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ERADICATING HPV INFECTION
BEFORE IT CAUSES CERVICAL CANCER
MODIFIEZ LE STYLE DU TITRE Corporate Presentation
June 2016
INNOVATIVE IMMUNOTHERAPIES
TO FIGHT INFECTIOUS DISEASES AND CANCER
2
DISCLAIMER
This document has been prepared by Genticel (the "Company") and is for information purposes only.
The information and opinions contained in this document are provided as of the date of this document only and may be updated, supplemented, revised, verified or amended, and thus such information may be subject to significant changes. The Company is not under any obligation to update the information or opinions contained herein which are subject to change without prior notice.
The information contained in this document has not been subject to independent verification. No representation, warranty or undertaking, express or implied, is made as to the accuracy, completeness or appropriateness of the information and opinions contained in this document. The Company, its subsidiaries, its advisors and representatives accept no responsibility for and shall not be held liable for any loss or damage that may arise from the use of this document or the information or opinions contained herein.
This document contains information on the Company’s markets and competitive position, and more specifically, on the size of its markets. This information has been drawn from various sources or from the Company’s own estimates. Investors should not base their investment decision on this information.
This document contains certain forward-looking statements. These statements are not guarantees of the Company's future performance. These forward-looking statements relate to the Company's future prospects, developments and marketing strategy and are based on analyses of earnings forecasts and estimates of amounts not yet determinable. Forward-looking statements are
subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the future. Forward-looking statements cannot, under any circumstance, be construed as a guarantee of the Company's future performance and the Company’s actual financial position, results and cash flow, as well as the trends in the sector in which the Company operates, may differ materially from those proposed or reflected in the forward-looking statements contained in this document. Even if the Company’s financial position, results, cash-flows and developments in the sector in which the Company operates were to conform to the forward-looking statements contained in this document, such results or developments cannot be construed as a reliable indication of the Company's future results or developments. The Company does not undertake any obligation to update or to confirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document.
This document does not constitute an offer to sell or subscribe or a solicitation to purchase or subscribe for securities in France, the United States or any other jurisdiction. Securities may not be offered or sold in the United States absent registration under the US Securities Act of 1933, as amended, or an exemption from registration thereunder. No public offering of securities may be conducted in France or abroad prior to the delivery by the French Autorité des marchés financiers (Financial Markets Authority) of a visa on a prospectus that complies with the provisions of Directive 2003/71/CE as amended. No offering of securities is contemplated in France or any jurisdiction outside France.
3
Benedikt Timmerman
PhD, MBA
• Founder, CEO
Martin Koch MsEng, MBA
• Chief Financial
Officer
Marie-Christine Bissery
PhD, Pharm.D
• Chief Development
Officer
Sophie Olivier MD, Gynecologist
• Chief Medical
Officer
Rémi Palmantier PhD, Immunology
• Chief Scientific
Officer
PhD in Molecular Genetics – Ghent University, Belgium & MBA - INSEAD, France. 20 years of experience in Academia & Industry. Management positions in R & D and Business Development in Biotechnology and Life Science companies, including Sandoz and Novartis
Sales Director, Oncology Cephalon Pharma France (2006 – 2007) and Controlling and Finance Director functions at Elan & Zeneus Pharma UK (2001 – 2005)
International Director of Oncology (2007 – 2008) and Deputy Head of Oncology (2005- 2007) at Sanofi-Aventis; Sr. Director of Experimental Therapeutics and Translational Research, Aventis Pharma (2000 – 2004)
Pediatrics Scientific Coordinator for the European Medicines Agency (notably vaccines), UK (2009-2014) and Senior Director Women’s Health & Bone Repair, Worldwide Project Leader, Wyeth Clinical Research & Development, USA (2001-2009) & France (1996 – 2000)
20 years of Research Management at GlaxoSmithKline, notably as Head Chronic Disorder Immunotherapeutic Program (2009- 2015) and as Head Cancer Preclinical Immunotherapeutics and Director, R & D, North America, GSK Biologics, Canada (2006-2009)
COMPLEMENTARY AND EXPERIENCED MANAGEMENT TEAM
4
Dr Thierry
HERCEND
President
Ed. De Rothschild Inv. Partners
Raphael WISNIEWSKI
Bpifrance Investissement
Dr Olivier MARTINEZ
Kurma Life Sciences Partners
Dr Philippe PELTIER
Wellington Partners
Dr Rainer STROHMENGER
Dr Gerald
MOELLER
Vice President
Dr Didier HOCH
Mary TANNER
Caroline LAPLANE
Supervisory Board Clinical Advisory Board
Prof. Pierre Van Damme, MD, PhD
University of Antwerp
Prof. Diane Harper, MD, MPH, MS
University of Louisville
Emeritus Prof. Chris Meijer, MD
University Medical Center Amsterdam
Prof. Anna-Barbara Moscicki, MD
University of California, San Francisco
Emeritus Prof. Margaret Stanley, BSc, PhD OBE
University of Cambridge
Dr Xavier Bosch, MD, MPH
Catalan Institute of Oncology, Barcelona
Industry experience of the Supervisory Board
ADVISED BY INDUSTRY EXPERTS & KEY OPINION LEADERS
5
SOLID CASH BALANCE
* As at March 31, 2016
Cash balance: € 18.8 million*
Corresponding to 2 year of financial visibility (mid-2018)
€70.1 million raised since inception,
incl. €34.7 million at IPO (04/2014)
15,554,666 shares outstanding*
6
AN ANTIGEN DELIVERY VECTOR SUITED TO DEVELOP IMMUNOTHERAPIES IN MULTIPLE INDICATIONS
CyaA, (adenylate cyclase),
a breakthrough vaccine carrier licensed from Institut
Pasteur based on Bordetella Pertussis
(cause of whooping cough)
Unique mechanism of action that triggers both killer and helper T cells
X
CyaA platform
Chosen antigen
Recombinant CyaA protein incorporating
the antigen of choice
Binding domain targets an integrin receptor of antigen-presenting cells
7
A BREAKTHROUGH ANTIGEN DELIVERY VECTOR WITH DUAL MECHANISM OF ACTION
The chosen antigen is incorporated in the CyaA protein
The recombinant CyaA protein delivers the antigen TO and INTO
human immune sentinel cells
Sentinel cells activate antigen-specific immune killer * T cells and
helper T cells
Killer cells eliminate cells
that contain the antigen
Antigen Presenting Cell (APC)
* cytotoxic
CyaA +
adjuvant
Chosen
antigen
Helper T cells
Killer T cells
Eradication
of infected
cells
8
GTL001, A “FIRST-IN-CLASS” THERAPEUTIC VACCINE TARGETING THE 2 MOST ONCOGENIC HPV TYPES
HPV 16 and 18 together cause 70% of cervical cancer cases
GTL001consists of 2 CyaA proteins
one carrying the E7 antigen of HPV 16
the other carrying the E7 antigen of HPV 18
16-
E7
18-
E7
CyaA-HPV16-E7
+ CyaA-HPV18-E7
+ Adjuvant (imiquimod cream 5%)
GTL001 first-in-class first-in-indication therapeutic
vaccine
2 inter-dermal injections 6 weeks apart
2 applications of imiquimod cream 5%, 15 minutes
and 24 hours after each injection
9
PHASE 2 PROOF OF
CONCEPT STUDY
222 HPV16 +/- 18 positive women (25-50)
W Europe - 7 countries GER, UK, FIN, SP, FR, BE, NL
39 centers
600 µg + imiquimod
Viral clearance
at M6 & 12
Maintenance of
viral clearance
n =111
Placebo + imiquimod
n =111
Last patient in Nov 14 H1 16 H1 17
STUDY
POPULATION
EFFICACY
ENDPOINTS
< 6 weeks >
< 6 weeks >
Women 25-50 yrs infected by HPV 16 and/or 18 with NILM, LSIL or ASCUS cytology, exclusion of CIN2+ by colposcopy/histology
Primary endpoint at M12 Efficacy of GTL001 + imiquimod to clear HPV 16 and 18 cervical infection
as compared to placebo Main secondary endpoints Sustained clearance at M24 Progression to CIN2+
M12 M24
GTL001 PHASE 2 TRIAL (RHEIA-VAC) HALFWAY THROUGH 24-MONTH PROTOCOL CONDUCT
Viral clearance
at M15 & 18
M18
10
18 MONTH INTERIM RESULTS AND CONCLUSIONS OF GTL001 PHASE 2 STUDY IN EUROPE
No unexpected safety events
Reactions are mostly local, as expected
All reactions are transient (<7 days), as expected
Good Safety Profile
Safety crucial for pursuit of collaboration with SIIL
Numerical, yet not statistical, difference between treatment and placebo in terms of viral clearance
Statistical differences found in subgroups for 12 month results were not confirmed at 18 months
Efficacy not confirmed
Study will continue* until the end at 24 months (Q1 2017)
Interim Conclusions Expectations at 24 months
Unblinding of data, verify by patient impact of stratification factors (age, HPV type, cytology)
Verify maintenance of viral clearance and progression to CIN2+ lesions.
Consequences until 24 month results.
Continue cash saving efforts
Strenghthen SIIL-Vaxiclase Program
Increase efforts in development of Company portfolio
* Under the condition that DSMB approves continuation during its next scheduled for early July 2016
11
PC10VAC02
Phase 2 (EU), ongoing
PC10VAC01
Phase 1 (BE)
Core study completed
Extension ongoing
Development depends on
PC10VAC02 results
• 47 women (25-50 yrs), HPV16 +/- 18 positive, NILM
• Dose escalation (100, 600, 1200 µg)
• Safety, tolerability & immunogenicity study
• 232 women (25-50 yrs), HPV16 +/- 18 positive, NILM or ASCUS/LSIL
• Proof of concept study
• Randomized, double-blind, placebo-controlled, 1 dose-
level
• Primary endpoint: Virology
PC10VAC05
Phase 1b (USA), bridging
• 20 women (25-65 yrs), HPV16 +/- 18 positive, NILM or ASCUS/LSIL
• Safety and immunogenicity
11
REMINDER OF GTL001 CLINICAL DEVELOPMENT PLAN
Results published in June 2016 Clinical Cancer Research
12
GTL002 (MULTIVALENT HPV) FOLLOW-ON THERAPEUTIC VACCINE CANDIDATE
IN VIVO PRECLINICAL PROOF OF CONCEPT
Immune response for each of the 6 HPV-
derived proteins in the vaccine
In vivo therapeutic efficacy shown by
tumor eradication
Robust manufacturing data
Will benefit from lessons learned from the
clinical development of GTL001
93 million HPV 16/18
% cervical cancer 70% 100%
300 million All HPV types
85%
#
HP
V i
nfe
cte
d w
om
en
158 million 4 additional HPV
GTL
00
2
GTL
00
1
Based on proprietary Vaxiclase platform Includes 6 oncoproteins from 6 most oncogenic HPV types,
including HPV 16 and 18.
13
SIIL, private company valued at $12 billion, world’s largest producer of vaccine doses: globally, two out of every three children are vaccinated by a vaccine manufactured by SIIL.
License agreement to evaluate Vaxiclase in development of multivalent vaccines containing pertussis antigens.
Agreement, limited to emerging markets, could provide $57 million in upfront & milestones payments plus single digit royalties on net sales.
Initial revenue received in 2015, next step H2 16
PARTENERSHIP WITH SERUM INSTITUTE OF INDIA LTD (SIIL)
Former pertussis vaccines: efficacious but not well tolerated.
Current acellular vaccines (aP): well tolerated but with an insufficient duration of efficacy.
Global resurgence of pertussis cases observed by WHO
Vaxiclase (as a pertussis antigen) could improve the duration of protection of aP vaccines but with a good tolerability2.
Estimated revenues for combination vaccines DTaP and Tdap containing aP > $2 billion per year
AGREEMENT WITH SIIL IMPROVE PERTUSSIS VACCINES
1 WHO: Weekly epidemiological record, 85, 2010 (http://www.who.int/wer); Klein et al., New England Journal of Medicine, 367(11), 2012;
2 Koepke, Journal of Infectious Disease, 210, 2014; [2] Cheung et al., Infection and Immunity, 74(12), 2006
14
Antigen inserted in N-terminal domain
Delivers antigen to sentinal cells of immune system
Activates antigen-specific T Killer1 cells and T Helper cells
Eradicates cells carrying targeted antigen
Safety confirmed by GTL001 of vectors based on CyaA
VAXICLASE - MECHANISM OF ACTION IN DEVELOPMENT OF IMMUNOTHERAPIES AND VACCINES
Vaxiclase alone as CyaA recombinant protein with no exogenous antigens.
Vaxiclase induces anti-CyaA antibodies CyaA neutralization of pertussis
Increases production of antibodies against other antigens, e.g., DTaP4
Induces TH1/TH17 cellular response “memory” immune response
VAXICLASE AS ANTIGEN VECTOR
USE BY GENTICEL FOR GTL002
VAXICLASE AS ACTIVE INGREDIENT (PERTUSSIS ANTIGEN2)
USE BY SIIL FOR GTL003
X Y Z
A
Vaxiclase with other antigens Vaxiclase without exogenous antigens
1 Cytotoxic 2 Whooping cough is caused by B. pertussis 3 CyaA = Adenylate Cyclase; 4 DTaP= Diphtheria, Tetanus, acellular Pertussis
15
NEXT STEPS
2015 License agreement on
Vaxiclase signed
with SIIL*
02/15
In vivo results for
GTL001 show ability to
treat & protect
04/15
In vivo preclinical proof
of concept of GTL002 05/15
FDA Clearance
for U.S. Phase 1 trial
of GTL001
06/15
US patent protecting
use of platforms to treat
cancer
09/15
1st US patient
vaccinated with GTL001 10/15
2016 Agreement with Roche to evaluate the
cobas® test for use in GTL001 Phase 3 Q1
GTL001
Phase 2
efficacy data at M12
Q1
GTL001
Additional results at 12 months of phase
2 trial
T2
GTL002
in-vivo immunology data (EUROGIN
2016)
T2
GTL001 Commercialized HPV tests validated Five-year stability demonstrated
H1
GTL001 Phase 2
efficacy data at M 15 & 18
T2
GTL001 US phase 1 tolerability results
H2
Vaxiclase 1st milestone with SIIL*
H2
2017
GTL001 End of phase 2 at M24
Q1
Increase business
development activities
* Serum Institute of India Ltd
16
Cash Preservation
Focus on business
development activities
Pipeline expansion: gain access to innovative development-stage molecules with a strong market potential.
STRATEGIC UPDATE FOR 2016
Continue GTL001 phase 2 trial until end at 24 months* (january 2017) and reevaluate program at that point in time.
Continue reducing expenses to extend Company’s funding beyond mid 2018.
Maintain core assets in immunology and clinical development
Strengthen partnership with Serum Institute of India Ltd
* Under the condition that DSMB approves continuation during its next scheduled for early July 2016
17
APPENDICES
▌ FINANCIALS – 2015 ANNUAL RESULTS
▌ GTL001, CLINICAL DATA
▌ IMIQUIMOD AS VACCINE ADJUVANT
18 18
FINANCIALS (31/12/15)
19
INCOME STATEMENT (IFRS)
Figures in line with company’s expectation Audited data in K€ 20141 2015
Revenues - 178
R&D expenses (11,190) (10,935)
Subsidies (CIR2) 2,904 2,940
G&A expenses (2,763) (3,599)
Operating result (11,049) (11,417)
Financial result 105 223
Net income (10,944) (11,193)
Net income per share (0.79) (0.72)
Advance on GLT001 phase 2 in EU
Initiation of a phase 1 in the U.S.
Non-recurring expenses (€0.7 million)3
Interest earned
from investing funds
1 2014 financial statements have been amended in application of IAS 8 (please refer to half-year 2015 financial statements for detailed information)
2 Research tax credit (crédit d’impôt recherche) in France 3 Onetime recruitment costs, ad-hoc market access studies,
Intellectual Property management expenses
20
BALANCE SHEET (IFRS)
Audited data in K€ 20141 2015
Non current assets 10,303 5,501
Current receivables 3,172 3,706
Current financial assets 12,557 5,022
Cash & equivalents 10,170 11,660
TOTAL ASSETS 36,202 25,889
Shareholders equity 30,217 20,335
Employee LT Obligation 380 322
Financial debts 2,158 2,522
Other liabilities 3,447 2,710
TOTAL LIABILITIES 36,202 25,889
1 2014 financial statements have been amended in application of IAS 8 (please refer to half-year 2015 financial statements for detailed information)
2 Total cash position results from €11,7 M in cash & equivalents, €5,1 M in non current assets
(capitalization contract) and €5 M in current financial assets (term deposits) in accordance with IFRS standards.
€5.2 million of capitalization contract
€5.0 million in short time deposits
Trade payables for €1.9 million
Total cash position of €21,8 million2
in line with pipeline development
advances
Incl. €2.9 million of Research Tax Credit 2015
Repayable advances for €2.6 million
21
CASH FLOW STATEMENT (IFRS)
Audited data in K€ 20141 2015
Cash flow from operating
activities (9,847) (11,744)
Cash flow from investing
activities (22,573) 12 585
Cash flow from financing
activities 38,752 649
Opening cash & equivalents 3,839 10,170
Variation 6,331 1,490
Closing cash & equivalents 10,170 11,660
Breakdown of change in WCR
Audited data in K€ 20141 2015
Other non-current financial assets 17 (7)
Inventories (net inventory
impairment) (13) 21
Other receivables 588 514
Trade payables and related
accounts (740) 776
Tax & social security liabilities (192) (37)
Other creditors & miscellaneous
liabilities 18 (1)
Total change (322) 1,266
1 2014 financial statements have been amended in application of IAS 8 (please refer to half-year 2015 financial statements for detailed information)
Growth in WCR (€1.2 million in 2015 versus -€0.3 million in 2014) mainly due to decrease in trade
payables between 2014 and 2015 (versus increase between 2013 et 2014)
22 22
GTL001, CLINICAL DATA
▌ PHASE 1
▌ PHASE 2 AT 12 MONTHS
23
GTL001, PHASE 1 COHORTS
Cohort 1 Open-label
N = 5
GTL001
100 µg solution +
imiquimod
Safety review
Cohort 2 Open-label
N = 5
GTL001
600 µg solution +
imiquimod
Safety review
Cohort 4 Open-label
N = 9
GTL001
600 µg powder +
imiquimod
Safety review
Cohort 3 Randomized, double-blind
N = 28
2:1:1 randomization
GTL001
600 µg solution +
imiquimod
GTL001
600 µg solution +
placebo cream
Placebo
injection +
imiquimod
Safety review
Published in June 2016 Clinical Cancer Research
24
GTL001, EU PHASE 1 STUDY PC10VAC01 DESIGN
Patients: HPV16 and/or 18-infected women with normal cytology
Study Objectives
Primary: general safety and local tolerance
● Incidence of general and local adverse events
● Changes in cervical cytology and HPV virology
Secondary: cellular and humoral immunogenicity
● Peripheral blood E7-specific T cell response (IFNg ELISPOT)
● Anti-CyaA and anti-E7 antibody responses (ELISA)
2 GTL001 formulations tested
Liquid form (5 x 0.2 ml id) - Powder form (1 x 0.2 ml id)
4 cohorts, including one randomized cohort
NB: not powered for statistical significance, no statistical analysis performed
Viral clearance and clearance maintenance for indicative purposes only
25
GTL001, TOLERABILITY IN PHASE 1
Local reactions
Mostly erythema, induration, pain
Generally mild to moderate and short-lived (less than 7 days)
More severe after second injection
Severe reactions reported by 5-15% of patients
Systemic reactions
Include flu-like symptoms (fever, headache, arthralgia/myalgia, and fatigue)
Mostly mild to moderate
No drop-out from the study
Minimal concomitant medication due to local or systemic reaction was (1 patient
took one dose of Tylenol)
Vaccines administered i.d., such as BCG or rage vaccines, also report transient
severe local reactions
26
No dose-limiting toxicity
No treatment-related Serious Adverse Effects (SAE)
No patients stopped trial participation (no drop-outs)
Reactions are mostly local, generally mild or
moderate, as expected
All reactions are transient (<7 d.), as expected
Demonstrated safety profile
Induced an E7- specific T cell
immune response
More patients treated with GTL001 and
followed for > 12 months remained virus free
17%
62%
0 20 40 60 80 100
Placebo
GTL001
43% (2)
0 20 40 60 80 100
Placebo
GTL001
33%
78% (3)
0 20 40 60 80 100
Placebo
GTL001
74%
More patients treated with GTL001
eradicated their HPV
(1) Warning: this phase 1 study was not designed to provide statistically significant efficacy data. Data
provided above are strictly for indicative purposes (data as at 31/12/2012 ; average of 16.6 months post 1st
vaccination ; pooled small groups; no statistical analysis)
(2) Natural clearance of HPV 16/18 is 40 to 50% after 1 year
(3) 8/9 without reinfection for the HPV type present at enrolment ; 7/9 without any reinfection
n = 19
n = 7
n = 18
n = 6 n = 3
n = 9
GTL001 PHASE 1 STUDY COMPELLING RESULTS ON 47 HPV 16 AND/OR 18 POSITIVE WOMEN (1) – NILM ONLY RESULTS PUBLISHED IN JUNE 2016 IN CLINICAL CANCER RESEARCH
27
VIRAL CLEARANCE AT 12 MONTHS IN PHASE 2 OF GTL001 CYTOLOGICAL STATUS - NATURAL POPULATION1 VS STUDY POPULATION
Viral clearance GTL001 Placebo p-value * / **
LSIL 38.5% 44.9% 0,549 / 0.560
ASCUS 54.8% 35.3% 0,127 / 0.018
NILM 62.5% 40% 0,127 / 0.018
NILM + ASCUS 58.7% 37.5% 0.021 / 0.0029
Total 48.7% 39.7% 0.188 / 0.110
73%
27%
11%
28%
1% 45% 15%
0%
25%
50%
75%
100%
Natural
population
GTL001 Phase 2
population
NILM ASCUS LSIL Other
1 Wright et al. Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test . Gynecol Oncol 2015: 136; 189-197. « Other » represents women, with high-grade lesions (ASC-H and HSIL) and with reported cancers, which would not have been eligible for the GTL001 phase 2 study.
Too small study groups of ASCUS / LSIL, to reflect the natural population, would not have produced any meaningful results
Over-representation of LSIL patients may have led to the absence of statistical separation at
12 months in the overall population
* Fisher exact test / ** CMH test controlling for age and HPV status
1
1
28
PHASE 1 TOLERABILITY
STUDY
Single arm, open label
20 HPV16 +/- 18 positive women (25-65)
US - 4 centers
Diane Harper, MD, lead investigator
600 µg + imiquimod
Primary endpoint:
tolerability
Last patient in
Q1 16 H1 16
STUDY
POPULATION
ENDPOINTS
< 6 weeks >
Women 25-65 yrs. infected by HPV 16 and/or 18 with Normal, LSIL or ASCUS cytology, exclusion of CIN2+ by colposcopy/histology
Primary endpoint at M3 Tolerability of GTL001, notably in the age group 50-65 (not studied
previously)
Secondary endpoint Immune response at M3
Warning: as with any phase 1 study, the study is not designed to provide statistically significant efficacy data.
n =20
2 cohorts: 25-50 and 50-65 years of age
M3
GTL001 US PHASE 1 STUDY STARTED IND GRANTED IN JUNE 2015 - STUDY STARTED
1ST patient in
10/2015
29
Q2 2016: COMPLETION OF TWO MAJOR MILESTONES IN PREPARATION FOR PHASE 3 PROGRAM OF GTL001
cobas® HPV test, only test both EU-labeled and FDA-approved
Only test approved in the US as first-line primary screening in women 25 years of age and older instead of cytology
Extensively tested in the Athena trial1 (more than 47,000 women)
HPV 16/ 18 genotyping (+ 12 other high-risk HPV)
GLOBAL CLINICAL PROGRAM: NEED FOR A WIDELY AVAILABLE HPV GENOTYPING TEST
Wright et al. Dépistage du cancer cervical primaire avec le virus du papillome humain : Fin de résultats de l'étude ATHENA utilisant HPV comme test de dépistage en première ligne , Gynecol Oncol 2015: 136; 189-197
TEST CONFIRMED, ABILITY TO USE CLINICALLY VALIDATED HPV TESTS
1
REGISTRATION STUDIES: NEED FOR SUFFICIENT PRODUCT STABILITY EQUIVALENT TO FUTURE MARKETED PRODUCT. 2
5 YEAR SHELF LIFE OF GTL001 DEMONSTRATED
30 30
IMIQUIMOD AS VACCINE ADJUVANT
31
Application at the site of GTL001 ID injection (upper thigh)
Used at doses < to normal approved usage
Acknowledged by FDA as an adjuvant in
GTL001 IND submission
IMIQUIMOD CREAM 5% SAFE AND EFFECTIVE TOPICAL ADJUVANT
Imiquimod (Aldara Cream) activates TLR7/TLR8 in humans
Binds to intracellular TLR7 in Antigen Presenting Cells (APC) leading to a TH1 cytokine profile promoting an effector T cell response
Immune response modifier marketed for topical applications on the skin (i.e., external genital and perianal warts and superficial basal cell carcinomas in adults)
Several generic versions available in the US
32
Imiquimod, a low molecular weight compound in the imidazoquinoline family, is a toll-like receptor (TLR) agonist that binds TLR7 and TLR8 in humans (Stary et al 2007; Schön and Schön 2008) but only binds to TLR7 in mice.
Animal and human studies have previously demonstrated that immune responses to a T cell protein-based vaccine can be enhanced by the topical application of imiquimod (Rechtsteiner et al 2005; Othoro et al 2009; Vasilakos and Tomai 2013; Fehres et al 2014; Adams et al 2008; Firbas et al 2010).
REFERENCES - IMIQUIMOD AS VACCINE ADJUVANT
Stary G, Bangert C, Tauber M, et al. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med. 2007;204(6):1441-51
Schön MP and Schön M. TLR7 and TLR8 as targets in cancer therapy. Oncogene. 2008;27(2):190-9.
Rechtsteiner G, Warger T, Osterloh P, et al. Cutting edge: priming of CTL by transcutaneous peptide immunization with imiquimod. J Immunol. 2005;174(5):2476-80.
Othoro C, Johnston D, Lee R, et al. Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun. 2009;77(2):739-48.
Vasilakos JP, Tomai MA. The use of Toll-like receptor 7/8 agonists as vaccine adjuvants. Expert Rev Vaccines. 2013;12(7):809-19.
Fehres CM, Bruijns SC, van Beelen AJ, et al. Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ Tcell cross-priming. Eur J Immunol. 2014;44(8):2415-24.
Adams S, O'Neill DW, Nonaka D, et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol 2008;181:776-784.
Firbas C, Boehm T, Buerger V, et al. Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine. Vaccine. 2010;28(12):2397-407.
33
CONTACTS
Copyright Genticel 2016
GENTICEL US INVESTORS MEDIA Valerie Leroy
Brian Ritchie
Caroline Carmagnol
+33 (0)1 82 82 00 20 +1 (212) 915 2578
+33 6 64 18 99 59
