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immunotherapeutics
Delivering the Power
Of Immunotherapy
A Step-Change
In the Treatment of Cancer
And Infectious Diseases
March, 20th, 2017
Annual Results 2016
Safe Harbour Statement
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 the Phase 2b part of the TIME trial will be predictive of future results with TG4010, (ii) regulatory
authorities will agree with the Company’s further development plans for TG4010, or (iii) the Company will find a
development and commercialization partner for TG4010 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. The Company’s ability to
commercialize its products depends on but is not limited to the following factors: positive pre-clinical data may
not be predictive of human clinical results, the success of clinical studies, the ability to obtain financing and/or
partnerships for product development and commercialization, and marketing approval by government
regulatory authorities.
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 Risque") section of the Document de Référence, 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 forwardlooking statements, even if new information becomes available in the future.
2
Agenda
1. Clinical development plan well underway
Philippe Archinard, Chairman & CEO
2. Improved financials
Jean-Philippe Del, VP, Finance
3. Acceleration of the clinical development plan to
deliver rich value-creating news flow over the
coming 12 months
Philippe Archinard, Chairman & CEO
3
immunotherapeutics
Highlights and Business Update
Major Achievements in 2016
Validate Transgene’s Strategy
Promising objectives for 2017
Major Achievements in 2016
Validate Transgene’s Strategy
Refocused clinical development on combi. trials with ICIs
•
•
Product
portfolio
2 clinical collaboration agreements for TG4010 and TG4001
Actively working on 5 combination clinical trials, 2 already recruiting
Good recruitment rate for Pexa-Vec in Phase 3 (PHOCUS)
First positive results of Phase 1/1b in HBV
•
Positive DSMB, part b (multiple dosing) actively recruiting
Promising preclinical development
•
Efficacy of a new generation of oncolytic virus demonstrated
Company funded until the end of 2018
Finance
Corporate
•
•
•
EIB loan (€10 million drawn down of €20 million facility)
Completion of a rights issue (€46.4 million)
Reduced net loss (-46%)
Completed restructuring and sale of production unit to ABL Europe
Strengthened management team
5
Management
Philippe Archinard, PhD
Chairman and Chief Executive Officer
Eric Quéméneur, PhD
Executive VP and Chief Scientific Officer
Christophe Ancel, PharmD
VP Quality and Qualified Person
Maud Brandely, MD, PhD
Chief Medical Officer
Jean-Philippe Del
VP Finance
Thibaut du Fayet, MBA
VP Marketing, Alliance and Project Mgt
John Felitti, JD, MBA
General Counsel and VP Legal
Hemanshu Shah, PhD, MBA
VP Corporate Development and Medical Affairs
6
Strategy based on Combining Immunotherapeutics
To Improve Patient Outcomes
A pioneer in developing
viral vector-based
immunotherapies
for cancers and infectious
diseases
Focus
2
5
Immunotherapy platforms
Immunotherapy products
at clinical stage
• Therapeutic Vaccines
• Oncolytic Viruses
Advanced and chronic diseases
Strategy
High unmet medical needs
despite new available treatments
Demonstrate the power of our immunotherapies
in combination with the new standard of care (ICIs)
7
The Power of Immunotherapy Combinations
Transgene’s immunotherapies in combination with ICIs
have delivered positive results in several preclinical tumor models
Transgene’s immunotherapies
Therapeutic Vaccines stimulate the
immune response to kill cancer cells
Oncolytic Viruses directly attack tumor
cells and boost the immune system
Immune Checkpoint Inhibitors
(ICIs)
ICIs block a pathway that acts as a brake
against the activated T-cells produced
by Transgene’s immunotherapies
Safe - Preserve healthy cells
Activated T-cells generated using Transgene immunotherapies
have an enhanced ability to attack cancer cells thanks to ICIs
in particular in patients with PDL1 positive tumors
8
Transgene Set to Deliver Rich News Flow and Clinical Data
In the Next 18 Months
Product
Preclinical
Indication
1
Clinical Phase
2
3
THERAPEUTIC VACCINES
Non-small cell lung cancer – 2nd line
+ nivolumab (ICI)
Non-small cell lung cancer – 1st line
+ ICI + CT
Non-small cell lung cancer
Neo-adjuvant (translational)
TG4001
HPV positive cancers
+ avelumab (ICI)
TG1050
Chronic hepatitis B
+ antiviral
TG4010
ONCOLYTIC VIRUSES
Pexa-Vec
TG6002
Hepatocellular carcinoma – 1st line (PHOCUS)
+ sorafenib
Hepatocellular carcinoma – 1st line
+ nivolumab (ICI)
Other solid tumors
+ ipilimumab (ICI)
Sarcoma – Breast cancer
+ cyclophosphamide
Solid tumors
Neo-adjuvant (translational)
Glioblastoma
Ongoing
About to start
In preparation
9
immunotherapeutics
Therapeutic Vaccines
Ideally Suited for Combination
Immunotherapy Regimens
Our Therapeutic Vaccines Platform
Immunotherapies to improve clinical outcomes
Vaccination
Site (SC injection)
Therapeutic
vaccines express
tumor/viral
antigens
to stimulate
a safe and specific
immune response
MHC-1
Tumor
Lymph node
(priming site)
APC
MHC-1
TCR
CD8
Muc-1
peptides
Activated
T-cell
(CTL)
T cell
(CD8+)
Tumor
cell
(Muc1+)
APC
APC
T cell
Antigen (MUC1) expression
leading to maturation of
Antigen Presenting Cell (APC)
Mature APCs present MUC1
antigen to naive T-cells
T-cells multiply, get activated
and reach the blood stream
Clinical and preclinical data have shown
important benefits when combined
with chemotherapy and ICIs
Activated T-cells infiltrate into the
tumor, recognize and kill MUC1+
tumor cells
Applications in cancers
and infectious diseases
11
TG4010 in Non-Small Cell Lung Cancer (NSCLC)
Phase 2 in Combination with Opdivo® (Nivolumab)
2nd line
treatment
Support of
Clear need to improve OS and the number of patients
responding to treatment, in “all comer” population
• ICIs have been approved
• ~265,000 eligible patients*
•
•
•
Collaborative agreement
– with UC Davis Medical Center (USA)
– and Bristol-Myers Squibb (supply of nivolumab)
First patient treated in March 2017 (NCT02823990)
First results expected around the end of 2017
Protocol
• Up to 33 patients
• Multi-center, single-arm, open label study
• Stage IV non-squamous NSCLC who have
progressed after one line of systemic therapy
Endpoints
 Primary endpoint: Objective response rate
(ORR)
 Secondary endpoints: progression-free survival
(PFS), overall survival (OS), duration of response
and safety
* Sources: EU, US, Japan, Globocan, company estimates
12
TG4010 in Non-Small Cell Lung Cancer (NSCLC)
Phase 2 in Combination with ICI + Chemotherapy (CT)
1st
line
treatment
Clear need to improve rate and duration of response
in particular for patients with tumors expressing low or
undetectable levels of PD-L1
• ~135,000 eligible patients*
• Preparation of a Phase 2 clinical trial
– TG4010 + ICI + standard chemotherapy
– in patients with tumors expressing low or undetectable levels of PD-L1
• First patient expected to be enrolled around the end of 2017
Transgene expects to conduct this trial with the support of a pharma.
Ongoing discussion
* Sources: EU, US, Japan, Globocan, company estimates
13
TG4001 in HPV-Positive Head & Neck Cancers
(HNSCC)
Phase 1/2 in Combination with Avelumab
Severe disease
Better
therapeutic
options needed
Support of
First ICIs recently approved in metastatic HNSCC
• Low response rate (<20%)
• Median OS: ≈ 9 months
•  Need to improve clinical outcomes
• Collaborative agreement
– with the alliance of Merck KGaA and Pfizer (supply of avelumab)
• Pr Christophe Le Tourneau, Institut Curie, Principal Investigator
• First patient expected in 2H 2017
Protocol
• Up to 50 patients (France)
• Multi-center, single-arm, open label trial
• Metastatic or refractory/recurrent HPV-16+
head & neck cancer, after failure of standard
therapy
Endpoints (Phase 2 part)
 Primary endpoint: Objective response rate (ORR)
 Secondary endpoints: progression-free survival
(PFS), overall survival (OS), duration of response
and safety
14
TG1050 in Chronic Hepatitis B (HBV)
Phase 1/1b in Combination with Standard Antivirals
Only ~3% of patients treated
with antivirals are cured
Chronic HBV
High risk of developing
cirrhosis and liver cancer
Large unmet medical need as cure rate
is extremely low.
Need to improve clinical outcome.
•
~500,000 eligible patients currently
controlled with lifelong treatment*
• Phase 1/1b clinical trial is progressing
– following positive recommendation of the Safety Review Committee in July 2016
• First data readout in 2H 2017
• Broad ongoing preclinical experiments
– with new treatment modalities that could become tomorrow’s SoC
(siRNA, Nucleocapsid inhibitors, …)
* Sources: Decision Resources: expert opinions, Company estimates, USA, Europe, Japan, 2015
15
immunotherapeutics
Oncolytic Viruses
A New Promising Therapeutic Class
Our Oncolytic Viruses Platform
• Act by directly attacking tumor cells
• And by stimulating immune response
Next generation of cancer immunotherapies
IT / IV administration
Oncolytic viruses
(OV) selectively
cause cell lysis in
the primary tumor
and boost the
immune response in
the tumor microenvironment
T cell
3
Infiltrated T cell
(CD8+)
oVV
1
4
2
1 OV infect tumor cells where
they selectively replicate
This replication leads to cell
lysis and virus propagation in
neighboring cells
2 Active payloads are secreted in
the tumor micro-environment
3 Cytotoxic T-cells enter into the
tumor, attracted by local
inflammation and danger signals
TAA
4 Infiltrated T-cells kill tumor
cells and boost anti-tumor
response by active release of
tumor antigens
Preclinical models show OV’s ability to reduce tumor burden and the number of
tumor metastases by boosting the immune system.
17
Pexa-Vec, Lead Oncolytic Virus
The Market Opportunity
Advanced HCC: a $300 million opportunity for Transgene(1)
25,000(2)
80%(3)
eligible patients in Transgene’s
territories
of “advanced” patients receive
Sorafenib (current standard of care)
Other solid tumor types
including colorectal & kidney
Transgene owns development and commercialization rights in Europe
•
•
Our partner SillaJen is responsible for conducting the Phase 3 trial
Transgene to pay SillaJen $6 million of development costs over 4 years
(1) Peak sales, Company estimates
(2) Source: Transgene territories (Europe), Globocan, 2012
(3) Source: Sorafenib is currently standard of care, Global Data, Company estimates
18
Ongoing Phase 3 Clinical Trial
1st Line Advanced Hepatocellular Carcinoma
Conducted by
Phase 3 study in combination with sorafenib (Kinase inhibitor)
•
Design
Endpoints
•
•
•
•
Pexa-Vec + sorafenib versus sorafenib (only approved drug for advanced
HCC)
N=600 patients (Europe, North America and Asia), 140 clinical centers
1:1 randomized trial
Primary: overall survival (OS)
Secondary: safety, time to progression, progression-free survival, overall
response rate and disease control rate
 Orphan drug designation granted
 SPA with FDA
• First patient enrolled in January 2016
• Recruitment going according to plan
• 1st patient expected to be treated in Europe shortly
First results expected in 2019
19
Pexa-Vec Trials
Comprehensive Clinical Plan to Deliver PoC in Combination with ICIs
Transgene’s Pexa-Vec Phase 1/2 trials in combination with ICIs
Advanced HCC
1st line
Pexa-Vec + Opdivo®
(nivolumab)
• Ongoing preparation
• Open label, single arm trial, expected
to start in Q2 2017 (US/EU)
Solid tumors
Pexa-Vec + Yervoy®
(ipilimumab)
• Centre Léon Bérard, sponsor of the trial
• 1st patient dosed in February 2017
• Financial support from INCA
First results: around the end of 2017
20
TG6002
Next Generation of Oncolytic Virus against Solid Tumors
Vaccinia Virus expressing FCU1 gene,
double deletion gene TK-/RR-
 Enhanced selectivity and safety
 FCU1 gene: codes for chimeric enzyme changing nontoxic prodrug 5-FC into the cytotoxic compound 5-FU
Advanced OV to modulate tumor micro-environment
Targeted chemotherapy
FCU1 gene
Viral oncolysis
Non-toxic
prodrug
5-FC
Prodrug
activating
enzyme
Cell
Toxic drug
death
5-FU
• Phase 1 trial in glioblastoma, open label, dose escalation, IV administration
• PI: Pr J-Y. Delattre (Pitié Salpétrière)
• INCA Grant
First-in-human trial
FPI in Q2 2017
Potential in other indications
(solid tumors)
21
Transgene Set to Deliver Rich News Flow and Clinical Data
over the next 18 Months
Product
Preclinical
Indication
1
Clinical Phase
2
3
THERAPEUTIC VACCINES
Non-small cell lung cancer – 2nd line
+ nivolumab (ICI)
Non-small cell lung cancer – 1st line
+ ICI + CT
Non-small cell lung cancer
Neo-adjuvant (translational)
TG4001
HPV positive cancers
+ avelumab (ICI)
TG1050
Chronic hepatitis B
+ antiviral
TG4010
ONCOLYTIC VIRUSES
Pexa-Vec
TG6002
Hepatocellular carcinoma – 1st line (PHOCUS)
+ sorafenib
Hepatocellular carcinoma – 1st line
+ nivolumab (ICI)
Other solid tumors
+ ipilimumab (ICI)
Sarcoma – Breast cancer
+ cyclophosphamide
Solid tumors
Neo-adjuvant (translational)
Glioblastoma
Ongoing
About to start
In preparation
22
immunotherapeutics
Key Financials
2016
Financial Highlights
€56.2 million
Cash & cash equivalents at 2016 year end
€30.6 million
Cash burn 2016,
incl. €5.0 million of restructuring costs
€33.0 million
Net operating expenses in 2016,
decreased by 28% compared with 2015
€25.2 million
Net loss in 2016,
reduced by 46% compared with 2015
24
P&L reflects the completed restructuring
of the Company
2016
2015
D
2014
10.3
9.9
0.4
11.1
Research and development expenses
(26.4)
(32.1)
5.7
(41.7)
General and administrative expenses
(6.2)
(5.8)
(0.4)
(7.6)
Other expenses
(0.3)
(7.8)
7.5
(1.3)
(33.0)
(45.8)
12.8
(50.6)
(22.7)
(35.8)
13.1
(39.5)
Interest expenses, net
(0.6)
(0.9)
0.3
(0.8)
Income from equity consolidated expenses
(0.9)
(1.2)
0.3
(0.8)
(24.2)
(37.9)
13.7
(41.1)
(1.0)
(8.5)
7.5
(7.4)
(25.2)
(46.4)
21.2
(48.5)
(0.45)
(1.20)
0.75
(1.26)
in € million
Revenue
Net operating expenses
Operating loss from continuing operations
Net loss from continuing operations
Net loss from discontinued operations
Total Net loss
Net loss per share (in €)
25
Balance Sheet
In € million
2016
2015
D
Cash, cash equivalents and other financial assets
56.2
31.7
+ 24.5
Other current assets
17.8
19.4
- 1.6
Non current assets
48.9
49.8
- 0.9
Total Assets
122.9
100.9
+ 22.0
In € million
2016
2015
D
Current liabilities
19.9
26.7
- 6.8
Non current liabilities
56.5
47.6
+ 8.9
Liabilities
76.4
74.3
+ 2.1
Shareholder’s Equity
46.5
26.6
+ 19.9
122.9
100.9
+ 22.0
Total Liabilities & Equity
26
Cash Flow Statement
2016
2015
D
(24.4)
(32.5)
8.1
(9.2)
(12.7)
3.5
(33.6)
(45.2)
11.6
Cash generated from investing activities
(2.1)
2.3
(4.4)
Cash generated from financing activities
60.2
8.7
51.5
24.5
(34.2)
58.7
(30.6)
(34.8)
4.2
56.2
31.7
24.5
In € million
Cash used in operating activities before change in working capital
Change in working capital
Cash used in operating activities
Cash burn
Cash burn (excluding capital increase & loan)
Cash & cash equivalents, at year end
27
immunotherapeutics
Outlook
Transgene on Track
To Deliver
a Rich Value-Creating News Flow
2017 Outlook
Poised to Generate a Significant Value-Creating News Flow
5
2
7
Immunotherapy products
at clinical stage
Immunotherapy
platforms
Clinical trials
to deliver news flow
in 2017
Product
portfolio
Advanced and diversified portfolio
Addressing high unmet medical needs
Clear clinical development plan for all key pipeline assets
Finance
Company funded until the end of 2018
2017 cash burn ̴€30 million
Corporate
Multiple partnering opportunities
29
Robust Clinical Portfolio
Poised to Generate a Significant Value-Creating News Flow
TG4010
•
•
2nd line: first results around the end of 2017
1st line: collaboration agreement and FPI in the Phase 2 trial
TG4001
•
Expected
development
news flow
in 2017
First patient dosed (2H 2017)
TG1050
•
•
First results (2H 2017)
Preclinical results
Pexa-Vec
•
•
•
Phase 3 in HCC, 1st line: 1st patient treated in Europe (2Q 2017)
Phase 2 in HCC, 1st line: 1st patient dosed (2Q 2017)
Phase 1 in Solid Tumors: First results around the end of 2017
TG6002
•
First patient dosed in Phase 1 trial (2Q 2017)
30
Save the Date - R&D Day: June, 22nd
Changing tumor
physical properties
Breaking
immune tolerance
Improving homing
of effector T-cells
To
“make cold tumors hot”
Learn more about our pioneering OV research
• how we will can modulate the tumor micro- environment
and embed multiple payloads in our OVs
Discover our leading-edge technologies
and their future applications
Discuss with world-leading scientists
and clinicians
31
immunotherapeutics
Questions
immunotherapeutics
Thanks for your Attention
immunotherapeutics
Appendices
34
Transgene Ownership
Key Shareholders
As of Jan. 31st, 2017
•
56.4 million shares outstanding
+ 1.1 million options and free shares
•
Market capitalization:
~ €150 million as of Feb. 28, 2017
•
•
•
Listed on Euronext Paris
ISIN: FR0005175080
Ticker: TNG
60 %
Free float
40 %
35
immunotherapeutics
Contact
Lucie Larguier
Director Corporate Communication and Investor Relations
+33 3 88 27 91 04 / +33 6 76 24 72 27
[email protected] / [email protected]
@TransgeneSA
Transgene
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