Since its creation in 2001, AB Science has specialized in the research, development and commercialization of drugs used in the treatment of cancerous tumors, inflammatory diseases and neurogenerative diseases. While AB Science's main drug, Masitinib, already has hope against Alzheimer's disease, it is also sending very good signals on the fight against COVID-19.

This company, whose market capitalization exceeded 526 million euros in October 2020, is constantly seeking to undertake new therapeutic feats. The floor was given to the CEO of AB Science Alain Moussy, to discuss this French innovation as part of our BlastingTalks project, which consists of focusing on the challenges that companies are facing during the evolution of the digital world and of this period of unprecedented health crisis.

AB Science is developing new drugs to treat diseases with high unmet medical needs such as inflammatory diseases, conditions affecting the peripheral and central nervous system and cancers. Could your treatments also help fight COVID-19?

Absolutely, in fact we have discovered that Masitinib possesses the double potential of being able to treat patients that are seriously ill with COVID-19 by preventing life-threatening complications associated with the disease, and also to act as a direct antiviral agent by blocking enzymatic activity crucial for COVID-19 infection and reproduction.

Many patients with moderate and severe COVID-19, develop a “cytokine storm” that leads to severe pulmonary inflammation and various thrombotic events associated with acute respiratory distress syndrome (ARDS) and potentially death.

The combination of Masitinib and Isoquercetin, which has demonstrated a synergistic effect against senescent cells, may prevent the development of these two complications. Based on this we have initiated a phase 2 study evaluating Masitinib combined with Isoquercetin in hospitalized patients with moderate and severe COVID-19.

In parallel, scientists from the University of Chicago conducted a preclinical study comparing 1,900 drugs to determine which could effectively inhibit viral replication. Masitinib was the standout drug with the study authors concluding that the anti-viral and anti-inflammatory properties of Masitinib could be a strong clinical trial candidate for treating COVID-19.

University of Chicago research is now focused on trying to demonstrate Masitinib’s antiviral action in animal models, which would be a major breakthrough.

How did AB Science react to the COVID-19 Crisis?

Our first response was to ensure the welfare of our teams, to ensure that the data integrity of our various programs was not affected, and to work closely with our contract research organizations to monitor the safety of patients who were still participating on studies. Fortunately, there was very little impact on our overall clinical development program as at that time many studies had just been completed and new confirmatory studies were not yet initiated. Delays in data readout and initiation of new patient enrollment were limited to just a few months.

Our next reaction was to study data being shared by scientists from around the world about this new disease and it soon became apparent that AB Science could contribute to the global effort to combat COVID-19. This led to initiation of a clinical program for Masitinib in COVID-19 and research collaborations to elucidate Masitinib’s antiviral properties.

You recently presented encouraging results in research against Alzheimer's disease. Can you describe how your technology is actually fighting this disease?

The potential therapeutic benefit of Masitinib in Alzheimer’s disease is linked to two possible mechanisms of action: the role of innate immune cells (mast cells and microglia) in neuroinflammation and regulation of the blood-brain-barrier permeability; and the inhibition of the protein kinase Fyn, which is involved in amyloid-beta signaling and tau phosphorylation.

It is estimated that there are 35 million cases of Alzheimer’s disease worldwide. Today, there is no treatment that can cure or improve life with this disease. What’s your position on this medical vacuum?

There is an immense need for treatments that can improve quality of life and slow or even stop the disease process at an early stage. In the United States, Alzheimer's disease affects 5.8 million patients and there are 1 million new cases each year. In France, there are 900,000 patients and 225,000 new cases each year. There are an estimated 35 million cases in the world and with an aging population the number of cases will increase further in the years to come. Based on the findings from our recent positive study in Alzheimer’s disease, we are going to launch a confirmatory study with a refined patient enrollment criterion to target a population that can best benefit from Masitinib.

Given that decades of research and development effort have failed to yield any new effective treatment for this disease, an innovative approach is almost certainly required. Masitinib’s mechanism is novel in its targeting of the innate immune system via mast cells and microglia.

Apart from the results of Masitinib in Alzheimer's disease, we can also conclude further evidence for its efficacy in 3 neurodegenerative diseases. Could you explain how this can possibly help these patients?

Following the results of Masitinib in Alzheimer's disease we now have three positive, late phase studies in neurodegenerative diseases, with progressive forms of multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) being the other two.

These clinical results, all at the same dose, are complemented by a growing body of preclinical data from our research partners and also independent laboratories. We believe that a key mechanism of Masitinib in each of these diseases is its ability to modulate two cells of the innate immune system; namely, mast cells and microglia. It is known that these cells exert profound effects on their surroundings and neighboring cells and can therefore contribute to a degenerative neuronal microenvironment. Masitinib modulates the activity of these cells, disrupting mast cell-microglia crosstalk (that is, interactions between mast cells, glial cells and neurons) and promotes a more neuroprotective microenvironment.

The therapeutic effects of this are a reduction of symptoms and slowing down of neurodegeneration, possibly even stabilization if patients are treated at an early enough stage of the disease, before irrevocable damage has occurred. Overall, this body of evidence makes for a compelling argument that Masitinib provides a real response to neurodegenerative diseases via an innovative mechanism of action that we hope will ultimately offer patients a much-needed new treatment option.

In December, your company announced the success of its capital increase for a total amount of 15 million euros. How will these funds be used?

These funds, together with other recent financing transactions, will ensure the initiation of new confirmatory studies.

We already have two confirmatory studies open to recruitment in mastocytosis and amyotrophic lateral sclerosis and we are going to launch others in Alzheimer's disease and progressive forms of multiple sclerosis (MS).

Since its IPO in April 2010, your company has come a long way. You seem to have a string of good news in recent years, can we say that your biotech is in very good health and what are your near-term plans?

To date, AB Science has positive late phase studies for Masitinib in six indications, mastocytosis, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, progressive forms of multiple sclerosis (MS), pancreatic cancer and severe asthma, many of which have had readouts in 2020.

Through its innovative mechanism of action, Masitinib unquestionably has great potential as a treatment for neurodegenerative disease and we will be pursuing confirmatory studies in Alzheimer's disease, MS and ALS. As for our programs in pancreatic cancer and severe asthma, we have now carried out two studies for each of these indications and will ask the Health Authorities if they consider that these data are sufficient to submit a marketing authorization request. We will also have results from the metastasized prostate cancer study in the near future.

Looking forward to the latter half of 2021, what are some plans and milestones that we can expect?

Although the COVID-19 crisis has presented many unforeseen challenges to our team and development program, it has also revealed the very exciting characteristic of Masitinib being an effective antiviral drug.

We continue to pursue this new avenue of research in 2021, including phase 2 studies in COVID-19 and further collaboration with the University of Chicago to demonstrate Masitinib’s antiviral properties in animal models.