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Biotech startup Ori Biotech raises $30M in Series Afunding to scale its cell and gene therapy (CGT) manufacturing platform.

Ori Biotech helps pharmaceutical and biotech companiesdevelop and manufacture cell and gene therapies. Its patented technology aimsto reduce the manufacturing cost of these life-saving treatments by up to 80%,allowing them to be more widely accessible for patients.

Ori Biotech Ltd (Ori),a leading innovator in cell and gene therapy (CGT) manufacturing, todayannounced the successful close of a $30 million Series A financing round,bringing the companys total funding to date to $41 million. The Series A roundwas led by the experienced life sciences investment team at Northpond Ventures, a leading globalscience, medical, and technology-driven venture fund, alongside Octopus Ventures, a leading Europeanventure fund. Northpond and Octopus invested alongside significant support fromOris existing institutional investors, Amadeus Capital Partners, Delin Ventures, and Kindred Capital.

The Future of Cell and Gene Therapy Manufacturing

Founded in 2015 by Dr. Farlan Veraitch and Professor Chris Mason, Ori Biotech is a London and New Jersey-based cell and gene therapy (CGT) manufacturing technology company. Ori has developed a proprietary, flexible manufacturing platform that closes, automates, and standardizes manufacturing allowing therapeutics developers to further develop and bring their products from pre-clinical process development to commercial-scale manufacturing. The mission of the Ori platform is to fully automate CGT manufacturing to increase throughput, improve quality, and decrease costs in order to enable patient access to this new generation of life-saving treatments.

The new funding will be used to help bring Oris innovativemanufacturing platform to the market. The Ori platform delivers scalablesolutions to flexibly address the critical clinical and commercialmanufacturing needs of CGT developers.

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.

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Ori Biotech Lands $30M for Cell and Gene Therapy Manufacturing Platform - HIT Consultant

TORONTO -- For the thousands of Canadians at risk of blindness, eight-year-old Sam is a beacon of hope.

He is the first Canadian to be treated with gene replacement therapy for a rare form of blindness which had left Sam unable to see sky on a cloudy day, and unable to make out shapes in the dark.

Sometimes you have to walk in the night and I couldnt see things and you bump into things, Sam told CTV News.

He had to have lights on always, and had trouble seeing his shoes or objects on the floor. And the condition was progressive, meaning things would get worse as he grew older -- a daunting prospect when there was no treatment available.

But now he can see cloudy skies, shoes and more. The best part of his improved vision, says Sam, are the stars at night.

I never saw stars before, he said. And I also never saw airplanes flying at night.

He was diagnosed after birth with a genetic disorder called retinitis pigmentosa, a form of genetic retinal degeneration resulting from mutations in the RPE65 gene.

You lose perception of light, Dr. Elise Heon, of Sick Kids Hospital, explained to CTV News. You end up in darkness and [its] slowly progressive, it's relentless, your visual field shrinks and shrinks and shrinks and shrinks.

Retinitis pigmentosa (RP) affects between 1 in 3,500 to 1 in 4,000 Canadians, according to Fighting Blindness Canada. It actually refers to a group of disorders, as there are numerous versions of RP depending on which pair of genes are damaged. More than 64 genes have been identified by scientists as potentially having mutations that cause RP.

Now, Canada has approved the first-ever gene replacement therapy for this form of blindness. Sick Kids Hospital has 29 children in its program with this mutation. The drug can be used on children and adults with the condition, but the earlier its used, the more sight it will save, doctors believe.

It's a huge deal, because for these patients before, theres no treatments, Heon said.

She said she had recently met two patients, brothers, who were suffering the same problem as Sam, and for the first time, she was able to provide hope.

They're 10 years old, and they're losing their vision, she said. If we do nothing, they're just going, fine, they'll just end up with no light reception. So for the first time [we were] able to say, well, actually we need to have a discussion. And it was just, it was priceless.

The gene therapy, which goes by the brand name Luxturna, was developed in the U.S by the drug company Spark Therapeutics.

It works by placing a copy of the healthy gene into inactivated viruses, which are then injected into the retina. The gene then allows cells to produce the necessary protein to convert light into an electrical signal in the retina in order to provide healthy vision and prevent progression of the disease.

It is the first targeted gene therapy to be approved by Health Canada, which gave it the all-clear this week.

Back in 2019, Sam and his family travelled to the U.S to get the new gene therapy because it wasnt available in Canada yet.

His mother, Sarah Banon, noticed changes quickly.

About a week later, I noticed he could get dressed by [himself], she said. He could get his shoes on by himself, independently.

His improvements have continued in the year since he first received the gene therapy.

He is so much more confident, his mother told CTV News. Like getting dressed by himself, matching clothes, doesnt have to have things enlarged. Being able to [see], even when its dark outside, no lights on and it is a cloudy day. He would have to, at school, keep the lights on.

Now he is able to function as a normal child.

With the approval of this gene therapy in Canada, doctors are hoping to be able to use it on more patients who qualify -- and the earlier the better.

Dr. Peter Kertes, a vitreo-retinal surgeon and Ophthalmologist-in-Chief at Sunnybrook Health Sciences Centre, told CTV News that the approval of the therapy is fantastic.

This is a huge breakthrough, he said. Most of the advances that we have in medicine are incremental. Every once in a while, once in a generation, something revolutionary like this comes along that really changes the course of therapy.

Luxturna specifically treats individuals with biallelic mutations of the RPE65 gene -- meaning they have mutations in that gene stemming from both parents -- which manifests as either RP or Leber congenital amaurosis (LCA). Its a very small patient group compared to the entirety of Canadians with inherited retinal diseases.

This may be just one gene therapy for one condition, but it will open to the door to this strategy being used in other scenarios, Kertes pointed out.

This is the tip of the iceberg. I think this is a vector that will prove to be very effective and holds great promise, he said. I think many people who are living with blindness or facing blindness, have much to look forward to. I think we're on the cusp of a revolution in this group of diseases.

The company licensing the therapy, Novartis Pharmaceuticals Canada Inc., isnt detailing the cost, but based on the price in the U.S it could top $1.1 million in Canada, making it among the most expensive drugs in the country.

The therapy is currently under review by both the Canadian Agency for Drugs and Technologies in Health (CADTH) and the Institut national dexcellence en sant et en services sociaux (INESSS).

Novartis said in a statement that they look forward to receiving their recommendations following Health Canadas approval.

They said they are eager to help eligible Canadians affected by this rare disease gain access to the first-ever gene replacement therapy as quickly as possible.

The Patented Medicine Prices Review Board will be disclosing their new guidelines in terms of capping drug prices in an online media briefing this Thursday.

As this will likely be the first of many gene replacement therapies -- with similarly high price tags -- Ottawa and the provinces will have to make the decision on whether it will be covered by provincial health plans. The question is an ongoing ethical debate, with some saying that drug companies will only take advantage of it if governments show that they are willing to pay.

Should it be the responsibility for the government to pay for any drug at any price? Marc-Andr Gagnon, a researcher with Carleton University who looks into pharmaceutical policy, told CTV News. The problem is, if we say yes to this question, you can be sure that the day after, all the drugs in the market will be asking for much higher prices.

Its a very expensive drug, Heon acknowledged.

However, she pointed out that this is a rare disease, and its not a recurrent treatment. Its a one-time injection to the eyes.

You treat both eyes and then thats it, she said.

To be able to change someone's life is quite a privilege. And to be able to prevent someone from going blind is a real privilege.

For Sam and his mother, the gift of independence has been priceless.

This is a story of hope, his mother said. A child told it is what it is.

And now, when he looks up at night, he can see stars.

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'I never saw stars before': Gene therapy brings back 8-year-old Canadian boy's sight - CTV News

Perhaps some of the most important contributions to science is the ability to manipulate DNA. A notable discovery is humulin, the genetically modified insulin. By reducing the cost and increasing the safety, the treatment improved the quality of life for millions of patients. Since humulins approval in 1978, hundreds of gene therapy treatments have been approved. Scientists can insert a normal gene to compensate for the defective one an individual was born with.

Over the past few decades, all the developments in gene therapy are countered by religious, ethical, and socioeconomic concerns over its misuse. The most prominent argument against gene therapy is whether we should edit the genes to treat disease. It is often regarded as unnatural and dangerous because we cannot foresee the effects down the line. The idea of picking and choosing your genes leads to comparisons between gene therapy and eugenics. It is important to note that the eugenics movement sought to increase desirable qualities of select races, whereas gene therapy seeks to improve the quality of life for patients.

Current drugs for a lot of diseases merely treat, rather than targeting the source of the illness. The vast majority of diseases have a genetic component. This makes it so critical to continue developing new therapies. People value their health and if gene therapy can improve the lives people would have had, then its worth it. There are therapies for hemophilia, sickle cell anemia, and certain kinds of cancer. If gene therapy is regarded as a form of enhancement, then consider all the other things people do to change themselves: plastic surgery, cosmetic improvements, diet and exercise. Scientists in the United Kingdom have been working to treat mitochondrial diseases by creating three parent embryos. This is a type of in-vitro fertilization that takes a healthy mitochondria from a third parent. Because the mitochondria, usually inherited only from the mother, has its own DNA, it can be said that the child has three parents.

With gene therapies, we are changing the course of evolution. Treating diseases at the level of DNA once seemed like science fiction. With all of the recent advancements in science, it is possible to turn it into a reality. Despite the ethical concerns, the number of treatments approved by the FDA show that they have potential to improve peoples lives.

The treatment is only as accessible as it is affordable. Novartis Pharmaceuticals new therapy Zolgensma made headlines for its hefty $2.1 million price tag. It is meant to treat spinal muscular atrophy; a muscular degenerative disorder where the patients only live a few years. Not all insurance companies cover Zolgensma, leaving families wondering how to acquire this life saving treatment. This is the most expensive therapy out there, but highlights how cost can leave families scrambling to provide relief for their children. The cost of all gene therapy medications should be made affordable so medication can do its job of improving quality of life. There is the fear that only the wealthy will have access to gene therapies.

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Gene Therapy: Healing remedy or harmful hoax? The Knight News - The Knight News

CSL bought the rights to EtranaDez off Netherlands company uniQure this year for $US450 million.

Its current haemophilia B treatment, Idelvion, has a 30 per cent market share, but Dr Storey believes that if EntranaDez is successful, this would rise to at least 40 per cent.

The upside to the CSL Behring division's earnings before interest, tax, depreciation and amortisation would be about 4 per cent, and potentially 6 per cent if it also acts as a defence to Idelvion against non-factor therapies being developed by competitors. Non-factor therapies have already disrupted the haemophilia A market.

Dr Storey said CSL's haemophilia business was an often "overlooked driver of margins".

Based on consultations with experts in the industry, he and co-author Melissa Benson set a success target of 20 per cent factor IX activity. Haemophilia B patients are deficient in factor IX, the protein that allows blood to clot. Most people have more than 50 per cent factor IX in their blood.

He said that if this level of activity was achieved, it would be a "knock-out" result, which would lead to meaningful clinical adoption.

The EtranaDez trial is likely to be a focal point of CSL's R&D day next Tuesday and clinical trial results are expected this month.

The gene therapy would be a one-shot option for haemophilia B patients and the duration that it would be effective for is unknown. However, the report by Wilsons suggested it would need a minimum durability of three to five years, but should ideally target an eight to 10-year timeframe, which would make reimbursement justification easier.

"Haematologists are hopeful it could last over 10 years," Dr Storey said. "You've only got one shot on goal with a gene therapy like this and it'll be a $US2-3 million shot so don't drop it."

If the drug was successful, Dr Storey said it could galvanise CSL's investment into gene therapy and spur more acquisitions by it in the emerging field.

He said there was no doubt CSL would invest more in gene therapy. "You're seeing so much competition on so many aspects of their business, they inevitably have to participate more and more in that.

"[In terms of acquisitions] it's more likely to be of the sorts developing alternatives to intravenous immunoglobulin.

"They need things that are fairly close to market. Looking at its R&D pipeline, the next big thing is CSL 112, which is still some years away, so they do have a gap in the pipeline."

The rest is here:
New CSL gene therapy could trigger a stock rerating - The Australian Financial Review

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/

Originally posted here:
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

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

(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

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