Autonomous Therapeutics Inc

AT191: An Inhaled & Precision Rna Therapeutic With Pan-variant SARS-COV-2 Efficacy - Project Summary/abstract This Phase Ii Sbir Will De-risk a New Class of Antivirals That Can Be Developed to Target Any Rna Virus From SARS-COV-2 to Influenza. the Effort Will Specifically Translate a Lead, Platform-derived SARS-COV-2 Candidate (AT191) Designed to Be Self-administered and to Prevent Hospitalizations or Deaths by Any SARS-COV-2 Variant. Despite Vaccines and 2 Blockbuster Antivirals Marketed to Prevent Hospitalizations, 900,000 Americans Were Hospitalized Due to SARS-COV-2 in 2023. Beyond Vaccine Hesitancy and Durability Concerns, Existing Antivirals Only Reduce Hospitalizations and Deaths by 40–50%. SARS-COV-2 Antivirals Are Further Limited by Contraindications (e.g. Paxlovid) and Safety Concerns (e.g. Molnupiravir). Moreover, There Is a Risk That Sars- COV-2 Acquires Resistance to All Existing Classes of Antivirals—as Occurred With All SARS-COV-2 Monoclonal Antibodies Prior to 2024. There Is a Clear Unmet Need for New Classes of Antivirals, Especially Antivirals That Can: (i) Be Used At-home to Prevent Hospitalizations, and (II) Maintain (variant-proof) Efficacy as Novel Variants Emerge. Encrypted Rna (ENCRNA) Is a New Class of Rna Developed by Autonomous Therapeutics. the Plug-and-play Platform Technology Can Develop Antivirals Against Any Rna Virus and Can Encode Any Therapeutic Protein. Unlike State-of-the-art Mrna, Each Platform-derived Encrna Only Activates Its (broad-spectrum) Antiviral Payload in Targeted Virus-infected Cells. More Specifically, Encrna Only Translate Encoded Proteins When Bound, Transcribed, and Amplified by Targeted Viral Rna Polymerase (RDRP) Complexes Conserved Across a Viral Species. Thus, Encrna Remain Translationally Inactive and Safe in Uninfected Cells (e.g. as Prophylactics). AT191 Is Our Lead, First-in-class Encrna Therapeutic Candidate Developed to Confer Inhaled and Variant-proof Efficacy Against All Variants of SARS-COV-2 (and SARS-COV-1). AT191 Confers Precision and Pan-sarbecovirus Efficacy—because AT191’S Antiviral Payload (ifn-β) Is Only Activated and Translated by Sarbecovirus RDRP. in Phase I-equivalent Studies, We Developed: (i) the Encrna Platform Technology, (II) the AT191 Lead Candidate, and (III) an Inhalable Lipid Nanoparticle (LNP) for Encrna Self-administration Using Marketed Nebulizers. We Further Demonstrated the (IV) Variant-proof Efficacy of AT191 Against Every Tested SARS-COV-2 Variant in Vitro, and the (V) Preliminary in Vivo Safety and Efficacy of AT191 in Both Mice and Hamsters. Here We Propose to Develop AT191 Into a Glp-ready Candidate Ready for Ind-enabling Studies. We Propose to Test the Pan-sarbecovirus Efficacy (SARS-COV-1 & 2) of AT191 in Vivo and to Perform Critical CMC, Inhalation, Dose-timing, and Dose-finding Studies in Hamsters. We Will Also Test Safety/efficacy in Non-human Primates. the Effort Will Culminate in a Pre-ind. If Successful in Follow-on Clinical Studies, AT191 Could Be Used At-home as a Prophylactic or Therapeutic: E.g. for Immediate Use After Exposure to an Infected Child or Family Member. Beyond SARS-COV-2, the Same Encrna-lnp Platform Technology Could Be Used to Develop Precision and Variant-proof Candidates for Any Rna Virus—including Viruses for Which No Safe and Effective Antivirals Exist.