Thierry Legon CEO, ASIT biotech

Transcription

1 Paris May Leader in Allergenic Peptide Immunotherapy Thierry Legon CEO, ASIT biotech 1

2 About ASIT biotech Mission To improve acceptance and compliance of allergy immunotherapy by developing short course treatments based on innovative allergenic peptides Main achievements Clinical efficacy of lead product in Grass Pollen Rhinitis confirmed in Phase 3 clinical study Validated technology platform to design, characterize, screen and produce novel product candidates Ongoing design and screening of product candidates in House Dust Mite Rhinitis and food allergy (peanuts, cow s milk and egg white) 2

3 About ASIT biotech ASIT biotech has dual market listing in Brussels (Belgium) and Paris (France) since May 2016 Raised 73 million since inception ( 23.4 million by IPO (2016) and 13.9 million by a private placement (2018)) 26 active and motivated collaborators Partnership with public and private internationally renowned institutions 3

4 4 Ever increasing number of allergic patients

5 Over 1 billion patients suffer today from Allergy and over 4 billion in 2050 Steadily increasing prevalence of allergic diseases More complex allergies with high morbidity leading to a heavy burden for health care system 30 to 40% of the world population would be affected by one or more allergic conditions Over 400 million patients suffer from Allergic Rhinitis Over 200 million patients suffer from Food allergies Over 300 million patients suffer from Asthma 5 World Allergy Week April 2011 EAACI

6 Allergic Rhinitis: up to 400 million people worldwide USA 12-30% EUROPE 23-30% CHINA 1,6-43% MIDDLE EAST 7,4-45,2% JAPAN 9,1-37,5% USA Europe China Japan Population (M) LATIN AMERICA 5,5-45,1% AFRICA 7,2-54,1% AUSRALIA 12-41,3% Bauchau V & Durham SR Eur Respir J 2004; 24: Katelaris, C.H. et al., Clinical and experimental allergy 42(2), pp C.F., M. & Tong Janice S.C. Lin, European Academy of Allergy and Clinical Immunology, pp Population with Rhinitis (M) Population with severe Rhinitis (M) TBD TBD 9

7 Food Allergy: more than 200 millions people worldwide 15 million of American, 17 million of Europeans suffer from food allergy 1 Increasing prevalence in both developed and developing countries 2 Peanut, cow s milk and egg white concern >74% children 3 Total annual food allergy management cost estimate/child in the US: $ 4, Commins et al and World Allergy Organization 2. Prescott et al Scott et al Gupta et al 2013

8 Allergy leads to symptoms impairing quality of life Reduced work productivity Eye symptoms Nasal symptoms Asthma Sleep deprivation Angiodema Reduced school performance 8 if not threathening life

9 Allergy: inappropriate immune response against harmless substance Th2 cell Allergens B cell First contact between allergen and mucosa 2. Allergen specific IgE antibody production Uptake & processing by APC T- cell activation allergen specific IgE antibody production 3. Loading of allergen specific IgE on mast cells 4. Bridging of the IgE by allergens 5. Allergic reaction IgE synthesis Mast cell 3 Basophil Mast cell 4 Basophil 5 Antigen Presenting cell Degranulation leading to histamine release Eosinophils recruitment and activation 9

10 Therapeutic options: Symptomatic vs Curative 10

11 Symptomatic drugs for allergic rhinitis Allergic rhinitis & asthma >95% of the market daily intake during allergen exposure (seasonal/perennial) no long-term effect poor effectiveness in case of low compliance $20 billion/year for respiratory allergies Food allergy no registered drugs available food avoidance epinephrine injection Interleukin specific blockers (mab) Mepolizumab (GSK) Reslizumab (Teva) Benralizumab (AZ) Dupilumab (Regeneron/Sanofi) IgE-specific blockers (mab) Omalizumab (Novartis/Genentech) Mast cell B cell IgE synthesis Basophil Th2 cell Mast cell Basophil Nonspecific immunosuppressors Intranasal steroids Inhaled steriods Leukotriene modifiers Allergen Antigen Presenting cell Degranulation leading to histamines release Eosinophils recruitment and activation Antihistamines Zyrtec Xyzal Allegra Claritin 11

12 Curative treatment: Allergy Immunotherapy Sub-cutaneous Sublingual 12

13 IL-10 IL-35 Allergy immunotherapy induces natural regulation of the immune system and provides better symptoms reduction Th2 cell 1. Regulatory T and B cells 2. Prevention of the seasonal increase of IgE 3. Induction of IgG4-associated blocking antibodies leading to clinical benefit during the pollen season. 4. Suppression of grass polleninduced basophil activation responsible for immediate allergic response IgE synthesis Mast cell B cell - Basophil IgG 4 & IgA synthesis Treg cell Breg cell Antigen Presenting cell Allergen Whole Allergens Degranulation leading to histamine release Mast cell Basophil Eosinophils recruitment and activation 13

14 Allergy immunotherapy market less than 1billion today Year 1 Year 2 Year 3 COMPLIANCE SCIT Subcutaneous immunotherapy SCIT Doctor visits < 25% SLIT Sublingual immunotherapy Daily administration 180 to 360 days/year < 12.5% 3 year long cumbersome treatment due to the use of whole allergen extracts 14

15 Whole allergen extract limitations Safety concerns: induction of histamine and proinflammatory substances Efficacy concerns: delay in reaching the optimal balance between IgG4 and IgE Allergen injectionsallergen Injections Symptoms IgG and IgG4 IgE Lymphocyte responses 15 6 months 2 years Time

16 ASIT Innovative technology 16

17 ASIT+ allergenic peptides allow short-course treatment improving patient adherence and compliance ASIT biotech s Offer 4 visits 4 doctor visits in 3 weeks before each pollen season 17

18 ASIT+ TM unique safe and efficient active ingredients Current Immunotherapy ASIT+ TM Immunotherapy Whole Allergens Advantages Clinically effective Safety: SLIT > SCIT Include all the necessary immunological information IgG 4 and blocking antibodies Applicable to all allergies Disadvantages Increased AEs 3 year treatment Poor patient compliance Need of adjuvants ASIT+ TM Technology Platform Optimally-sized natural allergenic peptides (1 10 kda) Short course SCIT Real-life clinical efficacy during grass pollen season confirmed Fast onset of optimal immunoregulation with blocking antibodies induction Applicable to all allergies No need of adjuvant Probable high patient adherence and compliance 18

19 ASIT+ TM technology platform to design, characterize, screen and produce novel product candidates Extraction of allergens from natural source Enzymatic hydrolysis Large proteins do not enter into the gel particles => shorter pathway through the column. ASIT+ TM allergenic peptides enter into the gel particles => longer pathway through the column. Selection of allergenic peptides according to size (1-10kDa) 19

20 ASIT Clinical Development 20

21 ASIT biotech pipeline: achieved milestones Pre-clinical Phase I Phase II Phase III Grass pollen gp-asit+ Q Positive phase III House dust mite Food Peanut - Egg white - Cow s milk hdm-asit+ Preclinical development program food-asit+ Q Positive Phase I/II 21

22 gp-asit+ Positive Phase III clinical study (BTT009) TRIAL # PATIENTS PRIMARY OBJECTIVE DESIGN Phase III 2:1 (active : placebo) 93% retention rate: 512 patients attended the last visit Clinical efficacy during pollen season based on reduction in the combined symptommedication score (CSMS) Double-blind Placebo controlled 67 centers in Europe symptom and drug intake reduction statistically significant -15.5% during the peak and -17.9% over the pollen season (p<0.05). all the results pointed to symptom improvement robust immunological results supporting the clinical efficacy and paving the road of the preclinical development of other ASIT+ TM products for other indications next Phase III in

23 ASIT mechanistic aspects Prof. Mohamed Shamji 23

24 Short Course treatment of Subcutaneous Peptide Hydrolysate from Lolium Perenne suppresses Basophil Responses and induces IgG-associated Blocking Antibodies: A RDPCT Mohamed Shamji, PhD. CS. FAAAAI Head, Immunomodulation and Tolerance Group Director, Immune Tolerance Network Distributed Centre of Excellence for Allergy & Asthma, UK Chair, Scientific Program Committee, European Academy, Allergy and Clinical Immunology Associate Professor in Immunology and Allergy, Allergy & Clinical Immunology, Imperial College London, UK 24 Media & Analyst Conference, Paris, France Thursday, 3rd May, 2018

25 Pathophysiology of Allergic Rhinitis and Mechanisms of AIT Natural exposure (Low-dose allergen) Dendritic cells (nasal mucosa) ILC2 Cell Th 0 CRTH2+ T cells Th2 Cell Tfh Cell CXCR5+ T cells IL- 9 IL- 5 IL-4 IL-21 IL-13 Mast Cell Eosinophi l B Cel l Basoph il Allergenspecific IgE Plasma Cell Shamji et al., JACI 25

26 SCIT Subcutaneous immunotherapy Year 1 Year 2 Year 3 SCIT doctor visits Compliance <25% SLIT Sublingual immunotherapy Daily administration 180 to 365 days/year <12.5% Novel Approach AIT 4-5 doctor visits 3 weeks prior each pollen season 26 Kiel et al., J Allergy Clin Immunol 2013;132:353-60

27 IgE binding (%) CD63+ basophils [%] Characterisation of Peptide Hydrolysate from Lolium Perenne (gpasit+ TM ) and its ability to bind to IgE compared to Grass Pollen extract Reproducibility Graph#8 Basophil activation e-4 0,001 0,01 0, Concentration Concentration [µg/ml] 4-P Fit: y = (A - D)/( 1 + (x/c)^b ) + D: A B C D R^2 Plot#2 (PROT 08J20 (1/3): Concentration vs %IN Plot#4 (PROT (1/3): Concentration vs %IN Pollen proteins - batch 1 Pollen proteins - batch 2 Plot#6 (PEP (1/3): Concentration vs %INHIB) Plot#10 (PEP 08K05 (1/3): Concentration vs %INH Weighting: Fixed Pollen peptides - batch 1 Pollen peptides - batch 2 Concentration [ng/ml] *p 0.05 **p 0.05 ***p 0.05 Shamji et al., JACI 2017

28 IgE binding (%) CD63+ basophils [%] Characterisation of Peptide Hydrolysate from Lolium Perenne (gpasit+ TM ) and its ability to bind to IgE compared to Grass Pollen extract Reproducibility Graph#8 Basophil activation e-4 0,001 0,01 0, Concentration Concentration [µg/ml] 4-P Fit: y = (A - D)/( 1 + (x/c)^b ) + D: A B C D R^2 Plot#2 (PROT 08J20 (1/3): Concentration vs %IN Plot#4 (PROT (1/3): Concentration vs %IN Pollen proteins - batch 1 Pollen proteins - batch 2 Plot#6 (PEP (1/3): Concentration vs %INHIB) Plot#10 (PEP 08K05 (1/3): Concentration vs %INH Weighting: Fixed Pollen peptides - batch 1 Pollen peptides - batch 2 Concentration [ng/ml] *p 0.05 **p 0.05 ***p 0.05 Shamji et al., JACI 2017

29 IgE binding (%) CD63+ basophils [%] Characterisation of Peptide Hydrolysate from Lolium Perenne (gpasit+ TM ) and its ability to bind to IgE compared to Grass Pollen extract Reproducibility Graph#8 Basophil activation e-4 0,001 0,01 0, Concentration Concentration [µg/ml] 4-P Fit: y = (A - D)/( 1 + (x/c)^b ) + D: A B C D R^2 Plot#2 (PROT 08J20 (1/3): Concentration vs %IN Plot#4 (PROT (1/3): Concentration vs %IN Pollen proteins - batch 1 Pollen proteins - batch 2 Plot#6 (PEP (1/3): Concentration vs %INHIB) Plot#10 (PEP 08K05 (1/3): Concentration vs %INH Weighting: Fixed Pollen peptides - batch 1 Pollen peptides - batch 2 Concentration [ng/ml] *p 0.05 **p 0.05 ***p 0.05 Shamji et al., JACI 2017

30 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+tm immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 30

31 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 31

32 Study design RDBCT Immune mechanisms analyses on participant from a single site - (Ghent, Belgium). Mechanistic analyses CSMS 32

33 CSMS during the peak pollen and the entire pollen season following LPP and Placebo CSMS Peak season CSMS Entire season Mösges and Shamji, Allergy

34 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) supresses CSMS and RTSS CSMS RTSS CSMS reduction in Belgium Peak period : -35.1%; P=0.03. Entire pollen season : -53,7%; P= Shamji MH et al, EAACI 2017 RTSS reduction in Belgium Peak period: -27.4%, P=0.04 Entire pollen season: -56.9%, P=0.01

35 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 35

36 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 36

37 Effect of LPP (gpasit+ TM ) immunotherapy on sige levels V8-V6 V2 = Before treatment V6 = After treatment V8 = After the grass pollen season 37 Shamji MH et al, EAACI 2017

38 Effect of LPP (gpasit+ TM ) immunotherapy on sige levels V8-V6 V2 = Before treatment V6 = After treatment V8 = After the grass pollen season 38 Shamji MH et al, EAACI 2017

39 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 39

40 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass pollen-induced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 40

41 Effect of gpasit+ TM and Placebo on CD203c high CRTH2 + Basophils * * * * * * * * * * * * 41 Shamji MH et al, EAACI 2017

42 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass pollen-induced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+ TM immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 42

43 Hypotheses - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+tm immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 43

44 Induction of Blocking antibodies following gpasit+ TM and Placebo Phleum Pratense Lolium Perenne * * 44 Shamji MH et al, EAACI 2017

45 Induction of blocking antibodies is associated with the induction of regulatory B cells in gpasit+ TM treated group. * * * * 45 Shamji MH et al, EAACI 2018

46 gpasit+ TM is associated with reduction of IL-4+Tfh cells induction of IFN-g+ Tfh cells and FoxP3+ Tfh cells * * * * * * 46 Sharif and Shamji MH et al, AAAAI 2017

47 Summary/Conclusions - 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpasit+ TM ) is associated with reduction in CSMS and RTSS during the peak and throughout the entire pollen season. - gpasit+ TM immunotherapy but not placebo blunts the seasonal increases of sige - gpasit+ TM immunotherapy but not placebo treatment suppresses grass polleninduced basophil hyperesponsivess and basophil reactivity. - A short-course of gpasit+tm immunotherapy induces IgG4-associated blocking antibodies that conferred clinical benefit during the pollen season and supresses pathogenic T cell responses. 47

48 Proposed Mechanisms of gpasit+ TM Natural exposure (Low-dose allergen) Dendritic cells (nasal mucosa) ILC2 Cell Th 0 CRTH2+ T cells Th2 Cell Tfh Cell CXCR5+ T cells IL-9 IL-5 IL-4 IL-21 IL-13 Mast Cell Eosinophi l B Cell Basophil Allergenspecific IgE Plasma Cell Immunotherapy (High-dose allergen) CTL-4 IL-10 Dendritic cells (under skin or oral mucosa) IL-27 Th 0 Th 1 Cel l itre TGF-β g + Tfr cell itreg IL-10 + ntre Foxp3 g + IL-10/IL-35 TGF-β Bregs cell Plasma Cell Allergen-specific IgG 4 & IgA IFN-γ IgG 4 and IgA competes with IgE for allergen binding 48 Shamji MH et al, JACI 2017

49 Acknowledgments Stephen Durham, MD.FRCP Oleksandra (Sasha) Fedina, Angeliki Karamani, BSc Rebecca Parkin, BSc Aliya Datoo Iesha Singh, MSc Lubna Kousar, PhD Hanisah Sharif, MSc Abigail Rob, Bsc 49 Jean Ceupens, MD Peter Helings, MD, Claus Bachert, MD, PhD Philip Gaevert, MD, PhD Lara Derycke, MD Gabrielle Holtapples, MSc Ralph Mösges, MD, PhD, Elena M. Kasche, MD, Esther Raskopf, PhD, Jaswinder Singh, MSc, Lea Sohlich Anatoli Astvatsatourov, PhD a, Kija Shah-Hosseini Ludo Haazen, MD Sabine Pirotton, PhD Nathalie Wathelet, PhD Marie-Alix Bonny Nicolas Bovy, PhD Julie Halkein, PhD Valeria Karusinova Gael Placier, PhD Jean Duchateau, MD, PhD Thierry Legon, MBA

50 hdm-asit+ for house dust mite rhinitis first in man clinical study: safety of ASIT+ TM confirmed TRIAL # PATIENTS AIM COMPLETED Phase I/IIa 36 patients randomized Assessment of the maximum tolerated dose Safety and clinical tolerability Immunogenicity Impact on reactivity to a challenge test Q patients treated with hdm-asit+ - 9 placebo. safety and tolerability of hdm-asit+ confirmed slight positive immunological and clinical impact in a limited number of treated patients new product prototypes in development to be tested by Prof. M. Shamji at ICL to optimize the product candidates immunogenicity 50

51 food-asit+ for food allergy product prototypes screening on-going PRE-CLINICAL DEVELOPMENT AIM COMPLETED Product prototype ex vivo screening Selection of product candidate peanut, cow s milk & egg white ex vivo safety and tolerability ex vivo immunogenicity Q non-dilutive funding from the Walloon Region to co-finance 55% 1 collaboration with Prof. M. Shamji (ICL), and Dr. S. Till (King s) first-in-man Phase I/II trial in peanut allergy expected to be conducted from H to end a recoverable cash advance granted in January 2017

52 ASIT biotech pipeline: next milestones Pre-clinical Phase I Phase II Phase III Grass pollen gp-asit+ FDA meeting - H Second Phase III Q Q House dust mite hdm-asit+ Selection of a new ASIT+ TM active ingredient - Q Second Phase I/II clinical trial with improved prototype - Q Food Peanut - Egg white - Cow s milk food-asit+ Selection of ASIT+ TM active ingredient for peanut - Q First Phase I/II clinical trial in food - H

53 Summary 53

54 Short course immunotherapy with ASIT biotech s allergenic peptides addresses the unmet needs of all stakeholders 4 visits/year Patient Efficient: Reduction of symptoms and rescue medication in the real life & Improved quality of life 4 doctor visits Time & Money saving Healthcare systems Documented safety and efficacy Improved acceptance Improved compliance Improved real-life efficacy Reduced direct & indirect costs Allergists New therapeutic option More patient accepting AIT Patients more compliant Fast onset of action Better patient follow-up Higher patient satisfaction 54

55 Paris May Leader in Allergenic Peptide Immunotherapy Merci pour votre attention! 55

56 Disclaimer THIS DOCUMENT AND ANY MATERIALS DISTRIBUTED IN CONNECTION WITH THIS DOCUMENT ARE NOT DIRECTED TO, OR INTENDED FOR DISTRIBUTION TO OR USE BY, ANY PERSON OR ENTITY THAT IS A CITIZEN OR RESIDENT OR LOCATED IN ANY LOCALITY, STATE, COUNTRY OR OTHER JURISDICTION WHERE SUCH DISTRIBUTION, PUBLICATION, AVAILABILITY OR USE WOULD BE CONTRARY TO LAW OR REGULATION OR WHICH WOULD REQUIRE ANY REGISTRATION OR LICENSING WITHIN SUCH JURISDICTION. THE DISTRIBUTION OF THIS DOCUMENT IN CERTAIN JURISDICTIONS MAY BE RESTRICTED BY LAW AND PERSONS INTO WHOSE POSSESSION THIS DOCUMENT COMES SHOULD INFORM THEMSELVES ABOUT, AND OBSERVE ANY SUCH RESTRICTIONS. This presentation has been prepared by the management of ASIT biotech SA (the Company). It does not constitute or form part of, and should not be construed as, an offer, solicitation or invitation to subscribe for, underwrite or otherwise acquire, any securities of the Company nor should it or any part of it form the basis of, or be relied on in connection with, any contract to purchase or subscribe for any securities of the Company, nor shall it or any part of it form the basis of or be relied on in connection with any contract or commitment whatsoever. This presentation is not a prospectus and recipients should not purchase, subscribe for or otherwise acquire any securities of the Company except on the basis of information in a prospectus or in the annual report approved by the FSMA. Copies of the prospectus and annual report issued are available on the website of the Company or at the Company s registered office. The information included in this presentation has been provided to you solely for your information and background and is subject to updating, completion, revision and amendment and such information may change materially. No person is under any obligation to update or keep current the information contained in this presentation and any opinions expressed in relation thereto are subject to change without notice. No representation or warranty, express or implied, is made as to the fairness, accuracy, reasonableness or completeness of the information contained herein. Neither the Company nor any other person accepts any liability for any loss howsoever arising, directly or indirectly, from this presentation or its contents. This presentation includes forward-looking statements that reflect the Company's intentions, beliefs or current expectations concerning, among other things, the Company s results, condition, performance, prospects, growth, strategies and the industry in which the Company operates. These forward-looking statements are subject to risks, uncertainties and assumptions and other factors that could cause the Company's actual results, condition, performance, prospects, growth or opportunities, as well as those of the markets it serves or intends to serve, to differ materially from those expressed in, or suggested by, these forward-looking statements. The Company cautions you that forward-looking statements are not guarantees of future performance and that its actual results and condition and the development of the industry in which the Company operates may differ materially from those made in or suggested by the forward-looking statements contained in this presentation. In addition, even if the Company's results, condition, and growth and the development of the industry in which the Company operates are consistent with the forward-looking statements contained in this presentation, those results or developments may not be indicative of results or developments in future periods. The Company and each of its directors, officers and employees expressly disclaim any obligation or undertaking to review, update or release any update of or revisions to any forward-looking statements in this presentation or any change in the Company's expectations or any change in events, conditions or circumstances on which these forward-looking statements are based, except as required by applicable law or regulation. In this presentation, references are made to the Company s product candidates, for which marketing authorisation has not yet been obtained. These product candidates are designated throughout this presentation by their internal project names at the Company. The names used are not meant to refer to these products (if and when they will be approved), as it is yet uncertain if and under what names these product candidates would be marketed in the future. Nothing in this presentation should be construed as endorsing or advertising such product candidates. 56

57 CONTACTS ASIT Biotech Thierry Legon CEO Tel.: investors@asitbiotech.com 57