A Problem Shared…

The ways in which individuals, organizations and companies can find solutions on the Internet is constantly expanding – from naming a new polar research vessel using an online vote (the Royal Research Ship Sir David Attenborough, if you’re interested) to funding innovative projects in art, science and technology through crowdfunding platforms like Kickstarter. But how can the crowdsourcing revolution benefit pharma? And how can companies strike the right balance between sharing their own data and protecting intellectual property? We spoke with Adrian Carter, Corporate Vice President and Global Head Discovery Research Coordination at Boehringer Ingelheim, Germany, to find out why he believes open innovation is important for securing a better future for pharma research and discovery.

How did you become interested in open innovation?

I “grew up” in discovery research – I’m a pharmacologist by training. But when I moved from the UK to Germany for a postdoctoral position in the research organization at Boehringer Ingelheim, I quickly developed an interest for neurobiology and spent 15 years working in that area. And then I crossed to the “dark side” – I moved into business development and spent 10 years there. In 2011, I moved back to research in a networking and coordination role at Boehringer Ingelheim that allowed me to bring together these two different parts of the collaboration puzzle. My broad aims were to examine how the pharmaceutical industry and academia could best work together, what advantages that brings, and also what needs to be done from the operational side to make it work well. It made me realize that, as an industry, we need to look further afield for new ideas.

It’s important to recognize that many discoveries in a pharma company do not actually come from inside their own four walls; to be successful in research and discovery, you need to seek out creative ideas from elsewhere. With this in mind, we developed a strategy document that assessed not only where and how we could find innovative ideas and approaches, but also how we could turn them into new medicines. One concept we hit upon was the idea of “opening up” the innovation process and inviting contributions from the scientific community to help solve current research puzzles.

This idea has its pros and cons: on the one side, you have the opportunity to tap into the creative power of scientific minds from all around the globe – someone might just hold the answer to the conundrum. The downside? You have to share some of your own hard-won knowledge. Some people within industry will balk at the idea of sharing propriety information with the public, but if you do it right, the pros far outweigh the cons.

The practice of opening up collaboration and publicizing data has its roots in the software industry in the 1980s. The industry was revolutionized by Richard Stallman, who used the open source approach to create an alternative to Unix, the operating software that large mainframe computers ran on at the time. He encouraged software programmers around the world to work together to develop operating software for mainframe computers that wasn’t tied to Unix’s developer, AT&T, who subsequently licensed it to IBM. The effort resulted in an alternative called Gnu, a recurring acronym “Gnu is not Unix”, which was combined with another open source software kernel, Linux – eventually going on to enormous success. Most of the computers in the world now run on Gnu/Linux software – and huge brands like Amazon, Google and Android, and many more, all use this open access software as the basis for their large servers. I think many people don’t fully appreciate how much of our modern technology is driven by this open access source material. And if an open access approach can have such a far-reaching impact on the software industry, just imagine what it could do for pharma!

What does open innovation mean to you?

“Open innovation” is a term that has evolved over the years. As it’s taken off, we’ve developed a variety of terms to describe the free movement of ideas and data (see “Behind the Buzzwords”). Science is seeing the effects too – many scientific journals today require scientists to make their data public so that others can use it, and more journals are making their papers open access. Large commercial publishers may prefer to keep their content behind a pay wall, but public funders are challenging the idea and demanding that the research they pay for is made publicly available. An open approach to science means that everyone gets to participate in the scientific process – but don’t let that put you off! You don’t have to give everything away for free to participate in open innovation. Different degrees of openness in the forms of project participation, scope and access may be appropriate, depending on your goals.

Open innovation has clear benefits for both pharma and academia. Developing new drugs is an expensive business model with a high failure rate. I call it the rule of 10: by the time you get a molecule to the preclinical development stage (which takes a huge amount of work), the chance it will make it from there to market is around 10 percent – and if it does, it will take around ten years on average. Despite all the effort, there’s no guarantee of success. I believe this is down to a lack of efficacy – candidate drugs often tick all the safety boxes, but fail because they don’t exhibit the desired improvements for patients. Why? One theory is that we simply don’t understand enough about human biology, and I believe that increasing our knowledge will help us overcome the efficacy wall we keep hitting.

Meanwhile, many academic institutions worldwide, which are filled with brilliant scientific minds, are lacking research funding and resources. Collaboration with the private sector is an attractive prospect in this climate – as long as both parties benefit and as long as researchers are not subjected to hidden and unnecessary “strings attached.”

How did opnMe come to be?

Boehringer Ingelheim’s open innovation portal – opnMe.com – started with our work with the Structural Genomics Consortium (SGC), a public/private partnership involving nine pharma companies. The idea was to encourage the scientific community to work on particular proteins that may be of interest by providing them with new tools. One such tool was a chemical probe for the bromodomain (BRD) family member BRD4; making it freely available catalyzed a great deal of research, thereby leading to a number of clinical programs and new biological knowledge on BRD4 (1).

Our work with the SGC helped us to understand the potentially huge advantages of making our chemical tools available to a wider scientific audience. We also learned that you get much better uptake if you provide the tools free of charge – and without any catches. The minute you start charging and adding caveats to the use of the tools you’re offering, people lose interest.

The success we saw with BRD4 led us to launch opnMe.com, a project with two main aspects: “molecules to order (M2O)” and “molecules for collaboration (M4C)”. M2O are chemical probes freely available to the academic world. These are molecules we’re no longer pursuing, for various reasons. Instead of having them sit in our vaults, gathering dust, we have made them available for other people to experiment with. And this option is truly free – no intellectual property restrictions, and no usage restrictions other than requiring that people don’t do anything irresponsible or dangerous, such as using an unapproved molecule in humans. We’d like nothing better than to have someone take one of these molecules, develop a new mechanism or make a discovery, and publish that in a high quality journal. Using this approach, we can advance scientific knowledge and provide helpful tools to researchers, at very little cost to the company.

We’ve taken a different approach with our M4C, which are still part of our ongoing programs. For organizations interested in working with us on these molecules, we provide them under a standard material transfer agreement, and this forms the basis for a more traditional collaboration. Providing these two options in our portal allows us to monitor what information we’re sharing, and how we share it. opnMe.com launched in mid-November 2017 – we are still working to spread the word and seek feedback from our users to help us improve the portal. Nevertheless, we have been pleased to see that the site has been frequently accessed thus far, and we have already received a steady stream of new orders. Embracing open collaboration is a process and I believe pharma will go through a similar transformation to the software industry as we seek new and better ways to work together. I would encourage other companies to follow suit and look at what information they could afford to share to help move science forward.

What’s your top advice for other companies wanting to establish an open innovation initiative?

Internally, you may face resistance: our industry is traditionally a conservative one, and some people may view sharing proprietary information as a big risk. You’ll need to develop a release procedure and criteria for choosing what you want to share, and how you’ll share it. The most important external consideration is how you’re going to connect with the people you need to crowdsource the answer to your problem. In short, you need a reliable Internet portal that functions well; people won’t be interested in what you’re offering if it is difficult to access.

Trust is also crucial. Academics can be wary of industry, so you may need to take the brave step of making the data or tools you want to share truly free – if you try and retrain too much control or place too many restrictions, people will be reluctant. Remember: the more you share, the more you stand to learn!

There are many passionate scientists in both industry and academia. And when you bring them together, the energy and enthusiasm you can generate is incredible. If we pursue the right environment of openness and collaboration to bring people together, I believe we can begin to push the boundaries of biological knowledge and see some truly exciting progress. To do that, we need the courage to do things differently. Some companies are already joining in (see “On the Open Road”), but I want to see everyone getting involved! The more we can get industry, academia and individual scientists to participate, the more we all reap the rewards.

Further Reading: Boehringer Ingelheim has written extensively about open innovation. Read more at http://go.nature.com/1YuLb5l