Potent Therapeutic Activity of NEO212 in Preclinical Models of Human and Canine Leukaemia and Lymphoma

ABSTRACT Haematological cancer types, such as leukaemia and lymphoma, represent diseases that are life‐threatening to canine and human patients alike, and better treatments are needed. We are developing a novel anticancer agent, NEO212, a conjugate of two cancer drugs, the alkylating agent temozolomide (TMZ) and the monoterpene perillyl alcohol (POH). NEO212 has revealed robust therapeutic activity in preclinical tumour models harbouring different human cancer types. In the comparative preclinical study presented here, a two‐species (canine and human) and two‐cancer (leukaemia and lymphoma) analysis was performed to determine whether the promising therapeutic activity of NEO212 would span species and cancer types. We investigated the activity of NEO212 in human and canine leukaemia and lymphoma cell lines in vitro and in corresponding mouse models in vivo. Our results show that in vitro NEO212 is significantly more potent than TMZ and POH in all cell lines and exerts activity even against strongly TMZ‐resistant tumour cells. In vivo, oral NEO212 strikingly extends the survival of mice harbouring human or canine leukaemia or lymphoma cells. At the same time, NEO212 is well tolerated in dogs at dosages higher than those that achieved therapeutic activity in mouse models. Our study introduces NEO212 as a novel oral cancer drug candidate for both human and veterinary oncology applications.