emoxypine (NP-178) / Algernon Pharma - LARVOL DELTA

Emoxypine succinate modulates behavioral and molecular responses in zebrafish model of iron Overload-Induced neuroinflammation via CDK5/GSK3- β and NLRP3 inflammasome pathway. (PubMed, Brain Res) - "Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1β, TNF-α, CDK-5, GSK-3β and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Hematological Disorders • Inflammation • Pain • CAT • GSK3B • IL1B • NLRP3 • TNFA

Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti-ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs. (PubMed, Drug Test Anal) - "Emoxypine (ethylmethylhydroxypyridine) is a synthetic derivative of vitamin B6...Metabotropic and antihypoxic effects of Mexidol were compared to the effects of meldonium or trimetazidine, both of which are included on the World Anti-Doping Agency (WADA) Prohibited List in category S4.4...Other related succinate-based drugs include Remaxol, Reamberin, and Cogitum. Mexidol and Cytoflavin and related substances exhibit similar biological effects as drugs on the WADA Prohibited List, and if they are used for performance enhancement by athletes, they could be worthy of consideration as prohibited substances in sport."

Journal • Review • Infectious Disease

Unauthorized ingredients in "nootropic" dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents. (PubMed, Drug Test Anal) - "Many popular nootropics are unauthorized food or DS ingredients according to the European Commission including huperzine A, yohimbine, and dimethylaminoethanol; unapproved pharmaceuticals like phenibut or emoxypine (mexidol); previously registered drugs like meclofenoxate or reserpine; EU authorized pharmaceuticals like piracetam or vinpocetine; infamous doping agents like methylhexaneamine or dimethylbutylamine; and other investigational substances and peptides. While stimulants and ß2-agonists are defined as doping agents by the World Anti-Doping Agency (WADA), many nootropics are not, although some may qualify as non-approved substances or related substances under catch-all language in the WADA Prohibited List. Synergistic combinations, excessive dosing, or recently researched pharmacology may justify listing certain nootropics as doping agents or warrant additional attention in future regulations."

Journal • Review

Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications. (PubMed, Curr Res Pharmacol Drug Discov) - "The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents."

Journal • Review • Acute Kidney Injury • Alzheimer's Disease • CNS Disorders • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease

Theoretical insights into the antiradical activity and copper-catalysed oxidative damage of mexidol in the physiological environment. (PubMed, R Soc Open Sci) - "MD can chelate Cu(II), forming complexes that are much harder to reduce than free Cu(II): MD chelation completely quenches the Cu(II) reduction by ascorbic acid and suppresses the rate of reduction reaction by that are the main reductants of Cu(II) in biological environments. Therefore, MD exerts its anti-HO activity primarily as an OIL-1 inhibitor."

Journal • CNS Disorders • Mood Disorders • Psychiatry

An effect of 3-oxypyridine and succinic acid derivatives on the time of reduction of anxiety and depression symptoms in alcohol withdrawal treatment (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "All the studied drugs reduced the duration of certain anxiety and depression symptoms during AWS treatment. The degree of this effect depended on the features of the chemical structure of a drug. Mexidol accelerated the reduction of «dread», «respiratory» and «cardiovascular» anxiety symptoms (HARS) by 25-50%. «Reduced appetite» and «concentration difficulty» (MADRS) improved by 28.5%. Reamberin reduced the duration of «gastrointestinal» and «respiratory» anxiety symptoms (HARS) by 17-50% and «inner tension» (MADRS) by 7%. Emoxypine accelerated the reduction of «insomnia» and «respiratory» symptoms (HARS) but did not affect the duration of objective depression symptoms (MADRS). Emoxypine and reamberin reduced the severity of affective and cognitive symptoms (BDI) by 32-37%. None of the drugs affected self-reported anxiety (ZSRAS). The most balanced treatment of depressive..."

Clinical • Journal • Cardiovascular • CNS Disorders • Depression • Gastrointestinal Disorder • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Algernon plans launch of first phase 2 trial on repurposed IPF or IBD compound by mid-2020 (Pulmonary Fibrosis News) - "Algernon Pharmaceuticals has announced its plans to launch its first Phase 2 clinical trial evaluating...NP-178 for inflammatory bowel disease (IBD) — in the second quarter of 2020."

New P2 trial

Algernon announces pricing and filing of amended and restated prospectus (GlobeNewswire) - "Algernon Pharmaceuticals Inc...is pleased to announce it has filed and received a receipt for an amended and restated short form prospectus...in connection with its marketed public offering....The net proceeds raised under the Offering will be used to fund the NP-178 IBD Trial or NP-120 IPF Trial, additional Phase 2 study planning and research and development."

Financing

Algernon Pharmaceuticals Announces Emoxypine (NP-178), a Top Selling Drug in Russia, as its Lead Drug for Inflammatory Bowel Disease (GlobeNewswire, Algernon Pharmaceuticals) - VANCOUVER, British Columbia, Aug 02, 2019 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc (CSE: AGN) (FRANKFURT: AGW) (OTCB: BTHCF) (the “Company” or “Algernon”), a clinical stage pharmaceutical development company, is pleased to report that its lead drug for inflammatory bowel disease (IBD) is Emoxypine (NP-178), an orally delivered small molecule. The Company observed that NP-178 (Emoxypine) exhibited highly statistically significant activity in both Chrohn’s disease (CD) and ulcerative colitis (UC) models, paralleling or outperforming standard of care treatment 5 amino salicylic (5-ASA). Further, in the UC study, Algernon’s NP-120 (Ifenprodil) which was recently announced as its lead drug for idiopathic pulmonary fibrosis (IPF), displayed significant anti-diarrheal properties. This is noteworthy because Pirfenidone, one of two approved therapies for IPF, often causes severe diarrhea which reduces compliance.

Clinical • Regulatory

Np-120 and Np-178: Repurposed Neurological Drugs with Efficacy in Animal Models of Ulcerative Colitis and Crohn’s Disease (DDW 2019) - "A second compound NP-121, which shares a common receptor target as NP-120, also demon- strated activity in the CD model, albeit with weaker efficacy than that of NP-120. Efforts are underway to elucidate the mechanism of action and clinical relevance of the compounds in advance of the planning for a Phase II clinical trial to test the efficacy of the compounds."

Preclinical

Nash Pharmaceuticals to Present Data on Its Inflammatory Bowel Disease Research Program at The Digestive Disease Week Annual Conference (GlobeNewswire, Breathtec Biomedical Inc.) - "Results of Nash’s recently announced Crohn's study demonstrated significant improvements in multiple measurements for both NP-120 and NP-178 including: NP-120 (30 mg/kg) reduced the histopathology severity score by 45.1% (p<0.01); NP-178 (160 mg/kg) reduced the histopathology severity score by 66.8% (p<0.001); Results of Nash’s recently announced ulcerative colitis study demonstrated significant improvements in multiple measurements for both NP-120 and NP-178 including: NP-120 (30 mg/kg) reduced the histopathology severity score by 81.6% (p<0.0001); NP-178 (160 mg/kg) reduced the histopathology severity score by 83.1% (p<0.0001)."

Preclinical

Nash Pharmaceuticals announces positive pre-clinical results for its lead compound NP-178 in a new study for Crohn’s disease (GlobeNewswire) - "Nash Pharmaceuticals...announce that in a recent in vivo animal study for Crohn’s disease (CD), NP-178, its lead compound for the treatment of ulcerative colitis (UC), performed equivalent to and in some measurements, better than 5-ASA, a current global standard of care treatment for inflammatory bowel disease (IBD)....In addition, the Company announces the discovery of a second compound, NP-120 that was also active in both of the Company’s UC and CD in vivo studies. Both NP-178 and NP-120 are currently used clinically for the treatment of neurological diseases. The Company believes that NP-178 & NP-120 may modulate novel targets for IBD..."

New molecule • Preclinical