In this interview, Nils Lonberg, a pioneer of cancer immunotherapy, explains how ipilimumab (Yervoy) achieved FDA approval by presenting a Phase 3 overall‑survival trial—the first to show a survival benefit in metastatic melanoma. He emphasizes that supportive senior leadership and risk‑tolerant boards were crucial for navigating the non‑linear development path and for enabling later PD‑1 therapies such as Opdivo. Lonberg recounts the journey from the small biotech Medarex, through its partnership and eventual acquisition by Bristol‑Myers Squibb (BMS), highlighting how BMS chose to keep the operation in the Bay Area, preserving a large oncology drug‑discovery site. He discusses how past acquisitions (e.g., Eli Lilly’s purchase of Hypertech) can catalyze local biotech ecosystems, and how the Bay Area’s mix of investors, talent, and academic institutions sustains this growth. The conversation then shifts to the UCSF Immunoprofiler, an open‑science collaboration that pools patient samples and data across pharma companies to map immune responses to therapies, illustrating a new model of academic‑industry partnership. Lonberg also describes how PD‑1 pathway drugs reveal commonalities across diverse cancer histologies, prompting a re‑classification of cancers to better match patients with therapies. Finally, he underscores that the Bay Area’s dense academic talent pool, venture capital (e.g., Kleiner Perkins), and healthcare infrastructure are essential for recruiting top scientists and advancing immunotherapy research at BMS.
Chapters
All right, we've got 10 minutes, so we're going to dive right in. Um, ipilimumab, also known as Yervoy, um, had a not easy journey but now is very successful, one of the early cancer immunotherapy drugs. Talk a little bit about, um, the key to winning FDA approval and, and maybe the support of an organization to getting a drug through that long process?
Well, the key to getting FDA approval— that was actually not that difficult once we presented the right data. So the Phase 3 trial that we took to the FDA for approval was an overall survival trial. And it was, in fact, the first drug that ever showed a survival benefit in metastatic melanoma. And that was, I think, fairly straightforward. But the path to get to that particular point, it's an understatement to say that it was not linear. I think any new technology, any drug typically does not have a linear trajectory. There are ups and downs. You have to have a supportive board if you're a biotech company, or a supportive senior management if you're a pharma company to look beyond some of the dips and be willing to take risks and move forward with something that is potentially a breakthrough. It's potentially very promising. And looking back, if ipilimumab had not been successful, I don't think any of the PD-1 drugs would have appeared. Merck didn't take their PD-1 drug into the clinic until after our phase 3 trial for ipilimumab. And I don't think that the Bristol-Myers board would have supported the investment that we've now made in Opdivo if it wasn't for the success of ipilimumab. So it's a good thing that there were supportive people who are willing to take risks, who are willing to look beyond the low points and push, you know, a new potentially breakthrough technology forward.
And this all started with a small company, Medarex, and you had the partnership with BMS and then the acquisition by BMS. I'd like to, during those years, way back when, people were telling me, especially during the Great Recession, oh, we don't want the Bay Area to become the next Seattle. Apologies to anyone from Seattle. But where a larger company would come in, acquire the assets, move them to the East Coast or wherever. So this was around the time of Onyx as well. A lot of that talent shifts, but how do you— how does the Bay Area maintain the presence it has in the biotech industry when companies do see attractive companies here and buy them? How do they keep it here?
Well, there's a lot of things to unwrap there. First of all, Bristol-Myers recognized the value in the Bay Area, and that's why they kept us in the Bay Area and let us, in fact, grow in the Bay Area. We've got a fairly large drug discovery site now. It's the largest drug discovery site for oncology for Bristol-Myers Squibb. But how does, how does a biotech community react to these acquisitions? Sometimes they thrive. I mean, I think the example of 1986, I think it was, that Eli Lilly acquired Hypertech in San Diego, and arguably That event sparked the proliferation of biotech companies in San Diego. People left Hybrotech and they went on to found other companies. And the investment that went into Hybrotech, the local investment, then got recouped from the acquisition by Lilly and that encouraged more investment. So within a particular local environment, it depends on investors. It depends on talent. It depends on all of these things. It's a very, it's a very complex landscape and it's an ecosystem where every, every single piece of it needs to get fed.
And talking of those pieces, one of the key pieces here is the academic infrastructure. I know BMS is involved with the UCSF immunoprofiler. I don't know if everyone's familiar with that, but I wrote about that back in January, but maybe you can talk a little bit about that program and what BMS is doing in this very sharing kind of program.
Yeah, I think that's a model for a kind of a partnership between an academic medical center and pharmaceutical companies. There are things that you can only do within an academic medical center where you're close to the patients, you're close to patient samples, and a number of pharmaceutical companies, not just Bristol-Myers Squibb, invested in this. It's a It's an information sharing program. We're not keeping any of the information to ourselves. The academic groups are going to publish all of the work. It's, I think, a perfect partnership that is required in a new field like immunotherapy where we don't have very many answers yet. We're just beginning to sort of uncover the basic science. And so we all need to sort of pool our resources and talent to, to understand this new landscape.
And maybe if you can expand on that a little bit more. This program is looking more at how the immune system responds to drugs and other therapy than just, okay, a certain type of cancer.— if you can dive a little deeper on that.
Well, you mentioned a certain type of cancer. The PD-1 pathway targeted drugs are very interesting because it's the first time probably since, you know, combination chemotherapy that a modality of therapy has worked so well across a variety of different types of cancer, different histologies. We call it. And we're learning that a lot of different cancers, you know, that, that arise from different tissue types actually have more in common with each other than they do with cancers that previously would have been viewed as being related. So one patient's kidney cancer might actually have a lot more in common with another patient's lung cancer than two different lung cancer patients' cancers. And that's what we're trying to uncover. We're trying to learn from this scientific endeavor how to better classify cancers so that we can better pick the right therapies for the right patients.
So some of your partners there, AbbVie, Amgen, anybody else?
I'm sure that we're missing a bunch.
But there, there are other companies here who are trying to do what BMS has done— acquire, consolidate, grow— Merck being one of them with their new headquarters going up, West Coast research headquarters in South San Francisco. You're in Redwood City. What has this ecosystem— how has this ecosystem benefited what BMS is trying to do in immunotherapy?
Well, the, the partnership with UCSF and various collaborations that we have with Stanford, UCSF, Berkeley over the years, that's, that's one example. Probably the most important is just the ability to recruit talented scientists. We are getting, you know, fantastic young scientists from these academic institutions around the Bay Area, and that's what's key to a good research organization, is good people.
And rather than recruiting them from elsewhere, I mean, people come to the Bay Area and they go, ah, a $17 piece of toast, really? So having that talent already here, Stanford, Berkeley, UCSF—
That's key. That's absolutely key. But I wouldn't be here if it wasn't for the larger ecosystem. So when we started up the first biotech company that I was involved in, in 1989, one of our investors was Kleiner Perkins. Kleiner Perkins wanted us to be local so that they could, you know, keep an eye on us. And so we set up shop here in the Bay Area. That company was then bought by Medarex. An East Coast company which was then bought by Bristol-Myers Squibb. But it's that access to investor capital, access to talent, access to healthcare institutions, all of that together makes up the landscape, I think.
Great. Well, we have 10 seconds left. I just want to take the time to thank you and thank The Atlantic hosting the event.
