Tourmaline Bio (TRML) Study Update summary

Study objectives and design

• Phase 2 TRANQUILITY trial evaluated pacibekitug, an IL-6 inhibitor, for quarterly and monthly dosing in patients with elevated hsCRP and moderate to severe CKD, with 143 participants enrolled and 126 in the primary analysis population.

• Participants were randomized to 25 mg or 50 mg quarterly, 15 mg monthly, or placebo, treated for six months with six-month follow-up.

• Primary endpoint: median time-averaged percent change in hsCRP through Day 90, adjusting for baseline levels.

• Key secondary endpoint: percentage of participants achieving time-averaged hsCRP below 2 mg/L through Day 90.

• Trial supports further development in ASCVD and AAA.

Efficacy results

• All active arms showed rapid, deep, and durable reductions in hsCRP, with median reductions of 75% (25 mg quarterly), 86% (50 mg quarterly), and 85% (15 mg monthly) vs. 15% for placebo.

• At Day 90, median percent reduction in hsCRP: 70% (25 mg quarterly), 85% (50 mg quarterly), 89% (15 mg monthly), vs 12% for placebo.

• Over 80% of participants in active arms achieved hsCRP below 2 mg/L through day 90, compared to 26% for placebo.

• Up to 94% achieved ≥50% hsCRP reduction at Day 90 in active arms; results were consistent across analyses.

• Efficacy was robust across pre-specified subgroups, with very few non-responders.

Safety and tolerability

• Pacibekitug was generally well tolerated, with adverse event rates similar between pacibekitug (54%) and placebo (56%) groups.

• Most common AEs: urinary tract infection, COVID-19, dizziness, and viral upper respiratory tract infection, mostly mild or moderate.

• Serious adverse event rates: 10% (pacibekitug) vs 11% (placebo); infection and serious infection rates were comparable.

• No association between higher dose and increased adverse events; one death (COVID-19) in lowest dose arm, unrelated to study drug.

• No significant changes in atherogenic lipids or severe hematologic adverse events; increases in HDL and apolipoprotein A1 observed.