From Bench to Business: Bridging Biomedical Research and Entrepreneurial Drug Development
SPECIAL LECTURE: From Bench to Business: Bridging Biomedical Research and Entrepreneurial Drug Development
Arie Belldegrun (University of California, Los Angeles)
Introduction by Stuart Holden (Prostate Cancer Foundation, University of California, Los Angeles)
View the Transcript Below:
From Bench to Business Bridging Biomedical Research and Entrepreneurial Drug Development
Stuart Holden, MD [00:00:08] It’s me again. I’d just like to make one editorial comment that’s not in the script or in the plan, but just a comment about Mike Milken’s talk, and I’m kind of glad that he’s left the building. So but I think to all of us who take care, are responsible for patient care and all of us who do research to try to improve the lives of patients, I think that was one of the great testimonials to me and one of the greatest sources of satisfaction to see somebody who was predicted to have 18 to 24 months of life expectancy have 32 and going strong, and think about what he’s contributed to society in the time that he’s been given to complete his projects like the last one that he showed 12 years in the making. So, it’s really a strong statement and to me I find it very motivating. So, my job now is to follow two great speeches and recognitions, one of a great medical oncologist and one of a great radiation oncologist with a great urological oncologist. Arie Belldegrun is well known to the urological community. Unfortunately, there are not very many of them here represented. It has been a lifelong dream of mine to get more urologists involved in PCF. But his career is quite extraordinary. So just to give you the brief initial points of his resume, he graduated from Hadassah Medical School at Hebrew University. He did a PhD in immunology at the Weizmann Institute, he did surgical training at the Sackler Medical School in in Jerusalem and then came to the United States and did another urology residency at the Brigham with Dr. Ben Geddes. Following that, he went to the NIH and became a surgical oncology fellow under the aegis of Dr. Stephen Rosenberg, who Mike mentioned was one of the Milken family’s first young investigators. So, I’m not gonna go through the rest of Arie’s biosketch because it will take up the entire time that he has to give his talk, and he’s gonna tell you what’s in his biosketch. So, I will only make two comments. One is I kind of remember a statement, I’m not sure when I first heard it, that a great chef has only one great restaurant in him, and I was thinking about what that really means. And what it really means is that in order to be great at something, you need to have a singular focus, and that’s what produces the greatness. I think that theory has been debunked. I think there are many chefs that have many great restaurants in them, and I think that kind of segues into Arie Belldegrun’s career. Arie is so generous among urologists and urological oncologists and actually physicians in the United States. So, he’s a great role model for the young people in the audience who are contemplating what their careers should be, and he’s really broken down the barriers of the silos between he’s a researcher or she, a clinician, both, a surgeon, not a biotech executive or an investor. And he’s done all of those. So, I’d like to welcome my friend and colleague from UCLA, Dr. Arie Belldegrun.
Arie Belldegrun, MD [00:03:47] Thank you, Skip. I hope this long intro is not on my time. It’s on it’s on your time.
Stuart Holden, MD [00:03:52] Yeah.
Arie Belldegrun, MD [00:03:54] Good. Well, at the same time here, not many urologists, but I want to recognize a new chairman of urology here, Scott Eggener, who I am sure will make, not MAGA, but they’ll say MUGA, Make Urology Great Again at UCLA. With that I was asked to give a little bit of a story of my 30 years of entrepreneurial experience in 30 minutes. I’ll try to do it quick. So, excuse me for just running on it. In any case, that introduction that Mike gave this morning, I hope leaves you with the idea that we, the entrepreneurs, in academic medicine are not in the dark side now. I think it’s in the bright side, in the sunny side, and if you don’t do it, you lose it. So, with that in mind, here’s just some of my disclosures. So, our experience, I’ll try to run to my personal journey to Agensys, Cougar. I don’t have time to go to UroGen, but to Kite, Allogene, and some of that to give you a flavor of what I’m actually most impressed in my career, and that is the six medicines that we had ideas, we started and today are used all over the world. But it all goes back to UCLA, to on the entrepreneurial and the nurturing ecosystem at the university. We started in the mid-90s, six of us that all wanted to build our academic career to get NIH grant and to work together on some projects. And you can see Owen Witte, Toni Ribas, Steve Dubinett, Jim Economou, Charles Sawyers, and myself looking how to collaborate. I did my work at NIH on TIL tumor infiltrated lymphocytes, IL-2 interferon, in kidney cancer. Steve Dubinett was doing the same at MGH, in TIL in lung cancer, Jim Economou in melanoma, and Toni Ribas worked in his lab, so we all started collaborating and working together and actually on the left upper you can see the first paper on in vivo gene therapy when we took TIL and NK cells mixed them together each one had a different gene then I operated a patient we took the kidney out and we could see that the TIL infiltrated into the tumor and the NK cells were in the periphery, the JCI paper. 1996 we decided to become a bit entrepreneurial and we started a company. I was a urologist so there we called the company Urogenesis, over time when we discovered multiple different non-Urological oncology genes, we changed it to Agensys. This actually was our first experience 120 employees later, 50 PhDs, 400 patents. This company was acquired by Astellas, but when I’m looking right now, what we were able to accomplish with low tech, with differential gene expression, and what did we identify? I’m not sure we did a good deal by selling that company at the time. PSEA was developed at the laboratory of Owen Witte. That’s the one we in-license to Agensys, all the rest are in-house, AGS-16, STEAP-1. One interesting specifically is the AGS-22, and we created another ADC, and this was in 2001. The ADC became Enfortumab or Padcev after Astellas acquired the company. And obviously you all know about the history of Padcev, which is now part of Pfizer. When I met with the leadership of Pfizer who acquired Seagen, they had no idea the history of where it came from, so we had to a little bit update there, update them. But this was kind of our beginning and learning experience of what to do. We then moved in 2003 and developing a prostate cancer company and obviously Zytiga came. This is a slide, original slide from me coming to PCF in 2004 without data. We had just in vitro data, and therefore I call it a potential novel targeted oral therapy for hormone refractory prostate cancer. The picture I found it yesterday in the archive here. There is somebody who keeps all the pictures of all the years of 32, so I got it, I just put it last night to show that the presentation. Well, four years later. We had already a company with several products, and we were in phase three. How come we did it so quickly? Here is the secret. One urologist with nine medical oncologists who know how to do it much better than anybody else. When you look at the names that we came together, you’ll see all the who’s and who of those days, Johann De Bono, Eric Small, Nick Vogelzang, Phil Kantoff, Howard Scher, Carducci, Smith, Higano, and Chris Logothetis. All of us were in the early trenches of how to develop a drug, and as you heard from Maha, 2004 was the year that chemotherapy was approved. So, how do you fight chemotherapy with a new drug? Well, with the help of everybody, the New England Journal of Medicine came four years later, and Zytiga became a part of J&J, and now again that’s a bit of a history. 2009, we sat together and we said, so what’s next? After all, at UCLA, all of us, the group of UCLA, we’re all immunotherapy. Why are we doing all of other things? Let’s move and focus on what we know and we love to do. And in 2009, we founded Kite. And In 1985, when I was a fellow at the NIH, I started working on NK cells on the role of in cancer. I moved to UCLA, started working on T cells because Rosenberg said NK, no durability, just T cells. So, we became all T cell guys. And this is essentially up to date. So, 2009, the same story. We put together the world leaders in cancer immunotherapy. We take Jim Allison, Jim Economou, you can see the whole list here, Ronald Levy. An amazing team that we set to set how do we develop immunotherapy, cell therapy for cancer. And we decided to focus on CAR T, chimeric antigen receptor T, based on very few patients at the NIH. We started 2014. You can see how the group consisted of very few patients, very few founders. When we were 2014, we took the company public, and three years later, 750 employees across the street in Santa Monica. The money that we got from IPO went to build the first anywhere manufacturing facility for engineered CAR T. How did we do it? The blind led the blind, we’ve never seen one, but we thought the best way of developing a manufacturing plant. Before getting approval, FDA heard about us, wanted to come and sit in the laboratory and they were there for two weeks. After two weeks sitting with the FDA and wasn’t the most pleasant FDA, the most pleasant time for us, very stressful, in the center you can see the commander Donald Ertel said you should be very proud of what you have accomplished. From the FDA means a lot. In any case, another New England Journal of Medicine paper that presented the first CAR T and Scott Gottlieb, at that time the commissioner of the FDA, to quote him, we are entering a new frontier in medical innovation with the ability to program patients’ own cells to attack deadly cancer. He’s writing a book; the book should be ready this year. I’ve just seen and sent him some pictures, then Logo or editorial at that time, and that was quite the beginning. At that time, we said this is the move to take it international. We went to the UK, we signed a deal in China with FOSUNKite, we developed CAR T, the first CAR T in China, which is now approved and used all over the world, and Daiichi Sankyo in in Japan, all of which came from the days of Kite. But more important than anything else is autologous cells for the first time taking a patient that had no chance of surviving more than three to four months and giving the patient infusion, one single infusion of CAR T, and you can see this patient we celebrated; Nature did a whole celebration for that cured ten years later of the patient. So that is what opened the door to multiple others CAR T companies. Well, this is complicated first generation low hanging fruit that we started in cell therapy. We then jumped immediately after that to do some collaboration with Pfizer, took all the allogeneic cell therapy from them and developed Allogene, took it public in 2018, and that is off the shelf CAR T. I believe that this is the next generation of CAR T and right now we have moved it to cema-cell, which is early-stage negative CT, negative MRI, only MRD positive cells after the first round of chemotherapy. This is a study that probably will read. Beginning end of this year, next year for sure. And with that we will have an idea if we can convert MRT positive to negative and what’s the durability of the disease. I believe that that is something that will move the whole field to earlier and earlier disease in medical oncology. The second program is our kidney cancer which we recently discussed because there was question is CAR T working in solely tumors? The answer is absolutely yes. I don’t know you might be some of the reviewers of the New England Journal of Medicine if yes just remember that what I feel is the case, but in any case, the last one is the allogenic 329 which is in autoimmune disease ongoing right now. This is with a Dagger technology which is, I don’t have time to go into all of that, but this is a CD19, CD70 which probably not require any lymphodepletion. Well, so with that passion of immunotherapy in two 2019 we got together, you can see Michael Milken and us, co-founders, five co-founders, which decided there’s not fair that there is the Broad institute of the east that is so successful. We are going to build the twenty-first century Broad institute of the West. Took us a little bit longer to study and to learn how to do it best, but you can see it here. This is a seven hundred fifty thousand square feet, ten minutes away from UCLA, which originally was supposed to be the center for Google, but we had an opportunity to get that space and this will be combined with the institute of quantum computer institute of AI, all of that under one roof. So, immunotherapy, AI quantum under one roof, I believe will be a very unique place that will be a hub for immunotherapy innovation in the West in association with UCLA, but this is the California Institute, so multiple other institutions will be there. So, what I try to run here is to show you some of the medications that I had the fortune to be involved with, and these medications are currently either run by Astellas, J&J, Gilead or other companies. We then decided, rather than to do one step at a time, one company at a time, to just invest in other companies as well. We raised a quite a large fund, and now we have Vida Ventures, which was founded in 2017, immediately after Gilead acquired Kite, and we have a group that expertise with early stage companies, early venture, and late stage private companies, outstanding principles which we trained and these are coming from MIT, Harvard, two MIT, two in our Boston, two and two in New York office. So, we are right now in means of growing the team I want to show you just some of the companies that we have some of them are already acquired recently just few months ago Capstan the in vivo CAR T was acquired by AbbVie, you can see here and then other companies as well. On the second line from above there is Halda, and Halda is a company that we invested and were early on investors in this company, a prostate cancer company. As we speak now at the triple conference in Boston they’re presenting their data and Chris Schade was kind enough to share with me the presentation that’s presented right now at the triple conference about the RIPTAC technology and the prostate and I think that very interesting technology that has a binding androgen receptor to a bromodomain 4 without going to all the discussion on patients with metastatic castrate disease but this technology with induced proximity it’s our second company with induced proximity the first one is with Chris Garcia InduPro and that’s kind of the second company but the technology is a proof of concept for a new type of this RIPTACs and just to show you the data that will be very briefly the data that will be presented today there, is you can see in blue, is the 25 milligram in the 50 milligram in kind of yellow the responses of the patients and after two cycles, and finally just to bring the PSA kinetics you can see responses. So, I, personally cautiously optimistic believe, that there will be a new New England Journal of Medicine paper there and that looks promising because it reminds me the early days of Zytiga. Well, finally, the final two slides is talking about immunotherapy. I put it this slide in order to show a young Skip Holden hiding there. And we try to have Steven Spielberg involved in immunotherapy. He listened, he learned our lingo and actually after that he said I think I should make a movie. If I have time, I’ll make a movie so everybody will know what does it mean on for the immune system to be active. Says you come over to us for dinner, and he had dinner we had a dinner for us in his wine cellar, and then that’s a quote that I took from him From the time of Lucy, our first human ancestors, our bodies have intrinsically known how to heal themselves. It’s time to turn science fiction into science. So, we have a job to do, and I’m still waiting for the movie. Well, this is kind of a tour de force, very quick summary of 30 years in 25 minutes. So, what did I learn from all of that? This the title is a talk that I gave in August for a biopharmaceutical company, a biopharmaceutical conference in Italy, and the title of my talk was Defy the Herd, Define the Future. And the idea is if I would have gone by all of those who said it’s impossible, it’s too toxic, it will never happen, too expensive, it’s not working, I probably wouldn’t be invited to speak today. So, my two cents are trust good science, stay close to patients, surround yourself with extraordinary people, trust your judgment, and most importantly, don’t just follow the future, define it. Thank you very much.