NV354, Potential Therapy for Mitochondrial Diseases, Shows Promise in Preclinical Studies

NeuroVive Pharmaceutical’s therapeutic candidate NV354 for mitochondrial diseases, such as Leigh syndrome, was able to restore the body’s own energy substrate — succinate — in an in vivo model of mitochondria dysfunction, preclinical results show.

Moreover, researchers observed that NV354 is efficiently delivered to the brain.

Magnus Hansson, PhD, NeuroVive’s chief medical officer, presented a poster, titled “NV354—A brain penetrant, orally bioavailable succinate prodrug in development for Leigh syndrome,” at The Evolving Concept of Mitochondria: From Symbiotic Origins to Therapeutic Opportunities meeting, running through Oct. 21 at the Cold Spring Harbor Laboratory (CSHL) on Long Island, New York.

“This is indeed very promising first efficacy data in a model highly relevant to patients with mitochondrial disease,” said Hansson, who is also the vice president of preclinical and clinical development at NeuroVive, in a press release.

Mitochondrial energy production depends on a chain of five main complexes that, if failing to work properly, lead to severe energy deprivation and cell death.

Leigh syndrome is a progressive neurodegenerative disorder whose symptoms arise during early childhood, due to defects in mitochondrial energy production, namely dysfunctions of the complex I. This and other pediatric mitochondrial diseases have few treatment options.

NV354 is the lead compound in Neurovive’s NVP015 program for genetic mitochondrial diseases that aims to develop therapies that can bypass mitochondria dysfunction.

The compound enables mitochondrial substrate succinate delivery to cells via prodrug technology, which ultimately increases cell energy production. A prodrug is an inactive drug that is activated after administration by transformation of its chemical structure.

The presented preliminary data supports the clinical development of NV354, showing that it is able to reach the brain in a model of Leigh syndrome, while retaining its stability in the blood.

Further studies are ongoing to assess the effectiveness of NV354 over the short and long term.

“We expect additional ongoing efficacy studies to provide further guidance for future clinical development, including the extensive studies planned at the Children’s Hospital of Philadelphia,” Hansson said.

“The most exciting finding from the ongoing studies is that through its drug properties, NV354 demonstrates potential to treat not only acute, but also chronic conditions in patients with mitochondrial disease, which expands therapeutic opportunities as well as commercial potential,” said NeuroVive CEO Erik Kinnman.