ASIT biotech Philippe Ghem, CCO Everard van der Straten, CFO · symptom and drug intake reduction...

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July 2018 Leader in Allergenic Peptide Immunotherapy

ASIT biotechPhilippe Ghem, CCOEverard van der Straten, CFO

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About ASIT biotech

Our 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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ASIT biotech has dual market listing in Brussels (Belgium) and Paris (France) since May 2016 (Isin : BE0974289218, Tiker : ASIT)

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:

About ASIT biotech

ASIT biotech on the stock market

Market data• Market: Euronext Brussels and Paris

• IPO price: €7.00 (11/05/2016)

• Current price: €4.049 (16/11/2017)

• Highest: €8.399

• Lowest: €3.150

• Number of shares (fully diluted) : 13,056,600

• Average volume: 10,760 shares / day (sinceIPO)

Stock market codes • Name: ASIT

• Ticker: ASIT

• ISIN code: BE0974289218

Change in stock price since the IPO

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1. Ever increasing number of allergic patients

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Over 1 billion patients suffer today from Allergyand 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.

(in M) USA Europe China Japan

Population 320 320 1379 127

with Rhinitis 43 73 TBD 38

with severe Rhinitis 24 25 TBD 9

USA12-30%

EUROPE23-30%

CHINA1,6-43%

LATIN AMERICA5,5-45,1%

AFRICA7,2-54,1%

AUSRALIA12-41,3%

JAPAN/KOREA9,1-35,7%MIDDLE EAST

7,4-45,2%


SOUTH EAST ASIA5,5-44,2%

Allergic rhinitis & asthma : $20 billion/year

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15 million of American, 17 million of Europeans suffer from food allergy 1.

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: $ 4,1844.

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


No Drugs available, excepted Epinephrine injection

8…if not threathening life…

Reduced work productivity

Eye symptoms

Nasalsymptoms

Sleep deprivation

Reducedschool performance

AngiodemaAsthma

Allergy leads to symptoms impairing 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

production

3. Loading of allergen specific IgE on mast cells

4. Bridging of the IgE by allergens

5. Allergic reaction


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2. 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.

1. Prevention of the seasonal increase of IgE.

2. Induction of IgG4-associated blocking antibodies leading to clinical benefit during the pollen season.

3. 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 € 1 billion 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 treatmentdue to the use of whole allergen extracts


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3. ASIT™ Innovative technology

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ASIT+™ allergenic peptides allow short-course treatmentimproving 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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4. ASIT™ Clinical Development

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ASIT biotech pipeline : achieved milestones

Pre-clinical Phase I Phase II Phase III

Grass pollenQ1 2017 Positive phase III(Safety & Efficacy)gp-ASIT+™

hdm-ASIT+™

Q2 2017Positive Phase I/II(Safety)

House dust mite

Preclinical development program

food-ASIT+™

FoodPeanut - Egg white - Cow’s

milk

4. ASIT™ Clinical Development

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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.

‒ 549 patients randomized

‒ 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‒ 2:1 (active : placebo)‒ 67 centers in Europe

TRIAL # PATIENTS PRIMARY OBJECTIVE DESIGN

Phase III

4. gp-ASIT+™ Clinical Development

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4. gp-ASIT+™ Clinical Development

Ig E

CD 203

CD 63+

Increase Immunogenicity *

Lower allergenicity (histamine release) *

T Cells stimulation

B Cells stimulation

Ig G4 (blocking Ab)

gp-Asit+TM Immunological signature validates the efficacy results

CSMS reduction in Belgium

Peak period : -35.1% (P=0.03)

Entire pollen season : -53,7% (P=0.03)

* Blood samples from Phase III

(representative subgroup : Belgium, n=33)

V6 V8

++++ ++++

++++ ++++

++++ ++++

V6 V8

- - - - - - - -

- - - - - - - -

- - - - - - - -

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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(improved)

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 2018

First Phase I/II clinical trial in food - H2 2018

5. ASIT™ mechanistic aspects

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Results

Results

Results

Expected clinical development timeline

gp-ASIT+™

2018 2019 2020 2021

H1 H2 H1 H2 H1 H2 H1 H2

ResultsPhase I/II Phase II

Phase III Short-term efficacy in adults

hdm-ASIT+™

Food-ASIT+™

Peanut

Others

2nd Phase III Short-term

efficacy in adults

Phase IIb if necessary

Registration

Selection of a second product candidate

Results ResultsPhase I/II Phase IISelection of a second product candidate

Preclinical development

Results ResultsPhase I/II Phase II

Pre-IND meeting with FDA



Selection of a second product candidate

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5. Summary

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

Patient

• Real reduction of symptomsand Improved quality of life

• Reprogrammation of theimmune system

Healthcare systems

• Documented safety and efficacy.

• Reduced direct & indirect costs (4 doctor visits vs >10 visits).

Allergists

• True innovative solution

• More patient accepting AIT, means more revenue

• Higher patient satisfaction

4 visits/year

6. Summary

… which should increase the AIT market

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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 ofinformation 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 theCompany 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.

DISCLAIMER

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CONTACTS

ASIT Biotech

Philippe GHEM– CCO

Tel.: +32 2 264 03 98

[email protected]

www.asitbiotech.com

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6. Annex (Mohamed Shamji, PhD. CS. FAAAAI)

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Short Course treatment of Subcutaneous Peptide Hydrolysate from LoliumPerenne 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, 2018

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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

Shamji MH et al, EAACI 2017


gpASIT+TM blunts the seasonal increases of sIgE (compared with Placebo)

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Effect of gpASIT+TM and Placebo on CD203chighCRTH2+ Basophils

****

*

******

*



gpASIT+TM suppresses grass pollen induced basophil hyperesponsivnessand basophil reactivity

gpASIT+TMIMPACT

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3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP, gpASIT+TM) supresses CSMS1 and RTSS 2

CSMS 1 RTSS 2

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



1 CSMS : Combined Symptom-Medication Score2 RTSS : Rhinoconjunctivitis Total Symptom Score

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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 andthroughout 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 blockingantibodies that conferred clinical benefit during the pollen season and supressespathogenic T cell responses.


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Pollen proteins - batch 1

Pollen proteins - batch 2

Pollen peptides - batch 1

Pollen peptides - batch 2

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[%

]

Shamji et al., JACI 2017

Reproducibility

Characterisation of Peptide Hydrolysate from Lolium Perenne (gpASIT+TM)and its ability to bind to IgE compared to Grass Pollen extract


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Hypotheses

3-week treatment with subcutaneous peptide hydrolysates from Lolium perenne (LPP,gpASIT+TM) is associated with reduction in CSMS1 and RTSS2 during the peak andthroughout the entire pollen season.

gpASIT+TM immunotherapy but not placebo blunts the seasonal increases of sIgE




1 CSMS : Combined Symptom-Medication Score2 RTSS : Rhinoconjunctivitis Total Symptom Score

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Study design – RDBCT

CSMS

Mechanistic analyses

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

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CSMS1 during the peak pollen and the entire pollen season following LPP and Placebo

CSMS – Peak seasonCSMS1 – PEAK season CSMS1 – ENTIRE season

Mösges and Shamji, Allergy 2018


1 CSMS : Combined Symptom-Medication Score

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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 SS during the peak andthroughout the entire pollen season.





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

V8-V6



V8 = After the grass pollen season Shamji MH et al, EAACI 2017


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Hypotheses






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Effect of gpASIT+TM and Placebo on CD203chighCRTH2+ Basophils

****

*

******

*



gpASIT+TM DIMINUE CLAIREMENT LES MANIFESTATIONS ALLERGIQUES

gpASIT+TMIMPACT

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Hypotheses






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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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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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6. Board of DirectorsBoard of Directors

Gerd Zettlmeissl,Chairman of the Board

Working in the biopharma & vaccine industry since 1985 : e.g. former CEO of the Austrian-based biotech Valneva SE (formerly Intercell AG), chairman of the

Board of GlycoVaxyn 2013-2015, member of the Board of Aeras

Thierry Legon,CEO

Everard van der Straten, Director and CFO

François Meurgey,Director

Jean Duchateau,Director & Co-founder

Allergist. One of the inventor of the 1st patents on toleranceinduction to allergy and graft

rejection, new LED tests, ownedby ASIT biotech

RE Finance Consulting SA, Independent Director

(represented by Yves Désiront)

Bruservices SA (represented by Henri De Meyer)

Meusinvest SA (representedby Marc Foidart)

Business AngelFounder & CEO Past VP, UCB

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Paris May 29 2018 Leader in Allergenic Peptide Immunotherapy

Thanks for your attention

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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+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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AIT market < 10% of the allergy drug market


Sources: Global Data “Allergic Rhinitis Immunotherapy Market 2018” (Sep-2014) ALK-

Abelló, Stallergènes and Allergy Therapeutics annual reports

A small marketlacking treatmentsboth easy to take

and effective

A good product can have a billion euros potential

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According to WHO statistics, allergies are the 4th global pathology after cancers, AIDS andcardiovascular diseases.

WHO predicts that in 2050, 1 in 2 people worldwide will suffer from allergies. We arewitnessing a resurgence of allergies whose rate is constantly increasing, especially inindustrialized countries.

Today, nearly 30% of the world's population suffer from allergies (respiratory, dietary,cutaneous, ...) against 3.8% in 1968. Food allergies, particularly common in young children,are constantly increasing in recent years. In France, the number of people suffering from anallergy has doubled in 20 years, especially among children and adolescents. 8% of childrenand 4% of the adult population suffer from a food allergy.

In France, asthma affects nearly 4 million people, one-third of whom are under 15 years ofage. In less than 20 years, the number of asthmatic adolescents has increased by more than40%.

In the United States, hay fever (allergic rhinitis) is diagnosed in 17.9 million adults, or about7.8% of the population.

Along with the increase in the number of people with allergies, the characteristics of allergymanifestations have evolved in recent years becoming more severe and persistent longer.People who have had severe protests and who need urgent consultation have beenmultiplied by 40 for 10 years.

All in all, in 30 years the prevalence x2 X3 an the frequency of severe and potentially fatalforms: x4 to 5 in 30 years (asthma and food allergies)

IDEES A RAJOUTER EVENTUELLEMENT

Prevalence of asthma and allergic rhinitis

Source : XXX

ASIT biotech Philippe Ghem, CCO Everard van der Straten, CFO · symptom and drug intake reduction...

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