The Backstory Behind What Hoos Hopes To Do At GSK
By Rob Wright, Chief Editor, Life Science Leader
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While at Bristol-Myers Squibb (BMS), Axel Hoos, M.D., Ph.D. brought ipilimumab (the pioneering CTL-4 immuno-oncology drug) to market, essentially launching the field of immuno-oncology. So, I was curious as to why he decided to join GSK, where he currently serves as SVP therapeutic area head for oncology R&D and head of immuno-oncology. But to understand Hoos’ (the subject of Life Science Leader magazine’s September 2016 feature article) path to GSK, you need to first know why he went to BMS in the first place. He says it was his strong desire to create a new paradigm for how to develop immunotherapies differently that led him to BMS. “For 30 years scientists have tried to use the immune system to treat cancer,” he explains. “Part of the reason why we weren’t previously successful in using the immune system to treat cancer is we always treated new approaches like chemotherapy. I had data points that supported a different approach, but I needed a place to try it.”
There were difficult periods, some related to the rest of cancer immunotherapy not doing so well. “We had only one asset, and people thought, ‘Why should yours be any different,’” he shares. “Well, for starters, we were doing it differently and not taking a chemotherapy-type approach.” For example, at the time, Pfizer also was working on a CTLA-4 blocking antibody for melanoma. “Both were in Phase 2/3 trials at the same time, and it was really a question of who was going to get there first,” he insists. Pfizer’s approach was Tremelimumab using a classic chemotherapy approach. “At BMS, we started with a chemotherapy approach, but when I came on board we converted to an immunotherapy technique,” he explains.
Of course, using the immune system to solve or prevent a disease-related problem is nothing new. For over 200 years doctors have used vaccines to stimulate the body’s immune system to produce T-lymphocytes and antibodies to fight infections (e.g., small pox, polio, etc.). According to Hoos, vaccines mostly stimulate, which is something you don’t want to necessarily do when treating cancer. Until fairly recently, what wasn’t understood with regard to using the immune system to treat cancer, is that it has a system of checks and balances. “We learned that you can use the immune system to stimulate at one end, and use a braking mechanism (i.e., an immune checkpoint) to stop the immune response from overshooting,” he explains. “That’s what CTLA-4s [cytotoxic T-lymphocyte-associated protein 4] do, function as checkpoint blockers to down regulate/brake the immune system response.” According to Hoos, it was that understanding and its translation into clinical development that resulted in ipilimumab being a breakthrough for BMS, and perhaps why Pfizer sold certain rights to tremelimumab to AstraZeneca in 2011.
What Hoos and his team did at BMS wasn’t just create a new drug, but a new paradigm that served as the inspiration for what we know today as immuno-oncology. “After the ipilimumab success was achieved at BMS, I wanted to do the same thing, only bigger — build an entire product portfolio from scratch,” he says. “I didn’t think BMS was the right environment in 2011.” This is because BMS, along with most of the companies developing immuno-oncology therapeutics, were focused on first and second generation IO products at the time. But Hoos wanted to start working on technologies he thought would become the next big thing in immuno-oncology. “So I was seeking a place where I thought I could do this,” he affirms. While Hoos admits it could have been another company, it turned out that GSK was interested and had the discovery performance unit (DPU) model he felt would play a critical role in order to have success.