Closely held Gamida Cell has shifted its focus to its second-generation stem cell product, NiCord, for the treatment of hematological malignancies and non-malignant hematological diseases in the wake of an FDA decision last year for another pivotal trial of its first stem cell product, StemEx.
“We view the clinical outcomes with NiCord as a paradigm shift in cord blood transplantation as this is the first technology that resulted in a long-term graft of hematopoietic stem cells expanded in culture,” president and CEO, Yael Margolin, says in an interview with BioTuesdays.com.
Jerusalem-based Gamida Cell is positioned to become a world leader in blood-derived cell therapy. It has developed several platform technologies to expand functional cell populations and a pipeline of cell therapeutics in the areas of cancer, hematological diseases, autoimmune diseases, inflammatory conditions and regenerative medicine.
Gamida Cell’s therapeutic products contain adult stem cells selected from non-controversial sources, such as umbilical cord blood (UCB), bone marrow and peripheral blood. These cells are then enriched in culture using the company’s proprietary expansion technologies.
Gamida Cell also has been successful in translating these technologies into manufacturing processes under GMP, which are cost effective and efficient for commercial production. More than 20 patents worldwide and patent applications protect its technologies and products.
Dr. Margolin points out that UCB has been used since 1988 as an alternative source of stem cells for transplantation to donor bone marrow, which must be matched with a recipient for a potentially life saving treatment in leukemia or lymphoma patients.
According to Dr. Margolin, more than 60,000 patients each year are indicated for a donor-derived, or allogeneic, bone marrow transplant, with only about 25,000 patients each year getting a transplant. “An alternative solution is needed.”
Dr. Margolin explains that the advantages of UCB include less matching, no risk to a donor, less risk of viral contamination and rapid availability from public cord blood banks. More than 10,000 UCB transplants have been performed since 1988, and some 700,000 units of UCB have been donated and are stored in public cord blood banks.
Nevertheless, there is a significant limitation in the use of UCB, she notes. Specifically, there are not enough stem cells in a unit of UCB for a transplant in adults, resulting in a lower incidence of successful bone marrow grafts.
“Even with two units of UCB, because they come from different donors and have different immune systems, after a transplant, one unit engrafts in the bone marrow of a patient, and the second unit is rejected and disappears,” she says. Each unit of UCB costs $45,000.
“Our solution is to multiply the stem and progenitor cell population in a cord blood to enhance engraftment and improve survival,” she adds.
NiCord was developed from Gamida Cell’s Nicotinamide (NAM) technology. In addition to hematological malignancies, NiCord is in development to treat sickle cell disease, thalassemia, and aplastic anemia. The NAM platform has also led to development of potential natural killer cell and mesenchymal stem cell therapies for the treatment of cancer and for regenerative medicine, respectively.
“Our studies have revealed that NAM is a biological modifier that decreases the changes in cell characteristics and functions, typically occurring following expansion in culture,” Dr. Margolin offers. The company’s NAM technology and the Copper Chelator technology, which led to creation of StemEx, are the brainchild of Tony Peled, Gamida Cell’s co-founder, CSO and VP of R&D.
In a recent first-in-man study at Duke University Medical Center and Loyola University, 11 patients with high-risk hematological malignancies received NiCord and an unmanipulated unit of embryonic cord blood.
Eight patients engrafted with NiCord in a median time of 10.5 days and also required a significantly shorter stay in hospital. Two patients engrafted with the unmanipulated UCB, and one patient had graft failure. No safety concerns surrounding the use of NiCord were raised. Two-year overall and disease-free survival was 68% and 65%, respectively.
Dr. Margolin says the results of this study justify the transplantation of NiCord without the support of a second unmanipulated cord blood unit.
Last September, Gamida Cell initiated a second Phase 1/2 study of NiCord as an alternative, experimental treatment for blood cancers. This is the first study researching the outcome of a unit UCB, expanded in culture and transplanted in patients with depleted bone marrow and without the support of unmanipulated stem cells derived from a second UCB unit.
Dr. Margolin suggests that the approach using NiCord, as a single stem cell graft, has the potential to broaden accessibility, reduce toxicity and improve the clinical and economic outcomes of cord blood transplantation. The company hopes to complete the study with up to 20 patients at Duke this year.
In November, Gamida Cell began another Phase 1/2 study of NiCord together with a second unmanipulated cord blood unit as an investigational treatment for sickle cell disease, which affects 90,000 to 100,000 mainly African-Americans and Hispanic-Americans.
The disease can be fatal, and to date, the only cure is stem cell transplantation from a family related matched donor. “NiCord is intended to reverse this situation and provide a readily available cure,” Dr. Margolin says.
The company also is planning to begin, in the U.S. later this year, another study of NiCord as a single unit in patients with sickle cell disease and thalassemia, an inherited blood disease where the body makes an abnormal form of hemoglobin.
Gamida Cell also plans to begin another Phase 1/2 study this year in collaboration with the National Institutes of Health to study NiCord as a treatment for severe aplastic anemia, a condition where bone marrow does not make enough blood cells for the body.
In addition to a variety of blood malignancies, hemoglobin disease and bone marrow failure syndromes, Dr. Margolin says the company hopes to use NiCord to address genetic metabolic diseases, where transplants are done mainly in newborns, and severe refractory autoimmune diseases, where a bone marrow transplant is the only cure and a patient essentially receives a new immune system.
“We are focused on bringing NiCord to the market as a treatment to patients with hematological malignancies. We intend to address the additional indications in a step-by-step manner and to continue the development of our diversified pipeline of products,” she adds.