The differences between NDC-1308 (MC1) and Dexamethasone proposed Mechanism of Action (MOA) support NDC-1308 (MC1) may have increased efficacy compared to Dexamethasone in all COVID-19 patient groups. By addressing the early signs of lung inflammation in COVID-19 patients, NDC-1308 (MC1) is projected to reduce the amount of time people spend in hospitals and prevent the use of a ventilator. Compared to Dexamethasone, NDC-1308 (MC1) shows substantial improvement to survival in COVID-19 patients.
NDC-1308 (MC1) has a single Mechanism of Action (MOA) for reducing lung inflammation that can be efficacious in all COVID-19 patient groups, as well as many other inflammatory lung viruses.
Proposed MOA
Dexamethasone
NDC-1308 (MC1)
T Cell Depletion
Dexamethasone
T cell depletion without macrophage polarization (Biomaterials 2015, Jan; 37: 367-382)
NDC-1308 (MC1)
None
Reduction in M1 Macrophages
Dexamethasone
Anti-inflammatory macrophages, but MOA is unknown
Reduction in numbers of M1 macrophages caused by dexamethasone binding to mineralocorticoid receptor (MR) in lung alveolar cells; may competitively inhibit aldosterone binding to the MR; aldosterone binding to MR causes upregulation of hyper-inflammatory M1 macrophages due to Ace1/Ace2 dysregulation from SARS-CoV-2 binding to Ace2 receptors (would result in increased numbers of pro-inflammatory Ace1 receptors and M1 macrophages)
(Critical Care, 2020, 24:318)
NDC-1308 (MC1)
Macrophage polarization to M2, anti-inflammatory state by directly upregulating gene and protein expression for lipoprotein lipase (LPL) and ApoC2 within lung macrophages
Clinical Studies
Dexamethasone
Reduces mortality in COVID-19 patients on ventillators by 33%, and by 20% in patients receiving oxygen
NDC-1308 (MC1)
Progressing to Phase 1 Clinical studies in COVID-19 patients
Pre-IND meeting completed with FDA