Medicine in development
Masitinib
TARGETED IMMUNOREGULATION
An approach designed to precisely regulate the cells involved in the immune response and support the development of treatments in four priority indications.
CLINICAL PROGRAMMES
4
indications in development
3 Phase 3 studies to be initiated1 Phase 1 study to be initiated
Overview
A molecule at the heart of immunoregulation
Masitinib is AB Science’s most advanced molecule. It belongs to a family of medicines known as kinase inhibitors, molecules that block certain signals within cells. It targets two components of the innate immune system in particular, mast cells and microglia, whose abnormal activation sustains inflammation in various diseases.
MASITINIB MECHANISM OF ACTION
Regulating the immune system’s “clean-up” response
Our immune system includes cells that destroy intruders, followed by cells that clear away the destroyed intruders. These latter cells belong to the macrophage family.
Macrophage-related cells include mast cells — found in the body and digestive system — and microglia — found in the brain. When the immune system becomes overactive, the clean-up response becomes excessive and produces too many mast cells and/or microglia.
An excess of these cells can do more harm than good. Immunoregulation acts upstream to limit the number of “clean-up” cells to what is strictly necessary.
01
A normal level
A normal level of mast cells and/or microglia allows waste resulting from the immune response to be cleared effectively.
02
An excessive level
An abnormally high level of mast cells and/or microglia prevents effective clearance of waste resulting from the immune response and creates disruption: inflammation spreads throughout the system, like dust that impairs the immune system’s ability to function.
03
Regulation by masitinib
Masitinib targets mast cells and microglia. The hypothesis under evaluation in phase 3 is that, by reducing the excess of these cells, it slows disease progression.
MECHANISMS OF ACTION BY INDICATION
An innovative approach for each indication
Regulation of inflammation
Neuroinflammation plays an important role in neurodegenerative disorders such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. Masitinib targets two cell types of the innate immune system, mast cells and microglia, which play a key role in modulating this neuroinflammatory process. The pro-inflammatory activity of these cells may act as a catalyst in the neurodegenerative process, suggesting that addressing their harmful role could be crucial in treating these diseases. Masitinib therefore acts across several indications through an anti-inflammatory mechanism.
Alzheimer’s disease
Mechanism of action
In Alzheimer’s disease, brain cells communicate less and less effectively and eventually die. The contact points between neurons, known as synapses, are among the first structures affected, and their loss accompanies memory decline. Around them, microglia and mast cells become activated and sustain inflammation that worsens the damage. Most medicines developed for this disease target abnormal protein deposits. Masitinib follows an innovative approach: it acts on these immune cells in the brain to reduce inflammation and preserve synapses.
Preclinical data: in animal models, masitinib restored learning performance and increased markers of synaptic health.
Development stage
Phase 3 to be initiated
Clinical results obtained
Masitinib slowed the deterioration of cognitive function in patients with Alzheimer’s disease, with cognitive function even improving over the 24-week treatment period in patients with mild Alzheimer’s disease.
Amyotrophic lateral sclerosis
Mechanism of action
In amyotrophic lateral sclerosis (ALS), motor neurons — the nerve cells that control muscles — progressively degenerate. Around them, immune cells become abnormally activated and sustain inflammation that accelerates this degeneration. Two cell families are particularly involved: microglia, which reside in the brain and spinal cord, and mast cells, which are found along nerves and within muscles. Masitinib blocks enzymes known as kinases, mainly CSF-1R and c-Kit, which control the proliferation and activation of these cells. By bringing them back under control, it aims to reduce inflammation around motor neurons and preserve the connection between nerves and muscles for longer. Its distinctive feature is therefore its action both within the central nervous system and in the periphery.
Development stage
Phase 3 to be initiated
Clinical results obtained
Among long-term survivors treated with masitinib, median overall survival was 121 months, compared with 42 months predicted by the ENCALS model, representing a residual median survival gain of 79 months.
Progressive forms of multiple sclerosis
Mechanism of action
Multiple sclerosis has two main forms: the relapsing-remitting form, characterised by disease relapses, and the progressive form, characterised by a constant and steady worsening of symptoms, without distinct relapses or periods of recovery.
In multiple sclerosis, the sheath that surrounds and protects nerve fibres, known as myelin, becomes damaged and nerve signals are transmitted less effectively. In progressive forms, disability develops slowly and continuously, without the relapses characteristic of relapsing forms. Existing treatments mainly act on the adaptive immune system, particularly lymphocytes, which partly explains their limited efficacy in these forms. Masitinib takes a different approach: it targets the innate immune system, which is permanently present in the nervous system, particularly microglia, macrophages and mast cells. By limiting activation of these cells, it seeks to reduce the inflammation that progressively damages nerve fibres and to slow the progression of disability.
Development stage
Phase 3 to be initiated
Clinical results obtained
Masitinib reduced disability progression by 37% (3-month confirmed progression). Masitinib significantly reduced the risk of reaching a level of disability severe enough to require patients to use a wheelchair.
Sickle cell disease
Mechanism of action
Sickle cell disease is a genetic disorder of red blood cells. The abnormal haemoglobin they contain becomes rigid, causing the cells to deform and circulate poorly through small blood vessels. These blockages, known as vaso-occlusive crises, cause severe pain and can damage organs. It is now known that this blockage is not purely mechanical: inflammation plays an active role, and mast cells in the blood vessel walls are among its drivers. Masitinib acts by blocking the kinases that control activation of these cells. The aim is not to correct the abnormal haemoglobin, but to defuse the inflammatory response that turns red blood cell deformation into a painful crisis.
Development stage
Phase 1 to be initiated
INDICATIONS IN DEVELOPMENT
Current programme status
| Molecule | Therapeutic area | Indication | Development stage |
|---|---|---|---|
| Masitinib | Neurodegenerative disease | Alzheimer’s disease |
Phase 3 to be initiated
|
| Masitinib | Neurodegenerative disease | Amyotrophic lateral sclerosis |
Phase 3 to be initiated
|
| Masitinib | Neurodegenerative disease | Progressive forms of multiple sclerosis |
Phase 3 to be initiated
|
| Masitinib | Blood disorder | Sickle cell disease |
Phase 1 to be initiated
|
DURATION OF EACH STUDY
Protocols tailored to each indication
Alzheimer’s disease
24
weeks
Amyotrophic lateral sclerosis
48
weeks
Progressive forms of multiple sclerosis
96
weeks
Sickle cell disease
12
weeks
TARGET POPULATION — EPIDEMIOLOGICAL ESTIMATE
Scale of need and market potential
Alzheimer’s disease
5,000,000
patients — Europe + United States
Amyotrophic lateral sclerosis
50,000
patients — Europe + United States
Progressive forms of multiple sclerosis
500,000
patients — Europe + United States
Sickle cell disease
130,000*
patients — Europe + United States
* 80 000 for the African continent
MARKET POTENTIAL — ESTIMATE BY INDICATION
Estimated market potential
Alzheimer’s disease
~€8
billion — Europe + United States
Amyotrophic lateral sclerosis
~€1.5
billion — Europe + United States
Progressive forms of multiple sclerosis
~€5
billion — Europe + United States
Sickle cell disease
~€2.5
billion — Europe + United States
Estimates provided by AB Science.