AUM001 is an orally available highly selective small-molecule MNK 1/2 inhibitor which belongs to the selective translation regulator (SRS) class of drugs. It has a well-defined mode of action, a strong safety profile and well-established pharmacokinetics (PK).
MNK1/2 are terminal kinases in key oncogenic signaling pathways, including KRAS-BRAF-MEK-ERK, acting at the level of RNA translation.
AUM001 inhibits phosphorylation at S209 on the eukaryotic translation initiation factor 4E (eIF4E) thereby downregulating eIF4E. eIF4E is a critical factor in mRNA translation and is overexpressed in a wide range of tumors. This over-expression leads to malignancy characterized by uncontrolled growth, metastasis and immune evasion. Normal cells can survive in the context of eIF4E downregulation as evidenced by both gene knock-out and gene knock-in experiments. Downregulation of eIF4E has no impact on normal cell growth, function and survival and makes them more resistant to oncogenic transformation. Increased levels of eIF4E are present in many tumor types and are necessary for the translation of oncogenic signaling mRNAs. Inhibition of eIF4E, therefore, results in an inability to translate oncogenic signaling mRNA while translation of housekeeping gene mRNA is unimpeded. Inhibition of eIF4E also restores immune sensitivity.
MNK1/2 integrate MAPK pathway signaling at the level of mRNA translation, resulting in decreased anti-tumor immune activity due to selective upregulation of several immune checkpoint receptors and specific immunosuppressive cytokines.
Our targeted therapies, including AUM001, have the potential to combine the benefits of multiple targeted therapies as well as immunotherapies in a single agent.
AUM001 has completed a first-in-human (FIH) single ascending dose (SAD). There were no drug related SAE and AUM001 was well tolerated. This molecule was granted a US IND under its former name, ETC-1907206 following which a phase I study using of ETC206 in combination with dasatinib was initiated in patients with certain types of blood cancers (ClinicalTrials.gov Identifier: NCT03414450). AUM Biosciences, upon licensing ETC-1907206 (AUM001), withdrew the study for lack of recruitment.
Additional safety and PK exploration in the form of a multiple ascending dose (MAD) study is expected to enroll the first subject in Q3 of 2019 with topline data readout expected in Q1 2020. Patient studies are also planned to start in 2020.