OpRegen®

OpRegen® is currently being evaluated in a Phase 1/2a open-label, dose escalation safety and efficacy study of a single injection of human retinal pigment epithelium cells (RPE cells) derived from an established pluripotent cell line and transplanted subretinally in patients with advanced dry AMD with GA. In November 2020, Lineage announced the completion of patient enrollment in this study.

In June 2021, Lineage reported that restoration of retinal tissue has now been observed in three patients enrolled in the Company’s Phase 1/2a study of OpRegen. Outer retinal layer restoration, which was observed using clinical high-resolution Optical Coherence Tomography (OCT), was evidenced by the presence of 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. These findings suggest integration of the new RPE cells with functional photoreceptors in areas that previously showed no presence of any of these cells. These effects were most prominent in the transitional areas around the primary area of GA. In addition to positive anatomical changes, all three patients’ visual acuity increased above baseline levels within 6 months post-transplant. 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.

Updated interim results from the ongoing Phase 1/2a study were reported at the 2021 Association for Research in Vision and Ophthalmology Annual Meeting (ARVO 2021) on May 1, 2021 by Christopher D. Riemann, M.D., Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institute and University of Cincinnati School of Medicine.

Dry AMD RPE degeneration and drusen accumulation

Image adapted from scienceofamd.org

The potential benefits of replacing RPE cells include:

  • RPE organization
  • Drusen reduction
  • Photoreceptor recovery
  • Preserved or improved sight

The FDA has granted OpRegen with Fast Track Designations and, as such, is on an expedited regulatory path that includes the ability for increased interfacing with the FDA during clinical development and enhanced favorability for marketing approval.

Clinical Data

2021 ARVO Presentation OpRegen Data Overview

At ARVO 2021, additional data were presented on 24 patients enrolled in the study, including all 12 patients treated in Cohort 4, which have better baseline vision and smaller areas of GA than earlier cohorts. Updated results presented at ARVO 2021 included a minimum of 4.5 months of follow-up in all 24 patients treated with OpRegen. Nine of twenty-four patients were treated with the “thaw and inject” formulation of OpRegen, two via a standard pars plana vitrectomy (PPV) and seven utilizing the Orbit™ Subretinal Delivery System (Orbit SDS).

Overall, 10/12 (83%) 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 4.5 months to approximately 3 years post-transplant. Improvements in best corrected visual acuity (BCVA) for Cohort 4 patients reached up to +19 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In contrast, 10/12 (83%) of the patients’ untreated eyes were below pre-treatment baseline values at the same time points. Among the newly reported data, three (50%) of the more recently treated Cohort 4 patients exhibited marked improvements in BCVA ranging from +7 to +16 letters at their last scheduled assessments of at least 4.5 months. Two additional Cohort 4 patients experienced a gain of 2 letters from their baseline values. One Cohort 4 patient measured 7 letters below baseline. Previously reported structural improvements in the retina, decreases in drusen density, and a trend toward slower GA progression in treated compared to untreated eyes continued. Overall, OpRegen has been well tolerated with no unexpected adverse events or serious adverse events, and evidence of durable engraftment of OpRegen RPE cells have extended to more than 5 years in earliest treated patients, supporting the potential for OpRegen to be a one-time treatment.

As part of an ongoing effort to administer the minimally effective dose and duration of immunosuppressive therapy, immunosuppression was utilized only during the perioperative period of approximately 3 months in Cohort 4 patients. One patient received a modified immunosuppressive regimen at baseline, which included no tacrolimus and only mycophenolate mofetil. One patient was diagnosed with COVID-19 shortly after treatment for whom all immunosuppression was halted and reinstated once the patient was asymptomatic. Both patients showed no signs of acute or delayed inflammation or rejection of OpRegen cells with 4.5 months of post-transplant follow up. Other than the reduced regimens described above, immunosuppressants have been discontinued as scheduled, typically within 90 days post-operatively, and no cases of acute or delayed rejection or inflammation due to OpRegen have been reported in any patients treated with OpRegen.

About the Phase 1/2a Clinical Study

OpRegen is currently being evaluated in a Phase 1/2a open-label, dose escalation safety and efficacy study of a single injection of human retinal pigment epithelium cells derived from an established pluripotent cell line and transplanted subretinally in patients with advanced dry AMD with GA. The study enrolled 24 patients into 4 cohorts. The first 3 cohorts enrolled only legally blind patients with BCVA of 20/200 or worse. The fourth cohort enrolled 12 better vision patients (vision from 20/65 to 20/250 with smaller areas of GA). Cohort 4 also included patients treated with a new “thaw-and-inject” formulation of OpRegen, which can be shipped directly to sites and used immediately upon thawing, removing the complications and logistics of having to use a dose preparation facility. The primary objective of the study is to evaluate the safety and tolerability of OpRegen as assessed by the incidence and frequency of treatment emergent adverse events. Secondary objectives are to evaluate the preliminary efficacy of OpRegen treatment by assessing the changes in ophthalmological parameters measured by various methods of primary clinical relevance. Additional objectives include the evaluation of the safety of delivery of OpRegen using the Orbit SDS. OpRegen is a registered trademark of Cell Cure Neurosciences Ltd., a majority-owned subsidiary of Lineage Cell Therapeutics, Inc. The Orbit subretinal delivery system is used under agreement with Gyroscope Therapeutics Limited. Orbit and Orbit SDS are trademarks of Gyroscope Therapeutics Limited.

Market Opportunity

AMD affects more than 30 million people worldwide and approximately 1.6 million people are newly diagnosed annually in the U.S.1 It is a leading cause of vision loss in people over the age of 60 in the developed world. There are two forms of AMD: “wet AMD,” which affects only 10% of patients and “dry AMD,” which affects 90% of patients.2 Currently, there are only two FDA-approved therapies for the less common wet AMD, yet they constitute an estimated market of more than $10 billion.3

There are no FDA approved medical therapies for the 90 percent of AMD patients who suffer from the dry form. We believe one of the most promising future therapies for dry AMD is the replacement of the layer of damaged RPE cells that support and nourish the retina.

AMD Market

Sources: (1) Pennington and DeAngelis, Eye and Vision, 2016 3:34; (2) JM Seddon, Epidemiology of age-related macular degeneration. (AP Schachat, S Ryan eds.) Retina, 3rd ed. St. Louis, MO: Mosby; 2001;1039-50 and (3) 2018 product sales summary based on publicly reported revenue figures for Lucentis and Eylea.

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