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Immunotherapies against cancer 22 July 2020 Corporate presentation

Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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Page 1: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Immunotherapies

against cancer

22 July 2020

Corporate presentation

Page 2: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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) theresults of pre-clinical work and prior clinical trials will be predictive of the results of the clinical trials currentlyunder 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 onsatisfactory terms and conditions, if at all. The occurrence of any of these risks could have a significant negativeoutcome 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 theRisk 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 speakonly 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.

Disclaimer

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Page 3: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Transgene |Company overview

• Clinical trials active in Europe and in the US

• Integrated R&D manufacturing unit (GMP)

• 200 registered patents, 100 pending patents

• Collaborations with

3

Virus-based immunotherapies against solid tumors

Strasbourg (HQ)

Lyon

• 150 employees

• Listed on the Paris stock exchange

Page 4: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Transgene | Virus-based immunotherapeutics4 clinical-stage products and 2 novel platforms

4

Multifunctional oncolytic viruses

HPV16therapeutic vaccine

Therapeutic Vaccines Oncolytic Viruses

✓ Large transgene capabilities

✓ Good safety profile

✓ Stimulate innate and adaptive immune response

TG4001 TG6002

Individualized therapeutic vaccines

Chemotherapy production

in the tumor

TG4050 BT-001

Page 5: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Strong R&D and clinical activity

5

€35.3 millionCash available as at March 30, 2020 (excluding €20 million credit line available) Cash burn for 2020 ≈ €25 million (financial visibility until 2022)

Finance

TG4001Promising clinical activity reported in exploratory Phase 1b/2 trial in advanced HPV16-positive cancers

Clinical Results

TG6002IV route - Last dose levels currently evaluatedIHA route - First patient dosed in Feb. 2020

# trials

1

2

Collaboration agreement with AstraZenecaBT-001: CTA submitted - entering clinic in 2H 2020

Two clinical trials with TG4050 active in Europe + USACollaboration with NEC – In-house GMP manufacturing unit

New Generations

2

1submitted

Page 6: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

• TG4050: First Phase 1 trials readout• TG6002 CRC – IHA route: First Phase 1 data (to be confirmed in September 2020)

• TG4001: Finalize protocol with KOLs to continue clinical development in a larger, controlled confirmatory study

• BT-001: First clinical trial approval and launch of the first-in-human trial• myvac® and Invir.IO™: Scientific presentations• Invir.IO™:

- Collaboration with AstraZeneca: Delivery of OVs – Possible option exercise- Select proprietary preclinical candidate and submit clinical trial application

Objectives for the coming 12 monthsPortfolio to deliver significant news flow

6

2H 2020

1H 2021

• TG6002 CRC - IV route: First Phase 1 clinical readout3Q 2020

Page 7: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

in HPV16-positive, recurrent metastatic cancer patients, having progressed after up to three lines of chemotherapy

Exploratory Phase 1b/2 trialwith TG4001 and ICI demonstrates clinical activity

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Page 8: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Better options needed for HPV16-associated cancer patients whose disease has progressed after at least one line of chemotherapy

KN040(1) N = 495 (1:1)

Phase 3Head and neck

CM141(2) N = 361 (2:1)

Phase 3Head and neck

Nivolumab(3)

NCI9673Phase 2Anal

KN028 and KN158(4)

Pooled analysisAnal

KN158(5)

Phase 2Cervical

TreatmentN

PembrolizumabN = 247

SOC*N = 248

NivolumabN = 240

SOC*N = 121

NivolumabN = 37

PembrolizumabN=25 (KN028)N=112 (KN158)

PembrolizumabN=98

ORR 36 (14.6%) 25 (10.1%) 32 (13.3%) 7 (5.8%) 9 (24%) 15 (11%) 12 (12.2%)

Med OS 8.4 m 6.9 m 7.5 m 5.1 m 11.5 m 11.7 m 9.4 m

Med PFS 2.1 m 2.3 m 2.0 m 2.3 m 4.1 m 2.1 m 2.1 m

Median PFS of approx. 2 months and median OS between 7 and 11 months

* SOC: methotrexate, docetaxel, cetuximab

(1) Cohen et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393:156–67(2) Ferris et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016;375:1856-1867(3) Morris et al. Nivolumab for Previously Treated Unresectable Metastatic Anal Cancer (NCI9673): A Multicentre, Single-Arm, Phase 2 Study. Lancet Oncol. 2017;18(4):446-453(4) Marabelle et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: Pooled results from the KEYNOTE-028 and KEYNOTE-158 studies. J Clin Oncol 38: 2020 (suppl; abstr 4020)(5) Chung et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019;10;37(17):1470-1478 8

Page 9: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

TG4001 | Therapeutic vaccine targeting HPV-positive cancers

9

❶ Targeted response against tumor cells carrying the HPV16 E6 & E7 antigens*

❷ Stimulate the infection-clearing activity of the immune system*

Designed to boost the patient’s immune system against the tumor

Transgenes

• HPV16 E6&7 antigens

• Human IL2

Optimized virus

• Attenuated MVA

Strong rationale for testing TG4001 in advanced stage HPV-positive cancers➔ High unmet medical need ➔ Target population: ~ 25,000 patients/year (EU28 + USA)**

SC injection

❸ Good combination candidate thanks to established safety profile

* Source: Harper et al., The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up, Gynecologic Oncology, April 2019** Company estimates, based on meta-analysis of Kreimer et al., Cancer Epidemiol Biomarkers Prev, 2005, IARC, Globocan, SEER

Page 10: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

TG4001 | Phase 1b/2 in combination with Avelumab in HPV+ cancers

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Principal Investigator• Pr Christophe Le Tourneau, Institut Curie

In collaboration with

Key Eligibility Criteria

• Histologically or cytologically documented metastatic / recurrent HPV16+ cancer (central)

• At least one prior line of systemic chemotherapy for the management of metastatic or recurrent disease

• ECOG PS 0 or 1• Agreeing to undergo a pre- and post-treatment tumor biopsies• At least 1 measurable lesion by CT scan• Adequate hematological, hepatic and renal function• No previous exposure to cancer immunotherapies

Treatment regimenTG4001: Recommended dose for Phase 2 = 5x107 pfu – administered SC • Weekly for 6 weeks, then every 2 weeks to M6, and every 12 weeks

Avelumab: 10mg/kg – administered IV • Every 2 weeks

34 evaluable patients received the recommended dose (pooled data)

Heavily pre-treated patients: one to three lines of chemotherapy prior to receiving the combination regimen

Page 11: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Selection criterion identified

• Population with particularly pronounced activity

• At 12 weeks, +50% of these patients had not progressed –while with current treatments, PFS is about 8 weeks (1-5)

PoC efficacy data for the combination of a MVA-based therapeutic vaccine with an immune checkpoint inhibitor (ICI)

Promising clinical activity reported in pooled analysisof the Phase 1b/2 data

11

Clinical activity in overall population

(34 evaluable patients)

• Durable responses observed in most responders

• Compares favorably with existing standards of care and ICIs’ historical data (1-5)

• Treatment well tolerated

• Translational analysis and patient follow up ongoing

• Detailed data to be presented at upcoming scientific conference

• Transgene intends to continue the clinical development of TG4001 in a larger, controlled confirmatory study

(1) Cohen et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393:156–67(2) Ferris et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016;375:1856-1867(3) Morris et al. Nivolumab for Previously Treated Unresectable Metastatic Anal Cancer (NCI9673): A Multicentre, Single-Arm, Phase 2 Study. Lancet Oncol. 2017;18(4):446-453(4) Marabelle et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: Pooled results from the KEYNOTE-028 and KEYNOTE-158 studies. J Clin Oncol 38: 2020 (suppl; abstr 4020)(5) Chung et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019;10;37(17):1470-1478

Page 12: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

► Creating individualized immunotherapies based on our molecular virology expertise

► First product TG4050 in two ongoing clinical trials

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Page 13: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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TG4050 | Individualized immunotherapy already in the clinic Targets the patient’s own neoantigens

NEC: a partner committed to develop AI in the IO field

• NEC brings state-of the-art AI technologies to generate individualized immunotherapies

• Covers 50% of the cost of the first two clinical trials of TG4050

MVA-based immunotherapy

• MVA vector: safe and immunogenic- Expected to induce broader and stronger T cell response- Prime/boost patient’s immune system to overcome the

immunosuppressive environment

• Based on the patient’s own cancer mutations; neoantigens are more immunogenic

• Secured workflow thanks to blockchain technology integration

• In-house GMP manufacturing

Page 14: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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TG4050 | Process for individualized neoantigen vaccination Combines bioengineering and digital transformation

PatientSelection

of 30 neoantigensNext generation

sequencingVaccine generation and manufacturing

Gene sequencingData processing,

Artificial intelligence

Gene editing,Manufacturing

Routine tumor biopsy

Treatment administration

Data demonstrating high accuracy of AI-based neoantigen prediction presented at virtual AACR Session II

Page 15: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

1 to 5% of tumor mutations are immunogenic - particularly difficult to identify

Remarkable specificity of our AI approach compared to the industry standard

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Expected to translate in enhanced activity in patients

Our neoantigen prediction tool was run on highly mutated tumors, thus generating a massive amount of mutations to analyze• 86+% of top ranked peptides identified by NEC/Transgene

were immunogenic • Our prediction system was also able to identify

immunogenic peptides that were not recognized by netMHCpan 4.0, the literature standard

Source: Mallone et al., “Performance of neoantigen prediction for the design of TG4050, a patient specific neoantigen cancer vaccine”, AACR, June 2020

Page 16: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Endpoints• Primary: safety and immunogenicity

TG4050 | Proof-of-concept Phase 1 ongoing

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Ovarian cancer after surgery and adjuvant chemotherapy

Protocol• Patients receive TG4050 monotherapy after complete

response to platinum-based chemotherapy

Study• Single arm, open label Phase 1 trial

(NCT: 03839524)• Sites in the USA and in France• 13 patients

Lead investigator: Matthew S. Block, MD, PhD Mayo Clinic (Rochester)

First patients enrolled in January 2020

First readout in 1H 2021

Page 17: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

First patients enrolled in January 2020

First readout in 1H 2021

TG4050 | Proof-of-concept Phase 1 ongoing

Endpoints• Primary: safety and immunogenicity

17

HPV negative head and neck cancers after surgery and adjuvant therapy

Protocol• Patients receive either TG4050 monotherapy after

completion of the adjuvant therapy or in combination with SoC at the time of recurrence

Study• Randomized two-arm, open label Phase 1 trial

(NCT: 04183166)• Sites in France and in the UK• 30 patients

This trial builds upon a long-termresearch collaboration betweenTransgene and the University ofSouthampton. I believe such perso-nalized vaccine approaches are thenext paradigm in cancer care.

Lead investigator: Pr. Christian Ottensmeier, University of Southampton

Page 18: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Our next generation multifunctionaloncolytic virus (OV) platform

18

TG6002

Page 19: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Invir.IO™| Optimized OVs (VVCop TK-RR-) tumor attacked on multiple fronts

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Superior oncolysis✓ Direct lysis of infected cells ✓ More specific replication in tumor cells

Increased and durable immune response✓ Induction of immunogenic cell death✓ Engagement of innate and adaptive anti-tumor immunity

High capacity and efficient immuno-modulating payloads delivery✓ Targeted delivery of anti-tumor modalities ✓ Synergistic with other MOAs (e.g. targeted CT or immune

modulation of TME)

Many routes to reach the tumor

(i.e. IV, IT)

Delaunnay et al., 2018

Foloppe et al., 2019

Fend et al., 2017

Kleinpeter et al., 2016

Marchand et al., 2018

Page 20: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

TG6002 | First multifunctional OV in the clinic

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❶ Excellent oncolytic properties

❷ Production of chemotherapy (5-FU) in the tumor with FCU1 gene

Expected increased efficacy without CT-associated side effects

FCU1 gene

• Unique and proprietary

• Oral 5-FC conversion into 5-FU

• Preclinical results confirm potency

Optimized virus

• Optimized and patented VVCop TK-RR- OVChinese rights sold to Tasly Biopharmaceuticals (July 2018)

Two ongoing Phase 1/2a clinical trials

Evaluating TG6002 in colorectal cancer patients

(IV and IHA administration)

Page 21: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

TG6002 | Two Phase 1/2a trials in 5-FU sensitive GI indications Two novel administration routes - IV and IHA

21

Protocol• Up to 75 patients

Regimen• TG6002 IHA + oral 5-FC• Additional cycles until disease progression

Principal investigator• Dr. Adel Samson, MB ChB PhD, St. James’ University

Hospital (Leeds, UK)• IND granted in the UK

First patient dosed in February 2020Enrolment has been paused; update on expected data in September 2020

Colorectal cancer patients with unresectable liver metastases (CRLM) – IHA route

Protocol• Phase 1 part (dose escalation): up to 24 patients • Phase 2a part (efficacy) in CRC: 35 patients

Regimen• TG6002 IV + oral 5-FC• Additional cycles until disease progression

Principal investigator• Prof Cassier, centre Léon Bérard (Lyon, France)• INDs granted in Belgium, Spain, France

Continued dose escalation First clinical readout late 2Q/early 3Q 2020

Gastro-intestinal adenocarcinoma with liver metastasis (colon cancer) - IV route

Page 22: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Collaboration and license option agreement with AstraZeneca Invir.IO™ platform validation

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5 novel oncolytic immunotherapies will be developed, integrating:

• Transgene Invir.IO™ based oncolytic viruses (improved VVCOPTK-RR- proprietary viral vector)

• Potent therapeutic payloads to be encoded in the OV

Conduct of the project:

• Transgene designs the OVs and conduct in vitro preclinical development

• AstraZeneca leads in vivo preclinical development

Transgene has received $10 million at signing (2019)

Possible option exercise in 2H 2020

Page 23: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

B T-001 | BT-001 expresses GM-CSF and anti-CTLA4 mAb

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BT-001

• Collaboration with BioInvent : Transgene’s Invir.IO™ OV + BioInvent’s full length human recombinant Treg depleting anti-CTLA4 mAb

Transgene’s VVCOP TK-RR- can express mAbs in the tumor

Kleinpeter et al., 2016

BioInvent’s anti-CTLA4 Abs promotes depletion of intratumoral Treg cells

Vargas F. et al., 2018

Combination of ICI and oncolytic VV treatments are additive

Marchand et al., 2018

• Clinical trial application filed in 1Q 2020

• Trial expected to start before end of 2020

Strong antitumor activity in several immunocompetent mice models

Higher concentration and prolonged activity of the anti-CTLA4 antibody vs. IV mAb administration

Expected improved tolerability owing to lower systemic antibody exposure in peripheral non-tumor compartments

Outstanding preclinical data

Page 24: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

B T-001 | Outstanding preclinical data for BT-001

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mBT-001 (1 % of full dose) increases activity of anti-PD1 mAb

mBT-001 has strong anti-tumoral activity

(70+% cure rate)

Source: Marchand et al., “BT-001, an oncolytic Vaccinia virus armed with a Treg-depletion-optimized recombinant human anti-CTLA4 antibody and GM-CSF to target the tumor microenvironment”, AACR, June 2020

Page 25: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Strong clinical activity in 2020

Outlook

Page 26: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Current pipeline

26* Research or clinical collaboration / ** Chinese rights sold to Tasly Biopharmaceuticals

Product IndicationPartner Preclinical Clinical Phase

Phase 1 Phase 2 Next step

THERAPEUTIC VACCINES

TG4001 Reccurent HPV positive cancer

TG4050Ovarian cancer

Head & neck cancers

ONCOLYTIC VIRUSES

TG6002Colorectal cancer – IV Route

Colorectal cancer – IHA Route

BT-001 Solid tumors

Proprietary OVs Solid tumors

5 OVs Confidential targets

+ avelumab (ICI)*

**

*

*

*

Finalize protocol for next clinical trial

Trial initiation 2H 2020

Candidate selectionCTA filing 2H 2020

1st trials readouts in 1H 2021

First data 2Q/3Q 2020

Potential option exercise

1H 2022 – TBC

Page 27: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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Our priorities for 2020/2021

TG4001 • Finalize protocol to continue clinical development in a larger, controlled confirmatory study • Present data at scientific conference

TG6002• Progress our clinical development to deliver readout

• Start clinical trial on BT-001 in 2H 2020• Select second clinical candidate, based on our unique VV backbone• Deliver all OVs to AstraZeneca – Potential option exercise

• TG4050 - progress two clinical trials and establish first clinical PoC

Page 28: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Appendix

28

Page 29: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

Promising efficacy data from Phase 1b - presented @ESMO 2019

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% C

han

ge f

rom

bas

elin

e (f

rom

cal

cula

ted

su

m)

Dose level 1 Dose level 2 PR according to RECIST 1.1*

*

**

% C

han

ge f

rom

bas

elin

e(f

rom

cal

cula

ted

su

m)

Dose level 1 Dose level 2

RECIST 1.1 evaluation:Partial response: 3Stable disease: 3

Best change in tumor size Individual patient data

Hard-to-treat population:• 1 to 3 prior systemic chemo lines - 100% with distant metastases

Source: Le Tourneau et al., Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic HPV16 positive cancers, ESMO 2019, Sept. 2019

Page 30: Immunotherapies against cancer€¦ · This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results

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 LarguierDirector Corporate Communication and Investor Relations+33 3 88 27 91 04 / +33 6 76 24 72 27

[email protected] / [email protected]

Contact

@TransgeneSA Transgene