Encouraging Clinical Data Generated from Ongoing Proof-of-Concept Study Conducted by the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget); Enrollment Expected to Complete in the First Half of 2020

Leverages Orchard’s Expertise in Treating Neurometabolic Diseases Using its Investigational Autologous Hematopoietic Stem Cell Gene Therapy

Builds Upon Orchard / SR-Tiget Partnership to Develop Novel Gene Therapy Candidates

Orchard Therapeutics, Fondazione Telethon and Ospedale San Raffaele today announced that Orchard has been granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the ex vivo autologous hematopoietic stem cell (HSC) gene therapy program for the treatment of Mucopolysaccharidosis Type I (MPS-I) developed by the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. The clinical-stage program is currently enrolling patients in an ongoing proof-of-concept study. As of data presented by SR-Tiget at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in April 2019, four patients have been enrolled in the trial with follow-up of up to nine months.

MPS-I is a progressive, debilitating and often life-threatening inherited lysosomal storage disorder. Patients often experience neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications, with the most severe form known as Hurler syndrome.

“We believe the use of ex vivo autologous hematopoietic stem cell gene therapy in MPS-I has the potential to fundamentally change the lives of patients born with this devastating and rapidly progressive condition,” said Mark Rothera, president and chief executive officer of Orchard. “This program leverages our expertise in developing ex vivo autologous HSC gene therapy candidates for neurometabolic disorders. Given the transformative potential seen in our MLD program, we hope we will be able to correct multiple aspects of the condition, including central nervous system dysfunction.” 

The terms of the deal include an upfront payment in cash as well as contingent payments on the achievement of future development, regulatory and sales milestones, as well as royalty payments on net sales.

The MPS-I program has shown promising clinical data in an ongoing proof-of-concept study in patients with the severe Hurler subtype, who were treated with ex vivo autologous HSC gene therapy, referred to as OTL-203, using a cryopreserved formulation and a lentiviral vector.

• Preliminary data in four patients presented at last month’s 22nd ASGCT annual meeting indicate treatment with gene therapy and the selected conditioning regime was well-tolerated in these patients.
• Engraftment and high alpha-L-iduronidase enzyme (IDUA) expression was seen in the first two patients with sufficient follow-up to assess these parameters.
• As of the data presented at ASGCT, four patients have been enrolled in the trial with up to nine months of follow up. The trial is expected to enroll up to eight patients by the first half of 2020, with preliminary findings after one year of follow-up.

“Developing safe and effective treatments for neurometabolic diseases has been a challenge that we believe ex vivo autologous HSC gene therapy has the potential to overcome,” said Luigi Naldini, director of SR-Tiget and head of the Gene Transfer Technologies and New Gene Therapy Strategies Unit. “Preliminary data obtained to date from the ongoing clinical trial for MPS-I show signs of metabolic correction in patients with the most severe subtype of MPS-I, known as Hurler syndrome. We are pleased to continue our partnership with Orchard as we work together to develop potential ex vivo HSC gene therapies to treat MPS-I and other devastating rare diseases.”