enGene Therapeutics (ENGN) Study result summary

Study design and patient population

• LEGEND phase II pivotal cohort enrolled 125 high-risk BCG-unresponsive NMIBC patients, median age 71, with 80% male and a median of 12 prior BCG doses.

• Majority had CIS only (60.8%), most declining or ineligible for cystectomy; nearly 40% had CIS plus papillary disease, and some had up to 11 recurrences before enrollment.

• Median of 2 prior NMIBC recurrences; 25% had prior non-BCG therapy.

• Protocol amendments in late 2024 expanded the post-amendment cohort to 94 patients, impacting subgroup analyses.

• LEGEND is an ongoing, open-label, multi-cohort Phase 2 trial evaluating detalimogene in high-risk NMIBC.

Efficacy and durability results

• Complete response (CR) at any time was 54%, with 43% at six months, 33% at nine months, and 13% at 12 months; median duration of response was 8.7 months.

• Kaplan-Meier estimated 12-month CR rate is 25% (95% CI: 11%-41%), aligning with approved products.

• 91% of responses occurred at the first disease assessment; 14% of non-CR patients converted to CR after re-induction.

• Low progression to muscle-invasive or advanced disease (3.2%).

• Lower CR rates were observed in the last 32 patients assessed (39% at any time, 32% at 6 months); further analysis ongoing.

Safety and tolerability

• 55% experienced treatment-related adverse events (TRAEs), mostly mild (Grade 1-2), with only 4.8% Grade 3 or higher events; one Grade 4 ALT elevation resolved without discontinuation.

• Most common TRAEs were fatigue (22%), dysuria (14%), urgency (12%), pollakiuria (12%), and bladder spasm (11%).

• Discontinuation and interruption rates due to TRAEs were both 2.4%.

• Overall tolerability profile is favorable for detalimogene.