Staff: Cell gene therapy sector needs reinforcements – Bioprocess Insider – BioProcess Insider

Cell and gene therapy manufacturers need staff with laboratory skills and GMP know-how, according to an expert from Texas A&M.

Cell and gene therapies attract a lot of attention. In recent years products like Yescarta, Kymriah and Zolgensma and the debate about their prices $373,000, $475,000 and $2.1m respectively have dominated the headlines.

In industry circles the focus has shifted to the manufacture of such therapies. Developers are working to ensure there are sufficient vectors, or to make production systems more cost efficient.

Ex-military personnel could be a good fit for the cell and gene therapy industry. Image: iStock/ChrisSuperseal

But biopharma should not forget its staff.

Even automated lines need skilled operators says Jenny Ligon, assistant director of workforce development at Texas A&Ms National Center for Therapeutics Manufacturing (NCTM).

For cell and gene therapy, technicians need to have a better understanding of molecular biology and even immunology and virology.

She told us: The reality is we just need more people with practical laboratory experience. In general, upstream manufacturing technicians seem to be in high demand, so those individuals with experience with good cell culture technique will be highly marketable.

With gene and cell therapy taking off, there will be an even larger demand for those with experience in mammalian cell culture.

Adaptability is key. Ligon told us: By and large, there arent any new unit operations in cell and gene therapy manufacturing, however, because of the novelty of this field, manufacturing processes are still evolving.

Staff training is dictated by resources. Large biopharma firms have systems in place to ensure staff have the right skills, but small companies may find it more difficult.

Many gene and cell therapy companies are still in start-up mode, Ligon said. For them, the critical need for technicians is an understanding of cGMP manufacturing processes as many of them may only be familiar with bench-scale manufacturing.

Fortunately, there is support according to Ligon, who cited a Texas A&M course funded by the National Institute for Innovation in Manufacturing Biopharmaeuticals (NIIMBL) as an example.

The course was developed by BTEC through NIIMBL funding and remains the only hands-on short course focused on vector manufacturing.NCTM will be offering the course beginning in the latter half of 2020.

Cell and gene therapy firms also struggle to find staff according to Ligon, who says competition for skilled employees will have negative consequences.

Current cell and gene therapy roles are being filled with those workers who have been in traditional biomanufacturing for several years, which will create a tremendous gap in positions for traditional manufacturers, confirming the demand for more trained workers, period.

Ligon suggests ex-military personnel could be a good fit for the cell and gene therapy industry.

Im still a strong advocate for former service members to fill many of the future jobs in this industry, given their strong sense of responsibility, dedication to accomplishing a mission, ability to innovate and identify solutions to challenging and demanding work environments, attention to detail, and understanding of following protocol and doing it right the first time.

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Biogen teams up with Sangamo in gene therapy deal worth up to $2.7B – MedCity News

A large biotech is partnering with a firm developing cell and gene therapies on treatments for neurological diseases like Alzheimers and Parkinsons.

Cambridge, Massachusetts-based Biogen said Thursday afternoon after markets closed that it had partnered with Brisbane, California-based Sangamo Therapeutics in a deal that could be worth up to $2.7 billion. The partnership will initially focus on two preclinical Sangamo gene therapy candidates ST-501 for tauopathies such as Alzheimers and ST-502 for synucleinopathies like Parkinsons disease, plus an undisclosed neuromuscular target. It also includes exclusive rights for up to nine other undisclosed neurological targets.

Biogen will pay Sangamo $350 million upfront, which includes a license fee and equity investment, while Sangamo will be eligible for up to $2.37 billion in milestone payments, plus royalties.

Shares of Sangamo were up more than 28% on the Nasdaq after markets opened Friday. The company had also announced its fourth quarter and full year 2019 financial results. Biogens shares were down 2.6%.

Sangamo had reached out to multiple companies in a competitive process. While declining to say how many companies the biotech had spoken to, Sangamo head of corporate strategy Stephane Boissel said in a phone interview that it had put together multiple term sheets.

Its a combination of economics, but also the expertise of that partner in that particular field, Boissel said, referring to why the company had chosen Biogen. Biogen, in the pharma world, is probably the best franchise when it comes to neurology.

Adrian Woolfson, Sangamos executive vice president for research and development, said in the same call that it was also because of an appreciation for Biogens enthusiasm and energy.

I think its fair to say we had a very good chemistry with them at a personal level when we went to meet with them in Boston, and we seemed to get along very well, Woolfson said.

Sangamo has existing partnerships with a number of other firms, including Pfizer and Gilead Sciences.

Biogens moves into Alzheimers disease have not been without controversy. The company plans to file for Food and Drug Administration approval of aducanumab, a monoclonal antibody targeting the amyloid beta protein that has long dominated Alzheimers research. The company initially halted the Phase III development program for the drug when it was predicted to fail, but revived it when a post-hoc analysis indicated potential efficacy. Investors have remained skeptical.

Still, that did not come up in the minds of Sangamos executives, Boissel said. While emphasizing that he could not compare the two companies approaches, Woolfson added that gene therapies are potentially better ways to address neurological diseases like Alzheimers because they can switch off genes completely rather than being limited to taking out specific proteins, as monoclonal antibodies are.

ST-501 targets tau, another protein that has been researched as a potential therapeutic target in Alzheimers. ST-501 and ST-502 use adeno-associated viral vectors to deliver zinc finger protein transcription factors (ZFP-TFs), a form of gene therapy that Sangamo said in its quarterly earnings presentation is ideally suited to neurological disorders due to its ability to up- or down-regulate gene expression.

Boissel did not disclose specific timelines for ST-501 and ST-502, but noted that the next steps in their development will be preclinical studies to enable them to enter the clinic.

Photo: John Tlumacki, The Boston Globe, via Getty Images

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CYTOO and AskBio Enter Research Agreement to Screen Gene Therapy Candidates for Rare Muscle Disorder – Yahoo Finance

GRENOBLE, France and RESEARCH TRIANGLE PARK, N.C., March 02, 2020 (GLOBE NEWSWIRE) -- CYTOO, a leading drug discovery company on muscle disorders, today announced that it has entered into a research collaboration aimed at selecting a gene therapy candidate for a rare muscle disorder withAsklepios BioPharmaceutical, Inc.(AskBio), a clinical-stage, fully integrated adeno-associated virus (AAV) gene therapy company. Under the terms of the agreement, AskBio and CYTOO will work together to develop an AAV-based screening platform derived from patient cells. The goal of the collaboration is to screen and select a preclinical candidate capable of restoring a healthy phenotype from patient cells culturedin vitro.

CYTOO has developed a muscle-on-a-plate platform using patients primary cells, called MyoScreen. MyoScreen is anin vitrosystem in which skeletal muscle cells mimic the physiology, contractile and metabolic functions of human musclein vivoand allow infection by AAV-based gene therapy vectors targeting muscle.

Dr. Philippe Moullier, Chief Scientific Officer, AskBio Europe, said, As a leader in the gene therapy space, the ability to quickly and efficiently screen potential therapeutic candidates will be invaluable. The expertise provided by CYTOO and the MyoScreen platform will potentially give us a better understanding of how those candidates perform in patient cells and improve efficiency throughout the R&D process.

Luc Selig, CYTOOs CEO, added, Gene therapy for muscle disorders is becoming a reality for patients and their families, and we are proud that AskBio has chosen our expertise to investigate a potential new treatment. We have developed MyoScreen as a laboratory model of patient-derived muscle that can be used to screen gene therapy candidates and QC clinical and commercial batches.

The financial terms of the agreement were not disclosed.

About CYTOOCYTOO is a preclinical-stage drug discovery company addressing muscular disorders (NMDs, muscle waste, muscle disuse, metabolic ageing). The company has developed MyoScreen, a versatile and high-throughput muscle-on-a-plate R&D platform, from patient-derived myotubes, that can be used to model any muscle disorder and screen any type of therapeutic candidate. The platform is open to partnering with biotech and pharmaceutical companies and has been the starting point of CYTOOs internal drug discovery program on Duchenne Muscular Dystrophy. Among partners of CYTOO: Daiichi Sankyo, Pfizer, Axcella. CYTOO has offices in Grenoble, France and Bethesda, MD, USA.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive AAV capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy type 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more atwww.askbio.comor follow us onLinkedIn.

Media Contacts:

FP2COMFlorence Portejoiefportejoie@fp2com.frMob: + 33 (0)6 07 76 82 83

AskBioRobin FastenauVice President, Communicationsrfastenau@askbio.com+1 984 275 2705

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CYTOO and AskBio Enter Research Agreement to Screen Gene Therapy Candidates for Rare Muscle Disorder - Yahoo Finance

Symbiosis on increased demand for viral vectors – BioPharma-Reporter.com

The growing prevalence of cell and gene therapies in both the clinical and the commercial side of the biopharmaceutical industry is leading to increased demand for viral vectors, with companies within the contract manufacturing sector building their capacity to meet clients needs.

BioPharma-Reporter (BPR) spoke to Colin MacKay (CM), CEO of viral vector manufacturer Symbiosis, about how companies in this sector are addressing the rising demand, how the lack of capacity is affecting the industry, and what are the other challenges that manufacturers face.

MacKay told us that the demand needs to be addressed with improved technical expertise, but the industry is learning experientially on how to deal with these new technologies.

Moreover, he explained how adding capacity has to come concurrently with ensuring compliance to regulations, and how the inherent biological nature of these products, and the sensitivity and complexity of their production systems, needs to be put under the spotlight.

BPR: What are the current challenges in viral vector manufacturing?

CM: The positive regulatory climate with regards to the approval of viral vector-based biopharmaceuticals is further fueling focused investment across the industry in drugs of this nature. In essence, the technology has been vindicated in a commercial setting. Although point-of-use pricing remains a contentious talking point, regulatory, technical and commercial tail-winds are driving the industry to adapt in many ways, and to do so quickly.With respect to manufacturing, for example, there is strong demand for both drug substance and drug product manufacturing, while CMOs like Symbiosis continue to invest in additional manufacturing capacity in direct response to that demand. With high demand, and relatively smaller supply, the foundation is laid for the value of strategic relationships to be realized and to gain prioritized access to manufacturing capacity, for example, while the commercial successes of those CMOs is providing relatively easier access to both internal and external financial resources to further grow overall manufacturing capacity.

Challenges include balancing supply versus demand for a growing business while ensuring that the competitive strengths that come from short lead-times to access manufacturing slots, for example, is positioned to support the accelerated development timeframes which drug developing client companies are working to.

BPR: How have the demands of the cell and gene therapies development market evolved during the past year?

CM: The successes of cell and gene therapy products being approved for market and their breathtakingly positive therapeutic impact on patients has, I believe, driven the market to evolve quickly. The overarching commercial driver in our industry to take investors dollars and to develop innovative and profitable new medicines is undiminished, and indeed has been amplified in niche sectors, such as cell and gene therapies.

In tandem, technology platforms are being validated, meaning that multiple further drugs in companies pipelines are being accelerated down the previously ploughed furrow of those pioneering therapies which went first. That is fueling demand for all services which support the development of cell and gene therapies and the appetite of investors to finance the profitable growth of those service providers.

BPR: What is the main challenge that cell and gene developers face?

CM: The technical challenges of developing, and then robustly and reproducibly manufacturing cell and gene therapy products to GMP is a major challenge, principally due to the inherent biological nature of these products and the sensitivity and complexity of their production systems.

Access to manufacturing capacity, particularly amongst the bigger CMO players, is challenging clients and their drug development timeline planning.

BPR: How does the CMO industry assist developers in overcoming technical challenges?

CM: The experiential learning in the industry, with respect to the technical and GMP manufacture of both drug substance and drug product, continues to grow and that learning is being reflected back into overcoming the principal technical challenges the industry faces. Processes are being refined and optimized to improve yields and productivity, making the development of biopharmaceuticals faster and relatively more cost-effective.

BPR: How do you see the current lack of capacity in the CMO industry changing?

CM: My understanding is that access to manufacturing capacity, particularly amongst the bigger CMO players, is proving a challenge to customers and their ability to achieve their preferred drug development timelines. The industry is responding and investing significantly in building new capacity, and new drug (vector) substance manufacturing capacity.

The relatively smaller CMO players, such as ourselves, are strategically working hard to increase in-house manufacturing capacity while doing so in a measured way to ensure continued compliance in line with that growth, while investing in strategic relationships with existing clients to ensure they have access to our capacity to align with the increasing manufacturing requirement of their maturing products.

In tandem, we are adding new capacity output from our existing manufacturing infrastructure, allowing us to continue to add new, high-value, clients to our existing client portfolio who can use that growing capacity. Strategically, and competitively, Symbiosis is therefore well-positioned to provide sterile GMP manufacturing capacity to clients who are experiencing frustrations with the wider industry and its lack of manufacturing capacity and access to it on a short timeframe.

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Prevail Therapeutics Announces Investigational New Drug Application Active for PR006 for the Treatment of Frontotemporal Dementia with GRN Mutation |…

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 03 March 2020 17:27Hits: 481

NEW YORK, NY, USA I March 02, 2020 I Prevail Therapeutics Inc. (Nasdaq: PRVL), a biotechnology company developing potentially disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Companys Investigational New Drug (IND) application for its experimental gene therapy program, PR006, for the treatment of frontotemporal dementia patients with GRN mutation (FTD-GRN), and that the Company may proceed with the initiation of its Phase 1/2 clinical trial.

PR006 is being developed as a potential one-time gene therapy for FTD-GRN, a progressive neurodegenerative disease caused by mutations in the GRN gene that reduce production of progranulin, a protein critical for lysosomal function, neuronal survival, and normal microglial activities. The progranulin deficiency leads to lysosomal dysfunction, ineffective protein degradation and recycling, neuroinflammation, and ultimately neurodegeneration and death, typically within three to ten years of diagnosis.

PR006 is designed to increase progranulin levels in the brains of FTD-GRN patients by delivering a healthy GRN gene using an AAV9 vector.

FTD-GRN is a serious and progressive neurodegenerative disease for which there are no approved treatments, said Asa Abeliovich, M.D., Ph.D., Founder and Chief Executive Officer of Prevail. Now that the PR006 IND is active, we look forward to advancing clinical development of PR006, which has the potential to positively impact the lives of patients by slowing or stopping the progression of this devastating disease.

The PROCLAIM Phase 1/2 clinical trial will investigate the safety and tolerability of PR006, and will also measure key biomarkers and exploratory efficacy endpoints in patients with FTD-GRN. The Company plans to begin dosing for PROCLAIM this year. We believe this makes PR006 the first gene therapy for FTD-GRN to enter clinical trials.

The FDA has granted Orphan Drug Designation for PR006 for the treatment of patients with FTD.

About Frontotemporal Dementia with a GRN MutationFrontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65, after Alzheimers disease. 50,000 to 60,000 people in the U.S. and 80,000 to 110,000 individuals in theEuropean Unionare affected byFTD. Frontotemporal dementia with a GRN mutation (FTD-GRN) represents 5-10% of all patients withFTD.FTDresults from the progressive degeneration of the frontal and temporal lobes of the brain, which control decision-making, behavior, emotion and language.In FTD-GRN patients, reduced levels of progranulin lead to age-dependent lysosomal dysfunction, neuroinflammation, and neurodegeneration. There are no approved treatments forFTDor FTD-GRN.

About Prevail TherapeuticsPrevail is a gene therapy company leveraging breakthroughs in human genetics with the goal of developing and commercializing disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases. The company is developing PR001 for patients with Parkinsons disease with aGBA1mutation (PD-GBA) and neuronopathic Gaucher disease; PR006 for patients with frontotemporal dementia withGRNmutation (FTD-GRN); and PR004 for patients with certain synucleinopathies.

Prevail was founded by Dr.Asa Abeliovichin 2017, through a collaborative effort withThe Silverstein Foundationfor Parkinsons with GBA and OrbiMed, and is headquartered inNewYork, NY.

SOURCE: Preavail Therapeutics

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Prevail Therapeutics Announces Investigational New Drug Application Active for PR006 for the Treatment of Frontotemporal Dementia with GRN Mutation |...

Avectas and CCRM Announce Collaboration to Accelerate Development of Novel Technology for Cell Therapies – Yahoo Finance

DUBLIN and TORONTO, March 3, 2020 /PRNewswire/ --Avectas, a cell engineering technology business,and CCRM, a leader in developing and commercializing cell and gene therapies, today announced they have entered into a collaboration to accelerate the translation of Avectas' non-viral cell engineering platform (Solupore) into the clinic.

Cell and gene therapies offer the potential to dramatically transform the treatment of diseases, including cancer, for millions of patients worldwide. However, a global viral vector shortfall could halt progress in the industry as very few CDMOs have the capabilities required to manufacture vectors that can deliver molecules to cells.

Avectas developed Solupore to address an urgent need for an efficient, non-viral cell engineering solution to facilitate therapeutic development in the areas of immuno-oncology and gene editing.Solupore is designed for use with mRNA, DNA, and proteins, including gene editing tools such as CRISPR. It achieves excellent engineering efficiencies for delivery of these payloads toprimary T cells and NK cells for immuno-oncology and gene editing applications.

Speaking today, Dr. Michael Maguire, CEO of Avectas, said: "We are delighted to partner with CCRMto leverage their deep experience in cell manufacturing processes to support the translation of our Solupore platform towards clinical applications." He continued: "Combining Avectas' novel cell engineering platform and CCRM's experience in the development of manufacturing processes for cell therapies will accelerate the transfer of the Solupore technology to our development partners."

Dr. Michael May, President and CEO of CCRM, said:"This collaboration demonstrates exactly how CCRM is able to support partners and the broader industry. It is evident there is a real need for a non-viral delivery platform to enable the manufacture of these lifesaving cellular therapies and we are eager to receive the Solupore platform and support the Avectas team in bringing this innovative platform to the clinic."

About Avectas

Avectasis a cell engineering technology business developingaunique delivery platform to enable the ex-vivo manufacture ofour partners' gene modified cell therapy products, which will retain high in-vivo functionality. Our vision is to be a leading non-viral cell engineering technology provider, integrated into manufacturing processes for multiple autologous and allogeneic therapies, commercialized through development and license agreements. For more information, please visit the Company's website at: http://www.avectas.com.

About CCRM

CCRM, a Canadian not-for-profit organization funded by the Government of Canada, the Province of Ontario, and leading academic and industry partners, supports the development of regenerative medicines and associated enabling technologies, with a specific focus on cell and gene therapy. A network of researchers, leading companies, strategic investors and entrepreneurs, CCRM accelerates the translation of scientific discovery into new companies and marketable products for patients, with specialized teams, funding, and infrastructure. CCRM is the commercialization partner of the Ontario Institute for Regenerative Medicine and the University of Toronto's Medicine by Design. CCRM is hosted by the University of Toronto. Visit us at http://www.ccrm.ca.

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SOURCE Avectas; CCRM

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Prevail Therapeutics Provides Clinical Advancement Update on PR001 for the Treatment of Parkinson’s Disease with GBA1 mutationsCompany Will Present at…

NEW YORK, March 03, 2020 (GLOBE NEWSWIRE) --Prevail TherapeuticsInc. (Nasdaq: PRVL), a biotechnology company developing potentially disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases, provided an update today on the clinical advancement of its gene therapy program PR001 for patients with Parkinsons disease with GBA1 mutations (PD-GBA). Enrollment in the PR001 Phase 1/2 PROPEL clinical trial is progressing, patient dosing continues, and the Company is on track to report interim data on a subset of patients in the second half of 2020.

The Company will present on its clinical progress at the Cowen & Co. Annual Healthcare Conference in Boston today.

We believe the PROPEL trial makes PR001 the first potentially disease-modifying gene therapy for PD-GBA patients to enter clinical trials. Its ongoing progress brings us a step closer to new treatment options for patients living with PD-GBA, said Asa Abeliovich, M.D., Ph.D., Founder and Chief Executive Officer of Prevail. We are excited about the potential of PR001 to slow or stop disease progression for PD-GBA patients.

The PROPEL trial is a randomized, double-blind Phase 1/2 clinical trial evaluating the safety and tolerability of two escalating dose levels of PR001 in up to 16 patients with moderate-to-severe PD-GBA. The trial also evaluates the effect of PR001 on biomarkers of disease activity and on Parkinsons disease clinical efficacy measures. Full trial details are available at clinicaltrials.gov.

PR001 utilizes an AAV9 viral vector to deliver theGBA1gene to a patients cells, correcting the lysosomal enzyme deficiency caused by PD-GBA patients GBA1 mutations. GBA1encodes the lysosomal enzyme, beta-glucocerebrosidase, or GCase, which is required for the disposal and recycling of glycolipids. PD-GBA patients have a mutation in at least one chromosomal copy ofGBA1.

In addition to the PROPEL clinical trial for patients with PD-GBA, PR001 is also being developed for neuronopathic Gaucher disease, a devastating disorder that shares the same underlying genetic mechanism. In December 2019, the Company announced that its IND for PR001 for the treatment of neuronopathic Gaucher disease is active.

About PD-GBAParkinsons disease is a chronic, progressive neurodegenerative disorder that affects up to one million people in the United States and more than seven million people worldwide. PD-GBA affects 7% to 10% of the total Parkinsons disease population worldwide and an estimated 90,000 individuals in the United States alone. GBA1 encodes the lysosomal enzyme, beta-glucocerebrosidase, or GCase. Mutations in the GBA1 gene lead to a deficiency of GCase, resulting in lysosomal dysfunction in CNS cells, which we believe leads to the inflammation and neurodegeneration present in PD-GBA. GBA1 mutations impact the risk of developing Parkinsons disease as well as many other aspects of the disease course, including the severity, age of onset and rate of progression of disease and the likelihood of dementia. There are no treatments available that modify the progressive course or the underlying disease process of Parkinsons disease.

About Prevail TherapeuticsPrevail is a gene therapy company leveraging breakthroughs in human genetics with the goal of developing and commercializing disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases. The company is developing PR001 for patients with Parkinsons disease with aGBA1mutation (PD-GBA) and neuronopathic Gaucher disease; PR006 for patients with frontotemporal dementia withGRNmutation (FTD-GRN); and PR004 for patients with certain synucleinopathies.

Prevail was founded by Dr.Asa Abeliovichin 2017, through a collaborative effort withThe Silverstein Foundationfor Parkinsons with GBA and OrbiMed, and is headquartered inNewYork, NY.

Forward-Looking Statements Related to PrevailStatements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Examples of these forward-looking statements include statements concerning Prevails ability to develop meaningful therapeutic advances for patients with neurodegenerative diseases, the continued progression of our PROPEL Phase 1/2 clinical trial, the continued dosing of patients and the expected timing for the delivery of interim data from a subset of patients from our PROPEL Phase 1/2 clinical trial. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Prevails novel approach to gene therapy makes it difficult to predict the time, cost and potential success of product candidate development or regulatory approval; Prevails gene therapy programs may not meet safety and efficacy levels needed to support ongoing clinical development or regulatory approval; the regulatory landscape for gene therapy is rigorous, complex, uncertain and subject to change; and the fact that gene therapies are novel, complex and difficult to manufacture. These and other risks are described more fully in Prevails filings with theSecurities and Exchange Commission(SEC), including the Risk Factors section of the Companys Quarterly Report on Form 10-Q for the period endedSeptember 30, 2019, filed with theSEConNovember 12, 2019, and its other documents subsequently filed with or furnished to theSEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Prevail undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Media Contact:Mary CarmichaelTen Bridge Communicationsmary@tenbridgecommunications.com617-413-3543

Investor Contact:investors@prevailtherapeutics.com

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Prevail Therapeutics Provides Clinical Advancement Update on PR001 for the Treatment of Parkinson's Disease with GBA1 mutationsCompany Will Present at...

Voyager Therapeutics Announces Fourth Quarter and Full Year 2019 Financial Results and Corporate Updates – Yahoo Finance

Protocol amendment being implemented for ongoing RESTORE-1 trial of VY-AADC (NBIb-1817) for Parkinsons disease; plan to initiate RESTORE-2 trial in 2H 2020

Update on VY-HTT01 for Huntingtons disease preclinical program expected in 2Q 2020

Strong financial position with ~$282M of cash at the end of 2019 and expected runway into mid-2022

CAMBRIDGE, Mass., March 03, 2020 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (VYGR), a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases, today reported its fourth quarter and full year 2019 financial results, program progress and corporate updates.

In 2019, we took important steps toward our vision of establishing Voyager as the leader in neurological gene therapy, including forming our strategic collaboration with Neurocrine Biosciences, expanding our partnership with AbbVie, and further progressing our wholly-owned and partnered programs, said Andre Turenne, President and CEO of Voyager. Turning to 2020, we are excited to continue this momentum across all programs. These initiatives include presenting longer-term data from the Parkinsons disease program, advancing our Huntingtons disease program, and further leveraging our novel capsid research and expertise in vector engineering and delivery toward additional pipeline programs.

Recent Corporate Highlights and Program Outlook

VY-AADC for Parkinsons Disease

VY-HTT01 for Huntingtons Disease

Early Pipeline and Platform

Corporate Updates

Anticipated Upcoming Milestones

VY-AADC for Parkinsons Disease:

VY-HTT01 for Huntingtons Disease:

Early Pipeline and Platform:

Fourth Quarter and Full Year 2019 Financial Results

Financial Guidance

Conference Call Information

Voyager will host a conference call and webcast today at 4:30 p.m. EST. The conference call may be accessed by dialing (877) 851-3834 for domestic callers, or +1 (631) 291-4595 for international callers. Please reference conference ID number 8461408 to join the call. The conference call will be webcast live from the Investors & Media section of Voyagers website at http://www.voyagertherapeutics.com and will be archived there following the call for 90 days.

About Voyager Therapeutics

Voyager Therapeutics is a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases. Voyager is committed to advancing the field of AAV gene therapy through innovation and investment in vector engineering and optimization, manufacturing, and dosing and delivery techniques. Voyagers wholly-owned and partnered pipeline focuses on severe neurological diseases for which effective new therapies are needed, including Parkinsons disease, Huntingtons disease, a monogenic form of ALS called SOD1, Friedreichs ataxia, Alzheimers disease, and other neurodegenerative diseases related to defective or excess aggregation of tau and alpha-synuclein proteins in the brain. Voyager has strategic collaborations with AbbVie and Neurocrine Biosciences. Founded by scientific and clinical leaders in the fields of AAV gene therapy, expressed RNA interference and neuroscience, Voyager is headquartered in Cambridge, Massachusetts. For more information, please visit http://www.voyagertherapeutics.com or follow @VoyagerTx on Twitter and LinkedIn.

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 may, might, will, would, should, expect, plan, anticipate, believe, estimate, undoubtedly, project, intend, future, potential, or continue, and other similar expressions are intended to identify forward-looking statements. For example, all statements Voyager makes regarding the initiation, timing, progress, activities, goals and reporting of results of its preclinical programs and clinical trials and its research and development programs, the potential benefits, timing and future operation of the collaboration agreements with AbbVie and Neurocrine Biosciences, including any potential future payments thereunder, its ability to identify and attract parties to participate in research and development collaborations, its ability to advance its AAV-based gene therapies into, and successfully initiate, enroll and complete, clinical trials, the potential clinical utility of its product candidates, its ability to continue to develop its gene therapy platform, its ability to perform under existing collaborations including those with AbbVie and Neurocrine Biosciences, its ability to add new programs to its pipeline, the regulatory pathway of, and the timing or likelihood of its regulatory filings and approvals for, any of its product candidates, its ability to operate its research and development activities efficiently and effectively, the utility and value of Voyagers patent portfolio, and Voyagers anticipated financial results, including Voyagers available cash, cash equivalents and marketable debt securities, the receipt by Voyager of revenues or reimbursement payments from collaboration partners, Voyagers operating expenses, and Voyagers ability to fund its operating expenses with its current cash, cash equivalents and marketable debt securities though a stated time period are forward looking. All forward-looking statements are based on estimates and assumptions by Voyagers management that, although Voyager believes such forward-looking statements 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 Voyager expected. Such risks and uncertainties include, among others, those related to the initiation and conduct of preclinical studies and clinical trials; the availability of data from preclinical studies and clinical trials; the expectations for regulatory communications, submissions and approvals; the continued development of the gene therapy platform; Voyagers scientific approach and general development progress; the ability to attract and retain talented contractors and employees; the ability to create and protect intellectual property; the sufficiency of cash resources; the possibility or the timing of the exercise of development, commercialization, license and other options under collaborations; and the availability or commercial potential of Voyagers product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Voyagers Annual Report on Form 10-K filed with the Securities and Exchange Commission, as updated by its subsequent filings with the Securities and Exchange Commission. All information in the press release is as of the date of this press release, and any forward-looking statement speaks only as of the date on which it was made. Voyager undertakes no obligation to publicly update or revise this information or any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Investors: Paul CoxVP, Investor Relations857-201-3463pcox@vygr.com

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Voyager Therapeutics, Inc.Selected Financial Information($-amounts in thousands, except per share data)(Unaudited)

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Voyager Therapeutics Announces Fourth Quarter and Full Year 2019 Financial Results and Corporate Updates - Yahoo Finance

First-Year Lab Experience Gave This Student the Confidence to Aim for a Ph.D. – UVA Today

A University of Virginia biomedical engineering student is trying to tackle the worlds No. 1 cause of death on a genetic level.

Rita Anane-Wae, from Ghana by way of Glendale, Arizona, and a third-year biomedical engineering student, is using a 2019 Harrison Undergraduate Research grant to seek a genetic solution to atherosclerosis, or the build-up of plaque in ones arteries, which impedes blood flow.

There are cells that will try to fix this problem by covering them and basically pushing the plaque down to allow blood flow, she said. These cells will try to reduce that plaque so that there is correct blood flow. In very serious cases, the plaque can harden and break off. Once it breaks, it can get lodged somewhere and cause a stroke or a heart attack.

Created through a gift from the late David A. Harrison III and his family, the Harrison Undergraduate Research Awards fund outstanding undergraduate research projects. Selected by a faculty review committee, awardees receive as much as $4,000 apiece to pursue their research interests, under the direction of a faculty mentor.

Anane-Wae started working in a laboratory run by Mete Civelek, an assistant professor of biomedical engineering, as a second-year student.

Civelek had already altered her life. Anane-Wae came to UVA to be a chemical engineer. She met Civelek when she signed up as a first-year student for a program that offered faculty mentoring.

At the time I was a chemical engineering major with an interest in biomedical engineering, Anane-Wae said. After talking with him, he was able to assuage my fears about biomedical engineering.

Biomedical engineering is a relatively new field and as such, I did not believe there were many jobs out there, and my parents were worried for the same reason, she said. Mete has a chemical engineering undergrad degree and a masters and Ph.D. in biomedical engineering, so he was the perfect person for me to talk to. He explained the two fields in a unique way, unlike what I had read and seen on YouTube.

Honestly, I love biomedical engineering. When I switched into biomedical engineering, literally in my first class, I though Oh, my God, this is home. I am learning about anatomy, physiology, genes and cells, and it is still all really exciting for me.

Civelek also suggested Anane-Wae participate in the research trip to Uganda through the UVA Minority Health & Health Disparities International Research Training program to perform research on congestive heart failure. While in Uganda, Anane-Wae made rounds with a doctor at a local hospital and met a 17-year-old girl suffering from congestive heart failure.

Her legs were all swollen, Anane-Wae said. She had edema and her stomach was filled with fluid. I was looking at her and thinking, This girl cant lay down because of all the swelling and she cant even be at rest. And I was thinking, She is about my age and I am fortunate enough to be traveling the world and she is here stuck in this hospital bed.

Her encounter with the girl became part inspiration to her and part reminder that congestive heart failure is not just for older patients.

I have a hard time accepting what I am capable of doing, Anane-Wae said. Being here, being in Uganda, working in the lab, it has taught me that I am basically capable of making change. I know what I am supposed to be doing with my time and my future and I know that doing it makes me happy and will make other people better.

In her lab work, Anane-Wae studies a specific gene melanoma inhibitor activity 3, or MIA3 that affects smooth muscle cells.

Smooth muscle cells are able to basically cover the plaque in that disease state, Anane-Wae said. We are running experiments to see how us modulating MIA3 affects the disease.

She said she and members of the research team in the lab also performed experiments knocking out the MIA3 gene from the cells, which led to a more serious disease state.

I think experiments like these are really important because we are not yet at the stage where we can do gene therapy on a person, Anane-Wae said. If you knock out specific genes, it will affect things that we dont understand yet.

Anane-Wae is working on a small section of a large field, but she thinks there is promise in the work she is doing.

The genome-wide association studies show that 161 different genes so far have been associated with coronary artery disease, she said. And we are studying just one. There is so much further that we have to go.

The path is really long, but we are trying to understand the mechanism by which one gene affects the disease and if we actually figure out that mechanism, we can try to apply it to the other genes and maybe understand the bigger picture.

Research can lead her down many blind alleys, which she understands. Anane-Wae is also very conscious of the law of unintended consequences, and how something that solves one problem can create other problems in the process.

We can say that about everything, she said. I think that is the way with all new development. You fix problems and new ones will arise, and then you fix those, too. So we can only do so much. But I think what I have learned is that I have found something about which I am passionate. I have found something that I enjoy and here at UVA, I have found a community of people who will help me develop my skills.

Included in that community, Anane-Wae cited Civelek and Redouane Aherrahrou, an American Heart Association Postdoctoral Fellow with whom she works.

Aherrahrou has known Anane-Wae since she joined the lab in 2018. When she first joined our lab, Rita knew only the fundamental lab skills and methods, he said. After a short amount of training, she learned rapidly and became very familiar with the cell culture techniques and appropriate lab handling. She performed the experiments independently. Her interactions with other lab members are both professional and friendly.

He described Anane-Wae as a diligent researcher, a gifted student, an inspiring person, and enjoyable to be around.

She has a great personality, is open to guidance and responds well to criticism, he said. She wants to apply to Ph.D. programs after she graduates, and I predict a great future in her career as a research scientist.

Civelek said he enjoys having Anane-Wae as part of his team.

She is hard-working, curious and eager to make a scientific impact, he said. I can see the joy in her face when she learns something new. She gets along well with everyone in the lab and is a role model to those who are junior to her. She has a bright future and I am very proud of her accomplishments.

Civelek said Anane-Wae was recently awarded a German Academic Exchange Research Internship in Science and Engineering, which is presented to only 300 students from the U.S. and Canada.

Redouane and Mete both have high standards for me and motivate me to do my very best, Anane-Wae said. They have instilled a confidence in me that I did not have prior to joining the lab, and they continuously push me to achieve great things. I am so fortunate to have these two individuals as mentors, in addition to all of the other members in the laboratory.

A Blue Ridge Scholarship recipient, Anane-Wae is member of the National Society of Black Engineers and the Society of Women Engineers. She also has received a Hugh Bache Scholarship.

Anane-Wae said she is looking at doing big things, such as gene therapy, but realizes that she has to take small steps at first, and that her friends in the lab will help her out when things go wrong.

She has also learned that research is a team effort, not a solo pursuit.

You cant do research by yourself, she said. You wont be able to get anything done. You will have to depend on other people and you have to be able to share what you have learned. You wont get anything done in any amount of time if you dont trust other people and work together.

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First-Year Lab Experience Gave This Student the Confidence to Aim for a Ph.D. - UVA Today

How does gene therapy work? – Genetics Home Reference – NIH

Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.

A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can't cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.

The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein.

Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.

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How does gene therapy work? - Genetics Home Reference - NIH

Nationwide Childrens among hospitals leading the way in gene therapy – The Columbus Dispatch

The Center for Gene Therapy at Nationwide Childrens Hospital is working to develop childrens gene therapy treatments. Officials say the gene therapy research and clinical trials there are starting to attract companies to central Ohio.

Nationwide Childrens Hospital is in the forefront of curing several genetic childhood diseases, transforming Columbus into a major medical hub, several gene therapy experts say.

The hospital's Center for Gene Therapy at the Abigail Wexner Research Institute is working to develop treatments for children, which is attracting patients and companies to Ohio, according to officials at Nationwide Childrens and JobsOhio, the state's economic development organization.

The illnesses that were making use of in gene therapy are devastating illnesses, said Dr. Kevin Flanigan, the director of Nationwide Childrens Center for Gene Therapy. These are ones we know that children would be significantly impaired for life or die because of the disease.

Gene therapy involves altering the genes inside the patient's cells in an effort to treat or stop disease. It gives doctors the chance to treat many previously untreatable rare and genetic diseases.

Gene therapy is currently available primarily in a research setting, with only four gene therapy products approved by the U.S. Food and Drug Administration for sale in the United States. One of the four, Zolgensma, started as a clinical trial for spinal muscular atrophy at Nationwide Childrens in 2014.

The hospital is working on a handful of gene therapy treatments for various childhood diseases that affect muscle, motor or mental functions, Flanigan said.

Gene therapy presents a tremendous opportunity for our medical system, and Columbus has been a huge part of that growth thanks to the work being done at Nationwide Childrens Hospital, Edith Pfister, chairwoman of the American Society of Gene & Cell Therapys communications committee, said in an email.

The FDA approved Zolgensma, a one-time treatment that intravenously delivers the gene that is missing in children with spinal muscular atrophy, on May 24.

SMA is a progressive childhood neuromuscular disease that is caused by a mutation in a single gene that attacks nerve cells. It causes major physical limitations including the inability to breathe, swallow, talk or sit up. Children born with SMA typically die or need permanent breathing assistance by the time they turn 2 years old.

Donovan Weisgarber was diagnosed with SMA type 1 at Nationwide Childrens in November 2015 when he was 5 weeks old. His parents, Matt and Laura Weisgarber, decided to participate in a clinical trial at the hospital and Donovan received Zolgensma.

Before the treatment, Donovan was unable to swallow and had difficulty breathing. Today, the 4-year-old has doubled his life expectancy and is able to talk, sit up, roll over and hold his head up on his own. He also attends the Early Childhood Education and Family Center on Johnstown Road on the East Side, which offers services from the Franklin County Board of Developmental Disabilities.

(Gene therapy) has given us an opportunity that we otherwise wouldnt have to love Donovan and experience him, said Matt Weisgarber, 33, of the Northeast Side.

A lot of people hear Ohio and think flyover state, but now Columbus is going to be a hub of the most groundbreaking science known to mankind and thats a really cool thing, he said.

Boston Childrens Hospital and Childrens Hospital of Philadelphia also have impressive gene therapy centers, but Columbus sets itself apart from those East Coast cities, said Severina Kraner, JobsOhios health care director.

The cost to operate, manufacture and live in Ohio is cheaper than Boston and Philadelphia, putting Ohio in a position to win cell and gene therapy companies, she said.

People are being priced out of these coastal cities, Kraner said.

One of the companies who has committed to building in Columbus is Sarepta Therapeutics, a Massachusetts-based biopharmaceutical company. Sarepta signed an agreement with Nationwide Childrens in May 2019, giving the company the licensing to a gene therapy treatment that came out of hospital research for limb-girdle muscular dystrophies, a group of diseases that cause weakness and wasting of the muscles in the arms and legs.

Sarepta is scheduled to open an 85,000-square-foot Gene Therapy Center of Excellence near Nationwide Childrens Hospital in the fall to do early research for all the companys gene therapy programs. A team of about 30 employees from Sarepta is currently working at a facility at Easton Town Center.

The region has every ingredient needed for a thriving gene therapy cluster: a strong academic foundation, world-renowned research hospitals, and, now, industry investment, Louise Rodino-Klapac, Sareptas senior vice president of gene therapy, said in an email. All of these contribute to creating a pipeline of talented people who will accelerate scientific advances that help patients.

Nationwide Childrens recently also announced it will be expanding its gene therapy research by creating Andelyn BioSciences, a new for-profit subsidiary that will manufacture gene therapy products for the biotechnology and pharmaceutical industries.

Were hoping, and we have a vision, that Andelyn can help capitalize a biotechnology hub in central Ohio focused on developing and advancing gene therapies, said Dr. Dennis Durbin, Nationwide Childrens chief science officer.

Andelyn BioSciences will launch this summer and operate out of the Abigail Wexner Research Institute, 575 Children's Crossroad. Nationwide Children's is trying to secure a permanent location for Andelyn and is looking at land on Ohio State Universitys West Campus.

Gene therapy treatment, however, comes at a high price.

The manufacturer set the price of Zolgensma at more than $2.1 million. Insurers can pay $425,000 a year for five years for one treatment.

Insurance companies are used to regular installment payments, but the single-dose nature of gene therapies are adding a level of uncertainty to health insurance structures, Pfister said in an email. A one-time administration gene therapy costs less overall, but it occurs in one upfront payment.

Pfister said she is hopeful the cost of gene therapy will go down.

Currently, most of the FDA-approved gene and cell therapies are tailored for the specific patient, but theres an incredible amount of research going into standardizing the components and delivery mechanisms behind gene therapy, Pfister said in an email.

Dr. Jerry Mendell helped usher in the era of gene therapy at Nationwide Childrens when he came to the hospital in 2004.

Nationwide Childrens first gene therapy trial was in 2006 for duchenne muscular dystrophy, a rare, inherited, degenerative muscle disorder that almost exclusively affects boys.

Things have really changed significantly in the gene therapy world because of the contributions weve made here, and its been a very gratifying experience, said Mendell, the principal investigator in Nationwide Childrens Center for Gene Therapy.

mhenry@dispatch.com

@megankhenry

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Nationwide Childrens among hospitals leading the way in gene therapy - The Columbus Dispatch

BioMarin gene therapy won’t need an AdComm as it nabs speedy FDA review – FierceBiotech

BioMarins hemophilia A drug has been set an Aug. 21 PDUFA date as the California biotech looks to gain a speedy approval for the first-ever gene therapy for the bleeding disease.

The company said Friday morning the FDA had granted its AAV5 gene therapy, valoctocogene roxaparvovec, a quick review and that, at the moment at least, it didnt see the need for an expert committee to assess the drug, giving it a smoother path to a potential approval.

The FDA has also accepted the premarket approval application for a companion diagnostic test for valoctocogene roxaparvovec, helping identify the patients it can treat. The test is made by ARUP Laboratories, a nonprofit enterprise of the University of Utah and its department of pathology, it said in a statement.

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The drug is also under a speedy review in Europe.

Its not all been smooth sailing: Three-year data on its candidate were reported last May but sparked concerns about the durability of the therapy, also known as "valrox," after factor VIII levels seemed to fall off after 12 to 18 months, raising the possibility that patients might need to be re-dosed to maintain protection against bleeds.

Its main competition could come from Pfizer and Sangamo Therapeutics hemophilia A gene therapy SB-525, which reported positive data late last year, with Roche/Spark Therapeutics also in contention with SPK-8011.

Spark, however, suffered a setback after two patients treated with SPK-8011 developed immune reactions, one of which had to be treated in a hospital, but reported encouraging results with its therapy last February. It has since been snapped up in a (protracted) $4.3 billion takeover by Swiss major Roche.

RELATED: BioMarin drops lower dose of its hemophilia gene therapy as it eyes submissions by year-end

The hemophilia community has been waiting for decades for gene therapies. The FDA acceptance of the filing and initiation of review for the first gene therapy for hemophilia A builds on years of scientific achievements in improving the standard of care for people with bleeding disorders, said Doris Quon, M.D., medical director at the Orthopaedic Hemophilia Treatment Center at the Orthopaedic Institute for Children.

As a treating physician, I look forward to the possibility of having more treatment options for people with hemophilia.

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BioMarin gene therapy won't need an AdComm as it nabs speedy FDA review - FierceBiotech

Gene therapy to halt rare form of sight loss – BBC News

Image caption Matthew Wood hopes the gene therapy will help him keep his remaining vision

A new gene therapy has been used to treat patients with a rare inherited eye disorder which causes blindness.

It's hoped the NHS treatment will halt sight loss and even improve vision.

Matthew Wood, 48, one of the first patients to receive the injection, told the BBC: "I value the remaining sight I have so if I can hold on to that it would be a big thing for me."

The treatment costs around 600,000 but NHS England has agreed a discounted price with the manufacturer Novartis.

Luxturna (voretigene neparvovec), has been approved by The National Institute for Health and Care Excellence (NICE), which estimates that just under 90 people in England will be eligible for the treatment.

The gene therapy is for patients who have retinal dystrophy as a result of inheriting a faulty copy of the RPE65 gene from both parents. The gene is important for providing the pigment that light sensitive cells need to absorb light. Initially this affects night vision but eventually, as the cells die, it can lead to complete blindness.

An injection is made into the back of the eye - this delivers working copies of the RPE65 gene. These are contained inside a harmless virus, which enables them to penetrate the retinal cells. Once inside the nucleus, the gene provides the instructions to make the RPE65 protein, which is essential for healthy vision.

Matthew Wood started losing his sight as a child, and is now registered blind. However, he does have some peripheral vision and can detect large objects and bright lights. He told the BBC: "Since I was a child I was continually told there was no treatment for this condition, so it's amazing to receive this gene therapy."

Mr Wood, from London, had his right eye treated during an hour-long operation at the John Radcliffe Hospital in Oxford.

His left eye will be injected in a few weeks. The surgery was carried out by Prof Robert MacLaren, who has pioneered research into gene therapies for preventing blindness.

He told the BBC: "This is very exciting - this is the first approved NHS gene therapy for an eye disease, but there are opportunities to use gene therapy to treat other diseases in future, not only in the eye."

The treatment is only suitable for patients who have some remaining vision. It should bring the biggest benefits to children with RPE65 retinal dystrophy, as it could halt sight loss before permanent damage is done.

It is not known how long the benefits of the treatment will last, but it's thought it could be several decades.

Jake Ternent, 23, from Durham, had his gene therapy at Moorfields Eye Hospital in London.

Like Matthew Wood, he is registered blind, but has some limited sight. He told the BBC: "I hope the treatment could improve my night vision, and possibly even my day vision, which would be incredible. I feel lucky and privileged to get this on the NHS."

Prof James Bainbridge - from Moorfields Eye Hospital - who treated Jake, told the BBC: "To be at the point now where we are able to offer this treatment on the NHS, is truly remarkable. This is the first example of what's anticipated to be a whole new generation of treatments."

It will take a month or two before Matthew and Jake know what changes the gene therapy has made to their vision. But even if it simply prevents further sight loss, both say they will be delighted.

Professor Stephen Powis, NHS medical director, said: "Loss of vision can have a devastating effect, particularly for children and young people, but this truly life-changing treatment offers hope to people with this rare and distressing condition."

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Gene therapy to halt rare form of sight loss - BBC News

With supply tight, Novartis readies gene therapy plant for production – BioPharma Dive

Supplies of Zolgensma, the gene therapy approved last year for spinal muscular atrophy, are tight.

Novartis, which sells the one-time treatment, can currently make about 700 to 800 doses a year at its manufacturing plant in Libertyville, Illinois. That's enough to cover the infants in the U.S. currently eligible to receive Zolgensma but leaves little room for treating a wider group of patients, which the Swiss drugmaker aims to do.

On Thursday, executives from AveXis, the Novartis unit that developed Zolgensma, opened a new facility in Durham, North Carolina, that the company views as a critical cog in its plans to expand supply of the gene therapy.

Initial production will begin this spring. But until the Food and Drug Administration licenses the plant, Novartis won't be able to use product made there for commercial sale. The company expects to gain approval next year.

Between now and then, Novartis also hopes to secure regulatory OKs for manufacturing Zolgensma at a site in Longmont, Colorado, bought last year, and through the contract manufacturer Catalent.

"There is a short-term challenge over the next six to nine months to make sure that we can manage the supplies that are out there," said David Lennon, president of Novartis' AveXis unit, in an interview.

"We feel comfortable where we are, but we'd love to have these other sites onboard to make sure we're really robust and don't face any risks of shutdowns or anything that could impact supply."

Limited supply has also kept Novartis from widening a program set up to make the gene therapy available free of charge to patients in countries where it's not yet approved. The "expanded access" scheme, which was launched in January, randomly allocates doses of Zolgensma for participating patients under the age of two with genetically confirmed spinal muscular atrophy.

This year, Novartis plans to distribute 100 doses through the lottery, which has been criticized as putting a child's life to chance.

"We obviously know that not everyone is happy with the program," said Lennon. "We're still considering what we might do, but we're open to making changes if it makes sense for the community and to meet the goals of the program."

Lennon said he hoped to expand the program as more manufacturing capacity for Zolgensma becomes available.

Novartis has committed upwards of $200 million to building out the site in Durham, which will employ about 400 staff by the end of the year.

Spanning 170,000 square feet, the facility will be used for both commercial Zolgensma manufacturing as well as to support clinical production of other gene therapies that Novartis is developing.

"This is as much an investment in the short term in building out our supply for Zolgensma, as it is for the long term to have the flexibility to deliver on a robust pipeline," said Lennon.

Novartis currently expects to treat about 100 infants every three months in the U.S. under Zolgensma's current label. But it's also working to expand the therapy's approval to treat older children over two using a spinal injection rather than an infusion.

That patient population is significantly larger and will test Novartis' ability to produce a steady supply of the drug, although the FDA has placed a partial "hold" on the study testing the new dosing.

Novartis' launch of Zolgensma is under significant scrutiny, both because of the $2.1 million price tag the drugmaker put on the therapy and due to a data manipulation scandal that engulfed the company last year.

Despite the high cost, insurers have largely covered treatment, leading to strong sales of Zolgensma in its first three quarters on the market.

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With supply tight, Novartis readies gene therapy plant for production - BioPharma Dive

New Gene Therapies Institute Aims to Address Regulatory Barriers – HealthITAnalytics.com

February 20, 2020 -The Institute for Gene Therapies (IGT), a new advocacy foundation focused on policy issues surrounding gene therapies, recently launched with the goal of modernizing US regulatory and reimbursement framework for gene therapies.

According to IGT, the US health system currently spends about 85 cents of every healthcare dollar managing the symptoms of chronic diseases over a patients lifetime. With gene therapies, providers could alter patients non-functioning genes or replace absent ones, leading to long-lasting effects and potentially reshaping the way thousands of diseases are treated.

While traditional biologic and pharmaceutical medicines help manage the symptoms of disease over time, gene therapies target the cause of disease at the DNA level, creating lasting changes in the body. Some gene therapies are also designed to be one-time treatments that offer lifelong benefits.

IGT will work to educate stakeholders across the healthcare system about the potential for gene therapies to treat and cure common and rare chronic diseases, and advocate for policies that help ensure patients who need gene therapies can benefit from them.

Existing regulatory and reimbursement structures were established and adjusted over time to support pharmaceutical and biologic medicines, IGT noted, and need refining to accommodate the potential of gene therapies.

READ MORE: Data Mining Techniques Could Improve Cancer Gene Therapies

Many crippling conditions like Charcot-Marie-Tooth (CMT), which I was diagnosed with before the age of two take hold at a very young age, cut lives far too short or cause ongoing daily suffering, said Susan Ruediger, CEO of the CMT Research Foundation (CMTRF) and member of the IGT Patient Advocacy Advisory Council.

Like so many diseases, CMT currently has no cure. I am proud to stand with other leading patient advocates, members of the research community and companies that are developing gene therapies to help ensure patients can fully realize the benefits of these giant leaps toward treatments and cures.

The FDA has already approved four gene therapy products, and researchers are studying hundreds more in clinical trials for rare and common diseases, including many types of cancer, neuromuscular diseases, blood disorders and infectious diseases, and other conditions.

The growth of innovative research and product development in the field of gene therapy is exciting to us as physicians, scientists and regulators, FDA Commissioner Stephen M. Hahn, MD, said in a statement.

We understand and appreciate the tremendous impact that gene therapies can have on patients by potentially reversing the debilitating trajectory of diseases. These therapies, once only conceptual, are rapidly becoming a therapeutic reality for an increasing number of patients with a wide range of diseases, including rare genetic disorders and autoimmune diseases.

READ MORE: Genetic Sequencing Study Identifies 102 Genes Associated with Autism

The FDA has also released six final guidance documents on gene therapy manufacturing and clinical development of products. These documents incorporate input from stakeholders across the healthcare industry and make important strides in designing a modern structure for gene therapy development.

As the regulators of these novel therapies, we know that the framework we construct for product development and review will set the stage for continued advancement of this cutting-edge field and further enable innovators to safely develop effective therapies for many diseases with unmet medical needs, said Peter Marks, MD, PhD, director of the FDAs Center for Biologics Evaluation and Research.

Scientific development in this area is fast-paced, complex, and poses many unique questions during a product review; including how these products work, how to administer them safely, and whether they will continue to achieve a therapeutic effect in the body without causing adverse side effects over a long period of time.

IGT will being together experts across the healthcare community, including corporate leaders, patient advocacy groups, and academic and scientific stakeholders, to ensure health policies reflect the latest advancements in gene therapies. The institute will also work to remove barriers that limit patient access to these therapies and promote sustainable, long-term solutions.

Experts will learn more about the value gene therapies bring to patients, their families, and the healthcare system as a whole. IGT will help advance chronic disease treatments and get to the root cause of some of the most debilitating, expensive conditions that affect patients throughout their lives.

READ MORE: 77% of Americans Are Optimistic About Genetics Research, Potential

The incredible scientific advancements in this space present unique opportunities to directly improve and save the lives of patients suffering from debilitating diseases, said IGT Chairman, and former Congressman Erik Paulsen.

This is not some far-off future patients are already benefiting from the first FDA-approved gene therapies. But we need policy to move faster toward this new reality where we can treat the causes of many diseases. The Institute for Gene Therapies and our members believe unique regulatory and reimbursement structures need to be established, novel development pathways need to be embraced and new value-based arrangements need to be tested.

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New Gene Therapies Institute Aims to Address Regulatory Barriers - HealthITAnalytics.com

First patient undergoes Luxturna gene therapy on NHS – PharmaTimes

The NHS has reported treating its first patient with Novartis Luxturna (voretigene neparvovec) a revolutionary new gene therapy that can restore eyesight, as part of its NHS Long Term Plan.

The therapy is for those born with an inherited retinal disorder - Lebers Congenital Amaurosis (LCA) - who have poor sight which swiftly deteriorates, with many ultimately losing their vision completely in childhood.

The life-changing treatment for children and adults is the first in a new generation of gene therapies that can be directly administered to patients, in this case through an injection. Many patients in the trials have recovered their night time vision with the treatment.

Jake Ternet, patient at Moorfields Eye Hospital was the first in the UK to receive the treatment.

Professor Stephen Powis, NHS medical director, said:Loss of vision can have devastating effects, particularly for children and young people, but this truly life changing treatment offers hope to people with this rare and distressing condition.

Once again, the NHS is at the forefront of the genomic revolution with patients in England among the first to benefit from this new form of treatment a modern day miracle as part of the Long Term Plan.

Back in September last year, The National Institute for Health and Care Excellence (NICE) recommended the use of Luxturna on the NHS for certain patients with RPE65-mediated inherited retinal dystrophies in those with vision loss.

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First patient undergoes Luxturna gene therapy on NHS - PharmaTimes

Bluebird’s gene therapy hits another delay, this time in the US – BioPharma Dive

Dive Brief:

Bluebird's commercial operations are just getting off the ground. In its latest earnings report, the Cambridge, Massachusetts-based biotech detailed how it has inked agreements with health insurers in Germany that should provide coverage for LentiGlobin, which is sold under the brand name Zyntegloin Europe, for up to 50% of eligible beta-thalassemia patients. Bluebird expects the first commercial patient to be treated before July.

Across the Atlantic, U.S. patients are looking at a longer timeline before LentiGlobin becomes available. Stifel analysts wrote in a note to clients that they don't foresee any stateside patients receiving the therapy commercially in 2020 "given what we anticipate will be a complicated negotiation process with payors."

Analysts at Raymond James, meanwhile, downgraded Bluebird to a "Market Perform" rating, writing that "execution issues on the regulatory, clinical and manufacturing side outweigh our support for the innovative drug products."

As Bluebird works through the latest delay in beta-thalassemia,it will also be preparing for an expanded research program in sickle cell. The company already intended to kick off a late-stage study in sickle cell patients with a history of vaso-occlusive crises in the first half of 2020. With Tuesday's earnings presentation, though, came plans to initiate a second late-stage study sometime this year, which will evaluate LentiGlobin's effects in about 18 children with sickle cell and elevated stroke risk.

A sickle cell approval, though a ways off, could boost Bluebird's bottom line. Beta-thalassemiais rarer in U.S. than other parts of the world, and certainly less common than sickle cell. According to estimates cited by the National Organization of Rare Disorders, roughly 3,300 U.S. patients have beta-thalassemiaversus the 100,000 who have sickle cell.

An expanded program could provide more evidence of LentiGlobin's benefit in this larger patient pool.Yet the updates don't seem to have alleviated investor concerns. Bluebird shares were down nearly 10% in late Wednesday morning, trading around $80 apiece.

"LentiGlobin in Sickle Cell Disease remains a bright spot, in our view, but with [late-stage studies] expected to get underway this year, we don't expect investor sentiment to change anytime soon," Stifel analysts wrote.

The investment bank models Zyntelgo bringing in $12 million worth of revenue in 2020 from the beta-thalassemia indication, increasing to $53 million in 2021 and $390 million by 2030. Conversely, it models $48 million in 2022 from the sickle cell indication, increasing to almost $2 billion by 2030.

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Bluebird's gene therapy hits another delay, this time in the US - BioPharma Dive

First Patients Begin Gene Therapy Treatment for Blindness through NHS – Interesting Engineering

Back in September, a breakthrough gene therapy was found to treat inherited retinal dystrophies. Now, people in the UK are being treated with it.

This gene therapy is meant for people who are born with retinal dystrophy. It happens when the patient inherits a faulty copy of the RPE65 gene from both parents. Babies lose sight as they grow older since this gene is crucial for providing the requirements that light-sensitive cells need to absorb light.

The trouble of sight starts with poor night vision and leads to complete blindness with the death of the current cells.

SEE ALSO:BLIND WOMAN PLAYS VIDEO GAME THANKS TO IMPLANT THAT JACKS DIRECTLY INTO THE BRAIN

NHS therapy is expected to halt sight loss and even improve vision in the process. In order to do this, working copies of the RPE65 gene is injected into the back of the eye. The copies are put inside a harmless virus and the virus penetrates the retinal cells.

After the virus is inside the nucleus, the gene provides the instructions to make the RPE65 protein. This provides a healthier vision.

The treatment is sadly only suitable for patients who have some vision remaining. It is expected to be beneficial to the children who have this eye disorder since it can stop sight loss before any permanent damage is done.

Matthew Wood is one of the first patients to receive the therapy. He started losing his sight as a child, and only had peripheral vision currently. His surgery was carried out by Professor Robert MacLaren.

In a BBC interview, MacLaren said, This is very exciting this is the first approved NHS gene therapy for an eye disease, but there are opportunities to use gene therapy to treat other diseases in the future, not only in the eye.

One downside of the treatment is the price point with 600,000. However, NHS England has stated that they have agreed on a discount with the manufacturer Novartis.

See more here:

First Patients Begin Gene Therapy Treatment for Blindness through NHS - Interesting Engineering

Spark R&D chief High exits in wake of Roche takeover – FierceBiotech

Spark Therapeutics co-founder and R&D head Kathy High has left the gene therapy specialist in the wake of its takeover by Roche. The Basel-based Big Pharma talked up its ability to cope with the loss of the R&D chief, pointing to the 450-person team High helped build to back up its confidence.

As a professor at Children's Hospital of Philadelphia (CHOP), High was involved in early efforts to give patients with an inherited vision loss disorder a functioning version of RPE65. The work led High to found Spark with Jeff Marrazzo, who became CEO of the biotech, and Steven Altschuler, the former president of CHOP, and ultimately to the approval of RPE65 gene therapy Luxturna.

High oversaw the development of Luxturna and the rest of Sparks pipeline. However, with Spark now part of Roche, High has decided to end her time in industry. Philadelphia Business Journal first broke the news, which Roche subsequently confirmed in a statement.

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Roches statement highlighted the central role High played in Luxturna, Sparks hemophilia A and B gene therapy candidates and its takeover of the biotech she co-founded. However, Roche also sought to downplay the risk that Highs departure could harm the prospects of the pipeline it acquired in the takeover of Spark.

Today, Spark has broad scientific knowledge and expertise in gene therapy, with the company now numbering more than 450 employees and continued growth expected in the future. This is why we dont expect any impact on the scientific expertise of our team or clinical programs. We expect that our scientific and clinical teams will continue their proven track record of innovation, progress and safety, the Roche spokesperson said.

Roche singled out a hemophilia A gene therapy as a Spark program that it remains committed to. The public commitment to the program follows a lull in news about the gene therapy. Spark shared phase 1/2 data late in 2018 and quietly began a lead-in study for a phase 3 trial last year. However, the gene therapy specialist said little about the program during its protracted takeover by Roche.

The period of radio silence now looks set to end, with Roche stating it will share an update on the program in due course. Roche will have to manage the program without the support of High, who is set to take some well-deserved time off and then will begin a new chapter in a sabbatical at a university, according to the Swiss Big Pharma.

Continued here:

Spark R&D chief High exits in wake of Roche takeover - FierceBiotech

Why So Many Biotechs Are Scrambling to Develop a Drug for the Same Rare Disease – The Motley Fool

Nearly 1.8 million Americans were diagnosed with cancer last year. Around the world, the total was close to 17 million. It's not surprising, then, that more than 700 biopharmaceutical companies have experimental cancer drugs in late-stage development.

Beta-thalassemia, on the other hand, is a rare disease that affects around 1,000 or so people in the United States. It's more prevalent in some countries but still impacts only one in 100,000 individuals.

You might expect one or maybe two biotechs could be developing therapies to treat beta-thalassemia. However, by my count, at least half a dozen companies have programs targeting the blood disorder. Why are a disproportionate number of biotechs scrambling to develop drugs for the same rare disease?

Image source: Getty Images.

Probably the main reason why a relatively large group of drugmakers are targeting beta-thalassemia is that the cause of the disease is straightforward. Understanding the why behind a disease is a critical prerequisite to treating it.

Beta-thalassemia is usually caused by a mutation in the HBB gene, which provides instructions on how to build beta-globin proteins. These proteins are part of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. The HBB mutations that cause beta-thalassemia result in dysfunctional red blood cells that can't carry enough oxygen, which leads to patients experiencing anemia.

Another potential reason why biotechs are attracted to beta-thalassemia, though, is that it's not the only disease that is caused by mutations in the HBB gene. Sickle cell disease (SCD) is a related disease where HBB mutations cause red blood cells to form a sickle (or crescent) shape. These misshaped red blood cells can get stuck in blood vessels and cause multiple health complications, including anemia, infections, frequent pain, and heart problems.

While beta-thalassemia is rare, SCD is the most common genetic blood disorder in the U.S. It affects up to 100,000 Americans. SCD is even more prevalent in Africa, impacting up to 3% of newborns in some parts of the continent.

Drugmakers that identify a way to treat beta-thalassemia can be on the right track to target sickle cell disease as well. And with a much larger patient population, the market potential for successful therapies is greater.

One product has already been approved by the FDA for treating beta-thalassemia. Acceleron Pharma (NASDAQ:XLRN) developed luspatercept in collaboration with Celgene. In November 2019, Celgene won FDA approval for luspatercept in treating transfusion-dependent beta-thalassemia. Bristol-Myers Squibb (NYSE:BMY) closed its acquisition of Celgene a few weeks later and is marketing the drug under the brand name Reblozyl. Luspatercept is also in a mid-stage clinical study for treating non-transfusion-dependent beta-thalassemia.

Bluebird bio (NASDAQ:BLUE) won European approval for Lentiglobin in June 2019 for treating transfusion-dependent beta-thalassemia. Lentiglobin is a gene therapy that transplants cells with healthy HBB genes into patients. The biotech launched the therapy in Germany in January with the brand name Zynteglo. Bluebird plans to roll out Zynteglo in other key European markets later this year and should file for U.S. approval within the next few months.

Several biotechs are developing gene-editing approaches to treat beta-thalassemia. The company with the most advanced gene-editing program is Sangamo Therapeutics (NASDAQ:SGMO). However, there are some worries about ST-400, the experimental gene therapy that Sangamo is developing with Sanofi. In December 2019, Sangamo announced preliminary results from an early stage clinical study that, while showing promise, raised safety concerns.

CRISPR Therapeutics (NASDAQ:CRSP) and its big partner, Vertex Pharmaceuticals (NASDAQ:VRTX), are evaluating CTX001 in early stage clinical studies for treating beta-thalassemia and SCD. CTX-001 uses CRISPR gene editing, a different method than the zinc-finger nuclease (ZFN) gene-editing approach that Sangamo uses. CRISPR Therapeutics and Vertex reported promising preliminary results in December 2019 from both of its clinical studies.

Editas Medicine (NASDAQ:EDIT) is also using CRISPR gene editing to target both beta-thalassemia and SCD. The biotech hasn't advanced its experimental therapy to a clinical study in humans yet but plans to file for FDA approval later in 2020 to begin clinical testing. Editas thinks that its gene-editing approach is superior to the ones being taken by CRISPR Therapeutics and Sangamo.

Trailing the pack is Syros Pharmaceuticals (NASDAQ:SYRS). In December, Syros and Global Blood Therapeuticssigned a deal to work together to develop drugs targeting beta-thalassemia and SCD based on Syros' gene control platform. Instead of trying to directly edit the gene mutations, Syros' gene control therapies attempt to control the expression of genes through genomic switches in other parts of DNA. The biotech hasn't said how soon it will be able to advance to clinical testing with its experimental drug.

There are a couple of big problems for investors with so many companies chasing after the same rare disease. First, it's impossible to know which experimental therapies will be successful. Second, if multiple drugs win regulatory approvals, the competition could be so fierce that no product is a huge moneymaker.

It's also important to know that several of the products being developed hold the potential to cure beta-thalassemia. These therapies could wipe out the opportunities for drugs that aren't curative.

One solution to this investor's dilemma is to avoid all of the biotech stocks that are focused on beta-thalassemia. However, that's like throwing the baby out with the bathwater. I think that a better alternative is to invest in the big drugmakers with beta-thalassemia programs.

Bristol-Myers Squibb already has one FDA approval under its belt for Reblozyl. BMS also owns 5.3% of CRISPR Therapeutics and is partnering with Editas on developing gene-editing therapies targeting cancer. Vertex is partnering with CRISPR Therapeutics and owns 10.2% of the small biotech. Both BMS and Vertex stand to win with their beta-thalassemia drugs but also have plenty of other growth drivers.

Read more from the original source:

Why So Many Biotechs Are Scrambling to Develop a Drug for the Same Rare Disease - The Motley Fool