John Lambert: A Thrill of a Career (Part 1)

Roger Pellegrini

John Lambert, Executive Vice President, Emeritus, and former CSO at ImmunoGen, had a career spanning academia and biotech, with the rare chance to start at a nascent company and watch it grow into one of the most successful biotech companies in the world. We spoke with Dr. Lambert about his career path, perspectives on the immunotherapy field, and advice for rising scientists.

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Dr. John Lambert.

Q: Tell us how you first became involved in research.

A: As a high school kid growing up outside Manchester, England, I was always interested in biology. At the end of high school, I applied to Cambridge to do an undergraduate degree in natural sciences, and the summer before starting college, I ended up working at ICI Pharmaceuticals (that later became Zeneca, which then became AstraZeneca). So I started doing protein biochemistry there in a lab before I'd even gone to college.

Q: How did you career path lead you to ImmunoGen?

A: I was an undergraduate at Cambridge and decided to stay and do a PhD in protein biochemistry. After, I came to do my postdoc in the US - to UC Davis where I worked on ribosome structure for 4 years. Then I went to the University of Glasgow and had a 2 year postdoctoral fellowship to work on a multi-enzyme complex. I was basically using that 2-year postdoc to look for a faculty position in biochemistry in England.

I saw an ad in Science to join a group funded by private investors looking for a protein chemist.

My life-plan got derailed by two women, you could say, who were important in my life. My American girlfriend followed me from Davis to Glasgow and we got married; in 1980, Mrs. Thatcher was in power, newly the PM, and she cut university funding by about 10% across the board. So for the 2 years of my fellowship, looking for a lectureship, there were no jobs. I started to look back to the states, and there were stories about the emerging biotechnology industry - Genentech was founded in 1976, Biogen in 1978. I saw an ad in Science to join a group funded by private investors looking for a protein chemist. I answered the ad, had an interview in August 1981, and I accepted the job. That's how I ended up at ImmunoGen, and it's the only job I ever applied for. Probably a little unique in the world of biotech - I found my calling, and the company is still in existence.

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Dr. Lambert and Dr. Ravi Chari, Head of Chemistry at ImmunoGen - colleagues for 31 years (and counting).

Q: As you transitioned from a scientist to management, what were some of the biggest shifts you experienced as your role changed? What are some tips you have for others making the same transition?

A: It was a shift to increasingly give up hands-on experimentation; I liked doing that, I was good at it. But as you start to manage larger groups, you end up doing less and less with your own hands. You have to give up that urge, and you have to really embrace that you're now looking at the big picture. You also have to really embrace people matters. One of the skills is just to be able to listen to people. I would also recommend coaching, which I found invaluable.

Q: You've also had the chance to see the trajectory of the company - what are some of the most surprising or notable changes you've witnessed in ImmunoGen's history?

A: After so many years, it’s hard to be surprised, but one of the surprising things is that ImmunoGen's mission is the same as when it started 35 years ago. ImmunoGen went public in 1989, taking an immunotoxin conjugate based on a mouse monoclonal antibody and a derivative of ricin as the payload into clinical trials to treat Non-Hodgkin’s lymphoma. The 1980s were the era of mouse antibodies in clinical trials. Humanization wasn’t invented until the end of the decade; early on, it wasn't realized that it would be necessary. However, by the early 1990s we had developed a humanization methodology, as did others, and also developed a potent small molecule payload platform to create antibody-drug conjugates (ADCs). Looking back, in '93, Centocor had a failure of an antibody drug, Centoxin. It nearly bankrupted Centocor and for a short period of time, just to mention you were using monoclonal antibodies, it was thought they were never ever going to be used to treat human disease. As a result, it became really hard to raise money to continue development of the ADCs. I wouldn't say it was a surprise that we survived, but it was hard work to survive that period. By the 2000s, we'd done a deal with Genentech, amongst others, and we then survived as a company by doing partnerships to get our ADC technology into clinical trials for treating cancer patients.

I wouldn't say it was a surprise that we survived, but it was hard work to survive that period.

So I don't know about surprising or notable changes - the ‘80s were mouse antibodies, the ‘90s were a period of surviving, and the 2000s were a period of partnerships, while we built on what we learned and got to the technology that worked. The 2010s saw the first approval of a product (Kadcyla) with ImmunoGen’s technology. Now is the time for us to invest in our own programs that will lead to a new wave of ADCs that hopefully become successful agents in treating cancer over the next several years.

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