StemCell Therapy

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TSHA-101 to be first bicistronic vector evaluated in human clinical trials; TSHA-101 designed to deliver both HEXA and HEXB transgenes within a single AAV9 vector construct

TSHA-101 CTA is the second clinical trial clearance received, in addition to TSHA-118s open investigational new drug application for CLN1

Interim data from Phase 1/2 trial anticipated in 2021

DALLAS, TX, USA I December 21, 2020 I Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system in both rare and large patient populations, today announced that Queens University in Ontario, Canada, received Clinical Trial Application (CTA) approval from Health Canada for its investigator-sponsored Phase 1/2 trial exploring TSHA-101, Tayshas investigational AAV9-based gene therapy, for the treatment of infantile GM2 gangliosidosis.

TSHA-101 will be the first bicistronic vector to enter a first-in-human clinical study, which is a significant milestone for Taysha and for the field of gene therapy, said Suyash Prasad, MBBS, M.SC., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development of Taysha. GM2 is a devastating lysosomal storage disease with no approved treatments and todays CTA approval marks a formative moment for children suffering from this rapidly progressive and fatal disease.

The trial will be a single arm, open-label Phase 1/2 trial evaluating the use of TSHA-101 for the treatment of infants with GM2. The study will be sponsored by Queens University and led by Jagdeep S. Walia, MBBS, FRCPC, FCCMG, Clinical Geneticist and Associate Professor Head, Division of Medical Genetics (Department of Pediatrics) at Queens, and Director of Research (Department of Pediatrics), at the Kingston Health Sciences Centre.

Preclinical evidence to date supports our belief that TSHA-101, when given intrathecally as a bicistronic transgene packaged into a single AAV9 vector, has the potential to address the lysosomal enzyme deficiency, to change the disease trajectory and to improve patient survival, said Dr. Jagdeep S. Walia. We are pleased to have the support of Health Canada as we continue to advance TSHA-101.

Todays CTA approval is a culmination of our teams and Dr. Walias tireless efforts and a momentous occasion for children affected by GM2 along with their parents and caregivers, said RA Session II, Founder, President and CEO of Taysha. We are grateful to our partners at Queens University for their work to advance this gene therapy into the clinic.

About GM2 Gangliosidosis

GM2 gangliosidosis is a rare and fatal monogenic lysosomal storage disorder and a family of neurodegenerative genetic diseases that includes Tay-Sachs and Sandhoff diseases. The disease is caused by defects in the HEXA or HEXB genes that encode the two subunits of the -hexosaminidase A enzyme. These genetic defects result in progressive dysfunction of the central nervous system. There are no approved therapies for the treatment of the disease, and current treatment is limited to supportive care.

About TSHA-101

TSHA-101 is an investigational gene therapy administered intrathecally for the treatment of infantile GM2 gangliosidosis. The gene therapy is designed to deliver two genes HEXA and HEXB driven by a single promoter within the same AAV9 construct, also known as a bicistronic vector. This approach allows the simultaneous expression of a 1:1 ratio of the two subunits of protein required to generate a functional enzyme. It is the first and only bicistronic vector currently in clinical development and has been granted Orphan Drug and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA).

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available at http://www.tayshagtx.com.

SOURCE: Taysha Gene Therapy

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Taysha Gene Therapies Announces Queen's University's Receipt of Clinical Trial Application Approval from Health Canada for Phase 1/2 Clinical Trial of...

Eli Lilly has stepped into the gene therapy space after announcing a deal to acquire Prevail Therapeutics, a company focused on developing adeno-associated virus (AAV)-based gene therapies for neurodegenerative diseases.

Lilly will acquire Prevail for $22.50 per share in cash, plus one $4 contingent value right dependent on the first regulatory approval of a product from Prevails pipeline.

This reflects a potential consideration of up to $26.50 per share in cash for a total consideration of approximately $1.04bn.

For Lilly, the acquisition will extend its focus into developing gene therapies, establishing an in-house gene therapy programme anchored by Prevails current portfolio and AAV-based technology.

Prevails pipeline spans clinical-stage and preclinical neuroscience assets, including lead gene therapies PR001 for patients with Parkinsons disease with GBA1 mutations (PD-GBA) and neuronopathic Gaucher disease (nGD) and PR006 for patients with frontotemporal dementia with GRN mutations (FTD-GRN).

The companys preclinical pipeline also includes PR004, a potential gene therapy for patients with specific synucleinopathies, as well as candidates for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders.

"The acquisition of Prevail will bring critical technology and highly skilled teams to complement our existing expertise at Lilly, as we build a new gene therapy programme anchored by well-researched assets, said Mark Mintun, vice president of pain and neurodegeneration research at Lilly.

We look forward to completing the proposed acquisition and working with Prevail to advance their ground-breaking work through clinical development, he added.

For Prevail to achieve the full value of the contingent CVR payment, the first regulatory approval arising from its current gene therapy pipeline must happen by 31 December 2024.

Failing regulatory approval by this date, Lilly said in a statement that the value of the CVR will decrease by approximately 8.3 cents per month until the expiration date 1 December 2028.

Within Prevails clinical pipeline, PR001 has already scored a US Food and Drug Administration (FDA) fast-track designation for the treatment of PD-GBA patients and nGD.

It has also been granted an FDA orphan drug designation for the treatment of Gaucher disease, and rare paediatric disease designation for the treatment of nGD.

Prevails PR006 gene therapy also has an FDA and European Commission orphan designation for the treatment of FTD, with the FDA also handing it a fast-track designation for FTD-GRN.

In November, Lilly signed a deal with Precision BioSciences focused on genome editing research, with an initial focus on developing in vivo therapies for Duchenne muscular dystrophy and two other undisclosed gene targets.

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Lilly picks up gene therapy programme in $1bn Prevail Therapeutics acquisition deal - PMLiVE

When former analyst Rachel McMinn started Neurogene from her apartment around three years ago, she would joke that theyd get office space as soon as her living room table was no longer big enough to hold company meetings.

We lasted about a year before my living room couldnt take it anymore, she said.

With several gene therapies for Batten disease and other lysosomal storage disorders in the preclinical and discovery stage, Neurogene is now bound for the clinic. And on Wednesday, they announced a $115 million Series B to get them there.

Gene therapy has generated so much enthusiasm for patients and families with these devastating disorders, but theres still a lot of science and innovation left on the table, McMinn said.

The CEO said Neurogene will split the Series B funds into four buckets, the first of which is advancing multiple gene therapy programs into the clinic. She anticipates filing the first IND in 2021 for CLN5, a rapidly progressive subtype of Batten disease caused by a variant in the CLN5 gene.

The second so-called bucket for the Series B funds will be expanding the companys portfolio, followed by another bucket for augmenting our resources for our novel technology platform, the CEO said. Then comes manufacturing.

Weve got the ability to make virus in-house, and the money from the financing will allow us to take that vector to the next stage and make GMP quality vector for use in dosing and clinical trials, McMinn said.

Because Neurogene manufactures products in-house, the biotech has gotten around the massive gene therapy manufacturing bottleneck, which has Big Pharma and big biotech spending billions on retrofitted plants and gene therapy factories.

The concept of gene therapy is simple: A viral particle is used to deliver a healthy copy of a gene to a patient with a dysfunctional gene. In the case of Neurogenes CLN5 candidate, viral vectors shuttle a payload into the body designed to make the CLN5 gene.

Over the next year, key milestones will be filing our first IND, completing the refurbishment of our GMP manufacturing facility, (and) advancing our programs towards the clinic, McMinn said. After CLN5, the goal is to file one to two INDs a year, she added.

The CEO previously served as an analyst at Piper Jaffray, Cowen and Bank of America Merrill Lynch, and as chief business and strategy officer at Intercept. During her time as an analyst, McMinn said most people would stay away from investing in neurology companies because drugs inevitably fail.

Theres really been nothing, very little innovation in devastating neurological disorders, for quite a long time, she said, adding that she was inspired to jump into R&D by an older brother who is neurologically impaired.

Neurogene attracted a slate of new and old investors, including EcoR1 Capital which led the round, and Redmile Group, Samsara BioCapital, Cormorant Asset Management, BlackRock, funds managed by Janus Henderson Investors, Casdin Capital, Avidity Partners, Ascendant BioCapital, Arrowmark Partners, Alexandria Venture Investments, and an undisclosed leading healthcare investment fund.

For me, I really want to make a difference, McMinn said, adding later, Im personally driven by developing something that is life-altering for people that really have no other option.

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After leaving Wall Street to launch a gene therapy upstart, Rachel McMinn nabs $115M to drive her first candidate to the clinic - Endpoints News

DUBLIN, Dec. 17, 2020 /PRNewswire/ -- The "Gene Therapy Global Market Report 2020-30: COVID-19 Growth and Change" report has been added to ResearchAndMarkets.com's offering.

Gene Therapy Global Market Report 2020-30: COVID-19 Growth and Change provides the strategists, marketers and senior management with the critical information they need to assess the global gene therapy market market.

Major players in the gene therapy market are Novartis AG, Bluebird Bio, Inc., Spark Therapeutics, Inc., Audentes Therapeutics, Voyager Therapeutics, Applied Genetic Technologies Corporation, UniQure N.V., Celgene Corporation, Cellectis S.A. and Sangamo Therapeutics.

The global gene therapy market is expected to decline from $3.22 billion in 2019 to $3.18 billion in 2020 at a compound annual growth rate (CAGR) of -1.30%. The decline is mainly due to the COVID-19 outbreak that has led to restrictive containment measures involving social distancing, remote working, and the closure of industries and other commercial activities resulting in operational challenges. The market is then expected to recover and reach $6.84 billion in 2023 at a CAGR of 29.09%.

The gene therapy market consists of sales of gene therapy related services by entities (organizations, sole traders and partnerships) that manufacture gene therapy drugs. Gene therapy is used to replace faulty genes or add new genes to cure disease or improve the body's ability to fight disease. Only goods and services traded between entities or sold to end consumers are included.

North America was the largest region in the gene therapy market in 2019.

The gene therapy market covered in this report is segmented by gene type into antigen; cytokine; suicide gene; others. It is also segmented by vector into viral vector; non-viral vector; others, by application into oncological disorders; rare diseases; cardiovascular diseases; neurological disorders; infectious diseases; others, and by end users into hospitals; homecare; specialty clinics; others.

In December 2019, Roche, a Switzerland-based company, completed its acquisition of Spark Therapeutics for $4.3 billion. With this deal, Roche is expected to strengthen its presence in the gene therapy segment, support transformational therapies and increase its product portfolio. Spark Therapeutics is a US-based company involved in gene therapy.

The high prices of gene therapy medicines are expected to limit the growth of the gene therapy market. The pressure to contain costs and demonstrate value is widespread. Political uncertainty and persistent economic stress in numerous countries are calling into question the sustainability of public health care funding. In less wealthy countries, the lack of cost-effective therapies for cancer and other diseases has influenced the health conditions of the population and has led to a low average life expectancy.

Luxturna, a one-time treatment for acquired retinal eye disease, costs $850,000 in the US and 613,410 in the UK, despite a markdown that is applied through Britain's National Health Service. Zolgensma, for spinal muscular atrophy, is valued at $2.1 million in the US and Zynteglo, which focuses on a rare genetic blood disorder, costs $1.78 million, thus restraining the growth of the market.

The use of machine learning and artificial intelligence is gradually gaining popularity in the gene therapy market. Artificial intelligence (AI) is the simulation of human intelligence in machines, which are programmed to display their natural intelligence. Machine learning is a part of AI.

Machine learning and AI help companies in the gene therapy market to conduct a detailed analysis of all relevant data, provide insights between tumor and immune cell interactions, and offer a more accurate evaluation of tissue samples often conflicted between different evaluators. For instance, since January 2020, GlaxoSmithKline, a pharmaceutical company, has been investing in AI to optimize gene therapy and develop off-the-shelf solutions for patients. It is also expected to reduce turnaround time and also the cost of gene therapies.

Key Topics Covered:

1. Executive Summary

2. Gene Therapy Market Characteristics

3. Gene Therapy Market Size And Growth 3.1. Global Gene Therapy Historic Market, 2015 - 2019, $ Billion 3.1.1. Drivers Of The Market 3.1.2. Restraints On The Market 3.2. Global Gene Therapy Forecast Market, 2019 - 2023F, 2025F, 2030F, $ Billion 3.2.1. Drivers Of The Market 3.2.2. Restraints On the Market

4. Gene Therapy Market Segmentation 4.1. Global Gene Therapy Market, Segmentation By Gene Type, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.2. Global Gene Therapy Market, Segmentation By Vector, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.3. Global Gene Therapy Market, Segmentation By Application, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.4. Global Gene Therapy Market, Segmentation By End Users, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

5. Gene Therapy Market Regional And Country Analysis 5.1. Global Gene Therapy Market, Split By Region, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion 5.2. Global Gene Therapy Market, Split By Country, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/fltbmv

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

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Global Gene Therapy Market Report 2020-2030 Featuring Novartis, Bluebird Bio, Spark Therapeutics, Audentes Therapeutics, Voyager Therapeutics,...

Taysha Gene Therapies went public with a bang earlier this year with a $157 million IPO just five months after its Series A financing. Now, with the help of the city of Durham, North Carolina, Taysha is plotting an expansive development and manufacturing facility to ramp up supplies for the clinic and potentially the commercial market.

The new 187,000-square-foot cGMP plant will create roughly 200 jobs for Taysha Gene Therapies, which formed in late 2019 with the sole focus of developing therapeutics for monogenic diseases using an adeno-associate virus methodology. The announcement continues a rapid ascent for Taysha, which launched Series A financing just in April, and a mere five months later had its own Nasdaq ticker, offering a $157 million IPO and pricing shares at $20 apiece.

The facility is the result of a public-private partnership between Taysha, the city of Durham and the state of North Carolina. Taysha will invest $75 million into the facility, with additional state and local incentives totaling another $9.4 million. All told, the 200 jobs will come to fruition over a two-and-a-half-year period across all functions, including gene therapy development, analytics, manufacturing and quality control testing.

Tayshas facility is expected to be fully operational by 2023 and will add 2,000 liters of capacity supporting all aspects of scalable gene therapy manufacturing. The company said in a news release it will now be able to meet the clinical and commercial demands within the field when combined with its existing collaborations with the University of Texas Southwestern Medical Center and CDMO Catalent.

With our outstanding team of experts leading the charge, we expect this facility will serve as a center of excellence for gene therapy development, from preclinical studies through commercialization, and will further our leadership position in gene therapy as well as support our next phase of growth, RA Session II, Tayshas president, founder and CEO, said in a press release.

The new facility will serve as an integral part of rapid expansion for the Dallas-based biotech, which said it expects to have four open Investigational New Drug applications in 2021. Tayshas most advanced of those is a drug being developed for the treatment of GM2 gangliosidosis, a family of neurodegenerative disorders that includes Tay-Sachs disease and Sandhoff disease.

The other three such programs are looking to treat Rett Syndrome, epilepsy and SURF1 deficiencies.

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Taysha Gene Therapies looks to build on rapid IPO with $85M dev-manufacturing plant in North Carolina - Endpoints News

NEW YORK and CLEVELAND, Dec. 21, 2020 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, today announced that abstracts detailing new interim results from its ABO-102 Phase 1/2 Transpher A study for MPS IIIA and ABO-101 Phase 1/2 Transpher B study for MPS IIIB have been accepted for platform oral presentations during the late-breaking abstract session at the 17th Annual WORLDSymposium being held February 8-12, 2021.

Children born with MPS IIIA and MPS IIIB experience progressive neurodevelopmental decline and loss of motor function that is life-threatening, said Michael Amoroso, Chief Operating Officer of Abeona. We are excited to share new analyses from the Transpher A study that will add to the understanding of the potential for ABO-102 to help preserve neurocognitive development in patients with MPS IIIA when they are treated at a young age, and new results from the Transpher B study that will provide insights into ABO-101s biologic effect in patients with MPS IIIB.

Presentation Details

Title: Updated Results of Transpher A, a Multicenter, Single-Dose, Phase 1/2 Clinical Trial of ABO-102 Gene Therapy for Sanfilippo Syndrome Type A (Mucopolysaccharidosis IIIA)Abstract Number: 390Presenter: Kevin Flanigan, M.D., Center for Gene Therapy at Nationwide Childrens HospitalDate/Time: Friday, February 12, 2021, time to be determined

Title: Updated Results of Transpher B, a Multicenter, Single-Dose, Phase 1/2 Clinical Trial of ABO-101 Gene Therapy for Sanfilippo Syndrome Type B (Mucopolysaccharidosis IIIB)Abstract Number: 407Presenter: Maria Jose de Castro, M.D., Hospital Clnico Universitario Santiago de CompostelaDate/Time: Friday, February 12, 2021, time to be determined

About the Annual WORLDSymposium The WORLDSymposium is designed for basic, translational and clinical researchers, patient advocacy groups, clinicians, and all others who are interested in learning more about the latest discoveries related to lysosomal diseases and the clinical investigation of these advances. For additional information on the 17th Annual WORLDSymposium, please visit https://worldsymposia.org/.

About the Transpher A Study The Transpher A Study (NCT02716246) is an ongoing, two-year, open-label, dose-escalation, Phase 1/2 global clinical trial assessing ABO-102 for the treatment of patients with Sanfilippo syndrome type A (MPS IIIA). The study, also known as ABT-001, is intended for patients from birth to 2 years of age, or patients older than 2 years with a cognitive developmental quotient of 60% or above. ABO-102 gene therapy is delivered using AAV9 technology via a single-dose intravenous infusion. The study primary endpoints are neurodevelopment changes and safety, with secondary endpoints including behavior evaluations, quality of life, enzyme activity in cerebrospinal fluid (CSF) and plasma, heparan sulfate levels in CSF, plasma and urine, and brain and liver volume.

About the Transpher B Study The Transpher B Study (NCT03315182) is an ongoing, two-year, open-label, dose-escalation, Phase 1/2 global clinical trial assessing ABO-101 for the treatment of patients with Sanfilippo syndrome type B (MPS IIIB). The study, also known as ABT-002, is intended for patients from birth to 2 years of age, or patients older than 2 years with a cognitive developmental quotient of 60% or above. ABO-101 gene therapy is delivered using AAV9 technology via a single-dose intravenous infusion. The study primary endpoints are neurodevelopment changes and safety, with secondary endpoints including behavior evaluations, quality of life, enzyme activity in cerebrospinal fluid (CSF) and plasma, heparan sulfate levels in CSF, plasma and urine, and brain and liver volume.

About ABO-102 ABO-102 is a novel gene therapy in Phase 1/2 development for Sanfilippo syndrome type A (MPS IIIA), a rare lysosomal storage disease with no approved treatment that primarily affects the central nervous system (CNS). ABO-102 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells of the CNS and peripheral organs. The therapy is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of glycosaminoglycans in the brain and throughout the body that results in progressive cell damage and neurodevelopmental and physical decline. In the U.S., Abeona holds Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations for the ABO-102 clinical program. In the EU, the Company holds PRIME and Orphan medicinal product designations.

About ABO-101 ABO-101 is a novel gene therapy in Phase 1/2 development for Sanfilippo syndrome type B (MPS IIIB), a rare lysosomal storage disease with no approved therapy that primarily affects the central nervous system (CNS). ABO-101 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the NAGLU gene to cells of the CNS and peripheral tissues. The therapy is designed to address the underlying NAGLU enzyme deficiency responsible for abnormal accumulation of glycosaminoglycans in the brain and throughout the body that results in progressive cell damage and neurodevelopmental and physical decline. In the U.S., Abeona holds Fast Track and Rare Pediatric Disease designations for ABO-101 and Orphan Drug designation in both the U.S. and EU.

About Sanfilippo Syndrome Type A (MPS IIIA) Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the CNS and is characterized by rapid neurodevelopmental and physical decline. Children with MPS IIIA present with progressive language and cognitive decline and behavioral abnormalities. Other symptoms include sleep problems and frequent ear infections. Additionally, distinctive facial features with thick eyebrows or a unibrow, full lips and excessive body hair for ones age, and liver/spleen enlargement are also present in early childhood. MPS IIIA is caused by genetic mutations that lead to a deficiency in the SGSH enzyme responsible for breaking down glycosaminoglycans, which accumulate in cells throughout the body resulting in rapid health decline associated with the disorder.

About Sanfilippo syndrome type B (MPS IIIB) Sanfilippo syndrome type B (MPS IIIB) is a rare and fatal lysosomal storage disease with no approved therapy that primarily affects the central nervous system and is characterized by rapid neurodevelopmental and physical decline. Children with MPS IIIB present with progressive language and cognitive decline and behavioral abnormalities. Other symptoms include sleep problems and frequent ear infections. Additionally, distinctive signs such as facial features with thick eyebrows or a unibrow, full lips and excessive body hair for ones age and liver/spleen enlargement are also present. The underlying cause of MPS IIIB is a deficiency in the NAGLU enzyme responsible for breaking down glycosaminoglycans, which accumulate throughout the body resulting in rapid decline associated with the disorder.

About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases. Abeonas clinical programs include EB-101, its autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa in Phase 3 development, as well as ABO-102 and ABO-101, novel AAV-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively, in Phase 1/2 development. The Companys portfolio also features AAV-based gene therapies for ophthalmic diseases with high unmet medical needs. Abeonas novel, next-generation AIM capsids have shown potential to improve tropism profiles for a variety of devastating diseases. Abeonas fully functional, gene and cell therapy GMP manufacturing facility produces EB-101 for the pivotal Phase 3 VIITAL study and is capable of clinical and commercial production of AAV-based gene therapies. For more information, visit http://www.abeonatherapeutics.com.

Forward-Looking StatementsThis press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. These statements include statements about the Company exploring all strategic options, including the sale of some or all of its assets or sale of the Company. We have attempted to identify forward-looking statements by such terminology as may, will, believe, estimate, expect, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to the potential impacts of the COVID-19 pandemic on our business, operations, and financial condition, the outcome of the strategic review, continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the outcome of any future meetings with the U.S. Food and Drug Administration or other regulatory agencies, the impact of competition, the ability to secure licenses for any technology that may be necessary to commercialize our products, the ability to achieve or obtain necessary regulatory approvals, the impact of changes in the financial markets and global economic conditions, risks associated with data analysis and reporting, and other risks disclosed in the Companys most recent Annual Report on Form 10-K and subsequent quarterly reports on Form 10-Q and other periodic reports filed with the Securities and Exchange Commission. The Company undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

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Abeona Therapeutics Announces Acceptance of Late-Breaker Abstracts Highlighting New Clinical Data for Novel AAV-based Gene Therapies in MPS IIIA and...

First gene therapy to receivefull EU marketing authorization for eligible MLD patients

One-time treatment with Libmeldy has been shown to preserve motor and cognitive function

Achievement shared with research alliance partners Fondazione Telethon and Ospedale San Raffaele

BOSTON and LONDON and MILAN, Italy, Dec. 21, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, and its research alliance partners Fondazione Telethon and Ospedale San Raffaele, today announced that the European Commission (EC) granted full (standard) market authorization for Libmeldy (autologous CD34+ cells encoding the ARSA gene), a lentiviral vector-based gene therapy approved for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in theARSAgene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

MLD is a very rare, fatal genetic disorder caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them, and most pass away before adolescence. Libmeldy is designed as a one-time therapy that aims to correct the underlying genetic cause of MLD, offering eligible young patients the potential for long-term positive effects on cognitive development and maintenance of motor function at ages at which untreated patients show severe motor and cognitive impairments.

Todays EC approval of Libmeldy opens up tremendous new possibilities for eligible MLD children faced with this devastating disease where previously no approved treatment options existed, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. Libmeldy is Orchards first product approval as a company, and I am extremely proud of the entire team who helped achieve this milestone. We are grateful for and humbled by the opportunity to bring this remarkable innovation to young eligible patients in the EU.

With Libmeldy, a patients own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a self-inactivating (SIN) lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying disease with a single treatment.

The EC approval of Libmeldy comes more than a decade after the first patient was treated in clinical trials performed at our Institute, and ushers in a remarkable and long-awaited shift in the treatment landscape for eligible MLD patients, said Luigi Naldini, M.D, Ph.D., director of the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. Our team at SR-Tiget has been instrumental in advancing the discovery and early-stage research of this potentially transformative therapy to clinical trials in support of its registration through more than 15 years of studies supported by Fondazione Telethon and Ospedale San Raffaele, and we are extremely proud of this achievement and what it means for patients and the field of HSC gene therapy.

MLD is a heart-breaking disease that causes immeasurable suffering and robs children of the chance of life, said Georgina Morton, chairperson of ArchAngel MLD Trust. As a community, we have been desperate for a treatment for young MLD patients, and we are incredibly excited to now have such a ground-breaking option approved in the EU.

The marketing authorization for Libmeldy is valid in all 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. Orchard is currently undertaking EU launch preparations related to commercial drug manufacturing, treatment site qualification and market access.

Data Supporting the Clinical and Safety Profile of Libmeldy

The marketing authorization for Libmeldy is supported by clinical studies in both pre- and early- symptomatic, early-onset MLD patients performed at the SR-Tiget. Early-onset MLD encompasses the disease variants often referred to as late infantile (LI) and early juvenile (EJ). Clinical efficacy was based on the integrated data analysis from 29 patients with early-onset MLD who were treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation. Results of this analysis indicate that a single-dose intravenous administration of Libmeldy is effective in modifying the disease course of early-onset MLD in most patients.

Clinical safety was evaluated in 35 patients with MLD (the 29 patients from the integrated efficacy analysis as well as six additional patients treated with the cryopreserved formulation of Libmeldy). Safety data indicate that Libmeldy was generally well-tolerated. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies (AAA) reported in five out of 35 patients. Antibody titers in all five patients were generally low and no negative effects were observed in post-treatment ARSA activity in the peripheral blood or bone marrow cellular subpopulations, nor in the ARSA activity within the cerebrospinal fluid. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For further details, please see the Summary of Product Characteristics (SmPC).

About MLD and Libmeldy

MLD is a rare and life-threatening inherited disease of the bodys 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, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50% and 44% at 10 years for juvenile patients.1

Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), also known as OTL-200, is approved in the European Union for the treatment of MLD in eligible early-onset patients. In the U.S., OTL-200 is an investigational therapy which has not been approved by the U.S. Food and Drug Administration (FDA) for any use. Libmeldy 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 global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs 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. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters inLondonandU.S.headquarters inBoston. For more information, please visitwww.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors 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 andLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, 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 Orchards investor relations website and may include additional social media channels. The contents of Orchards 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.

About Fondazione Telethon, Ospedale San Raffaele and the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget)

Based in Milan, Italy, the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) is a joint venture between the Ospedale San Raffaele, a clinical-research-university hospital established in 1971 to provide international-level specialized care for the most complex and difficult health conditions, and Fondazione Telethon, an Italian biomedical charity born in 1990 and focused on rare genetic diseases. SR-Tiget was established in 1995 to perform research on gene transfer and cell transplantation and translate its results into clinical applications of gene and cell therapies for different genetic diseases. Over the years, the Institute hasgiven a pioneering contribution to the field with relevant discoveries in vector design, gene transfer strategies, stem cell biology, identity and mechanism of action of innate immune cells. SR-Tiget has also established the resources and framework for translating these advances into novel experimental therapies and has implemented several successful gene therapy clinical trials for inherited immunodeficiencies, blood and storage disorders, which have already treated >115 patients and have led through collaboration with industrial partners to the filing and approval of novel advanced gene therapy medicines.

For more information:

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, 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, plans, 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, Orchards business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, and the therapeutic potential of Libmeldy, including the potential implications of clinical data for eligible patients. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards 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 Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the inability or risk of delays in Orchards ability to commercialize Libmeldy, including the risk that we may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. 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 Orchards quarterly report on Form 10-Q for the quarter endedSeptember 30, 2020, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards 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.

Contacts

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

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

1 Mahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature.Journal of Child Neurology2010, DOI:http://doi.org/10.1177/0883073809341669

View original post here:
Orchard Therapeutics Receives EC Approval for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) - GlobeNewswire

Zolgensma is a gene therapy designed to address the genetic root cause of SMA by replacing the missing or defectiveSMN1gene1.It is administered during an intravenous (IV) infusion, delivering a new working copy of the SMN1 gene into a patient's cells, halting disease progression and restoring production of SMN protein1.

"SMA can be a devastating diagnosis for families to receive. Without treatment, many children would not be able to meet important developmental milestones like lifting their head, sitting or walking.Even breathing and swallowing can become difficult in the severe, infant-onset form of this disease," said Dr. Hugh McMillan, Pediatric Neurologist at the Children's Hospital of Eastern Ontario in Ottawa."The approval of Zolgensma in Canada offers children an opportunity to maximize their developmental potential from this one-time therapy.The decision to treat based upon weight may allow children diagnosed slightly later to also benefit from this therapy."

"When I first started diagnosing SMA, I couldn't have imagined that we would see such scientific advancements," said Dr. Nicolas Chrestian, Chief of Paediatric Neurology, specialized in neuromuscular disorders at Centre Hospitalier Mre Enfant Soleil, Universit Laval in Qubec City. "Zolgensma offers, in a single dose, the possibility of halting the progression of this degenerative condition that can rob children of regular developmental milestones."

In Canada each year, approximately one in 10,000 babies are born with SMA,a rare, genetic neuromuscular disease caused by a defective or missingSMN1gene3. Without a functionalSMN1gene, infants with SMA lose the motor neurons responsible for muscle functions such as breathing, swallowing, speaking and walking2. Left untreated, muscles become progressively weaker2,3. In the most severe form, this eventually leads to paralysis and ultimately permanent ventilation or death by age 2 in more than 90%of cases4.

"The SMA community is thrilled to have another treatment option to offer hope to families grappling with an SMA diagnosis. The approval of Zolgensma couldn't come soon enough. We will continue to advocate until everyone who needs access to treatment can benefit from innovations like this," said Susi Vander Wyk, Executive Director, CureSMA Canada.

"Today's announcement about the Canadian approval of Zolgensma is a significant milestone in our journey to reimagine medicine by changing the treatment paradigm for children with SMA." said Andrea Marazzi, Country Head, Novartis Pharmaceuticals Canada. "Our commitment to the SMA community truly comes to life when those that could benefit most from Zolgensma can access it. This is why we continue to work collaboratively with the pan-Canadian Pharmaceutical Alliance, provinces and territories to make this happen as quickly as possible."

The efficacy and safety data supporting the approval of Zolgensma in treating pediatric patients with SMA are derived from completed and ongoing open-label, single-arm, clinical trials in patients with infantile-onset SMA and 2 copies of SMN2 gene; and presymptomatic genetically diagnosed SMA and 2 or 3 copies of SMN2 gene1.

Zolgensma is the only gene therapy approved by Health Canada for the treatment of SMA1. Thirteen treatment sites have been identified in leading healthcare institutions with SMA expertise. The sites are located in: Vancouver, BC; Edmonton, AB; Calgary, AB; Saskatoon, SK; Winnipeg, MB; London, ON; Hamilton, ON; Toronto, ON; Ottawa, ON; Montreal, QC; Quebec City, QC; Halifax, NS.

About Spinal Muscular AtrophySMA is the leading cause of genetic infant death2. Loss of motor neurons cannot be reversed, so SMA patients with symptoms at the time of treatment will likely require some supportive respiratory, nutritional and/or musculoskeletal care to maximize functional abilities5.This is why it is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt irreversible motor neuron loss and disease progression6.Early diagnosis is especially critical in the most severe form, where motor neuron degeneration starts before birth and escalates quickly5. Newborn screening for SMA is currently being implemented in Ontario and piloted in Alberta7,8.

About Novartis in Gene Therapy and Rare DiseaseNovartis is at the forefront of cell and gene therapies designed to halt diseases in their tracks or reverse their progress rather than simply manage symptoms. The company is collaborating on the cell and gene therapy frontier to bring this major leap in personalized medicine to patients with a variety of diseases, including genetic disorders and certain deadly cancers. Cell and gene therapies are grounded in careful research that builds on decades of scientific progress. Following key approvals of cell and gene therapies by health authorities, new treatments are being tested in clinical trials around the world.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2019, the company invested $51.8 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,500 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About Novartis globallyNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

Zolgensma is a registered trademark of Novartis Gene Therapies.

Novartis Gene Therapies has an exclusive, worldwide license with Nationwide Children's Hospital to both the intravenous and intrathecal delivery of AAV9 gene therapy for the treatment of all types of SMA; has an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for thein vivogene therapy treatment of SMA in humans; an exclusive, worldwide licensing agreement with Gnthon forin vivodelivery of AAV9 vector into the central nervous system for the treatment of SMA; and a non-exclusive, worldwide license agreement with AskBio for the use of its self-complementary DNA technology for the treatment of SMA.

References

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations, Julie Schneiderman, +1 514 633 7873, E-mail: [emailprotected]

Originally posted here:
Health Canada approves Zolgensma, the one-time gene therapy for pediatric patients with spinal muscular atrophy (SMA) - Canada NewsWire

I have heard about people using genes to treat diseases nowadays, but I am not sure what this gene therapy means.

Gene therapy involves trying to alter or modify the genes inside your bodys cells in order to treat or stop a disease.

Since 2017, the US Food and Drug Administration (FDA) has approved three different types of gene therapy.

Maybe we can start at the beginning: what are genes?

Genes are the basic physical and functional unit of heredity.

Our genes are made out of DNA (deoxyribonucleic acid).

Each person has two copies of each gene one inherited from your mother and the other inherited from your father.

Each human being has around 20,000 to 25,000 genes.

These genes code for the way your body and mind are structured.

Some genes act as instructions (a blueprint) for your body to make various proteins, which in turn form your cells and organs, and the enzymes and hormones that regulate your body.

Other genes do not code for proteins.

Most genes are the same for all human beings, which is why we all look like human beings (and not a kangaroo, fish, bird or an alien)!

However, just under 1% of our genes vary slightly between each person.

That is why we have different races, heights, propensity for different diseases, curly or straight hair, etc.

These small differences also contribute to why we all look different from one another.

Genes that dont work as they should also cause diseases in the human body.

What types of diseases are caused by faulty genes?

These are what we call genetic disorders.

A genetic disease is any type of disease caused by an abnormality in our genetic blueprint.

This abnormality can range from very minor to significantly major.

What we consider minor is, for example, a small mutation in the DNA of a single gene resulting in the change of a single base protein.

What we consider major is a gross chromosomal abnormality, such as the addition of a whole chromosome or the subtraction of one.

Some genetic disorders are inherited from our parents.

Others are caused by mutations due to our environment.

Examples of single gene disorders, which are caused by the alteration of just one gene in our bodies, are:

Examples of multifactorial inheritance, which are caused by a combination of environmental factors and mutations in many of our genes, are:

If we inherited these genes from our parents, then how can we possibly modify or alter them? This sounds terribly like science fiction.

We are rapidly approaching that era where what used to be science fiction could become part of our everyday life.

In gene therapy, scientists can:

How do they do this? Do they have to harvest my cells? Im scared just thinking about it!

Many of the vectors are viruses, especially adenoviruses (not coronaviruses!).

Viruses have a natural ability to deliver genetic material into our cells.

After all, their main purpose is to attach themselves to cells and reproduce themselves.

Sometimes, the vector or virus is injected straight into our bodies, where they will deliver the gene that will modify our cells.

They are injected straight into the part of our body that has those defective cells.

Other times, we have to harvest healthy tissue from our body that needs to be modified.

These are usually tissues containing immune cells or stem cells, e.g. blood or bone marrow.

These tissue samples are then taken to the lab and specific cells are separated out.

The viral vector containing the corrective gene is then introduced to the harvested cells in the lab.

The modified cells are left to multiply, and then injected back into us.

Once inside our bodies, they will continue to multiply and eventually treat the disease or correct the defect within us.

Learn more about gene therapy in the next Tell Me About column on Dec 31 (2020).

Dr YLM graduated as a medical doctor, and has been writing for many years on various subjects such as medicine, health, computers and entertainment. For further information, email starhealth@thestar.com.my. The information contained in this column is for general educational purposes only. Neither The Star nor the author gives any warranty on accuracy, completeness, functionality, usefulness or other assurances as to such information. The Star and the author disclaim all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.

Read more here:
What is gene therapy? - The Star Online

University of Minnesota Twin Cities researchers in the Department of Chemistry have created a new polymer to deliver DNA and RNA-based therapies for diseases. For the first time in the industry, the researchers were able to see exactly how polymers interact with human cells when delivering medicines into the body. This discovery opens the door for more widespread use of polymers in applications like gene therapy and vaccine development.

The research is published in the Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed multidisciplinary scientific journal.

Gene therapy involves altering the genes inside the bodys cells to treat or cure diseases. It requires a carrier that packages the DNA to deliver it into the celloftentimes, a virus is used as a carrier. Packaging of nucleic acids is also used in vaccines, such as the recently developed messenger RNA (mRNA) COVID-19 vaccine, which is enclosed in a lipid.

The research team is led by chemistry professor Theresa Reineke and associate professor Renee Frontiera. Reinekes lab synthesizes polymers, which are long-chain molecules that make up plastics, to use for packaging the nucleic acids instead.

Its kind of like ordering something from Amazon, and its shipped in a box, Reineke explained. Things get broken if theyre not delivered in a package. Thats basically what were doing here but on a nano-level. Were taking these really sensitive RNA and DNA cargo that are susceptible to enzymatic degradation, that wont get to their target unless you have something to protect them.

The researchers designed the copolymer using quinine, a naturally occurring substance used in tonic water, and 2-hydroxyethyl acrylate (HEA), which makes the material soluble and is used in a variety of personal care and medical materials. Because quinine is fluorescent, the research team was able to track the DNA package throughout the body and into the cells using Raman spectroscopy, a chemical imaging technique.

Weve discovered a new packaging tool with this natural product thats important for all of these high-flying, important fields like gene therapy and vaccines, said Reineke, who is also a Distinguished McKnight University Professor. And, it works in a variety of cell-types. On top of that, its got all of these cool featuresits fluorescent, we can track it, its Raman active, and that allowed us to understand a lot of fundamentals about these packaging systems that were impossible to probe before we incorporated this natural product.

Polymer-based drug delivery is significantly cheaper than using viruses, especially for gene therapy, which can cost up to $2 million for a single injection. However, the main barrier preventing widespread polymer use was that scientists didnt know a lot about how the polymer package actually interacts with cells in the body.

This research helps clear up that uncertainty. Frontieras lab specializes in chemical imaging. Using Raman spectroscopy, they discovered that a cells own proteins play a key role in unpacking the nucleic acid cargo once the polymer carrier enters the cell.

Its very satisfying to know how this is actually happening, what the process of delivery is, and to actually see that in real-time, Frontiera said. A key point is that these polymers also work very well. For all the beneficial attributes, theyre also incredibly effective at getting the payload into cells, and we were able to tell why, which doesnt always happen in this field.

Reineke and Frontiera have been collaborating since 2013. Reinekes lab has patented the quinine polymers, and the researchers hope that a company might license this technology in the future. The College of Science and Engineering team also collaborated with University of Minnesota Medical School Distinguished McKnight University Professor Jakub Tolar to test the effectiveness of the polymer carriers in relevant cell types.

Other members of the research team include chemistry researchers Craig Van Bruggen (Ph.D. student) and David Punihaole (postdoctoral associate), chemical engineering and materials science student Andrew Schmitz, and genetics Ph.D. student Allison Keith. This research was funded by the National Science Foundation and the National Institutes of Health.

Read the full research paper entitled Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism on the PNAS website.

Read more from the original source:
Researchers discover new way to deliver DNA-based therapies for diseases - UMN News

People with hemophilia B lack a protein that helps their blood clot, so they rely on lifelong infusions of that protein to manage their disease. UniQure and CSL Behrings hemophilia B gene therapy could transform chronic care into a one-time treatmentand its latest data suggest it could work for patients considered unsuitable for gene therapy.

The treatment, etranacogene dezaparvovec, curbed bleeding episodes and nearly eliminated the need for infusions of clotting Factor IX (FIX) in a phase 3 study testing it in severe or moderately severe hemophilia B. The study, HOPE-B, found that 26 weeks after treatment, the gene therapy had reduced bleeds that needed treatment by 91%, with 87% of 54 patients reporting such bleeds. Eighty-three percent of the patients reported no bleeds at all, including suspected bleeds that did not require treatment.

RELATED: BioMarin's hemophilia gene therapy 'Roc solid' after 4 years

Benefits of 5KL When Outsourcing Late-phase Biologics Drug Substance Manufacturing

During this webinar, attendees will learn about Thermo Fisher Scientifics new 5KL bioreactor and how it benefits clients who outsource late-phase biologics drug substance manufacturing. An introduction of the 5KL bioreactor will be provided, as well as application data around performance and scalability, process economy comparison with traditional stainless steel bioreactors, and decision criteria that could be helpful in choosing between different cell culture strategies. Register Today!

The treatment also boosted FIX activity to an average of 37.2%, up from less than 2% at the start of the trial, meeting its primary endpoint.

The study, to be presented virtually Tuesday at the annual meeting of the American Society of Hematology, found that nearly all the patients52 out of 54, or 98%no longer needed infusions of FIX to prevent bleeding episodes. Of the remaining two patients, one suffered an infusion reaction during treatment and did not get the full gene therapy dose, while the other had very high levels of antibodies that neutralize the adeno-associated virus (AAV) used to deliver the treatment.

Many people have a natural immunity to AAVs because theyre exposed to them in the environment. Though useful for fighting off infection, this immunity can render gene therapies ineffective. That appears not to be the case with uniQure and CSLs treatment. The patient for whom the gene therapy did not work was an outlier, with antibody levels nearly five times as high as the level expected in more than 95% of the general population. In patients with more typical antibody levels, investigators saw no correlation between the presence of those antibodies and FIX activity, the company said in a statement.

Importantly, these data also show that those patients in the trial who may not have been eligible for other gene therapies because they had pre-existing neutralizing antibodies (NAbs) have achieved results with etranacogene dezaparvovec that are comparable to the results of patients who did not have pre-existing NAbs, Steven Pipe, M.D., a professor of pediatrics and pathology at the University of Michigan and the studys lead investigator, said in a statement.

RELATED: CSL to pay $450M to buy uniQure's hemophilia B gene therapy

This is an important distinction as this is the only known clinical trial that has maximized patient eligibility in this way. The initial data also show that etranacogene dezaparvovec has been generally well tolerated to date, he said.

Most of the side effects were mild (82%). The most common treatment-related side effect was elevated liver enzymes, which affected 17% of patients but was treated effectively with steroids. Infusion reactions and flu-like symptoms each affected 13% of patients.

The data come five months after CSLpicked up the global rights to etranacogene dezaparvovec for $450 million upfront. These latest data set up the companies in a battle to bring a new hemophilia B gene therapy to market, pitting them against the likes of Pfizer and Spark/Roche.

The rest is here:
ASH: UniQure/CSL hem B gene therapy curbs bleeding in phase 3even in patients with anti-AAV antibodies - FierceBiotech

Bayer has established a new strategic platform focused on cell and gene therapy, following its AskBio acquisition in October.

The new cell and gene therapy platform will house both AskBio and another of Bayers recently acquired firms, BlueRock Therapeutics, under one roof.

Bayer will seek to strengthen its own internal cell and gene therapy capabilities, with the newly established platform also enabling it to pursue external opportunities to bolster its presence in this area.

This is a defining moment for Bayer. Cell and gene therapies are leading innovation in healthcare, and it is our goal to be at the forefront of this revolution in science, said Stefan Oelrich, a member of the board of management, Bayer AG and president Pharmaceuticals Division.

Bayer paid an initial $2bn to gain full rights to AskBios gene therapy platform, which included an intellectual property portfolio and an established contract development and manufacturing organisation (CDMO).

AskBios adeno-associated gene therapy platform has already shown promise in a number of diseases, with the companys lead research programmes focused on Pompe disease, Parkinsons and congestive heart failure.

The German pharma company also bought out its private equity partner Versant Venture and founders in its cell therapy joint venture BlueRock Therapeutics for $240m.

BlueRock was established in late 2016 with $225m in start-up funding from Bayer and investment firm Versant, shortly after Bayer backed gene-editing specialist Casebia via its Leaps by Bayer investment arm.

The goal [of the platform] is to build robust platforms with broad application across different therapeutic areas, Bayer added in a statement.

The company also said that it has a vibrant cell and gene therapy pipeline with five advanced assets, as well as over 15 preclinical candidates.

The emerging bio revolution represents a once-in-a-lifetime opportunity and a new era for Bayer, said Wolfram Carius, head of Bayers new cell and gene therapy platform.

A dedicated C> Platform is vital to accelerate innovation at its source, and to ensure its translation into tangible therapies for patients who have no time to wait, he added.

Go here to read the rest:
Bayer strengthens cell and gene therapy focus with new platform - PMLiVE

German pharma Bayer is moving into cell therapy R&D with its latest pact focusing on tough-to-treat lung cancers with Atara Biotherapeutics.

Bayer has been moving deeply into gene therapies over the past few years, but it's now entering the CAR-T research space in its Atara deal. CAR-T has been focused heavily on blood cancers, where there have been some amazing successes (but also serious safety worries), but this pact is focusing on a tougher area for cell therapy, namely solid tumors.

The deal focuses on off-the-shelf T-cell immunotherapy ATA3271 for high mesothelin-expressing tumors, with a focus on more rare and tough-to-treat high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small cell lung cancer.

Benefits of 5KL When Outsourcing Late-phase Biologics Drug Substance Manufacturing

During this webinar, attendees will learn about Thermo Fisher Scientifics new 5KL bioreactor and how it benefits clients who outsource late-phase biologics drug substance manufacturing. An introduction of the 5KL bioreactor will be provided, as well as application data around performance and scalability, process economy comparison with traditional stainless steel bioreactors, and decision criteria that could be helpful in choosing between different cell culture strategies. Register Today!

The financials break down like this: Atara gets $60 million upfront, with up to $610 million on the table in biobucks. The biotech will lead IND-enabling studies and process development for ATA3271, while Bayer will be responsible for submitting the IND and then will take over R&D and sales work.

Atara will continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and a test already started.

RELATED: Bayer creates cell and gene therapy platform to support partners

For a limited time, Bayer also has a nonexclusive right to negotiate a license for additional Atara CAR-T product candidates.

This transaction is a fundamental element of Bayers new Cell & Gene Therapy strategy. It strengthens our development portfolio through allogeneic cell therapies and consolidates our emerging leadership in the field, said Wolfram Carius, head of Bayers Cell & Gene Therapy Unit.

We look forward to collaborating with Atara to develop off-the-shelf CAR T-cell therapies for patients with difficult-to-treat cancers.

Germanys Bayer has moved into cell and gene therapies on multiple fronts in recent years, buying up induced pluripotent stem cell specialist BlueRock Therapeutics and adeno-associated virus gene therapy player Asklepios BioPharmaceutical while investing in a clutch of other biotechs. The deals have given Bayer a pipeline of five advanced assets and more than 15 preclinical prospects.

It has backed other CAR-T players over the years, including CAR alternative player Triumvira and Century Therapeutics, but the Atara deal takes it further into directly working on a cell therapy.

This exciting collaboration between Atara and Bayer will accelerate the development of mesothelin-targeted CAR T-cell therapies for multiple solid tumors and helps us advance the power of our allogeneic cell therapy platform to patients as quickly as possible, added Pascal Touchon, president and CEO of Atara.

Bayers proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Ataras capabilities and complements our leading allogeneic T-cell platform.

View original post here:
After boosting gene therapy focus, Bayer signs up to new cell therapy pact with Atara - FierceBiotech

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --The gene therapy etranacogene dezaparvovec substantially increased production of the blood clotting protein factor IX among 52 patients in the largest and most inclusive hemophilia B gene therapy trialto date. The trial is also the first to include patients with certain immune system markers and found that they did not appear to confer any increased risks, a finding that could significantly broaden the number of patients who may be eligible for gene therapy.

A majority of trial participants (96%) successfully discontinued factor IX replacement therapy after receiving the gene therapy and have been producing their own factor IX for six months. The findings suggest gene therapy could, with a single treatment, give patients the ability to maintain factor IX levels and reduce or eliminate the need for additional factor IX replacement therapy, according to researchers.

"Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life," said senior study authorSteven W. Pipe, MD,of the University of Michigan, Ann Arbor. "Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life."

Hemophilia B, which accounts for about one-fifth of hemophilia cases, is caused by an inherited mutation of the gene for factor IX. Lacking the ability to produce the blood clotting factor IX, patients with hemophilia B can suffer uncontrolled bleeding, including internal and joint bleeding that leads to joint deterioration and chronic pain.

Factor IX replacement therapy can reduce bleeding associated with hemophilia B, but it requires weekly or biweekly infusions to maintain factor IX levels, a burdensome regimen that costs several hundred thousand dollars per year. In gene therapy, viral particles are used to shuttle engineered genes to cells in the liver. These genes replace the patient's faulty factor IX gene, allowing the patient's own body to produce factor IX on an ongoing basis. While several gene therapies for hemophilia have shown promise in early phase trials, the study is the first phase III trial to test the approach in a large and diverse array of patients, said Dr. Pipe.

Fifty-four patients enrolled in the study; all were dependent on factor IX replacement therapy, and 70% had bleeding episodes in the six months prior to the study despite this prophylactic treatment. After receiving the etranacogene dezaparvovec gene therapy via a single infusion lasting roughly one hour, factor IX activity increased rapidly from a baseline of up to 2% (moderate to severe hemophilia) to a mean of 37% (very mild hemophilia) at 26 weeks, meeting the trial's primary endpoint. At that level, a patient's bleeding risk is essentially the same as someone without hemophilia, Dr. Pipe noted.

Seventy-two percent of patients reported no bleeding events in the 26 weeks after receiving the gene therapy. "This tells us that the bleeding phenotype can be corrected through this treatment, which is a remarkable achievement," said Dr. Pipe. Fifteen patients experienced some bleeding, which the researchers indicate is not unexpected given that many of the patients had severely affected joints entering the trial.

"What we've seen from patients in the study is that they really don't have to think about their hemophilia anymore," said Dr. Pipe. "The transformative nature that we hear from the patient stories is, to me, the most important outcome from this study."

The trial is also the first to attempt gene therapy in patients with neutralizing antibodies, a component of the immune system that helps the body fight pathogens. About 40% of trial participants had antibodies to adeno-associated virus serotype 5, or AAV5, the viral vector used in etranacogene dezaparvovec. "In any other trial protocol, these patients would not have been eligible to participate," Dr. Pipe noted.

Previous trials have excluded such patients from gene therapies that use viral vectors under the assumption that antibodies could either block the uptake of the viral vectors in the liver or trigger a dangerous immune response to the therapy. The trial found no evidence of either problem, suggesting neutralizing antibodies do not preclude successful gene therapy.

Two patients did not respond to the gene therapy. One did not receive a full dose because the infusion was stopped after the patient showed signs of a reaction to the infusion. The other had a level of neutralizing antibodies about five times higher than any other patient. Since other patients with neutralizing antibodies responded well to the therapy regardless of their level of antibodies, this finding suggests antibodies may pose a problem only at extremely high levels.

No treatment-related serious adverse events were reported. Adverse events were relatively common, occurring in 68% of patients, but most were mild and related to the infusion itself. Nine patients showed evidence of an immune response to the therapy, which was resolved in all cases with a course of corticosteroids.

The researchers will continue to follow patients for five years. Patients will be assessed for sustained factor IX production and effective bleed control over 52 weeks, as well as patient-reported outcome measures to assess impact on quality of life.

Steven W. Pipe, MD, University of Michigan, Ann Arbor, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Gene Therapy for Hemophilia B Found Safe and Effective in First Phase III Trial - PRNewswire

One of the ways scientists hope to offer better treatments for vision loss is through gene therapy, where carefully selected genetic material is injected into the eyes to address mutations. Researchers have been left surprised by the effectiveness of an experimental form of this treatment, which involved an injection into one eyeball yet improved vision across both.

Gene therapies have the potential to treat all kinds of health conditions, ranging from cancer, to diabetes in dogs, to obesity and damaged spinal cords. One area where we're seeing some really exciting progress is in hereditary vision loss, with studies demonstrating the potential of gene therapy to treat color blindness, progressive retinal diseases and glaucoma, with some recently receiving approval from the FDA.

This latest study was conducted by scientists at the University of Cambridge, the University of Pittsburgh and Paris Institut de la Vision, and focuses on a form of inherited vision loss called Leber hereditary optic neuropathy (LHON). This affects around one in 30,000 people and usually occurs in young folks aged in their 20s and 30s, destroying their retinal ganglion cells and in turn the optic nerve. Once the condition takes hold, vision can deteriorate to the point where the subject is considered legally blind in just a matter of weeks, with recovery occurring in less than 20 percent of cases.

The majority of patients suffer from the same mutation affecting the MT-ND4 gene, so the researchers were hopeful of targeting this mutation as a way of improving treatment outcomes for sufferers of LHON. They trialed their gene therapy as part of a study involving 37 patients who had suffered vision loss in the preceding six to 12 months. This meant injecting a viral vector packed with a modified complementary DNA called rAAV2/2-ND4 into the vitreous cavity at the back of just one eye, with a sham treatment injected into the other eye.

We expected vision to improve in the eyes treated with the gene therapy vector only, says study author Dr Yu-Wai-Man. Rather unexpectedly, both eyes improved for 78 percent of patients in the trial following the same trajectory over two years of follow-up.

To investigate the reasons behind this unexpected outcome, the team studied the gene therapys effects in macaques, which have a similar vision system to humans. This enabled them to analyze the tissues from different parts of the eye to see how the viral vector DNA had spread. This provided evidence of interocular diffusion, with the viral vector DNA turning up in the retina, optic nerve and anterior segment of the untreated eye.

As someone who treats these young patients, I get very frustrated about the lack of effective therapies, says senior investigator Dr Sahel, from the University of Pittsburgh. These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.

The research was published in the journal Science Translational Medicine.

Source: University of Cambridge

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Single gene therapy injection surprisingly boosts vision in both eyes - New Atlas

Shares in Rocket Pharmaceuticals have been living up to their name, shooting up following encouraging early-stage clinical trial results from a gene therapy for a serious inherited rare heart disease.

Results came from a phase 1 trial of RP-A501 for treatment of Danon Disease and sent shares up 75% on the Nasdaq to more than $56, a five-year high.

The surging stock price indicates the markets confidence in gene therapy products after the successful launch of products such as Roche/Spark Therapeutics Luxturna, a gene therapy for a rare inherited eye disease.

Danon Disease is a rare X-linked disorder caused by genetic mutations in the LAMP2 gene and the therapy works by instructing the body to express a healthy copy of the LAMP2B protein in order to correct the condition.

The disease that affects boys and men more severely causes accumulation of autophagosomes tiny structures that cause cells internal structures to break down in the heart muscle and other tissues.

Together with a build-up of glycogen this can lead to severe and frequently fatal degradation of the heart muscle.

RP-A501 could be the first gene therapy for the disease and the early data showed a positive increase in cardiac protein expression.

As of November, three patients have been treated with a low dose of the therapy and two have been treated with a high dose.

An early trial readout showed two patients with LAMP2B expression that was 50% more than normal, measured nine and 12 months after treatment.

A 15%-20% increase could lead to clinically meaningful improvements in cardiac function and the trial reported a 50% decrease in a key biomarker of heart failure.

There was also a reduction in myocardial cell disarray and a visible reduction in autophagic vacuoles, a hallmark of the disease.

The company also noted stabilisation of three other measures a heart failure biomarker known as BNP, plus levels of transaminases and creatine kinase that also indicate skeletal and heart muscle damage.

However one patient who received the highest dose and had a degree of immunity to the adeno-associated virus used in the therapy had an immune reaction classified as a serious adverse event.

Rocket said the event was likely due to complement activation, resulting in reversible thrombocytopenia and acute kidney injury requiring a short round of haemodialysis.

The patient returned to baseline within three weeks and regained normal kidney function.

DrBarry Greenberg, director of the Advanced Heart Failure Treatment Program atUC San Diego Health, Professor of Medicine atUC San Diego School of Medicine, and the principal investigator said: Children with Danon Disease live with a heavy disease burden. Young boys are often severely afflicted.

They show evidence of early onset skeletal muscle weakness and heart disease that can progress rapidly to end-stage with death occurring on the average before age 20. A heart transplant can be performed but is not curative and is associated with its own significant problems.

The results-to-date for this first investigational gene therapy for monogenic heart failure show the potential for direct clinical benefit without emergence of unanticipated side effects of therapy.

The company has also begun a stock offering of $175 million in shares to fund further development following the results.

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Rocket Pharmaceuticals in orbit after gene therapy read-out - - pharmaphorum

Study results from an open-label, single-dose, multi-center, multinational phase III trial, presented during the late-breaking abstract session of the all-virtual 62nd American Society of Hematology (ASH) Annual Meetings show that etranacogene dezaparvovec (previously known was AAV5-hFIXco-Padua; AMT-061; uniQure/CSL Behring), an investigational gene therapy for hemophilia B, is safe and effective.

The two most common types of hemophilia are hemophilia A, in which patients is lack of clotting Factor VIII, and hemophilia B, caused by a lack of the ability to produce the blood clotting factor IX as the result of an inherited mutation of the gene for factor IX.

Both types of hemophilia can lead to spontaneous and uncontrolled bleeding into muscles, organs, and joints as well as prolonged bleeding following injuries or surgery, which leads to joint deterioration and chronic pain.

Hemophilia B, which accounts for about one-fifth of hemophilia cases.

Clinical trialThe study of etranacogene dezaparvovec recruited adult male patients with severe or moderate-severe hemophilia B.

The results of the study demonstrated that a single administration of the gene therapy etranacogene dezaparvovec led to sustained increases of Factor IX to functionally curative levels capable of eliminating the need for regular infusions to control and prevent bleeding episodes. As a result, most patients were able to stop intensive intravenous regimens. The studys authors believe that the results may open doors for patients previously not included in gene therapy trials.

Blood clotting proteinIn the trial included 52 patients and is the largest and most inclusive hemophilia B gene therapy trial to date. The trial is also the first to include patients with certain immune system markers and found that they did not appear to confer any increased risks, a finding that could significantly broaden the number of patients who may be eligible for gene therapy.

A majority of trial participants (96%) successfully discontinued factor IX replacement therapy after receiving the gene therapy and have been producing their own factor IX for six months. The findings suggest gene therapy could, with a single treatment, give patients the ability to maintain Factor IX levels and reduce or eliminate the need for additional factor IX replacement therapy, according to researchers.

Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life, said senior study author Steven W. Pipe, M.D., of the University of Michigan, Ann Arbor, Michigan, who presented the result of the study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time.

Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life, Pipe added.

Replacement therapyFactor IX replacement therapy can reduce bleeding associated with hemophilia B, but it requires weekly or biweekly infusions to maintain factor IX levels, a burdensome regimen that costs several hundred thousand dollars per year.

In gene therapy, viral particles are used to shuttle engineered genes to cells in the liver. These genes replace the patients faulty factor IX gene, allowing the patients own body to produce factor IX on an ongoing basis. While several gene therapies for hemophilia have shown promise in early phase trials, the study is the first phase III trial to test the approach in a large and diverse array of patients, Pipe said.

Fifty-four patients enrolled in the study; all were dependent on factor IX replacement therapy, and 70% had bleeding episodes in the six months prior to the study despite this prophylactic treatment.

After receiving the etranacogene dezaparvovec gene therapy via a single infusion lasting roughly one hour, factor IX activity increased rapidly from a baseline of up to 2% (moderate to severe hemophilia) to a mean of 37% (very mild hemophilia) at 26 weeks, meeting the trials primary endpoint.

At that level, a patients bleeding risk is essentially the same as someone without hemophilia, Pipe noted.

Seventy-two percent of patients reported no bleeding events in the 26 weeks after receiving the gene therapy.

This tells us that the bleeding phenotype can be corrected through this treatment, which is a remarkable achievement, Pipe said.

Fifteen patients experienced some bleeding, which the researchers indicate is not unexpected given that many of the patients had severely affected joints entering the trial.

What weve seen from patients in the study is that they really dont have to think about their hemophilia anymore. The transformative nature that we hear from the patient stories is, to me, the most important outcome from this study, Pipe said.

Neutralizing antibodiesThe trial is also the first to attempt gene therapy in patients with neutralizing antibodies, a component of the immune system that helps the body fight pathogens. About 40% of trial participants had antibodies to adeno-associated virus serotype 5, or AAV5*, the viral vector used in etranacogene dezaparvovec.

In any other trial protocol, these patients would not have been eligible to participate, Pipe noted.

Previous trials have excluded such patients from gene therapies that use viral vectors under the assumption that antibodies could either block the uptake of the viral vectors in the liver or trigger a dangerous immune response to the therapy. The trial found no evidence of either problem, suggesting neutralizing antibodies do not preclude successful gene therapy.

Two patients did not respond to gene therapy. One did not receive a full dose because the infusion was stopped after the patient showed signs of a reaction to the infusion. The other had a level of neutralizing antibodies about five times higher than any other patient. Since other patients with neutralizing antibodies responded well to the therapy regardless of their level of antibodies, this finding suggests antibodies may pose a problem only at extremely high levels.

No treatment-related serious adverse events were reported. Adverse events were relatively common, occurring in 68% of patients, but most were mild and related to the infusion itself. Nine patients showed evidence of an immune response to the therapy, which was resolved in all cases with a course of corticosteroids.

The researchers will continue to follow patients for five years. Patients will be assessed for sustained factor IX production and effective bleed control over 52 weeks, as well as patient-reported outcome measures to assess the impact on health-related Quality of Life (hrQoL).

Note* Adeno-associated virus serotype 5- (AAV5-) based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials. Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). The investigational agent has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and access to the Priority Medicines (PRIME) regulatory initiative by the European Medicines Agency.

Clinical trialsHOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients NCT03569891

Reference[1] Pipe SW, Recht M, Key NS, Leebeek FWG, Castaman G, Lattimore SU, Van der Valk P, Peerlinck K, et al. LBA-6 First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies [Abstract LBA-6]

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ASH 2020: Novel Gene Therapy Found to be Safe and Effective in Treatment of Hemophilia B - OncoZine

bluebird bio has presented long-term data from its Zynteglo one-time gene therapy for the blood disorder beta-thalassaemia, as the company continues talks with payers in Europe to bring the ultra-pricey treatment to market.

The European Medicines Agency (EMA) has granted a conditional marketing authorisation for the drug that will be marketed as Zynteglo (betibeglogene autotemcel), meaning its licence must be renewed each year until confirmatory data is available.

Results announced at the American Society of Hematology could help bluebird make the case for the long-term use of the therapy as the treatment approaches the market in Europe.

In the US, Zynteglo has hit a speed-bump with the FDA, which is asking for more information about production facilities before a review of clinical data can begin.

Of the 10 patients enrolled in the ongoing long-term study (LTF-303) from a phase 3 programme, 9/10 (90%) were transfusion independent (TI) and all these patients remain transfusion independent.

David Davidson, chief medical officer at bluebird, said: All of the patients in our phase 3 studies who achieved transfusion independence have maintained it, with the durability of the treatment effect underscored by patients from our earlier studies reaching their five-year anniversaries of freedom from transfusions.

In a group of patients aged under 18 from the Northstar-2 and Northstar-3 phase 3 studies, 87% (13 out of 15) achieved TI and remained so.

In a long-term follow-up 53% of patients who achieved TI and restarted iron chelation have since stopped and 30% who achieved TI now receive phlebotomy to reduce iron levels.

Davidson added: Transfusion independence has been observed in paediatric, adolescent and adult patients and across genotypes suggesting outcomes with this gene therapy may be consistent regardless of age or genotype.

In Europe bluebird has set a price of up to $1.58 million euros for a single shot.

This is paid in instalments, with 315,000 euros paid up front and four additional payments due only if the treatment continues to be effective.

Zynteglo is already launched in Germany and is nearing the end of its year of free pricing.

But its fair to say that the therapy wont come cheaply even though most member states will likely end up negotiating a lower price.

In England, cost-effectiveness body NICE is reviewing Zynteglo and is due to publish draft document early in the new year.

Although its too early to say how the review will go, NICE will be looking for more certainty on the long-term effects of the therapy.

The latest data wont be part of the submission to NICE, but the company hopes that an ongoing review of the cost-effectiveness bodys methodology will help novel gene therapies get to market.

Nicola Redfern, general manager of bluebird bio UK, is hopeful that NICE will refine its existing Quality Adjusted Life Year (QALY) and find better ways to deal with uncertainties in clinical data.

How we deal with uncertainties is going to be fundamentally important, she said.

Another issue to address is the discount rate NICE uses to calculate the value of medicines and their long-term impact on patients lives.

The 3.5% discount rate currently used means that these benefits reduce quickly over time in the view of NICE and Redfern agrees with NICEs own proposals to adopt the 1.5% discount rate used by the Treasury.

We agree with NICE that there is already evidence to bring it in line with the rate in the Treasury Green Book.

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Bluebird trumpets long-term data from beta-thalassaemia gene therapy - - pharmaphorum

This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Childrens Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta-thalassemia. (Update: edit to fix attribution).

These diseases have long been linked when it comes to gene therapy ideas, because both of them have defects in the hemoglobin protein as their cause. And its long been thought that both could be treated by getting adults to re-express the fetal hemoglobin protein its on a different gene entirely, and thus does not have any of the genetic problems that affect the adult hemoglobin gene. The normal course of events is for babies to stop expressing the fetal form and switch over to regular hemoglobin, and its been worked out that a particular transcription factor called BCL11a is a key player in that transcriptional repression of the fetal hemoglobin gene. That plays right into the usual way that we tend to think about therapeutic possibilities: whether its enzymes, receptors, or expression of whole proteins, we have a lot more tools to mess things up and interrupt processes than we have to make them run faster or better. So the possibility of interrupting BCL11as function has been a tempting one for many years.

Its hard to do by traditional means, though. (Full disclosure: I have, at different times in my career, been involved with such efforts, but none have ever come near the clinic.) Transcription factors are notoriously hard to get a handle on with small molecule therapeutics, and many unsuccessful runs have been taken at BCL11a ligands to try to interrupt its functions in one way or another. My general impression is that the protein doesnt much care about recognizing small-molecule ligands (and its far from the only one in that category, for sure). Youd think that if you ran a few hundred thousand (or a few million) various molecules past any given protein that youd find a few of them that bind to it, but that assumption is too optimistic for most transcription factors. Youre also going to have a hard row to hoe (to use an old Arkansas expression) if you try to break up their interactions with their DNA binding sites: a significant amount of capital has gone down the chute trying to get that to work, with (as far as I can tell) not much to show for it.

Theres another complication: BCL11a has a lot of other functions. Every protein has a lot of other functions, but for transcription factors, the issue can be especially fraught. If you had a small molecule that really did interfere with its activity, what would happen if you just took a stiff dose of it? Probably a number of things, including some interesting (and not necessarily welcome) surprises. There have been a number of ideas about how to get around this problem, but a problem it is.

So its on to biological mechanisms. The BCH team reports on using RNA interference to do the job they get cells to express a short hairpin RNA that shuts down production of BCL11a protein, with some microRNA work to target this to the right cell lines. And the Vertex/CRISPR team, naturally, uses CRISPR itself to go in and inactivate the BCL11a gene directly. Both approaches take (and have to take) a similar pathway, which is difficult and expensive, but still the best shot at such therapies that we have. You want the fetal hemoglobin expressed in red blood cells, naturally, and red blood cells come from CD34+ stem cells in the bone marrow. Even if you havent thought about this, you might see where its going: you take a bone marrow sample, isolate these cells, and then do your genetic manipulation to them ex vivo. Once youve got a population of appropriately re-engineered cells ready to go, you go kill off the bone marrow in the patient and put the reworked cells back in, so theyre the only source there for red blood cells at all. A bone marrow transplant, in other words a pretty grueling process, but definitely not as much as having some sort of blood-cell-driven cancer (where the therapy uses compatible donor cells from someone else without such a problem), or as much as having full-on sickle cell disease or tranfusion-dependent thalassemia.

You can also see how this is a perfect setup for gene therapy: theres a defined population of cells that you need to treat, which are available in a specific tissue via a well-worked-out procedure. The problem youre trying to correct is extremely well understood in fact, it was the first disease ever characterized (by Linus Pauling in 1949) as purely due to a genetic defect . And the patients own tissue is vulnerable to chemotherapy agents that will wipe out the existing cell population, in another well-worked-out protocol, giving the newly reworked cells an open landscape to expand in. You have the chance for a clean swap on a defined target, which is quite rare. In too many other cases the problem turns out to involve a fuzzy mass of genetic factors and environmental ones, none of which by themselves account for the disease symptoms, or the tissue doesnt allow you to isolate the defective cells easily or doesnt allow you to clear them out for any new ones you might generate, and so on.

Both the Vertex/CRISPR and BCH techniques seem to work and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. Thats not a word we get to use very often. They are producing enough fetal hemoglobin, more than enough to make their symptoms completely disappear no attacks, no transfusions, just normal life. And so far there have been no side effects due to the altered stem cells. An earlier strategy from Bluebird (involving addition of a gene for a modified adult hemoglobin) also seems to be holding up.

These are revolutionary proofs of concept, but at the same time, they are not going to change the course of these diseases in the world not right now, anyway. Bone marrow transfusion is of course a complex process that costs a great deal and can only be done in places with advanced medical facilities. But what weve established is that anything that can cause fetal hemoglobin to be expressed should indeed cure these diseases that idea has been de-risked. As has the general idea of doing such genetic alteration in defined adult tissues (either RNA interference or CRISPR). From here, we try to make these things easier, cheaper and more general, to come up with new ways of realizing these same goals now that we know that they do what we hoped that they would. This work is already underway new ways to target the affected cell populations rather than flat-out chemotherapy assault, new ways to deliver the genetically altered cells (or to produce them on site in the patients), ways to make the switchover between the two more gradual, and so on. There are lot of possible ways, and we now know where were going.

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Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from Group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. These data are being presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease. Consistently achieving the complete resolution of severe vaso-occlusive events (VOEs) and VOEs between Month 6 and Month 24 follow-up is unprecedented other than with allogeneic stem cell transplantation. Importantly, our data show the potential for LentiGlobin for SCD to produce fundamentally disease-modifying effects with sustained pancellular distribution of gene therapy-derived anti-sickling HbAT87Q and improvement of key markers of hemolysis that approach normal levels, said David Davidson, M.D., chief medical officer, bluebird bio. In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD. These results provide insight into the potential real-life impact LentiGlobin for SCD may offer patients.

SCD is a serious, progressive and debilitating genetic disease. In the U.S., the median age of death for someone with sickle cell disease is 43 46 years. SCD is caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs.

In the HGB-206 study of LentiGlobin for SCD, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As a hematologist, I regularly see the debilitating effects of pain events caused by sickle cell disease. Pain has an overwhelmingly negative impact on many facets of my patients lives and can lead to prolonged hospitalizations, said presenting study author Alexis A. Thompson, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine and head of hematology at Ann and Robert H. Lurie Childrens Hospital of Chicago. The results observed with LentiGlobin gene therapy for SCD include the complete elimination of severe vaso-occlusive pain episodes, which is certainly clinically meaningful, but also for the first time, we have documented patients reporting that they are experiencing improved quality of life. This degree of early clinical benefit is extraordinarily rewarding to observe as a provider."

As of the data cut-off date of August 20, 2020, a total of 44 patients have been treated with LentiGlobin for SCD in the HGB-205 (n=3) and HGB-206 (n=41) clinical studies. The HGB-206 total includes: Groups A (n=7), B (n=2) and C (n=32).

HGB-206: Group C Updated Efficacy Results

The 32 patients treated with LentiGlobin for SCD gene therapy in Group C of HGB-206 had up to 30.9 months of follow-up (median of 13.0; min-max: 1.1 30.9 months).

In patients with six or more months of follow-up whose hemoglobin fractions were available (n=22), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin at Month 6. At last visit reported, total hemoglobin ranged from 9.6 15.1 g/dL and HbAT87Q levels ranged from 2.7 8.9 g/dL. At Month 6, the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin; median HbS was 50% and remained less than 60% at all follow-up timepoints. All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.

Nineteen patients treated in Group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD. There have been no reports of severe VOEs in these Group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after Month 6.

Hemolysis Markers

In SCD, red blood cells become sickled and fragile, rupturing more easily than healthy red blood cells. The breakdown of red blood cells, called hemolysis, occurs normally in the body. However, in sickle cell disease, hemolysis happens too quickly due to the fragility of the red blood cells, which results in hemolytic anemia.

Patients treated with LentiGlobin for SCD in Group C demonstrated near-normal levels in key markers of hemolysis, which are indicators of the health of red blood cells. Lab results assessing these indicators were available for the majority of the 25 patients with 6 months of follow-up.

The medians for reticulocyte counts (n=23), lactate dehydrogenase (LDH) levels (n=21) and total bilirubin (n=24) continued to improve compared to screening values and stabilized by Month 6. In patients with Month 24 data (n=7), these values approached the upper limit of normal by Month 24. These results continue to suggest that treatment with LentiGlobin for SCD may improve biological markers to near-normal levels for SCD.

Pancellularity

As previously reported, assays were developed by bluebird bio to enable the detection of HbAT87Q and HbS protein in individual red blood cells, as well as to assess if HbAT87Q was pancellular, or present throughout all of a patients red blood cells. In 25 patients with at least six months of follow-up, on average, more than 80% of red blood cells contained HbAT87Q, suggesting near-complete pancellularity of HbAT87Q distribution and with pancellularity further increasing over time.

HGB-206: Improvements in Health-Related Quality of Life

Health-related quality of life (HRQoL) findings in Group C patients treated with LentiGlobin for SCD in the HGB-206 study were generated using the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), a validated instrument in SCD.

Data assessing pain intensity experienced by nine Group C patients were analyzed according to baseline pain intensity scores relative to the general population normative value: 2.6 on a scale of 0-10, where 10 equals the most intense pain. Data were assessed at baseline, Month 6 and Month 12.

Of the five patients with baseline scores worse than the population normative value average, four demonstrated clinically meaningful reductions in pain intensity at Month 12; the group had a mean score of 6.0 at baseline and a mean score of 2.4 at Month 12. Of the four patients with better than or near population normative values at baseline, two reported improvement and two remained stable with a mean score of 2.3 at baseline and 0.8 at Month 12.

HGB-206: Group C Safety Results

As of August 20, 2020, the safety data from Group C patients in HGB-206 remain generally consistent with the known side effects of hematopoietic stem cell collection and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to LentiGlobin for SCD. There were no serious AEs related to LentiGlobin for SCD.

One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.

LentiGlobin for SCD Data at ASH

The presentation of HGB-206 Group C results and patient reported outcomes research are now available on demand on the ASH conference website:

About HGB-206

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=32). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events 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: regarding the potential for LentiGlobin for Sickle Cell Disease to treat SCD; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or planned clinical trials; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe...