The proposed Phase I SBIR will conduct IND-enabling studies to establish the pharmacokinetics (PK) and SARS-CoV-2 (CoV-2) antiviral efficacy of sangivamycin (Sang) in Golden Syrian hamsters. Sang is an adenosine nucleoside analog that we discovered to be a potent, dose- dependent inhibitor of CoV-2 during in vitro viral infectivity studies conducted at the NIAID- Integrated Research Facility (IRF) at Fort Detrick. Sang had significantly superior efficacy against multiple variants of CoV-2 compared with Remdesivir but Sang also was additive with Remdesivir when used in combination. CoV-2 is the causative agent of COVID-19, which was first documented in China in December 2019 and has since rapidly spread across the globe, leading the World Health Organization to declare a global pandemic on March 11, 2020. CoV-2 has infected greater than 600 million individuals worldwide with at least 6.4 million attributable deaths to date. OyaGen has held type B preIND meetings with the FDA (PIND 150794). Historically, Sang was safely tested in 88 human subjects during NCI cancer clinical trials but was abandoned due to its lack of efficacy against cancers in human subjects. In this Phase I SBIR OyaGen seeks to complete preclinical development of Sang as a therapeutic candidate for COVID-19 to facilitate an IND application to conduct appropriate clinical trials leading to regulatory approval and commercialization. In response to FDA guidance and comments to our preIND filing (150794) the goal of this proposal is to conduct PK of Sang in a hamster animal model (Aim 1) as well as to determine in vivo antiviral efficacy of Sang in the hamster COVID-19 model (Aim 2). The development of Sang as a therapeutic for infected patients is a medical countermeasure for immunocompromised people who may not benefit from immunization as well as a stop gap therapeutic for new strains of CoV for which current vaccines may be less effective. Importantly, our data support that Sang has the potential to enhance the efficacy of other therapeutics as a combination therapy option in the future.
Public Health Relevance Statement: There is an urgent need for the development and commercialization of highly effective treatments for COVID-19. Currently there are only limited FDA-approved therapeutics to combat the SARS- CoV-2 (CoV-2) virus that has caused the COVID-19 global pandemic, killing more than 6.4 million people worldwide to date. OyaGen has discovered that sangivamycin is a highly potent antiviral for CoV-2. Sangivamycin was proven safe when evaluated in human cancer clinical trials performed in the 1960's. It however was ineffective against cancer and abandoned. In this Phase I SBIR application, preclinical studies are proposed in response to FDA guidance that will be IND- enabling and a prerequisite to Phase I clinical trial safety and pharmacokinetics evaluation in healthy volunteers. The development of sangivamycin as a therapeutic for infected patients is a medical countermeasure for immunocompromised people who may not benefit from vaccine immunization as well as a stop gap therapeutic for new strains of CoV for which current vaccines may be less effective. Importantly, our data support that sangivamycin has the potential to enhance the efficacy of other therapeutics as a combination therapy option in the future.
Project Terms: Adenosine; Animals; Antiviral Agents; Antiviral Drugs; Antivirals; anti-viral agents; anti-viral compound; anti-viral drugs; anti-viral medication; anti-viral therapeutic; anti-virals; antiviral compound; antiviral medication; antiviral therapeutic; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Felis catus; Cats; Cats Mammals; Domestic Cats; Feline Species; Felis domestica; Felis domesticus; Felis sylvestris catus; Cells; Cell Body; chemical synthesis; Chickens; Gallus domesticus; Gallus gallus; Gallus gallus domesticus; China; Mainland China; Clinical Trials; Combined Modality Therapy; Multimodal Therapy; Multimodal Treatment; combination therapy; combined modality treatment; combined treatment; multi-modal therapy; multi-modal treatment; Canis familiaris; Canine Species; Dogs; Dogs Mammals; canine; domestic dog; Drug resistance; drug resistant; resistance to Drug; resistant to Drug; Ducks; Enzymes; Enzyme Gene; Ferrets; Future; Goals; Half-Life; Hamsters; Cricetinae; Hamsters Mammals; Mesocricetus auratus; Golden Hamsters; Golden Syrian Hamsters; Syrian Hamsters; Human; Modern Man; Immunization; In Vitro; Infection; intravenous injection; Lung; Lung Respiratory System; pulmonary; Macaca; Macaque; Mus; Mice; Mice Mammals; Murine; Persons; Nasal cavity; Ownership; Legal patent; Patents; Patients; Drug Kinetics; Pharmacokinetics; Phosphorylation; Protein Phosphorylation; Recommendation; Research; RNA; Non-Polyadenylated RNA; RNA Gene Products; Ribonucleic Acid; viral RNA; virus RNA; Safety; Family suidae; Pigs; Suidae; Swine; porcine; suid; Technology; Testing; Texas; Tissues; Body Tissues; Tritium; H3 radionuclide; radioactive hydrogen; Vaccines; Viremia; viraemia; viral sepsis; virusemia; Virus; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; World Health Organization; sangivamycin; Caymans; gRNA; Guide RNA; Immunocompromised; Immunocompromised Patient; Immunosuppressed Host; immunosuppressed patient; Immunocompromised Host; timeline; human subject; Label; Acute; Clinical; Phase; Variation; Variant; Coronaviridae; corona virus; Coronavirus; Chemicals; Evaluation; Blood Serum; Serum; Individual; Recovery; Licensing; Funding; Comment; Commentary; Editorial Comment; Viewpoint; Published Comment; Therapeutic; Intravenous; programs; Viral Load result; Viral Burden; Viral Load; fighting; Hour; Clinic; Upper respiratory tract; upper airway tract; Lower respiratory tract structure; lower respiratory tract; Viral; meetings; meeting; nucleoside analog; research facility; Animal Model; Animal Models and Related Studies; model of animal; Agreement; Maximum Tolerated Dose; Maximal Tolerated Dose; Maximally Tolerated Dose; Modeling; response; Phase I Clinical Trials; Early-Stage Clinical Trials; Phase 1 Clinical Trials; phase I protocol; Drops; Inflammatory Response; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; Pharmacologic Substance; small molecule; Dose; Control Animal; Data; National Institute of Allergy and Infectious Disease; NIAID; in vivo; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Development; developmental; pandemic disease; pandemic; preclinical study; pre-clinical study; attributable death; attributable mortality; designing; design; Outcome; anticancer therapeutic; anti-cancer therapeutic; healthy volunteer; commercialization; combat; FDA approved; effective treatment; effective therapy; resistance strain; resistant strain; antiviral efficacy; anti-viral efficacy; Regimen; Lung Inflammation; Pneumonitis; Pulmonary Inflammation; Formulation; oncology clinical trial; cancer clinical trial; pre-clinical development; preclinical development; therapeutic candidate; medical countermeasure; animal safety; COVID19; CV-19; CV19; corona virus disease 2019; coronavirus disease 2019; coronavirus disease-19; coronavirus infectious disease-19; COVID-19; 2019 novel corona virus; 2019 novel coronavirus; COVID-19 virus; COVID19 virus; CoV-2; CoV2; SARS corona virus 2; SARS-CO-V2; SARS-COVID-2; SARS-CoV-2; SARS-CoV2; SARS-associated corona virus 2; SARS-associated coronavirus 2; SARS-coronavirus-2; SARS-related corona virus 2; SARS-related coronavirus 2; SARSCoV2; Severe Acute Respiratory Coronavirus 2; Severe Acute Respiratory Distress Syndrome CoV 2; Severe Acute Respiratory Distress Syndrome Corona Virus 2; Severe Acute Respiratory Distress Syndrome Coronavirus 2; Severe Acute Respiratory Syndrome CoV 2; Severe Acute Respiratory Syndrome-associated coronavirus 2; Severe Acute Respiratory Syndrome-related coronavirus 2; Severe acute respiratory syndrome associated corona virus 2; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome related corona virus 2; Wuhan coronavirus; coronavirus disease 2019 virus; coronavirus disease-19 virus; hCoV19; nCoV2; 2019-nCoV; GS-5734; Veklury; remdesivir; COVID crisis; COVID epidemic; COVID pandemic; COVID-19 crisis; COVID-19 epidemic; COVID-19 global health crisis; COVID-19 global pandemic; COVID-19 health crisis; COVID-19 public health crisis; COVID19 crisis; COVID19 epidemic; COVID19 global health crisis; COVID19 global pandemic; COVID19 health crisis; COVID19 pandemic; COVID19 public health crisis; SARS-CoV-2 epidemic; SARS-CoV-2 global health crisis; SARS-CoV-2 global pandemic; SARS-CoV-2 pandemic; SARS-CoV2 epidemic; SARS-CoV2 pandemic; SARS-coronavirus-2 epidemic; SARS-coronavirus-2 pandemic; Severe Acute Respiratory Syndrome CoV 2 epidemic; Severe Acute Respiratory Syndrome CoV 2 pandemic; Severe acute respiratory syndrome coronavirus 2 epidemic; Severe acute respiratory syndrome coronavirus 2 pandemic; corona virus disease 2019 epidemic; corona virus disease 2019 pandemic; coronavirus disease 2019 crisis; coronavirus disease 2019 epidemic; coronavirus disease 2019 global health crisis; coronavirus disease 2019 global pandemic; coronavirus disease 2019 health crisis; coronavirus disease 2019 pandemic; coronavirus disease 2019 public health crisis; coronavirus disease crisis; coronavirus disease epidemic; coronavirus disease pandemic; coronavirus disease-19 global pandemic; coronavirus disease-19 pandemic; severe acute respiratory syndrome coronavirus 2 global health crisis; severe acute respiratory syndrome coronavirus 2 global pandemic; COVID-19 pandemic; COVID-19 therapy; COVID19 therapy; COVID19 treatment; SARS-CoV-2 therapy; SARS-CoV-2 treatment; coronavirus disease 2019 therapy; coronavirus disease 2019 treatment; severe acute respiratory syndrome coronavirus 2 therapy; severe acute respiratory syndrome coronavirus 2 treatment; treat COVID-19; treat COVID19; treat SARS-CoV-2; treat coronavirus disease 2019; treat severe acute respiratory syndrome coronavirus 2; COVID-19 treatment; COVID19 therapeutics; SARS-CoV-2 therapeutics; SARS-coronavirus-2 therapeutics; Severe acute respiratory syndrome coronavirus 2 therapeutics; coronavirus disease 2019 therapeutics; therapeutics against COVID-19; therapeutics against COVID19; therapeutics against SARS-CoV-2; therapeutics against SARS-coronavirus-2; therapeutics against Severe acute respiratory syndrome coronavirus 2; therapeutics against coronavirus disease 2019; therapeutics for novel coronavirus; COVID-19 therapeutics; COVID therapeutics; coronavirus disease therapeutics; therapeutics against COVID; therapeutics against coronavirus; therapeutics against coronavirus disease; coronavirus therapeutics; 2019-nCoV variant; 2019-nCoV variant forms; 2019-nCoV variant strains; COVID-19 variant; COVID-19 variant forms; COVID-19 variant strains; SARS-CoV-2 variant forms; SARS-CoV-2 variant strains; coronavirus disease 2019 variant; coronavirus disease 2019 variant forms; coronavirus disease 2019 variant strains; severe acute respiratory syndrome coronavirus 2 variant; severe acute respiratory syndrome coronavirus 2 variant forms; severe acute respiratory syndrome coronavirus 2 variant strains; SARS-CoV-2 variant; COVID-19 infection; COVID-19 virus infection; COVID19 infection; SARS-CoV2 infection; Severe acute respiratory syndrome coronavirus 2 infection; coronavirus disease 2019 infection; infected with COVID-19; infected with COVID19; infected with SARS-CoV-2; infected with SARS-CoV2; infected with coronavirus disease 2019; infected with severe acute respiratory syndrome coronavirus 2; SARS-CoV-2 infection; COVID-19 anti-viral; COVID-19 antiviral; SARS-CoV-2 anti-viral; SARS-CoV2 anti-viral; SARS-CoV2 antiviral; coronavirus disease 2019 anti-viral; coronavirus disease 2019 antiviral; severe acute respiratory syndrome coronavirus 2 anti-viral; severe acute respiratory syndrome coronavirus 2 antiviral; SARS-CoV-2 antiviral; Severe acute respiratory syndrome coronavirus 2 inhibitor; block SARS-CoV-2; block severe acute respiratory syndrome coronavirus 2; inhibit SARS-CoV-2; inhibit severe acute respiratory syndrome coronavirus 2; SARS-CoV-2 inhibitor; comparison control; compare to control
