Treatment of Inflammatory Complications of Respiratory Infection

Abstract Respana Therapeutics is advancing a proprietary first-in-class therapeutic monoclonal antibody (mAb), RT- 002, for the treatment of debilitating and often lethal inflammatory complications associated with acute respiratory conditions. We have identified a lead candidate, RT-002, and an equally promising alternative. RT-002 targets the surfactant protein A receptor SP-R210, a host-mediated target that holds the promise of efficacy regardless of pathogen evolution. Rigorous in vivo mouse studies have demonstrated not only reduction in mortality but restoration of lung health as well. Furthermore, RT-002 does not target an individual cytokine pathway, which can have negative effects. RT-002 thus has the potential to fill a significant gap in the therapeutics arsenal for influenza since the most widely used tools are vaccines to prevent infection and antiviral drugs to stop infection; however, these are limited by partial efficacy, vaccine hesitancy, and emergence of drug resistance. The objective of this Phase II proposal is to continue development of RT-002 and the backup with the goal of advancing the therapeutic toward clinical trials as quickly and efficiently as possible. Specifically, the Aims include: 1) Determine RT-002 pharmacological action in human blood through our functional immunophenotype assays to discern RT-002 target engagement and immune activation in human blood that will inform therapeutic design in alleviating aberrant immune activation in critically ill patients; 2) Establish pharmacological activity of RT-002 treatment for severe influenza utilizing humanized FcRn mice to establish safety, toxicity, pharmacodynamics, dosage, schedule, and duration of treatment to de-risk the development of RT-002 towards clinical trials in humans; and 3) Establish foundations for Phase I/IIa clinical trials for transition of RT-002 to clinical testing through existing partnerships with contractual research organizations, critical illness, and critical trials experts for production and GMP certification of RT-002 in stable CHO cells, and organization and planning of critical parameters from Aims 1 and 2 that are needed for pre-IND consultation with the FDA and the design of phase I/IIa clinical trials. Successful completion of the Aims will allow rapid progress toward IND-enabling studies, IND filling and initial clinical trials of a new therapeutic for an important and largely unmet clinical need for the treatment of life- threatening influenza illness.