Autolus announces license agreement with UCL Business PLC for clinical-stage product candidate in development for the treatment of B-cell malignancies
Autolus Limited, a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announced the execution of a license agreement under which Autolus has acquired global rights from UCL Business plc (UCLB), the technology-transfer company of University College London (UCL), to develop and commercialize a novel CD19 chimeric antigen receptor (CAR) T cell therapy with novel targeting properties for the treatment of B cell malignancies.
The product candidate, which we have designated as AUTO1, is an investigational therapy in which a patient's T cells are genetically modified to express a novel CD19-specific CAR designed to reduce side effects related to cytokine release syndrome (CRS). CD19 is a protein expressed by B-cell lymphomas and leukaemias. CD19 CAR T cells have proven effective in treating leukaemia and lymphoma, with efficacy dependent on engraftment and expansion of CAR T cells. However, rapid activation and expansion of CAR T cells can result in CRS, which in some cases can be life-threatening, particularly for elderly patients and patients with higher tumour burden that have poor tolerance for toxicity. Furthermore, excessive activation of CAR T cells can lead to cell exhaustion and limit their persistence.
AUTO1 is currently the subject of two Phase 1 studies, one in paediatric acute lymphoblastic leukaemia (ALL) and the other in adult ALL*. AUTO1 has been designed to recognise CD19 with a fast-off binding kinetic, which allows CAR T cells to efficiently recognize cancer cells, inject cytotoxic proteins to initiate the natural self-destruction process present in all human cells and then rapidly dissociate from them in order to engage the next cancer cell - a process also known as serial killing. We believe that avoiding prolonged residence on targeted cells may minimize excessive activation of CAR- T cells and reduce toxicity and CAR T cell exhaustion. In a UCL Phase 1 clinical study (CARPALL) in paediatric ALL patients evaluating the properties of AUTO1, investigators observed levels of efficacy similar to those in other reported studies, without observing grade 3 or 4 CRS and without the need to administer immunosuppressive drugs. Data from the CARPALL study were presented at the 2017 Annual Meeting of the American Society of Hematology*.
Dr Martin Pule, Chief Scientific Officer of Autolus Limited and Senior Lecturer in Haematology at UCL, commented: “Current CARs in the clinic are designed with high affinity binders that can engage the CD19 target for an extended period of time. This can lead to excessive T cell activation and cytokine release, as well as exhaustion of the T cell. We developed a CD19 CAR that is designed to bind to its target with a fast on-rate but then releases quickly, which is more similar to naturally occurring T cell activity. The initial clinical data supports the premise that