CLT-009 is an allogeneic megakaryoid progenitor (MKP) cell therapy in preclinical development for the treatment of severe thrombocytopenia in oncology indications and the ARS. The target patient population includes those at risk of life-threatening bleeding following radiation exposure or radio- and/or chemotherapy.
CLT-009 is a MKP cell product derived from pooled, normal HSC, like CLT-008. The CLT-009 manufacturing process is similar to the process for CLT-008 except that the ex vivo culture conditions promote the differentiation and expansion of HSC into megakaryoid instead of myeloid progenitor cells. CLT-009 contains Multipotent Progenitors (MPP, CD34+CD90+) and early (CD34+CD41+CD42neg) and late (CD34+CD41+CD42+) MKPs. Like CLT-008, CLT-009 is intended to be a universal 'off-the-shelf' cell therapeutic that temporarily produces platelets for the period of time when the patient's own bone marrow progenitor cells are unable to produce platelets.
When CLT-009 is injected into sub-lethally irradiated immunocompromised mice, human platelets are detected in the blood by 7 days, peak around day 14, and can still be found as long as 4 weeks after infusion. Platelet levels are increased 3-5-fold with the co-administration of thrombopoietin, a cytokine that promotes MKP maturation and platelet production. Additionally, the platelets produced in this model have been shown in vitro to be functional by ADP activation, similar to platelets isolated from human blood.
Thrombocytopenia is a condition in which there is a deficiency of platelets in the blood. Platelets are small, anuclear cells that are an important component of blood clotting and the immune response and are produced by megakaryocytes in the bone marrow. A healthy person will have approximately 150-450 million platelets per milliliter of blood and uncontrolled bleeding may occur when platelet levels drop below 10 million per milliliter. Thrombocytopenia may be caused by chemo- or radiation therapy for the treatment of cancer since these treatments kill normal dividing cells, such as MKPs, as well as the tumor cells. Individuals exposed to radiation from a nuclear accident or terrorist act may also become severely thrombocytopenic through the destruction of their bone marrow. In cancer patients, chemo- or radiation therapy induced thrombocytopenia may be treated with transfusions of donor platelets. Although platelet transfusions are effective in raising platelet levels, donors must be continuously recruited since platelets cannot be stored for more than 4-5 days nor can they be frozen. Additionally, platelets must be stored at room temperature which increases the risk of bacterial outgrowth. Lastly, cancer patients may need as many as a dozen transfusions during the course of their cancer treatment because platelets only circulate for about 7 days before they are removed from the blood. Repetitive donor platelet infusions often result in patients developing resistance to donor platelet infusions such that the treatment becomes less and less effective while undesirable side effects increase with each transfusion.
The CLT-009 program is in preclinical development focusing on improving the in vitro generation of MKPs to produce a more potent product for in vivo pre-GLP studies and clinical trials. This program is funded by a National Cancer Institute (NCI) Small Business Innovation Research (SBIR) grant.