AVROBIO Announces Neuronopathic Mucopolysaccharidosis Type II (nMPS-II) or Hunter Syndrome Clinical Trial Application (CTA) Accepted by U.K. Regulatory Agency to Initiate Pediatric Phase 1/2 Gene Therapy Trial

First in-human pediatric Phase 1/2 study to evaluate the safety and tolerability of first-in-class gene therapy targeting infants age ≥3 months and ≤12 months, diagnosed with nMPS-II

University of Manchester (U.K.) expects to initiate clinical trial later this year

U.S. Food and Drug Administration (FDA) previously granted rare pediatric disease and orphan drug designations for AVR-RD-05, AVROBIO’s investigational gene therapy for nMPS-II or Hunter syndrome

AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company working to free people from a lifetime of genetic disease, today announced that the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), Research Ethics Committee (REC) and Health Research Authority (HRA) have approved the clinical trial application (CTA) submitted by AVROBIO’s collaborators at the University of Manchester, U.K. (UoM) for initiation of the Phase 1/2 clinical trial of investigational autologous hematopoietic stem cell (HSC) gene therapy in infants diagnosed with neuronopathic mucopolysaccharidosis type II (nMPS-II) or Hunter syndrome. This rare and seriously debilitating lysosomal disorder primarily affects young males.

UoM’s 24-month, non-randomized, open label study will enroll up to five children aged ≥3 months and ≤12 months diagnosed with nMPS-II to evaluate the safety and tolerability, pharmacodynamic and clinical efficacy of HSC gene therapy. The gene therapy, which AVROBIO refers to as AVR-RD-05, is designed to transduce autologous (a patient’s own) HSCs ex vivo with a lentiviral vector encoding a brain-targeted iduronate-2-sulfatase (IDS) enzyme, which is deficient in these patients.

“We are thrilled to collaborate with the team at UoM to bring to infants and families living with Hunter syndrome a potential one-time therapy for this devastating disease. Hunter syndrome causes complications throughout the body, including severe neurological, cardiac and respiratory dysfunction, skeletal malformations and hearing impairment," said Geoff MacKay, president and CEO of AVROBIO. “This investigational HSC gene therapy which includes CNS-targeted gene expression has been designed to express supra-physiological levels of the IDS enzyme in transduced HSCs, with the intent to correct both the systemic and neurological manifestations of this disease.”

UoM expects to dose the first patient in the trial in 1H 2023. The study will be overseen by Robert Wynn, M.D., professor of Pediatric Hematology at Royal Manchester Children’s Hospital, part of Manchester University NHS Foundation Trust; Brian Bigger, Ph.D., professor of Cell and Gene Therapy at The University of Manchester; and Simon Jones, M.D., professor of Pediatric Inherited Metabolic Diseases at the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital, part of Manchester University NHS Foundation Trust.

“It’s incredibly exciting to have the opportunity to test our investigational brain-targeted HSC gene therapy in boys with Hunter disease,” said Professor Bigger. “There are currently no available treatments that target the brain in this devastating disorder, so the approach of tagging the IDS enzyme with a blood-brain-barrier crossing peptide will enable us to see if this approach can improve outcomes for patients.”

Professor Bigger has previously published preclinical data demonstrating that HSC gene therapy deploying a proprietary blood-brain-barrier crossing ApoEII tag fused to the human IDS gene, drives expression of IDS-ApoEII in blood cells, enabling both blood cells that naturally traffic into the brain in traditional HSC gene therapy and peripheral brain targeted IDS-ApoEII enzyme to both cross the blood-brain barrier, thus potentially addressing peripheral disease and normalizing brain pathology. In these mouse models of Hunter syndrome, brain-targeted HSC gene therapy showed improvement across multiple metrics, including normalization of skeletal features such as the cheekbone dimensions, the width of the humerus and femur bones, correction of neurons in the brain and the preservation of higher brain functions including working memory.

To find out more about the trial, contact mpsiitrial@manchester.ac.uk, Simon.Jones@mft.nhs.uk or Robert.wynn@mft.nhs.uk.

Previously, the U.S. Food and Drug Administration (FDA) granted rare pediatric disease and orphan drug designations for AVR-RD-05.

About Hunter syndrome

Hunter syndrome is caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (IDS), which is essential for breaking down large sugar molecules. It affects an estimated one in 100,000 to one in 170,000 males worldwide. Children with severe cases of Hunter syndrome typically show early symptoms of the disease in infancy and childhood and begin to regress developmentally, losing basic motor skills and cognitive function over a few years. The neuronopathic form of MPSII is characterized by cognitive, language and motor skills declining early in childhood.

The current standard of care is weekly enzyme replacement therapy (ERT), which can delay some peripheral disease complications but does not halt overall progression of the disease and has not been demonstrated to address the central nervous system (CNS) issues. Even with ERT, people with Hunter syndrome face life-limiting symptoms and a significantly reduced lifespan.


Our vision is to bring personalized gene therapy to the world. We target the root cause of genetic disease by introducing a functional copy of the affected gene into patients’ own hematopoietic stem cells (HSCs), with the goal to durably express the therapeutic protein throughout the body, including the central nervous system. Our first-in-class pipeline includes clinical programs for cystinosis and Gaucher disease type 1, as well as preclinical programs for Gaucher disease type 3, Hunter syndrome and Pompe disease. Our proprietary plato® gene therapy platform is designed to be scaled to support late-stage clinical development and commercialization globally. We are headquartered in Cambridge, Mass. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our preclinical and clinical product candidates, including AVR-RD-05 for the treatment of nMPSII or Hunter syndrome, the potential benefits and incentives provided by the FDA’s rare pediatric disease and orphan drug designations for AVR-RD-05, statements regarding the expectations or activities of our collaborators including timing of clinical trial initiation and dosing of patients, the design, commencement, enrollment and timing of planned clinical trials, preclinical or clinical trial results, product approvals and regulatory pathways, our plans and expectations with respect to interactions with regulatory agencies, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety profile of our preclinical and investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIO’s current expectations, estimates and projections about our industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIO’s product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato® platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIO’s product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO’s actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled “Risk Factors” in AVROBIO’s most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO’s subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.


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