One of the Plenary keynote speakers at Drug Discovery 2015, is Professor Tracy Hussell, Director of the Manchester Collaborative Centre for Inflammation Research (MCCIR), an innovative joint venture with the University of Manchester, AstraZeneca and GlaxoSmithKline. Professor Hussell has published in excess of 100 peer reviewed papers, served as a Trustee and Education Secretary of the British Society for Immunology and performs editorial duties for a range of immunological journals. Her research group, studying immune health and its deregulation in the lung, is particularly interested in how structure modulates innate immunity and how this is perturbed in chronic lung disease. In 2004, Professor Hussell was awarded a Personal Chair in Inflammatory Disease at Imperial College London.
In an exclusive interview with ELRIG’s Liz Quinn, she gives her opinion on the future of open innovation strategies for inflammation and the challenges involved in realizing the full potential of new therapeutic development using alveolar macrophages.
LQ: Tracy – what attracted you to move from London to Manchester? Can you tell us about the new Manchester Collaborative Centre for Inflammation Research (MCCIR)?
TH: At the time this opportunity came up, I wasn’t looking to move. After preliminary discussions, however, it was clear that this represented a novel opportunity to brainstorm areas of significant unmet need with Industry and then use our academic expertise to begin discovery in relevant areas. Furthermore, the collaborative atmosphere at Manchester was tangible and clinicians in multiple areas were willing to work closely with us. Drawing industry closer to academic research in Universities helps to nudge scientific discovery into areas where the development of new therapies is feasible. To date the centre has recruited 86 staff including 7 principal investigators, 4 research fellows and 3 clinical fellows.
Our mission is to bring industry closer to early-stage ground-breaking academic science, develop unique diversity of expertise around inflammation and use the funds to pump prime projects that can leverage additional research funding. Since launch in 2013 we have published 14 papers in journals with an impact >10, had amazing success of our early career scientists in securing prestigious fellowships, had 5 joint publications with industry in Nature Medicine, Blood, Mucosal Immunology and two in Nature Comm. We have developed world-class facilities in super resolution imaging and flow cytometry and galvanized clinicians to develop new research utilizing various large, unique and well-characterised patient cohorts.
LQ: What changes have you observed in the drug discovery landscape and what disruptive, transformational technologies do you predict we will see in the next 5 years?
TH: I think a lot of research in inflammatory disease in particular has followed a common theme: identify something that is in excess, block it, and then in most cases, drop it. We need different ideas and different approaches. Mopping up excesses in general hasn’t worked; it certainly hasn’t stopped disease progression. Therefore, I feel that transformational change will come from looking at processes generic to disease, such as repair and inflammatory resolution. I feel that a better understanding of health also has a lot to offer. In my opinion, single cell sequencing will enable an understanding of cellular heterogeneity in inflammation, identifying novel cell subsets and the discovery of novel pathways that restore health
LQ: As you work in an open innovation, pre-competitive environment with some of the UK’s largest pharmaceutical companies, what are some of the greatest advantages of open innovation strategies for inflammation research? What are some of the hurdles or challenges that the drug discovery industry needs to overcome in order to realize the full potential of these strategies?
TH: The greatest advantage for all parties is the speed at which ideas can be taken forward. In the past, we have essentially been running a relay race, handing the baton to each other after 100 meters. With open innovation we can run 100 meters at the same time. For example, we can decide relevant areas of unmet need together, design experiments to facilitate discoveries, determine intellectual property landscape from the beginning and perform a preliminary screen on drugability. This means that bench to bedside will be significantly faster. Both industrial partners have been incredibly open about their main programmes of interest, whilst maintaining compound structures as confidential. There are a number of projects of interest to both partners, which generates innovation on many levels.
The major hurdle, as ever, is time. The drug discovery industry needs to fund industrial scientists to actually work alongside the academic group. Simply aligning people with a project, when they are also working on a pipeline does not facilitate close interaction. I firmly believe that discovering new medicines should be performed by industry placing a group of people in an academic institution that contains strong clinical links and well characterized patient cohorts.
LQ: Your lab has been studying immune health and its deregulation in the lung for many years. Through your collaboration with GSK and AZ, has this enabled you to obtain preclinical data showing advantages with compounds compared to those currently in use? Where is therapeutic modulation of acute and chronic inflammation headed and what do you believe will be the next blockbuster drug?
TH: The collaboration with AZ and GSK has facilitated pre-clinical research in a number of important ways. We have been able to access precious archived tissues from past clinical trials, enabling us to perform proof of concept investigations on new pathways, we have been provided with compounds that interact with our pathways of interest, and finally we have used the financial contribution to MCCIR as industrial contributions to grant applications.
We would like more interaction in the design and delivery of clinical trials as we believe we could add mechanism to the observations and also stratify patient responses in more detail,
LQ: At the Drug Discovery 2015 conference in Telford, UK in September, you will be delivering a talk on the development of new therapeutics for respiratory inflammation. Can you give us a preview of your findings and how your work is being applied for new drug development?
TH: We have been working on a new concept that is relevant to many respiratory inflammatory conditions; airway macrophage adaptation in the repairing lung. This adaptation can be beneficial or detrimental and occurs because macrophages perform dual functions that require opposing responses. They are required to clear self-apoptotic cells and cellular debris in an anti-inflammatory manner, but respond to pathogenic microorganisms in an inflammatory manner. Thus, if an environment continually has a high cell and matrix turnover, your alveolar macrophages will be pre-occupied in an anti-inflammatory process, which means they won’t respond immediately to incoming pathogens. We believe such pathogenic adaptation is why some patients with COPD, asthma, CF and IPF experience frequent viral and bacterial infections. These patients are at the severe end of the disease spectrum and account for most of the NHS cost. We have discovered pathways in macrophages from such patients that contribute to this aberrant adaptation and are now working with industry to target them. I will discuss this concept and solution to the problem in September.