ABSCIENCES (EPA:AB) AB Science: recruitment of first patient in phase 2 study in metastatic melanoma

Transparency directive : regulatory news

13/01/2011 08:45

Paris, January 13th 2011 - 8.45 am

AB Science announces recruitment of first patient in phase 2 study in metastatic
melanoma

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 2 study evaluating masitinib in metastatic melanoma.

This is a prospective, multicentre, open-label, phase 2 study to evaluate
efficacy and safety of masitinib a t 9 mg/kg/day in monotherapy and combination
with dacarbazine in the treatment of patients with non-resectable or metastatic
stage 3 or stage 4 melanoma not carrying a mutation in the juxta membrane of
c-kit.

Masitinib is currently evaluated in phase 3 in the 5% of patients with
metastatic melanoma carrying a mutation in the juxta membrane of c-kit, with
first patients having been enrolled. This proof of concept phase 2 study
complements the phase 3 by targeting the remaining 95% of patients with
metastatic melanoma. This phase 2 in melanoma will test the monotherapy strategy
as in the phase 3 and the combination with chemotherapy strategy. This study is
fully financed

Alain Moussy, Chairman and CEO of AB Science declared " This development in
melanoma was initiated after observation of positive case reports in dogs
suffering from metastatic melanoma and treated with masitinib. After
registration of masitinib both in Europe and in the USA in canine mast cell
tumours, the veterinary platform creates also value for the development of
masitinib in human medicine by delivering information on what indications could
be pursued. This type of cross species development is encouraged by NCI
guidelines for drugs developable in the two species, which is the case of
tyrosine kinase inhibitors since kinases are fairly homologous across mammals ".

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

About NCI guidelines
The National Cancer Institute's Center for Cancer Research (CCR) has launched
the Comparative Oncology Program (COP) to help researchers better understand the
biology of cancer and to improve the assessment of novel treatments for humans
by treating pet animals-primarily cats and dogs-with naturally occurring cancer.
Further information is available at
https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home

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 on-going in pancreatic cancer, GIST, in metastatic melanoma expressing
JM mutation of c-Kit, and mastocytosis.

Further information is available on AB Science's website: www.ab-science.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.

                                     * * *

AB Science - Financial Communication & Press Relations

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

                                     * * *

                 DETAILS OF THE CLINICAL DEVELOPMENT PROGRAM

Scientific rationale for developing masitinib in metastatic melanoma.

Malignant melanoma continues to remain a significant health threat with death
often occurring as a result of metastasis. Moreover, metastatic melanoma is a
highly chemotherapy resistant tumour.

The use of newer targeted therapies, alone and in combination with chemotherapy
may offer new hope of improving treatment in this cancer.

Although it seems obvious to evaluate masitinib in monotherapy in the
sub-population of melanoma JM c-kit mutated population (phase 3 on-going), it is
also interesting to evaluate the efficacy of masitinib in combination with
chemotherapies in the population of melanoma not presenting a JM c-kit mutation.
Through its ability to block two kinases, FAK (Focal Adhesive Kinase), and
PDGFR, as well as the Wnt/beta-catenin Signalling pathway, masitinib combined
with chemotherapy, could prevent the development and progression of melanoma
lesions, as well as decrease the melanoma resistance to chemotherapy by
increasing the drug uptake and therapeutic effectiveness of chemotherapy.
Moreover, based on the results obtained in veterinary medicine in dogs with
melanoma not presenting a c-kit JM mutation, masitinib in monotherapy might also
represent a therapeutic option in human melanomas not presenting c-kit JM
mutation.

Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine
kinase involved in cancer progression and metastasis. It is found overexpressed
in a large number of tumours. FAK regulates integrin and growth factor
signalling pathways involved in cell migration, proliferation and survival.
These cellular processes, by promoting invasion and metastasis, are implicated
in the development and progression of cancer. Studies have shown increased in
the constitutive activation of FAK in melanoma cells. In vitro, masitinib (1µM)
reduces FAK kinase activity.

PDGFR is a transmembrane receptor tyrosine kinase reported to stimulate
angiogenesis and to recruit pericytes. Melanomas widely express PDGFR, and their
in vivo resistance to chemotherapy is attributable to high tumour interstitial
fluid pressure (IFP). Recent studies have suggested that PDGFR-beta inhibition
reduces tumour IFP, and thus increases the uptake of concomitantly administered
drugs. In vitro, masitinib is able to inhibit PDGFR kinase activity at
submicromolecular ranges (IC50 = 0.49 µM). In cell proliferation assays,
masitinib displays an interesting selectivity and inhibits PDGFR-dependent cell
proliferation (IC50 = 0.02 µM). These data suggest that masitinib may increase
drug uptake and therapeutic effectiveness of chemotherapy for melanoma by
inhibiting PDGFR kinase activity.

Wnt/beta-catenin Signalling has been shown to be involved in progression,
renewal of cancer stem cells and drug resistance of several tumours. This
pathway play a role in melanocyte development and could be involved in their
transformation in malignant melanoma. Therefore its inhibition could
potentially translate in a clinical benefit of patients with melanoma.

Characteristics of the phase 2 study in metastatic melanoma

This is a prospective, multicentre, open-label, two-parallel 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
non-resectable or metastatic stage 3 or stage 4 melanoma not carrying a mutation
in the juxta membrane of c-kit.

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.

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.

Masitinib is positioned in phase 3 in 5% of the melanoma carrying a mutation in
the juxta membrane of c-kit. In this patient population, masitinib is
administered in monotherapy at the dose of 7.5 mg/kg/day

Masitinib is also positioned in phase 2 in the other 95% of the melanoma Not
carrying a mutation in the juxta membrane of c-kit. In this patient population,
masitinib is evaluated in monotherapy and in combination with standard
chemotherapy, at the dose of 9 mg/kg/day.

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