KL1333 is a small molecule medicine developed by Yungjin Pharm to treat mitochondrial diseases. It is now in-licensed to NeuroVive Pharmaceutical for clinical development.

KL1333 could be used to treat different types of mitochondrial disease, including MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), Kearns-Sayre syndrome (KSS), CPEO (chronic progressive external ophthalmoplegia), progressive external ophthalmoplegia (PEO), Pearson syndrome, and MERRF (myoclonic epilepsy with ragged-red fibers).

The European Commission granted KL1333 orphan drug designation in December 2017.

How KL1333 works

Mitochondrial diseases occur when the mitochondria — structures inside cells that are responsible for energy production — fail to function properly.

KL1333 increases cells’ energy output in three ways. First, it restores and increases the availability of a substance called nicotinamide adenine dinucleotide (NAD+) that helps in the breakdown of nutrients, an essential process in energy production. Increasing NAD+ also helps cells produce new mitochondria, a process called mitochondrial biogenesis, that increases their energy production capacity. KL1333 also directly transfers energy inside cells to the mitochondria, bypassing the most common sites of dysfunctions. Thus, it enhances energy output by optimizing its use. Finally, KL1333 defends against the production of reactive oxygen species (ROS) that are toxic to cells.

KL1333 in clinical trials

The first clinical trial of KL1333 (NCT03056209) is underway in Korea. It is a Phase 1, double-blind, placebo-controlled, single-dose, dose-escalation study sponsored by Yungjin Pharm.

The trial aims to recruit 80 healthy male volunteers, ages 19-45 years, to test the safety and tolerability of seven different oral doses of KL1333 ranging from 25 mg to 800 mg taken for 15 days. The primary outcome is the number of reported adverse events. Secondary outcomes are the maximum concentration of KL1333 in the blood and the time it takes for half of the amount of the medication to be eliminated from the body (half-life).

Promising results obtained with the 25 and 50 mg doses has led the Korean Ministry of Food and Drug Safety to approve the study’s remaining higher dose groups.

A multiple-dose, Phase 1b study of KL1333, sponsored by NeuroVive, also is planned to begin in Europe and/or the U.S. in 2018.

Other information

KL1333 is complementary to another treatment in development, NVP015, intended to treat episodes of energy crises in patients with mitochondrial disease, and to NV556, designed to protect mitochondria in skeletal muscle and prevent muscle wasting.

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