sodium chlorite (NP001) / Neuraltus, Clinigen, Neuvivo - LARVOL DELTA

Mounting Evidence Demonstrates Neuvivo’s NP001 Spares Lung Function and Substantially Extends Survival in ALS Patients (Businesswire) - "Neuvivo...today announced promising new results from a fresh analysis of a previous study of its investigational immunotherapy platform NP001 to treat Amyotrophic Lateral Sclerosis (ALS), which builds on evidence that NP001 spares lung function and substantially extends survival in ALS patients...Results from this analysis targeting 'non-progressors' showed that the NP001 treated group significantly (p=0.02) slowed or halted the loss of vital lung capacity compared with the control group (~70% on riluzole). Vital capacity is a quantitative but separate measure from the ALSFRS-R test that more accurately assesses a patient’s lung function. Changes in vital capacity have been clearly associated with survival in ALS...In this non progressor group, slowing of vital capacity loss and extension of survival was accompanied by the correction of inflammatory abnormalities and associated neuronal damage marker NfL."

Retrospective data • Amyotrophic Lateral Sclerosis

Isolation and characterization of cellulose from spent ground coffee (Coffea Arabica L.): A comparative study. (PubMed, Waste Manag) - "This study compares several methods, such as sodium chlorite, nitric acid, and hydrogen peroxide treatments with alkali pre-treatments, for efficiency of extracting cellulose from spent ground coffee...The maximum degradation temperature of the spent ground coffee increased from 292.0 to 310.5 °C after treatment with 10 wt% hydrogen peroxide and alkali pre-treatment. In summary, these findings highlight the great potential of spent ground coffee as a source of cellulose."

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Synergistic effects of gamma irradiation/salmide®, a sodium chlorite-based oxy-halogen, on microbiological control and the shelf life of chicken breasts. (PubMed, World J Microbiol Biotechnol) - "Furthermore, a 16 day shelf life extension was achieved with gamma irradiation at 3 kGy, either alone or in combination with Salmide, resulting in a reduction of total aerobic bacteria by 5 logarithmic cycles. This study is the first to employ Salmide in conjunction with gamma irradiation as an innovative technology in a portable chamber to enhance the safety and shelf life of chicken breasts during storage in the designed portable chamber."

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Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression. (PubMed, Biomedicines) - "The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis. (PubMed, Biomedicines) - P2 | "The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Overall Survival Study (Businesswire) - P=NA | N=268 | "Neuvivo clinical investigators conducted a blinded, placebo-controlled, retrospective study looking at up to 11 years of patient data that demonstrated a pronounced extension of survival in people living with ALS (n=268). The study followed the original participants who were initially treated with NP001 for six months during its Phase 2a and 2b trials to determine the therapy’s long-term impact on survival. The total population (ITT), which included adults 80 years old and under, resulted in extended survival of 4.8 months (Hazard Ratio: 0.77; 95% CI: 0.57, 1.03). However, a subset of people 65 years of age and younger had an extended survival of 10.8 months (Hazard ratio: 0.69; 95% CI: 0.50, 0.95)."

Retrospective data • Amyotrophic Lateral Sclerosis

Identifying Practical Biomarkers Predicting Lung Function and Survival (Businesswire) - P=NA | N=NA | "Neuvivo’s biomarker identification study showed results from an analytical review of specific patients with moderate levels of inflammation (plasma C-reactive protein (hsCRP) level of > 1.13 mg/L) who participated in the 11-year Overall Survival study....In the biomarker study, median overall survival was extended by 17.1 months compared with a placebo (45.5 months vs 28.4 months, respectively; p = 0.005) in patients with moderate underlying inflammation and low baseline creatinine levels treated with six cycles of NP001."

Clinical data • Amyotrophic Lateral Sclerosis

Neuvivo Seeks FDA Approval for Its Breakthrough ALS Treatment NP001 (Businesswire) - "Neuvivo...announced it submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for NP001 (sodium chlorite infusion) to treat amyotrophic lateral sclerosis (ALS). NP001 is an investigational treatment that, if approved, could be the first disease-modifying therapy for ALS that restores balance over uncontrolled inflammation within the body’s own innate immune system."

FDA filing • Amyotrophic Lateral Sclerosis • Immunology

Cellulose nano-dispersions enhanced by ultrasound assisted chemical modification drive osteoblast proliferation and differentiation in PVA/HA bone tissue engineering scaffolds. (PubMed, Int J Biol Macromol) - "The ALP activity reached 1.71 ± 0.25 (ALP activity/mg protein). In conclusion, the scaffolds we developed have good biocompatibility and mechanical properties and have great potential in promoting bone defect repair."

Journal

Corncob-derived biodegradable packaging films: A sustainable solution for raspberry post-harvest preservation. (PubMed, Food Chem) - "It preserves raspberries for 7 and 5 more days at room temperature and refrigeration conditions, respectively, compared to polystyrene film. Overall, more value addition could be envisioned from agricultural residues to minimize post-harvest losses and food waste through biodegradable packaging, which also aids in mitigating plastic perils."

Journal • Infectious Disease

Life cycle assessment and techno-economic analysis of wood-based biorefineries for cellulosic ethanol production. (PubMed, Bioresour Technol) - "Minimum ethanol selling price below ethanol international market price is promising with higher-levels technology. Further work should be focused on technological breakthrough, consumable reduction or replacement."

HEOR • Journal

Efficacy of sodium chlorite in inactivating Vibrio parahaemolyticus attached to polyethylene terephthalate surfaces. (PubMed, J Microorg Control) - "At all pH values, the k values calculated for the attached cells were approximately half of those for the unattached cells. These findings indicate that a weakly acidic NaClO solution is effective in inactivating bacteria attached to hard surfaces."

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Comparison of peroxyacetic acid and acidified sodium chlorite at reducing natural microbial contamination on chicken meat pieces. (PubMed, Poult Sci) - "All wash treatments reduced the proportion of Salmonella positive samples, but the greatest reduction was observed for 225 ppm ASC. Both concentrations of ASC resulted in a greater reduction in total viable counts compared with chlorine."

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Neuvivo Raises $11M in Venture Financing to Develop Treatment for ALS (PRNewswire) - "Neuvivo...today announced that it has closed on an $11M round of financing led by PrimeStreet Capital. Neuvivo is pleased to announce that PrimeStreet Capital General Partner, Virit Vichitvadakan, will join the company's Board of Directors. 'We are delighted to have completed this key funding for the continued development of NP001 for the treatment of ALS and we warmly welcome Virit to our Board.'"

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders

Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS. (PubMed, Cells) - "To understand the role of the innate immune response in progressive VC loss we evaluated ALS clinical trial and biomarker results from a 6-month phase 2 study of NP001, a regulator of innate immune function...Plasma TGFB1 in high CRP treated patients was 95% higher than placebo at 6-months, confirming the activation and release of this anti-inflammatory factor by the innate immune alpha 2 macroglobulin (A2M) system. This report is the first to link a biomarker confirmed regulation of the innate immune system with a therapeutic approach for controlling VC loss in ALS patients."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Respiratory Diseases • A2M • TGFB1

New Study of Neuvivo's NP001 is First to Link Regulation of the Innate Immune System with Respiratory Function in ALS Patients (PRNewswire) - P=N/A | N=N/A | “Neuvivo today announced the publication of a peer-reviewed paper…The biomarker study used vital capacity (VC)…to highlight the relationship between a compromised innate immune system and ALS disease activity….In this study, NP001 was shown to have a significant positive impact on respiratory activity by augmenting the natural function of the innate immune system….NP001-treated patients with high CRP lost 0.75% of vital capacity per month. Placebo group patients with high CRP lost 2.1% of vital capacity per month. These data represent a 64% slower rate of decline in high CRP patients receiving NP001 (p=0.05). Importantly, plasma TGFB1, a dominant regulator of inflammation, was 95% higher after 6 months in high CRP treated patients compared with controls. (p < 0.02).”

Biomarker • Clinical data • Amyotrophic Lateral Sclerosis • CNS Disorders

Phosphorylated Cotton Cellulose as a Matrix for Generating Chlorine Dioxide. (PubMed, Polymers (Basel)) - "Our work presents a modified cellulose material, and the data obtained for the first time on the chlorine dioxide generation process when treating the material with a sodium chlorite alcohol solution...A promising technique for removing the excess ClO by the means of UV treatment is proposed: after 15 min of treating ClO in the gas phase, it disappears entirely. These materials could be used as disinfectants in different industries, such as food and industrial manufacturing."

Journal

Effectiveness and Safety of Over-the-Counter Tooth-Whitening Agents Compared to Hydrogen Peroxide In Vitro. (PubMed, Int J Mol Sci) - "(2) Human teeth (n = 60) were randomly assigned into 6 groups (n = 10), stained with coffee solution for 7 d, followed by a whitening period of 7 d with either placebo, bromelain, sodium bicarbonate, sodium chlorite, PAP or hydrogen peroxide. (4) The maximum effect achieved by all OTC bleaching agents was the removal of stains, whereas hydrogen peroxide was capable of further whitening the teeth. Bromelain treatment was neither cytotoxic, nor resulted in enamel surface alterations, and its whitening effect was less, yet still effective, compared to hydrogen peroxide."

Journal • Preclinical

Cytotoxic screening and in vitro effect of sodium chlorite against Leishmania major promastigotes. (PubMed, J Parasit Dis) - "The results of the present study showed that sodium chlorite could be used as an effective treatment for CL, especially in cases resistant to treatment with pentavalent compounds. However, the toxicity of this substance in high concentrations should be considered in clinical setting."

Journal • Preclinical • Dermatology • Infectious Disease

Neuvivo's NP001 for Treatment of ALS Slows Disease Progression Through Regulation of Microbial Translocation (PRNewswire) - P2a | N=136 | NCT01281631 | Sponsor: Neuraltus Pharmaceuticals, Inc. | “Neuvivo today announced the publication of a peer-reviewed paper…The goal of the biomarker-focused study was to test the relationship between NP001 macrophage-targeted immune regulation and the theory that microbial translocation contributed to ALS progression….NP001 treatment has been shown to restore the normal process of resolution in the inflammatory cycle…In this study, the immunoregulatory activity of NP001 treatment has been confirmed via the normalization of key blood biomarkers….Biomarker data showed that factors associated with harmful microbial translocation (LPS, LBP and HGF), monocyte trafficking (sCD163) and inflammasome activation (IL-18) were significantly decreased in NP001 recipients as compared to placebo over 6 months.”

Biomarker • P2a data • Amyotrophic Lateral Sclerosis • CNS Disorders

Macrophage-Targeted Sodium Chlorite (NP001) Slows Progression of Amyotrophic Lateral Sclerosis (ALS) through Regulation of Microbial Translocation. (PubMed, Biomedicines) - "Compared with baseline values, biomarkers related to MT were significantly decreased (LPS, LPS binding protein (LBP), IL-18, Hepatocyte growth factor (HGF), soluble CD163 (sCD163)) in NP001-treated patients as compared to controls, whereas wound healing and immunoregulatory factors were increased (IL-10, Epidermal growth factor (EGF), neopterin) by the end of study. These biomarker results linked to the positive clinical trial outcome confirm that regulation of macrophage activation may be an effective approach for the treatment of ALS and, potentially, other neuroinflammatory diseases related to MT."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • CD163 • CRP • EGF • HGF • IL10 • IL18 • LBP

Peroxyacetic acid and acidified sodium chlorite reduce microbial contamination on whole chicken carcasses obtained from two processing points. (PubMed, Food Microbiol) - "No significant difference between the three sanitizers was observed for the reduction of TVC, Campylobacter or Salmonella using carcasses obtained at either processing step. These results demonstrate that PAA or ASC could be implemented as a replacement or used in addition to sodium hypochlorite to effectively reduce bacteria on whole carcasses."

Journal • Gastroenterology • Gastrointestinal Disorder

Neuvivo’s NP001 - an Immune System Regulator - Has Effect on Biomarkers of Microbial Translocation in ALS Patients Responsive to Treatment (PRNewswire) - P2 | N= 138 | NCT02794857 | P2 | N=136 | NCT01281631 | Sponsor: Neuraltus Pharmaceuticals, Inc. | “Today, at the ENCALS Conference (European Network to Cure ALS) Neuvivo presented an abstract…In phase 2 studies with NP001 in ALS patients, clinical signs of disease activity and respiratory vital capacity were positively affected compared to controls. Plasma specimens obtained during the phase 2A study were evaluated for levels of inflammatory markers related to MT at baseline and after 6 months and compared to placebos. Baseline markers of MT (LPS, LBP, sCD163, IL-18) all decreased significantly in the NP001 treatment arm as compared to placebos (p = 0.04, 0.006, 0.02, 0.02, respectively) whereas the plasma levels of wound healing epidermal growth factor (EGF) and neopterin increased in patients treated with NP001 (p = 0.04 and 0.02 respectively).”

Biomarker • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

Neuvivo Closes on Additional Funding Round for NP001 Development (PRNewswire) - “Neuvivo…today announced that it has closed on an additional round of financing led by an international investment group. The Bay Area-based company is currently in regulatory discussions with the FDA around its lead candidate, NP001 for ALS.”

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders

Formulation of Chlorine-Dioxide-Releasing Nanofibers for Disinfection in Humid and CO-Rich Environment. (PubMed, Nanomaterials (Basel)) - "Chlorine dioxide was liberated into the gas phase in the presence of CO and water vapor, eliminating the bacteria. Sodium-chlorite-loaded nanofibers can be sources of prolonged chlorine dioxide production and subsequent pathogen inactivation in a CO-rich and humid environment. Based on the results, further evaluation of the possible application of the formulation in face-mask filters as medical devices is encouraged."

Journal • Infectious Disease