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Mitochondrial Disease: NeuroVive’s Mitodrug "KL1333"-Works Better Than CoQ10 And Idebenone-Frontiers In Neurology

|About: Neurovive Pharmaceutical AB (NEVPF)


$NEVPF stock on OTCQX hits 6 month high Friday at $0.63, up 19% on the day, up from all time low of $0.25 April 2018.

US volume thin for NEVPF, while Stockholm Nasdaq volume (NVP.ST) traded robust 3.3 million shares Friday, for Sweden's home team mitochondrial medicine company.

Market energized by reveal of how, and how well, KL1333 works on powering the mitochondria.

NeuroVive Pharmaceutical's genetic mitochondrial disease drug candidate KL1333 mechanism of action published in the scientific journal-Frontiers In Neurology.

Download and read the full scientific article for yourself here:

The Frontiers in Neurology paper is “KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts“.

NeuroVive Pharmaceutical AB, a public company listed on the Stockholm, Sweden Nasdaq (NVP.ST) and the American OTC QX (OTCQX:NEVPF) exchanges, based in Lund, Sweden, got its start in 2000 as a neuroprotection company, with an in-license from private American company Maas Biolab for cyclosporin as an acute brain injury treatment drug, followed by in-licensing of a superior intravenous lipid emulsion cyclosporin formulation from a private German company CicloMulsion. When NeuroVive found that its lead NeuroSTAT® drug, (cyclosporin in lipid emulsion) for traumatic brain injury's mechanism of action as a neuroprotectant was primarily through the mitochondria, the focus of the company grew to include other mitochondria protecting drugs. One of these drugs was the in-license from the public South Korean company Yungjin Pharmaceutical Corporation Ltd (South Korea Stock Market, KRX 003520), of their mitochondrial drug KL1333, to treat MELAS, and related genetic diseases.

MELAS is short for "Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes". MELAS is rare, but also the most common maternally inherited mitochondrial disease, affecting mainly children 2 to 15 years old. Up to 4000 children per year in the USA are born with a mitochondrial disease. Mitochondrial DNA mutations cause mitochondrial dysfunction, and in MELAS, the cells get overloaded with toxic lactic acid. MELAS is a progressive neurodegenerative syndrome in children leading to multiple organ failure at a young age caused by malfunctioning mitochondrial churning out excess lactic acid. Lactic acid is a normal byproduct of energy metabolism, but in excess is toxic. Lactic acid creates the burn felt in normal muscles during heavy exercise. In these MELAS children, the uncontrolled lactic acid production burns out their muscles, tissues and organs, even when they are at rest. MELAS children can be afflicted with stroke, permanent cognitive impairment, headache, vomiting, seizures, deafness, and muscle breakdown. Over the counter mitochondrial supplements CoQ10, vitamin C, creatine, sodium pyruvate, and L-arginine are used to try to treat MELAS, but are not adequately effective. The hope is that KL1333 will be the effective treatment for this and other mitochondrial diseases, NeuroVive has already obtained Orphan Drug designation for KL1333 to treat MELAS/mitochondrial diseases in both of the world's two largest markets of the USA and Europe. 

JungJin Pharmaceutical Company kept the rights to KL1333 for South Korea and Japan, so JungJin is conducting a Phase 1 clinical trial of KL1333 in normal healthy volunteers in Korea, and also this revealing research showing how the drug works. NeuroVive's Swedish CEO, Erik Myung-Jin Kinnman, has family connection to Korea, perhaps facilitating this successful in-license deal by a Swedish company from a Korean company, which also shows some of NeuroVive's international diversity. 

Briefly, KL1333 is an orally available, small organic molecule. KL1333 works inside the mitochondria by reacting with NAD(NYSE:P)H:quinone oxidoreductase 1 (NQO1), dramatically increasing production of intracellular NAD+ levels. Elevated NAD+ (nicotinamide adenine dinucleotide) then activates SIRT1, AMPK, and  PGC-1α. From the mitochondrial medicine, and longevity literature, you know that activated SIRT1, AMPK and PGC-1α are essential to mitochondrial neogenesis, or mitogenesis, which is the division and growth of healthy young new mitochondria. Enriched mitogenesis incidentally is seen as a means toward enhanced vitality and longevity in healthy adults, as well as helping those with various mitochondrial related diseases. KL1333 also increases the ATP energy levels, decreases lactic acidosis, and decreases production of free radical levels in MELAS cells. 

KL1333 is remarkably more effective than CoQ10, and even idebenone, in making mitochondria produce NAD+, and then ATP, the main high energy source of cells.

Recently a number of companies and researchers in the mitochondrial medicine space have proposed ways of increasing NAD+ toward boosting mitochondrial function for longevity, metabolism and health. For instance, Chromadex's (CDXC) nicotinamide riboside (Niagen®, Chromadex, NASDAQ - CDXC) increases mitochondrial biogenesis and whole-body metabolism, with robust premium price sales of competing products across the USA. Idebenone is championed as Roxone® by Santhera (OTCPK:SPHDF) as a treatment for Duchenne muscular dystrophy (Roxone®, Santhera Pharmaceuticals Holding AG OTC - $SPHDF). KL1333 is much more effective in raising mitochondrial production of ATP in normal and MELAS cells than either CoQ10 or idebenone in this publication. 

The researchers demonstrate that increasing NAD+ through KL1333, augments strongly production of ATP, mitogenesis, mitochondrial mass, membrane potential, reduces formation of toxic free radicals, and in the MELAS cells, reduces lactic acidosis. 

Next steps for NeuroVive will be to start their own KL1333 Phase 1 safety study in Europe or the USA, piggybacking on the safety work done by JungJin, toward treatments for the Orphan designation for MELAS and related mitochondrial diseases. Given the impressive results from these Korean researchers led by first author Kang-Sik Seo, it seems likely that KL1333 will have utility in other diseases, longevity and health, where mitochondria are thought to play an essential role. 

The NeuroVive stock is traded in the USA on the OTC QX with ticker NEVPF. The stock price is recently just off all-time lows of $0.25 in April 2018, and closed sharply up at $0.63 or 19% for the day, on Friday 7/6/2018 with the release of this KL1333 mechanism of action article.

The NEVPF stock price had its all time high of $11.37 in August 2014. The company has regrouped and rebuilt from the disappointment of a Phase 3 heart attack trial, reported to be a fail by Management. Now NeuroVive has a much broader base of assets, including the original NeuroSTAT cyclosporin formula for traumatic brain injury in Phase 2, this KL1333 mitochondrial drug for Orphan disease MELAS in Phase 1, a liver focus with cyclophilin inhibitor sangamide derivatives that have potential roles as treatments against hepatitis B and C, NASH, fibrosis, cirrhosis, and hepatocellular carcinoma.

The company has rebuilt, but the stock market price has not yet begun to catch up with the value. The NEVPF stock, I believe, represents an undervalued Swedish company with multiple mitochondrial drug assets, ready for clinical drug development, out-license deals, and acquisition by large pharma.

The Frontiers in Neurology paper is “KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts“.

The short abstract summary can be read here: KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts

The full scientific paper can be downloaded and shared for free (public access) here: KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts.

Visit the link to the NeuroVive website: A leader in mitochondrial medicine - Neurovive for the full R & D program. There are other mitochondrial assets and potential treatments in development with Cambridge, England based bioengineering synthetic chemists partner Isomerase Therapeutics (Home).

Disclosure: I am/we are long NEVPF.

Additional disclosure: Maas Biolab, LLC is a privately held American company that owns less than 5% of the NeuroVive stock. Maas Biolab, and a consortium of America-based investors, had previous Board representation at NeuroVive Pharmaceutical until April 2018. Neither Maas Biolab's Board, nor members of the America-based consortium, are on any Insider lists with NeuroVive, or the Swedish regulatory authorities (Finansinspektionen) and have no confidential NeuroVive information.