Stem cell therapy for retinal disorders to enter clinical trials

MARLBOROUGH, Mass.—Advanced Cell Technology Inc. (ACT), has entered into a memorandum of understanding with Roslin Cells LTD of Scotland, in which the two companies will work to establish a bank of Good Manufacturing Practice (GMP)-grade human embryonic stem cell (hESC) lines using ACT's proprietary "single-blastomere" technique for deriving embryonic stem cells without damage to the embryo.

"Until we developed our single blastomere technology, embryonic stem cell research had been synonymous with the destruction of human embryos," states Dr. Robert Lanza, chief scientific officer at ACT, recalling that then-President George W. Bush was vocally opposed to such research as a result. "In stark contrast to embryonic stem cell lines currently available for research, such as those on the NIH registry, our single-blastomere technique does not destroy the embryo. One of the benefits of an ability to create new hESC lines without destroying embryos is that it addresses ethical concerns of certain researchers."

The company's single-blastomere technique relies on isolating a single cell from a four- to eight-cell embryo utilizing a one-cell biopsy approach similar to that used in pre-implantation genetic diagnostics (PGD). According to recent literature, one-cell biopsy as part of PGD is carried out routinely around the world, and 1,000 to 2,000 children are born every year in the United States and Europe after being conceived by in-vitro fertilization using one-cell biopsy and PGD.

"The availability of our 'embryo-safe' hESC lines has sparked interest in many quarters, including institutions that have been opposed to conducting embryonic stem cell research in the past," Lanza observes. "We are exploring opportunities to provide our cells to those institutions."

First up, however, will be a 12-patient, multicenter Phase I/II clinical study to treat dry age-related macular degeneration (AMD) using retinal pigment epithelial (RPE) cells derived from hESCs. For that purpose—and to treat Stargardt disease, which causes juvenile blindness—the U.S. Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application.

Dry AMD is the most common form of macular degeneration in the world, affecting 10 to 15 million Americans. There are currently no treatments available for this prevalent disease of an aging global population. Supporting studies in rats and mice have shown promising restoration of cones and rods using RPE cells derived from hESCs. GMP-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose dependent fashion without teratoma formation or untoward pathological reactions. The collaboration contemplates that the hESC lines will be created and stored using protocols that meet the regulatory standards of the European Medicines Agency (EMA) and the FDA. Roslin Cells will be responsible for maintaining the banked hESC lines, which will be made available for both research and commercial purposes.

By utilizing GMP and careful characterization and documentation of the resulting hESC lines, it is intended that the banked hESC lines will be suitable to move readily from laboratory settings into clinic programs, thereby speeding translational research into human treatments. Predictability in price and commercialization terms is a key feature of the goals of the collaboration. Roslin Cells will promote access to the hESC lines from the bank as research reagents to both academic and commercial entities.

In addition, ACT and Roslin Cells will publish a commercialization license so that third parties will have a reasonable and predictable path to commercialization of products using the same hESC lines that they may use in animal model studies for preclinical data. Commercialization licenses will also provide access to the cell lines' biologics master file in order to establish regulatory compliance. Proceeds from commercialization licenses, including milestone and royalty payments, will e shared between ACT and Roslin Cells.

"The relationship with Roslin Cells has grown out of our initiatives in Europe over the past year, and comes as part of our close efforts with the Scottish Development agency. Along with the recent announcement of our European Orphan drug designation filing in our Stargardt's disease treatment program, the relationship with Roslin Cells signals the expansion of our commercial initiatives in Europe, and, more broadly, markets around the world," says ACT Interim Chairman and CEO Gary Rabin. "Through the creation of hESC lines derived using our proprietary 'embryo-safe' technique, we fully expect Roslin Cells to quickly become a leading hESC bank for Europe, North America and Asia. We foresee major demand for these embryonic stem cells from both researchers and commercial interests."