Remedy Plan Therapeutics has announced the initiation of a Phase 1 clinical trial for RPT1G, a first-in-class hyperbolic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor. The trial, which is being conducted in healthy adult volunteers in Australia, marks a significant step in the development of a novel therapeutic approach for cancers, autoimmune disorders, and metabolic diseases characterized by elevated NAMPT levels.
The Phase 1 trial (NCT06667765) is a randomized, double-blind, placebo-controlled study designed to evaluate the safety and pharmacokinetic properties of RPT1G. Researchers will also be exploring pharmacodynamic markers to better understand the drug's mechanism of action. The results from this trial are anticipated in the first half of 2025 and will inform the subsequent development of RPT1G in oncology, with a focus on acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS).
Novel Mechanism of Action
RPT1G is designed as a hyperbolic NAMPT inhibitor, a mechanism intended to selectively target cells with high NAMPT levels, such as those found in certain cancers, while sparing healthy cells. This approach aims to minimize on-target toxicity and preserve normal biological function, potentially leading to a more favorable safety profile compared to traditional NAMPT inhibitors.
Greg Crimmins, Ph.D., founder and CEO of Remedy Plan Therapeutics, stated, "RPT1G is not only the first hyperbolic NAMPT inhibitor, but also the first NAMPT inhibitor to be tested in a healthy volunteer study, showcasing the importance of our preclinical work that clearly highlights the favorable safety profile of our hyperbolic NAMPT inhibitors."
Preclinical Evidence
Preclinical studies have demonstrated that RPT1G exhibits a favorable efficacy and tolerability profile compared to previously developed complete NAMPT inhibitors. These findings support its potential utility in treating hematological malignancies and solid tumors. In addition to its single-agent activity, RPT1G has shown synergistic effects with standard-of-care drugs, including the ability to overcome cancer cell resistance to venetoclax, a common treatment for leukemia.
Broader Therapeutic Potential
Beyond oncology, RPT1G analogues are being investigated as potential therapies for autoimmune and metabolic diseases, given the established scientific evidence of NAMPT upregulation in these conditions. This highlights the broad therapeutic potential of this novel class of NAMPT inhibitors.
