– First in-human phase 1/2 trial to evaluate the safety, efficacy and tolerability of BGT-OTCD in paediatric patients with confirmed diagnosis of OTCD –

– University College London expects to initiate the clinical trial in Q3 2023 –

LONDON, UK I May 15, 2023 I Bloomsbury Genetic Therapies Limited, 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, announced today that that the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) and the Gene Therapy Advisory Committee (GTAC) have approved the clinical trial application (CTA) submitted by Bloomsbury’s collaborators at University College London (UCL) for the initiation of a phase 1/2 clinical trial of BGT-OTCD, the Company’s liver-targeted AAV-LK03 gene therapy, in paediatric patients diagnosed with OTCD.

The phase 1/2 trial of BGT-OTCD, Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn (HORACE) is an open-label, safety, efficacy and dose finding trial and will enrol up to 12 patients aged between 0 and 16 years old diagnosed with OTCD and is expected to begin in the UK in Q3 2023. UCL is the sponsor of the trial with financial support to be provided by Bloomsbury.

“This is a significant milestone for Bloomsbury as BGT-OTCD becomes the company’s first investigational gene therapy to be taken into a clinical trial,” said Adrien Lemoine, Co-Founder & Chief Executive Officer of Bloomsbury. “We are thrilled to collaborate with the teams at UCL and Great Ormond Street Hospital (GOSH) in London on this trial supporting the ongoing development of the BGT-OTCD program and our goal of bringing a one-time, potentially curative treatment to both children and adult patients suffering from this devasting disease.”

“Ornithine transcarbamylase deficiency is a rare genetic disorder that that is characterised by complete or partial lack of the OTC enzyme which causes too much ammonia to accumulate in the body. People with this disease suffer from symptoms including vomiting, impaired voluntary movement and progressive lethargy, which can all progress to brain damage, coma or death if left untreated,” said Dr Anupam Chakrapani, Consultant in Metabolic Medicine, GOSH and the trial’s Principal Investigator. “The capsid used in this investigational AAV gene therapy, AAV-LK03, was selected for its enhanced ability to transduce human hepatocytes, and in particular periportal hepatocytes where the urea cycle preferentially takes place. We hope the trial will show that BGT-OTCD could provide sustained curative effect following a single administration even in children with a growing liver.”

About Bloomsbury Genetic Therapies

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 £5M in Seed funding from UCL Technology Fund and is underpinned by world-leading gene therapy and rare disease expertise from the Company’s academic founders, Professor Paul Gissen, Professor Manju Kurian, Professor Ahad Rahim and Professor Simon Waddington.  Bloomsbury is building a pipeline of highly differentiated first- or best-in-class programs. For more information, please visit www.bloomsburygtx.com


BGT-OTCD is a liver-targeted 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 for the treatment of OTCD by the European Medicines Agency (EMA).

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 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 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.

SOURCE: Bloomsbury Genetic Therapies