A Novel Tie2 Agonist IV Medication for the Treatment of ALI/ARDS in Military Casualties and Civilians
Abstract
Topic Area: Vasomune Therapeutics, Inc., proposes the development of a novel drug for the treatment of a clinical syndrome, titled “Acute Respiratory Distress Syndrome” or ARDS. Our proposed project directly addresses the Fiscal Year 2019 Peer Reviewed Medical Research Program topic area of Acute Lung Injury (ALI), notably the Area of Encouragement, “Novel and/or innovative detection technologies or therapeutics to reduce the incidence and/or severity of ALI/ARDS and/or other lung injury secondary to trauma, transfusion, infection, burns, hemorrhagic shock, inhalation, and/or oxygen exposure.” A Pervasive Medical Problem: ARDS is a debilitating and lethal syndrome defined by specific clinical criteria demonstrating a major build-up of fluid in the lungs. ARDS occurs as a response to or escalation of various lung injuries, including direct insults to the lungs, such as viral or bacterial pneumonia, or indirect insults to the lungs, such as sepsis or cardiopulmonary bypass. It is a common syndrome, occurring in approximately 10 percent of all patients admitted to hospital Intensive Care Units and 23 percent of all patients who are placed on mechanical ventilation. The annual incidence alone is over a quarter of million patients with a mortality rate of approximately 40 percent. There are also significant socioeconomic ramifications, as ARDS patients have an average stay in the hospital of 17 days, resulting in an annual cost of 9.7-10 billion dollars. Compounding the issue is the lack of any effective medicines to treat patients with ARDS. Care focuses on what is called “supportive therapy,” referring to fluid management and/or further injury prevention via lung-protective ventilation. Applicability and Impact of the Research: Vasomune Therapeutics has developed a novel drug candidate, AV-001, for treatment of ARDS that addresses a critical driver of the syndrome, i.e., the accumulation of fluid in the lungs due to increased permeability of lung microvasculature. This occurs due to loss of barrier integrity of critical cells lining the microvasculature, known as endothelial cells. This loss of barrier integrity causes fluid to drain into the lungs and reduces the capacity of the lungs to provide life-giving oxygen to the blood supply, which drives lung dysfunction frequently culminating in death. AV-001 interacts with a pathway known as the Tie2/Angiopoietin signaling axis, thus promoting barrier integrity of endothelial cells, defending the lungs from vascular leakage. Vasomune Therapeutics has conducted extensive research in various different animal models that cumulatively demonstrates the vast potential of AV-001 as a targeted therapeutic against ARDS. Within this study, we intend to translate our preclinical findings to an ARDS drug candidate ready for clinical trials. Research activities included in this proposal are designed to satisfy outstanding toxicology and safety assessments of AV-001 necessary to support filing of an Investigational New Drug application and to provide guidance for the design of clinical studies for treatment of patients with ARDS. Treatment with AV-001 could result in a significant clinical and socioeconomic impact, as a (modest) 20% improvement in outcomes could save over 20,000 lives and billions of dollars annually.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010558
Entities
People
- Ghania Chikh
Organizations
- United States Army