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Applied Therapeutics announced new data and scientific presentations from the pivotal Phase 2 ACTION-Galactosemia trial. The full study data, originally planned to be presented at the Society for Inherited Metabolic Disorders conference this week, will be available on the company's website. The double-blind placebo-controlled ACTION-Galactosemia trial evaluated safety and pharmacokinetics of AT-007, a Central Nervous System penetrant Aldose Reductase Inhibitor in healthy volunteers, as well as safety, pharmacokinetics, and efficacy biomarkers in adult Galactosemia patients. The key biomarker outcome of the study was reduction in galactitol, an aberrant toxic metabolite of galactose, formed by Aldose Reductase in Galactosemia patients. Accumulation of galactitol causes long-term complications ranging from CNS dysfunction to cataracts. As previously announced, once-daily 20mg/kg AT-007 reduced galactitol levels by approximately 50% in Galactosemia patients. Reduction in galactitol levels was rapid and sustained throughout the treatment period of 27 days. Reduction in galactitol from baseline was statistically significant at the 20mg/kg vs placebo. The lower dose tested, 5mg/kg, demonstrated a similar trend in reducing galactitol levels approximately 20% from baseline. Reduction in galactitol was not accompanied by any increase in galactose. This data confirms that reduction of the toxic metabolite galactitol through Aldose Reductase inhibition does not result in derangement of other metabolites in the galactose pathway as previously demonstrated in animal models of Galactosemia. Patients treated with AT-007 demonstrated a positive trend in MRI outcomes, specifically on measures of edema and overall neuronal health. AT-007 treated patients demonstrated improvement in ventricular volume, a measure of edema, which has been shown to occur in the brain of Galactosemia patients due to osmotic dysregulation caused by galactitol. Patients treated with AT-007 also demonstrated improvements in N-acetyl-aspartate, a marker of neuronal health. Galactitol was visible on MRI in the brain of all patients at baseline, and a positive trend toward decreased brain galactitol levels in AT-007 treated patients was observed by quantitative MR Spectroscopy. As no drug-related adverse events were seen at the once-daily 20mg/kg dose, a once-daily 40mg/kg dose was subsequently studied in healthy volunteers and is ongoing in Galactosemia patients. The 40mg/kg dose was safe and well tolerated. Evaluation of once-daily 40mg/kg AT-007 in Galactosemia patients remains ongoing and this data will be shared when available. No drug-related adverse events were reported at any dose of AT-007 in ACTION-Galactosemia. This robust safety data includes all 80 healthy volunteers and 8 adult Galactosemia patients who received active drug during the core study. A 90-day safety extension study for ACTION-Galactosemia is ongoing. The extension study is open to patients from the core study and to new adult Galactosemia patients. A pediatric study with a safety and biomarker design similar to ACTION-Galactosemia is planned to commence in Q2 of this year. Both the extension study and the pediatric study are designed to incorporate primarily home health visits in order to limit travel and risk of exposure to COVID-19. More information on the pediatric study will be shared in coming weeks.