Orchard Therapeutics and Pharming Group N.V. enters into a strategic collaboration to research, develop, manufacture and commercialize OTL-105, a newly disclosed investigational ex vivo autologous hematopoietic stem cell (HSC) gene therapy for the treatment of HAE.
OTL-105 is an investigational HSC gene therapy designed to increase C1 esterase inhibitor (C1-INH) in HAE patient serum to prevent HAE attacks. OTL-105 inserts one or more functional copies of the SERPING1 gene into patients own HSCs ex vivo which are then transplanted back into the patient for potential durable C1-INH production. In preclinical studies, to date, OTL-105 demonstrated high levels of SERPING1 gene expression via lentiviral-mediated transduction in multiple cell lines and primary human CD34+ HSCs. Furthermore, the program achieved production of functional C1-INH protein, as measured by a clinically validated assay.
Under the terms of the collaboration, Pharming has been granted worldwide rights to OTL-105 and will be responsible for clinical development, regulatory filings, and commercialization of the investigational gene therapy, including associated costs. Orchard will lead the completion of IND-enabling activities and oversee manufacturing of OTL-105 during pre-clinical and clinical development, which will be funded by Pharming. In addition, both companies will explore the application of non-toxic conditioning regimen for use with OTL-105 administration.
“Given the combination of our expertise in HSC gene therapy with Pharming’s long-standing legacy and experience, we have the potential to reinvent the treatment paradigm for HAE by providing people living with this life-threatening disorder a sustained therapy with a single administration,” says Bobby Gaspar, M.D., Ph.D., CEO of Orchard Therapeutics: “This collaboration demonstrates the promise of the HSC gene therapy platform and how it can be applied to new therapeutic areas with larger patient populations. We believe the HSC gene therapy pipeline we are building could continue to be a source of future partnerships in areas where the biology supports our approach.”
“Pharming has been committed to the HAE community for more than two decades,” says Sijmen de Vries M.D., MBA, CEO of Pharming: “We have partnered with Orchard Therapeutics, a leader in the development of autologous HSC gene therapy, to develop a potentially curative treatment for HAE. Based on Pharming’s experience in HAE, we believe that HSC gene therapy has the potential for the highest probability of success. This confidence is based on the durability of effect and safety observed in approved treatments from Orchard’s HSC gene therapy portfolio and positive clinical data in several other programs. This a significant first step in developing a potentially transformative one-time treatment for HAE.”
“Great progress has been made in HAE treatment over the last 15 years. However, HAE remains a severe, debilitating disease with an ongoing burden of angioedema attacks or chronic medication use,” says Dr. Marc Riedl, Professor of medicine and Clinical Director of the U.S. Hereditary Angioedema Association Center at the University of California, San Diego: “This promising work toward treatment with the potential for durable long-term clinical benefit is encouraging and signifies an ongoing commitment to the HAE community. I look forward to these efforts to identify and carefully advance a potential cure for HAE.”