The vision of Life Science Leader is to help facilitate connections and foster collaborations in pharma and med device development to get more life-saving and life-improving therapies to market in an efficient manner. Connect, Collaborate, Contribute
Issue link: https://lifescienceleadermag.epubxp.com/i/406276
EXCLUSIVE LIFE SCIENCE FEATURE leaders leaders ROUNDTABLE LIFESCIENCELEADER.COM 44 NOVEMBER 2014 experiments to understand the essential combination components. Dr. Yong-Jun Liu, our new head of research, is a world leader in the field of immuno-oncology, so in addition to our focus on combinations, he has brought a whole new way of think- ing about how we approach combination therapy. B a c k b o n e t h e ra p y ? [BRADLEY] Obviously, the cornerstone of our immunotherapy strategy is combina- tions, and in those combinations there will be certain backbone approaches, but the optimal combinations are still being determined, and that is why there is so much activity at the moment to identify them. Still, although there is a great deal of talk about the second wave of immuno- therapy, the therapies that are in the lead today will likely be the backbone therapies for optimal combinations for a long time. C o m m e r c i a l i z a t i o n c h a l l e n g e s ? [JALLAL] There are no significant dif- ferences in the challenges for immu- notherapies and other types of cancer drugs. We deal with several stakeholders. The first one is the patient — we must make sure whatever we do is backed up with data. If we say our drug should be used in a combination, the use must bring more benefit to patients. The sec- ond stakeholder is regulatory authorities, such as the FDA. We must deliver data that supports putting the combination use on our label. The third stakeholder is the payer, to whom we must also show data that differentiates our treatment in combination, plus cost-effectiveness data. We are right on track with our stakeholders in all respects right now. Obviously, there are more complica- tions if the combination includes not only our drugs but also ones from other companies. However, we have a broad portfolio, and most of the combinations we are developing now consist of mol- ecules we have in house, and that gives us more flexibility and control over how we can price the combinations. We don't develop drugs just for the sake of devel- oping them — we want patients to have access to them. You have to work with all the stakeholders to make sure as many patients as possible can gain access to your drug. [BRADLEY] Another consideration: Immune-mediated therapies take time to generate the immune cells that trav- el to tumor sites and kill cancer cells. Sometimes the biological effects take weeks to months. Physicians must real- ize there is a different pace of response, and the tumor may even seem to get a little larger at first, due to an inflamma- tory response, but it will then shrink and sometimes go away. What is surprising is how quickly physicians have, in fact, learned to deal with some of the differ- ences in side effects. J U N O T H E R A P E U T I C S Developing novel immunotherapy platforms that harness the potency of memory T cells, redirecting them to targets expressed on or in cancer cells; three candidates in Phase 1 – 2. MARK W. FROHLICH, M.D. Executive Vice-President, Research & Development W h y c o m b i n a t i o n s ? Historically, combination therapy with traditional agents has been the corner- stone of oncology. With novel immuno- therapeutics, and an increased under- standing of mechanism of action, there has never been a stronger rationale for combining drugs. In the short term, we need to combine drugs with potentially synergistic mechanisms. In the longer term, we can potentially combine mul- tiple therapeutic avenues within our engi- neered T cells by modulating pathways within the T cells or using them as a vehicle to deliver molecules to the tumor microenvironment. For example, cyto- kines that would be toxic when delivered systemically could be delivered to the tumor by the T cells to provide poten- tially synergistic, or at least additive, anti- tumor effects. E s s e n t i a l c o m p o n e n t s ? Engineered T cell therapy and checkpoint blockade are two of the most exciting approaches. Checkpoint inhibitors are already approved for certain indications; they don't appear to be working in all tumor types or patients but will be an important building block with which we can start mixing and matching in rational combinations. Used together, taking the brakes off and pushing the accelerator —providing cells specifically activated to target the cancer — will be important to test, particularly in the challenging solid tumor setting. B a c k b o n e t h e ra p y ? Engineered T cells and checkpoints inhibitors can potentially serve as therapeutic backbones. However, ear- lier in the treatment paradigm, as in the adjuvant setting where only micro- scopic amounts of tumor remain, there may be insufficient antigen to stimu- late a T cell response to a checkpoint inhibitor or to stimulate the prolif- eration of engineered antigen-specific T cells. In those settings, a vaccine to simulate T cell proliferation may be important as one of the therapeu- tic backbones in combination with the others. COMBINATION CANCER IMMUNOTHERAPY — A VIRTUAL ROUNDTABLE By W. Koberstein The evolving science in cancer immunotherapy has a significant impact on clinical trial design. M A R K M A N S O U R , PH.D. Chief Executive Off cer