Drug repurposing offers opportunities not only for patients and for society, but also for the economy and for investors. Yet Hester Tak, MSc, senior investment manager at development agency Oost NL, often sees reluctance among investors and pharmaceutical companies. Reason for her to initiate the Drug Repurposing Venture Challenge together with ZonMw and FAST.

When Hester Tak broaches the subject of drug repurposing in talks with investors or pharmaceutical companies, she often notices a sceptical reaction. ‘We wanted to know why that was, and we had a student from the University of Amsterdam find out. It turned out that there are knowledge gaps among many stakeholders about the possibilities of developing a drug for an indication other than the one it was originally intended for. The pathway in repurposing is different from developing a new chemical, both in terms of patenting and funding. So it makes sense that people don’t know everything.’

According to Tak, drug repurposing offers opportunities for investors. A lot is already known about an existing drug, so developing it for a new indication requires less research. It is not only cheaper, but the risks are also lower, because side effects, for example, are already well mapped out. The risk of failure is therefore lower. And the returns can be significant: ‘If, for example, it is a drug for a common indication, a company that specialises in it can bring a good price for investors. Repurposing really does not have to be an obstacle in this respect. I therefore see drug repurposing as one of the options in the broad palette of investment opportunities, alongside other opportunities such as developing new treatments.’

Economic and social
According to Tak, the Drug Repurposing Venture Challenge is a great way to publicise drug repurposing. ‘I have been walking around in the world of knowledge transfer and innovation for about 20 years, and so I have also known Chrétien Herben of GameChanger Challenge for a long time. I knew that he and his team organise such a kind of challenge around non-animal innovations, for instance, and so the idea arose to do the same for drug repurposing. Among all parties, from investors to pharma companies and even funding bodies like NWO, there are big knowledge gaps, so there really is still a lot of missionary work to do’.

Unlike what you might expect from a missionary, Tak’s story is quite nuanced. ‘We invest from East NL in many different projects, certainly also in new compounds. As a regional development company, we want to see economic and social impact. The economic impact in the region, for instance in terms of employment, is similar for new compounds and repurposing existing resources. But the societal impact can be greater, because the drug reaches patients faster and also because the development costs are much lower and the risk is lower.’

For the investor, according to Tak, drug repurposing means spreading your risks: ‘When investing in new treatments, it is often the case that only a small part yields really great success, while the rest yields less or even fails. By including some repurposing projects in your portfolio, which usually have a lower risk and lower development costs, you increase the chance that several projects will yield a positive return. They don’t all have to achieve the highest result to still be valuable. It’s ultimately about spreading risk and strengthening the overall return within your portfolio.’

She says the lower costs and risk also provide opportunities to start the conversation about price, in the context of socially responsible licensing. ‘As a publicly funded organisation, this is an important focus for Oost NL in the whole, where we look for customisation every time. On the one hand, we think it is important that healthcare costs remain manageable, on the other hand it must also remain attractive for investors to put money into drug development.’

Broad definition
Branch argues that the definition of drug repurposing should be somewhat broader than just using an existing generic drug for a new indication, with the same dosage and the same formulation and form of administration. In this narrow sense, there are several problematic aspects, such as off-label use and reimbursement. For instance, under the current system, it is difficult for the manufacturer investing in a new indication to recoup that investment because there is no patent protection. The problems surrounding this form of drug repurposing contribute to the sceptical attitude of many investors and companies. ‘Repurposing can mean much more. For example, investing in research into the optimal dosage and form of administration and thus arriving at a patentable new drug for the new indication.’

And then there are all those drugs that fail somewhere in phase two or three of the development process. These include agents that could potentially be of value for other indications. Tak: ‘Because you know a lot more about such a substance anyway, development can be faster and cheaper. Nowadays, there are even investors who specifically target those drugs that are “on the shelf”, but I am convinced that much more would be possible if people were willing to critically examine those so-called failures.’

Even in the more classic definition of drug repurposing, Tak says there is still a world to be gained, both for patients’ unmet needs and economically. One industry that she believes deserves more attention in this is generic drug manufacturers. After all, they already have the production and distribution facilities. ‘Repurposing is close to their current activities, but at the same time it is innovative again. So this can give very nice collaborations with existing pharma, start-ups and investors. Such new partnerships also offer new investment opportunities again.’

Netherlands good position
“I think the Netherlands has a good starting position to become a leader in the field of drug repurposing,” says Tak. She points to the various grants in this field that Dutch research groups have secured, such as REMEDi4all, REPO4EU, IRDiRC. Dutch academic groups in Amsterdam, Nijmegen, Leiden and Maastricht, among others, have built up broad knowledge around drug repurposing for various conditions. The growing collaboration of these groups and companies under the umbrella of the FAST hub RARE-NL also strengthens the opportunities. ‘The Netherlands is well positioned to play a leading role in Europe. And I see that also in the rest of Europe there is an increasing focus on other innovation strategies, within which drug repurposing explicitly has a place, sometimes also in combination with new drugs. I hope we can contribute to this trend towards a new view of innovation, also with the Drug Repurposing Venture Challenge’.