HBL Hadasit Bio-Holdings Ltd., and Cell Cure Neurosciences Ltd. (Cell Cure) announced that Cell Cure has filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) seeking to initiate a phase I/IIa clinical trial of OpRegen in patients with geographic atrophy (GA), the advanced stage of the dry form of age-related macular degeneration (dry-AMD).

OpRegen consists of retinal pigment epithelial (RPE) cells derived from human embryonic stem cells and is intended to be administered as a single dose into the subretinal space of patients’ eyes in order to treat this leading cause of visual impairment.

The design of the proposed clinical trial, “Phase I/IIa Dose Escalation Safety and Efficacy Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Transplanted Subretinally in Patients with Advanced Dry-Form Age-Related Macular Degeneration with Geographic Atrophy,” is based on a pre-IND meeting with the FDA.. Patients will undergo a single transplantation and the study will explore three different doses of OpRegen. Following transplantation, the patients will be followed over 12 months at specified intervals and then at longer time periods, to evaluate the safety and tolerability of the product. A secondary objective of the clinical trial will be to explore the ability of transplanted OpRegen to moderate the disease progression.

“The filing of this IND is the culmination of 12 years of research and development starting at the Hadassah Human Embryonic Stem Cell Research Center at Hadassah University Medical Center, Jerusalem, Israel, under the direction of Prof Benjamin Reubinoff, and continuing at Cell Cure Neurosciences Ltd.,” said Charles Irving, Cell Cure’s CEO. “We look forward to initiating the clinical trial that will, for the first time, utilize xeno-free grade human embryonic stem cell derived RPE cells with high purity and potency, for the treatment of geographic atrophy, the most advanced stage of dry-AMD, age-based.”   

Age-related macular degeneration (AMD) is the leading  eye disease, age based, that is responsible for visual impairment of older persons in the US, Europe and Australia. AMD affects the macula, which is the part of the retina responsible for sharp, central vision that is important for facial recognition, reading and driving. There are two forms of AMD. The dry form (dry-AMD) advances slowly and painlessly until it progresses to the advanced form called geographic atrophy (GA). Once the atrophy reaches the fovea (the center of the macula), patients lose their central vision and may develop legal blindness. There is currently no effective treatment for dry-AMD. There are about 1.6 million new cases of dry-AMD in the US annually. About 7.3 million people in the US are at advanced stages of the disease, at least in one eye. The yearly economic loss to the gross domestic product in the United States from dry-AMD has been estimated to be $24.4 billion. The market opportunity for a treatment for GA has been estimated at over $5 billion globally. About 10% of patients with dry-AMD develop wet-AMD, which is an acute disease and can lead to visual loss in a matter of weeks. Wet-AMD can be treated with currently-marketed VEGF inhibitors such as Lucentis or Eylea, however, such products typically require frequent repeated injections in the eye, and patients often continue to suffer from the continued progression of the underlying dry-AMD disease process. The root cause of the larger problem of dry-AMD is believed to be the dysfunction of RPE cells. One of the most exciting therapeutic approaches to dry-AMD is the transplantation of healthy, young RPE cells to support and replace the patient’s old degenerating RPE cells and to head off the advancing atrophy before it reaches the fovea. One of the most promising sources of healthy RPE cells is cells derived from pluripotent stem cells.

Cell Cure's OpRegen consists of RPE cells that are produced using a proprietary process that drives the differentiation of human embryonic stem cells into high purity RPE cells. OpRegen is also “xeno-free," meaning that no animal products were used either in the derivation and expansion of the human embryonic stem cells or in the directed differentiation process.. OpRegen is formulated as a suspension of RPE cells. Preclinical studies in mice have shown that following a single subretinal injection of OpRegen as a suspension of cells, the cells can rapidly organize into their natural monolayer structure and survive throughout the lifetime of the animal. OpRegen will be an “off-the-shelf” allogeneic product provided to retinal surgeons in a final formulation ready for transplantation. Unlike treatments that require multiple injections into the eye, such as currently-marketed products like Lucentis and Eylea for wet-AMD, it is expected that OpRegen would be administered in a single procedure.

Cell Cure Neurosciences Ltd. was established in 2005 as a subsidiary of ES Cell International Pte. Ltd. (ESI), now a subsidiary of BioTime, Inc. Cell Cure’s second largest shareholder is HBL- Hadasit Bio-Holdings. Cell Cure is located in Jerusalem, Israel on the campus of Hadassah Medical Center.

HBL- Hadasit Bio-Holdings Ltd. (HBL) was established and issued by HADASIT (the technology transfer company of the Hadassah University Hospital) in 2006 with the aim to promote the knowledge and experience gained from the research laboratories of Hadassah Medical Center.

BioTime is a biotechnology company engaged in research and product development in the field of regenerative medicine.