Cellerant has successfully completed the Phase I feasibility research for the development of a neutrophil progenitor for the treatment of neutropenia e.g. during bone marrow transplantation, chemotherapy or after radiation exposure. In Phase I, the company demonstrated that human hematopoietic stem cells could serve as the seed inoculum for an 8 day production process that yields high levels of cultured myeloid progenitors (MPc). These progenitors can, in the presence of granulocyte-colony stimulating factor, go on to full neutrophil maturation, showing that they are poised to colonize the patient's immune cell reservoirs. In a mouse model of neutropenia, ex vivo expanded murine MPc protected irradiated mice from lethal fungal infection, whether given in an autologous (matched) or allogeneic (mismatched) setting. Furthermore, infusion of pooled MPc derived from several MHC disparate donors is as effective as MPc derived from a single allogeneic donor. Ex vivo expanded human MPc were introduced into an immune-restricted mouse model and the transfused cells proceeded towards neutrophil maturation rapidly. These accomplishments clearly indicate that the ex vivo expanded MPc product can be produced from human stem cells to yield a highly purified, potentially safe and effective cellular therapy. In Phase II, Cellerant will focus on addressing the most critical of preclinical tasks.
The Specific Aims will be: 1. development of cryopreservative methods, 2. optimization of culture medium and conditions, 3. evaluation of persistence and long term effects, and 4. evaluation of the risk of HLA sensitization. The accomplishment of these Specific Aims will support Cellerant in a meeting with FDA representatives on the regulation of MPc. If successfully approved for sale and successfully advanced to large scale production this cellular therapy would be a novel universal treatment that provides temporary but effective protection from fungal and bacterial infections of neutropenic patients. PROGRAM NARRATIVE Neutropenic patients at risk for lethal fungal and bacterial infections as a result of pre- transplantation conditioning, radiotherapy or chemotherapy have few effective alternatives for treatment. The successful development of a commercially available, universal Myeloid Progenitor cell therapy will have a significant positive impact on the survival of this population. The availability of a safe and effective, """"""""off-the-shelf"""""""" treatment will also have a significant positive impact on the ability of local and federal governments to respond to mass casualties as a result of a nuclear power plant accident, terrorist detonation, or other localized radiological disasters. ? ?
