AB Science — Regulatory Filings 2011

Jan 17, 2011

Paris,!January!17th,!2011!2!8:45!am

AB#Science#announces#authorization#to#initiate#phase#2#in#stomach# cancer#with#masitinib

Masitinib#clinical#development#program#in#solid#tumors################################################## now#accounts#for#11#indications

AB! Science! SA% (NYSE% Euronext% 4% FR0010557264% 4% AB),% a% pharmaceutical% company% specialising% in% the% research,% development% and% commercialisation% of% protein% kinase% inhibitors% (PKIs),% announced% today% the% authorisation%granted%by%Afssaps%to%start%a%phase%2%clinical%study%in%stomach%cancer.%

AB%Science%is%now%evaluating%masitinib%in%eleven%indications%in% solid% tumors,%eight%in%phases% 2,%in% second% line% treatment% of% gastro4intestinal% stromal% tumor% (GIST),% lung% cancer,% prostate% cancer,% colorectal% cancer,% triple% negative% breast% cancer,% metastatic% breast% cancer,% metastatic% melanoma,% and% stomach% cancer,% and% three%in%phase%3%in%pancreatic%cancer,% first%line%treatment%of%GIST%and%in%metastatic%melanoma%expressing% JM%mutation%of%c4Kit.

Except%for%GIST%and%melanoma%bearing%the%JM%mutation%of%c4kit,%where%masitinib%is%tested%in%monotherapy% because% the%main% target%is% the% JM%mutation% of% c4kit,%in% the% remaining% 9%indications%masitinib%is% tested%in% combination%with%standard%of%care%chemotherapy.%Indeed,%masitinib%has%proved%to%sensitize%in%vitro%and%in% grafted%mice%models%several%standard%of%care%chemotherapies%in%various%solid%tumors%cell%lines.

Alain% Moussy,% Chairman% and% CEO% of% AB% Science% declared% «! Besides! the! three! phase! 3! studies! already! launched!in!pancreatic!cancer,!GIST!first!line!and!melanoma!bearing!the!JM!mutation!of!c2kit,!the!objective! of! these! proof! of! concept! phases! 2! studies! in! solid! tumors! is! to! define! in! which! cancers! masitinib! can! improve!progression!free!survival!and!survival.!The!position!of!masitinib!is mainly!in!resistance!to!first!line! treatment!and!in!metastatic!tumors,!where!the!medical!need!is!the!maximum.!In!case!of!success,!this!set!of! indications! represents! a! huge! potential,! as! overcoming! resistance! to! chemotherapy! remains! a! daunting! problem.!These!eight!phase!2!studies!and!three!phase!3!studies in!oncology!are!fully!financed».

Details!of!the!clinical!development!program!(on!next!page).

About!masitinib

Masitinib%is%a%new%orally%administered%tyrosine%kinase%inhibitor%that%targets%mast%cells,%important%cells%for%immunity,%as% well%as%a%limited% number%of%kinases% that% play%key% roles%in%various%cancers.%Owing% to%its% novel%mechanism%of%action,% masitinib% can% be% developed% in% a% large% number% of% conditions% in% oncology,% in% inflammatory% diseases% and% in% certain% diseases% of% the% central% nervous% system.% Through% its% activity% of% inhibiting% certain% kinases% that% are% essential% in% some% oncogenic%processes,%masitinib%may%have%an%effect%on%tumour%regression,%alone%or%in%combination%with%chemotherapy.% Through% its% activity% on% the% mast% cell% and% certain% kinases% essential% to% the% activation% of% the% inflammatory% cells% and% fibrosing% tissue% remodelling,%masitinib%can%have%an%effect%on% the%symptoms%associated%with%some%inflammatory%and% central%nervous%system%diseases.

About!AB!Science

Founded% in% 2001,% AB% Science% is% a% pharmaceutical% company% specialising% in% the% research,% development% and% commercialisation% of% protein% kinase% inhibitors% (PKIs),% a% new% class% of% targeted% molecules% whose% action% is% to% modify% signalling% pathways%within% cells.%Through% these% PKIs,% the% Company% targets% diseases%with% high% unmet%medical% needs% (cancer,% inflammatory% diseases% and% central% nervous% system% diseases),% in% both% human% and% veterinary% medicines.% Thanks% to% its% extensive% research% and% development% capabilities,% AB% Science% has% its% own% portfolio% of% molecules.% Masitinib,%a%lead%compound,%has%already%been%registered%in%veterinary%medicine%in%Europe%and%is%pursuing%nine%phase% 3% studies% in% human% medicine,% including% four% studies% on4going% in% pancreatic% cancer,% GIST,% in% metastatic% melanoma% expressing%JM%mutation%of%c4Kit,%and%mastocytosis.

Further%information%is%available%on%AB%Science's%website:%www.ab4science.com

This!document!contains!prospective!information.!No!guarantee!can!be!given!as!for!the!realisation!of!these!forecasts,! which! are! subject! to! those! risks! described!in! documents! deposited! by! the! Company! to! the!Authority! of! the! financial! markets,!including!trends!of!the!economic!conjuncture,!the!financial!markets!and!the!markets!on!which!AB!Science!is! present.!

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AB%Science%4%Financial%Communication%&%Press%Relations%

Contacts Citigate%Dewe%Rogerson%:% Agnès%Villeret%4%Tel:%+33%1%53%32%78%95%4%agnes.villeret@citigate.fr%

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DETAILS!OF!THE!CLINICAL!DEVELOPMENT!PROGRAM!IN!SOLID!TUMORS

Status!of!program!of!clinical!studies!of!masitinib!in!solid!tumors!

Clinical!Studies	Status!at!IPO	Current!status
Masitinib!in!monotherapy!(JM!mutation!of!cKKit)
1%4%Gist%first%line%(phase%3)	Recruitment%on4going%	Recruitment%on4going
24%Metastatic%melanoma%bearing%JM%mutation%of%c4Kit%(phase%3)	Afssaps Not%initiated	Recruitment%on4going
3%4%GIST%second%line%(phase%2)	Recruitment%on4going	Recruitment%on4going
Masitinib!in!combination!with!chemotherapy
44%Pancreatic%cancer%(phase%3)	Recruitment%on4going	Recruitment%completed
5%4 Lung%cancer%(phase%2)	Authorised%(Afssaps)	Recruitment%on4going
6%4 Prostate%cancer%(phase%2)	Authorised%(Afssaps)	Recruitment%on4going
7%4 Colorectal%cancer%(phase%2)	Authorised%(Afssaps)	Recruitment%on4going
8%4 Breast%cancer%triple%negative%(phase%2)	Authorised%(Afssaps)	Recruitment%on4going
9%4 Metastatic%breast%cancer%(phase%2)	Authorised%(Afssaps)	Recruitment%on4going
10%4%Metastatic%melanoma%(phase%2)	Not%initiated	First%patient%enrolled
11%4%Stomach%cancer%(phase%2)	Not%initiated	Authorised%(Afssaps)

Scientific!rationale!for!developing!masitinib!in!solid!tumors!in!combination!with!chemotherapies

Masitinib% is% a% novel% inhibitor% targeting% specifically% c4kit,% FAK,% PDGFR,% and% FGFR3,% thus% it% could% limit% cell% proliferation,% cell%migration%and/or% tumour%vascularisation.%It% has%also% been% shown% that%it% can% potentiate% chemotherapeutic%agents%or%sensitize%resistant%cells%to%chemotherapeutic%agents.%

Masitinib%is%an%effective%antimastocyte,%exerting%a%direct%anti4proliferative%and%pro4apoptotic%action%on%mast% cells% and% reducing% secretion% of% mast% cell% mediators% through% its% inhibition% of% KIT% signalling.% Evidence% indicates%that%recruitment%of%inflammatory%cells,%especially%infiltration%by%mast%cells,%facilitates%the%growth% and% spread% of% some% cancers% by% producing% molecules% that% enhance% tumour% invasiveness.% Therefore,% inhibition% of% mast% cell% function% may% prove% to% be% therapeutically% beneficial% in% restraining% the% growth% of% numerous% cancers,%even% those%without%a% direct%association%with%mast% cell% proliferation.%In%addition% to%its% antiproliferative%properties,%masitinib%can%also%regulate%the%activation%of%mast%cells%through%its%targeting%of% Lyn%and%Fyn,%key%components%of%the%transduction%pathway%leading%to%IgE%induced%degranulation.%This%can% be%observed%in%the%inhibition%of%FcεRI4mediated%degranulation%of%human%cord%blood%mast%cells.%It%is%thought% that% inhibition% of% Lyn% kinase% activity% may% also% inhibit% IgE% independent% degranulation% and% as% such% has% potential%benefits%in%defence%against%metastasis%and%drug4resistance.%

Masitinib% may% reduce% angiogenesis% and% enhance% the% chemotherapy% sensitivity% and% availability% at% the% tumour%site%via%inhibition%of%PDGFR.%Recent%studies%have%suggested%that%PDGFR4β%inhibition%reduces%tumour% interstitial% pressure% and% thus,% increases% the% uptake% of% concomitantly% administered% drugs.% Inhibition% of% PDGFR% kinase% activity% may% also% result% in% direct% tumour% cell% growth% arrest% and% apoptosis% if% PDGFR% is% constitutively%activated.%

FAK%influences%cell%proliferation,%survival,%and%migration,%and%has%been%associated%with%tumour%progression,% metastasis%and%chemoresistance.%Masitinib%can%block%the%FAK%pathway%in%cells%through%the%inhibition%of%FAK% phosphorylation%activity,%without%blocking%its%enzymatic%activity.%

Altogether,% this% could% provide% a% mechanism% of% action% for% masitinib's% chemosensitisation% properties,% i.e.% through%the%reduction%of%tumour%progression%and/or%improved%drug%delivery%and/or%the%inhibition%of%mast% cell%migration%and%activation;%thereby%explaining%the%observed%therapeutic%benefits%of%masitinib.

Characteristics!of!the!phase!3!GIST!first!line!

A% prospective,%multicenter,% randomized,% open4label,% active4controlled,% 24parallel% group,% phase% 3% study% to% compare%efficacy%and% safety% of%masitinib%at% 7.5%mg/kg/day% to%imatinib%at% 400% or% 600%mg%in% treatment% of% patients%with%gastro4intestinal%stromal%tumour%in%first%line%medical%treatment%

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%at%7,5%mg/kg/day%
• Group%2:%Patients%will%receive%imatinib%at%400%or%600%mg%per%day

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!3!study!in!metastatic!melanoma!bearing!JM!mutation!of!cKkit

A% prospective,%multicenter,% randomized,% open4label,%active4controlled,% two4parallel%groups,% phase% 3% study% to% compare% the% efficacy% and% safety% of% masitinib% at% 7.5% mg/kg/day% to% dacarbazine% in% the% treatment% of% patients%with%non4resectable%or%metastatic% stage%3%or% stage%4%melanoma%carrying%a%mutation%in% the%juxta% membrane%domain%of%c4kit.

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%
• Group%2:%Patients%will%receive%dacarbazine

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!GIST!second!line

A% prospective,% multicenter,% randomized,% open4label,% 24parallel% group,% Phase% 2% study% to% compare% efficacy% and% safety% of%masitinib% at% 12%mg/kg/day% to% sunitinib% at% 50%mg/day% in% treatment% of% patients% with% gastro4 intestinal%stromal%tumor%resistant%to%imatinib

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%at%12%mg/kg/day%
• Group%2:%Patients%will%receive%sunitinib%at%50%mg/day

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase3!in!pancreatic!cancer

A%prospective,%multicenter,% randomized,%double4blind,%placebo4controlled,%24parallel%group,%Phase%3%study% to%compare%efficacy%and%safety%of%masitinib%at%9%mg/kg/day%in%combination%with%gemcitabine,%to%placebo%in% combination%with%gemcitabine,%in%treatment%of%patients%with%advanced/metastatic%pancreatic%cancer.%

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%at%9%mg/kg/day%plus%gemcitabine
• Group%2:%Patients%will%receive%matching%placebo%plus%gemcitabine

The% primary% criterion% will% be% the% Overall% Survival.% Progression% Free% Survival% (PFS)% will be% the% second% criterion.%

Characteristics!of!the!phase!2!study!in!lung!cancer

A% prospective,%multicentre,% randomised,% open4label,% 24parallel%groups,% phase%2% study% to%evaluate%efficacy% and safety%of%masitinib%at%9%mg/kg/day%in%combination%with%docetaxel%or%in%combination%with%gemcitabine in% the treatment% of% patients% with% metastatic% non4small% cell% lung% cancer% in% progression% after% first% line% treatment.

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%at%9%mg/kg/day%in%combination%with%docetaxel
• Group%2:%Patients%will%receive%masitinib%at%9%mg/kg/day%in%combination%with%gemcitabin

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!prostate!cancer

This%is%a%prospective,%multicenter,%randomized,%open4label,%24parallel%group,%Phase%2%study%to%evaluate%the% efficacy%and% the%safety%of%masitinib%at%9%mg/kg/day%in%combination%with%docetaxel%or%with%gemcitabine%in% metastatic%Hormone%Refractory%Prostate%Cancer%(HRPC)%in%progression%after%first%line%of%treatment.

Patients%will%be%randomized%in%two%groups:

• Group% 1:% Patients% will% receive% masitinib% at% 9% mg/kg/day% in% combination% with% docetaxel% and% prednisone
• Group%2:%%Patients%will%receive%masitinib%at%9%mg/kg/day%in%combination%with%gemcitabine%

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!colorectal!cancer

This% is% a% prospective,% multicentre,%randomized,% open4label,% 34parallel% groups,% phase% 2% study% to% evaluate% efficacy%and% safety% of%masitinib%at% 9%mg/kg/day%in% combination%with% oxaliplatin,% 54fluorouracil% (54FU)%and% folinic%acid%(FOLFOX)%or%in%combination%with%irinotecan,%54fluorouracil%(54FU)%and%folinic%acid%(FOLFIRI)%or%in% combination% with% gemcitabine% (GEM)% in% the% treatment% of% patients% with% metastatic% colorectal% cancer% in% progression%after%a%first%line%treatment.

Patients%will%be%randomised%in%three%groups:

• Group% 1:% Patients% will% receive% masitinib% in% combination% with% oxaliplatin 54fluorouracil% (54FU)% and% folinic%acid%(modified%FOLFOX%protocol);
• Group% 2:% Patients% will% receive%masitinib% in% combination% with% irinotecan,% 54fluorouracil% (54FU)% and% folinic%acid%(FOLFIRI%protocol);
• Group%3:%Patients%will%receive%masitinib%in%combination%with%gemcitabine.

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!breast!triple!negative!cancer

This%is%a%prospective,%multicentre,%open4label,%randomised,%phase%2%study%to%evaluate%efficacy%and%safety%of% masitinib%at%9%mg/kg/day%in%association%with%gemcitabine%or%carboplatin%or%gemcitabine%plus%carboplatin%in% patients%with%a%triple%negative%metastatic%or%locally%advanced%breast%cancer.

Patients%will%be%randomised%in%three%groups:

• Group%1:%Patients%will%receive%masitinib%at%9%mg/kg/d%in%association%with%gemcitabine;
• Group%2:%Patients%will%receive%masitinib%at%9%mg/kg/d%in%association%with%carboplatin;
• Group% 3:% Patients% will% receive% masitinib% at% 9% mg/kg/d% in% association% with% gemcitabine% plus% carboplatin.

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!metastatic!cancer

This%is%a%prospective,%multicentre,%open4label,%randomised,%phase%2%study%to%evaluate%efficacy%and%safety%of% masitinib%in%combination%with%gemcitabine%or%carboplatin%or%capecitabine%in%patients%with%a%metastatic%or% locally% advanced% breast% cancer% (all% hormonal% status% tumour% except% triple% negative% tumour)% and% who% relapsed%after%a%first%line%chemotherapy.

Patients%will%be%randomised%in%three%groups:

• Group% 1:% Patients% will% receive% masitinib% at% 9% mg/kg/d% or% 6% mg/kg/day% in% association% with% gemcitabine
• Group%2:%Patients%will%receive%masitinib%at%9%mg/kg/d%or%6%mg/kg/day%in%association%with%carboplatin%
• Group% 3:% Patients% will% receive% masitinib% at% 9% mg/kg/d% or% 6% mg/kg/day% in% association% with% capecitabine%

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!metastatic!melanoma

This%is%a%prospective,%multicentre,%open4label,%two4parallel%groups,%phase%2%study% to%evaluate%efficacy%and% safety%of%masitinib%at%9 mg/kg/day%in%monotherapy%and%combination%with%dacarbazine%in%the%treatment%of% patients% with% non4resectable% or% metastatic% stage% 3% or% stage% 4% melanoma% not% carrying% a% mutation% in% the% juxta%membrane%of%c4kit.

Patients%will%be%randomized%in%two%groups:

• Group%1:%Patients%will%receive%masitinib%in%association%with%dacarbazine
• Group%2:%Patients%will%receive%masitinib.

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.

Characteristics!of!the!phase!2!study!in!stomach!cancer

This%is%prospective,%multicentre,%open4label,%randomised,%phase%2%study%to%evaluate%the%efficacy%and%safety% of% masitinib% in% combination% with% 54fluorouracil% (54FU)% or% capecitabine,% or% masitinib% in% combination% with% irinotecan,% or% masitinib% in% combination% with% irinotecan,% 54fluorouracil% (54FU)% and% folinic% acid% (FOLFIRI% protocol),% as% second% line% therapy% in% patients% with% gastric% or% gastro4oesophageal% junction% metastatic% adenocarcinoma.

Patients%will%be%randomized%in%three%groups:

• Group% 1:% Patients% will% receive% masitinib% at% 6% mg/kg/day% or% 9% mg/kg/day,% in% association% with% 54 Fluorouracil%or%Masitinib%at%6%mg/kg/day%or%9%mg/kg/day%in%association%with%capecitabine%
• Group% 2:% Patients% will% receive% masitinib% at% 6% mg/kg/day% or% 9% mg/kg/day,% in% association% with% irinotecan
• Group%3:%Patients%will%receive%masitinib%at%6%mg/kg/day%or%9%mg/kg/day%in%association%with%FOLFIRI% protocol

The%primary%criterion%will%be%the%Overall%Progression%Free%Survival%(PFS),%defined%as%the%delay%between%the% date% of% randomisation% to% the% date% of% documented% progression% or% any% cause% of% death% during% the% study.% Overall%Survival%will%be%the%main%secondary%criterion.