What does a llama, a fungal plant disease and a town in Belgium all have in common? The punchline is Biotalys, and for the explanation we need to go back a few years.
“The platform was created to solve human problems,” begins CEO Patrice Sellès referring to the pharmaceutical origins of the company’s technology. He became CEO of Biotalys in 2019, when the company was then called Agrosavfre. The platform that Sellès refers to owes its origin to a chance discovery back in 1989 at Vrije Universiteit Brussels (VUB), when the antibodies of llama were found to have rather unique properties that could have applications in the pharmaceutical industry. The Biotalys platform is one of the descendants from further development work done at the Vlaams Instituut voor Biotechnologie (VIB) in the town of Ghent in Flanders. Another spin-off company from VIB and VUB was nanobody specialist Ablynx. French group Sanofi paid €3.9 billion euros (USD$4.23 billion) in 2018 to buy the company, also based in Ghent, which is the Belgian town in the opening question. But what is a nanobody?
Nanobody at home This is where we bring in the South American camelid. Llamas produce a unique type of tiny antibody – called a heavy chain-only antibody, from which the nanobody (or referred to as an agrobody for the specific applications of Biotalys) is derived. The nanobody is also known as variable VHH (variable heavy homodimers). These heavy
chain-only antibodies are smaller than human antibodies, and are produced in large numbers in response to all sorts of antigens.
(Source: Biotalys)
Schematic showing relationship between heavy chain-only antibody and nanobody
“There are few animals like the llama,” says Sellès. The llama, like other camelids, produce what might be described as simple structured antibodies. From these antibodies it is possible to extract the coding strand of DNA that carries the blueprint to the smallest VHH fragment that will retain the biological affinity against the original antigen. In the case of Biotalys, the plan is to manufacture the protein or agrobody in large quantities. “So that’s it. We start by taking a small protein. That’s the magic,” enthuses Sellès. This ability to generate thousands of potential agrobodies with selective affinity for the selected target from the DNA obtained in a small blood sample is the underlying power of the platform. “If we want to find a bactericide, we first identify the most representative potential targets (or antigen) specific to the bacteria or the species. The llamas are then our innovators. They are used to generate the antibodies.” Like in the case of a vaccine shot, the immune system of the llama once exposed to the antigen, or the target we are after, will generate millions of antibodies that will be the source of thousands of agrobody candidates. That’s the nature’s innovation part. The next stage is to turn that nanobody into a product. That requires the identification of the necessary fragment from the heavy chain only antibody. “Our equipment is essentially the data,” says Sellès.
Once the coding DNA fragments have been identified from the original antibodies, the DNA is incorporated into a yeast. The yeast then becomes the factory for the mass production of the protein. And that will be the plan. The company does not yet have commercial production facilities. Sellès is confident this technology is scalable, citing the established mass production of enzymes used in washing powders. From the question posed at the beginning, the connections for llama and a town in Belgium have been made. Now the fungal disease.
What about fungal disease? Plant fungal disease is the target for Biotalys’ first product, which will be launching at the end of 2022. The target in this case is the fungal disease Botrytis cinerea and powdery mildew. The protein-based product, named Evoca, will be sold as a water-soluble granule and is aimed at high-value fruit and vegetable crop markets. In December 2020, Biotalys submitted its first registration to the Environmental Protection Agency (EPA) in the United States for approval. Sellès is expecting approval to come first in Florida, after which the company is planning for a cascade of approvals in other states. Biotalys has established a subsidiary in the U.S. and will be responsible for gathering feedback on the product, in a process that Sellès describes as ‘market calibration’. The growers need to learn about the product, what it can be mixed with, for example. Sellès is under no illusions that the growers will need support and advice at the beginning. “It’s not like giving a child a new iPhone,” he quips. “We also need to continue learning about Evoca for our product development.” At the moment, the plan is for the next product to be lower cost, and still aimed at the high-value market.
Euronext listing In terms of financing the pipeline, the company went for an initial price offering (IPO) in July 2021, raising €52.8 million, bringing the total capital raised to date by the company to €117.4 million (USD$136 million exchange rate at time of writing). Sellès explains the decision-making to float involved strong debate within the company. “I’m a first-time CEO, and some contacts advised against an IPO, suggesting it was better to wait for a value inflection point.” But Sellès and the team decided to pursue the IPO. Visibility was a key factor. He also notes there are many companies in the biocontrol market with one or two products. At some point, consolidation will occur and Biotalys is looking to participate in that process, particularly since its ambition is not just in the pre-harvest biocontrol sector. Sellès stresses Biotalys is a food protection company, which is a reference to the possible use of its products for post-harvest applications. “We not competing only with chemical companies,” he notes. “The IPO was a risk to take, but the company is looking to play a different role in value creation.”
Gates Foundation grant Hot on the heels of the IPO, the company has been awarded a grant by the Bill & Melinda Gates
Foundation to leverage its AGROBODY technology platform. The title of the project award is Agrobodies for Crop protection and it focuses on using Biotalys’ technology to discover novel protein-based biofungicides with the ability to control Cercospora canescens – the fungal cause of leaf spot disease. The award states the product should be suitable for deployment to smallholder farmers. Over the duration of the four-year project, Biotalys will receive a USD$5.98 million (€5.14 million) grant in non-refundable instalments
to achieve, by the end of 2025, “proof-of-concept of effective on plant protection of the cowpea crop from leaf spot by an AGROBODY bioactive with potential cross-efficacy against other Cercospora diseases (such as C. beticola) for broader application across different crops.” “It was even an honour to submit the proposal. To be honest, we’re still processing winning the award,” says Sellès.
He elaborates that one of the outcomes for the project is that farmers will hopefully be able to sell more of the cowpeas at market, and in this regard, it is also contributing to the company’s mission to make an impact on food systems around the globe. The award is also a good example, says Sellès, of how the technology platform can be used to target a specific disease.
“We’ve been successful, and I’m super proud,” concludes Sellès, “but we’re working in the biotech environment, and if it was easy everyone would be doing it. More good news is to come, through registrations for example, but we need to be ready.” ●
Patrice Sellès, CEO, Biotalys
Plant fungal disease is the target for Biotalys’ first product, which will be launching at the end of 2022. The target in this case is the fungal disease Botrytis cinerea and powdery mildew.
The IPO was a risk to take, but the company is looking to play a different role in value creation.
The protein-based product, named Evoca, will be sold as a water-soluble granule and is aimed at high-value fruit and vegetable crop markets.
