Slide 1: Development of a Non-Viral Gene Therapy Platform for Mucosal Tissues
Exhibit 99.1 DEVELOPMENT OF A NON-VIRAL GENE THERAPY PLATFORM FOR MUCOSAL TISSUES enGene Controlled Release Society 2023 Meeting and Expo Las Vegas, July 2023
Slide 2: enGene: organ-localized non-viral gene therapies for mucosal tissues
enGene: organ-localized non-viral gene therapies for mucosal tissues Mucosal tissues are Mucosal tissues are attractive underserved by gene therapy target tissues for gene therapy: 1. Ease of accessibility Nasopharynx Carcinoma 2. Mucosal epithelium are vast tissues Rhinitis Mucosal vaccines 3. Prov
Slide 3: Presentation Outline
Presentation Outline 1. Solving for mucosal organ delivery: Development of the DDX platform 2. Transfection of the bladder epithelium and development of a potent immuno-oncology approach for bladder cancer: Preclinical MoA 3. LEGEND Clinical Trial: PoM and PoC demonstrated in human clinical trial 3
Slide 4: Development of the DDX Platform
DEVELOPMENT OF THE DDX PLATFORM enGene
Slide 5: Mucus is a formidable barrier to transfection of mucosal epithelium
Mucus is a formidable barrier to transfection of mucosal epithelium Filtering by interactions Filtering by size Traps cationic and Excludes large particles hydrophobic particles (>200-400 nm) Direction of flow Direction of flow Mucus Mucus 5 | © 2023 | enGene
Slide 6: DDX is the delivery vehicle that enables non-viral gene therapies for mucosal tissues
® DDX is the delivery vehicle that enables non-viral gene therapies for mucosal tissues Dually Derivatized Oligochitosan (DDX®): the mucosal tissue gene delivery vehicle Hydrophilic surface Minimize trapping by mucin layer Short-chain poly-D-glucosamine (chitosan) Cationic surface charge For efficie
Slide 7: Reversible coating of nanoparticles with PEG-b-PLE diblock copolymers
Reversible coating of nanoparticles with PEG-b-polyglutamic acid (PEG-b-PLE) diblock copolymers PEG Plasmid - - - - DNA - PGA + + peptide tail + In-line Mixing + In-line Mixing + + + DDX® polymer DDX®/DNA Reversibly PEGylated DDX®/DNA Nanoparticle Nanoparticle This novel reversible PEGylation techni
Slide 8: Reversible coating of DDX nanoparticles with PEG improves mucus penetration
® Reversible coating of DDX nanoparticles with PEG improves mucus penetration while preserving potency enGene’s novel reversible PEGylation of DDX® strongly improves Reversible PEGylation resolves the “PEG Dilemma” associated with mucus penetration conventional permanent PEGylation Transwell 12 DDX
Slide 9: Preclinical MoA: Transfection of the Bladder Epithelium
PRECLINICAL MOA: TRANSFECTION OF THE BALDDER EPITHELIUM & DEVELOPMENT OF A POTENT IMMUNO- ONCOLOGY APPROACH FOR BLADDER CANCER enGene
Slide 10: FDA guidance: single-arm registrational study for BCG-unresponsive NMIBC
FDA guidance: single-arm registrational study for BCG-unresponsive NMIBC • The Agency’s position is that no therapy exists for BCG-unresponsive NMIBC • Clearly defined patient population and entry criteria for BCG-unresponsive NMIBC • Approval is based on complete response rate, durability, and safe
Slide 11: Background: Non-muscle invasive bladder cancer (NMIBC)
Background: Non-muscle invasive bladder cancer (NMIBC) NMIBC is a clear unmet medical need Initial EG-70 pt. population Tis (carcinoma in situ) 2 Highest cost of all cancers to treat >550,000 new cases of bladder Ta (urothelium) 1 cancer per year T1 (lamina propria) BCG is the only approved first li
Slide 12: EG-70 (detalimogene voraplasmid): dual-immune activator
EG-70 (detalimogene voraplasmid) : dual-immune activator designed to produce meaningful efficacy in NMIBC RIG-I agonists: • Stimulate T cell recruitment and neo-antigen presentation • NK cell stimulation and suppressor cell attenuation promotes tumor killing environment • Clinical data with innate i
Slide 13: EG-70 mediated expression of functional IL-12 and RIG-I agonists
EG-70 mediated expression of functional IL-12 and RIG-I agonists Functional RIG-I agonists IFNg production in mouse splenocytes mouse urothelial cells (MB49) Bladder epithelial cells transfected with EG-70 produce functional IL-12 and RIG-I agonists transgene products 13 | © 2023 | enGene INT02-348
Slide 14: Transgenes expression in mouse bladder following intravesical administration
Transgenes expression in mouse bladder following single intravesical administration of mEG-70 A. mIL -12 prot ein B. eRNA11 RNA VA1 RNA C. Transgene products show dose-dependent expression in mouse bladders Each data point represents expression in a single mouse bladder. n=8/group; data are presente
Slide 15: EG-70 induces dose-dependent target engagement in bladders of tumor-bearing mice
EG-70 induces dose-dependent target engagement in bladders of tumor-bearing mice Ifnb Ifna2 Ddx58 Irf7 Isg15 Cxcl10 Ifit1 Ccl5 Tnfa Ifng Strong dose-dependent induction of RIG-I and IL-12 signaling in bladders of tumor-bearing mice treated with EG-70 n=8/group; data are mean +/- SEM; Mann Whitney t-
Slide 16: Multiple MoA of EG-70 result in profound antitumor efficacy
Multiple MoA of EG-70 result in profound antitumor efficacy Bioluminescence Experimental Design Survival (bladder tumor luciferase) Induction – 9 days Treatment Monitoring ns 10 10 Sham – 1% Mannitol 9 10 8 10 mEG-70 (5µg DNA/mL) 7 10 Luc-MB49 Cells 6 10 mEG-70 (20µg DNA/mL) 5 10 Instilled to induce
Slide 17: EG-70 mechanism of action: increased NK cell and reduced MDSC and TAM
EG-70 mechanism of action: increased NK cell and reduced MDSC and TAM ratios in bladder tissue MDSC Myeloid NK cells Macrophage *** **** *** **** 10 80 40 40 60 30 30 5 40 20 20 20 10 10 0 0 0 0 Sham mEG-70 Sham mEG-70 Sham mEG-70 Sham mEG-70 NK cells activation/maturation Cytokine profile CD69+/KLR
Slide 18: EG-70 mechanism of action: T-cell recruitment and infiltration
EG-70 mechanism of action: T-cell recruitment and infiltration into tumor microenvironment Lymph node Bladder CD4 CD8 CD4 CD8 **** **** 15 25 30 30 *** **** 20 10 20 20 15 10 5 10 10 5 0 0 0 0 Sham mEG-70 Sham mEG-70 Sham mEG-70 Sham mEG-70 H&E CD3 CD4 CD8 Sham mEG-70 mEG-70 promotes an anti-tumor a
Slide 19: Depletion of helper T cells results in loss of anti-tumor activity
Depletion of helper T cells results in loss of anti-tumor activity Study MB49-Luc IVI IVI Termination instillation Tx1 Tx2 FACS to confirm depletion (blood) Study timeline -3 -2 -1 1 3 6 10 13 17 20 24 27 29 Anti-mouse CD4/CD8α intraperitoneal injection CD4 depleted animals Bladder weight Survival D
Slide 20: EG-70 cured animals are protected from re-challenge
EG-70 cured animals are protected from re-challenge: demonstrates generation of anti-tumor immunity Bioluminescence after local intravesical rechallenge 85-days post-cure Naive control re-challenge 10 13 days post rechallenge 10 mEG-70-cured re-challenge Naïve re-challenge 8 10 6 10 4 10 mEG-70-cure
Slide 21: EG-70 systemic and antigen-specific protection
EG-70 systemic and antigen-specific protection Opens advanced disease: MIBC and Metastatic Disease Re-challenge MB49-Luc IVI IVI IVIS IVIS IVIS IVIS IVIS instillation Tx1 Tx2 MB49-Luc Study Day 1 10 17 73 80 86 94 101 108 mEG-70-cured : MB49-Luc SC re-challenge mEG-70 Disease induction mEG-70-cured
Slide 22: EG-70 induces strong target engagement: biomarkers translate across species
EG-70 induces strong target engagement of RIG-I and IL-12 signaling: biomarkers translate across species Ifng Ifnb1 Irf7 Tnfa Mouse Non-human primate Empty EG-70 Empty EG-70 Empty EG-70 Empty EG-70 Vector Vector Vector Vector Mouse data: n=8/group; data are mean +/- SEM; Mann Whitney t-test; tumor b
Slide 23: EG-70: strong efficacy coupled to a clean safety profile
EG-70: strong efficacy coupled to a clean safety profile Toxicology studies did not reveal a maximum tolerated dose (MTD) • Mice - no adverse findings attributable to mEG-70 • Monkeys - very well-tolerated with no systemic findings; • Local findings limited to transient mild inflammation consistent
Slide 24: EG-70 in NMIBC Patients Who Are BCG-Unresponsive and High-Risk NMIBC
EG-70 IN NMIBC PATIENTS WHO ARE BCG-UNRESPONSIVE AND HIGH-RISK NMIBC PATIENTS WHO HAVE BEEN INCOMPLETELY TREATED WITH BCG OR ARE BCG-NAÏVE NCT04752722 enGene
Slide 25: Phase 1/2 combined registrational study design
Phase 1/2 combined registrational study design enables speed to pivotal data and registration Phase 1 – completion 2H2022 Phase 2 – interim data 1H2024 N = <24 patients N ~100 patients Patients: High-risk NMIBC failed BCG, with Cis Patients: High-risk NMIBC failed BCG, with Cis EG-70 Dosing: 2 or 4
Slide 26: Phase study schema - design, dosing, and analysis
Phase 1 study schema - design, dosing, and analysis Overview Cohorts, dosing, and analysis Patients: High-risk NMIBC with CIS – failed BCG Dose-level 1 (N=3) - 250µg DNA/mL Dose-level 2 (N=3-6) - 800µg DNA/mL Treatment Cycle (SoC): 12 weeks Dose-level 3 (N=3-6) - 2,500µg DNA/mL EG-70 Dosing: -1 1 3
Slide 27: 70% Complete Response rate at 3-months with EG-70
70% Complete Response rate at 3-months with EG-70 in high 1 grade NMIBC patients with CIS that are BCG-unresponsive CR at 15* and 18* months ALL DOSE LEVELS 1 3-Months: 70% CR (14/20) DL1 2 6-Months: 39% CR (7/18) (2x250µg) 3 Patients continuing past 3-Months: 4 85% (17/20) DL2 5 (2x800µg) 6 RP2D: D
Slide 28: Urinalysis demonstrates EG-70 proof-of-mechanism
Urinalysis demonstrates EG-70 proof-of-mechanism Urine IL-12 in Phase 1 dose-escalation 1000 DL1 DL2 IL-12 quantified in all patients dosed to-date* 100 DL3 Drug is administered on Days 1 and 8 10 Urine collected prior to dosing 1 Dose-response, localized to the bladder Urine IL-12 levels in DL2 are
Slide 29: Excellent position to optimize EG-70 RP2D based on efficacy and biomarkers
Excellent position to optimize EG-70 RP2D based on efficacy and biomarkers – not based on toxicity! Reported AEs to-date are largely consistent with instrumentation/intravesical administration Grade 2 AEs Grade 1 AEs Grade 3 AEs Grade 4 AEs Grade 5 AEs (mild) (moderate) (severe) (life-threatening) (
Slide 30: Summary and Future Directions; LEGEND (EG-70-101)
Summary and Future Directions; LEGEND (EG-70-101) • EG-70 is a novel, non-viral gene therapy in development for NMIBC • In a first-in-human study, this preliminary analysis demonstrated • A safe and tolerable adverse event profile, with • A high level of efficacy, that is • driven by demonstrated lo
Slide 31: Acknowledgement
Acknowledgement We wish to thank all the patients, clinicians and staff from all the sites that participated in the LEGEND study. enGene, Inc. Clinical & Regulatory CMC Non-Clinical • Rosemary Mazanet • Carlos Fleet • Shauna Dauphinee • Christine Tossone • Daniel Veilleux • Jose Lora • Loraine Warne
Slide 32: Important Additional Information and Where to Find It
Important Additional Information and Where to Find It enGene Inc. and Forbion European Acquisition Corp. (“FEAC”) (Nasdaq: FRBN) have announced they have entered into a definitive agreement respecting a business combination. In connection therewith, a newly formed entity, enGene Holdings Inc. (“Newc