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Principal Investigator: Todd Wallach
Organization: ONCOSTING LLC
Fiscal Year: 2024
Award: $270,176
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Tuberculosis (TB) remains the topmost killer among infectious diseases globally, and is one of the world’s most
significant medical challenges. Approximately one quarter of the world population has been infected with
Mycobacterium tuberculosis (M.tb), the majority being latent cases that could give rise to active disease. Ten
million incident cases associated with 1.4 million deaths were reported in 2019. In the last 90+ years, Bacillus
Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has been the only available vaccine
against TB. The vaccine has been effective in preventing life-threatening extra-pulmonary TB in children, but has
variable efficacy in preventing pulmonary TB in adults, and is associated with side effects. With escalating
population movement around the globe, the need for improved TB vaccines that can prevent infection has
become critical. Yet, despite significant interest, vaccine development has been limited by insufficient funding,
as well as a lack of clear understanding of the nature of both innate and acquired immunity in the lung, and their
role in the protective immune response against M.tb. In order to address the need for improved versions of BCG
that provide better efficacy and safety compared to traditional BCG, OncoSTING is developing OS-101 and OS-
151, recombinant versions of BCG engineered to overexpress the potent STING agonist c-di-AMP for a two-
pronged mechanism of action: (i) induction of anti-TB immunity by the same mechanisms known to be elicited
by traditional BCG (BCG-WT ) and (ii) stimulation of the STING pathway leading to upregulation of a several pro-
inflammatory responses and enhanced “Trained Immunity” (TI) in macrophages. OncoSTING is the only
company developing STING agonist delivery by a live bacterial vaccine—BCG. As supported by preliminary
data, these improved versions of BCG offer potential both for greater protective efficacy that lasts into adulthood,
and an improved safety profile. A significant database has been compiled for OS-101, which is resistant to the
antibiotic kanamycin. However, the FDA does not allow advanced human clinical trials with BCG strains
harboring antibiotic resistance. OncoSTING has therefore generated OS-151, an antibiotic resistance-free
version of OS-101. In Phase I of this Fast-Track proposal bridging mouse immunogenicity and efficacy studies
will be conducted to support the use of data generated with the OS-101 strain in regulatory filings for OS-151. In
Phase II, OS-151 drug product formulation and manufacturing approach will be established, and pivotal GLP
toxicology studies will be conducted to position for an IND application and clinical trial initiation. A toxicology
study in guinea pig to characterize post vaccination toxicity and identify potential for vaccination site inflammatory
response, systemic toxicity, and long-term persistence of any adverse findings will establish that OS-151 is safe
to initiate a clinical trial. The results from this proposal will position OncoSTING to submit an IND and conduct a
U.S. Phase 1 first time in human trial (FTIH); with the ultimate goal of demonstrating superiority of OS-151 versus
BCG as a vaccine against TB.
Terms: <0-11 years old><2019-nCoV vaccine><21+ years old><Acceleration><Access to Care><Address><Adjuvant><Adolescent><Adolescent Youth><Adult><Adult Human><Advanced Development><Aerosols><Agonist><Animal Cancer Model><Animal Model><Animal Models and Related Studies><Antibiotic Resistance><Antitubercular Agents><Assay><Attenuated><Attenuated Vaccines><BCG Live><BCG Vaccine><BCG immunization><BCG vaccination><BCG-vaccinated><Bacille Calmette Guerin vaccine><Bacille Calmette-Guerin vaccinated><Bacille Calmette-Guerin vaccination><Bacille Calmette-Guérin><Bacillus Calmette Guerin Vaccine><Bacillus Calmette Guérin><Bacillus Calmette-Guerin vaccination><Bacillus Calmette-Guérin vaccination><Bacillus Calmette-Guérin vaccine><Bacterial Vaccines><Bacterin><Bioassay><Biological Assay><Bladder Cancer><Bone Marrow><Bone Marrow Reticuloendothelial System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 years><CV-19><Cause of Death><Cavia><Cessation of life><Child><Child Youth><Children (0-21)><Clinical Trials><Communicable Diseases><Coronavirus Infectious Disease 2019><Cricetinae><Cyclic GMP><DNA cassette><Data><Data Bases><Databases><Death><Detection><Development><Disease><Disease Progression><Disorder><Dose><Drug resistance><Drugs><Engineering><Evolution><Excipients><Fermentation><Formulation><Freeze Drying><Freeze Dryings><Funding><Generalized Growth><Goals><Growth><Guanosine Cyclic Monophosphate><Guinea Pigs><Guinea Pigs Mammals><HIV/Mtb><HIV/TB><HIV/mycobacterium tuberculosis><HIV/tuberculosis><Hamsters><Hamsters Mammals><Health Services Accessibility><Human><Immune response><Immunity><Immunological response><In Vitro><Infection prevention><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammatory Response><Innate Immunity><Interruption><Journals><Kanamycin><Kanamycin Resistance><Kinetics><Life><Liquid substance><Live-attenuated Vaccine><Lung><Lung Respiratory System><Lung TB><Lung Tuberculosis><Lyophilization><M bovis><M tb><M tuberculosis><M tuberculosis infection><M. bovis><M. tb><M. tb infection><M. tuberculosis><M. tuberculosis infection><M. tuberculosis/HIV><M.tb infection><M.tuberculosis infection><MTB infection><MTB vaccine><Macrophage><Magazine><Malignant Bladder Neoplasm><Malignant Tumor of the Bladder><Malignant neoplasm of urinary bladder><Medical><Medication><Messenger RNA><Methods><Mice><Mice Mammals><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Murine><Mus><Mycobacterium bovis><Mycobacterium tuberculosis><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis infection><Mycobacterium tuberculosis var. bovis><Myeloid Cells><Mφ><Native Immunity><Natural Immunity><Nature><Non-Specific Immunity><Nonspecific Immunity><Paper><Pathology><Pathway interactions><Performance><Pharmaceutical Preparations><Phase><Phase III study><Plasmids><Population><Position><Positioning Attribute><Prevent infection><Prevention><Production><Protocol><Protocols documentation><Public Health><Pulmonary TB><Pulmonary Tuberculosis><Recombinants><Recovery><Reporting><Research><Resistance><Resistance to antibiotics><Resistant to antibiotics><Role><Running><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccine><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><Safety><Saline><Saline Solution><Schedule><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Site><Stimulator of Interferon Genes><TB immunity><TB infection><TB vaccine><Time><Tissue Growth><Toxic effect><Toxicities><Toxicology><Training><Tuberculosis><Tuberculosis Vaccines><Tuberculostatic Agents><Up-Regulation><Upregulation><Urinary Bladder Cancer><Urinary Bladder Malignant Tumor><Vaccination><Vaccine for TB><Vaccine for Tuberculosis><Vaccines><Virulent><access to health services><access to services><access to treatment><access to vaccination><access to vaccines><accessibility to health services><acquired immunity><adulthood><anti-TB><anti-TB vaccine><anti-tuberculosis><antiTB><antibiotic drug resistance><antibiotic resistant><attenuate><attenuates><availability of services><cGAMP STING><cGAMP-STING><cGAMP/STING><cGAS/STING><cGMP><care access><co-infection><coinfection><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus 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against TB><immunity against tuberculosis><immunity in tuberculosis><immunity to TB><immunity to tuberculosis><immunogenicity><immunoresponse><improved><in vivo><infection due to Mycobacterium tuberculosis><integration cassette><interest><intravesical><juvenile><juvenile human><kanamycin resistant><kids><liquid><live vaccine><live vaccines><mRNA><manufacture><model of animal><mortality><mouse model><mtb><murine model><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><next generation><non-muscle invasive bladder cancer><novel><ontogeny><overexpress><overexpression><pathway><phase 3 study><population movement><prevent><preventing><promoter cassette><protective effect><protective efficacy><pulmonary><reporter cassette><resistance cassette><resistance gene><resistance locus><resistance strain><resistance to Drug><resistant><resistant gene><resistant strain><resistant to Drug><selectable cassette><selection cassette><service availability><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><side effect><small molecule><social role><stop cassette><systemic toxicity><transcription cassette><transcriptional cassette><transgene cassette><treatment access><tuberculosis immunity><tuberculosis infection><tuberculous spondyloarthropathy><vaccination access><vaccination availability><vaccine access><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against M. tuberculosis><vaccine against Mtb><vaccine against Mycobacterium tuberculosis><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine against TB><vaccine against tuberculosis><vaccine availability><vaccine candidates against SARS-CoV-2><vaccine candidates against tuberculosis><vaccine development><vaccine for novel coronavirus><vaccines preventing COVID><vaccines to prevent COVID><youngster>