Topol and Reed on a More Collaborative Drug Pipeline

; John C. Reed, MD, PhD


March 28, 2013

In This Article

The Path to Roche

Dr. Topol: Along the way, didn't you have an intersection with Roche with another drug or something else that you were working on? Or is this your first time working with them?

Dr. Reed: Yes, a very tortuous path has led me to Roche in the sense that one of the advanced cancer medicines that is now in their phase 3 pipeline, I had my fingerprints on. It goes back to the work we did in our laboratory years ago on a survival gene, an antiapoptotic gene called BCL2, involving B-cell lymphomas and leukemias. I happened to have done part of my dissertation and some of my postdoctoral work on that.

Dr. Topol: I thought BCL2 was your middle name.

Dr. Reed: It became so after many years. We discovered its involvement in one of the most common types of leukemia, chronic lymphocytic leukemia, and did a variety of similar experiments using various manipulations to show how important that gene was for the survival of the cancer cells, and particularly for makers of chemoresistance. You know -- "Why is it difficult to kill the cells when they become refractory to chemotherapy?" That led to a prototype medicine we created in the laboratory using synthetic DNA using this anticode or antisense technology with short pieces of synthetic DNA to try to silence the gene.

At the time, that medicine was licensed to a San Diego company that was involved all of the way through a phase 3 trial for chronic lymphocytic leukemia. It showed promising results, but not quite across the goal line, so that was part of the backdrop. Along the way, we started a small molecule using the discovery approach against the same target, and that became part of this same San Diego company, which was then acquired by Pfizer. And then through a tortuous set of things, the technology ended up going to Abbott and then to Genentech and now to the Roche pipeline.

So, some of the work that I started literally 20 years ago is now a phase 3 drug candidate in the Roche pipeline for chronic lymphocytic leukemia and is showing very exciting results. I'm hoping that it will be a new weapon to fight leukemia in the near future. But it has been 20 years and a very complex path that shows the perseverance it takes to bring forth new medicines with truly new mechanisms. It also shows the importance of collaboration and partnership, because this project has been in the hands of, and been touched by, so many talented scientists, physicians, and drug development specialists along the way. It's finally in what we hope is going to be its last step on the journey towards FDA approval.

Academic and Industry Partnerships

Dr. Topol: We sure hope so. You have been a model for this kind of academic and industry partnership, and as you said, it's not so easy to get a drug that really works out there [to patients]. What do you think now, with all of the consternation about the NIH's role in drug development? Has this type of partnership worked very effectively? What is the optimal way in which institutes and universities can interact with the life-science industry to propel useful therapeutics?

Dr. Reed: I think, at least in the early stages of drug discovery, that that's a great role for universities and research institutes to be more active in. Traditionally, that wasn't done at all in those environments. [Academia] would discover targets; we would validate them in animal models. We could sometimes validate them through studies in people using patient-oriented research approaches. But to actually take the early steps toward developing a therapeutic was really not the bailiwick of academia. In the past decade or so, thanks to some of the NIH initiatives, a variety of academic centers have now established the basic infrastructure for small-molecule drug discovery.

An example is the ability to do high-throughput screening to get chemicals that modulate the target that you can verify in animal models; prove the concept that there is a path forward. At least for academia, there is a great role to do that and to take those early steps to do what we call "chemically validate targets," meaning, can you actually modulate them with a chemical? If you can do that in an important disease area, then the pharma companies will jump and they'll pick it up from there and get things going. But there are so many targets that are considered high risk or not sufficiently validated, so the pharma companies don't take a chance on them.

This type of activity, where early drug discoveries are being performed in academia, is starting to create the opportunity to validate more targets than pharma can jump on and do what they do great: Make it very robust, a pharmaceutically well-behaved medicine that will move into the clinic.

The Lifestyle of a Triathlete

Dr. Topol: Before we go to the next chapter in your incredible career, I wanted to touch on something that I find striking about your triathlete world: You get up early in the morning. Can you give us a little insight into your lifestyle?

Dr. Reed: Yes, I'm a bit of an oddball, I guess. First of all, I get up very early every morning, typically 3:30 or 4 AM.

Dr. Topol: That's kind of early.

Dr. Reed: That's kind of early, yes. I'll say that it's my most productive time of the day. I don't stay up late, but I get up early.

Dr. Topol: What time do you usually get to bed?

Dr. Reed: I try to get to bed at 9:30-ish or something like that -- maybe 10.

Dr. Topol: Not a lot of sleep. Sleep makes you weak.

Dr. Reed: That's right. Thank God for coffee. But that actually started when I was going to be a surgeon. I started out my career thinking I was going to be a surgeon. Of course, we prided ourselves on being the first in the hospital and the last to leave, and so I can remember coming home bushed from the days in the clinic and still having my reading to do. And rather than falling asleep on my textbook, I started going to bed at about 9:30 PM and then getting up at 3:30 AM. I'd get a couple of hours of reading in and then get in the hospital by 5:30 or 6 AM. I started that routine and I've really stuck with it ever since.

Dr. Topol: You've been in the groove.

Dr. Reed: I've been in the groove, yes. It really came in handy, too, when we had children because then my wife gave me the bottle feeding at 3 in the morning because I was going to be up anyway. And I've always been a runner, a cross-country track runner, so along the way I got into triathlons and have been able to enjoy this with my oldest son, who has gotten very engaged in it and was doing it competitively in college.

Dr. Topol: Will you do the Iron Man?

Dr. Reed: Yes. I do an Iron Man every year, and often 1 or 2 half-Iron Men. An Iron Man is 140.6 miles and a half is 70.3, but I love it, you know?

Dr. Topol: How do you train? You go out at 3:30 in the morning?

Dr. Reed: Yes. I work for a couple of hours and then I go out and get a little exercise.

Dr. Topol: What would be your regular routine while getting ready for the Iron Man?

Dr. Reed: Just the normal routine Monday through Friday; on the workdays I just do an hour of swimming or biking or running. On the weekends I try to do some longer things [leading up] to an Iron Man -- 100 miles on the bike on Saturday, and then maybe run 15 miles on Sunday -- things like this.

Dr. Topol: How long is the swim for that?

Dr. Reed: 2.4 miles.

Dr. Topol: That is a feat. Have you ever had any pain in your joints or anything ever give up on you?

Dr. Reed: Knock on wood, I get a lot of sore muscles and tendons, but the joints have been holding out. But for me it's been sort of my escape; it's just a great thinking time for me. I just get lost in my thoughts about science and the Institute and things like that, so I'm working on things mentally.

Dr. Topol: So, while you're on that 100-mile bike ride, you're coming up with the next discovery?

Dr. Reed: I'm planning the next experiment or writing the next grant in my mind.


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