Kristen Hege

Dr. Kristen Hege, M.D. is the Corporate Vice President of Translational Development, Hematology/Oncology at Celgene. She is also a Clinical Professor of Medicine, Hematology/Oncology at UCSF Medical Center.

The following is a transcript of an interview dated 7/25/19. This interview has been edited and condensed for clarity.

Could you tell me a little bit about your career path?

I'm a physician, I don't have a PhD, but I did take a year off during medical school to do bench research so I'd had some exposure to the lab. I did my internal medicine rotation and decided to go into hematology and oncology. I came back to UCSF to do that fellowship, and realized that I was interested in something related to cancer and the immune system. I was intrigued by bone marrow transplants, which is all about how the foreign immune system can be transplanted in and eradicate cancer. This was sort of the dawning of the understanding that it's the T cells from the donor that come in and kill the cancer. So I wanted to spend a couple years doing research around re-targeting the immune system to kill cancer. I looked at a number of labs at UCSF and wasn't finding anything really translational and applied. At the time, UCSF was really focused on cancer genetics and what causes cancer, and there was clinical research on what drugs we use to treat cancer. One month, I was doing a rotation at the county hospital, and my attending physician happened to be the CEO of this local biotech company who worked a few months a year as a physician at this hospital. I was explaining my career interests, and he told me about how, at his company, they were re-engineering the immune system to kill cancer and HIV/AIDs-infected cells. He invited me to come do my two research years doing a postdoc-equivalent at this company. I had never really thought about doing anything other than running a lab at UCSF, but I talked to our program director. They agreed that I could go spend my two years at the lab at this biotech company.

I went there for a couple years, working on putting chimeric antigen receptors into hematopoietic stem cells in the lab to re-target the entire immune system. I did my two years of research, I finished my fellowship, and applied for a junior faculty position at UCSF. I came on as an instructor and found a lab looking at the effects of HIV on hematopoiesis. It wasn't exactly what I wanted to do, it wasn't immunotherapy. I wrote a K08 grant, and did that for about 6 months. And it just dawned on me: this wasn't what I wanted to do. I didn't want to be a physician, see patients, build a lab, hire technicians, and write grants. There were a lot of barriers in this academic environment. I was still in touch with the company. At that time they were filing an investigational new drug application putting these chimeric antigen receptor modified T cells into human clinical trial for AIDs patients. I talked to the CEO and said I would like to come back, and asked if it would be possible to do a split appointment where I would spend 80% of the time at my company in the lab, and 20% of my time as a physician. That was pretty unusual at the time. So I did that for the next 15 years. We built this clinical research programs, and did a number of chimeric antigen receptor trials in HIV and cancer, and cancer vaccines. At that time, it was all very much the fringes of cancer research. Nobody really believed that the immune system could target or kill cancer; there were only a couple of small companies working on this. Frankly, most of those trials failed. That company, after 15 years, had one of our trials fail in 2008, and the company had to close down.

After that, I moved on to a couple of consulting gigs. I was the Chief Medical Officer of an even smaller startup biotech, then in 2010 I got recruited to join Celgene and build up a translational and early clinical development program just as the cancer immunotherapy field became popular. We were able to help Celgene really build their program, and now 2/3 to ¾ of our pipeline is cancer immunotherapy.

It's fun now, because CAR-T therapy is really hot right now. Two treatments have been approved, and some really impressive results have been seen. Now, when we go back through the history, it's really cool to say, I actually ran the first clinical trials 20 years ago. Most people think the field just started in the last few years, but we were working on this in 1995.

What is your average day like at Celgene?

Oh boy. Let's see. My average day starts at 6am, because Celgene is headquartered in New Jersey. So 6am in California is 9am in New Jersey. It usually starts with conference calls. So, I'll just describe the scope of things I'm responsible for. On the CAR-T cell theme, one of the first things I did when I joined Celgene was convince our business development group that we should explore CAR-T cell therapy and that led to a collaboration with a little biotech company in Boston called Bluebird Bio. Turns out that their Chief Scientific Officer was someone I had worked with back at Cell Genesys, so we got together and decided that Celgene and Bluebird should partner on a CAR-T research program. We developed this program and put into clinical trials for multiple myeloma. Pretty impressive for something you're testing for the very first time in humans, to get an 85% response rate. As a result, that program has been on rapid-fire development path, and because the program has been kind of my baby, I have been leading it through its clinical trials. Even though it's not technically early drug development anymore, it's late drug development. That has consumed a lot of my time. In addition, I run our entire hematology/oncology pipeline, so we have about 20 different pipeline programs-small molecules, antibodies, bi-specific antibodies, antibody-drug conjugates, cell therapies, epigenetic therapies. It's a big pipeline. I have a team, physician, clinical scientist, operations people that run those phase I trials across our whole pipeline.

That's my Celgene work, but on top of the Celgene work I sit on two different boards of biotech companies, so I have some board responsibilities. And I'm on the board of the Society of Immunotherapy of Cancer. That takes some time. And then I have clinic every Monday. So, a typical day is juggling all of that. The long and short of it is that I work long days. I typically work 12-14 hour days.

As part of the Society of Immunotherapy of Cancer, we're doing some efforts there around women in science. We actually have a conference coming up for young women in science just starting their careers, typically closer to the end of their PhDs, early junior faculty, talking about what advice some of the senior women in their field can give them.

As a woman in science, what sort of advice to you give younger women?

It's not an easy answer. I think it's the standard ideas. Work hard. Lean in. Seek advancement. Don't doubt yourself. There's all kinds of studies on women feeling less capable than men. We also discuss what are the barriers, conscious or unconscious, that still are preventing women from advancing in academia and biotech. How do we make it more feasible for women to start young families and continue in their careers-how do we help women through those hard years when they're really juggling a lot? What are the real reasons why women leave science? There's a lot of attrition. There are a lot of women in science early on, but as you move up the ranks into executive positions at companies, or director/chairman-type positions in academia, you start to see this attrition of women, and more and more men. The answers to why that happens are not that simple, but we look at all of those reasons to make sure that women are getting promoted fairly, that women are getting opportunities fairly, that women actually put themselves out there for promotions and opportunities, that the workplace becomes more flexible so it's easier to juggle careers and families, that people are aware of their unconscious biases that everyone has. There's a lot going on there.

When reviewing job applications, what stands out to you?

The main people that I hire are physicians that have deep interest or experience in science. We're working at that bridge between discovery scientists and clinical development. I look at a lot of MDs or MD/PhDs that have a lot of bench experience that are just inherently curious about the why's-why do things work? How can we make things better? What can we understand about core pathology of cancer, predictors of why certain cancers respond to manipulation of one pathway or another? How do we measure that in a clinic? I'm looking for people that have excelled, have the curiosity to dig deep and understand the mechanism behind their observations, and that bridge the gap between scientists and patient treatment. It's a certain kind of phenotype-it's not everybody. You know it when you see it. I tend to recruit people from the premier academic programs, partly because they've done some filtering for you, and I look for that right phenotype that makes them a good fit in a translational research organization.

Reflecting on your career, is there anything you would have done differently?

It's interesting, I actually don't think so. It's taken some interesting twists. I ask myself sometimes, should I have spent 15 years at this one biotech company? I stayed there a long time, and I worked on what at the time was considered very fringe biology. Should I have worked on something more mainstream? The irony is that what was on the fringe in the 90s, is now mainstream today, so now I have this calling card of having been there in the early days and having decades of experience in a field that other people think is very new. In retrospect, I'm actually glad I stayed at that company for 15 years and spent all those years working on fringe programs in cancer immunotherapy. It's given me a lot of relevant knowledge and experience now that many of those programs landed. And then I spent some time at small biotechs, like 10 people, learning how to raise money, what programs to develop, where to spend your money, how to build a team. And then Celgene was a big company for me, I guess it's not that big. Now that we're getting acquired by Bristol Meyers Squibb, it's getting really big. That was a big adjustment for me, but that has given me huge opportunity in terms of the breadth and scope of what we work on, all the business development, partnering with small biotech companies, for which all of my experience with small biotech has come in handy. So, when I look back on it, it's been a pretty fun career. I'm quite happy with it.