Technology platform

Proprietary human brown fat discovery platform

Energesis was founded around the discovery by its scientific founders of human brown fat stem/progenitor cells. These primary cells can be massively expanded and used in drug discovery. When triggered to develop, they become brown fat cells with the RNA expression, protein expression, appearance, and mitochondrial respiration characteristics of human brown fat.

 

Energesis built a proprietary discovery platform to identify compounds capable of triggering these progenitor cells to become brown fat cells. The company has used the platform to screen compound libraries, including previously approved drugs, to identify brown adipogenic activity.

 
Human Cell System

Based on adult human brown adipocyte progenitor cells.

Drug Discovery Engine

Designed to identify compounds and targets that can promote brown fat formation.

Protected Pipeline

Patent filings cover the platform, EGS-2632, and earlier-stage compounds.

 
How the screen works

From human cells to drug candidates

Energesis has employed phenotypic screens using human brown fat progenitor cells, analogs of which also exist in mice and non-human primates.

1
Grow the cells

Natural, unmodified human progenitor cells are expanded in large quantities in the lab.

2
Screen libraries

The cells are exposed to various agents one at a time, including approved drugs, new chemical compounds, proteins and peptides.

3
Watch for brown fat

Within days, active agents turn the cells into brown fat cells, tracked by the change in appearance of the cells, as well as the production of thermogenic genes including UCP1.

4
Find and refine

The team identifies a promising agent’s target, then uses medicinal chemistry to make drug candidates more potent and selective.

 

When an agent turns the cells into brown fat, the team knows three things at once:

  • It reached its cellular target.
  • It changed the target in the right way.
  • It did not harm the cells.

The founding discovery: Energesis’ scientific founders identified adult human brown fat progenitor cells in the walls of blood vessels in skeletal muscle (Stem Cells, 2008). A year later, three landmark papers confirmed that adults have active brown fat. Before then, most scientists believed only infants did.

What it has found

New targets and a lead candidate

Two new drug targets

Screening thousands of approved drugs, new chemical compounds, proteins and peptides led to two drug targets no one knew could create brown fat.

EGS-2632

Energesis screened more than 1,200 previously approved drugs and picked the most active agents by the number of brown fat cells formed and by the level of thermogenic markers (PPARγ2 and UCP1) being expressed.

Follow-on compounds

Medicinal chemistry has turned early hits into candidates that are more potent and selective.

 

In mice with diet-induced obesity, the most promising compounds increased brown fat, raised resting energy expenditure, and reduced body weight and body fat. They also improved glucose metabolism.

Preclinical results may not predict human safety or efficacy.