Home to the European Commission (EC), Belgium holds a reputation for life sciences and innovation in Europe. In the port city of Ghent, the Vlaams Instituut voor Biotechnologie (VIB) wants to bridge the gap between biomolecular research and medical and environmental applications.
With nearly 2,000 scientists on board from about 80 countries, VIB, also known as the Flemish Institute for Biotechnology, conducts research in life sciences, predominantly inflammation and immunity, cancer, neuroscience, plant biology, and agriculture. The center has created 40 spin-offs, which have attracted around €2 billion ($2.28 billion) in investments since it was established by the Flemish government in 1995 to solve global challenges in health and agriculture.
As a result, an ecosystem of biotech, human health, and planetary health has been built in Ghent in Flanders, explained Jérôme Van Biervliet, managing director at VIB.
“These things are interdependent. One depends on the other, but you need all the pieces. And it absolutely starts with world-class scientific output,” said Van Biervliet.
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VIB’s Bio-Incubator spans across life science fields
The non-profit research center’s Bio-incubator in Ghent houses around 10 to 15 startups that utilize its lab facilities and to tap into the talent pool. These comprise entrepreneurial local biotechs, spinouts from universities, and international biotechs seeking a gateway into Europe. One such startup is Obulytix, which strives to address the global public health crisis of antimicrobial resistance. This occurs when harmful microbes evolve to withstand the medications designed to kill them, particularly antibiotics. The World Health Organization (WHO) estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths.
Antibiotic resistance, in particular, spiked by 40% from 2018 to 2023, according to a report by the Institute for Health Metrics and Evaluation, and it was recorded that one in six bacterial infections worldwide were resistant to antibiotics in 2023. Critically ill patients in intensive care units, as well as patients who have undergone transplant surgery, are at a significantly higher risk at contracting infections from antimicrobial resistant bacteria.
Obulytix’s approach to fight this growing threat targets Gram-negative bacteria. These are especially resistant to antibiotics because they possess a tough outer membrane that antibiotics find hard to get past. Pioneering a new class of drugs called Precision Lysin Therapeutics (PLTs), these are engineered enzymes called lysins, which act as molecular scissors to cut open the cell wall of these bacteria.
These lysins are taken from bacteriophages, which are viruses that infect bacteria and produce the enzyme. The enzyme is then modified to degrade the walls of specific pathogen and bypass resistance.
“Nature is always extremely creative,” so they had to come up with a creative way to combat resistance, explained Kristof Van Emelen, chief executive officer (CEO) of Obulytix.
Obulytix is the first to do this successfully in vivo in Gram-negative bacteria. Traditional lysins have been tested in the past but failed to make it out of preclinical trials because human cells neutralized them – a hurdle that Obulytix’s engineered lysins are overcoming. Phage cocktails, on the other hand – consists of a slew of engineered bacteriophages – are very effective but hard to scale.
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According to Van Emelen, the team at Obulytix is developing the “best of both worlds” by combining the principles behind traditional lysins and phage cocktails. The company’s technology has been tested against Acinetobacter baumannii among other Gram-negative pathogens and was found to reduce the number of bacteria in mouse models of bloodstream infection.
The company, a spinout Ghent University and KU Leuven in Belgium, has raised €4 million ($4.56 million) so far, with pharma giant Boehringer Ingelheim as its biggest financier.
“It’s really essential that in Europe we start funding innovation or we will lose our share of voice in the global pipeline. It’s as simple as that. We’ll be stuck becoming an importer of innovative goods and services.”
Accelerating partnerships: VIB welcomes funding and grants
Aside from hosting young startups to get a foot in the door with regards to funding and access to advancing their technologies, VIB is also engaged in several partnership programs. For instance, it helped get nanopore technology off the ground along with U.K.-based Oxford Nanopore Technologies.
VIB, along with Vrije Universiteit Brussel (VUB) in Belgium, discovered the bacterial pore protein CsgG, which is a channel found in the outer membrane of Gram-negative bacteria. Researchers at VIB mapped the structure and mechanism of the CsgG channel and found that its narrow constriction was ideal for capturing single-molecule electrical signals. Oxford Nanopore Technologies then licensed the technology and built devices like MinION and PromethION, portable DNA and RNA sequencers, revolutionizing the field of genomic sequencing.
Powered entirely by a USB connected to a laptop, it sequences genetic material by reading strands of genetic material. Enzymes help unwind these strands and guide it through the protein pore. Able to quickly identify pathogens, it helps track and map how diseases spread during outbreaks.
The research institute also partnered with KU Leuven & UZ Leuven to create a tool to diagnose ovarian cancer. Accounting for around 200,000 deaths annually, ovarian cancer is infamous for its poor prognosis, meaning that its often too late by the time the cancer has been diagnosed and has spread to other parts of the body.
Small molecules called PARP inhibitors have been established as a treatment for ovarian cancer, but a specific kind of ovarian cancer. While they’re effective against homologous recombination deficiency (HRD)-positive tumors, where there is a defect in the homologous recombination repair (HRR) pathway – a mechanism that cells use to fix DNA breaks – they don’t work in HRD-negative ovarian cancers. Detecting whether a patient has HRD-positive or –negative ovarian cancer is key to identifying the best treatment route.
Researchers came up with a HRD test, which sequences specific genes to hunt for mutations that show down the HRR pathway. By detecting what is known as genomic scars, which accumulate in tumor cells when the DNA is not properly repaired, the test can tell what kind of ovarian cancer a patient has.
In the U.S., a test like this was developed, but at a very high cost – around $5,000 for a single test. Patients in Europe and other parts of the world had to send their samples to the U.S. to hear back about their diagnosis after several weeks. The European Gynecological Oncology Society made a call for the European scientific community and said, “Look, we need a European solution which is better, cheaper, and faster,” explained Erwin Sablon, head of Business Development at VIB.
“They developed a test which was performance-wise equal or better than what was existing on the market and could be run at one-fifth of the cost of the American test,” said Sablon.
Currently, the Leuven HRD test is reimbursed and available to all patients in Belgium, with over 800 patients having been tested.
Marketing innovation: VIB spinouts take off with seed funding
Meanwhile, the research center has spunout various startups and biotechs over the years. Orionis Biosciences is among them, which along with Obulytix, operates out of the Ghent Bio-incubator. It has designed molecular glues that reprogram pathways that drive disease and take on undruggable targets.
These glues help stick two proteins together. The most common type links a target protein to an enzyme that causes the target to be broken down by the cell’s own protein degradation machinery. They have garnered the attention of big pharmas of late, and Orionis Biosciences’ recent deal with Novartis worth up to up to $1.4 billion and Genentech’s over $2 billion pact with the company last year are proof of this.
The Novartis deal involves the discovery of molecular glues with the help Orionis’ Allo-Glue platform. The platform uses artificial intelligence, and one of its features is being able to analyze protein-protein interactions in living cells through biological assays.
“AI is obviously a game changer for us, and we’re massively investing in all areas, because it allows us to work with these huge data sets that we derive from these patient samples, and really mine it for novel ideas, for novel mechanisms, and for novel insights that we can translate into patient input. But the same holds true in plants. It’s the same logic. So yeah, AI is a big thing. Technology is a big thing.”
Its own molecular glue, ORB-GX, is currently in investigational new drug (IND)-enabling stages.
Aside from biopharma applications, VIB is involved in agrotech. It spunout Rainbow Crops two years ago, in a bid to tackle the impact of climate change on crops.
“Our crops, our farmers face big problems. The crops are not adapted to these heat waves. This fast-changing climate has a big impact on crops,” said Tom Viaene, New Venture Manager at VIB’s Innovation & Business team.
If a heat wave occurs when a crop is flowering or setting seed, it affects about 10% of the yield.
“This is very significant. It impacts food availability. When the climate changes even more, this will have a big impact Europe-wide and even worldwide,” he said.
As developing crop varieties that are resistant to drought take a very long time, Rainbow Crops has combined genome editing and artificial intelligence (AI) to breed new crops quicker. To work on producing crops like sorghum and rice, the Gates Foundation awarded the spinout a $7 million grant. And just two weeks ago, it bagged €9.7 million ($11.25 million) in a seed round led by EuroInvest.
Other spinouts of VIB include Augustine Therapeutics, which is developing inhibitor drugs to treat the genetic condition, Charcot-Marie Tooth disease, and Nanobody technology developer Ablynx, which was purchased by Sanofi in 2018.
“VIB has a very strong track record of 40 spinouts in the last 30 years. We’re really good at that and it’s something we really like to do,” said Viaene.
Lack of funds not a unique problem
Although the institute aims to aid investments through networking, partnership, and grant funding programs, such as its biotech accelerator and pre-seed investor Biotope, Van Biervliet notes that funding is scarce, a growing sentiment across Europe.
“It’s really essential that in Europe we start funding innovation or we will lose our share of voice in the global pipeline. It’s as simple as that. We’ll be stuck becoming an importer of innovative goods and services,” he said.
As only about 2% of grants on thousands of submissions are funded, Van Biervliet believes that there are many “good ideas” that simply cannot take off because of the funding deficit.
“This is really not okay. It’s a disgrace. We need to change this. How can we develop the economy in the future if this is the success rate? This is not enough. It really needs to improve, and it really needs to increase,” said Van Biervliet.
Of late, VIB has seen an uptick in oncology, neuroscience, and AI research. Van Biervliet explained that being able to come up with new technologies and diagnostic tools based on cancer samples has been a big shift in the biopharma industry. So has the AI boom, as we’ve seen with its usage at companies like Orionis and Rainbow Crops at VIB.
“AI is obviously a game changer for us, and we’re massively investing in all areas, because it allows us to work with these huge data sets that we derive from these patient samples, and really mine it for novel ideas, for novel mechanisms, and for novel insights that we can translate into patient input. But the same holds true in plants. It’s the same logic. So yeah, AI is a big thing. Technology is a big thing,” he said.
He added that a lot of attention is also going toward treating dementia and Alzheimer’s. “It’s a huge problem,” he said, “We’re just starting to address that. It’s really just the very beginning of it.”
Moreover, inflammation has been a buzzword doing its rounds on health and wellness platforms. Van Biervliet thinks that it’s where the biopharma industry is headed as well.
“Inflammation has a big hype behind it now because the immune system is involved anywhere from the gut to the brain to the heart. Actually, the biggest improvements in cancer therapy are because we worked on the immune system,” he said.
Furthermore, VIB has been instrumental in shaping the EU Biotech Act as it serves as an advisor to policymakers. Van Biervliet believes that biomanufacturing is a key issue faced by the region that VIB and the Act want to avoid the reliance on U.S. and China markets.
“We’ve become so dependent on global supply chains for manufacturing. We are going through a kind of rude awakening on that front,” he said. “There’s really a need to build and strengthen the European biomanufacturing here.”
While VIB has framed the biotech and life science ecosystem in Belgium, its role in Europe at large has been becoming more prominent. Despite funding being a major challenge, it’s safe to say that research and innovation don’t stop in Flanders.
