AMXT 1501

P1/2, N=92, Recruiting, Aminex Therapeutics, Inc.

P1/2, N=289, Recruiting, Milton S. Hershey Medical Center | Not yet recruiting --> Recruiting

Responsiveness to DFMO was linked to decreased levels of its molecular target, the rate-limiting polyamine biosynthesis enzyme ODC1, and of the polyamine transporters ATP13A2 and ATP13A3. Increased expression of c-MYC was associated with enhanced sensitivity to the combination of DFMO and AMXT 1501, suggesting this oncoprotein as a potential predictive marker of response to the drug combination. In conclusion, targeting polyamine biosynthesis and polyamine uptake limits disease progression in models of acute leukaemia, supporting further preclinical and clinical investigation into this approach for acute leukaemia.

This finding resulted in the clinical development of polyamine transport inhibitors, including AMXT 1501, which is presently under clinical investigation in combination with DFMO...An association between high ATP13A3 expression and poor survival in neuroblastoma further supports a role of this transporter in neuroblastoma progression. Thus, this study identified ATP13A3 as a critical regulator of basal and DFMO-induced polyamine uptake and a novel therapeutic target for neuroblastoma.

P1/2, N=253, Not yet recruiting, Milton S. Hershey Medical Center | Initiation date: Feb 2025 --> Oct 2025

P1/2, N=15, Terminated, Aminex Therapeutics, Inc. | N=56 --> 15 | Active, not recruiting --> Terminated; Required re-formulation of DFMO from IV to capsule to maintain safety

P1/2, N=253, Not yet recruiting, Milton S. Hershey Medical Center | Trial completion date: Jul 2034 --> Dec 2034 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Jul 2032 --> Dec 2032

P1/2, N=56, Active, not recruiting, Aminex Therapeutics, Inc. | Suspended --> Active, not recruiting

P1/2, N=56, Suspended, Aminex Therapeutics, Inc. | Recruiting --> Suspended

P1/2, N=56, Recruiting, Aminex Therapeutics, Inc. | Phase classification: P1b/2a --> P1/2 | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P1/2, N=253, Not yet recruiting, Milton S. Hershey Medical Center

In contrast, a combination lorlatinib/AMXT-1501 treatment resulted in synergistic inhibition of cell growth in ALK-driven NB cell lines. Taken together, our results identify a novel role for the ALK receptor tyrosine kinase (RTK), working in concert with the MARCH11 E3 ligase, in regulating SLC3A2 protein stability and function in NB cells. The synergistic effect of combined ALK and polyamine transport inhibition shows that ALK/MARCH11/SLC3A2 regulation of amino acid transport is important for oncogenic growth and survival in NB cells.