Shifting the paradigm in bone marrow transplantation
According to the Leukemia and Lymphoma Society, blood cancers are the third leading cause of cancer mortality in the United States. More than 1.3 million Americans are living with blood cancers, and nearly one-third of patients will not survive five years after diagnosis.1
Allogeneic (donor derived) stem cell transplants, commonly referred to as bone marrow transplants, are one of the only curative approaches for high-risk blood cancers. Each year, nearly 70,000 patients are indicated for an allogeneic stem cell transplant. In order for transplantation to be successful, patients require a fully matched donor, which may limit patients’ options and leads to over 40 percent never finding a donor match.
Gamida Cell is addressing the limited availability of donors for patients with high-risk blood cancers, in need of an urgent allogeneic stem cell transplant, with its lead program, NiCord.
NiCord, based on the company’s NAM technology, is in phase 3 clinical testing as a universal bone marrow transplant solution. NiCord, a stand-alone graft, is a curative approach, potentially able to treat most patients with high-risk blood cancers who do not have a rapidly available, fully matched donor.
Patients transplanted with NiCord have shown rapid recovery of their blood and immune cells. NiCord has the potential to minimize bacterial and fungal infections following transplantation, reduce duration of hospitalization and minimize morbidity and transplant-associated mortality. NiCord achieved the first evidence of an ex vivo expanded graft providing a significant, long-lasting hematopoietic recovery following transplantation.
NiCord is designed to be smoothly integrated into current transplant protocols. Once designated for transplantation with NiCord, an eligible cord blood unit is rapidly selected, and the manufacturing process, spanning approximately three weeks, begins. During this time, the patient receives a standard conditioning regimen lasting approximately eight to eleven days.
NiCord has been granted breakthrough status by the U.S. Food and Drug Administration (FDA), making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. The phase 3 trial is actively enrolling patients with high-risk blood cancers at sites in the United States, Europe and Asia. For more information, visit www.clinicaltrials.gov.
Each year, approximately 100,000 patients in the United States are living with sickle cell disease (SCD), a disease for which bone marrow transplantation is currently the only clinically established cure. SCD disproportionately impacts African Americans, affecting one in every 365 births. Patients diagnosed with SCD who are indicated for bone marrow transplantation face significant challenges in finding donor matches:
Gamida Cell is harnessing the potential of NAM technology to address the issues faced by patients with sickle cell disease and other rare genetic diseases through the development of CordIn. CordIn is a potential curative treatment for rare genetic diseases where a bone marrow transplant is an established cure, including sickle cell disease, thalassemia and aplastic anemia.
CordIn has shown promise as a bone marrow transplant modality. In a recent phase 1/2 study, CordIn showed rapid engraftment and cure of disease symptoms in hard to engraft SCD and aplastic anemia patient populations.
Gamida Cell is studying CordIn in a phase 1/2 trial for patients with sickle cell disease and thalassemia. The company is also conducting an investigator-initiated study of CordIn, enrolling patients with severe aplastic anemia and hypoplastic myelodysplastic syndrome who do not have a donor match. For more information on the CordIn clinical studies, visit www.clinicaltrials.gov.
Gamida Cell has expanded the capabilities of its NAM technology to utilize natural killer cells, commonly known as NK cells, to treat patients with refractory blood cancers and solid tumors.
NK cells play an important role in the immune system’s fight to kill tumor cells. Through expansion of highly functional NK cells using NAM technology, NAM-NK Cells can be used to harness the immune system to attack cancer.
Donor NK Cells are a promising immune therapy to treat cancers because:
To date, the insufficient numbers of NK cells and the short lifespan of the infused cells in patients have limited the applicability of these cells in the clinical setting. These limitations are addressed by NAM technology, which expands the NK cells 100-fold while improving their functionality.
NAM expanded NK cells displayed superior in vivo lifespan, proliferation and infiltration into multiple organs including the bone marrow. This is supported by dramatic up-regulation of the expression of the homing receptor CD62L (L-selectin), which otherwise was consistently observed to decrease in ex vivo expanded NK cultures.
Additional studies have demonstrated NAM to potentiate direct killing mechanisms and secretion of inflammatory cytokines needed for the activation of other immune cells and amplification of the anti-tumor effect.
Based on pre-clinical findings, a manufacturing method to expand a clinical grade product has been developed. Currently NAM-NK Cell product is under phase 1 development in patients with relapsed or refractory B-cell lymphoma and multiple myeloma. For more information, visit www.clinicaltrials.gov.