Northumbria Healthcare NHS Foundation Trust

--Advisory Board to Provide Guidance for Company's Eosinophilic Esophagitis Clinical Program-- VICTORIA, BC, May 2, 2024 /PRNewswire/ - Eupraxia Pharmaceuticals Inc. ("Eupraxia" or the "Company") (TSX: EPRX) (NASDAQ: EPRX), a clinical-stage biotechnology company leveraging its proprietary DiffuSphere™ technology to optimize drug delivery for applications with significant unmet need, today announced the formation of a Clinical Advisory Board for its gastrointestinal ("GI") program. The Clinical Advisory Board is comprised of Dr. Evan Dellon (Chairman), Dr. Stephen Attwood, Dr. Albert Bredenoord, Dr. Donna Griebel, Dr. Ikuo Hirano and Dr. Roos Pouw. The Clinical Advisory Board will work closely with Eupraxia as it continues its development of EP-104GI for eosinophilic esophagitis ("EoE"), which is currently in a Phase 1b/2a clinical trial. "The formation of our Gastrointestinal Clinical Advisory Board comes at an exciting time for our Company, as we continue to generate clinical evidence in support of EP-104GI for the treatment of eosinophilic esophagitis," said Mark Kowalski, MD, PhD, Chief Medical Officer of Eupraxia. "As we advance the EoE program, we will now have access to an extraordinary group of renowned GI experts who will provide key insights and recommendations to help guide the program toward advanced stages of clinical development." "We are delighted to bring together such an impressive group of experts in the gastrointestinal space," said Dr. James Helliwell, CEO of Eupraxia. "EoE remains a significant but underserved rare disease with a patient population that has few therapeutic treatment options. Based on clinical data generated to date, we believe EP-104GI has shown significant potential to address this unmet medical need. The formation of our GI Clinical Advisory Board therefore represents the next logical step in the evolution of this program and will also play a critical role as we look to other indications, including benign strictures, which could present even larger opportunities. We are excited to have these highly accomplished individuals as advisors, and we look forward to further expanding our GI Clinical Advisory Board in the months ahead." "I am excited to be part of Eupraxia's GI Clinical Advisory Board at a time when the Company continues to make progress towards addressing the EoE patient population," said Evan Dellon, MD, MPH. "EoE is a challenging medical condition that is associated with several allergic co-morbidities, including allergic rhinitis, asthma, and IgE-mediated food allergies. Treatments with swallowed corticosteroids, particularly those traditionally adapted from asthma preparations, have limited utility due to suboptimal delivery to the affected area. Eupraxia's technology has shown the potential to more selectively concentrate drug delivery to the esophagus, which could significantly improve treatment outcomes for this patient population." About the Clinical Advisory Board Dr. Evan Dellon MD, MPH – Clinical Advisory Board Chairman Evan Dellon, MD, MPH, is a Professor in the Department of Medicine, Division of Gastroenterology and Hepatology, and adjunct Professor of Epidemiology at UNC School of Medicine. He has formal research training in epidemiology, clinical and translational research, and clinical trial design. He leads and collaborates with multidisciplinary research teams in the area of esophageal diseases in general and EoE in particular. His current research, which has been supported by the National Institute of Health ("NIH") funding, focuses on optimizing the diagnosis, characterizing the epidemiology, studying the pathogenesis, and refining the treatment and monitoring of EoE, with the overall goal of improving patient care and outcomes in EoE. Dr. Stephen E. Attwood, MD Stephen E. Attwood, MD, FRCSI, is honorary professor in health services research at Durham University, UK, and an independent consulting advisor on research and clinical practice for oesophageal diseases. He qualified from Trinity College Dublin and took his Surgical Fellowship at the Royal College of Surgeons in Ireland. Most recently, he was a consultant surgeon at Northumbria Healthcare UK. Since identifying EoE in 1989 and publishing the first description of the disease in 1992, Professor Attwood has spent his career caring for patients with EoE. He has been actively engaged in clinical trials of upper gastrointestinal diseases, including budesonide formulations for EoE; the ASPECT trial of cancer prevention in Barrett's esophagus; BEST3, a study of Cytosponge screening for Barrett's esophagus in general practices; the LOTUS trial (surgery vs proton pump inhibitor for Gastroesophageal Reflux Disease). He has authored more than 200 publications, including the recent BSG Guidelines on EoE. Dr. Albert J. (Arjan) Bredenoord, MD, PhD Albert J. (Arjan) Bredenoord, MD, PhD, is Consultant Gastroenterologist at the Amsterdam University Medical Center and professor of Neurogastroenterology & Motility at the University of Amsterdam. Dr. Bredenoord's main focus is on achalasia, reflux disease and EoE. He is one of the pioneers of high-resolution manometry and impedance monitoring of the esophagus. The esophageal clinic in the AMC Amsterdam hosts the largest population of benign esophageal diseases in the Netherlands. Dr. Bredenoord is an author of over 250 papers, books and book chapters and organizes regular courses in Europe, North America and Asia. Dr Bredenoord is President of the European Society of Eosinophilic Esophagitis, a member of the UEG Scientific Committee, and co-founder of the International HRM working group. Dr. Donna Griebel, MD Donna Griebel, MD, is a regulatory consultant with Griebel and Rosebraugh Consulting, LLC. She retired from the FDA in 2018 after having served as Division Director of the Division of Gastroenterology and Inborn Errors Products (with the Office of New Drugs in the Center for New Drugs and Research ("CDER")) for approximately a decade. Her prior CDER/FDA leadership roles included Deputy Director of Division of Reproductive and Urologic Drug Products and Clinical Team Leader in Division of Oncology Drug Products. Dr. Ikuo Hirano, MD Ikuo Hirano, MD, is a Professor of Medicine at Northwestern University Feinberg School of Medicine and the Director of the Kenneth C. Griffin Esophageal Center in the Division of Gastroenterology and Hepatology. He attended college at Yale University, medical school at the University of Pennsylvania and completed his medical residency and GI fellowship at Beth Israel Hospital in Boston. He is a site principal investigator for the NIH supported Consortium of Eosinophilic Gastrointestinal disease Researchers ("CEGIR") and has been recognized as a Castle Connolly Top Doctor since 2002 and as a leading esophageal investigator by Expertscape. Dr. Hirano has written over 250 scientific papers and book chapters on esophageal and swallowing disorders. He has focused interests on EoE and eosinophilic gastrointestinal disease and authored several society guidelines on the management of these increasingly recognized disorders. Dr. Roos Pouw, MD, PhD Roos Pouw, MD, PhD, was born in Rotterdam, the Netherlands. She obtained her degree in Medicine at the University of Utrecht and completed a research fellowship at Harvard Medical School in Boston, after which she started her career in gastroenterology with a PhD fellowship at the Academic Medical Centers, Amsterdam, the Netherlands. After finishing her training in 2017, Dr. Pouw was appointed staff member at the Dept. of Gastroenterology and Hepatology at AMC, currently known as the Amsterdam University Medical Centers. Dr. Pouw has received the United European Gastroenterology ("UEG") Rising Star award in 2020 for her work research on endoscopic management of early Barrett's neoplasia. Dr. Pouw is co-chair of the Young International Society for Diseases of the Esophagus ("ISDE"), secretary of the Dutch Upper Cancer Group, national representative for UEG, task force leader for a number of guideline initiatives and curricula on esophageal neoplasia for the European Society of Gastrointestinal Endoscopy and ISDE, and editorial (advisory) board member for the UEG Journal and Best Practice & Research: Clinical Gastroenterology. About Eosinophilic Esophagitis (EoE) EoE is an inflammatory-mediated disease in which white blood cells migrate into and become trapped in the esophagus, creating pain and difficulty with swallowing food. It affects more than 180,000 people in the U.S. and has been identified by the American Gastroenterological Association as rapidly increasing in both incidence and prevalence. Impacts from both symptoms and interventions frequently lead to mental health issues, compounding the disease burden of EoE for both the health care system and the individual. About Eupraxia Pharmaceuticals Inc. Eupraxia is a clinical-stage biotechnology company focused on the development of locally delivered, extended-release products that have the potential to address therapeutic areas with high unmet medical need. The Company strives to provide improved patient benefit and has developed technology designed to deliver targeted, long-lasting activity with fewer side effects. DiffuSphere™, a proprietary, polymer-based micro-sphere technology, is designed to facilitate targeted drug delivery, with extended duration of effect, and offers multiple, highly tuneable pharmacokinetic (PK) profiles. This investigational technology can be engineered for use with multiple active pharmaceutical ingredients and delivery methods. Eupraxia recently completed a Phase 2b clinical trial (SPRINGBOARD) of EP-104IAR for the treatment of pain due to OA of the knee. The trial met its primary endpoint and three of the four secondary endpoints. Eupraxia has expanded the EP-104 platform into gastrointestinal disease with the Phase 1b/2a RESOLVE trial for treating EoE. Eupraxia is also developing a pipeline of later- and earlier-stage long-acting formulations. Potential pipeline indications include candidates for other inflammatory joint indications and oncology, each designed to improve on the activity and tolerability of currently approved drugs. For further details about Eupraxia, please visit the Company's website at: . Notice Regarding Forward-looking Statements and Information This news release includes forward-looking statements and forward-looking information within the meaning of applicable securities laws. Often, but not always, forward-looking information can be identified by the use of words such as "plans", "is expected", "expects", "suggests", "scheduled", "intends", "contemplates", "anticipates", "believes", "proposes", "potential" or variations (including negative and grammatical variations) of such words and phrases, or state that certain actions, events or results "may", "could", "would", "might" or "will" be taken, occur or be achieved. Forward looking statements in this news release include statements regarding expected benefits from the formation of the Company's GI Clinical Advisory Board; the Company's product candidates, including expected benefits to patients; the results gathered from studies and trials of Eupraxia's product candidates; the potential for the Company's technology to impact the drug delivery process; and potential pipeline indications. Such statements and information are based on the current expectations of Eupraxia's management, and are based on assumptions, including but not limited to: future research and development plans for the Company proceeding substantially as currently envisioned; industry growth trends, including with respect to projected and actual industry sales; the Company's ability to obtain positive results from the Company's research and development activities, including clinical trials; and the Company's ability to protect patents and proprietary rights. Although Eupraxia's management believes that the assumptions underlying these statements and information are reasonable, they may prove to be incorrect. The forward-looking events and circumstances discussed in this news release may not occur by certain dates or at all and could differ materially as a result of known and unknown risk factors and uncertainties affecting Eupraxia, including, but not limited to: risks and uncertainties related to the Company's limited operating history; the Company's novel technology with uncertain market acceptance; if the Company breaches any of the agreements under which it licenses rights to its product candidates or technology from third parties, the Company could lose license rights that are important to its business; the Company's current license agreement may not provide an adequate remedy for its breach by the licensor; the Company's technology may not be successful for its intended use; the Company's future technology will require regulatory approval, which is costly and the Company may not be able to obtain it; the Company may fail to obtain regulatory approvals or only obtain approvals for limited uses or indications; the Company's clinical trials may fail to demonstrate adequately the safety and efficacy of our product candidates at any stage of clinical development; the Company may be required to suspend or discontinue clinical trials due to side effects or other safety risks; the Company completely relies on third parties to provide supplies and inputs required for its products and services; the Company relies on external contract research organizations to provide clinical and non-clinical research services; the Company may not be able to successfully execute its business strategy; the Company will require additional financing, which may not be available; any therapeutics the Company develops will be subject to extensive, lengthy and uncertain regulatory requirements, which could adversely affect the Company's ability to obtain regulatory approval in a timely manner, or at all; the impact of health pandemics or epidemics on the Company's operations; the Company's restatement of its consolidated financial statements, which may lead to additional risks and uncertainties, including loss of investor confidence and negative impacts on the Company's common share price; and other risks and uncertainties described in more detail in Eupraxia's public filings on SEDAR+ (sedarplus.ca) and EDGAR (sec.gov). Although Eupraxia has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking statements and information, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended. No forward-looking statement or information can be guaranteed. Except as required by applicable securities laws, forward-looking statements and information speak only as of the date on which they are made and Eupraxia undertakes no obligation to publicly update or revise any forward-looking statement or information, whether as a result of new information, future events or otherwise. SOURCE Eupraxia Pharmaceuticals Inc.

All patients achieved sustained engraftment and supraphysiological SGSH enzyme levels with median 1.5 years follow-up Four out of five patients demonstrated gain of cognitive skills in line with development in healthy children with one patient showing a marked improvement compared to disease natural history Treatment with OTL-201 was generally well-tolerated BOSTON, MA, USA and LONDON, UK I December 12, 2022 I Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced early clinical findings, including the first neurocognitive results, from its ongoing proof-of-concept (PoC) study of OTL-201, an investigational hematopoietic stem cell (HSC) gene therapy being developed for the treatment of mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A. The data are being featured as part of an oral presentation at the ongoing 64th American Society of Hematology (ASH) Annual Meeting & Exposition in New Orleans. “These are encouraging results for children living with MPS-IIIA and their families, who currently have no effective treatment options,” said Professor Robert Wynn, chief investigator at The Royal Manchester Children’s Hospital, part of Manchester University NHS Foundation Trust (MFT). “In addition to sustained engraftment of gene-corrected cells and supraphysiological SGSH enzyme levels in the periphery, the early neurocognitive findings show most patients are gaining skills in line with the development of healthy children. In one patient, we also have seen a marked improvement from disease natural history, and we hope to see similar results in the other patients with longer follow-up.” The oral presentation at ASH 2022 will showcase the first neurocognitive data for all five patients enrolled in the trial and extend upon previously presented biochemical results. Trial patients were 6 to 24 months of age at the time of administration of OTL-201, and the preliminary results are based on a median follow-up of 1.5 years (range: 9-24 months). Specifically, the biochemical results show the following in all patients: Early neurocognitive outcomes also indicate that: Treatment with OTL-201 was generally well-tolerated in the initial study population. Of the six serious adverse events (SAEs) reported to date, four were thought to be due to conditioning or leukapheresis and one was related to background disease. One patient had delayed platelet engraftment until day 52 post-treatment likely due to Cytomegalovirus infection around the time of infusion. The lentiviral vector integration profile was consistent with other lentiviral-based HSC gene therapy studies and there has been no indication of insertional oncogenesis and no evidence of clonal dominance due to integration into oncogenes in samples analyzed to date. “These promising findings continue to demonstrate the ability of our HSC gene therapy platform to enable the migration of gene-corrected cells into the central nervous system and the localized delivery of therapeutic enzymes and proteins to the brain to potentially correct neurodegeneration in multiple severe conditions, building on our programs in metachromatic leukodystrophy and MPS-IH,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “While these early results are encouraging, longer follow up is needed as the majority of the patients in this trial have not reached the age where the most severe stages of disease progression typically manifest. We are working with our collaborators at The University of Manchester and Royal Manchester Children’s Hospital to continue following patients in this ongoing study and more fully characterize the clinical profile of OTL-201.” Five patients aged 6 to 24 months, with a rapidly progressive MPS-IIIA phenotype confirmed by an independent metabolic disease expert, were administered investigational OTL-201 as part of this ongoing PoC trial, sponsored by The University of Manchester (UoM), conducted at Royal Manchester Children’s Hospital, and funded by Orchard Therapeutics. Primary study objectives include safety, tolerability and peripheral expression of SGSH in total leukocytes at 12 months. Secondary study objectives include overall survival and neurocognition as measured by the Bayley Scales of Infant and Toddler Development (BSID-III) or the Kaufman Assessment Battery for Children (KABC-II). The OTL-201 program and this investigator-led clinical trial follow over a decade of development and pre-clinical work by Brian Bigger, Ph.D., professor of cell and gene therapy at UoM. Patients enrolled in the ongoing PoC trial will be followed for a minimum of three years during which time the study investigators will continue to report additional biochemical and clinical outcomes. The OTL-201 program in MPS-IIIA presents multiple development and commercial synergies with Orchard’s other neurometabolic programs, and the condition represents a significant medical need given there are no approved therapies and treatment with allogeneic HSC transplant has not been shown to be effective for MPS-IIIA patients. Conference Call and Webcast A live webcast will be available under "News & Events" in the Investors & Media section of the company's website at www.orchard-tx.com . A replay of the webcast will be archived on the Orchard website following the presentation. About MPS-IIIA Mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A is a rare and life-threatening metabolic disease. People with MPS-IIIA are born with a mutation in the N-sulphoglucosamine sulphohydrolase (SGSH) gene which, when healthy, helps the body break down sugar molecules called mucopolysaccharides. The buildup of mucopolysaccharides in the brain and other tissues leads to intellectual disability and loss of motor function. MPS-IIIA occurs in approximately one in every 100,000 live births. Life expectancy of children born with MPS-IIIA is estimated to be between 10-25 years. About OTL-201 OTL-201 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IIIA. It uses a lentiviral vector to insert a functional copy of the human SGSH gene into a patient’s hematopoietic stem cells. OTL-201 has received rare pediatric disease designation from the U.S. Food and Drug Administration (FDA) and is currently being evaluated in an ongoing proof-of-concept clinical trial. About Orchard Therapeutics At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment. In 2018, the company 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. Today, Orchard is advancing a pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society 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 . About Manchester University NHS Foundation Trust (MFT) Manchester University NHS Foundation Trust (MFT) is the largest NHS trust in England and a leading provider of specialist healthcare services. Its 10 hospitals are home to hundreds of world class clinicians and academic staff, committed to finding patients the best care and treatments. Its hospitals are Manchester Royal Infirmary, Saint Mary's Hospital, Royal Manchester Children's Hospital, Manchester Royal Eye Hospital, North Manchester General Hospital, University Dental Hospital of Manchester, Trafford General Hospital, Altrincham Hospital, Wythenshawe Hospital and Withington Hospital. More information is available at: www.mft.nhs.uk . About The University of Manchester The University of Manchester is a member of the prestigious Russell Group and one of the UK’s largest single-site universities.  We have over 40,000 students, 12,000 staff and, with almost 480,000 former students from more than 190 countries, are home to the largest alumni community of any campus-based university in the UK.  We are ranked in the top ten of the Times Higher Education (THE) Impact Rankings globally; are the top UK University for graduate employability according to The Graduate Market in 2022 and no fewer than 25 Nobel laureates have either worked or studied here.  Visit www.manchester.ac.uk for further information or https://www.manchester.ac.uk/discover/vision/ for our latest strategic vision. i Cognitive function measured via standard scores, age-equivalent scores, development quotient (DQ) and gross scale equivalent [BSID-III] or [KABC-II] SOURCE: Orchard Therapeutics

All patients achieved sustained engraftment and supraphysiological SGSH enzyme levels with median 1.5 years follow-up Four out of five patients demonstrated gain of cognitive skills in line with development in healthy children with one patient showing a marked improvement compared to disease natural history Treatment with OTL-201 was generally well-tolerated Company to host conference call and webcast at 5:00 p.m. EST BOSTON and LONDON, Dec. 12, 2022 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced early clinical findings, including the first neurocognitive results, from its ongoing proof-of-concept (PoC) study of OTL-201, an investigational hematopoietic stem cell (HSC) gene therapy being developed for the treatment of mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A. The data are being featured as part of an oral presentation at the ongoing 64th American Society of Hematology (ASH) Annual Meeting & Exposition in New Orleans. “These are encouraging results for children living with MPS-IIIA and their families, who currently have no effective treatment options,” said Professor Robert Wynn, chief investigator at The Royal Manchester Children’s Hospital, part of Manchester University NHS Foundation Trust (MFT). “In addition to sustained engraftment of gene-corrected cells and supraphysiological SGSH enzyme levels in the periphery, the early neurocognitive findings show most patients are gaining skills in line with the development of healthy children. In one patient, we also have seen a marked improvement from disease natural history, and we hope to see similar results in the other patients with longer follow-up.” The oral presentation at ASH 2022 will showcase the first neurocognitive data for all five patients enrolled in the trial and extend upon previously presented biochemical results. Trial patients were 6 to 24 months of age at the time of administration of OTL-201, and the preliminary results are based on a median follow-up of 1.5 years (range: 9-24 months). Specifically, the biochemical results show the following in all patients: Engraftment is sustained to date, with supraphysiological levels of N-sulphoglucosamine sulphohydrolase (SGSH) enzyme measurable in leukocytes 38- to 91-fold above median normal range at one-month post-treatment.Supraphysiological SGSH levels were also rapidly detected in CD15+ cells, CD3+ cells, and plasma and have been maintained through the last follow-up visit for each patient. SGSH levels in cerebrospinal fluid (CSF) were within or above normal range by 6-months post-treatment and at the most recent follow-up.Abnormal heparan sulfate levels at baseline were rapidly reduced post-treatment in urine (>90 percent), plasma (>82 percent), as well as CSF, and has continued to be maintained at these levels in all evaluated patients. Early neurocognitive outcomes also indicate that: Since receiving the investigational gene therapy, four out of five patients showed gain of cognitive skills in line with development in healthy children compared to natural history of MPS-IIIA.i A marked improvement compared with natural history of the disease was observed in one patient at 18 months of follow up.Three additional patients are currently within the normal development quotient (DQ) range at 9 to 18 months post-treatment but require longer follow-up to assess outcomes.Gain of cognitive skills is assessed in this study through evidence of speech acquisition, continence and complex play requiring concentration. Treatment with OTL-201 was generally well-tolerated in the initial study population. Of the six serious adverse events (SAEs) reported to date, four were thought to be due to conditioning or leukapheresis and one was related to background disease. One patient had delayed platelet engraftment until day 52 post-treatment likely due to Cytomegalovirus infection around the time of infusion. The lentiviral vector integration profile was consistent with other lentiviral-based HSC gene therapy studies and there has been no indication of insertional oncogenesis and no evidence of clonal dominance due to integration into oncogenes in samples analyzed to date. “These promising findings continue to demonstrate the ability of our HSC gene therapy platform to enable the migration of gene-corrected cells into the central nervous system and the localized delivery of therapeutic enzymes and proteins to the brain to potentially correct neurodegeneration in multiple severe conditions, building on our programs in metachromatic leukodystrophy and MPS-IH,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “While these early results are encouraging, longer follow up is needed as the majority of the patients in this trial have not reached the age where the most severe stages of disease progression typically manifest. We are working with our collaborators at The University of Manchester and Royal Manchester Children’s Hospital to continue following patients in this ongoing study and more fully characterize the clinical profile of OTL-201.” Five patients aged 6 to 24 months, with a rapidly progressive MPS-IIIA phenotype confirmed by an independent metabolic disease expert, were administered investigational OTL-201 as part of this ongoing PoC trial, sponsored by The University of Manchester (UoM), conducted at Royal Manchester Children’s Hospital, and funded by Orchard Therapeutics. Primary study objectives include safety, tolerability and peripheral expression of SGSH in total leukocytes at 12 months. Secondary study objectives include overall survival and neurocognition as measured by the Bayley Scales of Infant and Toddler Development (BSID-III) or the Kaufman Assessment Battery for Children (KABC-II). The OTL-201 program and this investigator-led clinical trial follow over a decade of development and pre-clinical work by Brian Bigger, Ph.D., professor of cell and gene therapy at UoM. Patients enrolled in the ongoing PoC trial will be followed for a minimum of three years during which time the study investigators will continue to report additional biochemical and clinical outcomes. The OTL-201 program in MPS-IIIA presents multiple development and commercial synergies with Orchard’s other neurometabolic programs, and the condition represents a significant medical need given there are no approved therapies and treatment with allogeneic HSC transplant has not been shown to be effective for MPS-IIIA patients. Conference Call and WebcastA live webcast will be available under "News & Events" in the Investors & Media section of the company's website at www.orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation. About MPS-IIIAMucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A is a rare and life-threatening metabolic disease. People with MPS-IIIA are born with a mutation in the N-sulphoglucosamine sulphohydrolase (SGSH) gene which, when healthy, helps the body break down sugar molecules called mucopolysaccharides. The buildup of mucopolysaccharides in the brain and other tissues leads to intellectual disability and loss of motor function. MPS-IIIA occurs in approximately one in every 100,000 live births. Life expectancy of children born with MPS-IIIA is estimated to be between 10-25 years. About OTL-201OTL-201 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IIIA. It uses a lentiviral vector to insert a functional copy of the human SGSH gene into a patient’s hematopoietic stem cells. OTL-201 has received rare pediatric disease designation from the U.S. Food and Drug Administration (FDA) and is currently being evaluated in an ongoing proof-of-concept clinical trial. About Orchard TherapeuticsAt Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment. In 2018, the company 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. Today, Orchard is advancing a pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society 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. About Manchester University NHS Foundation Trust (MFT)Manchester University NHS Foundation Trust (MFT) is the largest NHS trust in England and a leading provider of specialist healthcare services. Its 10 hospitals are home to hundreds of world class clinicians and academic staff, committed to finding patients the best care and treatments. Its hospitals are Manchester Royal Infirmary, Saint Mary's Hospital, Royal Manchester Children's Hospital, Manchester Royal Eye Hospital, North Manchester General Hospital, University Dental Hospital of Manchester, Trafford General Hospital, Altrincham Hospital, Wythenshawe Hospital and Withington Hospital. More information is available at: www.mft.nhs.uk. About The University of ManchesterThe University of Manchester is a member of the prestigious Russell Group and one of the UK’s largest single-site universities. We have over 40,000 students, 12,000 staff and, with almost 480,000 former students from more than 190 countries, are home to the largest alumni community of any campus-based university in the UK. We are ranked in the top ten of the Times Higher Education (THE) Impact Rankings globally; are the top UK University for graduate employability according to The Graduate Market in 2022 and no fewer than 25 Nobel laureates have either worked or studied here. Visit www.manchester.ac.uk for further information or https://www.manchester.ac.uk/discover/vision/ for our latest strategic vision. Availability of Other Information About OrchardInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchard’s investor relations website and may include additional social media channels. The contents of Orchard’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933. Forward-looking StatementsThis press release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s business and product development strategy and goals, including the therapeutic potential of OTL-201, Orchard’s expectations with respect to regulatory submissions for its product candidates, including OTL-201, and Orchard’s expectations regarding its ongoing preclinical and clinical trials, including the timing of enrollment for clinical trials and release of additional preclinical and clinical data, and the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchard’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of OTL-201 will not continue or be repeated in Orchard’s ongoing or planned clinical trials of OTL-201, will be insufficient to support regulatory submissions or support or maintain marketing approval in the US or European Union, or that long-term adverse safety findings may be discovered; and the risk that any one or more of Orchard’s product candidates, including the OTL-201, will not be approved, successfully developed or commercialized. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchard’s most recent annual or quarterly report filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchard’s views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.______________________________i Cognitive function measured via standard scores, age-equivalent scores, development quotient (DQ) and gross scale equivalent [BSID-III] or [KABC-II]