Engene Therapeutics Inc. · NASDAQ:ENGN
Engene Therapeutics — Investor Presentation (November 2025)
31 slides from Engene Therapeutics's investor presentation, Nov 12, 2025
Slide 1: Corporate Presentation November 2025
Corporate Presentation November 2025 Exhibit 99.4
Slide 2: Disclaimers: Cautionary Statement Regarding Forward-Looking Statements
Disclaimers Cautionary Statement Regarding Forward-Looking Statements This Presentation contains certain forward-looking statements within the meaning of the federal securities laws and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking state
Slide 3: Detalimogene Voraplasmid for Non-Muscle Invasive Bladder Cancer
Detalimogene Voraplasmid for Non-Muscle Invasive Bladder Cancer Designed for Seamless Integration into High-Volume Urology Practices Transformational Market Opportunity in Area of High Unmet Need Novel class of drug: non-viral gene therapy Powerful and coordinated immune activation across two major
Slide 4: DDX Platform: Unique Non-Viral Gene Therapy Without the Headaches
DDX Platform: Unique Non-Viral Gene Therapy Without the Headaches Large Genetic Cargo Non-Immunogenic Low Cost of Goods/ No Specialized Handling Detalimogene
Slide 5: NMIBC Represents 75-80% of Bladder Cancer Diagnoses
NMIBC Represents 75-80% of Bladder Cancer Diagnoses NMIBC Patients Segmentation CIS +/- papillary tumors Papillary tumors only US Incident Bladder Cancer ~85,000/year Non-Muscle Invasive ~65,000/year HR NMIBC ~25,000/year US Prevalent Bladder Cancer ~730,000 Carcinoma in situ Non-invasive papillary
Slide 6: NMIBC: Slow Progression but High Incidence, Cost, and Recurrence Rate
MIBC = Muscle-invasive bladder cancer Sources: Mossanen M, Gore JL, Curr Opin Urol. 2014 Sep;24(5):487-91; Clark O et al., Pharmacoecon Open. 2024 Aug 18; https://seer.cancer.gov/statfacts/html/common.html#comparison, van den Bosch and Witjes, Eur Urol. 2011 Sep;60(3):493-500. NMIBC: Slow Progressio
Slide 7: While Curative, Cystectomy is a Last Resort: Vast Unmet Need Remains
While Curative, Cystectomy is a Last Resort: Vast Unmet Need Remains HR NMIBC Diagnosis BCG New Therapies Radical Cystectomy IVI Chemo Chronic supply shortage Poor long-term tolerability Used as BCG backstop Poor efficacy 6-15% mortality rate High morbidity Decreased QoL (e.g., stoma bag, sexual dys
Slide 8: FDA Guidance Highlights Unmet Need for Long-Term Bladder Preservation
FDA Guidance Highlights Unmet Need for Long-Term Bladder Preservation 2018 2019 2020 2021 2022 2023 2024 2025 FDA Guidance issued for single-arm (n~100) studies to promote development of new therapies Approved FDA Guidance revised; supports need for new therapies Approved Approved (combination with
Slide 9: Community Urologists Balance a Range of Needs in Selecting Treatments
Tolerability 12-month CR Rate 12-month DOR Rate Lack of Freezer Storage & Thaw Time Requirements Cost of Treatment/Coverage Ease of Administration Any time CR Rate Community Urologists Balance a Range of Needs in Selecting Treatments Community Urologist Treatment Considerations: Tolerability, Effica
Slide 10: Practice Operations are Strained: Time Savings are Economically Valuable
Buy+Bill 5% of revenue in 2008 and grown to 15-20% in 2025 Products requiring fewer clinical resources are preferred Practice Operations are Strained: Time Savings are Economically Valuable Sources: “The State of the Urology Workforce and Practice in the United States, 2024” American Urological Asso
Slide 11: Detalimogene: Designed to Meet the Needs of Urologists and Patients
Detalimogene: Designed to Meet the Needs of Urologists and Patients Preliminary evidence of clinical activity* Non-viral gene therapy designed for streamlined clinical experience *LEGEND phase 1 reported data and September 2024 and November 2025 preliminary pivotal phase 2 reported data Efficacy Eas
Slide 12: Non-Viral Coordinated Immune Activation Across Two Major Axes
Non-Viral Coordinated Immune Activation Across Two Major Axes Plasmid Encodes Three Immune-Stimulatory Genes to Activate Both Innate and Adaptive Pathways Bladder lumen Intracellular Detalimogene DNA plasmid dsRNA agonists of RIG-I Secreted IL-12 Activate intracellular RIG-I receptor Locally stimula
Slide 13: DDX Platform Designed to Support Industrial-Scale Manufacturing
DDX Platform Designed to Support Industrial-Scale Manufacturing e e e e e - - - - - (Stabilizes Nanoparticle) PEG-PLE Bulk Mixing In-line Mixing PEGylated DDX/DNA Nanoparticle (Non-Viral Drug Product) DDX/DNA Nanoparticle + + + + + + + Non-viral, lyophilized drug product No special delivery or handl
Slide 14: Multiple LEGEND Cohorts Maximize Detalimogene's Potential
Multiple LEGEND Cohorts Maximize Detalimogene’s Potential Detalimogene Voraplasmid (intravesical) Comprehensive IP Portfolio Through at Least 2040 *These additional non-pivotal cohorts of the LEGEND study provide further opportunity to demonstrate the potential use of detalimogene in clinical settin
Slide 15: Pivotal Study Target Enrollment Achieved
Pivotal Study Target Enrollment Achieved Patients: BCG-Unresponsive High-risk NMIBC with CIS Design: Global, single-arm, open label N = 125 (fully enrolled) Dosing2: Year 1: 800μg/ml IVI at weeks 1,2,5,6 Q3M Year 2-3 (Maintenance): 800μg/ml IVI at weeks 1,2 Q3M Primary Endpoint: Anytime CR rate Key
Slide 16: Enrollment Complete: Patients Enrolled in Pivotal Cohort
Enrollment Complete: 125 Patients Enrolled in Pivotal Cohort 125 Total Intention to Treat Population (ITT) Pts. 94 Post-Amendment Pts. (75%) 31 Pre-Amendment Pts. (25%) November update based on Oct. 24, 2025 data cut FDA review and agreement on Statistical Analysis Plan (SAP) will impact final patie
Slide 17: LEGEND Pivotal Cohort Pre- and Post-Protocol Amendment Characteristics
LEGEND Pivotal Cohort Pre- and Post-Protocol Amendment Characteristics Baseline characteristic POST N=94 PRE N=31 Gender, n (%) Male 76 (80.9) 25 (80.6) Female 18 (19.1) 6 (19.4) Age, years Mean (SD) 69.6 (10.1) 71.8 (10.4) Median (range) 70.5 (35, 85) 74 (46, 90) BCG Doses Median 12.5 12.0 Range 7,
Slide 18: Post-Protocol Amendment - Preliminary Data
Post-Protocol Amendment - Preliminary Data Post Protocol Amendment Any Time (N=62) 3 Month (N=62) 6 Month (N=37)** ITT N=62* CR Rate 63% (CI:51-74) 56% (CI: 44-68) 62% (CI: 46-76) KM Estimate 63% *ITT: Post-protocol amendment patients in Cohort 1 who received at least 1 dose of treatment and had at
Slide 19: Evolution of CR Rate With Protocol Amendment
Post-Protocol Amendment N=31 as of Oct. 2025 Any Time (N=31) 3 Month (N=31) 6 Month (N=27)** ITT Population* CR Rate 55% (CI: 38-71) 55% (CI: 38-71) 41% (CI: 25-59) KM Estimate 42% Evolution of CR Rate With Protocol Amendment Pre-Protocol Amendment N=62 as of Oct. 2025 Any Time (N=62) 3 Month (N=62)
Slide 20: Cohort Tolerability Update: All Patients (n = 125)
Cohort 1 Tolerability Update: All Patients (n = 125) * 2 patients experienced urinary tract infection, 1 experienced pyelonephritis. 0 discontinuations due to Grade 3 TRAEs. Data as of October 24, 2025; Data collection and cleaning is ongoing, TRAE = Treatment-Related Adverse Event. Any Grade Grade
Slide 21: Designed to Streamline Experience for Patients and Urology Practices
Patients Practice Designed to Streamline Experience for Patients and Urology Practices Fewer doses per 12-week cycle than BCG induction 1-hour total chair time in clinical trials and no thaw or pre-wash steps No urine bleaching or close contact precautions with loved ones Storage at 2-8°C* possible
Slide 22: Any Time CR Rate: Efficacy in Range With Novel Products
Any Time CR Rate: Efficacy in Range With Novel Products 6-Month CR Rate Trending Competitively These data are presented for informational purposes and are not based on any head-to-head or comparator clinical studies. Cross-trial comparisons are inherently limited and may suggest misleading similarit
Slide 23: Trending to Best-in-Class Tolerability for Detalimogene
Trending to Best-in-Class Tolerability for Detalimogene Investigational Agents based on TRAEs*** Deta n=125 Creto n = 112 Any Grade 42% 63% Serious 1.6% 1.8% Fatal 0 0 Dose Interruptions 1.6% Not reported Dose Discontinuations 0.8% 0 Source Internal Data* CG Investor Deck** Approved Products based o
Slide 24: Designed for Logistical and Post-Treatment Protocol Simplicity
Designed for Logistical and Post-Treatment Protocol Simplicity Ease of Use Non-Viral Gene Therapy Viral Gene Therapy Chemo Device Combination Bacterial Therapy Checkpoint Inhibitor No Complex Shipping & Storage ü û ü ü ü Short Single-Step Administration/Procedure ü û û ü ü No Viral/Bacterium Deconta
Slide 25: Logical Sequencing – A Critical Future Consideration for Long-Term Care
Logical Sequencing – A Critical Future Consideration for Long-Term Care HR NMIBC Diagnosis BCG Chemotherapy, CPI & Clinical Trials Radical Cystectomy HR NMIBC Diagnosis BCG Non-Viral Gene Therapy Chemotherapy Referral to Academic Center Viral Gene Therapy Checkpoint Radical Cystectomy Future Past
Slide 26: Experience Developing and Commercializing Highly Successful Medicines
Experience Developing and Commercializing Highly Successful Medicines RON COOPER Chief Executive Officer Chief Executive Officer, Albireo Pharma President, Europe, Bristol Myers Squibb ANTHONY CHEUNG, Ph.D. Chief Scientific Officer Co-founder, enGene Co-inventor All Key enGene Patents ALEX NICHOLS,
Slide 27: Detalimogene Voraplasmid: Designed to be the First Line After BCG
Detalimogene Voraplasmid: Designed to be the First Line After BCG Transformational Opportunity Streamlines Clinical Workflow Designed for Patient Impact Near-Term Planned Catalysts NMIBC market forecasted to be >$20B Non-viral DDX Platform Enables Gene Therapy Without the Headaches Demonstrated Clin
Slide 28: Thank You
Thank You
Slide 29: Protocol Changes
Protocol Changes Prior LEGEND Protocol Current LEGEND Protocol T1 disease at pre-enrollment screen Surgically resect lesion via TURBT Enroll patient Perform 2nd resection at lesion site and restage If residual T1 disease present, patient ineligible Ta disease detected at 3 months Response deemed “Pr
Slide 30: Pre-Protocol Amendment Data - Preliminary Data
Pre-Protocol Amendment Data - Preliminary Data Sept. 2024 Data Cut Updated With Additional Patients N=31 Data Cut Oct. 2025 Any Time (N=31) 3 Month (N=31) 6 Month (N=27)** ITT Population* CR Rate 55% (CI: 38-71) 55% (CI: 38-71) 41% (CI: 25-59) KM Estimate 42% N=21 Data Cut Sept. 2024 Any Time (N=21)
Slide 31: Enrollment Rate Heavily Skewed to Last Months
Enrollment Rate Heavily Skewed to Last 10 Months Bolus of 12-month Patient Evaluations in 2H 2026
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