BOSTON & LONDON—In July, Orchard Therapeutics announced two worldwide, royalty-bearing license agreements with GlaxoSmithKline plc (GSK). These deals allow Orchard the use of GSK’s proprietary lentiviral stable cell line technology (LV-SCLT) for its investigational hematopoietic stem cell gene therapies for Wiskott Aldrich syndrome (OTL-103 for WAS) and transfusion-dependent beta thalassemia (OTL-300 for TDT).
Under these new licenses, GSK has granted Orchard patents and pending patent applications related to its LV-SCLT. The terms of the licenses are not expected to have a material impact on Orchard’s financial position or near-term cash needs.
LV-SCLT permanently and stably enables all the lentiviral vector components to be introduced into a cell line in one step. Selection and expansion of a resulting clonal producer line in either suspension or adherent culture can deliver consistent levels of high-titer lentiviral production, comparable to those seen using conventional methods.
“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 Dr. Bobby Gaspar, 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.”
Gaspar continued, “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.”
WAS is a life-threatening inherited immune disorder that primarily affects men. It is characterized by recurrent and severe infections, autoimmunity, eczema and severe bleeding episodes, and 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. It is estimated that about one in every 100,000 males born worldwide are affected by WAS per year.
Scientists from both Orchard and GSK co-authored an overview of the LV-SCLT technology. This 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.
With headquarters in Boston and London, Orchard Therapeutics is a global gene therapy leader focused on developing innovative, potentially curative gene therapies for people affected by rare diseases. The company’s ex-vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. OTL-103 is an ex-vivo autologous hematopoietic stem cell gene therapy in development for the treatment of WAS. In 2018, Orchard acquired GSK’s rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry, spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist. Recently, Orchard received both orphan drug designation and rare pediatric disease designation from the U.S Food and Drug Administration for OTL-203, which is currently in development for the treatment of mucopolysaccharidosis type I.
In a statement on the company’s website, Gaspar also mentioned that SCLs are just one key component of the manufacturing strategy that Orchard is building to ensure that therapies, once approved, are scalable to meet patients’ needs. The company is actively evaluating other promising technologies to increase manufacturing efficiency and scalability, with one example being transduction enhancers, which are chemical agents that boost uptake of lentiviral vector into cells. Hematopoietic stem cells have historically been a difficult cell type to transduce, which necessitates the production of large quantities of viral vectors. Ongoing research at Orchard aims to identify transduction enhancers that can facilitate the same output of gene-transduced cells using a much smaller amount of viral vector.
Additionally, Orchard is invested in development of automated cell handling processes. Cell handling today is an extremely manual process, requiring multiple steps of cell manipulation in sterile environments. Recent technological advances in closed system manufacturing and automated cell handling could offer significant efficiencies, while ensuring adherence to exacting manufacturing standards.
“There is much work to be done to realize the full potential of HSC gene therapies,” Gaspar concluded. “Manufacturing innovations will play an essential role in shaping the future of this class of medicines. Orchard is committed to continuing to lead advancements in this area, with the ultimate goal of expanding the reach of HSC gene therapies to all patients who could benefit.”
Moving forward, Orchard plans to submit a biologics license application and marketing authorization application for OTL-103 for the treatment of WAS in the United States. and European Union, respectively, in 2021.