Gene Therapy in Ophthalmology Update 14: Early Positive Results in Ongoing Gene Therapy Wet AMD and Stargardt’s Disease Studies

Last week, Oxford BioMedica and its partner Sanofi announced positive results in their ongoing gene therapy clinical trials for wet AMD and Stargardt’s disease. In an interim review of their Phase I (RetinoStat) and Phase I/IIa (StarGen) trials, the Data Safetly Monitoring Board (DSMB), an independent panel of specialists in the fields of ophthalmology, virology and vectorology, gave the go ahead to proceed to a final patient cohort in the Phase I study in the case of the RetinoStat trial, and to a third patient cohort in the Phase I/IIa study of the StarGen trial.

The companies announced the following:

DSMB highlights of ongoing RetinoStat Phase I study:

● Nine patients treated to date (n=3 at each of dose levels 1, 2 and 3)

● No serious adverse events related to RetinoStat or its method of administration

● Long-term safety profile now up to 18 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. So far, expression is sustained for up to 12 months post-treatment at dose level 1 (n=3) and up to six months post-treatment at dose level 2 (n=3) (The extent of the followup to date on dose level 2. Longer term results are expected to be achieved.)

● DSMB support received to proceed to final patient cohort (n=9, confirmatory dose level)

The RetinoStat open label, dose escalation Phase I study will enrol 18 patients total with"wet" AMD and will evaluate three dose levels to assess safety and aspects of ocular physiology.

The study is led by Professor Peter Campochiaro at the Wilmer Eye Institute at Johns Hopkins, Baltimore and Oxford BioMedica has now opened a second clinical site at the Oregon Health and Science University, Portland with Dr Andy Lauer as principal investigator.

Further results from this study are expected in Q4 2012.

On the basis of pre-clinical data, it is anticipated that RetinoStat may require only a single administration which would give the product a significant advantage in the market over currently available treatments that often require frequent, repeated administration.

DSMB highlights of ongoing StarGen Phase I/IIa study:

● Eight patients treated at dose level 1 to date (n=4 severe level of disease, n=4 less severe)

● No serious adverse events related to StarGen or its method of administration

● Long-term safety profile now up to 12 months post-treatment (dose level 1)

● DSMB support received to proceed to third patient cohort (n=4, dose level 2)

The StarGen open label, dose escalation Phase I/IIa study will enrol up to 28 patients and will

evaluate three dose levels for safety, tolerability and aspects of biological activity.

In the US, the study is led by Professor David Wilson at the Oregon Health and Science University, Portland, Oregon. In France, Professor Jose-Alain Sahel leads the study at Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris.

StarGen has received European and US Orphan Drug Designation which brings development, regulatory and commercial benefits.

Further results from this study are expected in Q4 2012.

As noted above for the RetinoStat treatment, on the basis of pre-clinical data, it is anticipated that a single application of StarGen to the retina could potentially either provide long-term or permanent correction. There are currently no approved treatments available for Stargardt disease.

John Dawson, Chief Executive Officer of Oxford BioMedica, said:"The continued progress of our ophthalmology portfolio, supported by another positive DSMB review, is encouraging - particularly given that early RetinoStat data demonstrate sustained therapeutic protein expression in the eye following a single administration. The favourable safety profile of our novel ocular gene therapies further supports the wider LentiVector platform safety package with over 33 patients treated to date across the ocular and Parkinson's disease programmes."