NAMPT: core regulator of human biology

The NAMPT enzyme regulates cellular metabolism, the fundamental process that defines how cells use energy. There are >3,000 research articles highlighting NAMPT’s position at the intersection of human health and over 20 diseases, from oncology to autoimmune and metabolic disorders.

Cancer

For the last 100 years, scientists have known that cancer cells use far more sugar than normal cells, an effect called “Warburg metabolism.” NAMPT, and its product NAD, are required for Warburg metabolism across numerous cancer types.

Autoimmune

A change in cell metabolism is required for immune cell activation and inflammation. NAMPT is required for this shift in immunometabolism in T-cells and macrophages.

Obesity

NAMPT plays a central role in adipose signaling and metabolism, where it regulates fat expansion and weight gain.

NAMPT: challenges as a drug target

The central challenge with targeting NAMPT is achieving the desired effect in the cells causing the disease (e.g., cancer, immune, or fat cells) while also maintaining the proper function of healthy cells and tissues. The dual role of NAMPT in health and disease has confounded drug developers for the last 10+ years.

In numerous published mouse studies, inhibition of NAMPT was highly effective at decreasing tumor burdens, alleviating autoimmune disease symptoms, or preventing an increase in fat mass. However, all previous NAMPT drugs were also toxic to vital organs. This phenomenon is known as “on-target toxicity,” because it is the drug’s impact on NAMPT that is causing the damage to healthy tissues. Until now, there was no solution to meaningfully decrease NAMPT activity without causing on-target toxicity.

Remedy Plan breakthrough: efficacy without on-target toxicity

RPT1G is an oncology clinical drug candidate that specifically targets NAMPT, while avoiding the on-target toxicity that bedeviled previous NAMPT inhibitors. Due to an unprecedented allosteric mode of inhibition, RPT1G has a favorable preclinical safety profile. Remedy Plan’s unique approach unlocks opportunities to treat the multiple diseases caused by dysregulated NAMPT, from oncology to obesity.

The scientists at Remedy Plan unearthed the chemical foundation for RPT1G using a proprietary drug screening platform. Remedy Plan uses a high-throughput phenotypic screen to identify drug-like molecules that transform cell biology, then discovers and optimizes their novel mechanisms of action in preparation for clinical studies.