Science
NTS-104 is a prodrug that converts rapidly in plasma to NTS-105, a neuroactive steroid. NTS-105 readily crosses the blood brain barrier, reaches pharmacologic concentrations in the brain and plasma, and has multi-targeted mechanisms of action.
NTS-105 has a unique target receptor profile, with three equipotent receptor interactions, including:
- Full antagonist at androgen receptor
- Partial agonist to cellular progesterone receptor B
- Full antagonist at mineralocorticoid receptor
This results in potent anti-inflammatory, anti-apoptotic (inhibits cell death), and anti-edema activity in the brain and systemically.
NTS has performed rigorous preclinical evaluation of NTS-104 in multiple independent laboratories utilizing two acute ischemic stroke (AIS) models, including the transient and embolic middle cerebral artery occlusion models, tMCAO and eMCAO, respectively. The following results were published in Stroke (November 2022).
AIS was induced in the eMCAO model. NTS-104 was administered at four dose levels following the stroke. Results demonstrated that NTS-104 markedly improved the modified neurological severity score (mNSS) in a dose-dependent manner.
Motor function (foot fault) and sensorimotor/cognitive function (adhesive tape removal) were also assessed. NTS-104 treatment significantly reduced the number of foot faults and improved the time to removal of the adhesive tape in a dose-dependent manner.
Examination of the brains one month after eMCAO showed that treatment with NTS-104 reduced the size of the infarction in a dose-dependent manner.