Selectively targeting the foxo4-p53 binding in the nucleus of the senescent cell. 

Science

Selectively targeting the foxo4-p53 binding in the nucleus of the senescent cell. 

The lead compound NBT-103 selectively competes with the foxo4-p53 binding. activating the mal-functional mitochondria, resulting in apoptosis of the pro-inflammatory producing senescent cell.

Efficacy

The efficacy of NBT-103 has been validated by several international top research institutes in different animal models. The compound shows effect in disease models and in normal aging and fast aging mice models. Besides improvement in kidney and liver function and improvement of muscle function and total fitness all studies also revealed a decrease of the pro-inflammatory cytokine IL-6. Interesting is the discovery of up-regulation of functional regulatory T-cells (Tregs) by the compound NBT-103 most likely through eliminating cytokines like IL-6. (see mode of action)

Inflammatory IL-6

In a doxorubicin induced autoimmune model NBT-103 significantly reduces IL-6.

IL-6 in kidney

In a fast aging mice model NBT-103 significantly reduces the elevated IL-6 

Regulatory T-cells

In normal aging mice NBT-103 significantly increases regulatory T-cells ( Tregs)

The mode of action

Senescent cells are responsible for chronic low grade inflammation by producing pro-inflammatory cytokines such as IL-6. NBT-103 targets specifically these senescent cells where p53 is inactivated through binding to foxo4 in the nucleus. NBT-103 is competing with this foxo4-p53 binding resulting in release of p53 and activated p53 will migrate to the mitochondria. As a result the senescent cell will go into apoptosis. The specific elimination of senescent cells by NBT-103 results in lower pro-inflammatory cytokines such il-6. The down regulation  of IL-6 has a positive effect on the total number of regulatory T-cells ( Tregs) and a positive effect on the functionality of Tregs. The mode of action of NBT-103 has been confirmed in different international top research institutes.

Treatments

Numeric Biotech’s lead compound NBT-103 is a novel therapy for the potential use in a broad range of chronic (neuro) inflammatory diseases and in autoimmune diseases where low levels of Tregs and or high chronic inflammation play an important role.

NBT-103 targets the root cause of these diseases and due to its highly specific approach it is envisioned that the treatments will be effective with less side effects. 

Numeric Biotech has started its toxicology program for NBT-103 to comply with regulatory standards for a selected orphan drug lead indication. Clinical studies expected to start in Q2-2021.