Exploratory development of Aleta-001 (CD19-CD20 bridging protein) for a first in human clinical trial
Cancer Research UK
Aleta BioTherapeutics
Chimeric antigen receptor (CAR) therapy involves isolation of patient T cells followed by viral-mediated gene insertion and T cell expansion in culture. The resulting CAR T cells are infused into the patient. Patient T cells that express an anti-CD19 scFv chimeric antigen receptor (anti-CD19 CAR) can elicit durable and curative responses against CD19-positive B cell malignancies. However, up to 60% of patients who initially achieve a beneficial clinical response to this therapy relapse afterwards. Relapses typically happen in the first few months after therapy is administered.   Relapses occur when the CAR T cell population does not achieve optimal expansion and persistence after administration. T cell expansion and persistence require the availability of the CD19 antigen on the tumor cells and on normal B cells. In some patients the initial T cell expansion fails to eradicate all of the tumor cells, so they achieve a partial clinical response or, a complete clinical response is achieved, but CAR T cell number in circulation is below optimal. These patients will relapse. In some patients the expression of CD19 is lost from the tumor cells, which therefore become invisible to the CAR T cells. These patients will also relapse.   Aleta-001 is a CD19-anti-CD20 biologic designed to optimize anti-CD19 CAR T cell activity by creating a novel source of CD19 on the tumor cells. All NHL patient tumor cells are CD20-positive and the biologic binds to this CD20 with high affinity. In the case of suboptimal CAR T cell expansion, the biologic provides higher CD19 antigen density on the targeted cells to optimally stimulate the CAR T cell population. In the case of CD19 antigen loss, the biologic replaces CD19 via anti-CD20 binding, providing a de novo antigen source. This biologic is the only therapeutic specifically designed to optimize anti-CD19 CAR T cell therapy. The modality offers the clinician and patient a ready solution that can be administered by injection to optimally activate or reactivate the CAR T cell therapy the patients has already received.  The goal of the proposed collaboration with CDD is to fund early phase clinical trials at UK cell therapy centers of excellence. The clinical trials of this novel therapeutic will demonstrate safety and measure PD markers of response to treatment. Ultimately this funding will help us improve patient outcomes in the setting of anti-CD19 CAR T cell treatment of advanced B cell cancers.
6.1 Pharmaceuticals