Category Archives: Gene therapy

DetailsCategory: DNA RNA and CellsPublished on Friday, 16 October 2020 14:20Hits: 161

First therapy recommended for full marketing authorization in the EU for eligible patients with confirmed diagnosis of late infantile or early juvenile MLD variants

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

Libmeldy is backed by data across 35 patients with follow-up of up to 8 years post-treatment, demonstrating the potential durability of HSC gene therapy

BOSTON, MA, USA and LONDON, UK I October 16, 2020 I Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending full, or standard, marketing authorization for Libmeldy (cryopreserved autologous CD34+ cells encoding the arylsulfatase-A, or ARSA, gene), an investigational gene therapy for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in the ARSA gene 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.

The CHMPs positive opinion will now be reviewed by theEuropean Commission(EC), which has the authority to grant marketing authorization for Libmeldy in theEuropean Union(EU). A final decision by the EC for Libmeldy is anticipated before the end of 2020. If approved, Libmeldy would be the first commercial therapy and first gene therapy for eligible patients with early-onset MLD.

MLD is a very rare, severe genetic condition 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. A majority of these patients pass away in childhood, with palliative care often as their only option.

Todays positive CHMP opinion for marketing authorization of Libmeldy is a remarkable achievement that we share with the MLD community, as it brings us closer to delivering a one-time, potentially transformative therapy for eligible children suffering from this devastating disease, said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. Data from the Libmeldy clinical program have demonstrated the potential for long-term positive effects on cognitive development and maintenance of motor function, translating to individual preservation of motor milestones such as the ability to sit, stand and/or walk without support, as well as attainment of cognitive skills like social interactions and school attendance, at ages at which untreated patients show severe motor and cognitive impairments.

Libmeldy is designed as a one-time gene therapy, developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy, in which the 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 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 genetic condition with a single treatment.

This is an important milestone toward making the availability of HSC gene therapy a reality for more patients, and it also is extremely rewarding for our multi-disciplinary team at SR-Tiget who has worked relentlessly along this 15-year journey to move the seminal proof of principle studies to the first in-human testing of this therapy, said SR-Tiget director Luigi Naldini, M.D, Ph.D. The robust and durable clinical benefits observed in early-onset MLD patients who received HSC gene therapy are compelling, especially when compared to the natural history of the disease. These results also further illustrate our view that the HSC gene therapy approach has the potential to deliver transformative effects in other storage diseases as well, especially when the cells are designed to overexpress the functional enzyme and provide an enhanced supply of it to the affected tissues.

As a parent, watching your child start down a seemingly normal developmental path only to suddenly and rapidly lose some or all of his or her abilities is heart-wrenching, and the agony is even more acute knowing no approved therapies currently exist for MLD, said Georgina Morton, Chair of ArchAngel MLD Trust. Todays decision to advance Libmeldy to the final EC approval stage represents a huge step forward for the parents of these young children and for all of us in the MLD community.

We are extremely appreciative of the EMAs expedited and thorough review of Libmeldys marketing authorization application, considering the severity of MLD coupled with the limited treatment options available today for young patients, said Anne Dupraz, chief regulatory officer, Orchard Therapeutics. The Agencys collaboration on this assessment is a testament to their broader public health commitment to ensure timely evaluation of new medicines for diseases where a pressing unmet need exists.

Data Supporting the Clinical Profile of Libmeldy

The positive CHMP opinion is supported by clinical studies of Libmeldy in both pre- and early- symptomatic, early-onset MLD patients. Early-onset MLD encompasses the disease variants traditionally referred to as late infantile (LI) and early juvenile (EJ).

Clinical efficacy was based on the integrated analysis of results from 29 patients with early-onset MLD who were all treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation:

Clinical safety was evaluated in 35 patients with early-onset MLD:

Co-primary endpointsThe co-primary endpoints of the integrated efficacy analysis were Gross Motor Function Measure (GMFM) total score and ARSA activity, both evaluated at 2 years post-treatment. 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.

Pre-symptomatic LI and EJ patients treated with Libmeldy experienced significantly less deterioration in motor function at 2 years and 3 years post-treatment, as measured by GMFM total score, compared to age and disease subtype-matched untreated patients (p0.008). The mean difference between treated pre-symptomatic LI patients and age-matched untreated LI patients was 71.0% at year 2 and 79.8% at year 3. Similarly, the mean difference between treated pre-symptomatic EJ patients and age-matched untreated EJ patients was 52.4% at year 2 and 74.9% at year 3. Although not statistically significant, a clear difference in GMFM total score was also noted between treated early-symptomatic EJ patients and age-matched untreated EJ patients (28.7% at year 2; p=0.350 and 43.9% at year 3; p=0.054).

A statistically significant increase in ARSA activity in peripheral blood mononuclear cells was observed at 2 years post-treatment compared to pre-treatment in both pre-symptomatic patients (20.0-fold increase; p<0.001) and early-symptomatic patients (4.2-fold increase; p=0.004).

At the time of the integrated data analysis, all treated LI patients were alive with a follow-up post-treatment up to 7.5 years and 10 out of 13 treated EJ patients were alive with a follow-up post-treatment of up to 6.5 years. No treatment-related mortality has been reported in patients treated with Libmeldy.

Key secondary endpointsFor EJ patients who were early-symptomatic when treated with Libmeldy, meaningful effects on motor development were demonstrated when these patients were treated before entering the rapidly progressive phase of the disease (IQ85 and Gross Motor Function Classification (GMFC)1). By 4 years post-disease onset, an estimated 62.5% of treated, early-symptomatic EJ MLD patients survived and maintained locomotion and ability to sit without support compared with 26.3% of untreated early-symptomatic EJ MLD patients, representing a delay in disease progression following treatment with Libmeldy.

A secondary efficacy endpoint that measured cognitive and language abilities as quantified by Intelligence Quotient/Development Quotient (IQ/DQ) found:

Clinical safetySafety 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 5 out of 35 patients. Antibody titers in all 5 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. 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.

About MLD and Investigational Libmeldy

Metachromatic leukodystrophy (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 thearylsulfatase-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. Currently, there are no approved treatments for MLD. In its late infantile form, mortality at 5 years from onset is estimated at 50% and 44% at 10 years for juvenile patients.1Libmeldy (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), formerly OTL-200, is being studied for the treatment of MLD in certain patients. Libmeldy was acquired from GSK inApril 2018and originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their jointSan Raffaele-Telethon Institute for Gene TherapyinMilan, 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 theSan 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 in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

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

SOURCE: Orchard Therapeutics

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Orchard Therapeutics Receives Positive CHMP Opinion for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) | DNA RNA and...

Oct. 14, 2020 11:00 UTC

DALLAS--(BUSINESS WIRE)-- 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 it has received rare pediatric disease designation and orphan drug designation from the U.S. Food and Drug Administration (FDA) for TSHA-102, an AAV9-based gene therapy in development for the treatment of Rett syndrome. Taysha anticipates that it will submit an Investigational New Drug (IND) application for TSHA-102 to the FDA in 2021.

Rett syndrome is one of the most common genetic causes of severe intellectual disability worldwide, with a prevalence of over 25,000 cases in the U.S. and European Union (EU). It is an X-linked disease that primarily occurs in females, but it can be seen very rarely in males. It is usually recognized in children between six to 18 months of age as they begin to miss developmental milestones or lose abilities they had developed. Individuals with Rett syndrome also show symptoms that include loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments, breathing issues and sleep disturbances.

Patients with Rett syndrome are currently managed with symptomatic treatments as there are no therapies approved to treat the underlying cause of disease, said Berge Minassian, M.D., Chief Medical Advisor of Taysha and Chief of Pediatric Neurology at the University of Texas Southwestern Medical Center (UT Southwestern). Dr. Minassian is credited with describing the CNS isoform of the MECP2 gene which is responsible for neuronal and synaptic function throughout the brain. Gene therapy offers a potentially curative option for patients suffering with Rett syndrome.

Rett syndrome is caused by mutations in the MECP2 gene. TSHA-102 is designed to deliver a healthy version of the MECP2 gene as well as the miRNA-Responsive Auto-Regulatory Element, miRARE, platform technology to control the level of MECP2 expression. TSHA-102 represents an important step forward in the field of gene therapy, where we are leveraging a novel regulatory platform called miRARE to prevent the overexpression of MECP2, said Steven Gray, Ph.D., Chief Scientific Advisor of Taysha and Associate Professor in the Department of Pediatrics at UT Southwestern. In collaboration with Sarah Sinnett, Ph.D. to develop miRARE, our goal was to design a regulated construct that allowed us to control MECP2 expression to potentially avoid adverse events that are typically seen with unregulated gene therapies.

The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the disease manifestations primarily affect individuals aged from birth to 18 years. Pediatric diseases recognized as "rare" affect under 200,000 people in the U.S. The Rare Pediatric Disease Priority Review Voucher Program is intended to address the challenges that drug companies face when developing treatments for these unique patient populations. Under this program, companies are eligible to receive a priority review voucher following approval of a product with rare pediatric disease designation if the marketing application submitted for the product satisfies certain conditions. If issued, a sponsor may redeem a priority review voucher for priority review of a subsequent marketing application for a different product candidate, or the priority review voucher could be sold or transferred to another sponsor.

Orphan drug designation is granted by the FDA Office of Orphan Products Development to investigational treatments that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the U.S.

Obtaining these designations is a validation of decades-long work to identify and optimize a potential gene therapy treatment for this devastating disease, said RA Session II, President, CEO and Founder of Taysha. We are also excited to advance our miRARE platform whereby regulated expression of a transgene is possible on a cellular basis. The miRARE platform has broad applicability across a wide range of monogenic CNS disorders where there is a need to control transgene expression.

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.

About miRARE

For disorders that require replacement of dose-sensitive genes, we have combined high-throughput microRNA, or miRNA, profiling and genome mining to create miRNA-Responsive Auto-Regulatory Element, or miRARE, our novel miRNA target panel. This approach is designed to enable our product candidates to maintain safe transgene expression levels in the brain. This built-in regulation system is fully endogenous, and does not require any additional exogenous drug application. Instead, the miRARE system utilizes endogenous transgene-responsive miRNA to downregulate transgene expression in the event that overexpression occurs. miRARE may be applicable to a range of diseases where overexpression of a therapeutic transgene is a concern.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as anticipates, believes, expects, intends, projects, and future or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning or implying the potential of our product candidates, including TSHA-102, to positively impact quality of life and alter the course of disease in the patients we seek to treat, the benefits of, and our ability to develop product candidates using, miRARE, our research, development and regulatory plans for our product candidates, the potential benefits of rare pediatric disease designation and orphan drug designation to our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed. Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission filings, including in our prospectus dated September 23, 2020, as filed with the Securities and Exchange Commission (SEC) on September 24, 2020, pursuant to Rule 424(b) under the Securities Act of 1933, as amended, which is available on the SECs website at http://www.sec.gov. Additional information will be made available in other filings that we make from time to time with the SEC. Such risks may be amplified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201014005319/en/

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Taysha Gene Therapies Receives Rare Pediatric Disease Designation and Orphan Drug Designation for TSHA-102 as a Treatment for Rett Syndrome - BioSpace

Immuno-oncology and CAR T cells energized the field of regenerative medicine, but for cell and gene to deliver on their promises, new, disruptive technologies and new modes of operation are needed. Specifically, that entails improving manufacturing to control variables and thus ensure product consistency, and maturing the regulatory environment to improve predictability.

Manufacturing cells is not like manufacturing small molecules, Brian Culley, CEO of Lineage Cell Therapeutics, told BioSpace. For cell therapy products to mature into real products that deliver on the promises of 10 years ago, they must be scalable which drives affordability and they must solve their purity issues.

On the clinical side, cell and gene therapies must find places where small molecules, antibodies or other traditional approaches may not be the best option.

For example, The era of transplant medicine is unfolding before us, Culley said. Because of the transplant component, cell therapy may enable changes the body never could do alone.

Lineage is addressing dry AMD and spinal cord injuries with two of its therapeutics.

Our approach is fundamentally different from traditional approaches. We replace the entire cell rather than modulate a pathway. There is a rational hypothesis where cell therapy can win, but first we need to fix the operational hurdles, Culley said.

To address the manufacturing challenges, Culley said, We work only with allogeneic approaches. For us, not being patient-specific is a huge advantage.

Not long ago, the industry was focused on 3D manufacturing in bioreactors.

Were beyond that, Culley said. For our dry AMD product, we can manufacture 5 billion retinal cells in a three liter bioreactor. The advantage is that the cells exist in a very homogenous space and are 99% pure.

As a result, they are more affordable and can be harvested with little manipulation.

Manual manipulation affects gene expression, he pointed out, so minimizing that, as well as the vast quantities of plastics typically required, results in a more controlled process and a more consistent product.

Additionally, Lineage introduced a thaw and inject formulation, so the cell therapy can be thawed in a water bath, loaded into a chamber and injected, all within a few minutes. Traditional dose administration requires washing, plating and reconstituting the cells the before they are administered to a patient.

Getting rid of the prior day dose prep is one example of the maturation of the field, which we are deploying today to help usher in a new branch of medicine, Culley said.

At Lineage, were tackling problems that largely were intractable. For dry AMD, theres nothing approved by the FDA. No one know why the retinal cells die off, so we manufacture brand new retinal cells (OpRegen) and implant them, Culley said. Were seeing very encouraging clinical signs, including the first-ever case of retinal restoration.

Retinal cells compose a thin layer in the back of the eye, Culley explained.

They start to die off in one spot, and that area grows outward. When we inject our manufactured cells where the old ones died, weve seen the damaged area shrink and the architecture in previously damage areas completely restored, Culley said. Weve treated 20 patients for dry AMD in, ostensibly, safety trials, but you cant help but notice efficacy when a patient reads five more lines on an eye chart. Its hard to imagine our intervention wasnt responsible for that, especially when humans cant regenerate retinal tissue.

The spinal injury program (OPC1) may represent an even greater breakthrough. As with dry AMD, there is no FDA-approved therapy.

We manufacture oligodendrocytes and transport them into the spinal cord, to help produce the myelin coating for axons, he told BioSpace. Because of the oligodendrocytes, the axons grow, become myelinated, and begin to function. Small molecule and antibody therapies havent been able to do that.

So far, 25 people have been treated in a Phase I/II trial. Culley reported cases in which a quadriplegic man, after OPC1 therapy, is now typing 30 to 40 words per minute, and another who now can throw a baseball. Its not unusual for patients who initially were completely paralyzed to now schedule their treatments around college classes, Culley said.

Humans can have varying degrees of recovery from spinal cord injury, but these are higher than we would expect, Culley said.

Other cell and gene companies are advancing solutions, too.

Many companies with induced pluripotent stem cells (iPSCs) are trying to figure out how to get scalability, purity, and reproducibility to work for them. Its not a quick fix, he said.

One of the challenges is balancing the clinical and manufacturing aspects of development.

If you have a technology thats not yet commercially viable, but you have clinical evidence, its tempting to focus on the clinical side, Culley said.

Too many companies do that, and then find their candidate must be reworked for scale up. Therefore, consider scale up and manufacturing early.

Theres a need for balance at a more granular level, too. For example, he asked, How many release criteria do you need? Just because you know a cell expresses a certain surface marker, does that add to your process? Ive seen companies ruined by trying to be perfect, and others by rushing headlong, seeing evidence where evidence doesnt exist.

As Lineage matures its processes to support larger clinical trials, the greatest challenges have been time It takes 30 to 40 days to grow cells, Culley said and regulatory uncertainty. Often, there is no regulatory precedence so there are holes to be addressed. For example, cell and gene therapies sometimes have a delivery component such as a scaffold or delivery encapsulation technology that also must be considered. Real-time regulatory feedback isnt available, so you proceed, presuming that what youre doing will be acceptable to regulators.

The FDA recognizes that new, disruptive technologies and approaches are being used, and must be used, for cell and gene therapy to reach patients.

The FDA is responsive and is trying to push guidance out, Culley said, but it takes time.

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Disruptive Technologies and Mature Regulatory Environment Vital for Cell Therapy Maturation - BioSpace

(L-R) Jason C. Foster, MBAChief Executive Officer and Executive Director, Arman Amini, PhDHead of Cell Processing, Farlan Veraitch, PhDCo-founder and Chief Scientific Officer, William Raimes, PhDHead of Process Development, Jason JonesChief Business Officer

Ori Biotech, a cell and gene therapy manufacturing firm, has closed a $30m (23m) Series A financing round, bringing the companys total funding to date to $41m.

The new funding will be used to help bring Oris manufacturing platform to the market.

The Ori platform is designed specifically to address the requirements of a new generation of personalised cell and gene therapies. The platform fully automates and standardises CGT manufacturing allowing for scale from pre-clinical process development to commercial-scale manufacturing.

The Series A investment was led by Northpond Ventures, a science, medical, and technology-driven venture fund, alongside Octopus Ventures, a European venture fund.

Northpond and Octopus invested alongside significant support from Oris existing institutional investors, Amadeus Capital Partners, Delin Ventures, and Kindred Capital.

Closing a significant Series A round, during these uncertain times, further validates Oris disruptive approach to fully automating cell and gene therapy manufacturing to increase throughput, improve quality, and decrease costs, said Jason C. Foster, CEO of Ori Biotech.

We are excited to work with our top tier investors and development partners to bring our platform to market as fast as possible to achieve our mission of enabling patient access to life-saving cell and gene therapies.

The London and New Jersey based company was founded in 2015 by Dr. Farlan Veraitch and Professor Chris Mason.

This new funding will allow us to continue addressing the significant challenges of providing high throughput, high quality, and cost-effective CGT manufacturing and to bring our novel platform into the clinic as quickly as possible to support the important work of our therapeutic developer partners, added Dr. Veraitch, Co-Founder and Chief Scientific Officer.

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Ori Biotech's new cell and gene therapy platform raises 23m - BusinessCloud

Mercks New VirusExpress Platform Speeds Development of Cell and Gene Therapies

Darmstadt, Germany, October 13, 2020 Merck, a leading science and technology company, has bolstered its viral vector manufacturing capabilities with the launch of its VirusExpress Lentiviral Production Platform. This new platform helps to overcome lentiviral production challenges and can reduce process development time by approximately 40 percent, based on Mercks experience as a contract development and manufacturing organization.

Cell and gene therapies offer the potential for curative treatments and are being developed and commercialized in half the time it has taken traditional therapies, said Angela Myers, head of Gene Editing & Novel Modalities, Life Science, at Merck. We are committed to accelerating manufacturing of cell and gene therapies with the ultimate goal of getting these lifesaving treatments to patients faster. By increasing dose yields and dramatically reducing process development time, this new platform will help us reach this goal.

Using a suspension cell line rather than an adherent-based production, coupled with a chemically defined cell culture media and process with built-in scalability, Mercks VirusExpress Platform meets multiple market needs. In addition to accelerating process development, the suspension culture format allows each batch of virus to be larger yielding more patient doses. Additionally, suspension culture is amenable to true scale-up, while being less labor-intensive. The chemically defined medium eliminates the safety, regulatory and supply chain concerns related to animal- and human-derived materials.

Mercks VirusExpress Platform offers a simplified upstream workflow, making processes easier to manage, adjust and scale. Flexible licensing allows companies to manufacture vectors by using either Mercks contract manufacturing capabilities, a third-party contract development and manufacturing organization, or in-house development.

The Life Science business of Merck is a leading contract development and manufacturing organization combining an integrated portfolio of manufacturing solutions with proven commercialization experience. This new offering underscores Mercks continued investment in cell and gene therapies. In April 2020, the company announced a new 100 million, 140,000-square-foot manufacturing center at its Carlsbad, California, USA, location that will double the existing production capacity and support large-scale commercial manufacturing. Today, the Life Science business of Merck manufactures vectors for two of the first five FDA-approved cell and gene therapies.

The cell and gene therapy market is growing rapidly and continues to show great promise. According to market research leader Arizton, the cell and gene therapy market is expected to reach more than $6.6 billion by 2024[1]. Merck has been involved in this space since clinical trials for gene therapy began in the 1990s.

Operator manufacturing viral vector in a cGMP environment. Mercksnew VirusExpressPlatformincreases dose yields and reduces process development time for cell and gene therapies.

All Merck news releases are distributed by email at the same time they become available on the Merck Website. Please go to http://www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 57,000 employees work to make a positive difference to millions of peoples lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices the company is everywhere. In 2019, Merck generated sales of 16.2 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Mercks technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials.

[1] http://www.prnewswire.com/news-releases/the-cell-and-gene-therapy-market-to-reach-revenues-of-over-6-6-billion-by-2024---market-research-by-arizton-300957463.html

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Merck's New VirusExpress Platform Speeds Development of Cell and Gene Therapies - PharmiWeb.com

NEW YORK, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Axovant Gene Therapies Ltd. (NASDAQ: AXGT), a clinical-stage company developing innovative gene therapies for neurological diseases, today announced that it has received Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA) for AXO-AAV-GM2, a one-time gene therapy delivered directly to the central nervous system that is in development for GM2 gangliosidosis, also known as Tay-Sachs and Sandhoff disease. In addition to the Rare Pediatric Disease designation, AXO-AAV-GM2 has Orphan Drug Designation (ODD) and is the first gene therapy that has been administered to children with Tay-Sachs disease.

We are thrilled to bring AXO-AAV-GM2 one step closer to patients in need through this Rare Pediatric Disease designation. AXO-AAV-GM2 has the potential to be the first treatment approved for Tay-Sachs and Sandhoff disease, rare and fatal pediatric diseases with no current treatment options, said Sean OBryan, Senior Vice President, Regulatory Affairs & Quality.

Axovant expects to evaluate AXO-AAV-GM2 in a registrational clinical trial which consists of a Stage 1 dose-ranging study and a Stage 2 efficacy study. Previously, Axovant reported the first evidence for potential disease modification in Tay-Sachs disease from an expanded access study administering investigational AXO-AAV-GM2 gene therapy in two patients with infantile (Type I) Tay-Sachs disease. AXO-AAV-GM2 was successfully administered in both patients and has been generally well-tolerated to date, with no serious adverse events or clinically relevant laboratory abnormalities related to therapy.

GM2 gangliosidosis, also known as Tay-Sachs and Sandhoff disease, is a rare and fatal pediatric neurodegenerative lysosomal storage disorder (LSD) resulting from deficiencies in beta-hexosaminidase, a key enzyme in the lysosome. These genetic defects lead to the toxic accumulation of gangliosides, resulting in neurodegeneration and life expectancy shortened to just two to four years of age.

The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the disease manifestations primarily affect individuals aged from birth to 18 years. Pediatric diseases recognized as rare affect under 200,000 people in the United States.

About AXO-AAV-GM2

AXO-AAV-GM2 is an investigational gene therapy for Tay-Sachs and Sandhoff disease, which rare and fatal pediatric neurodegenerative genetic disorders within the GM2 gangliosidosis family, caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the -hexosaminidase A (HexA) enzyme. Both forms of GM2 gangliosidosis are caused by overwhelming storage of GM2 ganglioside within neurons throughout the central nervous system), which is normally degraded in the lysosome by the isozyme HexA. These genetic defects lead to progressive neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims to restore HexA levels by introducing a functional copy of the HEXA and HEXB genes via delivery of two co-administered AAVrh8 vectors.

In 2018, Axovant licensed exclusive worldwide rights from the University of Massachusetts Medical School for the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

About Axovant Gene Therapies

Axovant Gene Therapies is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurodegenerative diseases. Our current pipeline of gene therapy candidates targets GM1 gangliosidosis, GM2 gangliosidosis (also known as Tay-Sachs disease and Sandhoff disease), and Parkinsons disease. Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visit http://www.axovant.com.

Forward-Looking Statements

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as intended, "may," "might," "will," "would," "should," "expect," "believe," "estimate," and other similar expressions are intended to identify forward-looking statements. For example, all statements Axovant makes regarding costs associated with its operating activities are forward-looking. All forward-looking statements are based on estimates and assumptions by Axovants management that, although Axovant believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Axovant expected. Such risks and uncertainties include, among others, the impact of the Covid-19 pandemic on our operations, the initiation and conduct of preclinical studies and clinical trials; the availability of data from clinical trials; the scaling up of manufacturing, the expectations for regulatory submissions and approvals; the continued development of our gene therapy product candidates and platforms; Axovants scientific approach and general development progress; and the availability or commercial potential of Axovants product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Axovants most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 11, 2020, as updated by its subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. Axovant undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts:

Media & Investors

Josephine Belluardo, Ph.D.LifeSci Communications646-751-4361jo@lifescicomms.commedia@axovant.com

Parag MeswaniAxovant Gene Therapies Ltd.(212) 547-2523investors@axovant.com

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Axovant Gene Therapies Receives Rare Pediatric Disease Designation for AXO-AAV-GM2 for Tay-Sachs and Sandhoff Disease - GlobeNewswire

PARIS, France: A five-year-old girl with a rare neurodegenerative disease died in the US while taking part in a gene therapy trial run by French biotechnology company Lysogene, the firm said on Thursday.

The little girl was suffering from Sanfilippo syndrome or mucopolysaccharidosis type III, a rare genetic disease that alters brain development after birth and leads to premature death. In a statement Lysogene, a company developing gene therapy for central nervous system diseases in children, said "the immediate cause of death is currently unknown" and that there was as yet "no evidence that the event is linked to the study drug administration".

It said it was "profoundly saddened by the passing of this child" and was collecting "additional information" about the circumstances. The share price of the company dropped 19 percent to 2.05 euros in morning trading in Paris.

The girl was one of 19 people being treated in the trial conducted at eight hospitals in Europe and the United States. She died at home several months after receiving the therapy, consisting of a single injection, at one of four treatment sites in the US, Lysogene told AFP. In its statement the company said it was following the remaining 18 patients closely and remained "committed to the LYS-SAF302 development program".

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Child dies in US during gene therapy trial - The News International

ROCKVILLE, Md., Oct. 13, 2020 /PRNewswire/ --Foundation to Fight H-ABC, a non-profit organization dedicated to increasing awareness and driving development of a cure for the degenerative children's disease, H-ABC, today announced a sponsored research agreement with the University of Massachusetts Medical School and Yale University to advance a targeted gene therapy for H-ABC.

"We have high hopes to quickly prove efficacy with this approach to move research forward and find a permanent cure for this devastating disease," said Michele Sloan, Co-Founder, Foundation to Fight H-ABC.

H-ABC (hypomyelination with atrophy of the basal ganglia and cerebellum) belongs to a group of conditions called leukodystrophies, diseases that affect the white matter of the brain. These diseases disrupt the growth or maintenance of the myelin sheath, a protective layer that insulates nerve cells and allows for the transmission of messages between cells.

Caused by a mutation in the TUBB4A gene, H-ABC is a rare genetic disorder that affects certain parts of the brainspecifically the basal ganglia and the cerebellum, which control movement. H-ABC targets these important structures, reducing both their size and function. As a result, children who suffer from H-ABC often experience motor problems, cannot walk, talk, or sit on their own. Currently, there is no known cure for this disabling and life-threatening condition.

The teams of Dr. Guangping Gao (University of Massachusetts Medical School) and Dr. Karel Liem (Yale School of Medicine) will combine extensive expertise in the fields of Adeno-associated virus (AAV), a platform for gene delivery for the treatment of a variety of human diseases and H-ABC disease models, to develop AAV vectors to silence or outcompete the mutated TUBB4A gene.

"To date, AAV-based gene delivery system is the vector of choice for in vivo gene therapy of many currently untreatable rare diseases including H-ABC," said Guangping Gao, Ph.D. "We are very excited for starting close collaborations with Dr. Liem's team at Yale and the Foundation to Fight H-ABC to develop potential gene therapeutics for this devastating disease."

"With the support from the Foundation to Fight H-ABC, we are excited to build upon our mechanistic studies of the disease and to collaborate with Dr. Gao of the University of Massachusetts to develop and test AAV approaches to H-ABC," saidKarel F Liem Jr., M.D., Ph.D.

For more information, please visit https://www.h-abc.org/donate.

CONTACT: Sawyer Lipari, [emailprotected]

SOURCE Foundation to Fight H-ABC

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Foundation to Fight H-ABC, University of Massachusetts Medical School and Yale University Initiate Gene Therapy Study Targeting Cure for Rare Disease...

InYourArea Community

We are delighted that Stevenage is being recognised for its significant contribution to the cell and gene therapy field."

Stevenage Bioscience Catalyst campus

Submitted by Charlotte Connors

The Department for International Trade (DIT) has classified Stevenage, Hertfordshire, as a 'High Potential Opportunity' (HPO) zone in recognition of its thriving cell and gene therapy cluster of national and international significance.

The successful HPO nomination was made by Hertfordshire Local Enterprise Partnership (LEP) and is expected to help attract further overseas investment into the county.

Stevenage is at the centre of the largest cluster of cell and gene therapy companies outside of the US. The growing cell and gene therapy campus in Stevenage is delivering over 1,000 jobs and is home to over 45 companies, 13 of which are in the cell and gene therapy space.

The campus was awarded Life Science Opportunity Zone status for advanced therapies in 2019 by the Office for Life Sciences.

It is jointly anchored by Stevenage Bioscience Catalyst, whose occupiers have raised over 1.6bn of investment to date, of which over 65 per cent has been invested into cell and gene therapy companies; and the pioneering Cell and Gene Therapy Catapult, which has built its Manufacturing Centre in Stevenage, and which has been instrumental to the growth of the UKs cell and gene therapy industry.

DITs High Potential Opportunities programme was launched in 2018 to encourage and accelerate foreign direct investment into the UKs key growth sectors, in line with Governments Industrial Strategy.

There are currently 17 HPOs throughout the UK, and an additional 19 HPOs will be developed over the course of Round 2.

Sally Ann Forsyth, chief executive officer at Stevenage Bioscience Catalyst said:

Shine a spotlight on your neighbourhood by becoming an Area Ambassador.

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Stevenage named 'high potential opportunity' zone for cell and gene therapy - In Your Area

The success of the approved gene therapies has led to an upward surge in the interest of biopharmaceutical developers in this field, resulting in a significant boost in clinical research initiatives and several high value acquisitions

Roots Analysis has announced the addition of Gene Therapy Market (3rd Edition), 2019-2030 report to its list of offerings.

Encouraging clinical results across various metabolic, hematological and ophthalmic disorders have inspired research groups across the world to focus their efforts on the development of novel gene editing therapies. In fact, the gene therapy pipeline has evolved significantly over the past few years, with three products being approved in 2019 alone; namely Beperminogene perplasmid (AnGes), ZOLGENSMA (AveXis) and ZYNTEGLO (bluebird bio). Further, there are multiple pipeline candidates in mid to late-stage (phase II and above) trials that are anticipated to enter the market over the next 5-10 years.

To order this 550+ page report, which features 190+ figures and 355+ tables, please visit this link

Key Market Insights

Around 470 gene therapies are currently under developmentNearly 45% of pipeline drugs are in the clinical phase, while rest are in the preclinical / discovery stage. Gene augmented therapies presently represent 66% of the total number of such interventions that are in the pipeline. It is worth mentioning that majority of such product candidates are being developed as in vivo gene therapies.

More than 30% of clinical stage pipeline therapies are being designed for treating oncological disordersConsidering the overall pipeline, over 20% of product candidates are being developed to treat various types of cancers, followed by those intended for the treatment of metabolic (15%) and ophthalmic disorders (12%). It is also worth highlighting that adenovirus vectors are presently the preferred vehicles used for the delivery of anticancer gene therapies.

Over 60% of gene therapy developers are based in North AmericaOf the 110 companies developing gene therapies in the abovementioned region, 64 are start-ups, 26 are mid-sized players, while 18 are large and very large companies. Further, within this region, most of the developers are based in the US, which has emerged as a key R&D hub for advanced therapeutic products.

More than 31,000 patents have been filed / published related to gene therapies, since 2016Of these, 17% of patent applications / patents were related to gene editing therapies, while the remaining were associated with gene therapies. Leading assignees, in terms of the size of intellectual property portfolio, include (industry players) Genentech, GSK, Sangamo Therapeutics, Bayer and Novartis, (non-industry players) University of California, Massachusetts Institute of Technology, Harvard College, Stanford University and University of Pennsylvania.

USD 16.5 billion has been invested by both private and public investors, since 2014Around USD 3.3 billion was raised through venture capital financing, representing 20% of the total capital raised by industry players till June 2019. Further, there have been 28 IPOs, accounting for more than USD 2.2 billion in financing of gene therapy related initiatives. These companies have also raised significant capital in secondary offerings.

30+ mergers / acquisitions have been established between 2014 and 2019Examples of high value acquisitions reported in recent past include the acquisition of AveXis by Novartis (2018, USD 8,700 million) and Bioverativ by Sanofi (2018, USD 11,600 million).

North America and Europe are anticipated to capture over 85% of market share by 2030With a promising development pipeline and encouraging clinical results, the market is anticipated to witness an annualized growth rate of over 40% during the next decade. In addition to North America and Europe, the market in China / broader Asia Pacific region is also anticipated to grow at a relatively faster rate.

To request a sample copy / brochure of this report, please visit this link

Key Questions Answered

The USD 10 billion (by 2030) financial opportunity within the gene therapy market has been analyzed across the following segments:

The report features inputs from eminent industry stakeholders, according to whom gene therapies are likely to be the most promising treatment options for genetic disorders. The report includes detailed transcripts of discussions held with the following experts:

The research covers brief profiles, featuring an overview of the therapy, current development status and clinical results. Each profile includes information on therapeutic indication, targeted gene, route of administration, special designations, mechanism of action, dosage, patent portfolio, technology portfolio, clinical trials and recent developments (if available).

For additional details, please visit https://www.rootsanalysis.com/reports/view_document/gene-therapy-market-3rd-edition-2019-2030/268.html

or email [emailprotected]

Contact:Gaurav Chaudhary+1 (415) 800 3415+44 (122) 391 1091[emailprotected]

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Tag: Gene Therapy - The Think Curiouser