Neurotech's product, NT-501, consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. NT-501 is designed to continually deliver a low, safe and therapeutic dose of CNTF into the back of the eye.

The Company is currently studying NT-501 in geographic atrophy (GA) associated with dry age-related macular degeneration (AMD) and in retinitis pigmentosa (RP). In March 2009, Neurotech announced positive results and the achievement of proof of concept in a Phase 2 clinical study of NT-501 for the treatment of GA. In May 2009, Neurotech announced in two Phase 2 clinical studies of NT-501 in early- and late-stage RP subjects a statistically significant and dose-dependent biological effect on the retina that appears to be neuroprotective. This finding was further confirmed in a select number of subjects observed over a 24-month period following implantation and for whom significant photoreceptor preservation was demonstrated. Due to these promising Phase 2 results, the Company is actively planning for the initiation of the next stage of NT-501 clinical studies for both GA and RP.

A total of 184 patients enrolled across three Phase 2 studies of NT-501 have reached at least 18 months post-implantation. No serious adverse events have been reported that are associated with either the surgical procedure or implant. In general, the surgical procedure has been well-tolerated. There have been no reported incidences of retinal detachment, no increase in intraocular pressure, no infection and no serious inflammation.

Phase 2 Dry Age-Related Macular Degeneration/Geographic Atrophy Trial
In March 2009, Neurotech announced that NT-501 substantially slowed the loss of vision in a Phase 2 clinical trial of 51 subjects with GA. In the study, the high dose of NT-501 stabilized best corrected visual acuity (BCVA) at 12-months, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group. The strong trend in visual acuity stabilization at 12 months was preceded by a dose-dependent, statistically significant (p<0.001 and p=0.013 for high and low dose, respectively) increase in retinal thickness as measured by optical coherence tomography (OCT) that was observed as early as four months post-implantation. The observed structural change is consistent with preclinical studies of NT-501 in which CNTF was shown to increase the thickness of the retina and the outer nuclear layer of photoreceptors responsible for vision. This increase in retinal thickness may be responsible for photoreceptor rescue and protection as observed in numerous animal models of retinal degeneration. Patients were also evaluated for an increase in best corrected visual acuity (BCVA). However, no increase was observed, likely due to existing photoreceptor damage.

The Phase 2 study was a randomized, multi-centered, double-masked, sham-controlled study designed to evaluate trends in efficacy and safety of NT-501. Patients received either a high or low dose NT-501 implant or a sham-treatment in one eye only. A trend in best corrected visual acuity (BCVA) was the primary efficacy endpoint of this study. Neurotech has received Fast Track designation for NT-501 for the treatment of visual loss associated with dry AMD from the U.S. Food and Drug Administration.

Phase 2 Retinitis Pigmentosa (RP) Trials
In May 2009, Neurotech announced the results of two Phase 2 trials of NT-501 for the treatment of visual loss associated with RP—one trial consisting of patients with earlier stage disease (60 patients) and the second trial consisting of patients with later stage disease (60 patients). Both trials were randomized, multi-centered, double-masked, sham-controlled dose ranging studies designed to evaluate the efficacy and safety of NT-501. Patients enrolled in these studies received either a high or low dose NT-501 implant in one eye and a sham-treatment in the other eye. Best corrected visual acuity (BCVA) was the primary efficacy endpoint for the late stage RP study and visual field sensitivity was the primary efficacy endpoint for the early stage RP study.

In both studies, there was a statistically significant (p<0.001 for the high dose group in each study), dose-dependent increase in retinal thickness involving photoreceptor layers as measured by optical coherence tomography (OCT). This statistically-significant effect is similar to that observed in the Phase 2 NT-501 GA study. However, at 12 months no trend in visual benefit was observed in either study for these functions nor was any change in visual function observed for either active or control study arms, likely due to the slow progression of the disease. RP patients in general have a gradual progression of vision loss, often over many years or decades.

Of note, in a separate study of a select number of patients from the earlier stage NT-501 RP trial, it was observed with objective measurement that there was a highly statistically significant preservation of photoreceptors over a 24-month period following implantation in those subjects treated with NT-501 compared with those in the sham control group.

The Company is currently developing plans for the next trials of NT-501 to assess photoreceptor preservation in a patient population with RP. Neurotech has received Orphan Drug designation and Fast Track designation for NT-501 for the treatment of visual loss in RP from the U.S. Food and Drug Administration.

Phase 1 Retinitis Pigmentosa Study
A Phase 1 clinical study of NT-501 for the treatment of retinal degeneration associated with RP was completed in 2005 and results were published in the March 7, 2006 issue of the Proceedings of the National Academy of Sciences (PNAS). The primary objective of the study was to investigate the safety of NT-501 implants designed to secrete two dosage levels of ciliary neurotrophic factor (CNTF) over a six month period of implantation in 10 late stage RP patients. Results confirmed that CNTF can be safely delivered into the vitreous cavity of the eyes of patients with RP and that the Encapsulated Cell Technology (ECT) device was well tolerated by all patients. Visual acuity showed improved but variable trends from baseline in the treatment group while in the control arm, visual acuity was essentially unchanged. These results also encouraged Neurotech to study NT-501 in patients with an advanced stage of dry AMD affecting central vision, known as geographic atrophy, because this type of cone photoreceptor degeneration was similar to that seen in the late stage RP patients enrolled in the Phase 1 study. Click here to view the full text PNAS article containing the Phase 1 data.