GAME CHANGER IN IMMUNOTHERAPY
INVESTORS PRESENTATION
NON-CONFIDENTIALPRESENTATION
JANUARY 2019
Disclaimer
This presentation (“Presentation”) has been prepared by ASIT Biotech (“ASIT”) to provide an overview of the Company, it does not constitute a prospectus, an audit or due diligence review and should not be construed as such. While the information contained in this Presentation is believed to be accurate, 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 of its contents.
The Presentation includes forward looking statements and includes assumptions about future developments, operations and results. Although such statements are believed to be reasonable, there can be no assurances that such assumptions and views of the future are accurate, or that estimates and projections will be realized. 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. No representation, warranties or other assurances will be made by ASIT concerning the anticipated performance of the company.
This document and its contents may not be viewed by persons within the United States (within the meaning of Regulation S under the Securities Act) other than (i) by QIBs (qualified Institutional Buyers) or (ii) in “offshore transactions” within the meaning of Regulation S. 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 document 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 ASIT nor should it or any part of it from 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 from the basis of or be relied on in connection with any contract or commitment whatsoever.
2
WHO IS ASITBIOTECH ?
1
ASIT Biotech: Company Overview4
A CLINICAL STAGE
BIOPHARMACEUTICAL
COMPANY SPECIALIZED IN
ALLERGY IMMUNOTHERAPY
QUOTED ON THE BELGIAN
AND FRENCH STOCK
EXCHANGES
WWW.ASITBIOTECH.COM
ASIT HAS ROBUST SCIENTIFIC AND CLINICAL SUPPORT:
26 ACTIVE AND MOTIVATED COLLABORATORS AND
A NETWORK OF HIGH CALIBER COLLABORATIVE CENTERS
Raised €86 million since inception
€23.4M IPO (2016)
€15.4M private placement (2018)
€12M convertible bonds (2018)
Cash position (30.6.18) : €13.5 million, reinforced by
a €12 million convertible bond issued in July 2018.
ASIT Biotech: Management & Collaborators
MANAGEMENT
5
Michel Baijot, Managing Director & CEO
Yves Désiront, Director & CFO
Philippe Ghem, Chief Commercial Officer
Vincent Bille, VP CMC
Nicolas Bovy, Head of Research
Sabine Pirotton, Head of Project Management
Gilles Della Corte, Chief Medical Officer
Rémy von Frenckell, Head of Clinical Development
Vincent Theunissen, Head of Human Resources
DIRECTORSLouis Champion, Chairman
Michel Baijot , Managing Director
Refinance Consulting SA: Yves Désiront, Director & CFO
Everard van Straten, Director
Francois Meurgey, Director
Harry Welten, Director
Meusinvest: Philippe Degeer, Director
S.F.P.I.: François Fontaine, Director
Claus Bachert, MD, PhD
and Team
Stephen Durham, MD, FRCP
Mohamed Shamji
and Team
Ralph Mösges, MD, PhD
and Team
COLLABORATORS
THERE IS AN OPPORTUNITY IN EVERY CHALLENGE
2
PATIENTS
MARKET
DYNAMICS
* 7% severe, 58% moderate, 35% mild AR
ALLERGY
TREATMENT
MARKET IS
LARGE AND
GROWING
$12B
ONLY 45% ARE CORRECLTY DIAGNOSED*
400MPATIENTS
SUFFER
FROM
ALLERGIC
RHINITIS
(AR)
50%
DUE TO
DUST
MITE
55%
DUE TO
GRASS
POLLEN
MANY AR PATIENTS ARE
ALSO ASTHMATICS AND
ARE MORE LIKELY TO BE
RECEPTIVE TO A PREVENTIVE
APPROACH
The AIT market is <15% of the allergy drug market because of inefficient therapies
ALLERGOLOGISTS ARE EASY TO TARGET
< 100 REPS IN US AND < 100 REPS IN EU
7
1/3 OF PATIENTS WITH MODERATE TO
SEVERE AR ARE
NOT ADEQUATELY
CONTROLLED BY PHARMACOTHERAPY
ALLERGY
IMMUNOTHERAPY
MARKET
$1.8B
8
Long and cumbersome AIT treatments result in low acceptance and poor compliance
YEAR 1 YEAR 2 YEAR 3 TREATMENT SUCCESS
SCIT
SUBCUTANEOUS
IMMUNOTHERAPY
SLIT
SUBLINGUAL
IMMUNOTHERAPY
Only 50% of
patients offered
immunotherapy
accept it
40 TO 60 DOCTOR’S VISITS REQUIRED
DAILY DOSING UP TO 360 DOSES/YEAR
<10% of eligible
patients complete the
3 year treatment course**
Inefficient
intervention
generating a lot of
dissatisfaction
Eligible patients not
satisfied by
symptomatic treatments
COMPLIANCE*
End Y1
SCIT 80%
SLIT <40%
COMPLIANCE*
End Y2
SCIT <40%
SLIT <20%
* Source: Kiel MA et al. J Allergy Clin Immunol 2013; 132: 353-60
** (23% compliance for SCIT and 7% for SLIT after Y3)*acceptance rate (50%)
Inefficient
intervention
generating a lot of
dissatisfaction
PATIENTS
There is an opportunity in allergy immunotherapy (AIT) to migrate from old, inefficient therapies to a new generation of preventive treatment
9
ASIT BIOTECH
IS LEADING A
REVOLUTION IN
CREATION OF A
NEW GENERATION OF EFFECTIVE AND
EFFICIENT AIT
HUGE REMAINING
UNMET NEED
AND
MARKET POTENTIAL
CHANGE THE
GAME AND
BECOME A LEADER
IN THE FIELD
ASIT’S INNOVATIVE SOLUTION FOR AIT
3
ASIT has developed a versatile platform for allergy immunotherapy11
ASIT BIOTECH TREATMENTS CONSISTING OF A UNIQUE MIXTURE OF HIGHLY PURIFIED PEPTIDES FROM DIFFERENT SELECTED SIZES, PRODUCED FROM NATURAL SOURCES OF ALLERGENS, AND FREE OF ADJUVANT
THE ASIT+TM PLATFORM OFFERS:
A validated production process
at commercial scale
Validated QC procedures
A scalable solution that is
applicable to various allergens
(e.g., House Dust Mites, Peanuts)
Already available Ex-vivo
screening, immunogenicity and
therapeutic models
HIGH GRADE
PURIFICATION
OF ALL ALLERGENS
FROM NATURAL
EXTRACTS
STANDARD
ENZYMATIC
HYDROLYSIS
SELECTION OF
ALLERGEN
FRAGMENTS
BASED ON SIZE
DISTRIBUTION*
HIGHLY
PURIFIED
ALLERGEN
FRAGMENTS
WITH OPTIMAL
SIZE
DISTRIBUTION
* 1-10 kDa
Allergy is an inappropriate immune response against a harmless substance
Mast Cells
release histamine
and other pro-
inflammatory agents
Allergens are
processed by DC
activated by pro-
inflammatory agents
T Cells cause B Cells
to produce
pro-allergic IgE
antibodies
Dendritic Cells
activate
pro-allergic T Cells
IgE bind to
allergens and
attach to
Mast Cells
These chemicals
cause inflammation
and allergic symptoms
12
1 2 3 4 5 6
Sneezing Redness Severe Reaction
Cough Runny Nose
Allergic Reaction
B Cell
Plasma
Cell IgET CellDendritic Cell
Allergen
Histamine
IgE Bridging
Mast Cell
Mast Cells (and
Basophils) remain
inactive and do not
release histamine
ASIT allergen
fragments reprogram
the immune system
and activate
regulatory DC
Reg. T Cells cause Reg.
B Cells to produce
anti-allergic IgA
and IgG4 antibodies
+ reduction in IgE
Dendritic Cells
activate anti-allergic
Regulatory T Cells
IgA / IgG4 blocking
antibodies prevent
IgE antibodies from
binding allergens
There is no
inflammation or
allergic symptoms
1 2
3
4 5 6
Mast Cell
B Cell
Regulatory
B Cell
IgG4 / IgARegulatory T Cell
Regulatory
Dendritic Cell
gp-ASIT+TM
IgE bound
by gp-ASIT+ Inactive
Mast Cell
Allergen
gp-ASIT+™ allergy immunotherapy induces a natural regulation of the immune system in 3 weeks
Long term AIT
Pro inflammatory feedback
ASIT’s short course immunotherapy is much more efficient than current AIT13
YEAR 1 YEAR 2 YEAR 3 TREATMENT SUCCESS
CURRENT
IMMUNOTHERAPYCUMBERSOME SCHEDULE + POOR COMPLIANCE
UP TO 60 DOCTOR’S VISITS IN 3 YEARS
<10% of eligible
patients complete
the treatment course
ASIT+TM
IMMUNOTHERAPYMUCH EASIER SCHEDULE + BETTER COMPLIANCE
4 VISITS IN 3 WEEKS BEFORE EACH SEASON
Expected much higher
acceptance,
satisfaction and
compliance
ONLY 4 VISITS for gp-ASIT+™ treatment are expected to provide protection for the entire pollen season
…and protection mechanism are already in place 1 week after the last visit
European clinical development in grass pollen rhinitis14
Trial # patients Aim Timing Design
Phase IIaBTT007
65• Safety and clinical tolerability
• Immunogenicity
• Clinical efficacy assessed by CPT
2013
• Open-label
• Dose-escalation
• Single center in Germany
Phase IIbBTT008
200• Dose-finding assessed by CPT
• Immunogenicity
• Safety and clinical tolerability
2014
• Double-blind - placebo controlled
• Dose-escalation
• Multiple centers in Germany
Phase IIIBTT009
549• Clinical efficacy
• Safety and clinical tolerability2017
• Double-blind – placebo controlled
• 57 centers in Germany, Belgium,
France, Italy, Spain, Czech Republic
Phase IBTT004
27• Safety and clinical tolerability
• Immunogenicity 2010
• Double-blind - placebo controlled
• Dose-escalation
• Single center in Belgium
Note: CPT = conjunctival provocation test
✓
✓
✓
✓
Phase IIIABTT011
624• Clinical efficacy
• Safety and clinical tolerability2019
• Double-blind – placebo controlled
• 82 centers in Germany, Belgium,
France, Czech Republic, Hungary, Poland
Started
CLINICAL DATA FROM PHASE II AND PHASE III HAS BEEN PUBLISHED BY WORLD-CLASS SCIENTIFIC PARTNERS IN HIGHLY RANKED JOURNALS
In Phase III, gp-ASIT+™ demonstrated safety and efficacy15
PL: Placebo; LPP: Lolium Perenne Peptides (gp-ASIT+™)
* CSMS : Combined Symptom-Medication Score
** CPT: conjunctival provocation test (score from 1 to 4; most severe patients = CPT 3 & 4)
# ASIT received positive scientific advice from the German regulator, the Paul-Ehrlich Institute, and is now preparing a redesigned confirmatory Phase III study (First patient in planned in Jan 2019)
0
0,5
1
1,5
All patients Most severe**
CS
MS
Placebo
gp-ASIT+
CSMS OVER
ENTIRE
POLLEN
SEASON
P=0.03 P=0.05
0
0,5
1
1,5
2
All patients Most severe**
CS
MS
Placebo
gp-ASIT+
CSMS:
PEAK
POLLEN
PERIOD
P=0.04 P=0.05
17.9% 24.4%
15.5% 19.8%
In a Phase III study (BTT 009)
• gp-ASIT+™ resulted in a statistically significant improvement
in CSMS* during the peak pollen period and the entire pollen
season in the whole Phase III patient population
• The predefined absolute average 20% difference in CSMS*
between placebo and the treatment group was nearly achieved
over the peak season despite a poor results in Germany, which
was heavily weighted in the study#
• In a patient subgroup with the highest CPT** reactivity at
baseline (more than ½ of patients), CSMS* improvement was
even higher
Secondary endpoint
• Reactivity to the conjunctival provocation test (CPT) decreased
significantly in 60.0% of patients treated with gp-ASIT+™
compared with 35.6% in the placebo group
Reliable immunological data correlates with strong efficacy data *16
* Blood samples from a representative sub-group of Phase III patients in Belgium (n=32) were compared from V8 (after the grass pollen season) vs. V6 (after treatment before the pollen season)
** CSMS : Combined Symptom-Medication Score
The production of sIgE due to exposure
to natural allergens during the pollen
season was blunted in a sub-group of
Belgian patients* receiving gp-ASIT+™
compared to those receiving placebo
0
10
20
30
40
gp-ASIT+ Placebo
sIg
E(k
UA/L
) sp
ecif
ic
to g
rass
po
llen
P<.001
IgE PRODUCTION
DURING THE POLLEN SEASON
BELGIUM *
Data from 32 patients in Belgium
showed a 35% reduction in CSMS**
during the peak pollen period and
>50% reduction for the entire
pollen season (both highly
significant)
ABT 011CONFIRMATORY PHASE IIIFOR GP-ASIT+TM
4
ABT011 phase III study design18
‒ 1:1 (active : placebo)‒ 624 allergic patients
‒ PRIMARY : Clinical efficacy during pollen season based on reduction in the combined symptom-medication score (CSMS)
‒ SECONDARY : ‒ Safety and clinical tolerability‒ Immunogenicity (1 site in Belgium)
‒ Double-blind‒ Placebo controlled‒ 82 centers‒ 6 countries in Europe
(BE - CZ – DE – HU –FR – PO)
# PATIENTS OBJECTIVES DESIGN
Potential pitfalls of real-life exposure trials in grass pollen allergies
Addressing the complexity of
Operations
• overweighting of a centeror a country
• absence of pollen or out of order pollen traps
• weakly allergic patients' selection
• poor quality of medication use and symptom data due to a bad reporting by the patients
In gpASIT009:
3 CROs overseen by a reduced ASIT Team
30% of the patients had neither symptoms nor
medication intake during the season peak
Late start/recruitment
Pollen traps out of order around 2 large sites
Many missing data from patients (21.5% of patients
with less than 50% compliance to fill in the diary
19
1. The new Phase III study is subcontracted to a single Top Ten CRO experienced in allergy
studies, ICON.
2. Oversight is internally executed by a well-staffed clinical operations team including a
Team Leader with a 30-years clinical development experience, a Chief Medical Director with a
30-years clinical development experience, 2 Clinical Project Managers with 10-years clinical
development experience each.
3. Pollen count monitoring is centralized by the European Aeroallergen Network from the
University of Vienna in order to guarantee the reliability of the pollen count data used for
the statistical analysis.
4. High pollen count and high-quality data recording history has been used to select the
clinical centers.
9 Improvements to secure ASIT011 (1/2)20
Historical pollen data of the last 5 years provided by the European Aeroallergen Network (EAN)21
Site selection
Definition of patient visit planning
Sites
Bachert (Ghent)
Hellings (Leuven)
Rombaux (WSL)
Site
Volgmann (Hannover)
5. To avoid recruitment issues and overweighting of a single center or a country, 82 clinical
centers spread over 6 countries are involved in the current Phase III clinical study and each
center is limited to a maximum number of randomized patients.
6. A medical history over the last two years is required for each patient in order to select the
most allergic ones.
Only patients with moderate to severe RC during the 2017-2018 seasons based on strict criteria
(ARIA) AND significant sIgE level AND SPT wheal diameter
7. Online follow-up of the recruitment for each site according to a provisional agenda
established on historical grass pollen data over the last 5 seasons.
8. Paper diaries are replaced by electronic diaries (including an alert system) to significantly
improve patient engagement for better data recording and quality.
9. Earlier launch allowing a longer randomization and treatment period prior to the grass pollen
season.
9 Improvements to secure ASIT011 (2/2)22
Patient Recruitment
RECRUITMENT TARGET
23
Country # Sites # Screened# Randomized
in 2-2,5 months period
Enrollment Start
Date*
Enrollment End
Date**
Belgium 5 54 38 11-Jan-2019 03-Apr- 2019
Czech Republic 7 76 53 02-Jan-2019 25-Mar-2019
France 6 65 46 02-Jan-2019 17-Mar-2019
Germany 28 305 213 02-Jan-2019 03-Apr-2019
Hungary 9 98 69 02-Jan-2019 11-Mar-2019
Poland 27 294 205 02-Jan-2019 03-Apr-2019
Total 82 892 624
* start dates are country/site specific based on the start of the pollen season in the site area.
** end date is a conservative estimation based on the pollen data of the last 5 years provided by the
European Aeroallergen Network
24
ASIT+TM
PIPELINE
DEVELOPMENT:
HDM-ASIT+TM
25
Higher impact on asthmatic patients
Longer duration of exposure to the allergen
A recent market research confirmed the need for more convenient solutions
It is a global, growing epidemy
Higher unmet needs for House Dust Mites allergies (HDM) than for Grass pollen
26
House Dust Mite immunotherapy - hdm-ASIT+™
First Phase I/II showing
good safety and tolerability profile for the product candidate
no difference overall between treated group and placebo group with regard to immunogenicity parameters
Design of new prototypes with an immunogenicity profile equivalent to gp-ASIT+™
Characterization of the allergenicity and antigenicity of candidates in collaboration with Dr M. Shamji
Selection of a product candidate with an immunological profile equivalent to gp-ASIT+™
First-in-man
clinical trial
could start in
H2 2019
27
ASIT+TM
PIPELINE
DEVELOPMENT:
PNT-ASIT+TM
28
Most FA reactions are triggered by peanuts, milk, shell-fish, eggs, tree nuts and wheat.
However, peanut allergy is one of the most common and severe forms of FA, with a cumulative diagnosed prevalence of c. 6.0m18 both in the US and in the EU-5.
Caregivers reported a willingness-to-pay of USD20.8bn annually (USD3,504 per year per child) for food allergy treatment.
No treatment exists today for FA. 2 Pioneers have recently initiated an FDA submission for a Peanut AIT but they are far from offering an optimal solution, leaving substantial room for innovative therapies.
The immunotherapy market for Peanut allergies is estimated above $5 billions
Food allergies: 220m patients worldwide - A Leading cause of anaphylaxis
29
Program funded with 6 million euros by the Walloon Region to develop 3 new drug candidates for food allergies (peanut, cow’s milk and egg white)
First peptide-based product for immunotherapy of food allergy, using ASIT+™ platform
Selection of a product candidate with an immunological profile equivalent to gp-ASIT+™
Characterization of the allergenicity and antigenicity of candidates in collaboration with Dr M. Shamji
Completion of industrialization process for the manufacture of clinical batches of pnt-ASIT+™
Peanut immunotherapy - pnt-ASIT+™
First-in-man
clinical trial
could start in
H2 2019
ASIT Biotech expected milestones30
pnt-ASIT+™
(phase I)
Peanut:
pnt-ASIT+™
hdm-ASIT+™
(phase I )
House dust mite:
hdm-ASIT+™
Other food:
Egg white / cow’s milk
2019 2020
gp-ASIT+™
confirmatory phase IIIGrass pollen:
gp-ASIT+™
H1 H2 H1
Candidate Selection
FDA
Meeting
Results
Results*
Results*
Filing (GER)
H2
*Note: We are in contact with different compagnies for partnership and/or for the financing of our Phase 1
trials and we cannot predict the timing/outcome of those discussions
5 analysts
cover
ASIT biotech
Lead compound:
300-500 M€ peak sales
Early Pipeline:
>1 B€ peak sales
ANALYSTS PEAK SALES ESTIMATES
31
Peak sales per project Date Gp-ASIT(M€)
hdm-ASIT(M€)
Pnt-ASIT(M€)
Kepler Cheuvreux Nov 2018
360 300 860
Gilbert Dupont Nov 2018
384 325 N.A.
KBC Securities June 2016
280 240 N.A.
Bryan Garnier Sept2018
500 430 N.A.
Edison May 2018
403 373 1448
Valuations only consider US & EU5, leaving significant HDM market potential in Asia
ANALYSTS COVERAGE
Analyst Reco Target Price *
KBC Securities Hold 2,00 €
Kepler Cheuvreux Buy 3,00 €
Gilbert Dupont Accumulate 4,50 €
Bryan Garnier Corporate 4,50 €
Edison Corporate 6,30 €
32
* This information does not constitute an offer to sell or subscribe, or the solicitation
of an order to buy or subscribe for securities in France, Europe, the US or any other
country. Corporate: ASIT biotech have agreed on a service for the production and
distribution of financial analyses with Edison and Bryan Garnier. Status 16 Jan 2019.
SUMMARY4
Near-term critical milestones impacting company valuation
Phase III, low-risk innovative product opportunity for grass pollen allergy
immunotherapy with results expected in Q4 2019
Access to a pipeline of products for food and house dust mite allergies,
using a similar small peptide approach with strong IP, aiming at changing the
game in allergy immunotherapy. Start PhI/II in 2019.
First launch expected in 2-3 years
Additional clinical milestones supporting the efficacy/safety of our pipeline
OPPORTUNITY FOR A
POTENTIAL INVESTOR
* An allergy to grass pollen is the largest cause of allergic rhinitis, impacting millions of patients
34An investment opportunity in a new franchise with a novel approach to allergy immunotherapy
Short term opportunity (Around 12 months)
Mid term opportunity
Mid to Long term opportunity (commercialization together with committed partners)
▪ Low capitalization compared to
a solution adapted to millions of
patients
▪ Our technology adapts to most
allergies, a fast-growing market
with no real effective solution
An opportunity to gain market leadership in a large growing market with gp-ASIT+™,
a short course preventive treatment (3 weeks treatment), acting already 1 week after treatment completion
We plans to address the market in partnership with major players to continue the development and
the commercialization of gp-ASIT+™ and/or ASIT’s pipeline of potential new products, preferably through equity
www.asitbiotech.com
Registered address
Avenue Ariane 5
1200 Brussels, Belgium
Operations
Rue des Chasseurs Ardennais 7,
4031 Liège, Belgium
Contact: [email protected]