AB Science SA received a €5.9 million (US$7.8 million) funding boost for its Phase III development program of masitinib in Alzheimer's disease.

The Paris-based drug developer is leading a consortium that has obtained a total of €8.6 million in project funding from Bpifrance, the newly formed French public investment bank that has taken on the enterprise development functions of OSEO, CDC Enterprises and the French Strategic Investment Fund (FSI).

Masitinib, a tyrosine kinase inhibitor (TKI), recently entered a 400-patient Phase III trial in Alzheimer's, following a Phase II study which indicated that the drug improved cognition and memory in patients with mild to moderate disease. (See BioWorld Today, May 22, 2013.)

Masitinib already is marketed for a canine cancer indication, and it is undergoing European regulatory reviews in two human cancer indications, Gleevec-resistant gastrointestinal stromal tumor (GIST) and pancreatic cancer.

The drug has outperformed Sutent (sunitinib malate, Pfizer Inc.) in a Phase II head-to-head study in Gleevec-resistant GIST, and it is now undergoing a Phase III trial in the same setting. (See BioWorld Today, Feb. 8, 2012.)

It also provided an additional six-month survival benefit for pancreatic cancer patients with an aggressive form of disease who were already taking Gemzar (gemcitabine; Eli Lilly and Co.). Those with an aggressive course of disease were identified using a phenotypic biomarker developed by French diagnostics firm Skuldtech SAS. (See BioWorld Today, Nov. 7, 2012.).

Masitinib appears to act both by disrupting cancer signal pathways, as other TKIs do, but it also appears to have immunomodulatory effects, which are mediated by its targeting of c-Kit (also called CD117 and stem cell factor receptor) and Lyn, two tyrosine kinases that are expressed by mast cells.

Part of the project funding is earmarked for establishing mast cells as therapeutic targets in neurodegenerative disease. There is preliminary evidence, according to the company, that mast cells play a role in the trafficking of immune cells into the central nervous system (CNS). They may, therefore, have a role in the neuro-inflammatory aspects of Alzheimer's disease.

One recent review, which appeared in the Dec. 5, 2012, issue of the Philosophical Transactions of the Royal Society London, Biological Sciences, noted that mast cells can cross the blood-brain barrier when it becomes compromised due to CNS pathology. Its authors posited an "axis" of interaction involving mast cells and glial cells, which play a central role as immune effector cells in the CNS.

The project consortium also includes diagnostics firm Skuldtech, also of Paris, which will develop predictive companion tests to distinguish likely responders to therapy from and nonresponders. The same company has already developed a companion diagnostic for masitinib in pancreatic cancer. (See BioWorld Today, Nov. 7, 2012.).

The other participants in the project include the Brain and Spine Institute (ICM), at Hôpital Pitié Salpêtrière, in Paris, the MIRCen Molecular Imaging Research Center in Fontenay-aux-Roses, the National Institute of Health and Medical Research (Inserm), and the Imagine Foundation, a research institute located at the Necker Hospital, in Paris.

After peaking at €18.45 during trading Tuesday, shares in AB Science (PARIS:AB) ended the day at €17.81, a drop of 4 cents.

AB Science officials were not available for comment.