Immuno-Regulatory Candidates

Programming a Balanced Immune System

Immune dysfunction is a hallmark feature of autoimmune diseases and certain procedures such as allogeneic hematopoietic cell transplant (HCT) for cancer patients. The hyper-activation of the immune system in these conditions often leads to significant reductions in patient quality of life and a tremendous economic burden to the healthcare system. We are developing immuno-regulatory cellular therapies that are programmed to promote immune system homeostasis for patients undergoing hematopoietic cell transplantation and with immune disorders.




The First Line of Defense for Prevention of Life-Threatening Complications in Immunocompromised Patients

Allogeneic hematopoietic cell transplantation (HCT) is performed with curative intent for patients afflicted with hematologic malignancies and rare genetic disorders. Adoptively transferred immune cells from the donor graft, including T cells, are responsible for effectively fighting infections and killing residual cancer cells in immunocompromised patients undergoing allogeneic HCT and play a critical role in determining overall patient outcomes. However, donor T cells often become activated upon administration to a patient and attack healthy tissue in the liver, gut and skin, an immune response known as acute graft-versus-host disease (aGvHD). Complications resulting from dysfunction of adoptively-transferred donor T cells can be life-threatening, require hospitalization, impact the quality of life of patients and their caregivers, and place a significant economic burden on the healthcare system. There are no FDA approved therapies to prevent aGvHD or viral infections in allogeneic HCT patients.

ProTmune™ is a programmed cellular immunotherapy candidate consisting of donor-sourced mobilized peripheral blood cells, which have been functionally modulated using two small molecules, for the prevention of aGvHD and severe viral infections in HCT patients. Data presented at the 2015 ASH annual meeting showed that a single administration of programmed mPB cells resulted in a statistically-significant reduction in GvHD score and improvement in survival, as compared to vehicle-treated cells, in preclinical models of allogeneic HCT. Importantly, Fate has also demonstrated that the cancer-fighting properties of programmed mPB cells are preserved following adoptive transfer in preclinical models.

We plan to initiate a Phase 1/2 clinical trial of ProTmune™ in 2016 for the prevention of aGvHD and cytomegalovirus (CMV) infections in adult subjects with hematological malignancies undergoing allogeneic HCT. The study will be divided into two stages: the Phase 1 will assess the safety and tolerability and the randomized, controlled Phase 2 will assess efficacy.


PD-L1 CD34+ Cell


Turning the Checkpoint Axis to Rebalance Immune Dysfunction

Autoimmune disease is an umbrella term for approximately 80 distinct conditions with a unifying feature that the body’s immune system attacks and damages its own tissues. One strategy to counter these attacks is to suppress auto-reactive T cells.

The PD-1 / PD-L1 biological axis has been clinically validated as a potent immuno-suppressive pathway. In cancer, blocking the PD-1 / PD-L1 pathway with checkpoint inhibitors activates T cells, and has become an attractive therapeutic approach to enabling cytotoxic T cell killing of cancer cells.

Fate is seeking to turn this checkpoint mechanism in the setting of T cell-mediated immune disorders in order to suppress aberrant T cell activity. We have discovered that CD34+ cells can be pharmacologically programmed to upregulate certain immuno-regulatory factors, including PD-L1, to supra-physiological levels, and that programmed CD34+ cells have the capacity to traffic to sites of inflammation and suppress T cell activity. We are currently investigating our lead product candidate in several preclinical models of T cell-mediated immune dysfunction as a novel treatment for immune disorders.