Our military personnel are deployed throughout the globe, often far from medical facilities in areas with extreme risk for exposure to deadly human viruses. Over the last 20 years, we have witnessed numerous deadly outbreaks of Ebola, Zika, SARS, MERS, and now SARS-CoV-2. The spread of viral diseases, whether unintentionally due to exposure to infected individuals, or intentionally via biological terrorism, poses a significant risk to military health and readiness. At HDT Bio Corporation, we are developing an antiviral inhaler capable of preventing disease from a broad spectrum of deadly human viruses. This inhaler could become a standard part of a Soldier’s kit, allowing for rapid responses to intentional or unintentional outbreaks, interrupting the virus transmission chain, and allowing military members to remain in action.

Our product (HDT-201) combines RAR (RIG-I-activating RNA), a small ribonucleic acid (RNA) activator of the innate immune system, and LION, a nanoparticle formulation designed to protect and deliver RNA into the body. RAR triggers an innate immune response by binding to RIG-I (retinoic acid-inducible gene I), a protein in the cell designed to recognize RNA from viruses. Binding of viral RNA to RIG-I leads to a cascade of antiviral activities in the cell, which limit virus replication and instruct the body to mount an effective antibody response against the virus. We can take advantage of this antiviral pathway by delivering RAR to the cell with LION, tipping the body into an antiviral state to prevent viral transmission and halt infection and the progression to severe disease.

In this proposal, we aim to accomplish three key things. In Specific Aim 1, we will develop HDT-201 into a pressurized metered-dose inhaler (pMDI), similar to an asthma inhaler. We will test different formulations, canisters, and valves to find an optimal combination to provide enhanced stability, while maintaining biological activity required to prevent disease. While our product has already shown stability for a minimum of 3 months at room temperature, we anticipate storage in the inert environment inside a pMDI canister will enhance stability even further. In Specific Aim 2, we will perform the necessary safety and potency studies required by the U.S. Food and Drug Administration (FDA) to enter our product into clinical trials. We will determine which cells in the body take up RAR, the time-course of the immune response to our product, and the optimal dose and timing of delivery of HDT-201 to prevent disease from three respiratory viral pathogens - SARS-CoV-2, influenza, and respiratory syncytial virus. In Option Specific Aim 1, we will perform the final formal toxicology study required by the FDA to determine the maximum safe dose for entry into human clinical trials.

Upon completion of the proposed study herein, HDT Bio Corporation is poised to move quickly to advance our product. RAR is ready to enter large-scale manufacturing, while the LION formulation is already being evaluated in a late-stage clinical trial in India. Initial studies have shown LION to be safe and effective at delivering RNA to humans. Upon completion of the proposed project herein, we will quickly advance HDT-201 into clinical trials to significantly impact the readiness of military personnel to respond to infectious disease outbreaks or biological terrorism. Once developed, the product can also be used for the civilian population; when prescribed following a diagnosis of viral infection, HDT-201 will speed recovery and prevent severe disease, while having the added benefit of decreasing the overuse of antibiotics, thus helping prevent the development of antimicrobial resistance.