Decoding the Immune System’s Secrets: Inside the Discovery of a New Medicine

"Sometimes it can be like following a trail of breadcrumbs.”

That’s how Stephen Laroux, a senior scientist in foundational immunology and early discovery at AbbVie, describes the process of identifying a potential new target.

“It’s iterative, it always is. You start with a problem. You ask, ‘how do I approach this problem?’ You find a clue. You mentally pressure test it. If it seems plausible, think, ‘Is there precedent for this?’ Yes? Then, you have to play devil’s advocate. ‘Why wouldn’t this work?’ If the side that says it’s a good idea has more weight, then you go to the chemistry department,” Laroux says.

Since 1989, AbbVie’s 450,000 square foot Bioresearch Center in Worcester, Massachusetts, U.S.A. has been home to hundreds of dedicated scientists working in the fields of immunology and biologics discovery and development. Many of these scientists are focused on early discovery, where they have the challenging task of being step one on the long road to developing a medicine. And sometimes, that first step really can be the hardest.

We spoke to six research and development scientists at AbbVie to uncover the day-to-day challenges they face, and what inspires them even on days when those challenges seem insurmountable.

As project director, George defines scientific strategy and leads immunology project teams to deliver against key milestones.

“There is no typical day, which is what makes the job so much fun. It really helps that we have incredibly talented and creative scientists, and when you let them do their job, and give them some freedom to explore and experiment, to make suggestions, and to go down some uncharted paths, they help to define what our future is.

What keeps us going is the excitement around potentially being able to deliver a new medicine that could help patients with an autoimmune disease that do not have better options right now. And, the science is just so interesting. We're making progress in leaps and bounds, and the enthusiasm is palpable. What keeps us inspired to work hard is great science and great people.”

As a synthetic chemist, Davis helps to build the molecular compounds that get tested to become potential medicines.

“When I first started my career, a lot of the chemistry was more straightforward; there was in general less structural diversity in the target compounds. But, in the years that I've been at AbbVie, the molecules that we are targeting have become more complex and, as a result, we are doing much more challenging syntheses.

To be successful, we have to be willing to take on this more challenging work and not be afraid of going after some pretty complex molecules and, in some cases, less traditional approaches to drug discovery. Because of this it is so important to have the right team in place that can work together and develop the chemistry to deliver molecules that can rapidly drive the projects forward. Looking to the future, we have to do things that have not been done before to help patients who need different and better treatment options.”

Laroux seeks out new ideas and approaches to find the targets that his team could test to see if they have potential for treating disease.

“You can find inspiration in a totally different therapeutic area. Think about immunology compared to immuno-oncology: if something is being explored in oncology, you might want to try the exact opposite approach in immunology. If you have cancer, your immune system is suppressed, and that's how tumors have such a terrible impact, but if you have an autoimmune disease, it’s the opposite -- your immune system is running wild.

Every once in a while an idea for a new target will just pop up out of nowhere and it can come from any source whatsoever – reading the news, scanning scientific journals, or attending a conference. Then, you keep on digging a little bit deeper, looking for more information and if it turns out to be a good idea, you write it down and try to take it further.”

Murdock designs, implements and interprets many of the experiments that are part of the immunology drug discovery process.

“As a student, I started out as a pharmacy major, which would have led me to a career distributing medicine, but I realized pretty quickly that I wanted to be on the other side of it – developing drugs and coming up with the science behind them – so I switched and graduated with a biology degree.

Almost everybody knows someone who has rheumatoid arthritis or Crohn's disease and if you know someone that has one of these autoimmune disorders, it really reminds you how despite all the progress, there is still a need for new therapies are needed, and that one new drug can make a huge impact on patients' lives.

That's what keeps me coming back into the lab and trying to figure it all out: just the possibility of being able to help people. I've been lucky enough to work on projects that have moved into the clinical testing, so that's also incredible motivation for me: seeing what could be possible when our science works.”

Once a molecule has been identified as having potential to help people, Duignan tests how it gets processed within the body.

“The field of pharmacokinetics is all about understanding what the body will do to a medicine once it is taken, because it doesn’t stay there forever, your body eventually eliminates it. To help move that part of the discovery process along, I’ll design experiments to better understand to what degree the medicine is absorbed, metabolized and eliminated and to figure out which molecules might work best for our program. Then, if a molecule or chemical series looks promising, we will also need to conduct experiments to understand what potential molecular interaction risks might exist in patients that will be taking other medications. If there are risks, we will then work to mitigate these risks.

Right now in immunology, we are working on some relatively novel and non-traditional approaches which makes the work even more exciting. I also really like how our teams work closely together. A lot of informal conversations happen during the day and a lot of decisions can be made outside of meetings. The result is our work can be very fast-paced.”

Hoemann uses computational tools to model and design new molecules for the treatment of immunological diseases.

“When I first got to AbbVie a little over 10 years ago, one of the first things my boss said to me was that you have to try things that will fail sometimes. You may have a lot of knowledge and experience, and you may think an experiment is going to go a certain way, but don’t get in the mindset of telling someone 'no, that won’t work.' Let them go ahead and try the experiment. It may fail like you expect, and if it does, you learn from it. Then again, you might also get data that can lead you to new insights or a different direction.

We work very transparently and collaboratively, bouncing ideas off of each other, sometimes yelling back and forth from our seats across the hall. Our leadership at AbbVie has always been very supportive and encouraging of that environment.

It takes more than one person to discover a new medicine. It takes a lot of people and a lot of different steps along the way. Something I really love about my job is that any day I make a discovery – no matter how small – when combined with other discoveries from my colleagues, it can eventually lead to the innovative molecules with potential to help people in need.”