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.

Updated interim results from the ongoing Phase 1/2a study were presented at the 2020 American Academy of Ophthalmology Annual Meeting during the OP02V Retina, Vitreous Original Papers Session on November 15, 2020 by Christopher D. Riemann, M.D., Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institute and University of Cincinnati School of Medicine. Lineage also hosted a therapeutic expert call to discuss the interim results on November 17, 2020.

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.

Dry AMD RPE degeneration and drusen accumulation

Image adapted from scienceofamd.org

Clinical Data

OpRegen® is currently being tested in a Phase 1/2a clinical trial for the treatment of dry AMD with GA. OpRegen® is a cell-based product composed of retinal pigment epithelial (RPE) cells, derived from human embryonic stem cells (hESC) and administered as a cell suspension in ophthalmic Balanced Salt Solution Plus (BSS Plus).

OpRegen Data Update & Highlights from the 2020 American Academy of Ophthalmology Presentation Announced November 16, 2020

(data presented on 20 patients, dosed through October 5, 2020)

  • Continued progressive functional improvement.
    • In Cohort 4, 6 out of 7 (86%) of patients’ treated eyes measured above their baseline vision (Best Corrected Visual Acuity, or BCVA) at 12 months, a clinically relevant timeframe, or as of the longest available timepoint less than 12 months (data collection continues for more recently-treated patients).
    • Data to date demonstrate a localized slowing of GA progression in the treated areas with a trend towards slower GA growth in treated versus fellow eyes in pooled analyses.
  • Long-term engraftment is supported with imaging observations up to more than 4 years, even with a short immunosuppression regimen.
    • In all Cohort 4 patients receiving OpRegen TAI formulation, per protocol, immunosuppressants have been discontinued as scheduled, typically within 90 days post-operatively, and no cases of acute or delayed rejection or inflammation have been reported.
    • One Cohort 4 patient was treated only with mycophenolate mofetil and received no tacrolimus for immunosuppression.
  • Anatomical restoration of retinal tissue.
    • A Cohort 4 patient with evidence of retinal restoration and confirmed history of GA growth, which was first reported at 9 months, continues at month 23 to have an area of GA smaller than at baseline.
    • This patient also experienced additional improvement in BCVA from 9 to 23 months post-treatment, while the untreated eye has experienced further reduction in visual acuity.
    • Long-term monitoring on this patient is expected to continue.
  • Treatment overview.
    • As of October 5, 2020, 16 patients were treated via pars planar vitrectomy (PPV), while 4 were treated with the Gyroscope SDS.
    • As of November 10, 2020, 17 patients were treated via PPV, while 7 were treated with the Gyroscope SDS.
    • Enrollment in the phase 1/2a study is complete; follow-up continues for safety and efficacy.
  • Safety and tolerability.
    • The primary objective of the study is to evaluate the safety and tolerability of OpRegen at 12 months, and in patients which have reached this time point OpRegen appears well tolerated.
    • There have been no unexpected adverse events (AEs) or treatment-related systemic serious AEs reported in enrolled patients.
    • The most common and expected ocular AEs were the formation or exacerbation of mild to moderate epiretinal membranes (ERMs) and a single report of a retinal detachment, with cause unknown (all occurring in patients receiving OpRegen via the PPV route of administration).
    • The Gyroscope SDS is an alternative to the PPV route and is designed to avoid ERM formation.
      • Through October 2020, 16 patients were treated via PPV while 4 were treated with the Gyroscope SDS. ERMs were observed in 13 PPV patients.
      • One patient treated with the Gyroscope SDS developed a mild choroidal neovascularization (CNV) at the site of needle penetration 6 months post-treatment which was successfully treated with a single dose of an approved anti-VEGF agent. The cause was unknown.
      • One patient treated via PPV developed a mild CNV at > 24 months post-treatment.
    • Other changes observed following OpRegen treatment persisted through the last time point examined (> 4 years in some patients), including subretinal pigmentation and hyper-reflective areas seen on optical coherence tomography (OCT).
  • Visit our Media page for a replay of our therapeutic expert call to discuss the interim results, hosted on on November 17, 2020.

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 best corrected visual acuity (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. In total, 17 patients were treated via PPV, while 7 were treated with the Gyroscope SDS.  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. Additionally, for the patients in Cohort 4 that receive subretinal delivery of OpRegen utilizing the Gyroscope SDS, objectives will include the evaluation of the safety of delivery of OpRegen using the Gyroscope SDS.

OpRegen is a registered trademark of Cell Cure Neurosciences Ltd., a majority-owned subsidiary of Lineage Cell Therapeutics, Inc.

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.

Subretinal Delivery Partnership

Typical retinal delivery technique

In January 2019, Lineage entered into an exclusive partnership with Gyroscope Therapeutics (formerly Orbit Biomedical, Ltd.) to assess their approved Subretinal Delivery System, a vitrectomy-free delivery device for administration of OpRegen® within the ongoing Phase I/IIa clinical trial.

Orbit subretinal delivery technique using cannula resulting in stable bleb and no retinotomy

Gyroscope subretinal delivery

Many of the adverse effects that are observed in subretinal procedures are related to the delivery technique utilized during the surgery. The Gyroscope Subretinal Delivery System allows for access to the subretinal space via a suprachroidal approach without creating a hole in the retina and compromising its structural integrity. We believe that the use of this device could dramatically decrease the number of adverse effects as well as significantly improve dose control of cells in our clinical trials.

Lineage dosed its first patient with the Gyroscope Subretinal Delivery System in July 2019.

OpRegen is comprised of specialized retina cells which were derived from a cell line that is listed on the National Institutes of Health (NIH) Registry and are eligible for use in NIH funded research.

View our pipeline to see our other programs in development.