First believers
Guilhem de Vregille, Partner

Investing in Treefrog Therapeutics

We’re at the dawn of a new era where we are truly able to design biology. We used to grow our vaccines; now we can print them. We made exceptional progress in reading, copying, editing, and now writing DNA with tools like CRISPR. The first cells therapies that were approved by the FDA already required very sophisticated cell engineering. That’s just the beginning. In this bustling environment, pluripotent stem cells open new therapeutic avenues in regenerative medicine. They indeed constitute an infinite source of cells, to replace sick or aged cells in any organ. However, they require significant advances in cell line selection, bioproduction, and therapeutic delivery, to truly impact the lives of millions of patients suffering from currently incurable diseases, such as diabetes or Parkinson’ disease.

Talking about bioproduction, TreeFrog Therapeutics is a company founded in November 2018 in Bordeaux by a stem cell biologist and an expert in microfluidics. Together, they developed a high-throughput cell encapsulation technology allowing for the mass-production and differentiation of stem cells in industrial bioreactors. In 2021, they demonstrated that their biomimetic technology outperformed all existing technologies for stem cell expansion, in term of scale and quality.
But more importantly, they showed that their technology can turn stem cells into ready-to-transplant 3D microtissues, which better integrate in the host, thus allowing for faster therapeutic effects. To make it short, TreeFrog’s technology enables to mass-produce safer, more efficient and more affordable cell therapies, not just for a few hundreds of patients, but for millions of them.

The Treefrog Therapeutics team represents the next wave of bio entrepreneurs who are pioneering the frontier between physics and biology, liberating a new wave of productivity in biologic drug development. We are proud to have led their Series A two years ago, happy to significantly reinvest in this $75m fundraising, and I’m thrilled to continue to support the development of the company as a board member.

From a tech plateform to a fullstack, vertically intregrated company

I was particularly marked by this very powerful and symbolic way of Judy Savitskaya and Jorge Conde (Partners at A16Z) to present the revolution underway in the US in biotech:

 “Virtually every company in biotech claims to have a platform. But historically, platforms weren’t particularly productive when it came to producing multiple new therapeutics. If successful therapeutics are the golden eggs of the biopharmaceutical industry, platforms are the geese, most of which produce few (if any) golden eggs. That’s because each effort to discover a disease target, and develop a molecule that hits that target without causing toxicity elsewhere, is a low-throughput, bespoke process—thanks to biology’s incredible complexity, strategies and solutions that work against one target are likely irrelevant for the next one.

Since most of a company’s value has historically been ascribed to its therapeutic products (or “assets”), biotech companies have a multi-armed bandit problem: Why spend resources feeding the goose? Better to identify an asset that has a shot of being a golden egg and invest in incubators. So companies tend to starve their platform in order to nurture a potential product.

But fertile geese are coming. New kinds of platforms are taking us from bespoke craftsmanship to industrialized drug development. These new industrialized platforms will transform the industry in much the same way that happened when we went from single “job shops” in the early days of automobiles—where raw materials like steel and rubber crafted from start to finish by hand into a trickle of early cars—to assembly line production, with standard components that could be iterated for new models. They will change what we can make, how we make it (and how fast), and how the entire industry is structured.”

Treefrog Therapeutics is the worthy European representative of this revolution driven by the U.S. They started out as a bioproduction technology platform, with an unfair competitive advantage on the most challenging part of the value chain: the large-scale production of high-quality stem cells. Their “dominant design” as the Treefrog’s founders call it! Starting from there, they plan to re-design the entire drug development pipeline, from cell engineering to transplantation, by developing their own cell therapies. In 2018, they were the world’s firsts to implant stem-cell derived mature neurons in an animal model of Parkinson’s disease. They demonstrated full motor recovery twice faster than with other protocols, and are now preparing a first-in-human trial in 2024. Over the next 3 years, TreeFrog will expand its pipeline through in-house programs and partnerships, targeting neurodegeneration, cardiac and metabolic disorders, as well as blood and immune-related diseases.

With this first significant fundraising, they have the capability to heartily feed the goose and to incubate themselves the many golden eggs it produces! I am particularly enthusiastic about the idea of ​​seeing this entrepreneurial team revolutionize their sector and break current bottlenecks.

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