TP-317 ARDS Program

TP-317 Program for Acute Respiratory Distress Syndrome (ARDS)

ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs.

Causes of ARDS include bacterial and viral pneumonia, COVID-19, sepsis, trauma, aspiration, smoke inhalation and chemical-induced injury. A 2005 study of ARDS in the U.S. estimated that there were 190,000 ARDS cases and 74,000 ARDS-related deaths per year, indicating a case rate of 78.9 per 100,000 population and 38.5% mortality. This mortality rate is consistent with the findings of the 2014 LUNGSAFE study, a multicenter, prospective cohort study of patients in 50 countries investigating the ICU epidemiology and outcomes of ARDS. Thus, ARDS was an urgent public health problem in the U.S even before the COVID-19 pandemic, causing more deaths per annum than breast and prostate cancer combined.

To address this need, Thetis is developing TP-317, a small molecule Resolvin E1 (RvE1) therapy for treatment of ARDS. Unlike steroids, immunomodulators and biologics that work by suppressing the immune response, RvE1 is an endogenous autacoid discovered by Professor Charles Serhan (Harvard Medical School) that activates multiple pathways to resolve inflammation and promote tissue repair without inhibiting host defense. Through this differentiated mechanism of action (MOA), TP-317 has prospects to address the multi-faceted pathology of ARDS as monotherapy or in combination with other therapies.

Based on the pioneering research of Thetis scientific advisors, Professor Serhan and Bruce Levy, MD (Brigham & Women’s Hospital (BWH)), the unique, multifaceted immunoregulatory MOA of RvE1 has been demonstrated in multiple in vitro and preclinical animal models. These studies have shown important mechanistic effects including inhibition of inflammation via reduced immune cell infiltration into lung tissue and downregulation of inflammatory cytokines as well as inflammation resolution effects such as enhanced apoptosis, clearance of apoptotic neutrophils, and tissue repair.