Published April 24^th, is a special report in the biomedical journal Annals of Pulmonary and Critical Care Medicine regarding the medical-scientific rationale for its planned randomized, placebo-controlled, Phase 2 Study of OT-101 in COVID-19 patients with hypoxemic respiratory failure.

In this publication, we are proposing that COVID-19 is a TGF-β driven disease treatable with TGF-β inhibitor such as Mateon’s OT-101.  As the virus replicates it releases TGF-β which drives viral replication, drives water accumulation in the lung, and drives neutrophil mediated inflammation ultimately resulting in death from acute respiratory distress syndrome (ARDS) and its complications.

Viral replication is dependent on expression of TGF-β and the progressive increase in TGF-β with increasing viral load with has been implicated as an important pro-inflammatory cytokine in the pathophysiology of acute lung injury and ARDS that contributes to both increased permeability and failed fluid reabsorption in lungs leading to persistent and severe pulmonary edema. TGF-β profoundly impacts alveolar ion and fluid transport by regulating the epithelial sodium channel (ENaC) activity and trafficking via a Tgfbr1-mediated unique signaling pathway.

TGF-β has been identified as the exclusive master regulator of ENAC internalization by alveolar epithelial cells and its upregulation in ARDS causes an ENAC trafficking defect with marked reduction in the cell-surface abundance of ENaC on lung epithelial cells thereby rapidly and substantially impairing alveolar fluid reabsorption in ARDS patients and contributing to the persistence of their pulmonary edema. Mateon’s anti-TGF-β RNA therapeutic OT101 exhibited nanomolar in vitro potency against SARS-CoV-2 and is potentially targeting the root cause of COVID-19.