GMP manufacturing and IND Filing of IN-002, a potent inhaled muco-trapping antibody therapy for Respiratory Syncytial Virus

Title: GMP manufacturing and IND Filing of IN-002, a potent inhaled “muco-trapping” antibody therapy for Respiratory Syncytial Virus Project Summary (30 line limit) Respiratory Syncytial Virus (RSV) is the leading cause of viral hospitalization and death in infants and young children and is also a major cause of respiratory illness in immune compromised adults and the elderly. Unfortunately, there is currently effective therapy that can prevent RSV-hospitalization. For the millions infected with RSV in the U.S. every year, there is no treatment option available aside from symptom-management. Like many respiratory pathogens, RSV spreads in the lungs by shedding daughter virions from infected cells exclusively back into the airways. From there, RSV must traverse the airway mucus (AM) before infecting other neighboring cells, remaining restricted to the airways with little-to-no systemic viremia. This important mechanism of spread makes RSV difficult to target by systemically dosed therapies; the antiviral drugs need to make their way to the airway mucus in order to inactivate virions and halt infection. We believe an RSV-specific, safe, and effective antiviral therapy that can be inhaled directly into the respiratory tract using a hand-held device at home would provide a powerful treatment option. To meet this goal, Inhalon is advancing IN-002, a mAb that binds and neutralizes RSV F protein with picomolar binding affinity and neutralization potency, and has minimal risks of viral escape. Importantly, in addition to the well-established IgG Fc effector functions, IN-002 is also engineered to possess Fc N-glycans optimized to trap RSV in AM. Once trapped, RSV virions are quickly purged from the airways via natural mucociliary clearance mechanisms. We have further formulated IN-002 to be stably nebulized using a portable vibrating mesh nebulizer. By delivering IN-002 directly to the site of infection (the airways), we expect to achieve high drug concentrations with a lower dose of mAb, saving costs and potentially improving efficacy. In a neonatal lamb model of RSV infection, nebulized therapy with IN-002 reduced RSV viral load in the lungs and BALF to almost non-detectible levels, unlike placebo-treated animals. Inhalon is the first company to successfully complete a Phase 1 study for an inhaled mAb therapy (IN-006) for COVID, achieving very high levels of drug in the airways with an excellent safety profile. Inhalon has received FDA feedback on its pre-IND submission for IN-002, and is currently completing IND-enabling preclinical activities for IN-002, including GLP inhalation tox, GLP tissue cross reactivity, and GLP nebulization characterization. Further, Inhalon has already established a GMP-compliant master cell bank for production of IN-002, from which scaled up production of tox materials have already been generated. Here, we are seeking support to complete: (i) the production, vialing and characterization of IN-002 clinical trial materials produced under GMP (Aim 1), and (ii) IND submission to receive approval to initiate Phase 1 clinical studies (Aim 2). Successful completion of the proposed activities would allow us to advance IN-002 into first-in-human studies.