Juno Therapeutics President and CEO Hans Bishop leads one of the most dynamic, pioneering companies in the field of cancer immunotherapy. He describes this exciting, new strategy for destroying cancer cells as transformational, and he predicts it eventually will become the standard of care, replacing traditional approaches such as chemotherapy.
Before launching Juno, Bishop was an Executive in Residence at Warburg Pincus, a global private equity firm with significant investment experience in the pharmaceutical and healthcare industries. He also served as Executive Vice President and Chief Operating Officer for Dendreon, a Seattle-based biotechnology company that develops cancer immunotherapy products. Bishop also has held various positions with major pharmaceutical firms such as Bayer Healthcare, Glaxo Wellcome and Smithkline Beecham.
WuXi AppTec Communications recently talked with Bishop about his company’s groundbreaking research and development, the challenges in bringing a revolutionary new medicine to patients, and the exciting prospect of making significant progress in ending cancer. This interview is part of an exclusive series spotlighting the inside perspectives of thought leaders on topics shaping the future of new medicines.
WuXi: Do you see immunotherapy as one of the best new weapons against cancer?
Hans Bishop: Immunotherapy and cellular biologics, especially, are at the cutting edge of cancer therapy. We think that our cellular biologics can establish a new standard of care in oncology in the near-to-medium term. Longer-term, we think they could change the treatment of other diseases, outside of cancer, as well.
WuXi: Do you see immunotherapy eventually replacing established cancer treatments?
Hans Bishop: That is precisely our ambition. Current standard-of-care treatments such as chemotherapy and bone marrow transplant are frequently extremely challenging, often without durable remissions, and with treatment-related complications and long lasting negative impacts on a patient’s health. Our goal is not incremental improvement. We are working to create therapies that are transformative for patients.
WuXi: What kinds of cancer respond best to immunotherapy?
Hans Bishop: At present, Juno’s product candidates are targeted at blood cancers that express a protein called CD19, and we have seen encouraging early clinical results in these disease settings. We are also optimistic that cellular therapies can be applied to a broader range of cancers, including solid tumors such as breast and lung.
WuXi: What role will combination therapies play in cancer immunotherapy?
Hans Bishop: They are likely to be important. We are currently exploring the possibility of combining our cellular therapies with treatments that have the potential to both augment our drugs and turn on the patient’s own immune system. By combining different mechanisms of action we hope to drive a larger number of patients into durable remissions. An example of this is combining a CD19-directed CAR T with a PD-L1 checkpoint inhibitor. We also own our own small molecule adenosine A2A receptor, vipadenant, that has the potential to disrupt important immunosuppressive pathways in the tumor microenvironment in certain cancers. We intend to use this molecule in combination with our cellular biologics.
WuXi: Currently, check-point inhibitors seem to dominate. How do you see the cancer immunotherapy field evolving over the next five years, and what breakthroughs might we see? What’s the future of gene-editing-based oncology approaches?
Hans Bishop: Checkpoint inhibitors have been a real step forward for patients. But it is worth noting that they only help 25-35% of patients. We think we can do better than that. Cancer has a remarkable ability to adapt and evade treatment, and we are relatively early as a field in learning how to harness the potential and adaptability of the immune system to combat this disease. Many tools will allow us to better engineer cell T cells. Gene-editing is one of the important tools that we expect to utilize, and we are delighted to be partnering with Editas on a number of gene-edited technologies..
Five years is a short time in drug development, but our understanding of these products will grow exponentially over the next few years. In five years’ time we expect to begin implementing next-generation strategies that expand the number of patients we can treat, the number of cancers we can target, and the depth and duration of the remissions we can begin to expect. We not only expect to have our first products on the market, but to also be making substantial progress in bringing better medicines to a broader group of patients suffering from a multitude of cancers.
WuXi: Can you describe your immunotherapy research and how Juno’s approach compares to other immunotherapies? Why do you think it will succeed?
Hans Bishop: Our research is focused entirely on cellular therapy and cells of the immune system to battle cancer. We are working on multiple fronts to build on what we have done to date, including focusing on keeping engineered T cells active in the body for a longer period of time; controlling elements of cell expansion in order to improve tolerability; and better understanding what types of cells work best, cell signaling, and how to better equip cells to find cancer.
Juno believes that the type of cell we use is important, and we believe a defined cell product can better impact patient outcomes. Our first defined cell product candidate, JCAR017, which uses a manufacturing process that influences the phenotype and metabolic profile, and directly controls the number of CD8 and CD4 cells in the final product, is in development now. A defined cell product uses a controlled process, which has the potential for a better tolerability profile and to get a greater percentage of patients into durable remissions.
Juno is pursuing approval for JCAR017 as a treatment for relapsed/refractory non-Hodgkin lymphoma (NHL) as early as the second half of 2018. Given the strength of the preliminary data, we think JCAR017 can be a best-in-class product. Juno intends to pursue this technology across a range of B cell malignancies, including CLL and ALL. Importantly, we are also beginning to apply our early learnings to making therapies that we believe will have the potential to get an even greater percentage of patients into durable remissions. We expect to see data from some of these trials as early as this year.
The next step is understanding where else this technology can be applied. We are optimistic that the technologies we use and the biology we target is applicable in other cancers, and even beyond. For example, we recently began our first experience in multiple myeloma. Juno is also exploring other targets for our engineered T cells in a range of solid tumors. With our collaborators, we have clinical programs focused on mesothelioma, non-small cell lung cancer, triple negative breast cancer, and ovarian cancer.
WuXi: Is global partnership a part of your drug development strategy? Why or why not?
Hans Bishop: Global partnerships are indeed a part of our drug development strategy. We have a partnership with Celgene to develop and commercialize our products outside of North America and China. Last year Celgene opted into their first unit pipeline target, CD19. We are working together to start clinical trials first in Europe and then in other geographies.
In 2016, we also formed a new company called JW Therapeutics with WuXi AppTec, aiming to develop and commercialize engineered T cell products in China. The team based in Shanghai is building clinical and manufacturing capabilities for the Chinese market.
Global partnerships allow us to leverage local expertise in bringing this new area of medicine to patients. The people and capabilities at our global partners are essential for our success. At the same time, we can focus more of our energies and capital on both launching in our home geography and developing more and better therapies for patients.
WuXi: What are the top challenges your company currently faces?
Hans Bishop: This is a new area of medicine. It offers tremendous promise for leveraging the incredible learnings in biology and creating targeted, patient-specific drugs to optimize outcomes. We need to build the capabilities to reliably produce these drugs at scale with a distribution and re-imbursement framework that fosters access to broad populations across the globe.
WuXi: What is the next big milestone for Juno’s development?
Hans Bishop: 2017 will be a data rich year for Juno and B-cell malignancy programs will be at the forefront. Juno plans to initiate trials with our potential best-in-class product candidate JCAR017 in NHL and CLL, and have begun clinical trials in multiple myeloma and expect to have data from these studies and solid tumor product candidates as we move throughout the year.
The next big milestone for our company is the expected approval JCAR017, our defined cell candidate product that has been demonstrating a strong clinical profile and the potential to be best-in-class. We expect approval as early as the second half of 2018.
WuXi: Do you think there is room for small and mid-size companies to have an impact on immunotherapy development?
Hans Bishop: Absolutely. Cell and gene engineering is a potentially disruptive technology in how products are conceived, developed, and manufactured. Juno is a smaller company, and our ambition is to change medicine. Smaller, nimble biotech companies have a rich history of developing innovative and disruptive medicines. Monoclonal antibody therapy, for example, wasn’t developed by big pharma, but by smaller biotech firms. The capabilities we need to succeed are new, and that means that companies without entrenched infrastructure and people have the potential to move faster and be more innovative than larger, established companies. It does not mean that we will automatically win, but the environment is right.