Disc Medicine (IRON) Study result summary

APOLLO design and population

• Global, randomized, double-blind Phase III trial: 183 adults and adolescents aged 12+ with EPP or XLP received once-daily bitopertin 60 mg or placebo for six months.

• Co-primary endpoints: average monthly pain-free time in light during month six and percent change from baseline in whole-blood metal-free PpIX.

• Enrollment included 34 adolescents and 7% of participants with XLP; treatment arms were generally balanced on key baseline characteristics.

Efficacy results

• Both co-primary endpoints were met: PpIX changed −45.8% with bitopertin vs −4.4% with placebo, a 41.4% difference (P<0.0001); month-six time in light was 41.1 vs 28.9 hours, a 12.2-hour difference (P=0.001).

• Cumulative six-month pain-free time in light was 233.2 vs 174.6 hours, a 58-hour difference (P<0.0001).

• Phototoxic reaction incidence was 71% lower than placebo (IRR 0.29, P<0.0001); 71 reactions occurred with bitopertin vs 231 with placebo.

• In adults, daily sunlight exposure time to prodrome improved by 56 minutes vs placebo at month six (P=0.0077); PGIC and PGIS scores also favored bitopertin (both P<0.0001).

Safety and ongoing treatment

• Safety showed no new signals; TEAEs occurred in 85% with bitopertin vs 75% with placebo, and SAEs in 1% vs 2%. Three serious adverse events occurred, none considered treatment-related.

• Dizziness was the most common TEAE (50% vs 11%), generally mild or moderate, transient and early-onset; no bitopertin-treated participants discontinued.

• Bitopertin had been studied in more than 4,000 clinical trial participants; long-term EPP program exposure extended to 2.5+ years.

• HELIOS data indicate PpIX reductions persist for years and time in light continues to improve beyond six months; roughly 150 U.S. patients were enrolled, and 97% of APOLLO participants rolled over.