CalciMedica’s lead clinical compound, AuxoraTM, is a potent and selective small molecule inhibitor of Orai1-containing CRAC channels that is being developed for use in patients with acute inflammatory diseases, many of which have respiratory dysfunction, including ARDS, as a major component. Such diseases include acute flu pneumonia with respiratory failure/ARDS, acute pancreatitis with accompanying systemic inflammatory response syndrome (SIRS), and COVID-19 pneumonia. Evidence suggests that CRAC channels play a role in inflammation-induced injury of pulmonary endothelial cells, resulting in loss of alveolar-capillary barrier function and accumulation of fluid in the alveoli. Similarly, hyperactivation of CRAC channels results in excessive calcium influx into pancreatic acinar and ductal cells, which can lead to cell dysfunction and death and plays a pivotal role in cellular injury and the progression of acute pancreatitis. In each of these settings, local and systemic inflammation can exacerbate the problem, leading to organ failure and death.
In patients with hypoxemia secondary to SIRS in acute pancreatitis, Auxora has been found to accelerate patient recovery, decrease hospital stay and potentially protect lung and kidney function. Auxora has demonstrated reduced ventilator use and mortality as well as improved time to recovery in patients with COVID-19 pneumonia on low-flow supplemental oxygen therapy. CalciMedica is also exploring other acute inflammatory indications for Auxora such as viral pneumonia, acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI).