Clinical benefit of govorestat in ACTION-Galactosemia Kids trial; company plans to meet with FDA regarding potential NDA submission

The ACTION-Galactosemia Kids Phase III study was designed to evaluate the impact of govorestat treatment vs. placebo on clinical outcomes over time in 47 children age 2-17 with Galactosemia. The primary endpoint, the Global Statistical Test, was a composite sum of change comprised of four endpoints: OWLS-2 Oral Expression (OE), OWLS-2 Listening Comprehension (LC), BASC-3 Behavior Symptoms Index (BSI) and the BASC-3 Activities of Daily Living (ADL). An additional pre-specified sensitivity analysis included cognition in the primary endpoint (NIH-Toolbox Cognition Battery). Additional clinical outcomes were assessed as secondary endpoints, including adaptive skills and tremor. Clinical outcomes were assessed every 6 months by a firewalled independent Data Monitoring Committee (DMC).

Results; i.Treatment with govorestat demonstrated consistent and sustained clinical benefit on activities of daily living, behavioral symptoms, cognition, adaptive behavior and tremor. ii. While statistical significance defined as a p value of <0.05 was not met on the primary endpoint, systematic improvement over time was demonstrated for the overall primary endpoint (p="0.1030)" and for a pre-specified sensitivity analyses including cognition (p="0.0698).iii." individual speech and language components of the primary endpoint were not impacted, which is suspected to be due to lack of progression in the placebo group and concomitant speech therapy received by almost all children in the trial. of note, patients with severe speech deficits showed a favorable trend towards improvement with govorestat vs. placebo. iv. a post-hoc analysis of the global statistical test including behavior and activities of daily living but excluding speech & language components (owls-oe and owls-lc) demonstrated a highly statistically significant benefit of active treatment vs. placebo (p="0.0205)," which strengthened over time. v. govorestat provided a statistically significant benefit on tremor at 18 months (p="0.0428)," as measured by the archimedes spiral drawing test, and adaptive skills as assessed by the basc-3 adaptive skills index (p="0.0265)." vi. consistent with prior reported data, improvement in galactitol levels was sustained throughout the trial with no impact on gal-1p or galactose, further establishing the causal role of galactitol in disease pathogenesis. vii. govorestat continued to be safe and well-tolerated in all age groups; there were no treatment-related serious adverse events (saes) reported.

This data will be submitted for presentation at an upcoming medical conference.

The Company believes that there is compelling evidence of clinical efficacy and plans to move toward registration of govorestat for Galactosemia. The trial will be unblinded and placebo patients will be crossed to active treatment.

Galactosemia: is a devastating rare pediatric metabolic disease that affects how the body processes a simple sugar called galactose, and for which there is no known cure or approved treatment available. Galactose is found in foods, but the human body also naturally produces galactose on its own, so dietary restriction cannot prevent complications of disease. It is estimated that the U.S. Galactosemia population is approximately 2,800 patients.