Orchard Therapeutics Presents New Interim Data from OTL-203 Proof-of-concept Study for MPS-I

First Primary Outcome Measure Met with All Eight Patients Achieving Hematologic Engraftment

Improved Motor Skills, Stable Cognitive Scores and Normal Growth Seen in First Two Patients

One-year Follow-up Results and Initiation of Registrational Trial Expected in 2021

BOSTON, MA, USA and LONDON, UK I May 15, 2020 I Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced new interim data from an ongoing proof-of-concept clinical trial evaluating the safety and efficacy of OTL-203, an ex vivo autologous hematopoietic stem cell (HSC) gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I) at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. The results are being shared virtually in two presentations at the American Society of Gene & Cell Therapy (ASGCT) 23rd Annual Meeting, including the main dataset in an invited oral presentation today.

“We have made strong progress with the MPS-I clinical trial and are pleased to see these interim results, with all patients achieving hematological recovery in less than 45 days – a primary outcome measure – as well as supraphysiological levels of IDUA enzyme in the blood. In addition, the trial results to date have shown promising preliminary clinical effects on motor skills, IQ and growth in the first two patients with 12 and 18 months of follow-up,” said Maria Ester Bernardo, M.D., Ph.D., co-principal investigator at SR-Tiget. “We also observed reconstitution of enzyme activity in the cerebral spinal fluid (CSF) in the first two treated patients with 12 months of follow-up, complemented by a decrease in glycosaminoglycan levels in the CSF. We look forward to continuing to assess the outcomes of this investigational gene therapy for patients with this often-fatal condition.”

Interim Study Results
As of April 2020, all eight patients with the severe Hurler subtype of MPS-I have been treated with OTL-203. Patients have been followed for a minimum of three months, with the longest follow-up extending out to 18 months.

The primary outcome measures of the trial include overall survival, safety, hematological engraftment by day 45 following treatment and biological efficacy as measured by alpha-L-iduronidase (IDUA) lysosomal enzyme activity in the blood at one-year post-treatment. Treatment with OTL-203 and the selected conditioning regime were well-tolerated across all eight patients and demonstrated:

  • Rapid hematologic reconstitution, with neutrophil and platelet engraftment within 21 days following treatment – achieving a primary outcome measure of hematological engraftment within 45 days of infusion.
  • Biological efficacy demonstrated by supranormal IDUA enzyme expression in peripheral blood, with the first two patients treated achieving stable supranormal levels up to 12 months post gene therapy.

Key secondary and exploratory outcome measures include normalization of urinary glycosaminoglycans (GAGs), growth velocity and effects on motor and cognitive function at one- and two-years post-treatment. Treatment with OTL-203 demonstrated:

  • In all eight patients, interim data showed high levels of metabolic correction with reduction in GAG levels in urine and cerebral spinal fluid (CSF).
  • For the first two treated patients, with 18 and 12 months of follow-up, clinical data showed:
    • Rapid metabolic correction of GAG levels in the urine and CSF, reflecting restoration of IDUA enzyme expression in the periphery and in the central nervous system.
    • Improved motor function and acquisition of cognitive and language skills.
    • Continued growth progressing above the 50th percentile of normal.
    • Improved range of motion (an indicator of joint stiffness).
    • Improvement of brain and spine MRI scores.

“We are extremely encouraged by data emerging from the MPS-I program, where we are seeing correction of biochemical parameters as well as early clinical evidence of the potentially transformative effects of OTL-203,” said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. “These data further support the hypothesis that our hematopoietic stem cell gene therapy approach could have potential future applications to treat a range of genetic neurometabolic disorders. Given the historical difficulty in treating these types of conditions, we are committed to advancing our programs in this area as quickly as possible for patients in need and are excited by the opportunity to initiate the registrational trial for this program in 2021.”

The proof-of-concept study is ongoing and additional interim results are planned to be reported in the second half of 2020. The company also expects to release full proof-of-concept results and initiate the registrational study for OTL-203 in 2021.

About OTL-203 and MPS-I
Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (also known as GAGs). The accumulation of GAGs across multiple organ systems results in symptoms including neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I; approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome, and rarely live past the age of 10 when untreated.

Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is an ex vivo autologous hematopoietic stem cell gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

About Orchard
Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our 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. 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, Italy. 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.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit www.orchard-tx.com, and follow us on Twitter and LinkedIn.

SOURCE: Orchard Therapeutics

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