Corneal Opacity

Gene therapy being developed as a one-time treatment to address the underlying cause of the disease by inserting a functional copy of the human IDUA gene into a patient’s own hematopoietic stem cells HURCULES study to enroll 40 patients at clinical sites across the U.S. and Europe TOKYO, LONDON and BOSTON, Feb. 05, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, today announced the first patient has been randomized at the M Health Fairview Masonic Children’s Hospital in a registrational trial evaluating the efficacy and safety of OTL-203, an investigational hematopoietic stem cell (HSC) gene therapy, in patients with the Hurler subtype of mucopolysaccharidosis type I (MPS-IH). The trial, referred to as HURCULES, compares treatment with OTL-203 to standard of care with allogeneic hematopoietic stem cell transplant (HSCT), and is expected to enroll 40 MPS-IH patients at sites across the U.S. and Europe. MPS-I is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme resulting in the accumulation of glycosaminoglycans (GAGs) in multiple organs, including the musculoskeletal and central nervous systems, as well as the heart, eyes, and ears. It is estimated to occur globally in 1 in 100,000 live births. Approximately 60 percent of children born with MPS-I have the most severe subtype, MPS-IH, also called Hurler syndrome, and rarely live past the age of 10 when untreated. Current treatment options for MPS-IH include allogeneic hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy (ERT), both of which have significant limitations. “This is a substantial milestone in the development of OTL-203 as we work toward bringing an important new treatment option to children with MPS-IH and their families,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “Previously reported results from an earlier proof-of-concept study in patients showed robust metabolic correction, continued cognitive, motor, and physical development, as well as early improvements in skeletal, ocular and auditory health demonstrating that one-time treatment with OTL-203 has the potential to positively impact a broad range of clinical manifestations not fully addressed by the current standard of care.” In an earlier single-center proof-of-concept (PoC) study, eight patients diagnosed with MPS-IH were treated at Ospedale San Raffaele in Milan, Italy with investigational OTL-203 between July 2018 and December 2019. Throughout the follow-up period, a total of 26 serious adverse events (SAEs) were observed. The events were related to known complications of MPS-IH already present prior to treatment, protocol procedures or general illnesses of childhood, and all have resolved. One patient experienced an acute hypersensitivity reaction that was considered probably related to HSC gene therapy. OTL-203 has received Fast Track and Rare Pediatric Disease (RPD) designations from the U.S. Food and Drug Administration (FDA), as well as priority medicines (PRIME) status from the European Medicines Agency (EMA). The program was originated by, and initially developed in partnership with, the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) in Milan, Italy. “The complications associated with MPS-IH have a detrimental impact on patients’ quality of life, and while transplantation may help improve outcomes, it is associated with significant morbidity and mortality,” said Paul Orchard, M.D., a study investigator and professor in the Division of Pediatric Blood and Marrow Transplantation and Cellular Therapy Program at the University of Minnesota Medical School. “New options are needed to better address some of the more severe symptoms of the disease, such as neurocognitive function, growth and other skeletal issues. We look forward to working with the team at Orchard Therapeutics and other clinical sites around the world to facilitate enrollment in this study and characterize the potential clinical impact of OTL-203 on MPS-IH.” Currently, the University of Minnesota is actively recruiting patients with additional trial sites expected to begin recruitment in the coming months. Summary of Previous OTL-203 Clinical Results Interim results from the earlier PoC study published in The New England Journal of Medicine showed all patients had supraphysiological IDUA enzyme activity with an associated sustained decrease in GAG levels and stable cognitive performance post-treatment. In addition, all participants had progressed along expected growth percentiles of healthy children and exhibited longitudinal growth that was considered within the normal range adjusted for age and gender. In subsequent follow-up, study investigators have observed progressive acquisition of fine and gross motor skills, as well as evidence of continued growth within normal range and improvements in skeletal health with a median follow-up of 3.78 years (range: 3.14 to 4.58 years) as of May 2023. In addition, Dr. Maria Ester Bernardo, clinical coordinator, pediatric clinical research unit at SR-TIGET and the principal investigator of the PoC study, detailed the first findings on other treatment outcomes, including ocular (eye) symptoms and auditory (hearing) function at the European Society of Cell and Gene Therapy (ESGCT) 30th Annual Congress. The presentation outlined favorable results for disease manifestations not fully addressed by the current standard of care and further highlights the potential of genetically repaired HSCs to migrate into and correct abnormalities in multiple tissues and organs. Throughout the PoC study, treatment with OTL-203 has been generally well-tolerated with a safety profile consistent with the selected conditioning regimen. The viral vector integration profile was comparable with other Orchard Therapeutics lentiviral-based HSC gene therapy studies, and all participants had a stable and highly polyclonal repertoire. As part of the study, ERT was discontinued at least three weeks prior to any patient receiving gene therapy, and none of those patients needed to re-start ERT post-treatment. Patients who entered the study with anti-IDUA antibodies present because of prior ERT treatment were no longer antibody positive within two months of treatment with OTL-203. About the HURCULES StudyHURCULES—a study name that combines the target indication HURler syndrome and HerCULES, the classical mythological character—is a multi-center, randomized, active controlled clinical trial designed to evaluate the efficacy and safety of OTL-203 in patients with MPS-IH compared to standard of care with allogeneic HSCT. A total of 40 patients with a confirmed diagnosis of MPS-IH who meet the study inclusion criteria are being randomized 1:1 to receive either OTL-203 or allogeneic HSCT. The study is powered to demonstrate superiority of OTL-203 over allogeneic HSCT. The primary endpoint, which will be measured at two years post-treatment, comprises a composite of clinically meaningful outcomes, including death, the need for rescue transplant, treatment failure, immunological complications, as well as severe cognitive and/or growth impairment. Secondary endpoints include biochemical markers, additional clinical assessments, as well as safety and tolerability. The company expects to activate six sites in the United States and Europe. For more information, please visit www.clinicaltrials.gov (NCT06149403). About MPS-IMucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (GAGs). The accumulation of GAGs across multiple organ systems results in multiple symptomatic manifestations of the disease including severe neurocognitive impairment, skeletal deformities, cardiovascular and pulmonary complications, impaired motor function, loss of hearing and corneal clouding. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I. Approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome (MPS-IH), and rarely live past the age of 10 when untreated. Treatment options for MPS-I include hematopoietic stem cell transplant and enzyme replacement therapy, both of which have limitations, such as inadequate impact on some of the more severe manifestations of disease, as well as significant morbidity and mortality. At present, Newborn Screening (NBS) for MPS-I has been established in multiple geographies, including the United States and Europe. About OTL-203OTL-203 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IH. It uses a modified virus to insert a functional copy of the human IDUA gene into a patient’s cells. OTL-203 was originated by, and initially developed in partnership with, the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. OTL-203 has received Rare Pediatric Disease (RPD) and Fast Track designations from the U.S. FDA, as well as priority medicines (PRIME) status from the EMA. About Orchard TherapeuticsOrchard Therapeutics, a Kyowa Kirin company, is a global gene therapy leader focused on ending the devastation caused by genetic and other severe diseases 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 with a single treatment. Founded in 2015, Orchard’s roots go back to some of the first research and clinical developments involving HSC gene therapy. Our team has played a central role in the evolution of this technology from a promising scientific idea to a potentially life-transforming reality. Today, as a vital part of Kyowa Kirin’s global business, Orchard continuing to advance a pipeline of 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. For more information, please visit www.orchard-tx.com. About Kyowa KirinKyowa Kirin aims to discover novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients affected by a severe or rare disease. A shared commitment to our values, to sustainable growth, and to making people smile unites us across our four regions – Japan, Asia Pacific, North America, and EMEA/International. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com.

Ventegra® will list VEGZELMA®(bevacizumab-adcd) on its national formulary that serves more than 400 clients and more than 13 million members and patients in the U.S. Celltrion USA completes a contract with Ventegra to include YUFLYMA® as a preferred drug in its formulary in September 2023. This marks a significant step forward in offering clinically effective and cost-effective options for the oncology community in the U.S. JERSEY CITY, N.J., Dec. 11, 2023 /PRNewswire/ -- Celltrion USA today announced that Ventegra®, a major U.S. Medical Benefits Manager (MBM) who administers pharmacy benefits through its Pharmacy Services Administration (PSA) model, will place an FDA-approved biosimilar to Avastin® (bevacizumab), VEGZELMA® (bevacizumab-adcd), on its commercial formulary as a preferred brand. Ventegra's proprietary formulary program (which includes Formulary Shield and the Ventegra Specialty Inclusion Program) is available for access by more than 400 clients and 13 million members/patients that are enrolled with Ventegra. VEGZELMA was approved by the U.S. FDA in 2022 for the treatment of six types of cancer: metastatic colorectal cancer; recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer. "The inclusion of our FDA-approved bevacizumab biosimilar on Ventegra's preferred formulary status is another important milestone to help increase access to oncology treatment for those living with indicated cancer types across the U.S.," said Tom Nusbickel, Chief Commercial Offer at Celltrion USA. "We have been committed to introducing safe and effective biosimilars to the U.S. market because they hold tremendous promise for cost savings for patients, plans, and our entire health care system." "Our revolutionary Medical Benefits Manager (MBM) model goes beyond traditional pharmacy benefit management to help build efficiencies, lower costs, and improve the overall quality of care. Our decision to add another Celltrion's oncology biosimilar product to our formulary supports greater affordability and access across this entire treatment class," said Robert T. Taketomo, Pharm.D., MBA, President/CEO of Ventegra. "Our partnership with Celltrion USA allows us to reach more communities faster and enable comprehensive, affordable care that improves long-term health outcomes and fosters healthier communities." VEGZELMA® Important Safety Information Warnings and Precautions Gastrointestinal Perforations and Fistula: Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any organ. Surgery and Wound Healing Complications: In patients who experience wound healing complications during VEGZELMA treatment, withhold VEGZELMA until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer VEGZELMA for at least 28 days following a major surgery, and until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complication has not been established. Discontinue for wound healing complication of necrotizing fasciitis. Hemorrhage: Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage. Arterial Thromboembolic Events (ATE): Discontinue for severe ATE. Venous Thromboembolic Events (VTE): Discontinue for Grade 4 VTE. Hypertension: Monitor blood pressure and treat hypertension. Withhold if not medically controlled; resume once controlled. Discontinue for hypertensive crisis or hypertensive encephalopathy. Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue. Renal Injury and Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine. Infusion-Related Reactions: Decrease rate for infusion-related reactions. Discontinue for severe infusion-related reactions and administer medical therapy. Embryo-Fetal Toxicity: May cause fetal harm. Advise females of potential risk to fetus and need for use of effective contraception. Ovarian Failure: Advise females of the potential risk. Congestive Heart Failure (CHF): Discontinue VEGZELMA in patients who develop CHF. Pregnancy Warning Based on findings from animal studies and their mechanism of action, bevacizumab products may cause fetal harm in pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab products in pregnancy; however, these reports are insufficient to determine drug-associated risks. In animal reproduction studies, intravenous administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses approximately 1 to 10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects. Furthermore, animal models link angiogenesis and VEGF and VEGFR2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Most Frequently Observed Adverse Reactions Most common adverse reactions incidence (incidence > 10%) are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis. Please see full Prescribing Information for VEGZELMA® ( bevacizumab-adcd) About Celltrion USA Celltrion USA is Celltrion Healthcare's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion USA will continue to leverage Celltrion Healthcare's unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. Celltrion Healthcare endeavours to offer high-quality, cost-effective solutions through an extensive global network that spans more than 110 different countries. For more information, please visit: About Ventegra® Ventegra®, recognized as a "New Class of Trade," serves as a Medical Benefit Manager ("MBM") with Pharmacy Services Administrator ("PSA") as part of its portfolio of products. Ventegra is a single, turnkey solution for clients interested in managing their medical and pharmacy benefit services with integrity, quality, and complete transparency around data/costs of care. The Ventegra business model fundamentally realigns financial incentives focusing on value-based care and total healthcare cost. Ventegra understands the value of the coordinated care delivery model and can serve the needs of those with similar goals and objectives. Contact Lindsey Lucenta [email protected] +1 260-444-1306 Social Media Profiles Celltrion USA LinkedIn SOURCE Celltrion USA

Previously reported results from ongoing proof-of-concept study showed extensive metabolic correction, continued cognitive, motor, and physical development, as well as early improvements in skeletal health Additionally, study investigators presented favorable outcomes for other disease manifestations not effectively addressed by the current standard of care at ESGCT 2023 Global registrational trial expected to commence by year-end BOSTON and LONDON, Nov. 30, 2023 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to OTL-203, an investigational hematopoietic stem cell gene (HSC) therapy being developed for the potential treatment of the Hurler subtype of mucopolysaccharidosis type I (MPS-IH). Fast Track designation is intended to expedite the development of promising medicines that address serious medical needs. Therapeutic candidates that receive Fast Track designation may be eligible for enhanced interactions with the FDA, including potentially quicker submission and review timelines. MPS-I is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme resulting in the accumulation of glycosaminoglycans (GAGs) in multiple organs, including the eyes, ears, heart, as well as the musculoskeletal and central nervous systems. It is estimated to occur globally in 1 in 100,000 live births. Approximately 60 percent of children born with MPS-I have the most severe subtype, MPS-IH, also called Hurler syndrome, and rarely live past the age of 10 when untreated. Current treatment options for MPS-IH include allogeneic hematopoietic stem cell transplant (HSCT) and chronic enzyme replacement therapy (ERT), both of which have significant limitations. “At Orchard Therapeutics, we are applying our HSC gene therapy platform to indications where we believe it is clinically differentiated and has the greatest potential to make a paradigm-shifting impact on the treatment landscape,” said Leslie Meltzer, Ph.D., chief medical officer. “We are encouraged that OTL-203 has been granted Fast Track designation because new treatment options are urgently needed for children with MPS-IH, as the current standard of care is associated with significant morbidity and mortality. Moreover, existing treatment options do not adequately address the broad range of clinical manifestations of the disease, including those that are most burdensome and have a high impact on quality of life. We look forward to initiating our global registrational trial in December to evaluate the efficacy and safety of OTL-203 compared to allogeneic HSCT.” OTL-203 has previously received Rare Pediatric Disease (RPD) and priority medicines (PRIME) designations from the FDA and European Medicines Agency, respectively. Summary of the Clinical Development Program for OTL-203 In an ongoing single-center proof-of-concept (PoC) study, eight patients diagnosed with MPS-IH were treated at Ospedale San Raffaele in Milan, Italy with investigational OTL-203 between July 2018 and December 2019. Interim results published in The New England Journal of Medicine showed all patients had stable cognitive performance post-treatment. In addition, all participants had progressed along expected growth percentiles of healthy children and exhibited longitudinal growth that was considered within the normal range adjusted for age and gender. In subsequent follow-up, study investigators have observed continued cognitive development and evidence of continued growth within normal range and improvements in skeletal health with a median follow-up of 3.78 years (range: 3.14 to 4.58 years) as of May 2023. In addition to the biochemical, neurological and skeletal results previously reported, last month at the European Society of Cell and Gene Therapy (ESGCT) 30th Annual Congress, Dr. Maria Ester Bernardo, clinical coordinator, pediatric clinical research unit at San Raffaele Telethon-Institute for Gene Therapy (SR-TIGET) and the principal investigator of the PoC study, detailed the first findings on other treatment outcomes, including ocular (eye) symptoms and auditory (hearing) function. Results showed favorable results for disease manifestations not effectively addressed by the current standard of care and further highlights the ability of gene modified HSCs to migrate into and correct abnormalities in multiple different tissues and organs. Throughout the PoC study, treatment with OTL-203 has been generally well-tolerated with a safety profile consistent with the selected conditioning regimen. The viral vector integration profile was consistent with other lentiviral-based HSC gene therapy studies, and all participants had a stable and highly polyclonal repertoire. Anti-alpha-L-iduronidase (IDUA) antibodies present prior to gene therapy as a result of ERT were not seen in any patient within two months following treatment. In addition, ERT was discontinued at least three weeks prior to any patient receiving gene therapy treatment, and no patients have re-started ERT post-treatment. Global Registrational Trial Expected to Commence by Year-end Following the promising results observed in the PoC study, Orchard Therapeutics is initiating a multi-center, randomized, active controlled clinical trial designed to evaluate the efficacy and safety of OTL-203 in patients with MPS-IH compared to standard of care with allogeneic HSCT. A total of 40 patients with a confirmed diagnosis of MPS-IH who meet the study inclusion criteria will be randomized 1:1 to receive either OTL-203 or allogeneic HSCT. The study is powered to demonstrate superiority of OTL-203 over HSCT. The primary endpoint, which will be measured at two years post-treatment, comprises a composite of clinically meaningful outcomes, including death, the need for rescue transplant, treatment failure, immunological complications, as well as severe cognitive and/or growth impairment. Secondary endpoints include biochemical markers, additional clinical assessments, as well as safety and tolerability. The company expects to activate up to six sites in the United States and Europe. For more information, please visit www.clinicaltrials.gov (NCT06149403). About MPS-IMucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (GAGs). The accumulation of GAGs across multiple organ systems results in multiple symptomatic manifestations of the disease including severe neurocognitive impairment, skeletal deformities, cardiovascular and pulmonary complications, impaired motor function, loss of hearing and corneal clouding. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I. Approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome (MPS-IH), and rarely live past the age of 10 when untreated. Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have limitations, such as inadequate impact on some of the more severe manifestations of disease, as well as significant morbidity and mortality. At present, Newborn Screening (NBS) for MPS-I has been established in multiple geographies, including the United States and Europe. About OTL-203OTL-203 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IH. It uses a modified virus to insert a functional copy of the IDUA gene into a patient’s cells. OTL-203 is being developed in partnership with the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. OTL-203 has received Rare Pediatric Disease (RPD) and Fast Track designations from the U.S. FDA, as well as priority medicines (PRIME) status from the European Medicines Agency. 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 X (formerly Twitter) and LinkedIn. 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 (X; formerly 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, the therapeutic potential of OTL-203, the development timeline for OTL-203, including the timing of clinical trials, and the timing and likelihood of regulatory approvals for OTL-203. 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 the development of OTL-203 will be delayed, the risk that OTL-203 will not be successfully approved or commercialized and the risk that long-term adverse safety findings may be discovered. 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.