Laura Anderson and Helena Connors
The rapid development of the immunotherapy landscape has driven increased numbers of acquisitions and collaborations between pharmaceutical companies, biotech companies and academic organisations in recent years. These companies recognise the importance of having the right expertise in this relatively new and complex area, and also the benefits of sharing the associated risks and costs, driving numerous collaborations. The development of UCART-19, an allogeneic CAR-T cell therapy, provides an example of the wide variety of collaborative arrangements that may arise during the development of a new immunotherapy product.
UCART-19 is a potential treatment for acute lymphoblastic leukaemia (“ALL”), and is currently in phase I clinical trials. But where did it come from? Early research into CAR-T cell production and the RQR8 suicide switch, both of which are essential to the development of UCART-19, was carried out by researchers at University College London. Development of UCART-19 was then taken forward by Cellectis, a French biopharmaceutical company. In 2014, Cellectis announced that it had entered into a strategic collaboration agreement with Servier to develop and commercialise UCART-19, as well as five other product candidates. In 2015, Servier exercised an option to take exclusive rights to UCART-19. Servier then entered into a global licensing and collaborating agreement to co-develop UCART-19, with Pfizer responsible for marketing in the US and Servier responsible for potential commercialisation in the rest of the world.
Last year Pfizer sold its rights in its portfolio of allogeneic CAR-T therapies, including UCART-19, to Allogene Therapeutics Inc. Allogene was set up by Kite Pharma and Gilead specifically to develop allogeneic CAR-T therapies for cancer. UCART-19 is now Allogene’s lead investigational product. It is being developed in partnership with Servier, which is sponsoring the Phase I ALL trials in adult and paediatric patients. Allogene gained the commercialisation rights in the US from Pfizer, with Servier retaining its rights to potential commercialisation of UCART-19 in the rest of the world. UCL and King’s College London have also been running clinical trials into the application of UCART-19 in B-ALL.
At the American Society of Hematology (ASH) 2018 conference held in December 2018, Allogene announced that initial studies treating patients with an anti-CD52 immunosuppressive preparation regime alongside UCART-19 showed an 82% complete response rate with significant cell expansion. This potential breakthrough in patient response is likely to accelerate the development of UCART-19. However, it remains to be seen whether UCART-19 will change hands again on the road to marketing authorisation, or whether Allogene and Servier will continue to develop it all the way through phases II and III.
Although commercialisation of UCART-19 is still a long way off, it is further down the developmental pipeline than any other allogeneic CAR-T therapies currently in development. It gives a clear example of how collaboration underpins many of these new therapies.