IMI Programme Office: Why was a project like yours needed in the first place in Europe?
Ad IJzerman: Target binding kinetics was missing from the current protocols in the drug discovery pipeline. It is not something industry or an individual company can tackle alone: it could only be done together with academia, SMEs and industry.
IMI Programme Office: What exactly is target binding kinetics?
Ad IJzerman: I can make a comparison with visiting a website. Typically, a company that has a website registers all the clicks; they want to know how often the site is being visited. Drugs act in a similar way: they see a target and they click to it when they have an affinity for it. More interestingly, the time that it takes to browse a website, that would probably show the interest of a web visitor more than the actual clicks. The same is true for a drug; it really matters how fast a drug goes to the target or how slowly it goes off the target. That’s what we mean by target binding kinetics.
IMI Programme Office: What were the most important project achievements?
Anke Mueller-Fahrnow: There was a reason why binding kinetics was not considered too much in the drug discovery process 10 years ago. Part of that reason is because we didn’t really understand what properties of a compound lead to a certain kinetic behaviour. There were no assay methodologies to analyse the binding kinetics in a fast manner and we were not really aware of how reproducible the results are because there were few data points prior to K4DD.
Before we could really think about implementing target binding kinetics in the drug discovery process, we needed to lay the foundation and that meant developing assays: test systems that specifically interrogate the kinetic properties of a compound.
The output assays that we developed within the project have been published and can now be used on a routine basis by everyone in the scientific community. We have been using this data already within K4DD to deepen our understanding of compound properties that trigger certain kinetic behaviour. So we have laid the foundation to use this more broadly.
IMI Programme Office: Any other achievements you are proud of?
Ad IJzerman: When we started, there was little information on target binding kinetics. We added at least 10 times as much data as there had been at the beginning. So from a very fragmented dataset that was not very useful, we’ve built a comprehensive kinetics database that the research community can start using now.
Anke Mueller-Fahrnow: Thanks to K4DD, more and more scientists within pharma companies but also in academia are aware of the importance of binding kinetics. So something that has really been pretty exciting and novel 10 years ago, is something that is now broadly appreciated and used in the drug discovery process.
For example, we did a survey of the pharma companies that are partners within K4DD and we talked to pharma companies outside of K4DD at our open end-meeting. The survey showed that nowadays pharma companies use binding kinetics on a routine basis for decision making in the early discovery phases.
IMI Programme Office: So would you say that your project has been transformative in that regard in this field?
Ad IJzerman: I would definitely say that. We have gotten many invitations from symposia and conferences to speak on the importance of target binding kinetics. It has become a hot topic in the field over the last five years.
Furthermore, we have written publications not so much on the science but what we call viewpoints, so what are the pros and cons when you consider including target binding kinetics in your research protocols. We have also given courses to people mainly from industry.
Our own fellows that have been employed in the project have been trained very thoroughly. Now that the project has ended, they have found jobs, many of them in industry and they will keep telling the world about what they have learned about target binding kinetics.
IMI Programme Office: Could you tell me more about the benefits for industry? You mentioned that the project raised the awareness of kinetics, but what were some of the other benefits?
Anke Mueller-Fahrnow: We have developed a number of assays within the consortium and have laid the foundation to expand these test systems to other targets of interest. Nowadays, it is much easier to implement the relevant test systems to generate the data within the short period of time, so that we can really use the data within the design-make-test-analyse cycle that we use for optimising compounds.
Furthermore, these ideas have been taken up by small companies, and they have developed test kits that you can now buy off the shelf, which is quite an achievement. Also there was one SME within the consortium that developed a machine together with an academic partner. They have started the development within the K4DD project and building on the experience they have now developed the second generation of this instrument.
IMI Programme Office: What were the benefits for the academic community from this project?
Ad IJzerman: We got to know how things work in industry and I am saying this in particular because of the fellows in the programme. We had internships for them in industry, so the fellows who wanted could go there and quite a few did. They have learned what it means to do quality control of your data, something that is quite normal in industry.
Secondly, we got a lot from industry: the EFPIA partners provided us with compounds, cells, cell materials, reagents etc. That made it possible for us to get impactful papers with a lot more information than we could have generated otherwise.
IMI Programme Office: Would any of this have been possible without IMI and this public-private partnership?
Anke Mueller-Fahrnow: The EFPIA partners alone probably would not have come together to share their knowledge and experience, so we needed IMI for that and we definitely needed the scientific impact from the academic partners. It was also extremely helpful to have the SMEs on board. I believe that we would not have achieved nearly as much if everyone had continued to work individually on this topic.
Ad IJzerman: At the time when we started, we had been working on kinetics, and we felt it was very important but many of the ideas that we had were just ideas, and we simply didn’t have the means and the resources to do things that we accomplished within K4DD. We should not underestimate the synergy that occurs between partners when they are all oriented towards the same goal.
IMI Programme Office: Anke what was it like to be project coordinator?
Anke Mueller-Fahrnow: On the one hand, really a lot of fun and a tremendous experience for me. On the other hand, to make a consortium like this successful is quite a lot of effort. I had bi-weekly meetings with my colleague Ad and the whole project management team, and we organised two consortium meetings every year. So quite a lot of work, quite a lot of effort, but I think this is really needed if you want to be successful in a consortium like this.
IMI Programme Office: And what about the next steps? What is the sustainability plan now for the project outputs?
Ad IJzerman: There are three things. Firstly, our fellows are the leverage to bring kinetics further. We had close to 30 fellows, many of them ended up in industry and I am sure they are going to keep telling the world and their colleagues about the importance of target binding kinetics.
Secondly, we brought target binding kinetics to the international research community by being active, organising symposia and conferences, writing many papers to explain the concepts etc.
Thirdly, we built the kinetics database, which is a very concrete and sustainable net result of our project.