AB Science reports phase 3 study results of masitinib in combination with Gemzar® for treatment of pancreatic cancer.

  AB Science reports phase 3 study results of masitinib in combination with
  Gemzar® for treatment of pancreatic cancer.

European Medicines Agency accepts Marketing Authorization Application for
conditional approval of masitinib in the treatment of pancreatic cancer.

Business Wire

PARIS -- October 30, 2012

Regulatory News:

AB Science SA (NYSE Euronext - FR0010557264 - AB), a pharmaceutical company
specializing in the research, development and commercialization of protein
kinase inhibitors, announced today the results from a phase 3 study evaluating
the effect of masitinib in combination with Gemzar® (gemcitabine, Eli Lilly
and Company) on overall survival (OS) in patients with pancreatic cancer.
Briefly, masitinib in combination with Gemzar® significantly extended median
OS by 6 and 2.7 months in two independent patient populations, representing
65% and 45% of the overall population; namely, patients with a genetic
biomarker - collected from simple blood sample - indicative of aggressive
disease progression, and patients with cancer pain. Pain intensity and the
discovered genetic biomarker were shown to be of prognostic value for survival
under Gemzar® alone and at the same time predictive of increased survival with
masitinib in combination with Gemzar® for those patients identified as having
a poor prognosis with Gemzar® alone.

AB Science also announced that the European Medicines Agency (EMA) has
accepted to review a Marketing Authorization Application (MAA) for conditional
approval of masitinib in combination with Gemzar® in the treatment of
pancreatic cancer, following filing of this dossier.

Full data has been submitted for presentation at the American Society of
Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium (24-26 January
2013, in San Francisco, California).

Filing for the conditional approval of masitinib in combination with Gemzar®
in the treatment of non resectable, advanced adenocarcinoma pancreatic cancer
was accepted by EMA on the basis of results from a phase 3 study that showed
masitinib in combination with Gemzar® significantly extends overall survival
in two independent patient populations having the worst prognosis. These
populations consisted of patients with a gene expression profile (or genetic
biomarker) indicative of aggressive disease progression (65% of pancreatic
cancer patients), and patients with cancer pain (45% of pancreatic cancer
patients). In this prospective, international, randomized, double-blinded
clinical trial, 348 patients received either masitinib in combination with
Gemzar®, or placebo in combination with Gemzar®. A planned ancillary
pharmacogenomic study, based on RNA extracted from whole blood samples before
treatment start, was also conducted to identify genetic expression patterns
predictive for overall survival and/or treatment benefit.

AB Science made two important discoveries based on data from these studies.

  *First, pancreatic cancer patients characterized by the discovered genetic
    biomarker (approximately 65% of all patients) reported very poor survival
    when receiving placebo plus Gemzar®, with a median OS of 5 months.
    However, this same genetic biomarker was highly predictive of
    significantly extended survival in patients receiving masitinib in
    combination with Gemzar®, with a median OS increased by 6.0 months to 11.0
    months, corresponding to a hazard ratio of 0.29 (p=0.000038). OS rates at
    12 and 18 months were respectively, 41.4% and 18.5% in the masitinib plus
    Gemzar® treatment arm versus 11.1% and 4.2% in the placebo plus Gemzar®
    arm.
  *Second, patients presenting with a certain threshold of pain intensity at
    the time of study entry (approximately 45% of all patients) were revealed
    to have a very poor prognosis when receiving placebo plus Gemzar®, with a
    median OS of 5.4 months. In these patients, the combination therapy of
    masitinib plus Gemzar® showed a statistically significant extended
    survival, with median OS increased by 2.7 months to 8.1 months,
    corresponding to a hazard ratio of 0.61 (p=0.010). OS rates at 12 and 18
    months were respectively, 32.2% and 18.2% in the masitinib plus Gemzar®
    treatment arm versus 17.8% and 7.8% in the placebo plus Gemzar® arm.

Besides being predictive for masitinib plus Gemzar® treatment efficacy, these
two factors were also of prognostic value for overall survival in patients
treated with Gemzar® as a single agent. Regarding the genetic biomarker,
patients harboring this ‘aggressive genetic fingerprint’ had a median OS of
5.0 months whilst patients without this fingerprint had a median OS of 14.3
months. Regarding the prognostic factor of ‘pain intensity’, patients
exceeding a certain threshold of pain at baseline had a median OS of 5.4
months versus 15.4 months in patients without pain.

Results in the overall study population did not show a significant advantage
for masitinib in combination with Gemzar® as compared with Gemzar® treatment
alone. Median OS was 7.7 months in the masitinib plus Gemzar® treatment arm
versus 7.0 months in the placebo plus Gemzar® treatment arm (p=0.74; hazard
ratio=0.90). This finding of a non significant survival improvement in the
overall population is explained by the fact that masitinib is not indicated
when Gemzar® is highly efficient; namely, the situation defined by an absence
of both pain and genetic biomarker detecting “aggressiveness”.

Olivier Hermine, MD, PhD, President of the Scientific Committee of AB Science
commented: “The prognostic factors of ‘pain intensity’ and ‘aggressive genetic
fingerprint’ revealed by AB Science are two major discoveries in this
devastating disease that has a high unmet medical need. We previously knew
that pain was correlated with poor prognosis in pancreatic cancer. Our current
working hypothesis is that pain flags the presence of mast cells in the tumor
microenvironment and mast cell activation may help transform the tumors into a
more aggressive form. On the other hand, the genetic biomarker is really
revolutionary since it would be the first time that RNA expression from whole
blood samples is capable of predicting overall survival in patients depending
upon the treatment received. In addition, this genetic biomarker could be used
as a prognostic tool: patients with the ‘aggressive genetic fingerprint’ and
receiving the standard treatment of Gemzar® monotherapy had a median OS of
only 5 months, whilst patients without this genetic biomarker survived on
average for 14.3 months. It is encouraging that masitinib seems to improve
significantly survival in patients with the worst prognosis and who represent
the highest unmet medical need”.

Alain Moussy, CEO of AB Science declared: “We knew that masitinib had an
antimetastatic potential thanks to our recent GIST study as 2^nd line
treatment in Gleevec-resistant patients. That study revealed masitinib did not
outperform sunitinib, the current 2^nd line treatment for GIST, in terms of
PFS (progression-free survival) but did significantly improve median OS with a
hazard ratio of 0.29. The pancreatic cancer phase 3 study delivers a second
clinical proof of masitinib’s antimetastatic effect in cancer, again showing
comparable PFS between treatment arms whilst overall survival was
significantly increased in two independent subpopulations. In patients with
‘pain’ median OS was increased by 2.7 months with a corresponding hazard ratio
of 0.61, and in patients with the ‘aggressive genetic fingerprint’ median OS
was improved by an impressive 6.0 months with a hazard ratio of 0.29, when
treated with the masitinib plus Gemzar® combination. It seems that the
inhibition of mast cell activity in cancer is one of the key drivers of
masitinib. However, masitinib evidently does more since other tyrosine kinase
inhibitors of mast cells have failed in the pancreatic cancer or GIST
indications. Masitinib seems to touch key pathways that are involved with
metastatic progression in cancer, the very mechanism which eventually leads to
death”.

Masitinib received orphan drug designation in the treatment of pancreatic
cancer from both FDA and EMA.

About Pancreatic cancer

Incidence of pancreatic cancer has markedly increased over the last few
decades with more than 230,000 patients worldwide diagnosed with this
condition. Patients diagnosed with pancreatic cancer often have a poorer
prognosis compared with other cancers in part because early detection is
difficult. At the time of diagnosis, most patients with pancreatic ductal
adenocarcinoma present with locally advanced or metastatic disease and only
10-20% of cases are candidates for curative surgery. Median overall survival
from diagnosis is around 3 to 6 months; 5-year survival is much less than 5%
and complete remission is extremely rare [American Cancer Society, 2008].

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 tumor
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 remodeling, 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 specializing in the
research, development and commercialization of protein kinase inhibitors
(PKIs), a new class of targeted molecules whose action is to modify signaling
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. AB Science has
developed a proprietary portfolio of molecules and the Company’s lead
compound, masitinib, has already been registered for veterinary medicine in
Europe and in the USA, and is pursuing 8 on-going phases 3 studies in human
medicine in GIST, metastatic melanoma expressing JM mutation of c-Kit,
multiple myeloma, mastocytosis, severe persistent asthma, rheumatoid
arthritis, and progressive multiple sclerosis. The company is headquartered in
Paris, France, and listed on Euronext Paris (ticker: AB).

 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 realization 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.

                                    * * *

Contact:

AB Science - Financial Communication & Press Relations
Laurent Guy
01 47 20 00 14
investors@ab-science.com
 
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