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Immunotherapies against cancer 16 Sept. 2020 Corporate presentation
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Page 1: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Immunotherapies

against cancer

16 Sept. 2020

Corporate presentation

Page 2: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Transgene |Company overview

• Clinical trials active in Europe and in the US

• Integrated R&D manufacturing unit (GMP)

• Collaborations with

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Virus-based immunotherapies against solid tumors

Strasbourg (HQ)

Lyon

• 150 employees

• Listed on the Paris stock exchange

Page 4: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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

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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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Strong R&D and clinical activity

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€33.2 millionCash available as at June 30, 2020 followed by receipt of $22M (sale of 40% of the stake in Tasly BioPharmaceuticals in Aug. 20) - financial visibility until 2022

Finance

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

Clinical Results

TG6002IV route - Positive initial data from Phase 1IHA route - First patient dosed in Feb. 2020

# trials

1

2

Collaboration agreement with AstraZenecaBT-001: CTAs submitted – first-in-human trial to start in 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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

• Transition until December 2020

• Will remain a Board Member thereafter

Succession of the Chairman & CEO planned at the end of 2020

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Philippe Archinard, Chairman & CEO, to leave his position at the end of 2020

Hedi Ben Brahimto be appointed Chairman & CEOin December 2020

• Board member of Transgene since May 2019• Director of the Immunotherapy Department at

Institut Mérieux since 2018• Started his career at the French Ministry of

Economy and Public Accounts, then at the Ministry of Social Affairs and Health

• 8 years at Vallourec group, positions in sales, production, and strategy (France & USA)

• Engineer degrees from Ecole Polytechnique and Mines ParisTech

Page 7: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Transgene | 4 clinical-stage products and 2 novel platforms

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

Product IndicationPartner Preclinical Clinical Phase

Phase 1 Phase 2 Next step

THERAPEUTIC VACCINES

TG4001 Recurrent 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)*

**

*

*

*

Launch controlled confirmatory study

Trial initiation 2H 2020

Candidate selection

1st scientific communication in 2021

Continue dose escalation

Potential option exercise

1st observations in 2021

Page 8: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 9: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

TG4001 | Therapeutic vaccine targeting HPV-positive cancers

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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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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

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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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

► 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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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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

Page 15: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 scientific communication in 2021

Page 17: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

First patients enrolled in January 2020

First scientific communication in 2021

TG4050 | Proof-of-concept Phase 1 ongoing

Endpoints• Primary: safety and immunogenicity

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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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Our next generation multifunctionaloncolytic virus (OV) platform

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TG6002

Page 19: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

TG6002 | First multifunctional OV in the clinic

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❶ Excellent oncolytic properties

❷ Demonstrated 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)

Initial Phase 1 data confirm the safety profile and production of 5-FU in the tumor

Page 21: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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

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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 resuming after Covid-19 crisis in the UK

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

Protocol• Phase 1 part (dose escalation): up to 40 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 ✓ 1st clinical data demonstrate 5-FU production

in the tumor

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

Page 22: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 conducts in vitro preclinical development

• AstraZeneca leads in vivo preclinical development

Transgene has received $10 million at signing (2019)

Possible option exercise on each candidate

Page 23: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 applications submitted (France and Belgium)

• 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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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 · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Outlook

Page 26: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

Company funded to deliver multiple value generating milestones

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Free float40%

60%

OwnershipAs of August 31, 2020

• Listed on Euronext Paris• ISIN: FR0005175080 - Ticker: TNG

Valuation of Transgene’s stake in Tasly Biopharmaceuticals

$37 million

Cash and cash equivalentsas of June 30, 2020

€33.2 million

Financial visibility until 2022

Cash received in Aug. 2020 from the sale of 40% of the stake in Tasly BioPharma

$22 million

Credit line available€15 million

Page 27: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

• TG4050: First scientific presentation• TG6002 CRC – IHA route: First observations

• TG4001:

- Finalize protocol with KOLs to continue clinical development in a larger, controlled confirmatory study

- Present detailed Phase 1b/2 results at a scientific conference

• 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

- Select proprietary preclinical candidate and submit clinical trial application

Objectives for the coming 12 monthsPortfolio to deliver significant news flow

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2H 2020

2021

Page 28: Immunotherapies against cancer · 9/16/2020  · - Prime/boost patient’s immune system to overcome the immunosuppressive environment • ased on the patient’s own cancer mutations;

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


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