Cell therapy – especially beta cell regeneration – is one of the hottest areas of exploration for treating, and potentially curing, type 1 diabetes.

Some existing efforts include partnerships between Paris-based Sanofi SA and Evotec AG, of Hamburg, Germany, as well as endeavors by companies such as Cambridge, Mass.-based Semma Therapeutics Inc. – it boasts a strategic partnership with Novartis AG, of Basel, Switzerland – and San Diego-based Viacyte Inc., which counts Johnson & Johnson (J&J), of New Brunswick, N.J., as an investor. (See BioWorld Today, Aug. 10, 2015, March 25, 2015, and July 11, 2013.)

Nearly four years ago, Orgenesis Inc. stepped into the fray by securing rights to commercialize functional autologous insulin-producing cell regeneration technology in a licensing deal with Israel's Tel Hashomer Medical Research, Infrastructure and Services Ltd. The licensed portfolio was based on two decades of research by Sarah Ferber, director of the molecular endocrinology unit at the Centre for Stem Cells, Regenerative Medicine and Tissue Engineering at Sheba Medical Center in Tel Hashomer and associate professor of human genetics and molecular medicine at Tel-Aviv University's Sackler School of Medicine.

Ferber is thought to be the first researcher to demonstrate the possibility of using the liver to generate functional insulin-producing cells. Orgenesis is advancing that concept in a therapeutic approach the company calls autologous insulin producing (AIP) cell transplantation.

The goal is to create functional tissues from a patient's existing organs, thus circumventing issues associated with pancreas islet transplantation, such as the risk of rejection associated with donor tissue, explained Vered Caplan, Orgenesis' interim CEO.

More than a dozen scientific publications by Ferber and colleagues validated the concept scientifically, Caplan said, and the company's proof-of-concept studies demonstrated the capacity to induce a shift in the developmental fate of cells in liver and convert them into pancreatic beta cell-like cells, both in vivo in mice and in vitro in cells from some 70 human liver biopsies.

The goal now is to move studies into the clinic, a milestone the company hopes to achieve this year.

Orgenesis already developed a protocol for the process, which begins with a liver biopsy to collect a small amount of tissue that is subsequently propagated in vitro, expanding the number of available cells from about 1 million to 2 billion. The liver cells next are manipulated by the therapeutic agent PDX-1, potentially along with other growth and differentiation factors, to produce insulin and secrete it in a glucose-regulated manner. In the final step, the insulin-producing trans-differentiated liver cells are returned to the patient through standard infusion. The process takes about six weeks.

"This is a unique approach that we hope will provide a cure for diabetes," Caplan told BioWorld Today, noting that the process doesn't require any type of external medical device or the use of embryotic or placental stem cells.

Still, regulatory authorities want to see demonstration of good manufacturing processes for the cell-based therapy before approving human trials, "and we have been working extensively in that area," Caplan said.

TIME 'TO THINK OF A CURE AS A POSSIBILITY'

A year ago, Orgenesis inked an agreement to acquire Masthercell – parent organization of Masthercell SA and Cell Therapy Holding SA, of Gosselies, Belgium – which specializes in the industrialization of cell-based therapeutics, in exchange for approximately $24.6 million in Orgenesis common shares. That transaction was finalized in December when Orgenesis secured a $10 million financing, a condition for completing the acquisition.

Masthercell continues to function as a separate company, but the deal gives Orgenesis "our own GMP facility and our own GMP manufacturing capabilities," Caplan said. Once validation of the cell therapy product is complete, the company plans to launch clinical trials.

Germantown, Md.-based Orgenesis also has a three-year collaboration with the Global Stem Cell and Regenerative Medicine Acceleration Center of Korea and a cell therapy product development memorandum of understanding with Curecell Co. Ltd., of Seoul, South Korea, as an initial step to finalize a joint venture that could develop and bring the AIP cell therapy to market in that country. In November, Orgenesis inked an agreement with Russian firm Biosequel LLC to conduct trials in Russia using AIP cells.

In addition, Orgenesis is marshalling patient awareness through a collaboration with the New York-based advocacy organization Lyfebulb.

Traded over-the-counter (OTCQB:ORGS) since 2012, the company has a market cap of about $32 million. Orgenesis reported approximately $264,000 in cash and equivalents and an accumulated deficit of roughly $19.7 million as of Aug. 31. Partnering is the logical next step for the company to grow, according to Caplan.

Once the AIP program is in the clinic, "a whole range of possibilities will open up," she predicted. "We have seen a shift, with biopharma companies more and more open to looking at cell therapies as a viable option to treat patients."

Caplan cited Celgene Corp., of Summit, N.J., and J&J as examples of biopharmas that are "actively approaching" regenerative medicine companies and seeking opportunities to advance cell-based therapies.

"We're also seeing a lot more acceptance in the financing community," she said.

Cell therapy approaches in diabetes remain in their infancy, Caplan conceded, "but this whole field of regenerative medicine, whether using adult cells or using stem cells, holds the future of therapy for diabetes. It's time to begin to think of a cure as a possibility and not something beyond our imagination."

Immuno-oncology drug development has been at the forefront of the precision medicine movement, "but I think we will have something very similar when we talk about treatment for diabetes because we will be using each patient's own liver cells," she added.

"The therapy will be optimally adapted for that patient. We're focused for the moment on type 1 diabetes, but it will be interesting to see how this approach will translate for other diabetes patients, as well," Caplan said.