TreeFrog expands its development and presence in bioprocesses in Asia and the United States
TreeFrog Therapeutics, a private company based in Bordeaux, France specializing in stem cell-derived therapies, recently closed a $ 75 million funding round. The funds will be used to deploy the Biomimetic C-StemMT clinical grade manufacturing technology, at two new TreeFrog sites in Boston and Kobe, Japan.
The company claims that C-Stem offers “unprecedented scale and quality, enabling the exponential growth of human-induced pluripotent stem cells (hiPSC) and their differentiation into microtissues ready to be transplanted into industrial bioreactors.”
Preliminary results suggest that C-Stem maintains the genomic integrity of cells through large-scale expansion. Based on preclinical experience in Parkinson’s disease models, TreeFrog is preparing to launch human studies in 2024 and intends to further expand its pipeline through internal programs and partnerships.
To achieve exponential growth of stem cells, TreeFrog Therapeutics has developed a technology that mimics the microenvironment of pluripotent stem cells: C-Stem. Using proprietary microfluidics, hiPSCs are encapsulated at a high rate of over 1000 capsules per second. In each capsule, the stem cells self-organize to form an in vivo-like microtissue of stem cells, which promotes rapid, high-fidelity cell division.
“The capsule is designed to be biomimetic. It is a porous membrane, which allows the diffusion of nutrients, gases and growth factors in and out, ”said Kevin Alessandri, PhD, co-founder and CTO of TreeFrog. “But it is also a shield, which protects the stem cell niche from mechanical stresses in industrial processes. Once amplified, the microtissues of stem cells can be directly differentiated into functional tissue units ready for grafting in the same bioreactor, and the capsule can be easily removed within minutes to release the cell contents.
Why would a small French biotechnology company expand to two places so far apart? The answer lies partly in science and partly in the markets. Japan has always been at the forefront of iPS technology. TreeFrog hopes to tap into this expertise. At the same time, the United States is the center for the commercialization of regenerative therapies. Half of the 1,200 companies operating worldwide, and 70% of funding, are based in the United States.
The expansion of iPSC is challenged by scaling and genetic quality issues, as cells come into contact with non-physiological environments (eg, culture equipment or mechanical stresses induced by the turbine. ). These conditions cause stem cells to experience high death rates, spontaneous differentiation, and genetic drift, including genetic and chromosomal abnormalities linked to cancer.
In a study unveiled in May 2021, TreeFrog Therapeutics showed that C-Stem outperforms both 2D cell culture and standard suspension cultures for iPSC expansion. “But more importantly, preliminary results suggest that C-Stem is the only technology capable of containing the selection of oncogenic mutations within the framework of a large-scale iPSC culture,” says Frédéric Desdouits, PhD, CEO of the company. . “Two factors could explain these results. The capsule provides a biomimetic environment that promotes rapid growth and high-fidelity chromosomal segregation, and the capsule protects stem cells from mechanical stress, thereby greatly reducing cell death.
TreeFrog plans to begin a Phase I trial for Parkinson’s disease in 2024. Their clinical product, iPS-derived microtissues containing mature dopaminergic neurons, differs from cell therapies currently being investigated for this indication. “In our case,” explains Desdouits, “the product does not“ mature ”in the host’s brain. We transplant fully functional neurons, which have been shown to integrate into the brain and trigger complete recovery of motor function in preclinical models twice as fast as cell-based progenitor cell therapies – eight versus sixteen weeks.
In addition to therapeutic alliances, TreeFrog seeks to establish scientific partnerships to deploy C-Stem technology for clinical-grade manufacturing in the main European, American and Japanese markets.