Orchard Therapeutics burst into life today with a little seed money and backing from several major hospitals and universities as it looks to take on the challenging but potentially lucrative world of ex vivo gene therapy research.
The clinical-stage startup launched with operations in London and the U.S., beginning life with a £21 million ($33.4 million) series A financing round led by F-Prime Capital. Two of its founders are former GSK employees, who will now help Orchard develop a rival to GSK’s soon-to-be-approved “bubble boy” gene therapy Strimvelis.
As part of its launch, the company has also announced formal partnerships with University College London; Great Ormond Street Hospital; the University of Manchester; the University of California Los Angeles; and Boston Children’s Hospital for the development of transformative gene therapies for serious and life-threatening orphan diseases.
Orchard’s development programs are focused on ex vivo autologous haematopoietic stem cell gene therapy to restore normal gene function in primary immune deficiencies, metabolic diseases and haematological disorders.
This pioneering technology uses a sample of the patient’s own stem cells, which are modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. The use of the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years.
It’s a niche but growing area of R&D for biotech and pharma alike, with the only approved gene therapy in the western world being uniQure’s ($QURE) Glybera, which the EMA green lighted back in 2012 for the rare blood-clogging condition lipoprotein lipase deficiency. The drug costs around $1 million per treatment.
Novartis ($NVS) backed GenSight Biologics is also researching in this area in the form of its lead product candidate GS010, which targets the rare disease Leber’s Hereditary Optic Neuropathy (LHON), and is currently in Phase III.
The treatment works by fixing a DNA glitch that leads to LHON, using a harmless virus to deliver a corrective copy of the ND4 gene.
Glaxo ($GSK) is also set to see its gene therapy Strimvelis approved later this year in Europe for severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)--aka “bubble boy syndrome,” which affects just 350 people worldwide, making it an ultraorphan drug.
Strimvelis uses a virus to insert copies of a gene (in this case, ADA) into stem cells extracted from the bone marrow of patients. The cells are then reintroduced to the patient, who can expect to start making the gene on their own, repairing their immune system. The therapy has been developed by Italy's San Raffaele Telethon Institute for Gene Therapy and the Milanese biotech MolMed, which is based at the Institute. A deal between GSK and the groups was struck back in 2010.
And it is in fact Strimvelis that Orchard will be hoping to rival as, despite there being so few patients with the condition (only 15 are diagnosed in Europe), the small biotech is too developing an ex vivo autologous lentiviral stem cell gene therapy for ADA-SCID.
Its most recent interim clinical data from this program showed “significant immune reconstitution” and 100% survival in 32 patients treated at GOSH and UCLA, as of March 2016, according to the company.
Strimvelis gained the CHMP nod in early April based on the latest study for the drug, in which 18 children in a trial with Strimvelis were still alive up to 13 years after treatment--with median survival duration of 7 years.
Bone marrow transplants are the current standard of care for ADA-SCID but only in the minority of cases can this work and only where there is a well-matched donor. Children who are not treated will typically not survive beyond two years.
Looking ahead, should Orchard gain approval, it would need to at least match if not better GSK’s drug in terms of efficacy, and likely beat it on price too. GSK recently told FierceBiotech that it was already thinking about offering a staggered payment, or payment-by-results-type deal for its therapy--and that it would cost “significantly less” than Glybera.
Bobby Gaspar, Orchard’s CSO and Professor of Paediatrics and Immunology at the UCL Institute of Child Health and GOSH said: “Orchard’s founding scientists, also including Professors Adrian Thrasher and Waseem Qasim from UCL and GOSH, have been pioneering ex vivo autologous haematopoietic stem cell gene therapy for the last 20 years. We have seen promising effects in several different diseases and are hopeful that this technology will change the lives of many children with life-threatening conditions in the future.”
Orchard is also exploring the effects of ex vivo autologous lentiviral stem cell gene therapy in patients with mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo disease type A).
The biotech said it employs a “collaborative development model” for its research programs that sees it work closely with doctors and researchers at leading academic centers.
Orchard’s management team includes senior pharma leaders with experience in gene and cell therapy, including founders Andrea Spezzi, CMO, and Nicolas Koebel, SVP business operations--who prior to joining Orchard were involved in the clinical development and market access planning at GSK. Koebel was at GSK for 10 years until 2015. In 2011, he was appointed Global Commercial Lead to GSK's Rare Diseases Unit, to oversee the commercialization of GSK's programme of autologous ex vivo gene therapies. Spezzi served as VP and Medicine Development Leader at GSK's Rare Diseases Unit, after working for Takeda as it global medical director for R&D.
The biotech said in a statement: “Orchard’s mission is to be nimble and focused so that we can translate results from preclinical and early clinical research into commercially approved medicines. We believe that our strong academic partnerships and pioneering technology platform will allow us to harness the life-giving potential of gene therapy.”
Orchard’s Series A financing has been led by F-Prime Capital, a VC investment fund, with support from UCL Business and additional participation from the UCL Technology Fund.
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