A single infusion of one of our product candidates is intended to create mixed chimerism, which can induce donor-specific immune tolerance or immune quiescence. In solid organ transplant recipients, the carefully predetermined number of donor CD3+ T cells, along with other cells in our product facilitates engraftment of the donor CD34+ HSCs by selective depletion of recipient T-cells. These recipient T cells are the ones that would normally induce rejection of the donor HSCs.

Once engraftment of donor CD34+ HSCs occurs and mixed chimerism (donor and recipient cells co-existing harmoniously in the bone marrow) is established, donor-derived antigen presenting cells migrate and expand within the recipient thymus and lymphoid tissues, resulting in intrathymic (central) clonal deletion of newly developing donor-reactive host T-cells and extrathymic (peripheral) clonal deletion of existing donor-reactive host conventional T-cells, respectively. This prevents rejection of the donor-derived CD34+ HSCs, donor blood cells and, most importantly, the donor organ that was transplanted prior to infusion of our product candidates.

Thus, the organ transplant recipient becomes specifically tolerant to donor cells, tissues and organs, and may no longer need immunosuppressant (IS) drugs to prevent rejection. We define immune tolerance as a reduction in the normal tendency of a transplant recipient’s immune system to recognize and attack a transplanted organ or tissue, or donor-derived cell. Based on the clinical experience to date, including greater than 10 years of durability data from the time of transplant for HLA-matched living kidney transplant recipients, immune tolerance can reduce or eliminate the need for chronic immunosuppressive drug therapy and reduce the risk of eventual loss of function of the transplant organ.

Immune quiescence embodies the concept of utilizing cellular therapy to quell the immune-mediated pathophysiologic processes that underlie and are predictive of transplant kidney loss, such as acute rejection (inclusive of T cell-mediated rejection and antibody-mediated rejection), de novo donor specific antibody (dnDSA) formation, de novo interstitial fibrosis and/or tubular atrophy (IF/TA) and de novo allograft inflammation.