DRX_065



NAME OF DRUG : DRX_065

ALSO KNOWN AS : DRX_065

LABORATORY : POXEL

STATUS AND ADVANCEMENT

Type of drug : stabilized, preferred enantiomer of pioglitazone

Clinical trials advancement : Ongoing Phase 1

Estimated time to market : 129 months.

LABORATORY ABSTRACT ON THE DRUG

Pioglitazone, is a 1:1 mixture of two interconverting enantiomers. By stabilizing the enantiomers with deuterium, DeuteRx discovered that each enantiomer has dramatically different mechanistic properties. The (S)-enantiomer is a PPAR? agonist with the associated side effects of weight gain and edema. By contrast, the (R)-enantiomer exhibits mitochondrial function modulation and anti-inflammatory effects, likely due to mitochondrial pyruvate carrier (MPC) inhibition. The (R)-enantiomer is also devoid of the weight gain observed with racemic pioglitazone and the (S)-enantiomer in a rodent model of weight gain. Therefore, the (R)-enantiomer is likely responsible for the benefits of pioglitazone seen in animal and/or human studies for indications including Alzheimer's disease, NASH, ALD/AMN, and chronic obstructive pulmonary disease (COPD). The predicted beneficial effects of DRX-065 have been demonstrated by DeuteRx in two rodent models of NASH where DRX-065 exhibited equivalent or better activity than pioglitazone in the liver for measures of steatosis, inflammation, triglycerides, free fatty acids, and cholesterol.

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