TNO: Innovation In Action

TNO is an innovation organization that faces tough societal challenges like cancer drug development head-on. In the words of Principal Scientist Wouter Vaes: “We aim to bring new concepts to life that have impact and significance for companies, for society, or both.” Rather than focusing on a single domain, TNO typically develops and validates technologies that can be broadly used. As a partner of OncodeAccelerator, TNO’s broad expertise is applied to Demonstrator Projects: oncology drug discovery and development projects that receive co-funding from Oncode Accelerator. Senior Scientist Jennifer McCormack-Venhorst adds, “We connect technology with knowledge and work in collaboration with others, to have impact for science and society.”  

Unique Facilities in Action  

Accelerator Mass Spectrometry (AMS) is one of the cutting-edge technologies that TNO offers. Wouter Vaes explains its use in drug development: “AMS is an incredibly sensitive way to measure carbon-14, aradioactive molecule. Typically, carbon-14 is not used in drugs – but you can incorporate it if you need to. The sensitivity of AMS allows us to dose human subjects with very low amounts of radioactivity andthereby trace back everything related to how the body breaks down the drug, in so-called microtracer studies. For instance, we can assess the safety of the drug, and its potential interactions with other drugs.” 

Because radioactivity levels are very low but still traceable, AMS technology also makes another type of investigation possible: microdosing studies. “The dose makes the poison,” says Wouter, quoting Paracelsus, the Swiss physician credited as the father of toxicology. “If you lower the dose to extremely low levels you can give anybody otherwise toxic molecules in a harmless fashion. Because AMS is so sensitive, we can lower radioactivity doses by factors of a hundred to one thousand times – making possible radioactivity studies that otherwise would not be ethical. Microdosing and microtracer studies are reshaping the clinical development pipeline and are truly a paradigm shift.”  

AMS makes these early-stage studies of novel drugs possible. The cutting-edge technology is already used to assess small molecule therapies – and the scientists at TNO and Oncode Accelerator are collaborating to build it even further.  

“Currently, because of the difficulty with preparing samples for AMS, we only analyze a limited number of samples per study participant: one plasma, one urine, and one feces sample,” says Wouter. “We can get a lot of information out of these samples, but it would be better to make sample analysis faster, to be able to collect even more data.” In collaboration with the Small Molecules Workstream of OncodeAccelerator, the scientists at TNO are developing new technology that will enable exactly that: faster work, and collection of more information. 

Wouter adds: “There is also a lot of benefit in adopting human-translatable approaches earlier in drug development. In the end, models are just models, and animal models are often not consistent, giving very different data than what we see in humans. Performing microdosing studies can be crucially important in making the right choices early on, to avoid going into a phase 1 clinical study with the wrongdrug candidate. For me, setting up a small-scale microdosing study is a no-brainer.” 

Knowledge Meets Technology 

At TNO, you can also find experts in applying AI to challenges in drug discovery and development. For example, Jennifer McCormack-Venhorst and her colleagues use AI-driven algorithms to perform drug target safety assessments: a way to check early in drug development if targeting a specific protein in the body is likely to lead to unwanted side effects. In Jennifer’s words: “With a target safety assessment, the question is: which toxicological effects can occur when a drug inhibits or activates a target?” Knowing this early-on can reduce the risk of failure in a drug development project. 

Traditionally, drug target safety assessments are done manually, by reviewing scientific literature. “Reviewing all those publications requires substantial time and effort and is subject to human bias. Additionally, the growing availability of data increases the chance of missing crucial information,” says Jennifer. “We are trying to overcome this through automation, by asking a generative AI model to extract the relevant information out of papers and other textual documents,make safety claims, and assess what the highest risks are based on the available evidence.” 

Innovating, Together 

From Wouter and Jennifer’s perspective, a key reason to partner with Oncode Accelerator is to share their expertise, provide access to the innovative technologies at TNO, and thereby drive forward progress in oncology. “The technologies we are developing can have a big impact in oncology. But as well as tech, you need the right people around you to make progress happen. And Oncode Accelerator brings a lot of partners together,” says Wouter. 

Jennifer adds, “By working together and sharing our expertise, we can de-risk and speed up the whole drug development process, stop projects that won’t be successful early-on, save money and time, and make sure that good drugs are on the market sooner to benefit patients.” 

Wouter concludes: “Currently, 97 percent of oncology drugs fail in clinical trials. That’s disastrous. We can do better.” 

About TNO 

TNO is the innovation engine of the Netherlands. TNO is an independent, not-for-profit research organization that supports the Dutch government in carrying out statutory and other government tasks in the public interest and helps to boost the earning power of the Netherlands. Driven to push boundaries, TNO createsimpactful innovations for the sustainable wellbeing and prosperity of society by working together with (inter)national companies and organizations as well as the government. 

Website: https://www.tno.nl/en/