A conversation with Roland Beckmann, inventor of the DutaMab technology

Dutalys co-founder and chief scientific officer, Roland Beckmann, joined Roche at the time to support the integration of the DutaMab technology into Large Molecule Research. Since then, the first molecule developed with the technology (“DutaFab”) has entered the clinic and numerous other DutaFab projects are currently in the Roche Pharma Research and Early Development (pRED) portfolio. We spoke with him about his journey co-founding a biotech and how inventing a transformative therapy now has the potential to bring novel therapeutics to patients.

Most important have been the relationships I have developed along the way. The biggest difference between staying a small and independent biotech and working as a part of Roche is the ability to work with many colleagues and friends, as opposed to contractors. As a small biotech you tend to buy in solutions from contractors; with colleagues, you work out solutions together and there's shared commitment to a longer term goal.

For me it has been inspiring to learn from my colleagues of different backgrounds and specialisations, and also to learn together with them about the challenges we were facing and the solutions we were developing. After five years there is also friendship, and that is a wonderful spirit in which to commit to making medicines.

It is amazing and very humbling to see a concept turned into clinical reality after nearly 10 years. As a researcher, the ultimate satisfaction is seeing early conceptual research not just reflected in publications, new grants or another research opportunity, but really creating the chance to help someone who's suffering from a serious illness to get better. That is awesome.

I think for us, scientists, it is often very hard to pinpoint exactly how an idea originated. My personal answer would be that God gave me the idea.

But what is interesting is that the DutaFab concept was essentially a visual idea. I was thinking about antibody stability and examining antibody molecules on the computer screen when it struck me that we could accommodate two nicely separated binding surfaces on this beautiful shape of the human Fab fragment.

And this illustrates for me, then as it does now, the transformational effect that the computer visualisation of molecules has had on our research. When I studied biochemistry as an undergraduate, I used computers only to send emails. However now this modern visualisation of molecules is indispensable in our daily work – to both understand some lab results and prompt completely new ideas.

My dream for DutaFabs has never changed. I have seen the suffering caused by severe disease among my friends and family. My brother died from cancer when he was only 34 years old. And when someone has a severe illness, it is not only the patient who is impacted – families share both their darkest moments and their hopes.

My dream for the DutaFabs has always been that one day a patient and their family will say, "Oh thank God for this wonderful drug". We are not there yet, but I would say we are on the way. I hope that DutaFabs will continue to grow across Roche sites and therapeutic areas to include our colleagues in Zurich, but also Genentech Early Research & Development (gRED), Chugai and maybe even our future colleagues in gene therapy. The range of diseases and scientific problems and challenges is so diverse, and I believe strongly that the potential of DutaFabs is big enough that we can share the technology with many colleagues.

Those were momentous days. I remember the feeling of hoping to live up to the high expectations. My personal hope was that we would deliver, especially on the first one or two projects, and my concern was that we might fail on the first portfolio targets that we were challenged to address. Because in the end, it is experimental science and the outcome is never predictable. Thankfully those programmes got off to a good start.

Most importantly, Roche provided the projects to apply our technology to! Deciding which projects to embark on is one of the most critical decisions in our lives as researchers because we invest so much time and effort into each project. At Roche, this decision process is overseen by a team of experts who assess where the greatest patient need lies. I have been very fortunate to contribute to a number of new project proposals, helping to bring several DutaFab projects into the pipeline. Remarkably, Roche has numerous DutaFab portfolio projects in total now - about half are in Ophthalmology, but it has become much broader to also include several other. That is something that a small biotech could simply never do on its own.

For a small biotech company, success is generally founded in three areas: The first is technical success. The second is obtaining funding, which can be a big challenge. And the third is finding interested parties.

One might expect that the definition of success in large industry would be simpler because funding and interested parties are already a given, but in fact I have found ‘success’ to be more complex than that. For a drug to be developed, you need to succeed in achieving a strategic fit in the pipeline, supporting complex decision-making, performing prioritisation, exercising diplomacy and cross-functional negotiation and lots of careful stakeholder management – all in addition to technical success. I would say that I had to learn new skills and reassess my definition of success.

My impression is that biotechs are not only going faster, but also further than 10 years ago. Today at Roche, we have competitors who are small, very lean, well-funded and fast. Biotechs are now taking drug candidates all the way into the clinic and going head to head with us in our field. This says to me that for Roche, our sense of urgency and our agility are crucial. At the same time, biotechshave to focus their efforts very specifically. What is critical for them is choosing an application where there is a real and significant need, and developing their innovation so it is not just an alternative solution to a problem, but the best or only solution. Of course that is easier said than done, but if there is a good fit to a strong need then there is a way forward to develop the innovation.

Finding that fit with a real need is the key.

Rather than individual highlights, it is really the entire journey that has been most precious. It has been great to see the DutaFab molecules generated in a number of diverse indications, watching them improve and meet extremely challenging criteria. Also seeing my wonderful team members grow so much from being newcomers to the world of DutaFabs to now being experts in their own right. Being part of that journey has been an incredible privilege. Another fond memory is the openness and honesty we encountered from Roche from the very beginning, during the time of our first interactions. We were extremely happy, and I must say, a bit surprised, too, that Roche was playing with very open cards. There was never any bluff. That gave us the clear feeling that Roche was an honest, open andof people who would be great to work with.

That is what made us confident that Roche was the right home for the DutaMab platform.