Newron Pharmaceuticals (NWRN) investor relations material

FDA clinical hold and safety review

• FDA feedback on the U.S. ENIGMA-TRS 2 hold is under review; a fatal arrhythmic mechanism could not be excluded given evenamide’s sodium-channel blockade and small QTc shortening.

• Four deaths occurred among evenamide-treated patients versus one on placebo; incidence was 0.56% versus 0.27%, and adjusted mortality was 1.31 versus 1.81 per 100 patient-years. Investigators judged three deaths unrelated and one possibly related; autopsies found no compelling cause.

• Review covers more than 10,000 program ECGs from more than 700 patients, including independent cardiac electrophysiologist input; no cardiac-abnormality or arrhythmia pattern has been observed, including in a thorough QT study.

• Proposed ENIGMA-TRS 2 safeguards include genetic testing for Brugada syndrome/channelopathies, excluding QT <360 ms or family arrhythmia history, and excluding patients with QT shortening during the study.

• Amendment filing was expected in ~2 weeks, subject to third-party input; FDA review typically takes one month. U.S. sites remain on hold.

Phase III progress and milestones

• ENIGMA-TRS 1 had 514 patients randomized; enrollment was expected to complete by mid-October 2026 with at least 600 planned. Twelve-week topline results are expected in Q1 2027; 26-week results are also a key value inflection point.

• ENIGMA-TRS 1 is a 52-week randomized, double-blind, placebo-controlled study of evenamide 15 mg BID and 30 mg BID; the primary endpoint is change from baseline in PANSS at week 12.

• ENIGMA-TRS 2 targets 400 patients; 85 had entered screening, with enrollment continuing outside the U.S. and additional sites being added. No U.S. patients have been dosed with evenamide.

• The U.S. was planned to contribute 100 patients (~one quarter) to ENIGMA-TRS 2; management said 60–80 U.S. patients may enroll, with non-U.S. sites added to limit timeline impact.

• Planned value inflection points include ENIGMA-TRS 2 12-week results; timelines will be updated when visibility improves. The study is a 12-week randomized, double-blind, placebo-controlled trial of 15 mg BID versus placebo.

Funding and priorities

• Funding was expected to last through most of 2027, beyond anticipated ENIGMA-TRS data milestones.

• Near-term priorities include completing the FDA feedback assessment, submitting a response, advancing non-U.S. ENIGMA-TRS 2 enrollment, and preparing for planned data readouts.