2016 WMIF | Fireside Chat: Giovanni Caforio, MD, CEO, Bristol-Myers Squibb

Good afternoon everyone. Good afternoon Meg. I'll keep my comments really short because I look forward to the Q&A. I want to thank the organizers for inviting me. It's a really important time. From my perspective, we've never been closer to finding meaningful cures for patients with many types of cancers. I'd like to comment on three topics: the importance of keeping the patient at the center, following the science, and the critical role of partnerships between industry and academia. These are central to our work at BMS in immuno-oncology. A few months ago, my leadership team met a 31-year-old Indian actress who was diagnosed with Hodgkin lymphoma six years ago. She didn't respond to the first five lines of therapy, but five years later she enrolled in a clinical trial with one of our immuno-oncology medicines and had an 80% regression. She started acting again. She reminded us that she was in 80%, not 100% remission, so we needed to keep going. As proud as we are of the progress, there is still a lot to be done. The second concept: following the science. Years ago, when we began working on one of our immuno-oncology molecules, we recognized that patients who appeared to be progressing were actually pseudo-progressors. We worked to change response criteria. Fast forward, Opdivo had five phase three trials stopped early due to overall survival. The third point: collaboration. We partnered with Medarex, created an international immuno-oncology network with key academic institutions, and a network of community-based oncologists. These principles – patient centricity, following the science, collaboration – have been critical. We are focused on advancing combinations of immunotherapy, have one approved regimen, and invested in eight new molecules in early development. I want to close by noting our patient's comment that medicines should be affordable and reach a broad population. It's an exciting time, but I think primarily about the patients we are not helping yet. Thank you.

For me, when I think about it, it's the telephone calls from patients calling my dad, who was a physician, during lunchtime and dinner at home. I was never told I had to be a physician, but it was in the water and the air. That's one reason I have such a clear focus on patients.

I moved to industry and R&D right away. I was in an oncology unit as I completed medical school, and those were the days when good clinical practices were beginning. I wanted to be involved in developing new medicines and decided to work for a pharmaceutical company for one year before going back to the hospital, but 28 years later I'm still here.

I never felt I was further away from patients because of the work I've done. The ability to see the full scope from discovering to developing and delivering medicines to patients is fascinating. I enjoy it every day.

If you look at the last 18 months, it's an extraordinary story. A new medicine with a different mechanism of action approved in five new indications across three tumor types, all phase three studies showing overall survival in a little over 12 months. I remember when we worked on Yervoy for metastatic melanoma – a 10-15% probability of being alive after one year. Now with our combination regimen, 69% overall survival at two years. We are just at the beginning. It's about taking immuno-oncology to tumors like head and neck cancer and Hodgkin lymphoma, investigating combination therapies, and understanding the tumor microenvironment. It's a source of pride and a big responsibility.

I wasn't CEO then, but we saw a confluence of our deep knowledge in oncology and focus on immunology. The partnership with Medarex had a strong scientific fit. We recognized it was high-risk – there was skepticism about immuno-oncology a few years ago. We understood it might not work, but if it did, it would be transformational. That's why we pushed the button. We eventually acquired Medarex, and 95% of the original scientists are still there, and the site has tripled in size.

It's a good point. We have a clear focus on oncology, but we also invest in areas where we have leading science to diversify. We let scientists tell us the best path forward, and we have a disciplined process to progress programs stepwise. That's why our R&D organization has been so productive.

The combination of Yervoy and Opdivo sets a high bar. We are focusing new combinations on patients who don't respond to current agents, those who progress rapidly, and tumors where we haven't seen major progress. We are beginning to understand the tumor microenvironment. Many of our eight new molecules are early-stage, and we've done a lot of partnerships. We need to think differently about traditional phase one-two-three development because science is moving so fast. We're investing most in translational research to identify the most promising combination signals.

We have an international immuno-oncology network with academic institutions. They do basic research on the tumor microenvironment, help develop animal models, and we analyze tissue and blood samples from previous trials to confirm hypotheses. The goal is to have a deeper understanding of how science correlates with clinical findings to move more targeted into expensive phases of development.

We have a long history of partnerships; many of our most important medicines were partnered early. We look for strong scientific collaboration, where two companies together can accelerate a program better than alone. There are complexities, but we let scientists create a collaborative environment. We've developed alliance management capabilities, but it starts with respect for the science.

We definitely look at it. If a new medicine doesn't reach a patient due to access barriers, it won't generate a positive outcome. The increasing cost of healthcare requires attention. We work with regulators, payers, and providers. Medicines are 10% of the cost; we need to work on the other 90%. We're open to different payment models and need more flexibility, especially for combinations. Our system in the U.S. is fairly rigid.

Having both medicines in a combination is an advantage – you can develop them faster, understand both, and have better discussions with payers. But it would be a mistake to focus entirely on that assumption. Science comes first. If the best combination requires two companies, we want to work on that too.

I think about it as a really important tool. Years ago, people said we were going against the wave of personalized medicine because immuno-oncology is broader. From the beginning, we focused on a solid biomarker program with every trial. Our ability to identify meaningful biomarkers is just beginning. As science matures, segmentation and biomarkers will become more important.

We're just at the beginning. We will move quickly, but we're at the beginning.

Many groups around the world are focused on immuno-oncology. We invested in a research facility here in Boston and increased our presence in the Bay Area because proximity enables cooperation. A few years ago there was skepticism; now there is enthusiasm, providing resources to progress more quickly.

We always think about cure, but become concerned about using the word. Patients treated with Yervoy 10 years ago are still alive – you could call them cured. Responses to immunotherapy are long-lasting. But we are at the beginning of understanding when to stop therapy and re-challenge. There's no definitive answer yet.

Thank you, Meg. Thank you.