AAV-LK03.hOTC

London, UK, 24 October 2024 – Bloomsbury Genetic Therapies Limited (“Bloomsbury”), a clinical-stage biotechnology company developing potentially curative treatments for patients suffering from rare neurological and metabolic diseases based on clinically proven gene therapy technologies, today announced that clinical data for BGT-OTCD, the Company’s AAV-LK03 gene therapy candidate for the treatment of ornithine transcarbamylase deficiency (OTCD), has been presented for the first time in a poster presentation at the 31st Annual Meeting of European Society of Gene & Cell Therapy (ASGCT), which is being held in Rome, Italy from 22-25 October 2024. BGT-OTCD is an investigational AAV-LK03 gene therapy designed to provide a potentially curative solution to OTCD patients following a one-time intravenous (IV) injection. Current standard of care in OTCD involves protein-restricted diets and ammonia-scavenger medications; however, these approaches can have a significant impact on patients’ quality of life and patients still face a lifelong risk of decompensation and neurological damage resulting in intellectual disability, developmental delays, and movement disorder. Over 10,000 patients suffering from OTCD have been identified worldwide. In the poster presentation, titled “First patient treated in the phase 1–2 trial of AAVLK03hOTC gene therapy for ornithine transcarbamylase deficiency in children”, clinical data from the HORACE trial (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn; NCT 05092685), BGT-OTCD’s ongoing phase 1/2 clinical trial, was shared publicly for the first time. The poster showcases data obtained following the IV administration of a single dose of 6×10^11vg/kg of BGT-OTCD in a 10-year-old male with late-onset OTCD. Previous clinical history included recurrent episodes of hyperammonaemia treated with dietary protein restriction and daily intake of ammonia scavengers (Ravicti®). Following treatment with BGT-OTCD, the patient has been able to progressively reduce his use of Ravicti and achieve full withdrawal at 9 months, while maintaining metabolic control. The patient tolerated the gene therapy administration remarkably well with no treatment-related SAEs. Raised transaminases at 7 months after gene therapy administration were successfully treated with a short course of oral prednisolone and tacrolimus. “We are very encouraged by the data collected on the first patient treated in the HORACE trial, especially remarkable as the results have been achieved with such a low vector dose,” said Professor Paul Gissen, Professor of Metabolic Medicine and Head of Gene and Stem Cell Therapy at UCL Great Ormond Street Institute of Child Health and co-primary investigator for the HORACE trial. “This is testament to the choice of the AAV-LK03 capsid, which is uniquely suited to the treatment of OTCD thanks to its high tropism for periportal hepatocytes, where the urea cycle is preferentially happening.” “The first findings from the HORACE trial confirm BGT-OTCD’s potential to be a best-in-class treatment providing curative benefit to patients living with OTCD following a single treatment administration,” said Adrien Lemoine, Co-Founder & Chief Executive Officer of Bloomsbury. “We look forward to our collaborators at UCL progressing the HORACE trial to confirm the safety and efficacy of BGT-OTCD.” Details of the poster presentation at ESGCT Annual meeting: Title: First patient treated in the phase 1–2 trial of AAVLK03hOTC gene therapy for ornithine transcarbamylase deficiency in children Session: Poster Session III, Thursday 24 October, 14:00 to 15:30 Poster Number: P0873 Presenter: Paul Gissen, University College London ENDS Enquiries JW Communications Julia Wilson Tel: +44 (0)7818 430877 About Bloomsbury Bloomsbury is a clinical-stage biotechnology company, developing potentially curative treatments for patients suffering from rare neurological and metabolic diseases based on clinically proven gene therapy technologies. The Company was spun out of University College London and launched in October 2022 with funding from UCL Technology Fund. Bloomsbury is building a pipeline of highly differentiated first- or best-in-class programs. For more information, please visit www.bloomsburygtx.com About BGT-OTCD BGT-OTCD is an investigational AAV-LK03 gene therapy designed to provide a potentially curative solution to OTCD patients following a one-time intravenous injection. AAV-LK03 was selected for its high tropism for liver cells and its success in other liver disorders such as haemophilia A. BGT-OTCD has been granted Orphan Drug Designation (ODD) for the treatment of OTCD by the European Commission (EC) and the US Food and Drug Administration (FDA) as well as Rare Pediatric Disease Designation (RPDD) from the FDA. BGT-OTCD is currently being evaluated in HORACE (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn; NCT 05092685), a Phase 1/2 clinical trial initiated in November 2023. About Ornithine Transcarbamylase Deficiency Ornithine transcarbamylase deficiency (OTCD) is a rare, X-linked genetic disorder that is characterised by complete or partial lack of the OTC enzyme. OTC enzyme is a key component of the urea cycle and patients with OTCD accumulate nitrogen waste in the form of excess ammonia (hyperammonaemia) in the blood, causing hyperammonaemic decompensations with symptoms including vomiting, impaired voluntary movement and progressive lethargy. If left untreated, these may progress to coma and life-threatening complications. While later onset disease can occur in adults with a milder form of the disorder, symptoms present within a few days of birth of males with severe OTCD. Patients are rapidly diagnosed (urine and blood biochemical analyses, gene sequencing) when they present at hospital/are admitted to intensive care with acute hepatic decompensation and hyperammonaemia. Current standard of care involves protein-restricted diets and ammonia-scavenger medications; however, these approaches can have a significant impact on patients’ quality of life and patients still face a lifelong risk of decompensation and neurological damage resulting in intellectual disability, developmental delays, and movement disorder. Liver transplant is the only curative option, but is often unavailable and comes with significant morbidity/mortality risk and lifelong immunosuppression and arginine supplementation. Over 10,000 patients suffering from OTCD have been identified worldwide.