An interview with Broad Institute scientist, Steven Ferrara
Steven Ferrara dedicates his working life to developing new ways of treating cancer. He is a research scientist in the Center for the Development of Therapeutics at the renowned Broad Institute of MIT and Harvard. His decision to become a scientist was personal, “When I was very young, my mom had cancer. There was no standard of care for her type of cancer; however she was lucky as surgery and subsequent radiotherapy were enough to cure her. An experience like that really opens your eyes as to how close cancer can hit people. From a young age I was interested in science and trying to help people get over their disease. So, I tailored my career to this.”
As part of his work at the Broad Institute, Steven spent six months at Bayer’s Pharmaceuticals headquarters in Berlin, Germany. Bayer and the Broad Institute jointly discovered a now clinical candidate that blocks the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in the production of DNA building blocks that cells need for cell division. By inhibiting this enzyme, cancerous cells do not receive enough DNA building blocks to continue dividing and spreading in the body.
We caught up with Steven to hear more about his work on the project and the collaboration with Bayer:
Can you tell us about your role in the project on the DHODH inhibitor?
My role in the DHODH project was lead chemist in Boston. The Broad Institute, along with scientists from Massachusetts General Hospital, identified a new mechanism of action for patients with acute myeloid leukemia, and Bayer had a set of compounds from a previous project that were known DHODH inhibitors. Bayer noticed some key liabilities from previous projects that had stopped these molecules from becoming oral drugs. My initial involvement was to carry out some investigative synthetic chemistry to develop a molecule that was suitable for use in animal studies. At this point, Bayer got involved and I moved to Berlin to work with the lead optimization team. We were given six months to fully optimize the molecule into a drug-like substance.
Why did you have to optimize the molecule? Can you explain the key challenge?
The molecule was great at inhibiting the biological function of DHODH, but the metabolic stability of the compound was poor. When developing drugs for human diseases we need them to be stable to have the desired effect, and so the goal was to improve its stability and make it suitable for use in humans.
So, as a chemist by trade, is this the first project you have worked on that is moving into clinical development?
Yes! DHODH is my first ever project to move into clinical development. It’s been great to experience this for the first time. I’ve been in my professional career for four years and it’s amazing to see conceptual science developed on the bench have an impact in critically sick patients. It’s awesome to see a project in which I played a key role have a clinical application. We aren’t just doing science for science, we do science help people live healthier and better lives.
Yes, that’s true, and how do you feel about that?
It’s exciting to know that there are people on this planet that have access to a molecule in clinical trials that I worked on, and that they are putting their faith into it to help get over their cancer. It’s unbelievable to think that we might be able to help these patients who had previously been told that there was little the healthcare system could do for them.
And can you tell us a little more about what it’s like working in collaboration with Bayer?
I’ve been very impressed with the collaboration. We had weekly video conference calls with Bayer colleagues where data was shared openly. We both bring very different skillsets to the table. Bayer is driven and focused on the final goal of delivering a drug to patients to help their lives. Coming from an academic perspective at the Broad Institute, we work to understand the underlying science. Bayer showed great flexibility during the collaboration, including the willingness to not only deliver drugs to clinic, but also to enable the academic endeavor of science. I found that Bayer was adaptive and open to looking at unique ways of doing science.
There are certain technologies that I used at Bayer that have prompted me to sit down and think about how we could scale them to use at the Broad Institute. I have been able to adapt some of my science to Bayer’s style, but on a scale more suited to the Broad Institute.
And do you think that’s why the Broad-Bayer collaboration works so well?
When looking at the DHODH project in particular, we began the drug discovery effort at the Broad Institute by using our knowledge and understanding of disease areas and validating targets, before transferring this to Bayer. Then Bayer’s expertise came into play – they can develop a project and move it into clinic, something the Broad Institute might not be able to do itself. Complementary collaboration brings different sets of skills and we can advance science quicker. The DHODH project moved quickly; the drug discovery effort, which was developed during the collaboration, moved from a research proof of concept to an Investigational New Drug (IND) within two and half years – this would never be possible without such a great partnership.
If you could think back to the biggest learning from the project, what would it be?
Just simply being exposed to the drug discovery process. As a young scientist working in an academic environment, it’s easy to overlook the bigger picture. When you’re focused on your own day-to-day science it’s easy to forget that we are trying to help people. Collaboration, in this case with Bayer, helps to align what we are ultimately trying to do: help people, not just develop science. Science can only have an application if we help people to live better lives or make their lives easier. Having that business mentality from Bayer has opened my eyes on how to move things forward.
And aside from the project itself, how was your time in Berlin with the Bayer team?
When it was initially proposed, I was excited about the opportunity to actually meet the scientists that I work with on an everyday basis via phone or email. I found the staff in Berlin very accommodating and welcoming. I had the chance to work with quite senior employees at Bayer – I can’t imagine that would be the case in all such collaborations. I now work on new projects with some of the people I met in Berlin. It was great to see the other side and to experience how Bayer does science – which is different to how I do science.
It sounds like you had a good time at Bayer!
Yes, I definitely did. I even came back to Berlin one year later for a second stint of five months, this time working on a different project. We get scientists from Bayer in Berlin coming to Boston to do scientific exchanges to see how we do science. It’s enlightening to them and we bring them up to speed with how we do things. We may have the Atlantic Ocean separating us, but this really is a team of scientists – not two departments of scientists – working towards the same goal.