UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 6-K

 

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the month of September 2019

Commission File Number: 001-38722

 

ORCHARD THERAPEUTICS PLC

(Translation of registrant’s name into English)

 

108 Cannon Street

London EC4N 6EU

United Kingdom

(Address of principal executive offices)

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F. Form 20-F ☒    Form 40-F ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐

 

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On September 4, 2019, Orchard Therapeutics plc issued the following press releases, a copy of which are attached hereto as Exhibits 99.1 and 99.2 and are incorporated herein by reference.

 

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EXHIBITS

 

 

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

 

 

  

Exhibit 99.1

 

Orchard Therapeutics Presents an Integrated Data Analysis Demonstrating Sustained Clinical Benefit of OTL-200 for the Treatment of Metachromatic Leukodystrophy

 

Further Demonstration that OTL-200 Provides Meaningful Clinical Benefit on Cognitive and Motor Function

 

No Standard Treatment Options Available, Regulatory Submission in Europe Planned for First Half of 2020 and U.S. Approximately One Year Later

 

BOSTON and LONDON, Sept. 04, 2019 -- Orchard Therapeutics (Nasdaq: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, today announced results from an integrated data analysis of OTL-200, a gene therapy in development for the treatment of metachromatic leukodystrophy (MLD) at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. The results, which demonstrate positive clinical effects of OTL-200 in the treatment of MLD and a consistent safety profile, were featured today in an oral presentation at the Society for the Study of Inborn Errors of Metabolism (SSIEM) symposium in Rotterdam, the Netherlands. MLD is a devastating and rapidly progressing disease with no standard treatment options. In its most severe forms, patients will not survive beyond their first few years of life.

 

“We recognize the urgent need for patients and families suffering from the devastating impacts of MLD and are pleased to present additional integrated data from a total of 29 patients treated with OTL-200,” said Dr. Valeria Calbi, a hematologist at San Raffaele Scientific Institute and SR-Tiget. “This analysis confirms and expands upon previously reported results for the primary efficacy endpoint, with significantly superior gross motor function measure scores compared with untreated patients, along with positive effects on cognitive function. These data demonstrate that the majority of patients treated with gene therapy at pre-symptomatic and early symptomatic stages of their disease experienced clinical benefit, while all patients in the natural history cohort showed the expected rapid decline in motor and cognitive function.”

 

As part of this integrated analysis, data from 29 early-onset MLD patients (16 late infantile and 13 early juvenile) treated with gene therapy were analyzed to assess the efficacy and safety of OTL-200. As of the date of last follow-up, 26 patients are alive and have completed up to 7.5 years of follow-up (median 3.2 years) post-gene therapy. The three patient deaths were deemed unrelated to treatment with OTL-200. Results from patients treated with OTL-200 were compared with those from an age-matched natural history cohort of 31 untreated MLD patients.

 

“The results of the integrated data analysis further underscore our commitment to bring one-time, potentially curative treatment options to patients living with MLD and other devastating rare genetic diseases that lack meaningful treatment options,” said Mark Rothera, president and chief executive officer of Orchard. “We are encouraged by the data presented today, which brings us one step closer to our anticipated submissions for regulatory approval in Europe in the first half of 2020 and the U.S. approximately one year later and further confirms the potential of our platform approach to treat MLD and other inherited diseases.”

 

 

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Efficacy Data from the Integrated Analysis
With the addition of nine patients treated through expanded access programs, the integrated analysis of OTL-200 has demonstrated the following:

 

 

 

 

 

 

Safety Data from the Integrated Analysis

 

 

 

 

Next Steps for OTL-200 

 

The company intends to complete the necessary development work and prepare a marketing authorization application, or MAA, for submission in Europe in the first half of 2020.  Work is also underway to prepare a biologics licensing application, or BLA, for submission in the U.S. approximately one year later. 

 

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A bridging study is currently underway to assess a cryopreserved formulation of OTL-200 in patients with pre-symptomatic MLD, with data expected by the end of 2019. For more information, please visit https://clinicaltrials.gov/ct2/show/NCT03392987.

 

About MLD and OTL-200
Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s metabolic system occurring in approximately one in every 100,000 live births. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, the gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged and patients with MLD will experience neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures, finding it more and more difficult to move, talk, swallow, eat and see. Currently, there are no effective treatments for MLD. In its late infantile form, mortality at 5 years from onset is estimated at 50% and 44% at 10 years for juvenile patients.¹ OTL-200 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MLD. OTL-200 was acquired from GSK in April 2018 and originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their joint San Raffaele-Telethon Institute for Gene Therapy in Milan, initiated in 2010.

 

About Orchard
Orchard Therapeutics is a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

 

Orchard’s portfolio of ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis^®, a gammaretroviral vector-based gene therapy and the first such treatment approved by the European Medicines Agency for severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD), transfusion-dependent beta-thalassemia (TDT) and mucopolysaccharidosis type I (MPS-I), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK in April 2018 and originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy initiated in 2010.

 

Orchard currently has offices in the U.K. and the U.S., including London, San Francisco and Boston.

 

Forward-Looking Statements
This press release contains certain forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” and “future” or similar expressions that are intended to identify forward-looking statements.  Forward-looking statements include express or implied statements relating to, among other things, Orchard’s expectations regarding the timing of regulatory submissions for approval of its product candidates, including OTL-200 for the treatment of metachromatic leukodystrophy, the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates, the timing of announcement of clinical

 

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data for its product candidates, including OTL-200, and the likelihood that such data will be positive and support further clinical development and regulatory approval of its product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. 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, the risks and uncertainties include, without limitation: the risk that any one or more of Orchard’s product candidates, including OTL-200, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchard’s ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchard’s product candidates, the delay of any of Orchard’s regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchard’s product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchard’s ability to commercialize its product candidates, if approved.  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 annual report on Form 20-F for the year ended December 31, 2018 as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, 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.
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¹Mahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010, DOI: http://doi.org/10.1177/0883073809341669 

 

Contacts

 

Investors
Renee Leck
Director, Investor Relations 
+1 862-242-0764
Renee.Leck@orchard-tx.com

 

Media
Molly Cameron
Manager, Corporate Communications
+1 978-339-3378
media@orchard-tx.com

 

 

Exhibit 99.2

 

Orchard Therapeutics Announces Encouraging

Update from Proof-of-Concept Study of OTL-203 for the

Treatment of Mucopolysaccharidosis Type I (MPS-I)

 

Six of Eight Patients Treated to Date with Follow-up Out to 12 Months in First Patient to Receive Treatment

 

Evidence of Engraftment and Peripheral Blood Alpha-L-iduronidase (IDUA) Enzyme Overexpression Across Cohort

 

BOSTON and LONDON, Sept. 04, 2019 -- Orchard Therapeutics (Nasdaq: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, today announced data from an ongoing proof-of-concept clinical trial evaluating the safety and efficacy of OTL-203, a gene therapy for the treatment of mucopolysaccharidosis type I (MPS-I) developed at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan. The results presented in an oral presentation at the Society for the Study of Inborn Errors of Metabolism (SSIEM) symposium include up to 12 months of follow-up for the first patient treated.

 

MPS-I is a progressive and often life-threatening inherited lysosomal storage disorder affecting children, with the most severe form known as Hurler syndrome. Patients with MPS-I often suffer from a constellation of devastating symptoms, including neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications.

 

Maria Ester Bernardo, M.D., Ph.D., co-principal investigator at SR-Tiget commented, “We have been making good progress with the MPS-I clinical trial and are encouraged by these interim results, with multiple patients achieving stable engraftment of gene-corrected blood stem cells and expression of the IDUA enzyme and promising preliminary clinical effects in the patient with 12 months of follow-up. We look forward to completing enrollment and formally assessing proof of concept for this investigational new therapy for patients with this often-fatal condition.”

 

Interim Study Results
As of the date of last follow-up, six patients with the severe Hurler subtype of MPS-I have been treated with the cryopreserved formulation of OTL-203 gene therapy. All treated patients were followed for a minimum of two months, with the longest follow-up extending out to 12 months. At the time of treatment, patients ranged in age from 14 months to 35 months. Five out of six patients had previously been treated with enzyme replacement therapy (ERT) and discontinued ERT treatment three weeks prior to enrollment, consistent with trial protocol.

 

The primary endpoints of the trial are safety, hematological engraftment by day 45 following treatment and preliminary efficacy as measured by IDUA enzyme activity (up to supraphysiologic levels) at one-year post-treatment. Treatment with OTL-203 demonstrated:

 

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Key secondary and exploratory endpoints include normalization of urinary glycosaminoglycans (GAGs), growth velocity and effects on motor and cognitive function at one- and two-years post-treatment.

 

 

 

“The data emerging from the MPS-I program adds to the growing body of evidence that our approach – the expression of the targeted gene delivered via gene-modified blood stem cells – has the potential to permanently correct multiple neurometabolic disorders,” said Andrea Spezzi, MBBS, FFPM, chief medical officer of Orchard. “We believe our gene therapies could fundamentally change the lives of patients born with MPS-I and other devastating and rapidly progressive diseases affecting the central nervous system and remain committed to advancing our programs in this area as quickly as possible.”

 

The proof-of-concept study is ongoing and expected to enroll eight patients by the first half of 2020, with primary endpoint results reported after one year of follow-up.

 

About MPS-I and OTL-203
Mucopolysaccharidosis type I (MPS-I) is a rare inherited neurometabolic disease caused by a deficiency of the IDUA (alpha-L-iduronidase) lysosomal enzyme required to break down glycosaminoglycans (also known as GAGs or mucopolysaccharides). The accumulation of GAGs across multiple organ systems results in the symptoms of MPS-I including neurocognitive impairment, skeletal deformity, loss of vision and hearing, hydrocephalus, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births.¹ There are three subtypes of MPS-I; approximately 60 percent of MPS-I patients have the severe Hurler subtype and, when untreated, these patients rarely live past the age of 10.^Id Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele-Telethon Institute for Gene Therapy in Milan, Italy.

 

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About Orchard
Orchard Therapeutics is a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

 

Orchard’s portfolio of ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis®, a gammaretroviral vector-based gene therapy and the first such treatment approved by the European Medicines Agency for severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD) and transfusion-dependent beta-thalassemia (TDT), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK in April 2018 and originated from a pioneering collaboration between GSK, Fondazione Telethon and Ospedale San Raffaele initiated in 2010.

 

Orchard currently has offices in the U.K. and the U.S., including London, San Francisco and Boston.

 

Forward-Looking Statements
This press release contains certain forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” and “future” or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, planned marketing and licensing application submissions and next steps for Orchard’s programs, the therapeutic potential of Orchard’s product candidates, including OTL-203 for the treatment of MPS-I, and Orchard’s expectations regarding the timing of announcement of clinical data or enrollment in clinical trials for its product candidates, including OTL-203, the likelihood that such data will be positive and support further clinical development and regulatory approval of its product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. These statements are neither promises nor guarantees, but 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, the risks and uncertainties include, without limitation: the risk that any one or more of Orchard’s product candidates, including OTL-203, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchard’s ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchard’s product candidates, the delay of any of Orchard’s regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchard’s product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchard’s ability to commercialize its product candidates, if approved. 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 annual report on Form 20-F for the year ended December 31, 2018 as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, as well as

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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.

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¹ Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759

 

Contacts

 

Investors
Renee Leck
Director, Investor Relations
+1 862-242-0764
Renee.Leck@orchard-tx.com

 

Media
Molly Cameron
Manager, Corporate Communications
+1 978-339-3378
media@orchard-tx.com