ABSCIENCES (EPA:AB) AB SCIENCE: Recruitment of first patient in phase 3 study in metastatic melanoma expressing c-Kit JM mutation

Transparency directive : regulatory news

03/01/2011 17:52

Paris, January 3rd, 2010 - 5.45 pm

AB Science announces recruitment of first patient in phase 3 study in metastatic
                      melanoma expressing c-Kit JM mutation

AB Science SA (NYSE Euronext - FR0010557264 - AB), a pharmaceutical company
specialising in the research, development and commercialisation of protein
kinase inhibitors (PKIs), announced today the recruitment of the first patient
in the phase 3 study comparing masitinib versus dacarbazine in metastatic
melanoma bearing the juxtamembrane (JM) mutation of c-Kit.

This is an international, randomised, open-label, 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 non-resectable or metastatic stage 3 or stage 4
melanoma carrying a mutation in the juxtamembrane domain of c-Kit. The trial
will enrol approximately 200 patients, across 80 centres around the world,
randomised equally between the masitinib and dacarbazine treatment arms.

The mutation of the c-Kit gene is expressed in canine mast cell tumours where
masitinib is already registered in Europe and in the USA. This mutation is also
present in Gastro Intestinal Stromal Tumours (GIST) where masitinib is currently
in a comparative phase 3 study against imatinib.

Alain Moussy, Chairman and CEO of AB Science declared " There is a race in this
indication between Novartis which is starting a phase 3 with nilotinib and AB
Science which is already starting a phase 3 with masitinib. Masitinib has been
granted authorisation to start phase 3 from FDA without performing a phase 2,
leapfrogging competition, mainly due to its results in canine mast cell tumours
and GIST. AB Science considers indications where the juxtamembrane mutation of
c-Kit is present as priority development for masitinib because these indications
hold the highest probability of registration. This phase 3 in melanoma is 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 three studies on-going in pancreatic cancer, GIST and mastocytosis.

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.

                                     * * *

         AB Science is listed on NYSE Euronext Paris (compartiment B) -
                                FR0010557264 - AB
Further information is available on AB Science's website: www.ab-science.com

CONTACTS :
Agnès Villeret (investors & analysts)
Tel : +33 1 53 32 78 95 - agnes.villeret@citigate.fr
Lucie Larguier (press)
Tel : +33 1 53 32 84 75 - lucie.larguier@citigate.fr

                                     * * *

                    DETAILS OF THE CLINICAL DEVELOPMENT PROGRAM

Scientific rationale for developing masitinib in metastatic melanoma expressing
the JM mutation of c-Kit.

There exists a strong scientific rationale for developing masitinib in the
treatment of metastatic melanoma expressing the juxtamembrane (JM) mutation of
c-Kit.

1. A large proportion of mucosal melanoma (39%), acro-lentiginous melanoma
(36%), and melanoma-induced by sun exposure (28%) express the JM mutation of
c-Kit.

2. Clinical data has shown that the single agent administration of imatinib
(Glivec), an inhibitor of c-Kit, could induce a prolonged partial tumour
response in patients with melanoma expressing the JM mutation of c-Kit.

3. Masitinib is a potent and highly specific inhibitor of c-Kit, and in
particular the JM mutation of c-Kit.

- Masitinib is registered in treatment of canine mast cell tumours with
   confirmed JM mutation of c-Kit. In this population, it has been shown that
   subjects receiving masitinib have a statistically significant longer median
   survival time (241 days versus 83 days).

- Masitinib is under development in a phase 3 study for treatment of GIST,
   which is caused by the same JM mutation of the c-Kit receptor. In a phase 2
   study for this indication, with over 4 years of patient follow-up, the median
   survival has not yet been reached and the rate of survival at 4 years
   was 76%. Median survival without progression was 41.3 months.

Characteristics of the phase 3 study in metastatic melanoma

This is a prospective, multicentre, open-label, active-controlled, two-arm,
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 nonresectable or metastatic
stage 3 or stage 4 melanoma carrying a juxtamembrane mutation c-Kit

A total of 200 patients will be randomised in two groups:
Group 1: 100 patients will receive masitinib;
Group 2: 100 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.

Positioning of masitinib in the treatment of melanoma

Melanoma is a malignant tumour that develops from cells called melanocytes,
which are present primarily in the skin but are also found in the eye and mucous
membranes of the mouth, nose, sinus, rectum and genitals.

The incidence of melanoma has multiplied ten-fold in 50 years. The American
Cancer Society estimated there were 68,000 newly diagnosed melanoma cases in the
US with 8,700 related deaths in 2009. In France, it is estimated that 7,000 new
cases of melanoma are diagnosed each year.

Positioning of masitinib within targeted therapies

Of the new targeted therapies currently under development in the various forms
of melanoma:
  - For metastatic melanoma expressing the BRAF mutation (i.e. 40% to 60% of
    melanoma patients), one compound developed by Plexxikon and Roche is
    currently undergoing phase 3 evaluation.
  - For metastatic melanoma expressing the JM mutation of c-Kit (i.e. 5% of
    melanoma patients), other than masitinib, two other molecules are under
    development for this indication. Nilotinib (Novartis) has recently
    initiated a phase 3 study and dasatinib (Bristol-Myers Squibb) is currently
    in phase 2.

There exist important differences between nilotinib and masitinib beyond their
common capacity to inhibit the JM mutation of c-Kit; namely, masitinib also
blocks the signalling pathways of WNT/betacatenine and LYN/FAK, two pathways
that are important for the proliferation of metastatic melanoma.

Positioning of masitinib within other forms of metastatic melanoma

Chemotherapy is proposed for treatment of metastatic melanoma; however, it does
not generate satisfactory clinical results, with a median survival of between
just 6 to 12 months (palliative chemotherapy). In metastatic melanoma, a
monoclonal antibody developed by Bristol-Myers Squibb, ipilimumab, aimed at
stimulating the response of certain cells of the immune system against the
melanoma, has been shown to improve median survival by 3.7 months (10.1 months
compared to 6.4 months with standard treatment). This product has been filed for
registration.

Masitinib is positioned at phase 2 in the treatment of these forms of metastatic
melanoma, as monotherapy or in combination with standard chemotherapy.

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ABSCIENCES (EPA:AB) AB SCIENCE: Recruitment of first patient in phase 3 study in metastatic melanoma expressing c-Kit JM mutation

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