Eight Lessons from Arie Belldegrun (Kite/Allogene)
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Arie Belldegrun is the Co-Founder of Kite Pharma, Allogene Therapeutics, and countless other biotechnology companies as well as a Professor of Urology at UCLA. His career has spanned work in immunotherapy, urology, surgery, and cell therapies. Kite Pharma was able to get the second CAR-T cell therapy approved after Novartis, and now Allogene is positioned to get the first allogeneic CAR-T approved.
1.“First, I have three decades of immunotherapy experience. It's not something new. Now, everyone wants to position their product as an immunotherapy product -- because that's the buzz. But for years, it was not so. It was hard work, just working at the bench, creating data and providing what today is modern immunotherapy.
Essentially, over the last five decades, the approach to cancer was to hit the cancer cells wherever they are, in a non-specific way. Which means chemotherapy. It kills the good cells and the bad cells. You treat 100 percent of the patients for a 15 to 20 percent response.
A lot of people are getting all the side effects, very few are benefiting. But you couldn't personalize who should be getting what. So the field moved to what's called targeted cancer therapy, meaning: learn the basic mechanisms and pathways by which the cancer cell operates, and try to block these roads, either by blocking their blood supply or blocking their way of proliferating and growing.
Immunotherapy is something completely different. You do not attack the cancer. You manipulate the immune system. The immune system works in a simple way, asking: “Are you mine or you are not mine? Do you belong to my body or you do not? If you do not belong to my DNA, my body, I will reject you.” And who is rejecting it? Killer cells called T-cells. And these are kind of at the center of everything that's happening today: they recognize ‘mine’ and ‘not mine.’”
Arie helped pioneer the use of immunotherapy to treat cancer. Chemotherapy had been the standard-of-care and target therapies, enabled by monoclonal antibodies, emerged and immunotherapies that activate the immune system rather than attacking a cancer directly are becoming first-line therapies.
2. “Throughout my business history, exits were never the strategy. You build a company to grow it and bring in more products, and if along the way you prove to be of interest to big companies, that’s great. But I never put up a ‘for sale’ sign. When I started the negotiations over Kite Pharma with Gilead, the price discussed was $7 billion. In the end the deal was signed at $12 billion. How? Because I told them 'you approached me, I didn’t come to you'. We talked for seven months until they were convinced.
The sale of Cougar Biotechnology to Johnson & Johnson was similar. We started talking at $500 million and settled on $1 billion, and that was at the height of the 2008 financial crisis when everyone thought the world was falling apart.”
Arie’s career has been highlighted by larger and larger exits. However, the best way to get acquired, especially at favorable terms, is to build a company to last.
3.“We were so impressed that T cells were killing cancer cells in vivo, in 1985. That’s where it started. Since then we’ve continued to work.”
Immunotherapies and cell therapies have been ~4 decades in the making.
4.“I was an active surgeon/physician/scientist building a laboratory at the Johnson Cancer Center, at UCLA. I started realizing that while we are doing great surgeries, but there is a limit to what we can achieve with our knife. And I started looking for other alternatives. We started the first company, called Agensys, which was a gene discovery company that was fully dedicated to studying different genes involving cancer, creating monoclonal antibodies that at that time was quite new, but today is a household name. And these are antibodies were then converted to medications, some of which are approved now by the FDA. I have started another company called Cougar Biotechnology, which was interesting in that when we started that that company in the early 2000, there were very few new treatments for prostate cancer. You, Mike, were the impetus of starting the research then. We then established a company that developed eventually a drug called abiraterone, today known as Zytiga. That drug is now distributed all over the world by Johnson and Johnson and making a lot of difference in the life of patients with metastatic prostate cancer.”
Arie was the rare triple threat: physician, scientist, founder.
5.“I received my medical degree in Israel and did my residency at Harvard University followed by a surgical oncology fellowship at the National Cancer Institute (NCI) under Dr. Steve Rosenberg, a mentor who stirred my early interest in immunotherapy as a treatment pathway for cancer. Back in the 1980s, few institutions were either attracted to this area or had embraced its potential, but I learned quickly that UCLA was the exception. As a result, I joined the medical school faculty as an assistant professor in urologic surgery and signed on as a researcher at the university's Jonsson Comprehensive Cancer Center. With several colleagues who, like me, remain on the UCLA faculty today, we worked to raise the profile of cancer immunotherapy and gene therapy research by soliciting joint grants from the National Institutes of Health (NIH) and other granting agencies.”
When Arie was starting off his career, immunotherapy was not a hot field, but over several decades transformed medicine and patient lives.
6. “For years, immunotherapy did not get attention. But recently, with new genetic engineering technologies, you can take those very same T-cells and engineer them to do whatever you want them to do, rather than what the cancer wants them to do. Suddenly, everything has changed.”
7.“Our mission at Kite, quite ambitious at the time, was to develop the first engineered cancer immunotherapy company around the autologous chimeric antigen receptorI-cell (CAR-T) platform. It was a dream that we were able to turn into a reality for patients. We developed Yescarta (axicabtagene ciloleucell), the first autologous CAR-T therapy to be approved by the FDA for non-Hodgkin lymphoma (NHL).”
Kite definitely accomplished their goal.
8. “Targeted cancer therapies don't cure anybody. They extend life. However, our drugs are for the first time, you can say, going for the cure. And in some patients, they are completely cured: a patient who had three months to live is now playing golf and jogging five years later. That's a cure. We are going for the cure. Everything before went to convert a deadly disease to a chronic disease.”
Technologies like CAR-T have shown the ability to make cancer a chronic disease.