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March 27, 2025 Investor Presentation Unlocking the Full Potential of the Immune System Against Cancer
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Disclaimer 2 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 and prior clinical trials will be predictive of the results of the clinical trials currently under way, (ii) regulatory authorities will agree with the Company’s further development plans for its therapies, or (iii) the Company will find development and commercialization partners for its therapies in a timely manner and on satisfactory terms and conditions, if at all. The occurrence of any of these risks could have a significant negative outcome for the Company’s activities, perspectives, financial situation, results and development. For a discussion of risks and uncertainties which could cause the Company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risques”) section of the Universal Registration Document, available on the AMF website (http://www.amf-france.org) or on Transgene’s website (www.transgene.fr). Forward-looking statements speak only as of the date on which they are made and Transgene undertakes no obligation to update these forward-looking statements, even if new information becomes available in the future.
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Click to edit Master title style Transgene in a Snapshot Lead program TG4050 to deliver data and create significant value in early setting solid tumors between 2025 and 2028 Unique and highly potent viral vector-based immunotherapies Additional programs and R&I activity to deliver news flow and fuel Transgene’s portfolio in the mid term 3
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Click to edit Master title style myvac® – A Novel Individualized Cancer Immunotherapy Platform 4 • Building upon proof of principle of TG4050, leading myvac®-based cancer vaccine: Randomized Phase II part currently enrolling patients based on promising Phase I data • Potential further acceleration based on innovation in the adjuvant setting of operable Head & Neck cancer and other indications Targeting head and neck patients – designed to prevent relapse Only neoantigen cancer vaccine targeting this indication in adjuvant situation Potential to address other indications in perioperative setting Comprises up to 30 neoantigens selected using NEC’s artificial intelligence and machine learning Induces broad and specific immune response – Almost all patients treated develop a polyepitopic response* Excellent safety profile Proven immunogenicity in challenging immune contexture MVA VECTOR BENEFITS THE RIGHT NEOANTIGENS INDICATION *Source: G. Le Tourneau et al., “Randomized Phase I Trial of Adjuvant Individualized TG4050 Vaccine in Patients with Locally Advanced Resected HPV- negative Head and Neck Squamous Cell Carcinoma (HNSCC)”, SITC November 2024, Poster presentation − Analysis based on research assay.
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Click to edit Master title style Innovative Clinical-Stage Immunotherapy Portfolio Based on Viral Vectors 5 * IV: intravenous administration, IT: intratumoral administration, R: randomized Product Indication Collaboration Discovery Phase I Phase II LEAD ASSET: INDIVIDUALIZED NEOANTIGEN CANCER VACCINES (myvac® platform) TG4050 Individualized neoantigen therapy Head and neck cancer (adjuvant) Clinical Proof of Principle 24-month follow-up (Q2 2025) Completion of randomization of Ph. II part (Q4 2025) Other indication Additional Ph. I trial to start (Q4 2025) Other viral vector-based assets TG4001 Shared antigens cancer vaccine Cervical and anogenital HPV+ cancers Clinical data presented (Q2 2025) BT-001 Oncolytic virus Solid tumors (IT*) Updated data expected (H2 2025) TG6050 Oncolytic virus Lung cancer (IV*) Initial data expected (Q2 2025) Research & innovation Internal programs R R R
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Neoantigen Therapeutic Cancer Vaccine Focused on delivering the promise of individualized cancer vaccine
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Click to edit Master title style Clinically-validated Artificial Intelligence & Bioinformatics powered approach one patient • one genome • one vaccine MVA viral vector: a powerful platform for vaccine development Strongly immunogenic vector o Demonstrated capability to express complex antigen structures and have them presented by APCs o Ability to elicit strong, durable and specific immune response o Established safety profile Rapid, integrated and scalable manufacturing process – Ongoing progress myvac® - TG4050 | Combines Unique Know How and Expertise 7 *Source: Mallone et al., “Performance of neoantigen prediction for the design of TG4050, a patient-specific neoantigen cancer vaccine”, AACR, June 2020, Poster presentation Click here Technology well suited for early setting solid tumors to prevent relapse after/with standard treatment Neoantigen identification • Based on multiple parameters to identify neoantigens from whole tumor exome analysis* • NEC’s AI and machine learning environment Optimal neoantigen display • VacDesignR® for optimal design of the recombinant virus • Improve vaccine production • Property of Transgene AI powered and cutting-edge software environment • Dedicated tools for TG4050 end-to-end production
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Click to edit Master title style TG4050 | Operable Head and Neck Cancer - Trial after Surgery and Adjuvant Therapy 8 Compelling initial immunological and clinical data presented at SITC 2024 (32 patients) ➔ All treated patients remain disease-free ✓ Primary objectives: safety and tolerability ✓ Secondary objectives: feasibility, disease-free survival (DFS) ✓ Exploratory objectives: immunogenicity, exploratory tumor biomarkers (TMB, PD-L1) With currently approved treatments, approx. 25% patients relapse within 24 months after surgery + adjuvant therapy* Promising data obtained in randomized Phase I part Need to prevent or delay relapse Surgery + Adjuvant chemoradiotherapy TG4050 (single agent) Repeated injections Patient monitoring (no treatment) RANDOMIZATION (1:1) Complete Clinical Response LEAD INVESTIGATOR: Pr. Christian Ottensmeier, Clatterbridge Cancer Care Center, Liverpool Phase I/II trial design Approx. 80 patients with locoregionally advanced HPV-negative SCCHN** (NCT: 04183166) * Sources: Cooper JS et al. NEJM, 2004; DY Lee et al. Head Neck, 2020 ** Squamous cell carcinoma of the head and neck Ongoing Phase II part ➔ Completion of patient randomization expected in Q4 2025 ➔ Primary objective: 24-month DFS
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Click to edit Master title style TG4050 | Promising Signals of Clinical Activity in Adjuvant Setting 9 Head & Neck Cancer Trial 32 patients randomized – September 2024 Arm A: TG4050 single agent Arm B: Control arm 6 months 12 months 18 months 24 months 30 months 36 months TG4050 monotherapy TG4050 + SOC Patient Follow-up Relapse Progressive disease according to RECIST 1.1 Death No related SAEs Good safety profile Median follow-up of 24.1 months 42 months All 16 treated patients remained disease-free Only patients in the control arm relapsed Source: G. Le Tourneau et al., “Randomized Phase I Trial of Adjuvant Individualized TG4050 Vaccine in Patients with Locally Advanced Resected HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)”, SITC November 2024, Poster presentation
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Click to edit Master title style TG4050 | Generates and/or Expands Tumor Specific T Cells 10 Neoantigen-specific T-cell responses were detected De novo responses were detected in a majority of patients 10 Number of positive responses per patient (Elispot assay) Head and Neck Cancer (Phase I part) De novo responses Amplified responses Stable responses* NB: analysis based on research assay; independent GCLP-like analysis to be conducted Patient ID # of neoantigens / targets Despite low mutational burden, immunogenic targets could be selected for all patients Source: G. Le Tourneau et al., “Randomized Phase I Trial of Adjuvant Individualized TG4050 Vaccine in Patients with Locally Advanced Resected HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)”, SITC November 2024, Poster presentation ARM A ARM B *Immunoreactive T-cells detected at baseline but not amplified post treatment
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Click to edit Master title style TG4050 | Persistent Specific Cellular Response Following Vaccination 11 Patients displayed sustained neoantigen-specific CD8+ responses against multiple selected targets over 7 months Induction period Boost period 1 dose/week during 43 days 1 dose/3 weeks during 1 yearSource: G. Le Tourneau et al., “Randomized Phase I Trial of Adjuvant Individualized TG4050 Vaccine in Patients with Locally Advanced Resected HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)”, SITC November 2024, Poster presentation
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Click to edit Master title style TG4050 | Potential to Extend Remission Period and Address Significant Medical Need 12 one patient • one genome • one vaccine Phase I part – 24-month follow up to be presented in Q2 2025 Potential acceleration in evolving treatment landscape Could address other solid tumors in perioperative settings w or w/o ICIs – Significant market opportunity Ongoing Phase II part – Last patient to be randomized in Q4 2025 Excellent safety profile Induces neoantigen- specific immune response Induces broad T cell response Signs of clinical benefit Additional Ph. I trial to start in Q4 2025 in new indication Expansion in other early-setting cancer indications with high risk of relapse Head & Neck program
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Other viral vector-based assets Rapidly Generating Multiple Virus-Powered Off-the-Shelf Drug Candidates Targeting Solid Tumors
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Click to edit Master title style incl. cervical, vulvar, vaginal, penile and anal cancers NCT: 03260023 Randomized Phase II trial in patients with HPV16+ cervical and anogenital cancer (n=90) TG4001 | Phase II Trial in Patients with HPV16+ Cervical and Anogenital cancer 14 • Primary objective (improvement in progression-free survival) not met in the overall patient population • Positive efficacy trend in cervical cancer patients observed in pre- planned subgroup analysis Full analysis ongoing prior to decision on the best way forward Transgene plans to communicate clinical data at a scientific conference in Q2 2025 TG4001 + avelumab Patients with recurrent / metastatic disease Randomized (1:1) Avelumab single agent Treated in 1st line or in 2nd line (with a maximum of 1 prior systemic chemotherapy) Checkpoint-blocker naïve, without liver metastasis at baseline Including all levels of PD-L1 expression Top line data Clinical collaboration with for avelumab free supply Possible path to approval in evolving cervical cancer landscape - awaiting full data analysis
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Click to edit Master title style Cancer cell death through multiple MOAs Our Oncolytic Viruses (OV) – Combined Effects of Vector, Payload and Immune Stimulation Compelling Clinical Data Support Intravenous (IV) Route of Administration 15 Antitumor activity generated by THERAPEUTIC PAYLOADS Virus-induced direct and specific TUMOR ONCOLYSIS Induction of IMMUNE MECHANISMS against tumor cells Patented Backbone VVcopTK-RR- vector with multiple competitive advantages: Encode numerous and various payloads Multiple routes of administration (IV, IT, locoregional) and extend OV market beyond IT administration Potential to target multiorgan lesions and warm up TME Address broad range of solid tumors Proof of principle obtained • Good safety profile • Able to reach tumors, selectively replicate and express payload, incl. via intravenous administration Goal: to target multiorgan lesions and reverse tumor resistance
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Click to edit Master title style The right virus + payload BT-001 | Promising Antitumor Activity of OV Armed with Anti-CTLA4 Ab + GM-CSF Completed Phase I/IIa Trial Assessing IT Route of Administration 16 VVcopTK-RR- oncolytic armed with BioInvent’s potent anti-CTLA4 Ab + GM-CSF o Activates and increases T-effector cells o Treg depleting activity o Stimulates immune cells (incl. APC) Promising antitumor activity* monotherapy and combination w. anti-PD1 Converts the TME from “cold” to “hot” Replicates and persists in tumor tissue Anti-CTLA4 expressed in the tumor with no detectable systemic exposure Partial responses in 2/6 patients (combination regimen) & stable disease in 4/18 patients (monotherapy) Tumor shrinkage in injected and non-injected lesions BT-001 Click here Completed Phase I (NCT04725331) monotherapy and combination w. anti-PD1 50/50 collaboration with BioInvent IT: intratumoral administration TME: Tumor microenvironment Can be developed for multiple cancer indications Ph. I part B (pembrolizumab combination) – Enrolment completed Additional data expected in H2 2025 Collaboration with MSD which provides pembrolizumab (KEYTRUDA®) *Champiat et al, “Initial clinical results of BT-001, an oncolytic virus expressing an anti-CTLA4 mAb, administered as single agent and in combination with pembrolizumab in patients with advanced solid tumors” ESMO 2024, September 14, 2024, Poster presentation
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Click to edit Master title style TG6050 Administered IV | IL-12 and anti-CTLA4 Produced Directly in the Tumor Ongoing Phase I Trial to Assess Systemic Route of Administration 17 Initial goal demonstrate potential of IV administration in “cold”, non-resectable metastatic tumors TG6050 Oncolytic armed with IL-12 and anti-CTLA4 Ab • Triggers a powerful antitumor immune response • Restores the immune defenses within the tumor • Outstanding preclinical data* (strong antitumor activity) remodeling TME (AACR 2023 and JITC, July 2024) Potential to address a major oncology market Phase I trial - Indication: metastatic and PD1 failed tumors • Advanced or metastatic NSCLC after failure with available treatment options, including anti-PD1/PD-L1 – Intravenous (IV) administration • Inclusions completed (NCT: 05788926) • Initial data (single agent) in Q2 2025 – Could be combined with ICIs *Azar et al, TG6050, “TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment” JITC, July 2024.
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Outlook 18
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Click to edit Master title style TG4001: Full analysis ongoing prior to deciding on the best way forward Transgene plans to communicate detailed results at a scientific conference in Q2 2025 BT-001: Phase I data presentation (H2 2025) TG6050: Initial Phase I data (Q2 2025) Company Funded to Deliver Multiple Value Generating Milestones 19 Business funded until the end of April 2026 Enables Transgene to deliver significant milestones with myvac® platform and other viral vector-based immunotherapies Proof of principle already obtained in Head and Neck cancer (adjuvant) ➔ Clinical benefit for patients and strong immunogenicity, persistent cellular immune response Ongoing randomized Phase I/II (head and neck cancer) – 80 patients overall ➔ Phase I part: 24-month follow up data to be presented in Q2 2025 ➔ Phase II part: randomization of the last patient in Q4 2025 Other indication ➔ Plan to launch new Phase I in additional indication in Q4 2025 | Neoantigen vaccine − TG4050 Other viral vector-based assets
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Appendices 20
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Click to edit Master title style New Leadership to Take Transgene to the Next Level 22 ALESSANDRO RIVA, MD Chairman & CEO MAURIZIO CEPPI, PhD VP , Chief Scientific Officer EMMANUELLE DOCHY , MD VP , Medical Affairs, Chief Medical Officer CHRISTOPHE ANCEL, PharmD VP , Chief Quality Officer and Qualified Pharmacist JOHN FELITTI VP , Legal, General Counsel CHRISTELLE SCHWOERER VP , Human Resources LUCIE LARGUIER VP , Chief Financial Officer 30+ years experience JOHN C. BELL Member of the Scientific Advisory Board PEDRO ROMERO Member of the Scientific Advisory Board JAMES WENTWORTH VP , Chief Business Officer SIMONE STEINER VP , Chief Technical Officer
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Click to edit Master title style Environmental, Social and Governance Commitments 22 To patients To our partners To our employees To our shareholders and investors To society and the regions To the planet Transgene’s ESG strategy is based on 6 commitments Our ESG policy is detailed in the chap. 4 in the URD 2023 URD 2023 URD 2023 44/100 Vigeo Eiris (+20 pts) ESG rating higher than industry benchmark (Pharma/Biotech) TOP 5 French companies with the best ESG performance for 2023*. *with < 250 employees, according to the Gaia EthiFinance 2024 Award study LinkedIn / Website Study Study 85/100 Gaïa EthiFinance Award (+8 pts) 99/100 Equal Employment Index
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Click to edit Master title style TG4050, an Individualized Neoantigen Vaccine Combining Unique Capabilities Combines Bioengineering and Digital Transformation Patient ROUTINE TUMOR BIOPSY Next generation sequencing STANDARD GENE/EXOME SEQUENCING Identification of 30 neoantigens DATA PROCESSING, ARTIFICIAL INTELLIGENCE Vaccine generation VacDesignR GENE EDITING Production of the individual batch GMP MANUFACTURING Patient TREATMENT ADMINISTRATION Sequencing Lab 23
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Click to edit Master title style Exploration of Tumor TME Arm A: TG4050 single agent PD-L1 TMB (mt/Mb) TME functional class Tumor cell proliferation Medium 3.19 Immune Desert Medium Medium 1.99 Immune Desert Low Medium 4.34 Imm. Enriched, NF Medium Low 3.28 Immune Desert Medium Medium 3.42 Immune Desert Medium Medium 1.9 Imm. Enriched, NF Low Medium 3.16 Fibrotic Medium Low 4.2 Immune Desert Medium Medium 1.99 Imm. Enriched, F Low Medium 4 Imm. Enriched, NF Low High 1.37 Imm. Enriched, NF Medium Low 2.41 Immune Desert High Low 3.05 Immune Desert Medium Medium 7.7 Imm. Enriched, F Medium Medium 1.68 Imm. Enriched, NF Medium Medium 1.46 Immune Desert Low PD-L1 TMB (mt/Mb) TME functional class Tumor cell proliferation Medium 3.02 Immune Desert Medium Medium 1.6 Immune Desert Medium Low 4.26 Immune Desert Medium Medium 3.02 Immune Desert Medium Medium 3.36 Immune Desert Medium High 3.28 Imm. Enriched, NF High Low 3.64 Immune Desert Medium Medium 7.95 Fibrotic Low Medium 1.9 Immune Desert Medium Medium 0.34 Immune Desert Medium Medium 2.77 Immune Desert Medium Medium 5.24 Immune Desert Low Medium 2.91 Imm. Enriched, NF Medium Medium 0.03 Imm. Enriched, NF Medium Low 2.1 Immune Desert Medium Medium 3.56 Immune Desert Medium Arm B: Control arm Challenging population with high prevalence of low/negative PD-L1 expressors and relatively poor pro-immune infiltrates Source: G. Le Tourneau et al., “Randomized Phase I Trial of Adjuvant Individualized TG4050 Vaccine in Patients with Locally Advanced Resected HPV- negative Head and Neck Squamous Cell Carcinoma (HNSCC)”, SITC November 2024, Poster presentation TME: tumor micro-environment, TMB: tumor mutational burden, F: fibrotic, NF: non-fibrotic 24
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C O N T A C T 400 Boulevard Gonthier d’Andernach | Parc d’Innovation | CS80166 67405 Illkirch Graffenstaden Cedex | France Tél.: + 33 (0)3 88 27 91 21 | www.transgene.fr Lucie Larguier Chief Financial Officer investorrelations@transgene.fr 25