Thierry Legon CEO, ASIT biotech...26 Year 1 Year 2 Year 3 SCIT Subcutaneous immunotherapy SLIT Sublingual immunotherapy Daily administration 180 to 365 days/year SCIT 40-60 doctor

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Paris May 03 2018 Leader in Allergenic Peptide Immunotherapy

Thierry LegonCEO, ASIT biotech

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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)

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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

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Ever increasing number of allergic patients

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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

World Allergy Week April 2011EAACI

✓ Over 400 million patients suffer from Allergic Rhinitis✓ Over 200 million patients suffer from Food allergies✓ Over 300 million patients suffer from Asthma

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Allergic Rhinitis:up to 400 million people worldwide

Bauchau V & Durham SR Eur Respir J 2004; 24: 758-764 Katelaris, C.H. et al., 2012. Clinical and experimental allergy 42(2), pp.186–207C.F., M. & Tong Janice S.C. Lin, 2015. European Academy of Allergy and Clinical Immunology, pp. 62–63.

USA Europe China Japan

Population (M) 320 320 1379 127

Population withRhinitis (M)

43 73 TBD 38

Population withsevere Rhinitis (M)

24 25 TBD 9

USA12-30%

EUROPE23-30%

CHINA1,6-43%

LATINAMERICA5,5-45,1%

AFRICA7,2-54,1%

AUSRALIA12-41,3%

JAPAN9,1-37,5%

MIDDLE EAST7,4-45,2%

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• 15 million of American, 17 million of Europeans suffer from food allergy1

• Increasing prevalence in both developed and developing countries2

• Peanut, cow’s milk and egg white concern >74% children3

• Total annual food allergy management cost estimate/child in the US: $ 4,184

1. Commins et al. 2016 and World Allergy Organization2. Prescott et al. 20133. Scott et al. 20114. Gupta et al 2013

Food Allergy:more than 200 millions people worldwide

8…if not threathening life…

Reduced work productivity

Eye symptoms

Nasalsymptoms

Sleep deprivation

Reducedschool performance

AngiodemaAsthma

Allergy leads to symptomsimpairing quality of life

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Allergy: inappropriate immune response against harmless substance

Th2

cell

BasophilMast cell

B cell

Eosinophils

recruitment and activation

Allergens

Antigen

Presenting

cell

Degranulation leading to

histamine release

IgE

synthesis

BasophilMast cell

1

54

3

2

1. First contact between allergen and mucosa

2. Allergen specific IgE antibody production

‒ Uptake & processing by APC

‒ T- cell activation‒ allergen specific IgE

antibody production3. Loading of allergen specific IgE on

mast cells4. Bridging of the IgE by allergens5. Allergic reaction

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Therapeutic options: Symptomatic vs Curative

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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

AntihistaminesZyrtecXyzal

AllegraClaritin

IgE-specific blockers (mAb)

Omalizumab (Novartis/Genentech)

Interleukin specific blockers (mAb)

Mepolizumab (GSK)Reslizumab (Teva)Benralizumab (AZ)

Dupilumab(Regeneron/Sanofi)

Nonspecific immunosuppressorsIntranasal steroids

Inhaled steriodsLeukotriene modifiers

B cell

Th2

cell

IgE

synthesis

BasophilMast cell Eosinophils

recruitment

and

activation

Allergen

Antigen

Presenting

cell

Degranulation

leading to

histamines

release

BasophilMast cell

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Sub-cutaneous Sublingual

Curative treatment: Allergy Immunotherapy

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1. Regulatory T and B cells 2. Prevention of the seasonal

increase of IgE3. Induction of IgG4-associated

blocking antibodies leading to clinical benefit during the pollen season.

4. Suppression of grass pollen-induced basophil activation responsible for immediate allergic response

Th2

cell

IgE synthesis

BasophilMast cell Eosinophils

recruitment and

activation

Allergen

Antigen

Presenting

cellWhole Allergens

BasophilMast cell

Treg

cell Breg

cell

B cell IgG4 & IgA

synthesis

-

-

-

+

+ IL-1

0IL

-35

1

2

3

2

4

Degranulation leading to

histamine release

Allergy immunotherapy induces natural regulation of the immune system and provides better symptoms reduction

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Allergy immunotherapy market less than €1billion today

SCITSubcutaneous

immunotherapy

SLITSublingual

immunotherapy

Year 1 Year 2 Year 3

SCIT 40-60Doctor visits

Daily administration

180 to 360 days/year

COMPLIANCE

< 25%

< 12.5%

3 year long cumbersome treatment due to the use of whole allergen extracts

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Whole allergen extract limitations

Allergen injections

IgG and IgG4

IgE

Lymphocyte responses

6 months 2 years

Allergen Injections

Time

Symptoms

Safety concerns: induction of histamine and proinflammatory substances

Efficacy concerns: delay in reaching the optimal balance between IgG4 and IgE

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ASIT™ Innovative technology

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ASIT+™ allergenic peptides allow short-course treatment improving patient adherence and compliance

4 doctor visits in 3 weeks before each pollen season

4 visits

ASIT biotech’sOffer

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ASIT+TM Immunotherapy

✓ 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

Optimally-sized

natural allergenic peptides

(1 – 10 kDa)

Current Immunotherapy

Whole Allergens

Advantages

✓ Clinically effective

✓ Safety: SLIT > SCIT

✓ Include all the necessary immunological information

✓ IgG4 and blocking antibodies

✓ Applicable to all allergies

Disadvantages

Increased AEs

3 year treatment

Poor patient compliance

Need of adjuvants

ASIT+TM unique safe and efficient active ingredients

ASIT+TM Technology Platform

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ASIT+TM technology platform to design, characterize, screen and produce novel product candidates

Large proteins do not enter into the gel particles=> shorter pathway through the column.

ASIT+TM allergenic peptides enter intothe gel particles=> longer pathway through the column.

Extraction of allergens from natural source

Enzymatic hydrolysis

Selection of allergenic peptides according to size

(1-10kDa)

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ASIT™ Clinical Development

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ASIT biotech pipeline: achieved milestones

Pre-clinical Phase I Phase II Phase III

Grass pollen

Q1 2017 - Positive phase III

gp-ASIT+™

hdm-ASIT+™

Q2 2017 - Positive Phase I/II

House dust mite

Preclinical development program

food-ASIT+™

FoodPeanut - Egg white - Cow’s milk

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gp-ASIT+™ Positive Phase III clinical study (BTT009)

• 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 2019

‒ 2:1 (active : placebo)‒ 93% retention rate: 512

patients attended the last visit

‒ Clinical efficacy during pollen season based on reduction in the combined symptom-medication score (CSMS)

‒ Double-blind‒ Placebo controlled‒ 67 centers in Europe

TRIAL # PATIENTS PRIMARY OBJECTIVE DESIGN

Phase III

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ASIT™ mechanistic aspects

Prof. Mohamed Shamji

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

Media & Analyst Conference, Paris, France

Thursday, 3rd May, 201824

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ILC2Cell

Th2Cell

B Cel

l

Eosinophil Plasma

Cell

Th0

Mast CellAllergen-

specific IgE

Natural exposure(Low-dose allergen)

Dendritic cells(nasal mucosa)

Basophil

Pathophysiology of Allergic Rhinitis and Mechanisms of AIT

TfhCell

CRTH2+ T cells

CXCR5+ T cells

IL-5

IL-9

IL-4IL-21IL-13

Shamji et al., JACI

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Year 1 Year 2 Year 3

SCITSubcutaneous

immunotherapy

SLIT

Sublingual immunotherapy

Daily administration

180 to 365 days/year

SCIT 40-60 doctor visits

4-5 doctor visits 3 weeks prior each

pollen season

Novel

Approach AIT

Compliance

<25%

<12.5%

Kiel et al., J Allergy Clin Immunol 2013;132:353-60

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Pollen proteins - batch 1


Pollen peptides - batch 1


Basophil activation

*p ≤ 0.05

**p ≤ 0.05

***p ≤ 0.05

Concentration [µg/ml]

1e-4 0,001 0,01 0,1 1 10 100 1000

0

20

40

60

80

Graph#8

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... -0.72 0.973 0.0861 95.7 0.999

Plot#4 (PROT 00597 (1/3): Concentration vs %IN... 4.86 0.835 0.0905 97.9 1

Plot#6 (PEP 00597 (1/3): Concentration vs %INHIB) -8.18 0.269 136 143 0.999

Plot#10 (PEP 08K05 (1/3): Concentration vs %INH... -12.8 0.227 497 170 0.998__________

Weighting: Fixed

IgE

bin

din

g (

%)

Concentration [µg/ml] Concentration [ng/mL]

CD

63

+ b

aso

ph

ils[%

]

Reproducibility

Characterisation of Peptide Hydrolysate from Lolium Perenne

(gpASIT+TM) and its ability to bind to IgE compared to Grass Pollen

extract

Shamji et al., JACI 2017

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Basophil activation

*p ≤ 0.05

**p ≤ 0.05

***p ≤ 0.05


1e-4 0,001 0,01 0,1 1 10 100 1000

0

20

40

60

80

Graph#8






Weighting: Fixed

IgE

bin

din

g (

%)


CD

63

+ b

aso

ph

ils[%

]



extractReproducibility


29





Basophil activation

*p ≤ 0.05

**p ≤ 0.05

***p ≤ 0.05


1e-4 0,001 0,01 0,1 1 10 100 1000

0

20

40

60

80

Graph#8






Weighting: Fixed

IgE

bin

din

g (

%)


CD

63

+ b

aso

ph

ils[%

]


Reproducibility



extract

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Hypotheses

- 3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne(LPP, gpASIT+TM) is associated with reduction in CSMS and RTSS during thepeak and throughout the entire pollen season.

- gpASIT+TM immunotherapy but not placebo blunts the seasonal increases ofsIgE

- 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-associatedblocking antibodies that conferred clinical benefit during the pollen season andsupresses pathogenic T cell responses.

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Hypotheses

- 3-week treatment with subcutaneous peptide hydrolysates from Loliumperenne (LPP, gpASIT+TM) is associated with reduction in CSMS andRTSS during the peak and throughout the entire pollen season.



- A short-course of gpASIT+TM immunotherapy induces IgG4-associated blockingantibodies that conferred clinical benefit during the pollen season andsupresses pathogenic T cell responses.

Study design – RDBCT

CSMS

Mechanistic analyses

Immune mechanisms analyses on participant from a single site - (Ghent, Belgium).

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CSMS during the peak pollen and the entire pollen season following LPP and Placebo

CSMS – Peak seasonCSMS – Peak season CSMS – Entire season

Mösges and Shamji, Allergy 2018

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3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpASIT+TM) supresses CSMS and

RTSS

CSMS RTSS

CSMS reduction in BelgiumPeak period : -35.1%; P=0.03.Entire pollen season : -53,7%; P=0.03

RTSS reduction in Belgium

Peak period: -27.4%, P=0.04

Entire pollen season: -56.9%, P=0.01

Shamji MH et al, EAACI 2017

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Hypotheses

- 3-week treatment with subcutaneous peptide hydrolysates from Loliumperenne (LPP, gpASIT+TM) is associated with reduction in CSMS andRTSS during the peak and throughout the entire pollen season.




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Hypotheses


- gpASIT+TM immunotherapy but not placebo blunts the seasonal increasesof sIgE



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V8-V6

V2 = Before treatment

V6 = After treatment

V8 = After the grass pollen season

Effect of LPP (gpASIT+TM) immunotherapy on sIgE levels


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Effect of LPP (gpASIT+TM) immunotherapy on sIgE levels

V8-V6

V2 = Before treatment

V6 = After treatment

V8 = After the grass pollen season


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Hypotheses


- gpASIT+TM immunotherapy but not placebo blunts the seasonal increasesof sIgE



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Hypotheses



- gpASIT+TM immunotherapy but not placebo treatment suppresses grasspollen-induced basophil hyperesponsivess and basophil reactivity.


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Effect of gpASIT+TM and Placebo on CD203chighCRTH2+

Basophils

****

*

******

*


42

Hypotheses



- gpASIT+TM immunotherapy but not placebo treatment suppresses grasspollen-induced basophil hyperesponsivess and basophil reactivity.


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Hypotheses




- A short-course of gpASIT+TM immunotherapy induces IgG4-associatedblocking antibodies that conferred clinical benefit during the pollenseason and supresses pathogenic T cell responses.

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Induction of Blocking antibodies following gpASIT+TM and Placebo

Lolium PerennePhleum Pratense

* *


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Induction of blocking antibodies is associated with the induction of regulatory B cells in gpASIT+TM treated group.

*

* * *


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gpASIT+TM is associated with reduction of IL-4+Tfh cells induction of IFN-g+ Tfh cells and FoxP3+ Tfh cells

* ** *

* *

Sharif and Shamji MH et al, AAAAI 2017

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Summary/Conclusions




- A short-course of gpASIT+TM immunotherapy induces IgG4-associatedblocking antibodies that conferred clinical benefit during the pollen season andsupresses pathogenic T cell responses.

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ILC2Cell

Th0

IL-27

Immunotherapy(High-dose allergen)

Dendritic cells (under skin or oral

mucosa)

Th2Cell

B Cell

Eosinophil Plasma Cell

Th0

Mast CellAllergen-

specific IgE

Natural exposure(Low-dose allergen)

Dendritic cells(nasal mucosa)

Basophil

Proposed Mechanisms of gpASIT+TM

TfhCell

Th1

Cell

IFN-γ

Bregscell

IL-10/IL-35 Allergen-specificIgG4 & IgA

IgG4 and IgAcompetes with IgE for allergen

binding

TGF-β

Plasma Cell

IL-10

iTreg

IL-10+

nTregFoxp3+

iTregTGF-β+

Tfrcell

CTL-4

CRTH2+ T cells

CXCR5+ T cells

IL-5

IL-9

IL-4IL-21IL-13

Shamji MH et al, JACI 2017

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Acknowledgments

Angeliki Karamani, BSc

Rebecca Parkin, BSc

Aliya Datoo

Iesha Singh, MSc

Lubna Kousar, PhD

Hanisah Sharif, MSc

Abigail Rob, Bsc

Stephen Durham, MD.FRCP

Oleksandra (Sasha) Fedina,

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

Ralph Mösges, MD, PhD,

Elena M. Kasche, MD,

Esther Raskopf, PhD,

Jaswinder Singh, MSc,

Lea Sohlich

Anatoli Astvatsatourov, PhDa, Kija

Shah-Hosseini

Claus Bachert, MD, PhD

Philip Gaevert, MD, PhD

Lara Derycke, MD

Gabrielle Holtapples, MSc

Jean Ceupens, MD

Peter Helings, MD,

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hdm-ASIT+™ for house dust mite rhinitisfirst in man clinical study: safety of ASIT+TM confirmed

• 27 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

‒ 36 patients randomized‒ Assessment of the maximum tolerated

dose ‒ Safety and clinical tolerability‒ Immunogenicity ‒ Impact on reactivity to a challenge test

‒ Q2 2017

TRIAL # PATIENTS AIM COMPLETED

Phase I/IIa

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‒ Selection of product candidatepeanut, cow’s milk & egg white

‒ ex vivo safety and tolerability‒ ex vivo immunogenicity

‒ Q2 2018

PRE-CLINICAL DEVELOPMENT AIM COMPLETED

Product prototype ex

vivo screening

food-ASIT+™ for food allergyproduct prototypes screening on-going

• 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 H1 2018 to end-2019

1 a recoverable cash advance granted in January 2017

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ASIT biotech pipeline: next milestones

Pre-clinical Phase I Phase II Phase III

Grass pollen

gp-ASIT+™ FDA meeting - H2 2018Second Phase III Q4 2018 - Q4 2019

hdm-ASIT+™House dust mite

Selection of a new ASIT+TM active ingredient - Q2 2018Second Phase I/II clinical trial with improved prototype - Q1 2019

FoodPeanut - Egg white - Cow’s milk

food-ASIT+™ Selection of ASIT+TM active ingredient for peanut - Q2 2018First Phase I/II clinical trial in food - H2 2018

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Summary

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Short course immunotherapy with ASIT biotech’s allergenic peptides addresses the unmet needs of all stakeholders

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

4 visits/year

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Paris May 03 2018 Leader in Allergenic Peptide Immunotherapy

Merci pour votre attention !

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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 SUCHJURISDICTION. THE DISTRIBUTION OF THIS DOCUMENT IN CERTAIN JURISDICTIONS MAY BE RESTRICTED BY LAW AND PERSONS INTO WHOSE POSSESSION THISDOCUMENT 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 berelied 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 inconnection 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 andamendment and such information may change materially. No person is under any obligation to update or keep current the information contained in this presentationand 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 losshowsoever 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, theCompany’s results, condition, performance, prospects, growth, strategies and the industry in which the Company operates. These forward-looking statements aresubject to risks, uncertainties and assumptions and other factors that could cause the Company's actual results, condition, performance, prospects, growth oropportunities, 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-lookingstatements. The Company cautions you that forward-looking statements are not guarantees of future performance and that its actual results and condition and thedevelopment of the industry in which the Company operates may differ materially from those made in or suggested by the forward-looking statements contained in thispresentation. In addition, even if the Company's results, condition, and growth and the development of the industry in which the Company operates are consistent withthe forward-looking statements contained in this presentation, those results or developments may not be indicative of results or developments in future periods. TheCompany and each of its directors, officers and employees expressly disclaim any obligation or undertaking to review, update or release any update of or revisions toany forward-looking statements in this presentation or any change in the Company's expectations or any change in events, conditions or circumstances on whichthese 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 productcandidates are designated throughout this presentation by their internal project names at the Company. The names used are not meant to refer to these products (ifand 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 presentationshould be construed as endorsing or advertising such product candidates.

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CONTACTS

ASIT Biotech

Thierry Legon – CEO

Tel.: +32 2 264 03 90

[email protected]

www.asitbiotech.com

Documents

Thierry Legon CEO, ASIT biotech...26 Year 1 Year 2 Year 3 SCIT Subcutaneous immunotherapy SLIT Sublingual immunotherapy Daily administration 180 to 365 days/year SCIT 40-60 doctor