OP005: AT-007 significantly reduces toxic galactitol in ACTION-galactosemia kids - the 1st therapeutic interventional clinical trial in children with classic galactosemia

Classic Galactosemia (CG) is a rare, autosomal recessive disease where galactose not metabolized properly due to severe deficiency or absence of the GALT enzyme (galactose-1-phosphate uridyl transferase). At abnormally high levels, becomes an aberrant substrate for aldose reductase, resulting in conversion abnormal and toxic metabolite, galactitol. Newborn screening implementation galactose-restricted diet has reduced newborn acute symptoms significantly decreased fatalities. However, despite early dietary intervention, children continue develop significant morbidities speech, cognition, behavior, motor function, which have been shown progressively worsen with age, as well cataracts primary ovarian insufficiency females. AT-007 oral CNS penetrant reductase inhibitor, prevents galactitol, that development treatment CG. Reduction circulating galactitol by halt progression rat model Galactosemia. ACTION-Galactosemia Kids sequential, two-part, randomized double-blind, placebo-controlled study evaluating clinical benefit, safety, pharmacokinetics pharmacodynamics pediatric patients Patients were 2:1 placebo. Disease demographics, genetic variant, patient history assessed at baseline. Additionally, functional tests cognition behavior performed baseline all enrolled study. The biomarker endpoint was reduction plasma over minimum 30 days target dose vs Baseline 30-day levels drawn under fasted conditions evaluated via validated liquid chromatography-mass spectrometry assay. correlation severity linear incorporating skills assessments. Forty-seven ranging age from 2 17, 3 US sites across three predefined groups (2-6 years old; 7-12 13-17 old). predominantly White (98%), had mean 9 51% female/49% male. most common characteristics included learning disorders (∼50%), apraxia (∼40%), anxiety (∼35%), vitamin (∼30%), tremor (∼20%) ataxia (∼20%). All female older than 12 insufficiency. ∼10% suffered seizures ∼5% onset cataracts. demographic balanced placebo groups. Galactitol correlated total this population (p=0.004). Treatment resulted 40.2% when compared on (p<0.001). consistent among associated changes galacose-1-phosphate (Gal-1p). safe tolerated. results demonstrates metabolite severity, 17