This Phase 1 SBIR project is to perform go-/no-go evaluation of the proprietary protein, angiocidin, as a novel therapy for the treatment of acute myeloid leukemia (AML). AML is a significant medical burden as existing therapy based on cytotoxic drugs has a low efficacy rate and is contraindicated in many elderly people, who comprise the largest and fastest growing population of AML patients. Angiocidin, whose mode of action is to drive differentiation of leukemic blast cells, has the potential to revolutionize leukemia therapy, especially in the elderly. Differentiation therapy is a well-investigated concept in AML. This has been driven by the dramatic clinical success of differentiation agents (ATRA and arsenic trioxide) in acute promyelocytic leukemia (APL), a subtype of AML. Unfortunately, the remaining AML subtypes do not respond to these agents or others which are mechanistically similar. The work of Diffregen and its consortium partner, Temple University, has demonstrated angiocidin's ability to drive differentiation of leukemic cells in vitro and has begun to elucidate the novel mechanism of this activity. Here we are proposing a series of animal studies to evaluate the in vivo utility of angiocidin as a differentiation agent for AML. Feasibility work will focus on three areas: (1) establish a foundation for manufacturing angiocidin for proof-of-feasibility studies and for future GMP work;(2) evaluate angiocidin's efficacy, alone and in combination with standard of care cytotoxic drugs, in an animal model regularly used by drug developers to evaluate the performance of new AML therapies;(3) broaden our knowledge of angiocidin's utility in other acute leukemias in an animal model of acute lymphocytic leukemia (ALL). ALL is an important extension of angiocidin's potential utility because despite the success of standard of care in children, adults with ALL have the same poor outcomes as patients with AML. Successful completion of Diffregen's planned studies will provide the preclinical efficacy data needed to support the initiation of IND- directed development work and progression toward clinical studies in man, and will establish the dataset required to make educated decisions on the commercial viability of the product.
This project will evaluate whether a novel protein, angiocidin, could be used as a revolutionary treatment of acute myeloid leukemia (AML). Today's treatment options for AML have poor outcomes and, because of severe side effects, are not suitable for the elderly, who comprise the majority of AML patients. Angiocidin offers the potential to improve treatment outcomes for AML patients, especially the elderly.