Currently, only 25,000 patients a year in Europe and the USA have an allogeneic bone marrow transplant, whereas over 75,000 people need one. The Smart Immune solution currently under development overcomes this problem.
“We are the first company in the world capable of developing clinical-grade T-cell progenitors, in just seven days instead of 15 months in human physiology. They are the basis of the new generation cell therapy that we are developing to re-arm the immune system of the patient to fight infections and tumors,” said Karine Rossignol, Smart Immune CEO and co-founder. “This changes the prognosis completely.”
By biomimicking cell differentiation ex vivo for the first time in human medicine, Smart Immune cultivates allogeneic T-cell progenitors which, once infused into the patient, will be differentiated in the thymus into a fully potent immune repertoire in three months. The aim is to have an “off the shelf” product for personalized, safer, more effective and more accessible medicine.
Today the most common procedure is a bone marrow transplant. This consists of sorting the blood stem cells after a bone marrow sample is taken from a donor who is compatible with the patient. But during chemotherapy, the immune system is weakened or may even no longer be functional. This is the case with leukemia patients. However, with bone marrow transplants, it takes at least 18 months for this transplant to be of use to the patient, the time needed for the hematopoietic stem cells (HSCs) to reach the thymus and be educated to be able to kill the cells infected by the virus or the tumor cells. This time window is fatal for patients in almost half the cases (at three years). Smart Immune has therefore taken up the challenge of reducing this window of vulnerability.
Bone marrow transplants have led to the creation of CAR T-cells. These are T-cells that are genetically engineered for a specific type of tumor. This technology is based on mature T-cells, already educated on a thymus (autologous or allogeneic treatment), whereas the Imagine Institute (Paris) spin-off offers access to immature cells that are not yet educated and that it can produce in vitro in seven days. These progenitors are tolerated by the thymus. The advantage is therefore twofold – autologous treatment does not generate any reaction against the host and allogeneic treatment makes it possible to use donor cells that may be available off the shelf.
A first phase I/ II trial has started in France and in Italy with bubble babies. “Initial results are very encouraging. Sick patients very soon rebuilt their immune system, a lot more quickly than in the control arm,” Karine Rossignol said.
Another clinical trial targeting acute leukemia refractory to chemotherapy is being carried out in the USA with adults, with the same Smart Immune lead asset, SMART 101, an allogeneic cell therapy product produced from healthy donors’ mobilized peripheral blood to fight relapses. This will include 34 patients over time. “We are the first in the world to be able to use these cells in patients in clinics. It’s great to be able to lead the way!” the CEO declared.
This study could also have an even greater impact, as it will contribute to understanding how to reverse the T-cell deficit associated with HIV. SMART 101 could therefore constitute a first step towards a so-called “universal” allogeneic cell therapy product that is resistant to HIV.
“This recognition by the Bill & Melinda Gates Foundation is a true validation of the science developed by Smart Immune. The grant and the commitment of the EIC are also an enormous validation, especially in terms of our business model and our ability to create economic value on the European continent.(…) This support and these funds should allow us to remain agile and stay ahead of our US competitors at an extremely exciting point in the life of the company,” Karine Rossignol, CEO and co-founder of Smart Immune.
This phase I/II funding for these clinical trials will be in part guaranteed by a €50 million fundraising operation, which will take place this year, and also by the new investor in the startup – the renowned Bill & Melinda Gates Foundation. On April 17, 2023, Smart Immune was pleased to announce the Foundation’s investment of $5 million, a rare event for the institution. This amount will also serve to speed up the development of ProTcell, the platform based on the startup’s T-cell progenitors.
At the end of March, Smart Immune was also successful in a highly competitive call for offers by the EIC (European Innovation Council). Just 39 companies from approximately 500 applicants (in all industrial sectors) were awarded funds. Smart Immune (along with 16 other European businesses, with variable amounts) was awarded a capital participation commitment of €15 million, in addition to a grant of €2.5 million. This investment by the EIC was made through its EIC Accelerator Fund designed to support small and medium-sized enterprises (SME), in particular startups and spin-outs, in order to develop and scale game-changing innovations.
The biotech company was established in 2017 by Karine Rossignol (PharmD-HEC) and researchers Marina Cavazzana (Irène-Joliot-Curie 2012 Prize; MD-PhD) and Isabelle André (PhD). In March it was selected to be part of the first cohort of the French Tech Health20 program, alongside 20 other companies. This program aims to support startups seeking to innovate in order to promote the technological, industrial and health sovereignty of France.