Why do so few cancer medicines originate from the Netherlands despite the high quality of Dutch fundamental research?
Alain: “Key discoveries in Dutch labs often remain on the shelf. Researchers frequently lack the expertise and financial means to set up the trajectory necessary to turn their discovery into a medicine.”

“Pharmaceutical companies, on the other hand, will only start to invest in the research and development of a drug once it’s clear that the scientific discovery in question can really make a difference. But to be able to determine this, an invention needs to be at a relatively advanced stage already. As a result of this Catch 22, precious research knowledge that could have resulted in viable cancer medicine goes to waste.”

Friso: “Even when new prospective drugs are being developed, the chance of them entering the market is low. Most candidate cancer medicines do not survive the clinical trial phase, during which they are being tested by patients to see if they work. This is not just the case in the Netherlands, but a world-wide problem.”

What makes prospective cancer treatments so prone to failure?
Friso: “Cancer is a notoriously heterogeneous disease. The typical lung, bowel or other type of cancer patient doesn’t exist. This is because tumours aren’t just characterised by their place in the human body but can also differ in terms of genetic features or other modifications. Also, each patient is unique in the way their immune system can battle cancer. This makes the development of personalized cancer medicine imperative.”

“But rather than having individual patient needs steer the medicine creation process, the patient currently only comes in at the end of the cancer medicine research & development chain, when the developed prospective medicine is tested in a clinical trial. This is usually done in cancer patients who are in the final stage of disease. Scientists and pharmaceutical companies greatly benefit from the valuable data generated in such trials, for instance on medicine safety. But the participating patients rarely do since the drug they tried was never developed for their specific tumour type. This is not only to the detriment of these patients, but potentially to other patients as well. In case of an overall high failure rate, the medicine won’t be further developed and brought onto the market – even if it could benefit a certain subpopulation of cancer patients.”

Alain: “The lack of focus on specific patient groups, and the resulting high failure rate of candidate cancer drugs in clinical trials, also has other significant drawbacks. It results in huge financial losses for pharmaceutical companies. To compensate for these high costs, they put up the prices of the few cancer medicines that do make it onto the market. A case in point is the pricing of Revlimid, a drug directed at Kahler’s disease, a type of bone marrow cancer. The price dropped 99% after the patent was expired.”

“That’s not all, however. The fear of suffering high losses on a failed cancer medicine is a main reason for pharmaceutical companies to tread so cautiously when it comes to the translation of scientific discoveries into cancer medicines.

How does Oncode-PACT want to solve this challenge?
Alain: “By revolutionising the way the cancer medicine pipeline works. De-risking the preclinical stage and integrating it with clinical trials is an important pillar of this process. This can be achieved through the usage of organoid technology and predictive artificial intelligence, together with collection of huge amounts of patient data.”

Friso: “In fact, we have already started that process. Upon diagnosis, every cancer patient is enrolled in the National Cancer Registry When a patient consents to this, scientists gain access to his or her electronic medical records as well as to small amounts of both tumor and healthy tissue that were being taken away as part of diagnostic processes or surgery. Fortunately, the response rate has been very high; most patients indicate they are happy to do so to help beat cancer.”

“This tissue is then used to grow mini organs and tumours in the lab – the so-called organoids – which scientists can then use for analysis and to test candidate medicines on.”

Alain: “Oncode-PACT will also invest in the Dutch drug development infrastructure, both by expanding existing labs and medicine manufacturing places and by building new facilities. These include a National Organoid Center as well as an Artificial Intelligence technology platform aimed at facilitating the preclinical cancer drug development stage. These changes will ensure that organoids can be used on a large scale in the preclinical process by scientists. As such, Oncode-PACT addresses important gaps in the current drug development infrastructure when it comes to the shift to preclinical testing.” 

Emil: “Of course innovation doesn’t just depend on technical advances, but also on people with experience in the field. Another important goal of Oncode-PACT is to bring together all relevant Dutch stakeholders in cancer medicine development, including hospitals, biotech and pharmaceutical companies and academia, to work with each other to improve and use this new way of preclinical development of cancer drugs. This collaboration will further strengthen the already strong Dutch infrastructure around cancer medicine development.”

This all sounds highly promising. But how can we know that organoid technology will really work, as a new technology?
Alain: “While organoids are still a relatively novel technology, their value for drug development is already well-established. For instance, research shows that lab-grown organoids do accurately reflect the patient tissue they were derived from – meaning that they can indeed be used to find out how the tumour in question will respond to a certain medicine.”

“The benefits of organoid testing are also already visible in the field of cystic fibrosis. Just like cancer, this illness is characterised by a large variety in genetic mutations, which can complicate the working of medicines. Following organoid testing, researchers were able to ascertain for which patient groups a certain medicine could indeed work – upon which patients in these subgroups also received this medicine.”

Emil: “We’ve also already seen it work in a drug development context. Dutch pharmaceutical company Merus tested a new medicine in the clinic, that was tested first on organoids.”

The Oncode-PACT proposal has been submitted as an application to the National Growth Fund. This governmental fund only allocates funding to projects that have ‘the highest potential of contributing to our national earning capacity and to durable economic growth’. How does Oncode-PACT seek to achieve this?
Alain: “The PACT proposal could in various ways work as a magnet for entrepreneurial activity and, in the process, create jobs. For one thing, given the novelty of such an innovative infrastructure, foreign companies are likely to want to invest in it or use it, for which they would be charged a fee. Combined with the improved and integrated Dutch cancer research and health ecosystem, it is also likely that some new foreign companies would want to settle here. This would lead to an influx of foreign investments as well as valuable new jobs.”

“Meanwhile, the new insights generated through working with innovative technologies like organoids and predictive artificial intelligence systems, are likely to find their way into the broader Dutch knowledge economy, thereby strengthening it.”

Emil: “In the meantime, the more targeted way of cancer medicine testing that Oncode-PACT promotes, could also boost Dutch entrepreneurship around new cancer medicines. Scientists and companies that can determine more accurately for which patient population a prospective medicine had best be developed and tested, will stand a higher chance of successfully developing a new cancer drug.”

“But that’s not all. By de-risking the preclinical stage, and by making it more focused, the trajectory towards the creation of a new cancer drug can become shorter and cheaper, given that there is no longer a need for large-scale randomized clinical trials.”

“Over time, this could change the Netherlands from a country that imports its cancer medications, to a country that also exports them. Which would not just boost the Dutch knowledge economy but could potentially also cut public spending on cancer treatments. As such, the benefits of Oncode-PACT go well beyond individual cancer patients and can benefit Dutch society as a whole.”

* PACT is an abbreviation for Preclinical Accelerator for Cancer Treatments.