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Aprea Therapeutics to Treat Myelodysplastic Syndromes

Aprea Therapeutics has launched a mutant p53 reactivating compound APR-246 in combination with chemotherapy drug azacitidine for the treatment of Myelodysplastic Syndromes (MDS) in patients having a susceptible TP53 mutation.

The myelodysplastic syndromes are known as a group of cancers in which enough numbers of healthy blood cells cannot be produced by the bone marrow.

Nearly 30-40 per cent of patients having the condition progress to Acute Myeloid Leukemia (AML) and mutation of the p53 tumor suppressor protein are believed to contribute directly to disease progression and a poor overall prognosis.

Considered to be the most frequently mutated gene in human cancer, the p53 tumor suppressor gene occurs in about 50 per cent of all human tumors.

The mutations are generally related to resistance to anti-cancer drugs and poor overall survival, hence representing a significant unmet medical need in cancer treatment.

By restoring wild-type p53 conformation and function, APR-246 has shown reactivation of mutant and inactivated p53 protein thereby inducing programmed cell death in human cancer cells.

The pre-clinical anti-tumor activity has been observed with APR-26 in MDS, AML, ovarian cancer, and other solid and hematological cancers.

Besides pre-clinical testing, a Phase 1/2 clinical program with APR-246 has been completed. A favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene have been demonstrated with the results.

Currently, a pivotal phase 3 clinical trial of APR-246 and azacitidine for MDS is ongoing.