Gene-therapy company Orchard Therapeutics entered into two worldwide royalty-bearing license agreements with GlaxoSmithKline (GSK) for use of their proprietary lentiviral stable cell line technology (LV-SCLT) for Orchard’s investigational hematopoietic stem cell gene therapies for Wiskott Aldrich syndrome (OTL-103 for WAS) and transfusion-dependent beta thalassemia (OTL-300 for TDT).
“Utilization of a stable cell line provides an opportunity to generate lentiviral vector of consistently high titer and eliminates the need to purchase plasmids prior to the production of each viral vector batch, providing more efficient production processes and shorter lead times,” said Bobby Gaspar, MD, PhD, CEO of Orchard. “By increasing the efficiency of the vector manufacturing process, this technology can provide a key competitive advantage and supports our focus on manufacturing innovations that enable commercial scalability.”
The LV-SCLT permanently and stably enables all the lentiviral vector components to be introduced into a cell line in one step, according to GSK. Selection and expansion of a resulting clonal producer line in either suspension or adherent culture reportedly can deliver consistent levels of high titer lentiviral production comparable to those seen using conventional methods.
An overview of this technology, co-authored by Orchard and GSK scientists, was presented at the European Society of Gene & Cell Therapy (ESGCT) Annual Congress in October 2019 using work done in the OTL-300 program for TDT. Under the licenses, GSK has granted patents and pending patent applications related to its LV-SCLT.
According to Gaspar, “We believe the work completed with OTL-300 utilizing a stable cell line can be leveraged and applied to future development plans in OTL-103 for WAS, which will be especially useful in a commercial setting given the large number of patients diagnosed and living with the disease.”
Orchard plans to submit a biologics license application (BLA) and marketing authorization application (MAA) for OTL-103 for the treatment of WAS in the US and EU, respectively, in 2021.
The terms of the license are not expected to have a material impact on Orchard’s financial position or near-term cash needs.
OTL-103 is an ex vivo autologous hematopoietic stem cell gene therapy in development for the treatment of WAS, a life-threatening inherited immune disorder that primarily affects males and is characterized by recurrent and severe infections, autoimmunity, eczema and severe bleeding episodes. It is caused by a mutation in the gene that produces the WAS protein, which results in abnormal function of white blood cells and low platelets.
Without treatment, the median survival for children born with WAS is 14 years of age. The global incidence of WAS is estimated to be about one in every 100,000 male births per year.