Our bodies rely on the food we eat—specifically sugar and fat—to fuel our cells' mitochondria, the internal powerhouses that provide the energy needed for all our vital functions. However, over time, as mitochondria convert fuel into energy, they naturally accumulate damage caused by free radicals. These highly reactive molecules, known as reactive oxygen species (ROS), are a byproduct of mitochondrial activity.

An excess of these molecules can lead to oxidative stress and cellular damage via an iron-dependent cell death mechanism called ferroptosis. If left unchecked, this damage can contribute to a range of serious health conditions, impacting everything from metabolic processes to neurological function.

In case of metabolic disorders, energy expenditure in mitochondria may also be suppressed, which promotes further disruption of mitochondrial function and metabolism and exacerbates obesity and comorbidities.

The Challenge of Protecting Mitochondria

There are antioxidant molecules that can neutralize ROS in laboratory settings, but effectively targeting oxidative stress within mitochondria has been a challenge. Many antioxidants distribute throughout the body but fail to reach the mitochondria in sufficient quantities to offer meaningful protection.

A New Approach: Targeted Mitochondrial Action

Our groundbreaking drug candidates directly address mitochondrial function and energy expenditure. By specifically targeting and neutralizing ROS within the mitochondria, they help protect against oxidative damage. Mild mitochondrial uncoupling action of our lead compound also significantly enhances energy expenditure, increasing the rate of burning lipids for energy. This novel approach not only safeguards mitochondrial health but also regulates key biological processes involved in many serious diseases, such as rare mitochondrial disorders and metabolic disorders, offering potential for significant therapeutic benefits.

Neurodegenerative Disorders

Mitotech is pioneering a "first-in-class" small molecule designed to specifically target and inhibit ferroptosis at its origin—within the mitochondria. By blocking ferroptosis, particularly in neurons within the central nervous system ( CNS), our lead candidate holds promise for halting or slowing the progression of neurodegenerative diseases.

Our lead candidate demonstrated robust efficacy in models of Friedreich’s Ataxia (FA) and Multiple Sclerosis (MS).

  • Protection of FA patient fibroblasts from ferroptosis-mediated cell death in vitro using low doses of SkQ1 alone and enhanced protection in combination with omaveloxolone.
  • Significantly reduced disease scores and histology inflammation scores, as well as reduced plasma levels of neurofilament light chain (Nfl), in mouse EAE model of MS.
Brain

Metabolic diseases

Mitotech’s innovative, mitochondria-targeted orally bioavailable candidate is designed to address key cellular processes involved in obesity and related metabolic disorders. This small molecule targets the root causes of metabolic dysfunction at the mitochondrial level by increasing energy expenditure and protecting organ tissue from ferroptosis and inflammation. In preclinical models of obesity our compound demonstrated several robust benefits from rapid weight loss to preserving muscle mass.
Mouse
Liver
In Metabolic Dysfunction-Associated Steatohepatitis (MASH), by blocking ferroptosis, the molecule aims to halt the development and progression of steatosis and fibrosis and potentially prevent long-term liver damage.

In preclinical MASH models, our treatment led to significant improvements in several key biomarkers associated with liver health and metabolic function.