Authors: Eleonora Lugara, Jun Hon Pang Edited by: Márcia Costa
The field of immunotherapy is booming with major pharmaceutical companies establishing their presence and capabilities, most notably Novartis, Gilead and GSK. In parallel to the UK’s commitment to driving the biosciences industry forward, two prominent London-based companies in the field of immunotherapy, Autolus and Cell Medica , have gathered significant investments and reputation in T-cell therapies. Both companies were among the first partners of the £60 million cell and gene therapy manufacturing centre created by Cell and Gene Therapy Catapult. The Stevenage-based centre was officially opened on 23rd April 2018.
We spoke to the founders of Cell Medica and Autolus, Gregg Sando and Dr. Martin Pule respectively. Both of them were speakers at the SIULondon ‘Advances in Immunotherapy’ event on 2nd May 2018. In this interview, Gregg revealed the exciting journey that led to the creation of Cell Medica, the duties and responsibilities of managing a biotechnological company and the reasons why he chose to invest in allogenic approaches. Martin shared his point-of-view of spinning out Autolus as an academic, and the challenges and current improvements in commercializing engineered T-cell therapies, which also includes allogenic approaches.
GREGG SANDO, FOUNDER AND CEO OF CELL MEDICA
Mr. Gregg Sando is the founder and CEO of Cell Medica. He previously had a career in investment banking in New York and London. He holds a BA Biochemistry from Harvard University, MBA from University of Chicago and MSc Immunology from Imperial College London.
What motivated you to move to this field after 22 years in investment banking and why did you decide to found Cell Medica?
I started initially as a Biochemistry student at Harvard, intending to go to Medical School. After a while, my attention shifted towards the business side of science and this led me to enrol into a finance-oriented business course, at the University of Chicago. Later on, I was recruited by several large investment banks, which brought me to work in Wall Street first and in London afterwards. It was an exciting and dynamic time: my role was mainly advising on merging and acquisition of financial institutions all over Europe. Nevertheless, during these years, I always remained interested in science. Hence, in 2004, I left investment banking and enrolled in an innovative immunology course at Imperial College. During the course, I learnt about cutting-edge techniques in immunology and specifically I recognised the potential of the immune system in treating cancer, infections and autoimmune diseases. During these years, I have been very much influenced by two personalities: Professor Hans Stauss and Professor Emma Morris (both now at UCL). They explained to me the theory of T cell immunotherapy and encouraged me to launch what would have become one of the first cellular immunotherapy companies, Cell Medica. By then, the evidence from academic research and early stage clinical trials was very convincing, therefore the next step was to develop a convincing business plan to translate this academic research into a commercial product. Given the strength of the underlying science and my belief we would solve the major business challenges, I was comfortable in deciding that cell-based immunology was the area where I wanted to focus my attention, energies and my new career.
As CEO, what is your role at Cell Medica and can you give us some insight into your daily routine?
In a nutshell, my role is managing the company. This involves both managing the business by setting the goals and ensuring financing for the company. Internally, I guide the senior team who are directly responsible for covering all the areas of drug development: the chief medical officer, the chief scientific officer, the head of manufacturing, the head of clinical operations, etc. The other half of my time I spend talking with investors, explaining the vision of our company, how we create value and a successful product, giving them the confidence to invest in the company. A good internal execution plan, assuring that we are achieving objectives in a realistic timeline and assessing the product portfolio, is a pivotal role of my everyday job at Cell Medica.
Can you tell us about Cell Medica? What makes it different from other companies in the field of immunotherapy?
Cell Medica started as a company focused on infections. Despite our product being clinically effective and commercialized in several countries in Europe, the market was too small. After realising the dramatic data coming from engineered T cells, we decided then to move our attention to cancer. This is now a very active field for the treatment of cancer but given the huge potential and the relatively few companies with clinical stage products, the overlap of products and interests is not a big problem for our chosen areas of focus. Each company has a slightly different technology. Our major interests involve developing cell therapies for solid tumours as a therapeutic focus and establishing an allogenic (off-the-shelf) platform as our technology strategy. Normally speaking, cell therapies are custom made, the so-called autologous therapy. Autologous therapy begins from the patients’ own cells and the advantage is in that the risk of rejection is really low.
The allogenic approach is made possible by engineering healthy donor cells with state of the art technologies (such as CRISPR and silencing RNA). This modification will allow the genetically engineered immune cells from a healthy donor to exist in the patient at least for a sufficient time to recognise and kill the cancer cells.
The potential of this field is huge and we are very close to launching our first clinical trial with the allogenic product later this year. There is so much to learn and so much to prove about which one of these technologies is the best!
In your opinion and experience, what is the main obstacle that the field of immunotherapy is facing currently? And what are the challenges in the future?
The main long-term obstacle is probably manufacturing. At the moment, we are able to show how these cells work and how they can treat different types of cancer, but we are adding more features to the cell using genetic engineering. There are not just academic researchers involved now, but also biotech engineers and people from many fields of expertise, all trying to solve key problems for large scale manufacturing. We now have a basic understanding of how to manipulate the immune system - how to switch it off (in case of autoimmune disease) or on (for cancer and infections).
The next big question in the immunotherapy field is how to commercialize a personalized cell therapy. Theoretically, we should make a cell product for each individual. This is indeed a serious commercial challenge! The solution to that, in our vision, is to make an off-the-shelf product.
DR. MARTIN PULE, FOUNDER AND CSO OF AUTOLUS, ACADEMIC AT UCL
Dr. Martin Pule is the Chief Scientific Officer of Autolus Ltd, and also a Clinical Senior Lecturer in the Department of Haematology at University College London (UCL) Cancer Institute. He founded Autolus in 2014 as an academic spin-off, focusing on commercialization of engineered T-cell immunotherapy products using chimeric antigen receptors (CAR) and T-cell receptors (TCR). He is named as BBSRC Most Promising Innovator 2016 based on his contributions to T-cell medicine.
You hold simultaneous positions in academia (UCL) and industry (spin-off Autolus). Can you tell us about your journey towards this achievement? And presently how do you manage your time and effort between both organizations?
The field of T-cell engineering has become increasingly commercial and I have always wanted to spin-off a company to allow more rapid development of CAR T-cells. The funding environment within the UK a few years ago wasn’t great, and there weren’t many suitable venture capitalist funds. I initially pitched to Cell Medica, which is one of the UK's oldest cell therapy companies, as well as some other potential investors, but I did not get far.
The scene changed with the founding of Syncona back in end of 2013, which is a life-science focused investment fund established initially by the Wellcome Trust. That was a really brilliant investment track to get on. As an academic, you are not really equipped to run a biotech company. Syncona has a lot of experienced people and was able to loan the company some of their staff (e.g. a CEO after series A financing) and had actively recruited senior staff for the company. They pretty much helped in every way I could think of - as well as supplying the capital of course.
In the initial stages, the spin-off company was very dependent on UCL: there was a lot of overlap and tech transfer and it made sense to keep my academic position at UCL. Despite Autolus continuing to grow and now being completely independent of UCL, I have continued my lab at UCL while being CSO at Autolus. This works well for me personally since the intellectual challenges are different and complementary. Autolus has industrial muscle and focus, while in the academic sphere it is possible to perform open-ended and more theoretical research.
Can you tell us briefly about your latest projects?
What I am most proud of recently is the results from two clinical studies. The first is a CAR study targeting GD2 which is tested in a paediatric cancer called Neuroblastoma. Early data from this study shows evidence of activity without on-target off-tumour toxicity. This was recently presented at a plenary session in AACR.
A second study tests a new type of CAR against paediatric refractory B-cell leukemia. This CAR dubbed CAT19 (or catalytic CD19 CAR) was designed to allow CAR T-cells to better engraft in patients and to be highly active but cause less toxicity. We presented clinical data from this study at ASH last year.
Both of these projects started in UCL but can be commercialized by Autolus. In UCL, my research focuses on studying the basic biology of T-cell engineering for cancer applications. I am also interested in the interface between biology and nanotechnology.
You have the subject expertise in immunotherapy and the translational experience of this area towards patients. Can you tell us the key challenges of bridging the gap between the science, translation and commercialization of such therapies?
To me, translation means taking something from research and testing it to patients. In this regard, UCL has pretty decent infrastructure for translating T-cell engineering studies. There are labs performing clinical grade manufacturing in the UCL Cancer Trial Centre, and there are internal organisation handling the regulatory side of things. UCL is well equipped to translate studies. What the university does not directly do is commercialization in the broader sense. Commercialization, however, is the only way new therapies can be brought to large numbers of patients.
A good example of challenge in CAR T which is being solved by industry and commercialization (but not suitable for academia) is the practical challenge of CAR T-cell therapies logistics. This typically includes systems to harvest T cells from patients, transporting T cells to the lab, manufacturing the cells and bringing them back to the patients. With most CAR T-cell approaches, each product is made individually for each patient. Clearly this adds more cost and complexity compared to standard antibody or small molecule drugs. This formed an initial barrier to commercialization since many investors and pharma companies could not really foresee how such cell therapies can be commercialized.
However, like everything else in our civilization: if something works really well and there is demand for it but is complicated and expensive, eventually there will be ways to make it simpler and cost effective. For example, a company called Trakcel has made progress in digitizing logistics around T-cell manufacturing and delivery. In terms of manufacturing cells, there are several companies that are making automated cell manufacturing platforms such as Miltenyi Biotec.
In short, academia has worked on the CAR T-cell approach for quite a few years and got it to the stage where there is clinical evidence of efficacy. Industry now can take over and industrialize the process of making CARs to treat different cancers and solve the problems of large-scale manufacture and delivery of these new therapies.
What is your vision for the future of immunotherapy?
I would like to see engineered T-cell therapies becoming the main modality for advanced cancers leading to lower long-term toxicity and greater long-term efficacy and replacing bone marrow transplantation and combination chemotherapy. I think the main focus of engineered T-cell therapy will be cancer but I also think that engineered T-cells will find applications in autoimmune disease and chronic viral infections.