Yumanity Therapeutics reported that its lead product candidate, YTX-7739, in development for the treatment of Parkinson’s disease (PD), demonstrated dose-dependent decreases in target fatty acids, which can be interpreted as evidence of in vivo target engagement, in a Phase 1a multiple ascending dose (MAD) clinical trial in healthy volunteers. Inhibition of stearoyl-CoA desaturase (SCD) has been shown to improve motor function and other disease markers in transgenic mouse models of PD. YTX-7739 was also observed to be generally well tolerated in the Phase 1a study. YTX-7739 was discovered through company’s target discovery and drug development platform that is designed to identify disease-modifying therapeutics against newly identified targets for neurodegenerative diseases. Preclinical work has shown that SCD inhibition by YTX-7739, an orally available, brain penetrant small molecule, can overcome the toxicity of pathogenic a-synuclein, a known risk factor for PD, both in vitro and in animal models. Further, the fatty acid desaturation index (FA-DI) which measures the ratio of SCD’s product to its substrate has demonstrated utility as a biomarker to gauge SCD inhibition in animals treated with YTX-7739. The pharmacology of YTX-7739 observed preclinically has translated nicely to the clinical experience observed in this part of the study. Furthermore, the potential to correlate changes in the plasma FA-DI with drug exposures support the use of FA-DI as a biomarker to help assess clinical response to YTX-7739 and potentially identify patients most likely to benefit, for inclusion in later phase trials. The company look forward to the results of company's ongoing Phase 1b safety and biomarker study to assess the effect of chronic dosing in patients with Parkinson’s disease. Topline results from the Phase 1b part of the study are expected in mid-2021. This part of the Phase 1, placebo-controlled, randomized, double-blind study, investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once daily oral administration of two doses of YTX-7739 (15 mg and 25 mg) for 14 to 28 days in 16 healthy male and female volunteers. The study included two cohorts of eight subjects each, randomized to treatment or placebo in a 6:2 ratio. YTX-7739 was observed to be generally well tolerated in this part of the study. There were no serious adverse events and all treatment emergent adverse events were either mild or moderate in severity. Plasma pharmacokinetics support once daily dosing, and relevant drug concentrations were measured in the cerebrospinal fluid. Target engagement was achieved, as evidenced by dose dependent decreases in the plasma FA-DI, within the range associated with restoration of motor function in animal models of Parkinson’s disease. Study data will be presented at Yumanity’s upcoming R&D Day on May 17, 2021 and at a future medical conference.