Retinitis pigmentosa is a group of hereditary diseases of the eye that lead to progressive loss of vision due to cells in the retina becoming damaged and eventually dying.

Pre-clinical studies carried out in disease models by the our academic collaborators have demonstrated that, when transplanted into the retina, our hRPC technology has the potential to preserve existing photoreceptors, potentially reducing or halting further deterioration of vision. In addition, these hRPC cells have been shown to mature into functional photoreceptors that are capable of becoming engrafted into the photoreceptor layer.

A Phase I/IIa clinical trial in RP subjects is currently ongoing in the US. This study which has been conducted at three sites – Massachusetts Eye and Ear Infirmary in Boston, Retinal Research Institute in Phoenix and Casey Eye Institute, Oregon  – is an open-label, dose escalation study to evaluate the safety, tolerability and preliminary efficacy of a single, sub-retinal injection of the hRPC stem cell therapy candidate in patients with advanced RP. Approval has now been obtained from the MHRA and the Spanish Regulatory Agency to open sites in the UK and Spain – the Oxford Eye Hospital, with Professor Robert MacLaren as Principal Investigator and the Institut de la Màcula, Barcelona, with Dr Jordi Mones as Principal Investigator.

The primary endpoint of the study is safety, with patients being followed up for 12 months post-treatment, which includes measurements of visual acuity.  Expansion into the Phase IIa element of this study involves subjects with some retinal functionality, in contrast to the very poor vision and lack of potential for improvement of the subjects in the Phase I.

In October 2019, positive interim efficacy data from patients treated in the Phase 2a segment of the ongoing Phase 1/2 study were announced by the Company and subsequently presented by Dr. Pravin Dugel at the American Academy of Ophthalmology Meeting in San Francisco.  The data showed a group of subjects who had had a successful surgical procedure with sustained clinically relevant improvements in visual acuity compared with baseline, as measured by the number of letters read on the ETDRS chart (the standardised eye chart used to measure visual acuity in clinical trials).

In June 2020 (and updated in November 2020), subsequent long-term efficacy data from the study continued to show a meaningful clinical effect from the therapy at all time points out to twelve months post-treatment.  The degree of efficacy observed varies between patients, with mean results as set out in the table below:

Months post-treatment Mean change from baseline in visual acuity in treated eye* Mean change from baseline in visual acuity in untreated eye* Difference in mean change between treated eye and untreated eye*
1 +7.9 letters (n=9) + 0.2 letters (n=9) + 7.7 letters  (n=9)
2 +8.0 letters (n=9) + 1.2 letters (n=9)   + 6.8 letters (n=9)
3 +10.8 letters (n=9) + 4.4 letters (n=9)   + 6.4 letters (n=9)
6 +9.6 letters (n=9) + 3.4 letters (n=9)   + 6.2 letters (n=9)
9 +7.1 letters (n=8) + 1.2 letters (n=8) + 5.9 letters (n=8)
12 +9.9 letters (n=7) – 3.2 letters  (n=7)   + 13.1 letters (n=7)

* In patients with a successful surgical procedure

An improvement of + 23 letters is equivalent to reading an additional four lines of letters on the ETDRS eye chart, the standardised eye chart used to measure visual acuity in clinical trials.  An improvement of at least + 15 letters from baseline on the ETDRS chart is considered to be clinically meaningful by the US Food and Drug Administration (FDA), as stated in their recent guidance on gene therapy for retinal disorders.  As a comparator, the difference between a patient with 20/20 vision and 20/200 vision (the latter being the legal definition for blindness in terms of central visual acuity) would be the equivalent of being able to read an extra ten lines on the ETDRS chart.

The Company has received regulatory approval to expand the Phase IIa study in RP patients. The Company is treating patients under the revised approved study protocol, but announced in June 2021 that dosing was temporarily suspended. Following necessary approvals, the study was then reopened in the US, UK and Spain. Five out of nine patients have now been treated under the revised approved study protocol. On this basis, the Company expects to present further data from the expanded Phase 2a clinical trial in Q1 2022 and, subject to having sufficient data from the study, this should enable it to seek approval in 2022 to commence a single pivotal clinical study with its hRPC cell therapy candidate in RP.

For an article published by the Foundation for Fighting Blindness regarding this trial click here..