Rafael (RFL) Study result summary

Study design and patient population

• Phase III double-blind, placebo-controlled study conducted in 13 countries at 27 sites with 94 patients randomized 2:1 to Trappsol Cyclo or placebo, ages 3 to 70 years.

• Patients received Trappsol Cyclo 2,000 mg/kg IV every two weeks plus standard of care for 96 weeks.

• Primary endpoint was change from baseline in the four-domain NPC Clinical Severity Scale (4D) at week 96.

Efficacy results

• Trappsol Cyclo did not reach statistical significance on the primary endpoint but showed a directionally favorable effect versus placebo in slowing disease progression at week 96.

• In a pre-specified subgroup (83% of patients) on background miglustat and/or leucine, Trappsol Cyclo achieved a statistically significant mean difference of -1.105 (P=0.046), slowing progression by 71%.

• Improvements were most notable in the swallowing domain, a key factor in morbidity and mortality.

Safety and tolerability

• Trappsol Cyclo was well-tolerated; most adverse events were mild to moderate and consistent with underlying disease, with no new safety signals.

• Serious adverse events occurred more frequently in the Trappsol Cyclo group (35.9%) than placebo (16.7%), but treatment-related serious events were similar between groups.

• Hearing-related adverse events were mostly mild to moderate; only one severe case required hearing aids or resulted in bilateral deafness.

• No deaths were reported; one withdrawal due to adverse event.