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Immunotherapies
against cancer
22 July 2020
Corporate presentation
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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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
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Virus-based immunotherapies against solid tumors
Strasbourg (HQ)
Lyon
• 150 employees
• Listed on the Paris stock exchange
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
Strong R&D and clinical activity
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€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
• 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
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
7
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
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
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
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
► Creating individualized immunotherapies based on our molecular virology expertise
► First product TG4050 in two ongoing clinical trials
12
13
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
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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
1 to 5% of tumor mutations are immunogenic - particularly difficult to identify
Remarkable specificity of our AI approach compared to the industry standard
15
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
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
First patients enrolled in January 2020
First readout in 1H 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
Our next generation multifunctionaloncolytic virus (OV) platform
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TG6002
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
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)
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 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
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
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
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
Strong clinical activity in 2020
Outlook
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
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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
Appendix
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Promising efficacy data from Phase 1b - presented @ESMO 2019
29
% C
han
ge f
rom
bas
elin
e (f
rom
cal
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ted
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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
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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
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