OATD-02

OATD-02 is currently undergoing clinical evaluation in a phase I/II trial (NCT05759923), which will further elucidate its safety and therapeutic impact. These findings highlight the potential of arginase-targeted therapies in cancer treatment and underscore the value of MALDI-MSI as a powerful tool for tracking metabolic responses to therapy.

P1, N=40, Recruiting, Molecure S.A. | Trial completion date: Nov 2024 --> Dec 2025 | Trial primary completion date: Nov 2024 --> Dec 2025

The study is ongoing. Clinical trial information: NCT05759923.

Bortezomib exacerbates MM-mediated LV systolic dysfunction in a mouse model of MM, while an arginase inhibitor partially prevents it. Endothelium does not mediate either these adverse or beneficial effects. This suggests that proteasome inhibitors should be used with caution in patients with advanced myeloma, where the summation of cardiotoxicity could be expected. Therapies aimed at the NO pathway, in particular arginase inhibitors, could offer promise in the prevention/treatment of cardiotoxicity in MM.

10 software.Arginase inhibitorOAT-1746 arginase inhibitor (Molecure SA) was administered intraperitoneally at doses of 5 or 20 mg/kg twice daily, starting from the second or the fifth day before the bacterial challenge, respectively...Finally, ARG inhibitor decreased L. monocytogenes burden in MM-bearing mice. Altogether, our results show that accumulation of CECs during MM progression leads to impaired bacterial infection control, at least partially dependent on ARG2 activity.

OATD-02 is a potent small-molecule arginase inhibitor with optimal drug-like properties, including PK/PD profile. Excellent activity against intracellular ARG2 significantly distinguishes OATD-02 from other arginase inhibitors. OATD-02 represents a very promising drug candidate for the combined treatment of tumours, and is the only pharmacological tool that can effectively address the benefits of ARG1/ARG2 inhibition. OATD-02 will enter clinical trials in cancer patients in 2022.

Treatment with OAT-1746 modified the TME resulting in reduced glioma growth and increased antitumor effects of the anti-PD-1 antibody. Our findings provide the evidence that inhibition of ARG1/2 activity in tumor cells and myeloid cells in the TME unblocks antitumor responses in myeloid cells and NK cells, and improves the efficacy of the PD-1 inhibition.