- The stock price of Lineage Cell Therapeutics, Inc. (NYSE American: LCTX) increased by over 8% during intraday trading today. This is why it happened.
The stock price of Lineage Cell Therapeutics, Inc. (NYSE American: LCTX) – a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs – increased by over 8% during intraday trading today. Investors are responding positively to the company reporting updated interim results from its ongoing, 24-patient Phase 1/2a clinical study of its lead product candidate OpRegen.
OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium (RPE) cells — administered in a single surgery to the subretinal space for the treatment of dry age-related macular degeneration (AMD) with geographic atrophy (GA). And these updated results include a minimum of 9 months of follow-up in all 12 patients treated in Cohort 4, which as a group had better baseline vision and smaller areas of GA at the baseline than earlier cohorts. In the study (N=24), OpRegen has been well-tolerated to date and there have been no new, unexpected ocular, or systemic adverse events or serious adverse events not previously reported.
OpRegen Phase 1/2a Interim Clinical Results
— Overall, 8/12 (67%) of the Cohort 4 patients’ treated eyes were at or above baseline visual acuity at their last assessment, based on per-protocol scheduled visits ranging from 9 months to over 3 years post-transplant. Conversely, 9/12 (75%) of the patients’ untreated eyes were below baseline visual acuity at that assessment.
— Improvement in best-corrected visual acuity (BCVA) reached up to +24 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart for a Cohort 4 patient.
— Comparing all treated eyes to all fellow (untreated) eyes showed an average difference of 10.8 letters read in Cohort 4 patients at their last assessment.
— In those Cohort 4 patients with a benefit in treated as compared with fellow eye (10/12), the average difference between treated and untreated eyes was 13.6 letters read at the last assessment, which exceeded 3 years post-transplant for some patients.
— Among the 6 Cohort 4 patients treated between September and November 2020, three (50%) continue to exhibit marked improvements in BCVA, ranging from +5 to +18 to +24 letters read at the patient’s last scheduled assessment, which was at least 9 months post-transplant.
— Among the other 3 Cohort 4 patients treated in the Fall of 2020, one patient showed a gain of +1 letter read and two patients measured -2 and -6 letters below baseline at their last assessment.
— Across the study, in patients with previously reported structural improvements in the retina, decreases in drusen density, and a trend toward slower GA progression in treated compared to untreated eyes have continued to be present.
— Evidence of durable engraftment of OpRegen RPE cells has extended to more than 5 years in the earliest treated patients, supporting the potential for OpRegen to be a one-time treatment.
Retinal Tissue Restoration Update
— 3 patients with evidence of retinal restoration and confirmed history of GA growth continue to demonstrate areas of retinal restoration as of their last per-protocol assessments, ranging from 9 months to 33 months following treatment.
— The first Cohort 4 patient with evidence of retinal restoration and confirmed history of GA growth, demonstrated zero growth in atrophy (GA) 33 months following treatment with OpRegen.
— The second patient with evidence of restoration of critical retinal structures showed a 10% reduction at approximately 8 months after treatment, as assessed by square root transformation (SQRT).
a.) Based on historical images of the patient’s treated eye taken ~2 years prior to treatment, the area of GA had increased from approximately 2.39 mm to approximately 2.81 mm at baseline.
b.) Following OpRegen transplantation, the atrophic lesion measured approximately 2.28 mm at the patient’s month 2 per-protocol assessment visit, which was smaller than the historical size of 2.39 mm from the image taken ~2 years prior to treatment.
c.) Additional follow-up showed the lesion size calculated as approximately 2.53 mm at the patient’s month 8 per-protocol assessment visit, which continued to be smaller than baseline.
— The third case of restoration demonstrated clinically meaningful improvements in visual acuity, having gained +18 letters on the ETDRS chart since OpRegen transplantation, supporting the view that the changes in retinal structure observable on Optical Coherence Tomography (OCT) can result in functional benefit.
As previously described, outer retinal layer restoration was observed using clinical high-resolution OCT. And to be considered as suggestive of retinal restoration, new areas of RPE monolayer with overlying ellipsoid zone, external limiting membrane, and outer nuclear layer — which were not present at the time of baseline assessment had to be present post-treatment with OpRegen. These findings — observed in 3 Cohort 4 patients — suggest integration of the new RPE cells with functional photoreceptors in areas that previously showed no presence of these cells. These effects were most prominent in the transitional areas around the primary area of atrophy. The use of OCT allows for a more precise determination of changes in retinal thickness, organization, and overall health of the retina in areas of potential atrophy, benefits which are possible with cell transplant therapy.
The loss of RPE cells over time creates progressively larger areas of atrophy in the adult retina — leading to impaired vision or complete blindness, a condition known as atrophic AMD. And humans lack the innate ability to regenerate retinal tissue and replace lost retina cells, which led to a presumption that progression of GA may someday be slowed or halted but could not be reversed. The unique findings from the ongoing OpRegen clinical study support a different view in which an RPE cell transplant can potentially replace or rescue retinal cells in patients who suffer from retinal lesions or degeneration. The totality of these findings supports the view that atrophic AMD is not an irreversible, degenerative condition and that some portion of diseased retinal tissue may be recoverable.
“I am particularly encouraged by the OCT findings in the second retinal restoration patient. Based on historical growth patterns, we knew this patient was a slower progressor than many other patients enrolled, and therefore less likely to benefit from treatment. Despite this, we have been able to demonstrate a reduction in the atrophic area as quickly as 2 months post-treatment and a marked slowing of disease progression. Further, even in patients with an incomplete coverage of OpRegen over the primary area of atrophy, we have observed resolution of not only lesions of iRORA (incomplete retinal pigment epithelial and outer retinal atrophy), but also resolution of areas with features of cRORA, which is a state of complete loss of the RPE and outer retinal tissue. Additionally, the structural benefits may help explain the improvement in visual acuity. I eagerly look forward to new data as they are collected.”
— Jordi Monés, M.D., Ph.D., Director of the Institut de la Màcula and Barcelona Macula Foundation
“While competing efforts are focused on reducing the growth rate of geographic atrophy, Lineage has reported several patients whose areas of atrophy have stabilized or reduced in size. These observations, which are present across clinically-meaningful periods, indicate a reversal of the degeneration of critical retinal tissue layers which support vision, consistent with the proposed mechanism of an RPE cell transplant. Importantly, all three of the patients exhibiting restoration had confirmed historic growth rate in these areas and these data have been collected using multiple imaging modalities. The durability of the improvements to visual acuity, when coupled with the clear structural improvements we’ve seen in patients which received fuller coverage of OpRegen across their GA, strongly suggest that cell therapy may be able to achieve therapeutic benefits that are beyond the reach of targeted drugs or antibodies. We are extremely pleased that our data is moving in a positive direction with each interim update we provide. We will continue to collect follow up data and work towards a meeting with FDA to discuss key aspects of our program. Our objective with OpRegen is to demonstrate the potential for allogeneic cell therapy to deliver the best available clinical outcomes and apply our technology to additional areas such as cancer, spinal cord injury, and other attractive opportunities.”
— Brian M. Culley, Lineage CEO
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