detalimogene voraplasmid (EG-70) / enGene - LARVOL DELTA

enGene’s Detalimogene Selected for FDA Manufacturing Pilot Program to Support Manufacturing Readiness (Businesswire) - "The FDA created the CDRP Program to facilitate CMC development for therapies with compressed clinical development timeframes based on the anticipated clinical benefits of earlier patient access to the therapy. The initiative is designed to promote earlier and more structured engagement between sponsors and FDA on CMC development strategies, and since its inception, has led to increased collaboration with the FDA so sponsors can confidently scale up manufacturing capacity while clinical development is ongoing."

Clinical • Bladder Cancer

Gene Therapy for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Current Evidence and Future Directions. (PubMed, Cancers (Basel)) - P1/2, P2, P3 | " Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS)...Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • IFNA1

CONTEMPORARY EXPERIENCE USING GENE THERAPIES FOR NMIBC AT AN ACADEMIC CENTER: OUTCOMES AND SEQUENCING (SUO 2025) - "These are: nadofarogene firadenovec-vncg, cretostimogene grenadenorepvec, and detalimogene voraplasmid...Of these, 5 (24%) were retreated with the same agent and eight (38%) were treated with gemcitabine/docetaxel... In this single-institution experience, intravesical gene therapy offered a bladder-preserving option for patients with BCG-unresponsive NMIBC, including those with high-risk CIS and T1 disease. While high-grade recurrence remained common, treatment with an alternative GT agent offers durable disease control in a subset of patients, with additional salvage possible with the same GT agent or gem/doce in well selected patients. These findings highlight the evolving role of gene therapy in the management of BCG-unresponsive NMIBC and the opportunity for future work to refine sequencing strategies and optimize long-term outcomes."

Gene therapy • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Solid Tumor

ENGN: Non-viral gene therapy for NMIBC achieves 62% six-month CR rate, targeting 2027 approval (TradingView)

Approval • P1/2 data • Bladder Cancer

Anticipated upcoming milestones (Businesswire) - "Following agreement with the FDA on the SAP and the accumulation of sufficient 12-month CR data points, enGene expects to provide a data update on the LEGEND trial’s pivotal cohort in the second half of 2026; The Company continues to expect to file the BLA in the second half of 2026, with a potential FDA approval in 2027."

FDA approval • FDA filing • P1/2 data • Bladder Cancer

Detalimogene Demonstrates Improved Complete Response Rate of 62% at 6 Months (Businesswire) - "Data from 62 patients enrolled under the amended protocol with at least one post-baseline disease assessment demonstrated: 63% complete response (CR) rate at any time (n=62); 56% CR rate at 3 months (n=62); 62% CR rate at 6 months (n=37), with 4 patients having successfully converted to CR post reinduction; and All 5 patients who completed the 9-month assessment had a CR....The Company completed enrollment of 125 patients in the pivotal cohort, exceeding its target by 25%. Data from these patients demonstrated a favorable tolerability profile: 42% of patients experienced a treatment-related adverse event (TRAE); 1.6% of patients experienced dose interruptions due to TRAEs; and 0.8% of patients experienced dose discontinuations due to TRAEs."

P1/2 data • Bladder Cancer

Additional LEGEND trial updates (Businesswire) - "Following recent discussions with the FDA, the primary endpoint for LEGEND’s pivotal cohort will change to CR rate at any time from a primary endpoint of landmark 12-month CR rate, with its key secondary endpoint becoming duration of response (DOR) for patients in CR...The Company plans to engage with FDA on a statistical analysis plan (SAP) to determine which patients will be included in the final efficacy evaluable population; Cohort 2a, evaluating detalimogene in NMIBC patients with CIS who are naïve to treatment with BCG, has enrolled 30 patients; Cohort 2b, evaluating detalimogene in high-risk NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment, has enrolled 45 patients; Cohort 3, evaluating detalimogene in BCG-unresponsive high-risk NMIBC patients with papillary-only disease, has enrolled 36 patients."

Trial status • Bladder Cancer

enGene Holdings...announced that it will host a conference call and webcast tomorrow, November 11, 2025, at 8:00 a.m. ET to discuss new preliminary data from its pivotal cohort in the ongoing LEGEND trial of its novel, non-viral gene therapy candidate, detalimogene voraplasmid...for patients with high-risk...BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ (Businesswire)

P1/2 data • Bladder Cancer

SYMP-27: Preliminary Results From Legend: a Phase 2 Study of Detalimogene Voraplasmid, a Novel, Investigational, Non-Viral Genetic Medicine for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) (SIU 2025) - No abstract available

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Preliminary Results From Legend: a Phase 2 Study of Detalimogene Voraplasmid, a Novel, Investigational, Non-Viral Genetic Medicine for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) (SIU 2025) - No abstract available

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Reimagining Bladder Cancer Immunotherapy: Local Non-Viral Gene Delivery of DNA-Encoded Immune Checkpoint Inhibitors (SITC 2025) - P1/2 | "Therapeutic efficacy of ICI-expressing DDX formulation is currently being evaluated in a humanized PD-1 murine orthotopic bladder cancer model.Results The expression constructs for pembrolizumab and nivolumab demonstrated dose-dependent expression in vitro...IVI of DDX-packaged nanoparticles containing the ICI-expressing plasmid in C57BL/6 mice led to sustained, dose-dependent expression in the bladder lasting over 28 days. Importantly, systemic exposure remained minimal—approximately 1,000-fold lower than that observed following intravenous administration of recombinant ICI at clinically relevant doses—highlighting the advantage of this localized delivery approach.Conclusions These data demonstrate the potential utility of the DDX platform for localized, sustained expression of DNA-encoded ICI monoclonal antibodies in the bladder with significantly reduced systemic exposure."

Checkpoint inhibition • IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and practical implementation. (PubMed, Curr Opin Urol) - "Gene-mediated therapy is gradually advancing NMIBC care, with expanding indications and potent combinations positing itself to improve bladder preservation and long-term outcomes."

IO biomarker • Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

enGene…Provides Business Update (Businesswire) - "Anticipated Milestones: (i) Updated preliminary data from LEGEND trial’s pivotal cohort in 4Q 2025; (ii) Trial in progress updates from LEGEND’s additional cohorts, including HR-NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); HR-NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive HR-NMIBC patients with papillary-only disease (Cohort 3), in 4Q 2025."

P1/2 data • Trial status • Bladder Cancer

Mechanism of Action and Translation to the Clinic of Detalimogene Voraplasmid – A Novel, Investigational, Non-viral Genetic Medicine for Non-muscle-invasive Bladder Cancer (NMIBC) (MA-AUA 2025) - No abstract available

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Preliminary Results from LEGEND: A Phase 2 Study of Detalimogene Voraplasmid, a Novel, Investigational, Non-viral Genetic Medicine for High-risk Non-muscle Invasive Bladder Cancer (NMIBC) (MA-AUA 2025) - No abstract available

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Target enrollment of 100 patients with high-risk, BCG-unresponsive NMIBC with CIS achieved (Businesswire) - "enGene plans to provide an update from LEGEND’s pivotal cohort in 4Q 2025; Biologic License Application (BLA) submission planned for 2H 2026."

Enrollment status • FDA filing • Bladder Cancer

FDA Grants RMAT Designation for enGene’s Detalimogene, Enabling Potential for Expedited Review in High-Risk, Non-Muscle Invasive Bladder Cancer (Businesswire) - "enGene Holdings Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to detalimogene voraplasmid (also known as detalimogene, and previously EG-70), the Company’s lead investigational therapy for the treatment of high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)...The designation was based on previously disclosed preliminary results from the ongoing pivotal LEGEND study..."

FDA event • Bladder Cancer

enGene Reports Second Quarter 2025 Financial Results and Provides Business Update (Businesswire) - "LEGEND study enrollment update: Over the course of the first and second quarters of 2025, the Company expanded its clinical footprint for the LEGEND study with the addition of trial sites in Europe and Asia. The pivotal cohort evaluating detalimogene voraplasmid (also known as detalimogene, and previously EG-70) in high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) remains on track for our planned BLA in mid-2026. The Company expects to provide an update from LEGEND’s pivotal cohort in the second half of 2025."

FDA filing • P2 data • Trial status • Bladder Cancer

LEGEND: A phase 1/2 study of detalimogene voraplasmid (EG-70), an intravesical monotherapy for patients with high-risk non–muscle-invasive bladder cancer (NMIBC). (ASCO 2025) - P1/2 | "All patients provide written informed consent. The Phase 2 portion of the study is enrolling and will recruit approximately 300 patients across all cohorts, from sites in the USA, Canada, Europe, and the Asia-Pacific region."

Clinical • Monotherapy • P1/2 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

A Phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer – Trial in progress (EAU 2025) - No abstract available

Clinical • Monotherapy • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

EAU 2025: A Phase 1/2 Study of Detalimogene Voraplasmid (EG-70) Intravesical Monotherapy for Patients with High-Risk Non-Muscle Invasive Bladder Cancer – Trial in Progress (UroToday) - "The phase 1 (dose-escalation) portion of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 is complete. Dr Guerrero described the ongoing phase 2 portion of the study, which opened to enrollment in May 2023....Patients receive Detalimogene voraplasmid (EG-70) at 0.8 mg/mL in 50 mL via intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for a total of four cycles. Treatment response is evaluated through cystoscopy, cytology, and bladder biopsy. Patients achieving a complete response at the end of cycle 4 proceed to maintenance treatment, receiving Detalimogene voraplasmid on weeks 1 and 2 of each 12-week cycle for up to four additional cycles. If a complete response is maintained at cycle 8, patients may either continue treatment for up to four more cycles or transition to follow-up."

Clinical protocol • Bladder Cancer

LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve (clinicaltrials.gov) - P1/2 | N=350 | Recruiting | Sponsor: enGene, Inc. | N=222 ➔ 350 | Trial completion date: May 2027 ➔ Nov 2028 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

enGene Reports First Quarter 2025 Financial Results and Provides Business Update (Businesswire) - "LEGEND study trial site expansion: Over the course of the first quarter of 2025, the Company expanded its clinical footprint for the LEGEND study with the addition of trial sites in Europe and Asia. In addition, all four of LEGEND’s cohorts are now open for enrollment....The amended LEGEND protocol allows patients from all cohorts who are in complete response at 12 months to continue receiving detalimogene on a dose-reduced maintenance schedule throughout their second year of treatment.....The maintenance regimen is intended to evaluate the potential of longer-term detalimogene treatment to improve or maintain durability of response with the lower patient burden associated with a less frequent dosing regimen.....Additional preliminary data from ongoing LEGEND study of detalimogene in BCG-unresponsive NMIBC with CIS, including pivotal cohort, anticipated in 2H 2025. Biologics License Application (BLA) filing planned for mid-2026 remains on track."

FDA filing • P2 data • Trial status • Bladder Cancer

A phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC). (ASCO-GU 2025) - P1/2 | "All patients provide written informed consent. The Phase 2 portion of the study is enrolling and will recruit up to 300 patients from sites in the USA, Canada, Europe, and the Asia-Pacific region."

Clinical • Monotherapy • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Mechanism of action and translation to the clinic of detalimogene voraplasmid (EG-70): A novel, investigational, non-viral immunotherapy for non-muscle-invasive bladder cancer (NMIBC). (ASCO-GU 2025) - P1/2 | "These preclinical findings demonstrate that detalimogene voraplasmid delivers genetically encoded immunostimulatory payloads locally to the bladder. The mechanism of action described preclinically has been translated into the clinic in the Phase 1 part of the LEGEND study."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • IL12A