공고 • May 09
enGene Therapeutics Inc. Announces Updated Interim Results From Legend Pivotal Cohort
enGene Therapeutics Inc. reported additional interim results from the pivotal cohort of its ongoing, Phase 2 LEGEND trial of detalimogene voraplasmid (also known as detalimogene) in high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) patients with carcinoma in situ (CIS) with or without concomitant papillary disease, which enrolled 125 patients. These data, as of April 21, 2026, demonstrated that patients treated with detalimogene achieved a 54% complete response (CR) at any time and a 43% CR rate at six months. The progression rate to muscle-invasive or advanced disease was low, at 3.2%. Detalimogene was generally well tolerated with 55% of patients having experienced a treatment-related adverse event, mostly mild (Grade 1 and 2). The interim analysis is based on the 125 patients enrolled in Cohort 1. Patients who discontinued without any disease evaluation or who discontinued after a CR were considered not evaluable for subsequent landmark CR analysis. 54% (95% CI: 45%, 63%) CR at any time (67/124). 91% of responses occurred at first disease assessment. 43% (95% CI: 34%, 52%) CR rate at 6 months (52/121) with 14% (6/43) of patients having successfully converted from non-CR to CR post re-induction. Two re-induced patients have not yet had a 6-month assessment. Of the 52 responders at 6 months: 37/44 patients who had a 9-month assessment were in CR; an additional 8 patients are pending evaluation. 13/22 patients who had a 12-month assessment were in CR; an additional 11 patients are pending evaluation. A maximum of 21 patients, including the 2 currently undergoing re-induction, still have the potential to achieve a CR at 12 months. The Kaplan-Meier (KM) estimate of the 12-month duration of response (DoR) is 25% (95% CI: 11%, 41%). The KM estimate for median DoR is 37.3 weeks (range: 31.6-43.9 weeks). Low rate of progression to muscle invasive or more advanced disease (3.2%). 55% of patients experienced a treatment-related adverse event (TRAE). Among patients with any TRAE, 91% experienced Grade 1-2 TRAEs. Grade =3 TRAEs were reported in 6 patients (4.8%). Low percentage of patients experienced TRAEs leading to treatment interruption (2.4%) and treatment discontinuation (2.4%). Among the 32 patients who had their first disease assessment after the last data analysis (October 24, 2025, reported November 11, 2025), CR rates were lower than previously reported results. The CR rate at any time was 39% and at 6 months was 32% for these patients. A preliminary subgroup analysis has not revealed any material differences in demographics or key disease characteristics. A more comprehensive analysis of these patients, including potential contributing factors, is ongoing. As a beneficiary of FDA’s RMAT designation and a participant in the FDA’s CDRP program, enGene has completed the required FDA manufacturing validation batches and submitted a Statistical Analysis Plan (SAP) to the agency. The Company plans further engagement with the FDA as it approaches a potential Biologics License Application (BLA) filing and plans to provide an update in the second half of 2026. The Company plans to share these data with the broader medical community at a Plenary Presentation at the upcoming American Urological Association meeting on May 15, 2026. The overall tolerability profile associated with detalimogene is favorable. Of the 125 patients assessed for safety in Cohort 1, 69 patients (55%) experienced at least one TRAE, which were mainly Grade 1/2 in severity. The most common TRAEs were fatigue (22%), dysuria (14%), micturition urgency (12%), pollakiuria (12%), and bladder spasm (11%). Six patients experienced Grade =3 TRAEs, including one Grade 4 TRAE, which has resolved. There were no Grade 5 TRAEs reported. TRAEs leading to dose discontinuations (2.4%) and dose interruptions (2.4%) were rare. Detalimogene is a novel, investigational, non-viral gene therapy for patients with high-risk, non-muscle invasive bladder cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response. Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, reduce complexities related to safe handling and cold storage, and streamline both manufacturing processes and administration paradigms. Detalimogene has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the U.S. Food and Drug Administration (FDA) based on its potential to address the high unmet medical need for patients with BCG-unresponsive carcinoma in situ (CIS) NMIBC with or without resected papillary tumors who are unable to undergo cystectomy. These designations are intended to expedite the development and review of drugs to serious or life-threatening conditions and fill an unmet medical need. Detalimogene has also been selected for the FDA’s Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program, designed to facilitate CMC development for therapies with compressed clinical development timeframes based on the anticipated clinical benefits of earlier patient access to the therapy. Detalimogene is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk NMIBC. LEGEND’s pivotal cohort (Cohort 1) consists of 125 patients with high-risk, BCG-unresponsive NMIBC with CIS (with or without papillary disease) and is designed to serve as the basis of the Company’s planned Biologics License Application (BLA) filing. In addition to this pivotal cohort, LEGEND includes three additional cohorts, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3).
