The Journey from Bench to Market: Human Embryonic Stem Cells at Hadassah

The Journey from Bench to Market: Human Embryonic Stem Cells at Hadassah

Hadasit subsidiary Cell Cure Neurosciences, via its parent company Lineage Cell Therapeutics, recently signed a deal with Roche and its Genentech arm to license and further develop the investigational eye drug OpRegen® – a retinal pigment epithelium (RPE) therapy prepared for a form of advanced dry age-related macular degeneration (AMD). According to the terms of the agreement, Roche will pay Lineage $50 million upfront and, potentially, up to an additional $620 million in milestone-based payments and sales royalties. “This is the biggest cell therapy-related deal, outside the oncology field,” said the CEO of Lineage. Click here to read more.

This news is very exciting, but perhaps even more extraordinary, is the story behind this successful commercialization. It all began more than two decades ago, on the lab bench of Prof. Benjamin Reubinoff at Hadassah University Hospital.

Human embryonic stem cells (hESCs) were first derived in 1998, and Israeli researchers played a significant role in this breakthrough. Prof. Benjamin Reubinoff, Director of the Sidney and Judy Swartz Embryonic Stem Cell Research Center at the Goldyne Savad Institute of Gene Therapy, and Chairman of the Department of Obstetrics and Gynecology at Hadassah, was one of the pioneers in the stem cell field. Together with researchers in Australia and Singapore, he was the second in the world to derive hESC lines, and the first to show their somatic differentiation in vitro¹. Given Professor Reubinoff’s great enthusiasm for the potential of using hESCs for regenerative therapy, he has been focusing on overcoming the barriers to developing hESCs for clinical transplantation therapy ever since.

Given the successful derivation of the hESCs and their great promise for regenerative therapy, a generous donation from Sidney and Judy Swartz laid the foundations for the establishment of the Embryonic Stem Cell Research Center at Hadassah with the goal of developing hESCs for clinical applications. The potential of hESCs for transplantation therapy also led to the establishment of the Hadasit spin-off company Cell Cure Neurosciences in 2002, with Prof. Benjamin Reubinoff as co-founder and  Chief Scientific Officer. Cell Cure focused on the development of stem cell-based therapies on the basis of technologies that were developed at Hadassah, and were subsequently transferred to Cell Cure.

Prof. Reubinoff’s first step towards fulfilling the goal of cell therapy was the derivation of new hESC lines that would be suitable for clinical applications. At that time, the existing hESC lines were only suitable for research purposes. The Hadassah hESC Research Center was the first to develop hESC lines without the use of animal-derived reagents and under GMP conditions², and thus, they were suitable for use as starting materials in clinical transplantation applications.

Next, Prof. Reubinoff  searched for a clinical indication that was a suitable candidate for developing an hESC-based cell therapy. The Center was developing progeny for the treatment of various neural and retinal degenerative disorders, but RPE cells for transplantation therapy in AMD evolved as the most promising. This was related to the Center’s success in developing a novel and efficient methodology to direct the differentiation of hESCs into functional RPE cells, indications in the literature suggesting that RPE regeneration may halt progression of AMD and lack of an effective FDA-approved treatment for AMD.

In collaboration with Professor Eyal Banin, Head of the Center for Retinal and Macular Degeneration at the Department of Ophthalmology at Hadassah, they showed that transplantation of the hESC-derived RPE cells could partially rescue vision loss in an animal model of AMD³ and they further focused on developing hESC-derived RPE cells for transplantation in AMD(4).

Clinical-grade hESCs and the technology for deriving RPE cells from them were transferred to Cell Cure Neurosciences, Ltd(1). The company successfully manufactured pure RPE cell cultures from the hESCs, under xeno-free, and GMP conditions. They proved that these cells were safe and effective in mice and rats. Subject to approvals by the Israeli Ministry of Health and the FDA, Cell Cure launched a multi-center phase I/IIa clinical trial of RPE cell transplantation in advanced form of dry-AMD in Israel and the USA. Initial patients were transplanted at Hadassah. Primary results from the clinical trial are encouraging (2).

In recent years, Cell Cure was supported by the California-based biotechnology company Lineage Cell Therapeutics, Inc. (NYSE and TASE: LCTX), previously known as BioTime, Inc., which became the full owner of Cell Cure Neurosciences in 2017.

The phase I/IIa clinical trial’s evidential success led to the execution of the licensing deal described above towards further clinical development and global commercialization of the breakthrough technology by Roche.

This exquisite success story highlights the potential of human embryonic stem cell lines for clinical applications, and the role of partnering academic research with the development of therapeutic entities for regenerative medicine.

Prof. Reubinoff’s journey in the area of pluripotent stem cells is further described in Nature Biotech (March 2021). The Hadassah hESC Research Center, continues to supply clinical and research-grade hESCs to academic and commercial entities for the promotion of hESC-based clinical therapies for drug discovery, disease modeling, and basic research. The Center is committed to serving the biomedical community by providing high-quality cell lines that have the potential to treat unmet global healthcare needs.

Parties interested in collaboration with the Hadassah hESC Research Center are invited to contact our team through the website, or to email to Dr. Sarit Batsir, VP BD for Pharma at Hadasit, SaritBa@hadassah.org.il.

REFERENCES

  1. Reubinoff, BE, Pera MF, Fong CY, Trounson A, Bongso, A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol, 2000 Apr; 18(4):399-404. doi: 10.1038/74447
  2. Tannenbaum SE, Turetsky TT, Singer O, Aizenman E, Kirshberg S, Ilouz N, Gil Y, et al. Derivation of Xeno-Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications. PLoS ONe, June 20, 2012, https://doi.org/10.1371/journal.pone.0035325
  3. Idelson, M, Alper R, Obolensky, A, Ben-Shushan, E, Hemo, I, Yachimovich-Cohen, N, Khaner H, et al. Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell. 2009 Oct 2; 5(4):396-408. doi: 10.1016/j.stem.2009.07.002
  4. Crow, D. From Cell Stem Cell to Clinical Trials: The Biotech Journey of Two Papers. Profile: Cell Stem Cell. 2017 June 01: 20(6):746-748. https://doi.org//10.1016/j.stem.2017.05.013
  5. Reubinoff, BE and Tannenbaum , SE. Human embryonic stem cells – from derivation to clinical regenerative applications. Bioengineering: Nature Biotechnology Blog. 2021, March 17.
  6. Professor Reubinoff is both co-founder and the Chief Scientific Officer of Cell Cure Neurosciences, Ltd.
  7. https://lineagecell.com/products-pipeline/opregen/