French biotechs / medtechs that advance science (1/3)

With an impressive number of scientific publications in internationally renowned journals and record fundraising in 2020, French biotechs promise to advance research on major themes of the future (Euronext 2021). Biotechs are increasingly involved in the life of applied research in the life sciences and often explore new approaches to therapy (Kauffman Fellows 2015), sometimes unprecedented. This is why studying the pipeline of these early stage companies can be very enlightening both from a scientific and an investment perspective.

The short series of articles that we offer is not intended to constitute an objective selection of the most promising companies on the industrial level but a simple highlighting of innovative scientific approaches which will perhaps constitute the standards of medicine. and the therapeutics of tomorrow.

Treefrog therapeutics

Listed within the FrenchTech210, TreeFrog Therapeutics is a company specializing in cell therapies derived from induced Pluripotent Stem Cells (CSPi) (La French Tech 2021). IPSCs are immature cells generated from an adult (mature) cell that has regained the ability to differentiate into any cell type of the organism from which it is extracted. IPSCs are to be differentiated from embryonic stem cells, which form the internal cell mass of the embryo and can give rise to all types of cells that make up the body. Induced pluripotent cells were first described in 2006 by Japanese physician and researcher Shinya Yamanaka (Yamanaka and Takahashi 2006) in a mouse model. The following year, Yamanaka demonstrated that it was possible to obtain iPSCs from adult human fibroblasts. The discovery of the concept of human iPSCs paved the way for the development of models to study human pathologies, technological platforms for drug discovery and expanding the field of possibilities in autologous cell therapy (Bar and Benvenisty 2020).

Historically reserved for medical research, iPSC-based techniques were not widely used before the arrival of TreeFrog, due to the complexity, cost and absence of techniques allowing their mass production and therefore their industrialization on a large scale. ladder. IPSCs received particular media attention when the 2012 Nobel Prize for Medicine was awarded to Dr Gurdon and Yamanaka (Nobel Prize 2012). However, the translational research exercise required for future therapeutic use of cell therapies derived from iPSCs requires mass production in order to move from the “bench” to preclinical and clinical trials. The transition from a research batch to a “clinical batch” is thus a step that can cost in the order of million (s) of euros, namely a major obstacle to therapeutic innovation both for therapeutic areas. little highlighted or companies with limited financial means (MT ten Ham 2020, 388-397). Through its proprietary technological platform "C-Stem" Treefrog Therapeutics proposes to divide by 10 the production cost of iPSCs and to open the way to all companies whose approach to therapy would require the use of such technologies (Treefrog Therapeutics 2021).

The young Bordeaux company from ENSTBB has already raised tens of millions of euros and forged partnerships with historical players in pharmaceutical innovation in France. In 2021, it is preparing a new, even more ambitious fundraising ...

Tissium

The TISSIUM company, founded in 2013, offers an original approach to tissue reconstruction by developing biomorphic and programmable polymers, in therapeutic areas as varied as they are complex: neurology, gastroenterology, otorhinolaryngology or even cardiology. A fine example of multi-professional and multidisciplinary development of health products of the future! In principle, this developing polymer technology is based on a combination of known compounds, reputed to be safe, such as glycerol and sebacic acid (obtained by the decomposition of ricinoleic acid, itself extracted from the oil of castor). A prepolymer could be precisely applied to tissue during a surgical procedure. The high viscosity of the prepolymer would allow it to be applied with precision, with minimal displacement by body fluids. The viscous prepolymer would then be activated within seconds with the aid of blue light at the desired time, producing an airtight and elastic barrier by mechanically interlocking with the surface of the tissue. The resulting bond would be both adhesive and elastic, allowing the polymer to mimic the shape of the underlying tissues while remaining strongly adherent to them, before resorbing without further intervention. The glue would be bio-absorbed by a mechanism of surface erosion (hydrolysis) without disturbing the natural healing process of the operated lesion. In addition, since the glue is not of biological origin, the possibility of viral transmission that may exist with other types of glue (i.e. fibrin) would be minimized. Preclinical and clinical work is currently exploring its use for multiple indications (Pellenc et al. 2019, 1-13).

(crédit: https://tissium.com/technology/)

Armed with an innovative technological platform and built on technology from the Massachusetts Institute of Technology (MIT), the applications of these polymers could also be combined with the formulation model allowing the sustained and controlled release of active ingredients. These efforts to offer a radically different view of tissue regeneration seem to be paying off. Indeed, the company managed to raise the very large sum of 39 million euros during its second round of funding, in 2019 (Les Echos 2019).

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Autor: Matthieu Argaud (Head of the Biotechs/Medtechs division)

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Bibliography

1. Bar, Shiran, and Nissim Benvenisty. 2020. “Human pluripotent stem cells: derivation and applications.” 2020. https://www.nature.com/articles/s41580-020-00309-7.

2. Euronext. 2021. “Euronext news.” Euronext. https://www.euronext.com/fr/news/barometre-biotech-s2-2020.

3. Kauffman Fellows. 2015. “The Evolving Landscape of the Life Sciences Sector: New Approaches in Therapeutic R&D.” https://www.kauffmanfellows.org/journal_posts/evolving-landscape-of-life-sciences-sector-new-approaches-in-therapeutic-r-and-d.

4. La French Tech. 2021. “Dashboard.” Explore the French Ecosystem. https://ecosystem.lafrenchtech.com/companies/treefrog_therapeutics.

5. Les Echos. 2019. “Tissium lève 39 millions d'euros pour ses polymères chirurgicaux programmables.” https://www.lesechos.fr/pme-regions/innovateurs/tissium-leve-39-millions-deuros-pour-ses-polymeres-chirurgicaux-programmables-1149295.

6. M.T. ten Ham, Renske. 2020. “What does cell therapy manufacturing cost? A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings.” Cytotherapy 22 (7): 388. https://doi.org/10.1016/j.jcyt.2020.03.432.

7. Nobel Prize. 2012. “Prix Nobel de Medecine 2012.” Nobel Prize. https://www.nobelprize.org/prizes/medicine/.

8. Pellenc, Quentin, Joseph Touma, Raphael COSCAS, Grégoire EDORH, Maria PEREIRA, Jeffrey KARP, Yves CASTIER, Pascal DESGRANGES, and Jean Marc ALSAC. 2019. “PRECLINICAL AND CLINICAL EVALUATION OF A NOVEL SYNTHETIC BIORESORBABLE, ON-DEMAND, LIGHT-ACTIVATED SEALANT IN VASCULAR RECONSTRUCTION.” The journal of cardiovascular surgery 46, no. PRECLINICAL AND CLINICAL EVALUATION OF A NOVEL SYNTHETIC BIORESORBABLE, ON-DEMAND, LIGHT-ACTIVATED SEALANT IN VASCULAR RECONSTRUCTION (01). 10.23736/S0021-9509.19.10783-5.

9. Treefrog Therapeutics. 2021. “C-Stem.” https://treefrog.fr/c-stem-cell-large-scale-manufacturing-cgmp-ipsc-cell-therapy/.

10. Yamanaka, Shinya, and Kazutoshi Takahashi. 2006. “Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors.” Cell, 2006. https://www.cell.com/cell/fulltext/S0092-8674(06)00976-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867406009767%3Fshowall%3Dtrue.