Guard Therapeutics Intl (GUARD) Study Result summary

Study background and objectives

• POINTER phase 2B was a randomized, double-blind, placebo-controlled trial evaluating RMC-035 in open-heart surgery patients at risk for acute kidney injury, aiming to confirm AKITA study benefits and identify optimal dosing.

• 170 patients were randomized to two RMC-035 dose groups (30 mg, 60 mg) and a placebo group, with dosing before surgery and at 6 and 24 hours post-dose.

• The primary endpoint was change in eGFR from baseline to Day 90; the key secondary endpoint was MAKE-90, defined as death, dialysis, or ≥25% loss of eGFR.

Key results and interpretation

• The study did not meet its primary endpoint; no statistically significant difference in eGFR change between RMC-035 and placebo at Day 90 (placebo-adjusted change: -2.76 mL/min/1.73 m²; p = 0.17).

• MAKE-90 was also not met, with a common relative risk of 0.89 (p = 0.76), showing no significant benefit.

• Efficacy results contrast with previous AKITA study, raising concerns about reproducibility.

• RMC-035 was generally well tolerated, with no new safety concerns identified.

Dose and exposure considerations

• 60 mg dose achieved target blood levels similar to efficacious AKITA dose; 30 mg showed numerically better outcomes than 60 mg.

• Removal of the 48-hour dose (present in AKITA) was for safety reasons and may have impacted efficacy, though this cannot be fully excluded.

• Exposure in POINTER matched target levels, supporting dose selection rationale.