Lloyd Klickstein, M.D., Ph.D.: Rapamycin, mTOR inhibition, and the biology of aging

**Peter Attia** (0:11)
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Now, without further delay, here's today's episode.
I guess this week is Lloyd Klickstein. Lloyd's the Chief Scientific Officer at RestoreBio. So that's little, R-E-S, big, T-O-R, little, B-I-O. Get it, Tor, T-O-R. RestoreBio is a clinical stage biopharm company that develops meds that are primarily aimed at targeting Tor, targeted rapamycin. We'll talk a lot about that throughout this episode. So prior to joining RestoreBio, Lloyd was the Global Head of Translational Medicine for the New Indication Discovery Unit at Novartis. And prior to that, he was an academic physician at the Brigham and Women's Hospital, which is one of the flagship programs at Harvard. Lloyd received his bachelor's from Tufts and an MD PhD from Harvard. He's got more accolades than you could shake a stick at. So accolades aside, the reason I wanted to speak with Lloyd was because he is really one of the few people on this planet that has a really nuanced understanding of the clinical application of rapamycin and rapalogs. And we talk a lot about one of them in particular called everolimus.
Lloyd was the senior author on a paper that I have spoken about many times on this podcast, which we'll go into in great detail here. December 2014 paper, Joan Manick was the lead author on that paper. And that was the study that was basically the turning point in my personal evolution or thinking when it came to the use of rapamycin for the purpose of longevity. Prior to that, there had been a lot of studies that had certainly suggested in animal models that rapamycin could be a true longevity agent, but it was the Manick Klickstein paper of December 2014 that was the real turning point in my thinking. And that's really where we're going in this discussion, along with talking about all that's been done since then. It is important before we start this interview that I mention, of course, that Lloyd is an employee of RestoreBio. RestoreBio is a for-profit company that is working on mTOR inhibition, so please caveat everything that we discuss through that lens. Before this podcast begins, I wanna note that we recorded this interview in September 2019 Now, in the interview, we discussed an upcoming phase three trial from RestoreBio.
Since that time, the results have been published, and the study did not meet its primary endpoint. Now, I frankly left the option to Lloyd as to whether or not he wanted to still have the podcast air, and he felt that that would be fine to do. And so we're gonna go ahead with it. And eventually, I'm going to be interviewing his colleague, Joan Manick, along with Nir Barzil. I'm gonna have the two of them back on an episode where we're going to discuss a whole bunch of things that'll be quite interesting.
And this gets more complicated because I think I have a pretty clear understanding of why that study failed, and what it does and doesn't say about selective inhibition of agents like it. Nevertheless, I think the most logical thing to do is to go ahead and proceed with this interview, which is one of my favorite interviews on this subject matter, and just know that there are going to be a number of things that are left as open-ended questions from this discussion that we're gonna pick back up with Joan Manick when we do that interview, which I'm scheduled to do a few weeks from now, and hopefully, we'll try to get that one out at a much quicker turnaround. There were a number of issues that delayed the release of this, not the least of which being some of the COVID stuff, but I can promise you that there will be a shorter gap between when you are hearing this and you will hear the follow-up to this than there was between the recording of this and when you're hearing it. And without further delay, please enjoy my conversation with Lloyd Klickstein.
Lloyd, thank you so much for making the trip up to San Francisco today. I know you didn't come here specifically to see me, but I appreciate you carving out a little extra time to meet today.