Posted Apr 16, 2023, 8:00 AM
The amount – five million dollars – is modest, but it is a first for a French company. The Bill & Melinda Gates Foundation takes a stake in the biotech Smart Immune. In its line of sight: a cell therapy technology called ProTCell, which strengthens the immune system in an accelerated way.
It is the fruit of fifteen years of work under the aegis of the public institute Imagine by the teams of Pr Marina Cavazzana (of the Necker hospital) and Isabelle André, who created Smart Immune in 2017 with the support of Father “bubble babies”, Alain Fischer, to exploit the registered patent.
T for killers
The ProTCell technology is currently in clinical trials on leukemia patients requiring bone marrow transplantation. The Gates Foundation wants to test her against AIDS. With the AIDS virus penetrating immune cells, the hope is that ProTCell will make immune cells ‘tight’ to the virus and thus prevent infection.
Normally, blood stem cells take fifteen months to mature into so-called “T lymphocyte progenitors” or “ProT” cells that the thymus transforms into T lymphocytes that kill viruses and infections, also called white blood cells. In case of acute disease, fifteen months is too long and the ProTCell technology aims to accelerate the production of proT by culture in the laboratory.
“Immature cells have long been inaccessible because they are almost impossible to isolate from the blood of patients. We are the first to know how to produce large quantities of proT cells from blood stem cells from donors, thanks to a patented culture process,” underlines Karine Rossignol, former general secretary of Imagine and managing director of Smart Immune, of which she is one of the three co-founders.
Injection post-greffe
In three weeks, ProTCell thus provides injectable ProT in the thymus which in u to three months transforms them into T lymphocytes. These come from the patient’s own thymus, there is no risk of rejection and their lifespan is long (seven to ten years). For leukemia patients, “ProTCell reduces from eighteen months to three months the time necessary for the reconstitution of full immune capacities post-bone marrow transplant, with the hope of reducing the current mortality of approximately 50% observed in three years after the transplant”, summarizes Karine Rossignol.
If the phase 1-2 results are conclusive, the next step will be to genetically modify the proTs so that they become “super T lymphocytes” capable, for example, of identifying certain tumor cells. Or to be impossible to penetrate by the AIDS virus. This would be the case if a receptor present on the surface of immune cells and which betrays their presence were masked, making them invisible to the virus.
Institutional investors
To support Smart Immune, the Gates foundation could have paid a grant, like those granted to two other French biotechs, Medincell and Osivax. “His entry into the capital marks his long-term involvement,” says Karine Rossignol. Because the road remains long.
Since its creation, Smart Immune has only raised around twenty million and is owned by family offices and business angels, with the balance going to the three co-founders. It’s time to bring in institutional investors. A capital increase of around fifty million is planned for this purpose this year. The 15 million recently promised by the European Council for Innovation are part of it, like the 5 million from the Gates Foundation, which will therefore be a symbolic shareholder, for less than 10%, and will not sit on the council.
In 2025-2026, the results of phase 1-2 of the current clinical trials, if they are conclusive, will be accompanied by a new fundraising of 150 to 200 million, this time of “series B” (for more mature biotechs), to launch phase 3, the results of which are expected within five years, and initiate the clinical phase (i.e. on humans and not animals) of the AIDS trial .
In total, from the test of genetically modified proT cells on mice to the end of phase 3 of clinical trials on patients, “the trial on AIDS should take seven to eight years”, estimates Karine Rossignol.
From now on, a blood test is enough to donate your bone marrow
No more excuses for not donating your bone marrow, because today there is no longer any need for a lumbar puncture, “all you need is a blood test session lasting a few hours, where the donor is seated”, underlines Karine Rossignol, director of biotech Smart Immune, recalling that there are “25,000 bone marrow transplants per year in the United States and Europe, but the needs are 2 to 3 times higher”.
In France, 40,000 donors registered in 2022, according to the Biomedicine Agency, compared to 25,000 in 2021. But only 1,100 transplants were performed last year, for 2,000 patients waiting. The difficulty is to find a compatible donor. And doctors are hesitant about the risk of immune rejection of the graft, because three-year survival is only 50% in transplanted leukemia patients (those for whom chemotherapy has not worked).
Grafts from young donors are better tolerated, as well as those from male donors, because they do not have the antibodies developed by women during pregnancy. In France, the median time span is eight years between registration in the donor register and the actual call for a donation.
