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COVID-19 nanoFenretinide Concept Paper

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COVID-19 Therapeutic Opportunity: ST-001 nanoFenretinide may offer additional support in the battle against the COVID-19 pandemic. SciTech’s concept paper on ST-001 nanoFenretinide enhanced retinoid treatment of viral SARS (severe acute respiratory syndrome). For more info visit https://www.scitechdevelopment.com/covid-19

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COVID-19 nanoFenretinide Concept Paper

  1. 1. ST-001 (nanoFENRETINIDE IV): Enhanced Retinoid Treatment of Viral SARS β-caretenoids anti-oxidant activity vitamin-A reduces pneumonia in measles fenretinide ↓ CRS (IL-6, IL-10, IL-12, TNFα) in murine model2 -vitamin-A SOC in measles1 -fenretinide reported activity in vitro and in murine models Fenretinide (HPR) • Top 50 SARS-CoV-2 treatment candidate, amongst 5,406 (60% of US FDA-approved drugs) (Ko 2020) • Best tolerated, clinically-active retinoid derivative • Safer than Vitamin A (Moon 1979) o ~300 mg/kg/dx5 qWk oral retinyl acetate or ATRA = mouse LD50, but fenretinide non-toxic • 1Vitamin A supplementation improves clinical outcomes in children with severe measles (Hussey 1990, Ellison 1932) • Plasma concentration of 25 μM at safe dose in humans through 120 hr continuous infusion (Mohrbacher 2017) • Inhibits MERS-CoV at 2.8 μM (Ko 2020) • All properties of Retinoid, PLUS direct effects on viral replication and cytokine storm • 4 hr infusion of 40 mg/m2 to achieve calculated plasma concentration of 20 μM (SciTech IND #135475) • Inhibits SARS-CoV-2 at 2 μM • Only triglyceride-free IV formulation to avoid previously observed hypertriglyceridemia toxicity • Compatible with monoclonal antibody therapies in preclinical models Viremia Immune Response Recovery Cytokine Storm (CRS) ↑ IL-6, ↑ IL-22 Tissue Inflammation/ Free-Radical Alveolar Damage - ↑ extracellular heme - ↓ ascorbate, Cyt b561 - Fe3+ oxyradical damage ARDS Pneumonia RETINOIDANTIVIRALKNOWLEDGEBASE ST-001 (nanoFENRETINIDE IV) β-caretenoids anti-oxidant activity vitamin-A reduces pneumonia in measles fenretinide ↓ CRS (IL-6, IL-10, IL-12, TNFα) in murine model2 -vitamin-A SOC in measles1 -fenretinide reported activity in vitro and in murine models Viremia Immune Response Recovery Cytokine Storm (CRS) ↑ IL-6, ↑ IL-22 Tissue Inflammation/ Free-Radical Alveolar Damage - ↑ extracellular heme - ↓ ascorbate, Cyt b561 - Fe3+ oxyradical damage ARDS Pneumonia

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