From The Editor | August 21, 2019

AbbVie's Dr. Howard Jacob: Improving The Drug Pipeline With Genomics

Matt Pillar

By Matthew Pillar, Editor, BioProcess Online


I visited AbbVie HQ in North Chicago this summer for a tour of the company’s Development Design Center and Genomics Research Center. While there, I sat down with Dr. Howard Jacob, Vice President and Head of Genomic Research at AbbVie.  We talked about his work there, how it’s influencing biopharma, and what impact it might have on the future of biologics manufacturing.

Dr. Jacob joined AbbVie just 19 months ago following a storied career in academia, during which he was famously called on to leverage genetic sequencing to identify a gene mutation causing a rare and unidentified disease in a young boy named Nicholas Volker. Dr. Jacob’s team did just that, and the boy recovered following a bone marrow transplant.

Today, Dr. Jacob is working with a team dedicated to improving the drug pipeline using genomics tools, work that finds him building genomic-level blueprints of people to better determine how medicine works at the individual level. The importance of the relationship between therapies and genetic composition to the future of medicine can’t be overstated, and Dr. Jacob understands the gravity of his work firsthand. He decoded his own genome, learning during the course of that exercise that some 23 commonly-prescribed medicines wouldn’t work effectively—and in some cases wouldn’t work at all—in his body. That’s some handy information to have on hand in the examining room.

We’re a long way from pre-emptively prescribing a genome map to every U.S. citizen to inform preventive care and direct the treatment of their ailments, but we’re but we’re slowly moving in that direction. The first human genome cost billions of dollars and took more than 15 years to sequence. Dr. Jacob spent around $9,000 out of his own pocket a few years back to sequence his genome. Today, thanks to automation, better sequencing technologies, and cheap computing power and storage (one human genome equates to about a TB of data), the cost of clinical whole genome sequencing is now just north of $1,000 with analysis costing a few thousand more. AbbVie has the capacity to sequence about 500 human genomes per year in the lab I toured with Dr. Jacob.

There’s also the fact that out of 6 billion chemical units in our DNA, yours and mine differ by only a tenth of a percent. Those 4 million-to-6 million places of differentiation are obviously very important, but they’re a miniscule place to focus in the grand sequence of things.

The research going into genomics holds untold promise to improve the way medicine works. But to realize that improvement, it’s not too early to start thinking about how what we learn will impact the process and manufacture of medicine. Here’s what Dr. Jacob had to say on the matter.

BPO: As genomic research continues to inform the efficacy of therapies and drives more personalized medicine, what effects/impacts will we see on the process/manufacturing side?

Dr. Jacob: Any organism you can modify DNA-wise has the ability to be modified in production. That applies to anything we’re using to produce biologics, whether medicine, food, or consumer goods. So because gene editing will allow us to change virtually whatever we want, we’re going to see a lot of changes at the process level.

Until recently, there wasn’t much work done on the process itself with respect to readily modifying the organism. Maybe we knew that “these cells do X,” but how do we make them do “X” better? Or how do we make “X” that doesn’t have a contaminator? Through biological processing we’re going to be able to better understand how biology works in those cells. Then we can modify the cells to produce more of what we want. That’s going to drive some big changes in how we produce things. Not just pharmaceuticals, but anything being produced from a protein.

Specific to medicine, we’re harnessing the power of genetics and genomics to identify new insights into the pathophysiology of disease. Genomics can help accelerate the development of new medicines and has already informed our approach in key areas. Researching specific DNA may shorten the time it takes to identify new treatments, and our goal is to use genomic data to predict which treatment options are likely to be most effective on an individual level.

While genomics research offers great potential in the development of new therapies, there are many unique things to consider when processing and manufacturing personalized medicines.

For example, personalized medicine batches are not the typical scale compared with conventional manufacturing and therefore processes need to be repeated rather than scaled up, which is the normal practice in manufacturing. Timelines are also contracted, so everything needs to happen faster – but be more specialized.

We’re working to identify efficient solutions to process and manufacturing challenges like these to bring potentially transformational medicines to patients as quickly and safely as possible.

AbbVie has 14 manufacturing, planning and distribution centers in the United States, Puerto Rico, Ireland, Netherlands, Italy, Germany and Singapore, where AbbVie employees continue to look for new ways to ensure our scientific discoveries can be consistently delivered to patients safely, reliably and with the highest quality.

BPO: How much exposure do you have to the manufacturing groups?

Dr. Jacob: We’re doing some work with our protein sciences team, and we recently had a meeting to discuss helping them with some challenges they’re working on. We’re working to help them look at different cell types, exploring a way to understand how to produce it better and faster. That’s a protein processing and genomics manufacturing challenge. We’re privileged here, as we touch discovery, development and manufacturing. In some senses, it’s all DNA, it’s just a different question that you’re answering at each stage.

BPO: And to folks in your wheelhouse, the sexy part comes early, right? The manufacturing part comes well after the exciting work is done?

Dr. Jacob: I don’t think so! I find it fascinating not just what you can do with DNA, but how you can modify it to get what you want out of it. So to me, it’s all cool science and the output of that science on the manufacturing or production side is interesting. If you think about it from a business perspective, the better, faster, and safer we can research to understand, manipulate, and produce things, the more efficiently we can positively affect patients. We’re all working toward that same thing. Though we may be asking different questions, we’re leveraging the same technologies.

BPO: Do you miss academia at all?

Dr. Jacob: I don’t. I’m actually doing more science now than I was when I was in academia. I do miss having more direct contact with patients though. Of course, we were affecting perhaps a hundred people a year then. Now we’re talking about how to help millions. So it’s a little bit longer a time horizon, but with a much bigger impact.

BPO: You discussed the growing bank of genomic data available to AbbVie for research and clinical trial intelligence purposes. How do you grow that bank and ensure its diversity?

Dr. Jacob: There are continuous conversations happening about how to expand diversity, and how we get to and build on some of the other biobanks out there.

The search is continuous, and as a group of companies, we’re exploring many other potential cohorts, but we face complexity around each of them. What data comes with it? How good and diverse is that data? These are thing you have to look at as you’re walking in, because if you don’t have all this in place, it turns into a prospective study much like what we’re doing in a clinical trial. The pace is slower because now you have to find the patients, qualify them, study them, get their DNA, and sequence their DNA.

That exercise stands in stark contrast to leveraging existing and well-funded projects like those in England, Finland, and some of the other Nordic countries where rich biobanks and associated EMRs are already in place.

That’s why you’re seeing those biobanks coming online faster, because the infrastructure is already in place. We’ll see a bunch come out of Genome England. The U.S. has launched the VA’s Million Veteran Program and the All Of Us Research Program at the NIH, both of which will increase biobank resources here. And the sampling diversity problem is less a problem here. That’s a great thing about the U.S. and genomic data—there’s a great deal of diversity built into the population here.