For the immunocompromised, the COVID-19 threat remains. But a Belgian company is harnessing nanobodies from llamas to fight the virus and other diseases

Llamas are quirky, long-necked animals, infamous for spitting and occasionally humming when tired, bored, or agitated. They also have a very unusual immune system that could be a secret weapon against COVID-19 and other infectious diseases.  

Thanks to a fluke of nature, llamas produce unique antibodies, known as nanobodies, that are about half the size of human antibodies. They are also more precise and more stable than human antibodies, making it easy for scientists to control and manipulate them.

A Belgian company, ExeVir, is using fragments from llama nanobodies as building blocks to generate new antibodies that can target bacterial cells or viral particles.

© Exevir

Fiona du Monceau

“Because they are smaller, these antibodies can attach themselves to areas of the virus that are inaccessible to human antibodies,” says ExeVir Chief Operating Officer Fiona du Monceau. “By blocking the virus from connecting with other cells, they can stop the threat.”

“Also, they can be put together like building blocks to create multi-specific antibodies”.

ExeVir is harnessing these unique antibodies to develop a therapeutic, called XVR012, which could treat and prevent COVID-19 in immunocompromised and elderly people. The European Investment Bank is supporting ExeVir with €25 million of venture debt financing, signed in December 2022.

The pandemic never ended for the immunocompromised

For the immunocompromised, the COVID-19 pandemic is far from over. They continue to isolate from friends and families and live in constant fear of infection, hurting their quality of life and causing mental distress.

There are about 14.5 million people in Europe with health conditions that compromise or suppress their immune system.  Because of their reduced ability to fight infection and disease, they are more susceptible to severe illness and death from COVID-19. They are 82 times more likely to get infections than the general vaccinated population, even when they have been vaccinated, and 485 times more likely to be severely ill.

Vaccines reduce the risk of infection and severe illness for many immunocompromised people, but there are still many who are insufficiently protected.

“The virus mutates rapidly, making previous antibodies lose their potency against the currently circulating variants,” says du Monceau. “You need to be sure that you have a treatment that will not be impacted by the changes.”

ExeVir’s XVR012 can neutralise all the previous and current variants without relying on the patient’s immune system. That means it offers long-lasting protection for those for whom the vaccine is not enough.

Supporting innovation and biotech in Belgium 

From drug discovery to clinical trials, it can take more than ten years to bring a drug to market.

“The number one challenge is to prove that your compound is safe and effective, and this is a bit tricky with infectious diseases that mutate,” says du Monceau.

For biotech companies, financing is essential. They need to pay for lab space, equipment, salaries, and other expenses associated with research. Clinical trials and manufacturing costs in particular are significant. But many early-stage companies struggle to find the necessary funding. “It is a challenging market, with not many players investing in mutating diseases,” du Monceau adds.

© Exevir

ExeVir is a spinout of Vlaams Instituut voor Biotechnologie (VIB) the leading Belgium-based life sciences research institute

Supporting European biotech companies is vital to strengthening the European Union’s position in the global biotechnology market. Through its venture debt financing, the European Investment Bank will help advance ExeVir’s therapeutic into clinical trials.

“Venture debt loans take the pressure off early-stage innovative companies to repay their loans quickly by providing them crucial liquidity,” says Viorica Revenco, a venture debt banker in biotech and life sciences at the European Investment Bank. “Contrary to other venture capital investors, we offer long-term, stable and non-dilutive financing, adapted to the needs of the companies, so they can continue to grow and innovate.”

The financing is backed by the InnovFin Infectious Diseases Finance Facility. “The facility has helped us finance innovative, early-stage companies active in the field of infectious diseases,” says Gergely Krajcsi, a senior investment officer in the life science and biotech team at the European Investment Bank. “We have provided close to €650 million in funding to 30 companies all over Europe.”

Preparing for the next pandemic

Infectious disease outbreaks are inevitable. But COVID-19 showed us that we can lessen their impact by investing in prevention and pandemic preparedness.

“Nanobodies may provide a distinct advantage in pandemic scenarios due to their ease of manufacture and high stability, allowing for large-scale production of treatments that can be rapidly and easily deployed,” says Valeria Iansante, a life sciences specialist at the European Investment Bank.

ExeVir’s innovation could also be applied to treat other infectious diseases which disproportionately impact people from low- and middle-income countries. The company is developing antibodies against dengue, a  disease that’s an increasing global health problem because global warming and urbanisation are favourable to the mosquitoes that carry it.

 “Our work can serve as a blueprint,” says du Monceau, “for the development of antibodies for subsequent pandemics.”