Frontrunners in the Latest Stem Cell Technology

TreeFrog Therapeutics is leaping ahead in cell therapies through
resources such as new technologies and investor partnerships.

For more than a decade, manufacturers have been exploring new ways to improve the efficiency of cell therapy production to make it more cost-effective and accessible to those in need. Many companies have been working in this field, including US-based CAMP4 Therapeutics and Stealth Biotherapeutics’ and France-based TreeFrog Therapeutics SAS, and innovative approaches have now been developed to provide viable stem cells, at scale.

Scalable C-Stem technology

In 2018, Erwan Bezard, Jean-Luc Treillou, Kevin Alessandri, Laurent Cognet, Maxime Feyeux, and Pierre Nassoy co-founded Bordeaux-based TreeFrog Therapeutics with the sole mission to establish a secure cell production process based on their proprietary 3D C-Stem scalable technology to improve the accessibility and affordability of induced pluripotent stem cell (iPSC)-based therapeutics (1).

In July 2022, Peter Nell, PhD, joined TreeFrog as an independent board member. He previously worked at Bayer Healthcare and has extensive knowledge about business development and licensing and clustered regulatory interspaced short palindromic repeats (CRISPR) technology (2).

Attracting investor attention

In January 2022, the company was recognized as one of the top 25 BioTech start-ups (1). Since its conception, it has attracted US$86.9 million (€80.8 million) in series A and B funding from private equity investors, including Leonard Green and Partners, XAnge, AQUITI Gestion, BNP Paribas Développement, and Bpifrance, as well as Bristol Myers Squibb, Aquitaine Science Transfer, and the European Commission (1).

The company has utilized this funding to leverage its C-Stem technology to generate a pipeline of innovative products which include iPSC dopaminergic neurons to treat Parkinson’s diseases (enter Phase I in 2024); and preclinical programmes using hematopoietic stems cells for bone marrow transplant, cardiomyocytes for myocardial infarction, iPSCs platform and NK and T cells for immune‑oncology (3).

First-in-human trial expected in 2024

TreeFrog’s lead programme targets Parkinson’s disease via the generation of three-dimensional (3D) neurospheres which contain mature dopaminergic neurons. Following promising pre-clinical studies, the company is expecting to enter first-in-human (FIH) trials in 2024 (3).

On 11 Oct. 2022, TreeFrog’s collaboration with the contract development and manufacturing organization (CDMO) Invetech, came to fruition, and the first good manufacturing practice (GMP)-grade cell encapsulation device was installed and will be used to produce TreeFrog’s PD cell therapy candidate.

The device combines microfluidics and C-Stem cell biology to generate biomimetic alginate capsules seeded with iPSCs. The encapsules iPSCs rapidly expand and differentiate in 3D culture to produce ready-to-transplant microtissues. The capsule helps to reduce the impact impeller shear stresses exerted on iPSCs cells in large-scale bioreactors which can generate more than 1000 capsules per second, and are suited to seed reactors from 200 mL to 10 L (4).

In 2023, the GMP-grade cell encapsulation device will be transferred from TreeFrog to the CDMO to manufacturer clinical grade batches for Treefrog Parkinson’s Disease programme, and three additional GMP encapsulation devices will be delivered to Invetech to support TreeFrog’s pipeline programme.

TreeFrog taps into new technologies through strategic partnerships

TreeFrog has forged several partnerships to tap into new gene editing technologies by leveraging its C-Stem technology.

In June 2022, Treefrog teamed up with iPSC engineering Umoja Biopharma, USA, to use it synthetic rapamycin-activated cytokine receptor (RACR) technology in combination with TreeFrogs C-Stem platform to generate off-the-shelf iPSC-derived allogenic products that target immune cells in solid and haematological malignancies (5).

Geographical expansion to drive C-Stem adoption

TreeFrog has ambitious plans to drive adoption of its C-Stem technology across the globe. The company has started expanding its workforce and facilities; in 2022, the company aimed to double its laboratory capacity for the development and production of iPSC therapies.

During 2022, it opened technological hubs in Boston in the United States and Kobe, Japan, and aimed to establish strategic alliances with leading academic and biopharma players.

In 2022, TreeFrog awarded several Stem Cell SpaceShot grants to leading academic institutions including the University of Sheffield, UK; MCR Laboratory of Molecular Biology, Cambridge, UK; Harvard University, USA; University of California, USA; R&D Center for Cell Therapy, Kobe, Japan; and CNRS, France, which brought together experts in stem cell, gene editing and biophysics to drive further innovations in this field (6).

What does the future hold for TreeFrog?

Investors will be watching this unicorn stock closely to see if the company delivers on its business goals, providing three additional GMP-grade devices to Invetech in 2023 and initiating a FIH trial for iPSC targeting Parkinson’s Diseasein 2024.

Additionally, it is anticipated to bring more news during 2023/2024 regarding further partnerships/licensing deals across the globe, as the company leverage its C-Stem technology with leading academic institutes and biopharma companies.

Competition in this field will increase as new technologies come to the forefront and investment in competitor companies such as CAMP4 Therapeutics (7) and Stealth Biotherapeutics’ (8) have products nearing the market.

References

1. Crunchbase. TreeFrog Therapeutics, Company Profile & Funding. TreeFrog.fr (accessed 13 Dec. 2022).
2. TreeFrog Therapeutics. Peter Nell joins TreeFrog Therapeutics as Independent Board Member. Press Release, 25 July 2022 (accessed 13 Dec. 2022).
3. TreeFrog Therapeutics. Cell therapy pipeline. TreeFrog.fr (accessed 13 Dec 2022).
4. TreeFrog Therapeutics. Treefrog Therapeutics Moves to GMP Manufacturing with Cell Encapsulation Device Delivered by Invetech. Press Release. 11 Oct. 2022.
5. Umoja Biopharma. Umoja Biopharma and TreeFrog Therapeutics Announce Collaboration to Address Current Challenges Facing Ex Vivo Allogeneic Therapies in Immuno-Oncology. Press Release. 10 June 2022.
6. TreeFrog Therapeutics. 3 PhD Students from King’s College London Win the $100,000 Stem Cell SpaceShot Grant. Press Release. 20 Oct. 2022.
7. CAMP4. CAMP4 Secures $100 Million Series B Financing to Accelerate Expansion of its Novel Regulatory RNA-Targeting Platform and Advance Lead Programs into the Clinic. Press Release. 20 July 2022.
8. Stealth BioTherapeutics. Programs and Pipeline. Stealthbt.com. (accessed 13 Dec. 2022). 

About the Author

Cheryl Barton is the director of PharmaVision.

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