age-related macular degeneration (AMD) affects an estimated 25 to 30 million people worldwide and the incidence of AMD is expected to triple by the year 2025 (source: AMD Alliance International) . The “wet” form of AMD, where the risk of severe sight loss is much greater, accounts for 10 – 15 per cent. of all AMD (source: AMD Alliance International). Wet AMD is responsible for 90 per cent. of cases of severe vision loss associated with AMD with up to 4.5 million patients worldwide (source: AMD Alliance International). Genentech’s drug LUCENTIS® is the market leader at present with sales in excess of US$4.2 billion per annum (source: Novartis/Roche actual sales for LUCENTIS® in 2013).

Our approach

RetinoStat® is a gene-based treatment for neovascular “wet” AMD and could also be used for diabetic retinopathy (DR). RetinoStat® aims to preserve and improve the vision of patients through anti-angiogenesis, the process of blocking the formation of new blood vessels. The product uses the Company’s LentiVector® platform technology to deliver two genes encoding the anti-angiogenic proteins endostatin and angiostatin directly to the retina by injection. This creates genetically modified cells at the injection site that act as endogenous factories for the two anti-angiogenic proteins which are then released locally and prevent disruptive vascularisation of the retina. As with all LentiVector® platform products the Company expects that only a single administration of RetinoStat® will be required, giving the product a significant market advantage over LUCENTIS® which requires injections into the eye to be repeated every 4-8 weeks.


Clinical status:

In a recently completed Phase I dose escalation safety study of RetinoStat® the primary end points of safety and tolerability at 6 months post-surgery were met. In the US, the study was led by Professor Peter Campochiaro at the Wilmer Eye Institute at Johns Hopkins, Baltimore and by Dr Andy Lauer at the Oregon Health and Science University, Portland, Oregon. Further information can be found by visiting http://clinicaltrials.gov/

The results of the Phase I study, which used the Group’s lentiviral vector technology, were announced in May 2015. The study, which was conducted with patients suffering from severe, late-stage, wet age-related macular degeneration (Wet AMD) met the primary endpoints of safety and tolerability and patients also showed signs of clinical benefit, with visual acuity stabilisation and a reduction in vascular leakage consistent with the mechanism of action of endostatin and angiostatin. The data from the Phase I study was published in the journal Human Gene Therapy.

The Phase I study was primarily designed to evaluate the safety and tolerability of RetinoStat® for the treatment of severe wet AMD following a single subretinal injection and represented the first time a lentiviral based vector had been administered to the human eye. Twenty-one subjects with highly fibrotic retinas who were refractory to anti-VEGF therapy following a prior responsive history were treated. As previously announced, the results of the Phase I study indicated that RetinoStat® met the primary endpoint of safety and tolerability. Importantly, therapeutic gene expression, measured in these patients as a secondary endpoint, was found to be dose-dependent and maintained at the last measurement (2.5 years in 8 subjects and >4 years in two subjects).

Market opportunity

The industry standard treatments for wet AMD and other related ocular conditions achieved global sales in excess of US$7.0 billion in 2013 (Source: Novartis, Roche, Regeneron). On the basis of pre-clinical data, it is anticipated that RetinoStat® may require only a single administration. If confirmed, this would give the product a significant advantage over currently available treatments in the market that require frequent, repeated administration.

Proof of concept

RetinoStat® has demonstrated clear proof-of-concept in industry standard animal models for “wet” AMD and these results have been published in the peer reviewed article: Balaggan et al. Gene Ther. 2006 Aug;13(15):1153-65. The ongoing Phase I clinical study is being led by Professor Peter Campochiaro at the Wilmer Eye Institute at Johns Hopkins, Baltimore (USA) with two other sites at the Oregon Health & Science University, Portland, USA and the University of Iowa, USA. Planned recruitment for the Phase I clinical trial has been completed. Highlights from the trial include long-term safety profile now up to 35 months post-treatment (dose level 1); successful retinal transduction, as shown by substantial increase in expression and secretion of endostatin and angiostatin proteins measured in the anterior chamber of the eye following a single administration of RetinoStat®; long-term protein expression now sustained for up to one year post-treatment for the first three cohorts; and preliminary data show a dose response, with the escalation to dose levels 2 and 3 yielding a proportional increase in average protein expression.

Key publications:
Balaggan et al. Gene Therapy (2006), 1–13: “EIAV vector-mediated delivery of endostatin or angiostatin inhibits angiogenesis and vascular hyperpermeability in experimental CNV”

K. Binley et al. Human Gene Therapy (2012), 23:980-991: "Safety and Biodistribution of an Equine Infectious Anemia Virus-Based Gene Therapy, RetinoStat®, for Age-Related Macular Degeneration"



The industry standard treatment for “wet” AMD and other related ocular conditions had global sales in excess of US$7 billion in 2013 (source: Novartis, Roche, Regeneron)

Normal vision

Normal vision

A scene as it might be viewed by a person with normal vision.
Courtesy: National Eye Institute, National Institutes of Health (NEI/NIH) Ref#:EDS01

Vision: AMD

Vision: AMD

A scene as it might be viewed by a person with age-related macular degeneration.
Courtesy: National Eye Institute, National Institutes of Health (NEI/NIH) Ref#: EDS05