Transgene Sa · EURONEXT:TNG
Transgene Sa — Investor Day (September 2022)
188 slides from Transgene Sa's investor day presentation, Sep 27, 2022
Slide 1: Virus Powered Immunotherapies against Solid Tumors
Virus Powered Immunotherapies against Solid Tumors R&D Day September 27, 2022
Slide 2: Disclaimer
Disclaimer Click to edit Master title style This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. There can be no guarantee that (i) the results of pre-clinical work
Slide 3: Introduction
Click to edit Master title style Introduction HEDI BEN BRAHIM Chief Executive Officer Transgene 3
Slide 4: A World-Leader in Virus Powered Immunotherapies
A World-Leader in Virus Powered Immunotherapies Click to edit Master title style + Remarkable Positive Unparalleled Pioneer novel Integrated Highly Transgene’s progress initial data research routes of GMP productive technologies over the last on all our capabilities administration manufacturing coll
Slide 5: Therapeutic Vaccines
transgene : | ‘transgene \ . . | Fi : Therapeutic Vaccines \ vaccine Y
Slide 6: Agenda
Agenda Click to edit Master title style T H E R A P E U T I C VA C C I N E S TIME TOPIC SPEAKER Therapeutic Vaccines: Potential Game Changers 2:10 pm – 2:15 pm Maud Brandely in Immuno-Oncology 2:15 pm – 2:25 pm Viral vectors could be transformational to treat cancer Éric Quéméneur 2:25 pm – 2:40 pm
Slide 7: Therapeutic Vaccines: Potential Game Changers
Click to edit Master title style Therapeutic Vaccines: Potential Game Changers in Immuno-Oncology MAUD BRANDELY, MD, PhD Chief Medical Officer Transgene 7
Slide 8: Vaccines Could Be Game Changers in Immuno-Oncology
Vaccines Could Be Game Changers in Immuno-Oncology Click to edit Master title style Immunotherapy The number of Treatment resistance Virus-based has become responders can the 4th pilar of still be improved could be overcome cancer vaccines cancer treatments by better Along with surgery, in many indi
Slide 9: Therapeutic Cancer Vaccines: an Attractive Concept
Therapeutic Cancer Vaccines: an Attractive Concept Click to edit Master title style Induce strong and specific immune responses Well tolerated with very good safety profile Can be used alone or in combination with most modalities Source : Hu Ott Wu, ‘’Towards personalized, tumour-specific, therapeut
Slide 10: Targeting the Right Antigens to Deliver Improved Patient Outcome
Targeting the Right Antigens to Deliver Improved Patient Outcome Click to edit Master title style IMMUNOGENICITY Selected TYPE EXPRESSION PREVALENCE EXAMPLES neoAgs Physiologically expressed in fetal cells but CEA, PSA, Oncofetal re-expressed in cancer Shared by a large WT1, MAGE, cells number of pa
Slide 11: Therapeutic Cancer Vaccines: Need to Select the Right Platform
Therapeutic Cancer Vaccines: Need to Select the Right Platform Viral vectors induce strong and durable stimulation of innate and adaptive immunity Source : Blass and Ott, ‘’ Advances in the development of personalized neoantigen- based therapeutic cancer vaccines, Nature Rev Clin Oncol, 2021 11
Slide 12: Viral Vectors Could Be Transformational To Treat Cancer
Click to edit Master title style Viral Vectors Could Be Transformational To Treat Cancer ÉRIC QUÉMÉNEUR, PharmD, PhD Chief Scientific Officer Executive VP Transgene 12
Slide 13: The Key Role of the Vector and Related Challenges
Therapeutic Cancer Vaccines _ The Key Role of the Vector and Related Challenges Click to edit Master title style Criteria of choice Antigen Patient Industrial Clinical Immunological foorprint use properties • Versatility, • Safety and • Target CD8+ T cells, the main Vector large toolbox suitability
Slide 14: Therapeutic Cancer Vaccines, Which Technology?
Therapeutic Cancer Vaccines, Which Technology? Click to edit Master title style I obviously agree for Advantages, but can’t agree on general statements for Challenges considering the large diversity of viral vectors qualified for vaccine design Source: Sahin U, Türeci Ö. Science, 2018. Personalized
Slide 15: Viral Vaccines Prime Both Long Lasting Innate and Adaptive Immunity
Viral Vaccines Prime Both Long Lasting Innate and Adaptive Immunity Click to edit Master title style Post-exposure time Few hours – few days (<48h) Few days Few Weeks Few Months Granulocytes Dendritic cells CD8+ T cells Macrophages CD4+ T cells B cells Plasma cells Antibodies Innate immunity NK cell
Slide 16: Lessons Learned from Two Decades of Cancer Vaccination with MVA
Lessons Learned from Two Decades of Cancer Vaccination with MVA Click to edit Master title style Proven safety in Versatility and Strong immune Ability to disrupt Combinable with multiple routes flexibility response immune tolerance most standards of of administration care (CT, ICIs, RT) (i.e. IV, I
Slide 17: Optimized antigen display: TG4001 and TG4050
Optimized antigen display| The Examples of TG4001 and TG4050 Tipapkinogen sovacivec – TG4001 TG4050 MVA-HPV16(E6/E7)-IL2 MVA-30 neoantigens Del III Described in US2005/0159386A1 Described in WO2018/234506 Specific deletions in E6 and E7 proteins to eliminate MVA viral vector designed to target up to
Slide 18: Randomized Trials Consistently Showed the Superiority of the MVA Arm
Randomized Trials Consistently Showed the Superiority of the MVA Arm Click to edit Master title style TG4010 (MVA:IL2/Muc1) TG4001 (MVA:IL2/HPV16-E6E7) TG4040 (MVA:HCV-NS3,NS4,NS5B) Combination with chemotherapy for 1st line treatment Randomized Phase II trial in CIN2/3 Combination with pegylated-IF
Slide 19: A Solid Experience in Vectorology and GMP Manufacturing
A Solid Experience in Vectorology and GMP Manufacturing, as Well as in Poxvirus Biology Makes Click to edit Master us a Leader in Viral Vector-Based Cancer Vaccine title style PCPV, a novel vector (...) Ramos et al. Clin Transl Immunology. 2022 19
Slide 20: Summary
Summary Click to edit Master title style Ongoing research opens new vistas for : • Further development of MVA- Strong arguments, both in terms based products in personalized of immunology, convenience of use, Among them, MVA, a non cancer immunotherapy. (Cost and industrial operations, in favor repl
Slide 21: TG4001, a HPV16 Therapeutic Vaccine in Phase II
TG4001, a HPV16 Therapeutic Vaccine in Phase II JEAN-PIERRE DELORD, MD, PhD General Manager of IUCT Oncopole of Toulouse 21
Slide 22: IUCT-Oncopole: Leading Player at the Heart of Networks
IUCT- Oncopole |Leading Player at the Heart of Networks Click to edit Master title style 22
Slide 23: IUCT-Oncopole: A Collective Expertise to Fight Cancer
IUCT- Oncopole | A Collective Expertise to Fight Cancer Click to edit Master title style IUCT-Oncopole is: • A referral centre within the French Expert Network for Head and Neck Cancers • Accredited early phase trials center (CLIP2) • Member of numerous INCa clinical research networks The immuno-mon
Slide 24: IUCT-Oncopole: Key Figures 2021
IUCT- Oncopole | Key Figures 2021 Click to edit Master title style 24
Slide 25: HPV is Associated with a Broad Variety of Anogenital Cancers
HPV is Associated with a Broad Variety of Anogenital Cancers Click to edit Master title style Incidence of anogenital HPV16 positive cancers % of HPV induced cancers by localization w/o liver metastases Newly diagnosed patients with metastatic disease and patients with recurrent disease 70% Orophary
Slide 26: Increasing Role of Immunotherapy in Standards of Care
Increasing Role of Immunotherapy in Standards of Care In first Click and to edit second Master lines of treatment title style CERVIX ANAL VULVAR / VAGINAL PENILE 1L: 1L: 1L: 1L: platinum-based platinum-based platinium single agent, platinum-based chemotherapy +/- chemotherapies platinum-based chemot
Slide 27: HPV16-Associated Cancer Patients Need Better Treatment Options
But Still, HPV16-Associated Cancer Patients Need Better Treatment Options Click to edit Master title style Nivolumab KN028 + KN158 [ref] (pooled CARACAS [ref] KN158 [ref] CM 358 [ref] NCI9673 [ref] analysis) Phase 1b (KN028) Phase 2 Phase 2 Phase 2 Phase 2 and Phase 2 (KN158) Anal 2L Cervical 2L Cer
Slide 28: TG4001: Therapeutic Vaccine Targeting HPV-Positive Cancers
TG4001 | Therapeutic Vaccine Targeting HPV-Positive Cancers Click to edit Master title style ANTIGENS INTERLEUKIN 2 28
Slide 29: TG4001: Therapeutic Vaccine Targeting HPV-Positive Cancers
TG4001 | Therapeutic Vaccine Targeting HPV-Positive Cancers Randomized Click to edit MasterPhase title styleII trial in CIN 2/3 Complete resolution at 6 months (%) (1) Strong data for TG4001 in CIN 2/3(1-2) TG4001 single-agent (3 injections) vs placebo Strong and specific response against tumor cell
Slide 30: TG4001 + Avelumab: Heavily Pretreated Patients with Metastatic Cancer
TG4001 + Avelumab (Ph Ib/II) | 34 Heavily Pretreated Patients with Metastatic Cancer Updated data title Click to edit Master – Cut-off style date Sept. 2021 (NCT03260023) Patients without liver Patients with liver Overall metastases metastases (N=36) (N=25) (N=11) Age (years) Mean 60.8 52.9 58.4 Ran
Slide 31: TG4001 + Avelumab: Administration Schedule
TG4001 + Avelumab (Ph Ib/II) | Administration Schedule Collaboration Click to edit Master title style with TG4001: Recommended dose for Phase 2 = 5x107 pfu – administered SC Avelumab: 10mg/kg – administered IV 31
Slide 32: TG4001 + Avelumab Demonstrated Anti-Tumor Activity
TG4001 + Avelumab Demonstrated Anti-Tumor Activity in Overall Patient Population Updated data title Click to edit Master – data style cut off date Sept. 2021 Overall 36 evaluable 1 COMPLETE 7 PARTIAL population patients RESPONSE RESPONSES Patient with anal cancer Two patients and peritoneal extensio
Slide 33: Patient Population Identified from Trial Data
TG4001 + Avelumab (Ph 1b/II) | Patient Population Identified from Trial Data Promising results, Click to edit Master particularly in patients without liver metastasis title style Metastatic patients w/o liver metastasis (n=25) Compares favorably to ICIs in vs patients with liver metastasis (n=11) mo
Slide 34: Treatment Induced Long-Lasting Responses
TG4001 + Avelumab (Ph 1b/II) | Treatment Induced Long-Lasting Responses Click to edit Master title style Evolution of tumor size – End of Aug. 2022 in metastatic patients without liver metastases 1 patient still treated after 4+ years 2 patients with 2+ years follow up Responses were also observed i
Slide 35: Induced Specific T-Cell Response Against HPV16 E6 & E7
TG4001 + Avelumab (Ph 1b/II) | Induced Specific T-Cell Response Against HPV16 E6 & E7 Click to edit Master title style Patients with a detected response against target antigens (Ex vivo ELISPOT response against E6 and E7) At baseline, no patient showed a 50 30 300 80 100 200 200 specific response ag
Slide 36: (cell/mm²) Change in infiltrated CD8 + cells infiltrated CD8 + cells
Change in infiltrated CD3 + cells CD3+ (cell/mm 2) (cell/mm²) Change in infiltrated CD3 + cells 10 100 1000 (cell/mm²) 0 500 1000 1500 CD3+ (cell/mm 2) Change in infiltrated CD3 + cells CD3+ (cell/mm 2) (cell/mm²) B 1000 10000 10000 0 1000 1500 Ba as se el 10 10 100100 1000 10000 0 500500 1000 1500
Slide 37: Expanded Trial Focuses on Patient Population with Improved Benefit
Expanded Trial Focuses on Patient Population that Derived Improved Clinical Benefit in Phase Ib/II Click to edit Master title style Patients with HPV16-positive anogenital cancer including cervical, vulvar, vaginal, penile and anal cancers With recurrent/metastatic disease Treated in first line or i
Slide 38: Randomized Controlled Phase II Trial Supported by Clinicians
TG4001 | Randomized Controlled Phase II Trial Supported by Clinicians Trial to enroll up to ~ 150 patients (NCT03260023) Randomized (1:1) Arm A Patients with TG4001 + avelumab Patients with HPV16+ Anogenital Cancer recurrent/metastatic disease Avelumab single agent Arm B PRIMARY ENDPOINTS SECONDARY
Slide 39: Inclusions in Phase II Part Were in Line with Forecast
Inclusions in Phase II Part Were in Line with Forecast Click to edit Master title style TG4001.12 study Phase II part 2 - Recruitment curve Patients without liver mets 60 Sufficient number 50 of patients has been 40 enrolled to allow interim analysis 30 in Q4 2022 20 10 0 17 active sites planned act
Slide 40: An Adaptive Trial to Optimize Patient Inclusions
An Adaptive Trial to Optimize Patient Inclusions Click to edit Master title style Total number of patients to be adjusted based on: the results obtained in the interim analysis the recommendations of the IDMC 40
Slide 41: A Methodologically Sound Phase II Trial to Further Validate TG4001
A Methodologically Sound Phase II Trial to Further Validate the Potential of TG4001 Click to edit Master title style Interim analysis data expected Q4 2022 Positive final results could lead to the launch of a registrational trial in anogenital cancers 41
Slide 42: Maud Brandely, MD, PhD
Click to edit Master title style MAUD BRANDELY, MD, PhD Chief Medical Officer Transgene 42
Slide 43: Cancer Vaccines: Demonstrating Efficacy in Several Clinical Settings
Cancer Vaccines – Demonstrating Efficacy in Several Clinical Settings Ongoing trial will be the first Phase II randomized trial with a therapeutic vaccine to read out in Based on this PoC, anogenital cancers Transgene is progressing Phase Ib/II results are very solid proof of with a very differentia
Slide 44: Medical Needs and Current Gaps
Medical Needs and Current Gaps – Moving Therapeutic Vaccines Up Treatment Lines Click to edit Master title style Surgery + First-line of advanced disease Adjuvant therapy therapy and beyond Strong NEED TO INCREASE and EXTEND REMISSION Remission / periods Minimal residual disease Ideal opportunity fo
Slide 45: Monotherapy Administration in Patient with Residual Disease
Monotherapy Administration in Patient with Residual Disease AClick strategic positioning to edit Master title style Patients with moderately mutated tumors Ovarian and Head & Neck cancers DESIGNED Patients in clinical remission with minimal residual disease TO TREAT that could be followed by additio
Slide 46: A Vaccine Targeting Patient-Specific Neoantigens
A Vaccine Targeting Patient-Specific Neoantigens To stimulate Click to edit Masterstrong title styleand durable anti-tumor immune response Patient-Specific Neoantigens are: Private neoantigens which means that the targets are specific to each patient, addressing the issue of tumor heterogeneity 100%
Slide 47: AI Use and Perspective at Transgene
AI Use and Perspective at Transgene KAÏDRE BENDJAMA Program Director Transgene 47
Slide 48: AI is More Than the Buzzword of the Decade
AI is More Than the Buzzword of the Decade AI istowidely Click developed edit Master title style and used in our daily lives Over the last decade performance of AI system vastly improved allowing implementation in low risk/low regulation application (e.g. suggested reply on your message app), to mor
Slide 49: Applications of AI in Healthcare Became a Reality
Applications of AI in Healthcare Became a Reality in the Last Years Numerous usetitle Click to edit Master cases style have been registered and commercialized Sources: Benjamens S, et al. Npj Digital Medicine, 2020 49
Slide 50: AI in Oncology and Precision Medicine
AI in Oncology and Precision Medicine Foundation models Oncology progresses Click to edit Master title style very fast toward increased performance and unprecedented complexity Data Deep learning intensity netMHC Bioinformatic “predictions” Digital pathology Machine learning Oncology 4.0 and statist
Slide 51: Deep Learning Has Allowed Tremendous Increase in Performance
Deep Learning Has Allowed Tremendous Increase in Performance in Complex Tasks Deep Click to neural networks edit Master title style have driven performance up by using large amount of data More data ! 2011 2016 Deep neural Performance networks Traditional machine learning 26% errors 5% errors 3% err
Slide 52: Deep Neural Networks Handle Vast Amounts of Data
Deep Neural Network are Particularly Good at Handling Vast Amount of Data Each Click tolayer of atitle edit Master neural style network will filter the information to only keep data that is actually relevant to the final output X T0=X T1 T2 T3 (Feature / Image) (Input Layer) (Hidden Layer 1) (Hidden
Slide 53: Neoantigen Cancer Vaccines are a Typical Use Case for AI
Neoantigen Cancer Vaccine are a Typical Use Case for AI-Based Systems Highly parametric Click to edit – High heterogeneity Master title style Mutations vary significantly across patients, along ~1% of Mutations are neoantigens the therapeutic journey and across cells in a given cancer: Mutation Burd
Slide 54: Our Vaccine Design Process Today
Our Vaccine Design Process Today Deep learning allows feature agnostic antigen selection ROUTINE DATA PROCESSING, GENE EDITING, TUMOR BIOPSY GENE SEQUENCING ARTIFICIAL INTELLIGENCE MANUFACTURING Patient Next Selection of Vaccine Treatment generation 30 neoantigens generation and administration seque
Slide 55: Is the AI Used in our Trials Doing Better Than Other Approaches?
Is the AI Used in our Trials Actually Doing Better Than Any Other Approach? Method Click to edit benchmark Master title style is unlikely to be achieved but AI contribution is tangible Across 6 patients treated: We expect ~200 actual targets in the pool of 2119 mutations identified in our study pati
Slide 56: Beyond Antigen Selection & Product Design
Beyond Antigen Selection & Product Design Exploitation oftitle Click to edit Master comprehensive style genomic data and real time contextualisation in clinical knowledge pave the way to accurate patient selection Advanced analysis of genomic information allows deep characterization of patient PI3K
Slide 57: In a Nutshell
In a Nutshell Click to edit Master title style AI HAS THE POTENTIAL Further to drive a MAJOR IMPROVEMENT TO VACCINE DESIGN in EFFICACY OF THERAPY STILL A LONG JOURNEY AHEAD toward a definitive clinical validation AI approach Contextualize Leveraging Treating this but AI based approaches will help fi
Slide 58: Maud Brandely, MD, PhD
Click to edit Master title style MAUD BRANDELY, MD, PhD Chief Medical Officer Transgene 58
Slide 59: myvac: An Integrative Approach Capitalizing on Multiple Technologies
myvac® | An Integrative Approach Capitalizing on Multiple Cutting-Edge Technologies Taking the Click to edit Treatment Master title style of Each Patient to a New Level MVA Viral Vector: a Powerful Multiple Proprietary Innovative Technologies Platform for Vaccine Development Well-established safety
Slide 60: From the design of the myvac platform to first readouts
Click to edit Master title style From the design of the myvac® platform to first immunological and clinical readouts CHRISTIAN OTTENSMEIER, MD, PhD, FRCP University of Liverpool The Clatterbridge Cancer Center NHS Foundation Trust La Jolla Institute for Immunology 60
Slide 61: Cancer Immunotherapy in a Nutshell
Cancer Immunotherapy in a Nutshell Click to edit Master title style The puzzle then: An intriguing challenge: Can we re-establish immune control If cancer develops What does ‘immune control’ look like the immune system patient level: cancer disappears must have failed cellular level: what does this
Slide 62: Exploiting the Immune System for Treatment
Exploiting the Immune System for Treatment Click to edit Master title style Clinical response to aPD1/aPDL1 First example: allogeneic bone marrow meaningful cure rates - but much toxicity transplantation immunotherapy has become Since 2011 standard treatment stunning clinical benefit in responders C
Slide 63: Measuring Immune Attack: Counting T Cells
‘Measuring Immune Attack’: Counting T Cells Click to edit Master title style Ward et al, BJC 2014 To understand biology: Wood et al, Oncotarget 2016 WE NEED MORE SOPHISTICATED TOOLS! Ottensmeier, CaRes 2016 63
Slide 64: Mechanistic Insights Gained
Mechanistic Insights Gained: long Click tolived CD8+ edit Master titleTstyle tissue resident memory are: Presence of CD103 (IHC) predicted patient survival above that of CTLs highly effective killers expand in cancer tissue express unique, actionable targets are easily quantified reproduced in multi
Slide 65: Key Questions
Key Questions Click to edit Master title style What targets can immune cells recognize in cancer? IMMUNOGENICITY Selected How many cells are there that see one antigen? neo Ags Which target is ‘most recognized’? Oncoviral Ags Immunologically appealing: neo-epitopes: Shared Ags Tumor no central toler
Slide 66: At the Heart of the Matter: TCR-MHC Interactions
At the Heart of the Matter: TCR-MHC Interactions Imagine the TCR as a fingerprint It defines the identity for the individual T cell From: Joglekar AV, Nature Methods, 2021 66
Slide 67: The Toolset
The Toolset Click to edit Master title style Ongoing programme of systematic probing 1 COLLECT BLOOD 2 FIND CELLS 3 IDENTIFY T CELL (Apheresis product) REACTIVE RECEPTOR 6 DEFINE withTumour antigen ‘molecular barcode’ OVERLAP = antigen reactive T cells in tissue • Number 4 COLLECT 5 ALL T CELLS: • Q
Slide 68: Molecular Profiling of Antigen-Reactive T Cells
Molecular Profiling of Antigen-Reactive T Cells Click to edit Master title style Viral antigens in Shared antigens Neo-epitope cancer in cancer antigens in cancer Possible for any antigen to define T cell repertoire: Cancer antigens Sites of toxicity… Platform in the adjacent non - any tissue (skin,
Slide 69: Inception of myvac: Demonstration of Concept
Inception of myvac® – Demonstration of Concept Click to edit Master title style THE QUESTION: CD3 CD4 CD8 CD103 100 DO IMMUNE COLD CANCERS 75 50 % Positive cells CONTAIN NEOEPITOPE REACTIVE 25 20 T CELLS? 12.0% 12.9% 4.4% 1.8% 15 PD-1 PD-L1 MHC I MHC II 10 THE PROMPT: 200µm 5 0 A PATIENT IN TROUBLE
Slide 70: Neoantigen Selection for Personalized Vaccination
Neoantigen Selection for Personalized Vaccination Click to edit Master title style TP01: 23 variants involving 18 genes: 22 missense and 1 DEL/frameshift Somatic Mutation Subcellular Gene Symbol Entrez Gene Name Effect GO Biological process bp AA Localisation COG2 Component of oligomeric golgi compl
Slide 71: Immunogenicity Testing in Autologous Setting
Immunogenicity Testing in Autologous Setting Click to edit Master title style TCR rescue, Day 1: SetDay up 1: IVSSet up IVS Day 13: Cell Dayharvest, 13: Cell set up IFNg harvest, setELISpot up IFNg ELISpot sequences reproduced in: PBMC PBMC PBMC PBMC Plate in triplicate: Plate in triplicate: Circula
Slide 72: Immunogenicity Testing in HHD Model
Immunogenicity Testing in HHD Model Click to edit Master title style MVA-based neoantigen MVA-based vaccine vaccine Vaccination: D1 and D8 incorporating 18 mutated gene sequences tested in the human x2 HLA-A*02-restricted transgenic mouse model Harvest splenocytes: D15 HLA-A*02- (HHD) restricted tra
Slide 73: Improving on State of the Art
Improving on ‘State of the Art’ Click to edit Master title style CURRENT STANDARD EXCEEDING STATE OF THE ART Enough of the right kind of cells Training more Anti-PD1 solves of the right cells the cancer problem 73
Slide 74: TG4050: Clinical Translation of Exemplar Data
TG4050 – Clinical Translation of Exemplar Data Aim: To establish the relevance of cancer vaccines To demonstrate the power of neo-epitope vaccines Choose optimized setting Evaluate clinical impact Minimal High unmet • Safety • Feasibility • Benefit • Option immunosuppression clinical need to measure
Slide 75: Extensive Immunomonitoring Program in the Two TG4050 Trials
An Extensive Immunomonitoring Program in the two TG4050 Clinical Trials Sampling and analyses Click to edit Master title style plan – Document immune cell responses Regular CT scans Vaccine manufacturing Screening Vaccination (induction period) Vaccination (Boost period) D0 D8 D22 D43 D64 D85 D211 S
Slide 76: Unprecedented Rate of T Cell Response Against Tumor Specific Epitopes
Unprecedented Rate of T Cell Response Against Tumor Specific Epitopes Profound Remodeling Click to edit Master title style of Immune Cells Consistent with Anti Tumor Response Induction of multiple T cell responses Differentiation of CD4 and CD8 into effector cells are in treated patient consistent w
Slide 77: TG4050 Induces Broad and Specific T Cell Responses
Number of spots / 400.000 PBMC Number of spots / 400.000 PBMC 0 5 10 15 20 25 0 5 10 15 20 25 media media 1 1 2 2 Click to edit Master title style 3 3 4 4 5 5 D64 6 6 Baseline 7 7 8 8 9 9 10 10 Number of spots / 400.000 PBMC Number of spots / 400.000 PBMC 0 10 20 30 40 50 0 10 20 30 40 50 m m ed ed
Slide 78: Profound Remodelling of Immune Cells
Profound Remodelling of Immune Cells consistent with Anti Tumor Response Suggesting that Click to edit Master titlethe styleVaccine is Able to Effectively Prime the Immune System Priming of innate immunity Immune differentiation during response to immunotherapies Response Naïve Memory Effector Naive
Slide 79: ctDNA Changes Consistent with CA-125 and Clinical Outcome
ctDNA changes are Consistent with Changes in CA-125 and Clinical Outcome Click to edit Master title style Patient 1 Patient 2 ctDNA Tumor molecule/mL of plasma ctDNA Tumor molecule/mL of plasma 2.0 400 4 400 CA-125 CA-125 1.5 300 3 300 CA-125 CA-125 (U/mL) (U/mL) ctDNA ctDNA 1.0 200 2 200 0.5 100 1
Slide 80: A Large Clinical Need
A Large Clinical Need: Click to edit Master title style HPV negative patients Enriched for TIL low (clinically ‘self declared’) High stage, nodal involvement, ECS The bad end of ‘immune cell low cancers’ Expected median PFS ~1 year 80
Slide 81: TG4050: HPV-Negative Head and Neck Cancer Trial
TG4050 | HPV-Negative Head and Neck Cancer Trial after Surgery and Adjuvant Therapy Click to edit Master title style TG4050 is designed to Arm A INCREASE and EXTEND REMISSION period TG4050 TG4050 + SOC (single agent) (incl. checkpoint Randomized Repeated injections blockers) Phase I Trial Recurrence
Slide 82: Update on Extremely Promising First Signals of Clinical Activity
Update on Extremely Promising First Signals of Clinical Activity Repeated Injections Click to edit Master title styleof single agent TG4050 in patients with minimal residual disease Head & Neck Cancer Trial No related SAEs At end of August 2022 Good safety profile 6 months 12 months 18 months Arm A:
Slide 83: State of the Art: Effector T cells
‘State of the Art’ Click to edit Master title style Effector T cells are a ‘conditio sine qua non’ for immunotherapy CHECKPOINT CANCER INHIBITORS VACCINES benefit a small percentage The only tool to ‘train’ anti cancer of patients T cells ‘Awaken’ or ‘release’ pre-existing Will form the backbone of
Slide 84: TG4050 Combines All Key Features
TG4050 Combines all key features to deliver clinical efficacy TG4050 trials encompass decades of adaptive learning MVA backbone Immunogenic Optimized clinical setting to demonstrate efficacy Well-tolerated TG4050 Randomized, multi center trial reduces or eliminates selection bias Neoantigens targeti
Slide 85: TG4050
TG4050 ASTOUNDING EFFECT TG4050 in early data: SMART DESIGN: We will be able to quantify the impact on Early data measurable disease Safe Immunogenic support HNSCC trial: at recurrence in arm B CLINICAL BENEFIT Ovarian trial Carefully designed biomarker program to demonstrate MOA Small sample size s
Slide 86: Outlook
Outlook Click to edit Master title style Poised to deliver a landmark change • By demonstrating • Clinical benefit of a cancer vaccine • Efficacy of MVA based vaccination And most importantly: • By enabling: • Offer hope to patients • Definiton of the ‘optimal patient setting’ with terrible and fata
Slide 87: Personalized Therapeutic Vaccine in the Treatment of Ovarian Cancer
Click to edit Master title style Personalized Therapeutic Vaccine in the Treatment of Ovarian Cancer MATTHEW S. BLOCK, MD, PhD Immunologist and medical oncologist at the Mayo Clinic Associate Professor of oncology 87
Slide 88: Investigator Interests
Investigator Interests Click to edit Master title style I study therapeutic vaccines The focus of my research is to and oncolytic viruses as better understand the approaches to induce anti- As a medical oncologist, mechanisms by which cancers tumor immune responses, I treat patients with interact wi
Slide 89: The Need For Better Treatments For Ovarian Cancer
The Need For Better Treatments For Ovarian Cancer Ovarian cancer is most often diagnosed at Stage III or Stage IV, as early-stage disease is typically asymptomatic, and there is no effective screening test. Those patients fit for aggressive treatment receive cytoreductive surgery and chemotherapy wi
Slide 90: Maintenance Therapies For Ovarian Cancer
Bevacizumab—PFS Bevacizumab—OS Maintenance Therapies For Ovarian Cancer Due to the high recurrence rate of ovarian cancer, maintenance therapies after first-line chemotherapy are commonly tried. Burger, et. al., NEJM, 2011 Bevacizumab (anti-VEGF) is approved for use Tewari, et. al., J Clin Oncol, 20
Slide 91: Detecting Residual/Recurrent Disease in Ovarian Cancer
Detecting Residual/Recurrent Disease in Ovarian Cancer Click to edit Master title style has long been used as a tumor marker for ovarian Onset of 2nd-line chemotherapy CA 125 cancer (the secreted portion of MUC-16) increases to > 2 x ULN about 3-6 months before patients develop clinical recurrence c
Slide 92: TG4050: Ovarian Cancer Trial after Surgery and Adjuvant Chemotherapy
TG4050 | Ovarian Cancer Trial after Surgery and Adjuvant Chemotherapy Phase I Trial Click to edit intitle Master upstyle to 13 Patients (NCT03839524) TG4050 is designed to Complete response INCREASE and EXTEND Approx. 80% of patients REMISSION periods experience CR Asymptomatic relapse with 12-month
Slide 93: AACR Update on Extremely Promising First Signals of Clinical Activity
AACR Update on Extremely Promising First Signals of Clinical Activity From Click to Repeated Injections edit Master title style of TG4050 as Monotherapy in Patients with Minimal Residual Disease Ovarian Cancer Trial Data updated end of August 2022 Expected time of clinical progression[1] 6 months 12
Slide 94: First Patient Treated with TG4050 in Ovarian Cancer Trial
First Patient Treated with TG4050 in Ovarian Cancer Trial Normalization Click to edit Masteroftitle CA-125 style and ctDNA without Clinical Progression for 9 Months 73-year-old female Relevant medical history and treatments Delord et al, “Phase 1 studies of personalized neoantigen vaccine TG4050 in
Slide 95: Summary
Summary Click to edit Master title style Asymptomatic patients with evidence of recurrent ovarian While the number of patients cancer (CA 125 or imaging) do Personalized vaccine treated is limited, early results not benefit from immediate manufacturing is feasible, suggest that the TG4050 initiation
Slide 96: Maud Brandely, MD, PhD
Click to edit Master title style MAUD BRANDELY, MD, PhD Chief Medical Officer Transgene 96
Slide 97: TG4050: Next Steps
TG4050 | Next Steps Click to edit Master title style Additional data These immune and to be communicated clinical data will serve in H1 2023 to identify the most appropriate path to take TG4050 to Phase II and forward one patient • one genome • one vaccine 97
Slide 98: Q&A
Q&A 98
Slide 99: Break
BREAK LET’S MEET AGAIN IN 15 MINUTES AT 4:15 PM CET 99
Slide 100: Oncolytic Viruses (OVs)
transgene Oncolytic viruses (OVS)
Slide 101: Agenda: Oncolytic Viruses
Agenda Click to edit Master title style O N C O LY T I C V I R U S E S TIME TOPIC SPEAKER 4:15 pm – 4:30 pm Clinical positioning and advantages of poxviruses Eric Quéméneur 4:30 pm – 4:50 pm Assessing novel routes of administration with TG6002 Adel Samson 4:50 pm – 5:05 pm New Invir.IO™ candidate: a
Slide 102: Clinical Positioning and Advantages of Poxviruses
Click to edit Master title style Clinical Positioning and Advantages of Poxviruses ÉRIC QUÉMÉNEUR, PharmD, PhD Chief Scientific Officer Executive VP Transgene 102
Slide 103: The Two Families of Viral Vectors-based Immunotherapeutics
The Two Families of Viral Vectors-based Immunotherapeutics Turning Click to editfoes into Master friends title style Priming and activation Local induction of immuno- ③ ④ Trafficking of Viral-vector vaccine stimulatory pathways T-cells to tumors Antigen Expression of presentation cancer antigens ② O
Slide 104: Oncolytic Vectors Combine Multiple Modes of Action
Oncolytic Vectors Combine Multiple Modes of Action in the Tumor Micro-environment Click to edit Master title style Tumor cell lysis upon Triggering of Local delivery of viral replication the immune system recombinant payload ONCOLYTIC VIROTHERAPY aims at creating a DYNAMIC SYNERGY in the REMODELLING
Slide 105: VVcopTK-RR- is a Strong Inducer of Immunogenic Cell Death
VVcopTK-RR- is a Strong Inducer of Immunogenic Cell Death Click to edit Master title style HALLMARKS OF IMMUNOGENIC CELL DEATH 105 Fend et al. Cancer Research (2017)
Slide 106: Our Technological Platform for Engineering Innovative OVs
Our technological platform for engineering innovative OVs Click to edit Master title able style to address challenging tumors Targeted insertion of recombinant payload at selected loci in the Vaccinia genome Several payloads PRODRUG can be encoded ACTIVATOR in one multi- e.g. targeted armed OV IMMUN
Slide 107: BT-001, a Remarkable Example of the Invir.IO Platform
BT-001, a Remarkable Example of the Potential of the Invir.IO™ Platform Click to edit Master title style 4-E03, anti-CTLA-4 antibody A first-in-class anti-CTLA4 IgG1 selected from the n-CoDeR®/F.I.R.S.T™ platform at BioInvent for its potential to deplete intra-tumoral Tregs, cloned as a full-length
Slide 108: mBT-001 Induces Cures Across Various Syngeneic Cancer Models
mBT-001 Induces Cures Across Various Syngeneic Cancer Models Click to edit Master title style CT26 A20 EMT6 MC38 B16 Colon carcinoma, Balb/c B-cell lymphoma, Balb/c Breast carcinoma, Balb/c Colon carcinoma, C57BL/6 Melanoma, C57BL/6 Hot tumor Cold tumor Treated / untreated with mBT-001 Treatment sch
Slide 109: mBT-001 Elicits Robust Systemic CD8+ T Cell-Dependent Immunity
mBT-001 Elicits a Robust Systemic CD8+ T Cell-Dependent Anti-Tumor Immunity Click to edit Master title style Tumor-specific Vector-specific Induction of memory response CT26 in BALB/c model T cells T cells Rechallenge experiment Intra-tumoral mBT-001 treatment mBT-001 mBT-001 + CD4 depl. + CT26 chal
Slide 110: Systemic CD8+ T Cell Immunity Translates into Abscopal Response
Systemic CD8+ T Cell Immunity Translates into Abscopal Response Click to edit Master title style Contralateral Ipsilateral Large remodeling of TME ↑ effector CD8+ T cel i.t. injection ↓ exhausted CD8+ T cells No ↓ intratumoral Tregs treatment CT26 CT26 in BALB/c syngenic model No Injected Contralate
Slide 111: Differential Gene Expression Confirmed Large Immune Remodeling of TME
Differential Gene Expression Analysis Confirmed Large Immune Remodeling of the TME, and Click to edit Induction Master title style of DC-Dependent Antigen Cross-Presentation GO terms enriched in the set of 352 differentially cDC1-associated transcripts expressed genes, in CT26 tumors treated differe
Slide 112: BT-001: Ongoing Phase I/II Trial
BT-001 | Ongoing Phase I/II Trial (NCT04725331) Leverage the ITtitleRoute Click to edit Master style to Accelerate Development with Anti-PD1 Patients with metastatic or Positive initial Phase I part A readout Repeated and advanced injectable solid ascending doses of tumors BT-001 alone is well toler
Slide 113: Transgene & AstraZeneca to Co-Develop Novel Invir.IO OVs
Transgene & AstraZeneca to Co-Develop 5 Novel Invir.IO™ OVs Click to edit Master title style Transgene and AstraZeneca entered into a collaboration and exclusive license option agreement in 2019 For 5 innovative Invir.IO™ based armed oncolytic immunotherapies Integrating one or more transgene(s) cho
Slide 114: An Area of Active Internal Research and Collaboration
An Area of Active Internal Research and Collaboration Click to edit Master title style Supporting our strong aspiration to leadership in the IV route CHALLENGES OF OV IN THE INTRAVENOUS ROUTE Internal projects exploring Combination with nano- various arming of VV-COP formulated mRNAs 5 patent applic
Slide 115: A Strong Strategic Axis Built on Lessons Learned
A Strong Strategic Axis Built on Lessons Learned from Two Products Click to edit Master title style in Clinical Development and Strong Preclinical Investments THE BEST IS CERTAINLY YET TO COME 115
Slide 116: Assessing novel routes of administration with TG6002
Click to edit Master title style Assessing novel routes of administration with TG6002 ADEL SAMSON, MBCHB, MRCP, PHD Consultant Medical Oncologist & Associate Professor at The Leeds Teaching Hospitals NHS Trust and The University of Leeds 116
Slide 117: The Leeds Team
The Leeds Team Click to edit Master title style MY LABORATORY RADIOLOGISTS EARLY PHASE TEAM SURGEONS GROUP Emma West Jai Patel Alan Anthoney Raj Prasad Karen Scott Chris Hammond Chris Twelves Vijay Anand Rebecca Brownlie Tze Wah Fiona Collinson Vivek Upasani Fay Ismail Olly Hulson Angela Bennett Pet
Slide 118: In Which GI Cancers Could OV Make an Impact?
In Which GI Cancers Could OV Make an Impact? Click to edit Master title style Hepatocellular carcinoma: Colorectal cancer: Cholangiocarcinoma: • Immune sensitive cancer • 5FU sensitive • No current neoadjuvant • No current neoadjuvant therapy • dMMR Vs pMMR or adjuvant therapy • No standard second l
Slide 119: Oncolytic Viruses: Route of Delivery
Oncolytic Viruses – Route of Delivery Click to edit Master title style Intratumoral injection Intravenous Locoregional • Ensures virus reaches tumor • Less invasive; allows easier • Intrahepatic artery • BUT: Limited distribution of virus recurrent administration • Isolated limb perfusion within a d
Slide 120: Pexa-Vec: Triggers Antitumor Immunity after Single IV Administration
Pexa-Vec | Triggers Antitumor Immunity after Single IV Administration Prior Click to to editplanned Master titlesurgery style of locally advanced, poor prognosis or metastatic cancers Single i.v. Pexa-Vec Surgery Post-surgery Pexa-Vec shown to: d1 d2 d3 d5 d14 ± 4d 1m 3m • Selectively target tumor t
Slide 121: Virus Carriage in Blood
Virus Carriage in Blood Click to edit Master title style 121
Slide 122: Virus Tumour Specificity
Virus Tumour Specificity Click to edit Master title style 122
Slide 123: Stimulation of CD8 T-Cell Tumor Infiltration
Stimulation of CD8 T-Cell Tumor Infiltration Click to edit Master title style 123
Slide 124: Stimulation of Adaptive Anti-Cancer Immunity
Stimulation of Adaptive Anti-Cancer Immunity Click to edit Master title style 124
Slide 125: PreOp Pexa-Vec Summary
PreOp Pexa-Vec Summary Click to edit Master title style Induction if interferon response Intravenous • Stimulates innate anti-cancer Stimulation immunity Pexa-Vec reaches • Migration of cytotoxic T-cells to of T-cell anti-cancer metastatic tumors immunity sites of virus infection/replication, i.e. t
Slide 126: TG6002: Chemotherapy Produced Directly in the Tumor
TG6002 | Chemotherapy Produced Directly in the Tumor Interim Click to editPhase I data Master title style (IV*) presented at ESMO 2022 The right virus + payload The right indication 5-FU sensitive cancers Oncolytic armed with FCU1 Current SoC in 2L: bevacizumab + folfiri/folfox gene, prodrug activat
Slide 127: TG6002: Phase I/IIa Trial of Intravenous Administration
TG6002 | Phase I/IIa Trial to Evaluate Intravenous Administration of VVcopTK-RR- (NCT03724071) Click to edit Master title style Phase I (inclusions completed) Administration schedule 1x106 to 3x109 pfu - 3 infusions optimization Arm A in 3 weeks (days 1, 8 and 15) Patients with 6 cohorts advanced ga
Slide 128: TG6002: Updated Phase I Data Presented at ESMO 2022
TG6002 | Updated Phase I Data Presented at ESMO 2022 Clinical PoC Click to edit of title Master Feasibility of IV Route for our Patented VVcop TK-RR- Virus thestyle TG6002 replicates in tumor 5-FU is expressed in tumor Long-lasting expression tissue without sign of tissue in most of the of 5-FU acro
Slide 129: TG6002: Clinical PoC of the Feasibility of IV Route
TG6002 | Clinical PoC of the Feasibility of IV Route for the VVcopTK-RR- Virus Click to edit Master title style ONSET OF NEUTRALIZING ANTIBODY RESPONSE IS NOT ASSOCIATED WITH A DECREASED BIOLOGICAL ACTIVITY OF THE PRODUCT Onset of neutralizing antibodies Absence of correlation between Peak neutraliz
Slide 130: Assessing a Locoregional Route: IHA Trial with TG6002
Assessing a Locoregional Route | IHA Trial with TG6002 Intrahepatic Artery Route (IHA) Routinely used to deliver Could efficiently deliver a higher concentration therapeutic agents into patients of TG6002 to the liver metastases (visible or with liver tumors not visible with CT scan) Phase I (inclus
Slide 131: TG6002.03 Intra-hepatic Artery Trial
TG6002.03 Intra-hepatic Artery Trial Click to edit Master title style TG6002: Copenhagen strain VV, TK and RR deleted Encodes cytosine deaminase and uracil phosphoribosyltransferase proteins Conversion of prodrug 5-FC into the cytotoxic 5-FU Phase I-IIa study: • Two IHA infusions in liver-dominant a
Slide 132: TG6002.03 Intra-hepatic Artery Trial
TG6002.03 Intra-hepatic Artery Trial Click to edit Master title style 132
Slide 133: TG6002.03 Intra-Hepatic Artery Trial
TG6002.03 Intra-Hepatic Artery Trial Click to edit Master title style The SRC concluded that no Maximum Starting dose 1x106 pfu, Tolerated Dose was Treated 15 patients escalating to reached and that no to date 1x109 pfu further dose escalation was planned according to the protocol. 133
Slide 134: TG6002: Effect on Immune Infiltration into Tumors
TG6002 | Effect on Immune Infiltration into Tumors Intra-hepatic Click to edit Masterarterial title style infusion alters the immune environment within tumors CD4 EXPRESSION Cohort 1 Cohort 2 Cohort 3 Cohort 4 800 1500 500 400 1000 500 400 600 300 300 CD4 T cells/mm2 CD4 T cells/mm2 CD4 T cells/mm2
Slide 135: TG6002: Peripheral Immune Cell Activation
TG6002 | Peripheral Immune Cell Activation Intra-hepatic Click to edit Masterarterial title style infusion stimulates immune cells within the blood CD69 CD4 CD8 NK NKT B cells Monocytes ✱ ✱ ✱ 6 4 6 4 4 10 ✱ 8 3 3 3 Fold change Fold change Fold change Fold change Fold change Fold change 4 4 6 2 2 2 4
Slide 136: TG6002: Peripheral Immune Cell Activation
Fold change Fold change 0.0 0.5 1.0 1.5 2.0 2.5 0.0 0.5 1.0 1.5 2.0 C BS C BS 1D 1D 1- 1- 6h TIM-3 rs rs ✱ CTLA-4 C 1D 2 2 C 1D 4 4 C C CD4 CD4 1D 6h C1D C1D 1D 15 15 C C 1D 1D 29 29 C C 1D 1D 43 43 Intra-hepatic Fold change Fold change 0.0 0.5 1.0 1.5 2.0 2.5 0.0 0.5 1.0 1.5 2.0 C BS C BS 1D 1D 1-
Slide 137: TG6002: Antigen-Specific T Cell Recall Response
TG6002 | Antigen-Specific T Cell Recall Response Intra-hepatic Click to edit Masterarterial title style infusion stimulates antigen-specific T cells against both tumor-associated antigens and virus CEA TG6002 25 400 Fold-change spot-forming units Fold-change spot-forming units 20 15 10 300 200 Respo
Slide 138: TG6002: Calreticulin Secretion in Response to TG6002
TG6002 | Calreticulin Secretion in Response to TG6002 Intra-hepatic Click to edit Masterarterial title style infusion stimulates the release of calreticulin; an indicator of immunogenic cell death Cohort 1 Cohort 2 Cohort 3 Cohort 4 400 400 400 400 300 300 300 300 200 200 200 200 100 100 100 100 CRT
Slide 139: TG6002: qPCR of Patient Biopsies for Presence of TG6002
TG6002 | qPCR of Patient Biopsies for Presence of TG6002 Click to edit Master title style Leeds, UK, analysis of TG6002 tumor DNA 1x106 pfu Positive in: - 1x106 pfu; 0/4 patients - 1x107 pfu; 1/3 patients 1x107 pfu - 1x108 pfu; 2/3 patients 1x108 pfu 139
Slide 140: In which GI cancers could OV make an impact?
In which GI cancers could OV make an impact? Click to edit Master title style Hepatocellular carcinoma: Colorectal cancer: Cholangiocarcinoma: • Immune sensitive cancer • 5FU sensitive • No current neoadjuvant • No current neoadjuvant therapy • dMMR Vs pMMR or adjuvant therapy • No standard second l
Slide 141: New Invir.IO Candidate: an IL-12 Construct
Click to edit Master title style New Invir.IO™ Candidate: an IL-12 Construct ÉRIC QUÉMÉNEUR, PharmD, PhD Chief Scientific Officer Executive VP Transgene 141
Slide 142: VV-IL12-X: A Potent Invir.IO Product
VV-IL12-X : A Potent Invir.IO™ Product to Target Immune-Resistant Tumors Click to edit Master title style Product description Target product profile VACVCOP(DJ2R,DI4L,DM2L,A56Rmut) Immuno-suppressed solid tumors where immune remodeling of the TME can be beneficial (e.g. poorly T-cell infiltered tumo
Slide 143: IL-12, a Must-Have?
IL-12, a “Must-Have”? IL-12 is a POTENT PRO-INFLAMMATORY TYPE 1 CYTOKINE that is able to engage multiple effector mechanisms, and to reverse tumor-induced immunosuppression IL-12 is master regulator of both innate and adaptive anti-tumor immune responses, which directly : • stimulates growth and cyt
Slide 144: IL-12, Strong Justification for Intratumoral Delivery
IL-12, Strong Justification for Intratumoral Delivery Despite encouraging success in preclinical studies, the early stages of IL-12 clinical trials did not meet expectations, mostly because of its very high toxicity when administered in the intravenous route The maximal tolerated dose is generally c
Slide 145: A Strong Competition Which Reveals the Consensus on IL-12
A Strong Competition Which Reveals the Consensus on IL-12 Click to edit Master title style Current IL-12 delivery strategies and results in monotherapy Our ambition is to become the first OV in the intravenous route 145
Slide 146: Preclinical Antitumoral Activity in Immunocompetent Models
Preclinical Antitumoral Activity in Immunocompetent Models Click to edit Master title style CT26 (colon carcinoma) in C57BL/6 EMT6 (mammary carcinoma) in Balb/c LLC1 (Lewis lung carcinoma) on C57BL/6, a (Th1 immune bias), reference model in (Th2 bias) an immuno-sensitive model resistant model to sin
Slide 147: Induction of a Specific Antitumoral Immune Response
Induction of a Specific Antitumoral Immune Response Elispot analysis of circulating T cell specificities after VV-IL12-X treatment in the CT26 model Analysis at day 10 Stimulation Agent AH1 : MHC-I CT26-specific peptide S9L8 : VACV-specific peptide Analysis at day 14 CT26wt : CT26 protein lysate 147
Slide 148: Memory Cells are Engaged in the Antitumoral Immune Response
Memory Cells are Engaged in the Specific Antitumoral Immune Response Rechallenge experiments Click to edit Master title style in the CT26 model 148
Slide 149: Key Role of CD8+ T Cells
Key Role of CD8+ T Cells Specific CD4, CD8 or NK depletion experiments in the CT26 model Placebo Ctrl groupes mVVIL12-X mVVIL12-X+ NK depletion + CD4 depletion mVVIL12-X + CD8 depletion + NK depletion + CD4 depletion + CD8 depletion Placebo CD8+ T cells are essential CD4+ T cells are much less NK ce
Slide 150: Local Immune Response Translates into Systemic Effect
Local Immune Response Translates into Systemic Effect Abscopal response in the CT26 model i.t. injection of mVV-IL12-X ± anti-PD1 CT26 Contralateral 1000 Treated Control 100 Control CTRL CTRL Tumor volume (mm 3) 800 Empty virus virus Empty virus Empty virus Percent survival mTG6050 mVV-IL12-X mVV-IL
Slide 151: Large Involvement of Multiple Pathways in Anti-Tumor Response (1/2)
Very Large Involvement of Multiple Pathways in Anti-Tumor Response (1/2) Differential transcriptomic Click to edit Master title style analysis (3' RNASEQ), CT26 model, early time points (D11, 15, 17) "Empty" vector VS mVV-IL12-X Day 11 Day 15 Day 17 Treatment by mVV-IL12-X induced much more transcri
Slide 152: Large Involvement of Multiple Pathways in Anti-Tumor Response (2/2)
Very Large Involvement of Multiple Pathways in Anti-Tumor Response (2/2) Differential transcriptomic Click to edit Master title style analysis (3' RNASEQ), CT26 model, early time points (D11, 15, 17) Treatment by mVV-IL12-X induced the upregulation of several innate and adaptive immune pathways 152
Slide 153: Deconvolution of Immune Cell Subtypes Using Expression Signature
Deconvolution of Immune Cell Subtypes Using Expression Signature TIMER 2.0Master Click to edit - Quantiseq title style Empty vector mVV-IL12-X D11 D15 D17 Treatment by mVV-IL12-X induced tumor infiltration by CD8, neutrophils, DC and Treg 153
Slide 154: Summary and Next Steps
Summary and Next Steps VV-IL12-X is a novel candidate product which incorporates all lessons learned from our experience with oncolytic virotherapy in the IV : improved vector (DM2L), potent payloads, stronger promoter for rec. MAb, improved GMP manufacturing process Tumor-specific delivery of IL-12
Slide 155: Invir.IO, a Versatile Platform Enabling Multiple Collaborations
Click to edit Master title style Invir.IO™, a Versatile Platform Enabling Multiple Collaborations with Potential Future Value STEVEN BLOOM Chief Business Officer Transgene 155
Slide 156: Invir.IO Oncolytic Viruses Are Designed to Address Most Cancer Indications
Invir.IO™ Oncolytic Viruses Are Designed to Address Most Cancer Indications Competitive Advantage of the Patented Backbone VVcopTK-RR- from Invir.IO™ Platform Safety and Selectivity Tumor eradication including metastases Multiple modes of action Patented TK-RR- deletion for enhanced tumor selectivit
Slide 157: Oncolytic Virus Technology Evolution
Oncolytic Virus Technology Evolution Key events Click to in oncolytic edit Master title style virus drug development 1904 1960s 1996 2005 2011 2021 First documentation Parvovirus and NDV First engineered OV Shanghai Sunway’s AMGN acquired Conditional approval of viral infection- found to induce ente
Slide 158: Oncolytic Virus Development is an Active Space
Oncolytic Virus Development is an Active Space NUMBER OF DRUGS BY CLINICAL PHASE Marketed 4 | 2% PH III 3 | 2% Preclinical 103| 64% PH II 21 | 13% PH I 31 | 19% Source: Pharmaprojects, June 2022 158
Slide 159: 2022 Oncolytic Virus (OV) Landscape
2022 Oncolytic Virus (OV) Landscape Market Click to editLeadership Race – IV route of administration is the big prize Master title style IV administration of an OV’s are being Combination strategies 112 OV programs are OV creates many developed for with CPI’s could in clinical development potential
Slide 160: Oncolytic Virus (OV) Development
Oncolytic Virus (OV) Development Target Indications Click to edit Master title style Drugs by indication Solid tumor 82 Melanoma 31 Pancreatic cancer 23 Lung cancer 20 More than a Colorectal cancer 17 half of OV’s Non-small cell lung cancer 15 are developed Breast cancer 14 in solid tumors Prostate
Slide 161: Oncolytic Virus Development: Leading Encoded Genes by Cancer Type
Oncolytic Virus Development – Leading Encoded Genes by Cancer Type Top Encoded Genes In Oncolytic Virus Therapies Source: Pharmaprojects, June 2022 161
Slide 162: Oncolytic Virus Development Landscape
Oncolytic Virus Development Landscape Company Portfolio Click to edit Master Leadership title style Top competitors in the oncolytic virus space Preclinical Phase I Phase II PsiOxus Replimune Transgene DNAtrix EpicentRx Astellas Pharma ImmVira Merck & Co Sorrento… Turnstone Biologics Vyriad -2 -1 0
Slide 163: Transgene Invir.IO Collaboration Strategy
Transgene Invir.IO™ Collaboration Strategy Assisting Companies Click to edit Master title style Throughout the LCM Planning Process Salvage “pharma partner” de-prioritized Novel OV constructs Synergize mechanisms programs Life cycle management (AZ and BioInvent with IO programs Toxicity signal (LCM)
Slide 164: Transgene Invir.IO Value Proposition
Transgene invir.IO™ Value Proposition Great Science, Click to edit Growing Master title style Pipeline, Focused Business Plan Transgene will continue Transgene aspires Transgene is to grow the invir.IO™ Transgene is a partner to be a world leader committed platform of programs of choice for in innov
Slide 165: Q&A
Q&A 165 165
Slide 166: Business, Scientific and Medical Perspectives
3 Business, Scientific and Medical Perspectives
Slide 167: Agenda
Agenda Click to edit Master title style BUSINESS, SCIENTIFIC, AND MEDICAL PERSPECTIVE TIME TOPIC SPEAKER 5:25 pm – 5:45 pm Opportunities in the immuno-oncology field Pedro Romero 5:45 pm – 5:55 pm Closing remarks Hedi Ben Brahim 167
Slide 168: Opportunities in the immuno-oncology field
Click to edit Master title style Opportunities in the immuno- oncology field PEDRO ROMERO, MD, PhD Chief Editor of the JITC Deputy scientific managing director of the Lausanne Branch of the Ludwig Institute for Cancer Research 168
Slide 169: Potential Impact of Single Agent and Combination Cancer Immunotherapies on Survival
A Model Illustrating The Potential Impact of Single Agent and Combination Cancer Immunotherapies on Survival Therapeutic ~70% vaccines HOT TUMORS Emens L et al. Eur J Cancer 2017 169
Slide 170: The Goals for Cancer Vaccines
The Goals for Cancer Vaccines Elicit (de novo) Recruit the High levels of Achieve tumor Long lived tumor antigen highest TCR tumor reactive infiltration and a memory T cell specific T cell affinity/avidity CD8 T cells type I polarity immunity responses clonotypes 170
Slide 171: Molecularly Defined Vaccines
Molecularly Defined Vaccines Antigen Adjuvant Carrier 171
Slide 172: Cancer Vaccines Based on CTL-Defined Tumor Antigens
Cancer Vaccines Based on CTL-Defined Tumor Antigens 1 2 3 4 5 Shared, tumor Mutated, unique Virus encoded Differentiation Overexpressed specific antigens antigens antigens antigens antigens (e.g: MAGE-A3, (e.g: MUM-1, (e.g: HPV-16 E6/E7, (e.g: gp100, PSA, CEA) (e.g: HER-2/neu, WT-1) NY-ESO-1) idioty
Slide 173: Intense Early Clinical Trial Testing in Cancer Vaccines
Intense Early Clinical Trial Testing, Even Phase III and One Approval in Cancer Vaccines Click to edit Master title style Breast cancer: Prostate: Renal Cell Lung cancer: WT-1 in Provenge (PSMA), Carcinoma: MAGRIT (MAGE-A3), neoadjuvant in GVAX, Prostvac IMA 109 (eluted Tecemotide TNBC; dHER2/AS15 (
Slide 174: Nature, January 2019
Nature, January 2019 Click to edit Master title style 174
Slide 175: Reasons for Cancer Vaccines' Modest Clinical Impact
Reasons for Cancer Vaccines’ Modest Clinical Impact Click to edit Master title style Tolerant T cell Monovalent antigen repertoire to self Delivery methods vaccines which lead Immune suppressive antigen, hence the of the vaccine remain to immune selection microenvironment value of neoantigens subopt
Slide 176: A New Generation of Tumor Specific Antigens: Neoantigens
A New Generation of Tumor Specific Antigens: the « Neoantigens » Click to edit Master title style Somatic mutations No central tolerance Highly individual Schumacher & Schreiber, Science 2015 176
Slide 177: Neoantigen-based Anti-Cancer Vaccine
Neoantigen-based Anti-Cancer Vaccine Click to edit Master title style Sahin U et al. Nature 2017 Ott PA et al. Nature 2017 177
Slide 178: The personalized neoantigen vaccine
Click to edit Master title style The personalized NEO-PV-01 plus NEO-PV-01-specific NEO-PV-01 induces neoantigen vaccine nivolumab T cells have epitope spreading Neo-PV-01 plus stimulates durable cytotoxic potential consistent with nivolumab is feasible neoantigen specific and can traffic to vaccine
Slide 179: Melanoma FixVac (BNT111) RNA-LPX Vaccine
Melanoma FixVac (BNT111), an Intravenously Administered Liposomal RNA (RNA-LPX) Vaccine (Lipo-MERIT trial, Click to edit Master ClinicalTrials.gov identifier NCT02410733) title style Alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkp
Slide 180: Immunogenic Tumor Cell Death
Immunogenic Tumor Cell Death Click to edit Master title style Workenhe ST et al, Oncoimmunol 2021 180
Slide 181: Vaccinia Virus Life Cycle
Vaccinia Virus Life Cycle Click to edit Master title style Guo et al, J Immunother Cancer 2019 181
Slide 182: Conventional Versus In Situ/In Vivo Vaccination
Conventional Versus In Situ/In Vivo Vaccination Click to edit Master title style Sheen MR & Fiering S, WIREs Nanomed Nanobiotechnol 2019 Melero I et al, Nat Rev Clin Oncol 2021 182
Slide 183: Oncolytic Virus-Mediated in Situ Vaccination
Oncolytic Virus-Mediated in Situ Vaccination Click to edit Master title style An OV selectively replicates in tumor or/and stromal cells. This leads to induction of ICD, presenting both “find OV me” (extracellular HMGB1 and ATP) Tumor Tissue Danger signals and “eat me” signals on the cell surface 31
Slide 184: Immune Fitness, Aging and Immune Senescence
Immune Fitness, Aging and Immune Senescence Click to edit Master title style Mauracher AA & Henrickson, Front Systems Biol 2022 184
Slide 185: Closing Remarks
Click to edit Master title style Closing Remarks HEDI BEN BRAHIM Chief Executive Officer Transgene 185
Slide 186: All our Candidates and Platforms Progressed in 2022
All our Candidates and Platforms Progressed in 2022 Click to edit Master title style TG4001 Initiate trial in the US TG4050 Include the required number of patients Generate and present new positive data On tracks to deliver IA readout at major congresses in Q4 2022 Inclusions completed in the two Ph
Slide 187: Multiple Opportunities to Transform Solid Tumor Therapy
Multiple Opportunities to Transform Solid Tumor Therapy Product Click to editTarget/transgene Master title style Indication Collaboration Preclinical Phase I Phase II Next step THERAPEUTIC VACCINE Anogenital HPV+ TG4001 HPV16 E6 – E7 cancers Interim analysis Q4 2022 Head and neck Additional Ph. I da
Slide 188: Thanks for your attention
Thanks for your attention 188