Orchard Therapeutics Unveils Details on New HSC Gene Therapy Research Programs as Part of R&D Investor Event Tomorrow at 9

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• OTL-204 for GRN-FTD: Orchard’s preclinical program in GRN-FTD seeks to introduce a working copy of the GRN gene into HSCs, which can differentiate into microglia and secrete progranulin in the central nervous system, potentially correcting the underlying cause of the disease.
  • Preclinical work completed to date demonstrates that gene-modified HSCs can lead to GRN expression and secretion in the culture medium and uptake by GRN-negative cells.
  • Epidemiological studies suggest the FTD prevalent population in the U.S. and Europe is more than 50,000 patients with approximately 5% caused by mutations in the GRN gene, resulting in up to 2,500 GRN-FTD prevalent patients in the U.S. and Europe, with approximately 800 new patients diagnosed each year.¹
• ALS research program: Orchard’s new gene therapy research program in ALS will aim to restore healthy, non-activated microglia with genetically modified HSCs to favorably modulate neuroinflammation, improve symptoms and prolong survival.
  • Preclinical work previously undertaken by Prof. Biffi at BCH is based on exploiting shRNA mediated suppression of NADPH oxidase 2 (NOX2) activity to modulate neuroinflammation and neurodegeneration.
  • Rather than focusing on restoring gene function in patients with specific genetic susceptibility, this approach targets neuroinflammatory responses to support neuronal survival and could be applicable to a broader population of ALS patients.

Prof. Biffi commented, “The ability of HSC gene therapy to restore healthy microglia function supports the use of this technology for the development of treatments for a variety of diseases with central nervous system involvement. In GRN-FTD, initial in vitro data shows progranulin expression and secretion in culture and uptake indicative of cross-correction. My previous work at BCH researching ALS supports the novel approach of treating this severe neurodegenerative condition by targeting the NOX2 pathway.”

OTL-104 for NOD2-CD

Orchard’s preclinical program in CD targets mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene, which plays a role in immune cell response to bacterial peptides in the gastrointestinal (GI) tract. The company’s proposed approach leverages this link, using gene modified HSC-derived cells (monocytes) to replace GI resident macrophages, thus potentially correcting the inflammation and colitis associated with NOD2-CD.