Shares of AVROBIO wereup nearly 20% in premarket trading after the company posted positive clinical data from its gene therapy trials in three different rare lysosomal diseases, Fabry, Gaucher type 1 and cystinosis.

The data from the Phase II study assessing AVR-RD-01, an investigational ex vivo lentiviral gene therapy for Fabry disease, was particularly promising. This morning, Cambridge, Mass.-based Avrobio said a second kidney biopsy conducted on the first patient dosed with AVR-RD-01 showed 100% clearance of the toxic substrate Gb3.

Kidney substrate reduction is the primary endpoint of the Phase II study and has been a cornerstone for evaluating and approving treatments in Fabry disease, Avrobio noted. Avrobio said the patient came in with significant toxic buildup in his kidneys, which is quite common with Fabry disease. One year after the gene therapy treatment was administered in the trial, two independent pathologists foundzero markersof toxic substrate across all the 99 biopsy slides each evaluated.

The first biopsy conducted on the patient showed an 87% clearance of the substrate. In addition to the substrate clearance in the Fabry disease study, AvroBio reported continued strong and durable results in other key metrics across all nine Phase I and Phase II Fabry patients. All patients are now producing the functional enzyme they need to clear toxic substrate from their cells and seeing a concurrent drop in plasma substrate. The farthest patient is out 3.5 years, the company said.

Avrobio Chief Executive Officer Geoff MacKay hailed the data and said it was a thrilling way to begin 2021. The data announced this morning builds on the breadth of strong clinical data weve reported across our leading lysosomal disorder pipeline of single-dose gene therapies, he added.

The Fabry disease study wasnt the only positive news from Avrobio. The company also announced six-month data from the first patient dosed in the Phase I/II study of AVR-RD-02, an investigational ex vivo lentiviral gene therapy for Gaucher disease type 1. That data showed plasma chitotriosidase and the toxic metabolite lyso-Gb1, which are key biomarkers of Gaucher disease, had both dropped 49% below the patients baseline levels that had been achieved on enzyme replacement therapy (ERT) before gene therapy was administered. Also, Lyso-Gb1, the toxic metabolite that builds up in cells throughout the body in Gaucher, is down 44% below the patients ERT baseline. Avrobio said this is an early sign of efficacy.

Based on the data observed to date, we believe lentiviral gene therapy drives down toxic metabolites below levels of ERT, supporting our view that gene therapy has the potential to prevent, halt or even reverse progression of these devastating diseases with a single infusion, MacKay said.

For the cystinosis study, Avrobio said three patients who are taking part in the study are now off of standard-of-care treatment. The first study patient has had sharp reductions in crystal density in the eyes and skin and a marked improvement in photophobia, which is an extreme sensitivity to light that is associated with the disease.

With 13 patients dosed across three clinical programs, we have observed sustained and potentially transformative improvements in key biomarkers and functional metrics, with data from our Fabry disease program out 3 years after dosing. Additionally, enrollment activities for our Fabry disease trial are accelerating, giving us added confidence in our efforts to meet our goal of having dosed a cumulative 30 patients across all our clinical programs by the end of the year. With this strong momentum, we look forward to clarifying the regulatory pathway with regulatory agencies, MacKay said in a statement.

Full data from the studies will be presented later this week and WORLDSymposium, an annual meeting dedicated to lysosomal disorders.

Most Read Today

Follow this link:

Avrobio Gene Therapy Shows Early Promise in Fabry, Other Rare Lysosomal Diseases - BioSpace

NICE Draft Guidance Recommends that Patients be Denied Access to bluebird bios Gene Therapy for Life-Limiting Rare Blood Disease

This guidance fails to recognise the severe burden for patients with transfusion-dependent -thalassaemia (TDT), who depend on lifelong blood transfusions every two to five weeks to survive1 and have an average age of death of around 452

NICEs decision threatens the future of gene therapies in the UK, despite the governments clear commitment to bring these transformative treatments to patients

bluebird bios ZYNTEGLO(betibeglogene autotemcel gene therapy; beti-cel) is a one-time gene therapy that addresses the underlying cause of TDT and offers eligible people living with the disease the potential to live life free from transfusions3,4,5

BASINGSTOKE, UK 11 February 2021bluebird bio, Inc. today expressed significant concern that eligible people in England and Wales with transfusion-dependent -thalassaemia (TDT) could be denied access to its gene therapy, beti-cel, under draft guidance issued by the National Institute for Health and Care Excellence (NICE). NICE is recommending against routine NHS funding for this innovative, one-time therapy, despite recognising it as a potentially curative treatment. The draft guidance disregards the significant burden TDT has on peoples quality of life and life expectancy, and outlines their intention to use a health economic model to assess the value of beti-cel, which NICE itself has acknowledged needs to be updated in order to appropriately evaluate gene therapies. We are shocked and disappointed by this recommendation and strongly believe that NICE has failed to act in the best interests of people with TDT and their families in England and Wales, comments Nicola Redfern, UK General Manager at bluebird bio. It is baffling that NICE disregarded the testimonies of patients, advocacy groups and clinicians and, despite recognising beti-cel as a potential cure for patients with TDT, has chosen to deny access and has dismissed the obvious unmet need. This decision is deeply concerning and will not only come as a huge blow to the TDT community, but also sets a dangerous precedent which could limit access to other gene therapies in the UK in the future.

Living with thalassaemia is a difficult and challenging experience not just for patients but for their entire families, said Romaine Maharaj, Executive Director, UK Thalassaemia Society. Our main aim at the UKTS is to improve the quality of life and experience of people living with thalassaemia through education, one to one support, research, service improvements and policy changes. We aspire to provide our members with empathy and the necessary hope to be optimistic about their futures. We are extremely disappointed with NICES decision not to recommend betibeglogene autotemcel as a treatment option in the UK. We also feel disheartened that our patient experts were misquoted and used out of context and feel that NICE needs to rectify this. Having an option and the access to a potentially curable treatment is vital and should be offered to patients.

People with thalassaemia inherit a faulty gene that means they are unable to produce normally functioning haemoglobin the protein responsible for carrying oxygen around the body.6,7 TDT is the most severe form of the disease8,9 and requires life-long blood transfusions every two to five weeks.1 However, these transfusions carry significant risks of iron overload, and even when treated optimally, excess iron will build up in tissues, leading to unavoidable and progressive multi organ damage.6 Having to rely on regular blood transfusions has a significant impact on day-to-day life, including education, work, and mental and physical wellbeing.10,11

TDT impacts life expectancy and quality of life for sufferers, and involves gruelling, life-long treatment, said Professor John B. Porter, MA, M.D., FRCP, FRCPath, University College London Hospitals, London, UK. Gene therapy could offer a potentially transformative option for eligible patients with TDT, by freeing them from the burden of regular blood transfusions and enabling them to live a more normal life. As a clinician who has worked to advance therapies for patients with TDT over the last three decades and understands the demands and limitations of current therapies, as well as the potential of gene therapy from first-hand experience, I very much hope that people with TDT in England and Wales will soon have the opportunity to benefit from this significant advancement.

The position outlined by NICE in its Appraisal Consultation Document (ACD) recommends against the routine funding of beti-cel for people with TDT in England and Wales, aged 12 years and over, who do not have a 0/0 genotype and for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available. In its ACD, NICE has recommended against applying the 1.5% discount rate to beti-cel, an economic principle NICE developed to ensure that the value of treatments with long-term health benefits could be accurately assessed. By failing to apply this discount rate, NICE has chosen to use a reimbursement framework that is not fit to evaluate transformative treatments such as gene therapies and places the UK at risk of falling behind other nations in advancing the best possible care for patients.

Under the NICE review process beti-cel was assessed in comparison to the current standard of care for all TDT patients, which is regular blood transfusions and therapy to reduce iron overload. Clinical data submitted to NICE showed that, of 24 people living with TDT, 83.3% achieved blood transfusion independence (living transfusion-free for at least 12 months) after being treated with beti-cel.5 In preparation for the next NICE appraisal committee meeting, bluebird bio will be submitting updated data from the ongoing Phase 3 Northstar-2 study, which showed that 89% of people (n=17) treated achieved transfusion independence (defined as living transfusion-free for at least 12 months).12

This guidance is draft and open for consultation until 4 March 2021, during which time anyone wishing to comment can do so on the NICE website.

About beti-cel The European Commission granted conditional marketing authorisation (CMA) for betibeglogene autotemcel (beti-cel; formerly LentiGlobin gene therapy for -thalassemia), to be marketed as ZYNTEGLOgene therapy, for people 12 years and older with transfusion-dependent -thalassaemia (TDT) who do not have a 0/0 genotype, for whom HSC transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for beti-cel, supported by data from 32 patients treated with beti-cel, including three patients with up to five years of follow-up.5

The CMA for beti-cel is valid in the 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).5 The U.S. Food and Drug Administration (FDA) granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more

information about the ongoing clinical studies, visit clinicaltrials.gov and use identifier NCT02906202 for

Northstar-2 (HGB-207) and NCT03207009 for Northstar-3 (HGB-212).

This medicinal product is subject to additional monitoring.

About bluebird bio

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

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

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; Zug, Switzerland; Munich, Germany; Milan, Italy; Utrecht, the Netherlands; Hampshire, United Kingdom; Paris, France; and Athens, Greece.

For further information, visit bluebirdbio.co.uk

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

Media:

sa Josefsson, +41 79 679 1217

ajosefsson@bluebirdbio.com

Callum Haire, +44 (0) 7867 429 637

callum.haire@madano.com

Investors: Ingrid Goldberg, +14 10 960 5022

igoldberg@bluebirdbio.com

References

1 Trompeter S et al. Thalassaemia International Federation. 2014. Chapter 2. Available from: https://www.ncbi.nlm.nih.gov/books/NBK269390/.

2 Jobanputra et al. British Journal of Haematology. 2020.

3 Thompson A, Walters M, Kwiatkowski J, et al. Northstar-2: Updated Safety and Efficacy Analysis of LentiGlobin Gene Therapy in Patients with Transfusion-Dependent -Thalassemia and Non-0/0 Genotypes. Poster presentation (Abstract #3543). 61st American Society of Hematology (ASH) Annual Meeting; 2019 Dec 7-10; Orlando, Florida, USA.

4 Lal A, Locatelli F, Kwiatkowski J, et al. Northstar-3: Interim Results from a Phase 3 Study Evaluating LentiGlobin Gene Therapy in Patients with Transfusion-Dependent -Thalassemia and Either a 0 or IVS-I-110 Mutation at Both Alleles of the HBB Gene. Oral presentation (Abstract #815). 61st American Society of Hematology (ASH) Annual Meeting; 2019 Dec 7-10; Orlando, Florida, USA.

5 European Medicine Agency. Zynteglo: EPAR Product Information. European Medicines Agency. 3 June 2019. Available from: https://www.ema.europa.eu/documents/product-information/zynteglo-epar-product-information_en.pdf.

6 Galanello and Origa, Orphanet Journal of Rare Diseases 2010;5:11.

7 NHS. Beta Thalassemia. 2018. Available at: https://www.nhs.uk/conditions/thalassaemia/. Accessed November 2020.

8 Cappellini et al. 2014. Thalassemia International Federation: Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT), 3rd Edition.

9 Olivieri, N.F. 1999. The beta-thalassemias. N Engl J Med, 341, 99-109.

10 Shah et al. Blood. 2019;134 (Supplement_1):3550.

11 Paramore et al. The Patient-Patient-Centered Outcomes Research. 2020.

12 Porter JB et al. Improvement in erythropoiesis in patients with transfusion-dependent -thalassemia following treatment with betibeglogene autotemcel (LentiGlobin for -thalassemia) in the Phase 3 HGB-207 study. Oral presentation (Abstract S296). 25th European Hematology Association (EHA25) Annual Congress; Virtual Congress, 11-21 June 2020.

Visit link:

NICE Draft Guidance Recommends that Patients be Denied Access to bluebird bio's Gene Therapy for Life-Limiting Rare Blood Diseas - PharmiWeb.com

New data shows FLT201 could yield sustained levels of -glucocerebrosidase (GCase) variant 85 to help treat patients with Gaucher disease.

Freeline Therapeutics Holdings announced the data with 1 oral and 3 e-poster presentations the 17THAnnual WORLDSymposium showing the benefit of FLT201 allowing them to move forward with the first ever in-human dose finding studies of the gene therapy.

FLT201

The treatment leverages Freelines proprietary high-potency adeno-associated virus capsid (AAVS3).

In addition, GCasevar 85, which is being compared to a wild-type GCase, has shown a greater than 20-fold increase in half-life in lysosomal pH and a 6-10 fold increase in half-life in serum, which produces a 20-fold increase in potency of the vector.

The gene therapy is a combination of AAVS3 capsid and a liver-specific promoter that drives the expression of GCasevar85.

These data demonstrate preclinical proof-of-concept for the potential of the program to provide functional cures in patients with the most common form of Gaucher disease, Type 1. Included in these data are demonstration of GCase expression, cellular uptake, tissue penetration, enzymatic activity, and clearance of disease causing substrate, glucosylsphingosine (lyso-Gb1), Romuald Corbau, PhD, Chief Scientific Officer of Freeline, said in a statement. Considered in totality, these data suggest FLT201 may be able to deliver sustained GCase expression in difficult-to-reach tissues, such as bone marrow and lung, as evidenced by the substrate clearance.

The Studies

In the first study, involving a wild-type mouse, FLT201 resulted in robust GCase expression in the liver and sustained GCase secretion into the plasma, with enhanced and sustained GCase uptake observed in key tissues involved in Gaucher disease including spleen, bone marrow and lung.

In addition, the researchers used Gba-deficient mice and found the treatment resulted in the restoration of GCase activity in difficult-to-reach tissues, observed by decreased levels of disease causing substrate, lyso-Gb1, increased concentrations of plasma GCase and reduced activated macrophages and inflammation in the lung.

The investigators also found from in vitro studies the treatment allowed GCasevar 85 to be taken up by human peripheral blood mononuclear cells and macrophages at levels comparable to those seen with ERT.

Finally, the gene therapy treatment in rhesus macaques was well-tolerated with rapid and robust increases in plasma GCase levels.

In the second poster, the researchers found variant 85 showed the highest level of GCase activity when transduced using AAVS3 in Huh7 cells, with more than an 80-fold increase in activity compared to wild-type GCase. GCasevar85 also showed increased stability in different physiological media compared with enzyme replacement therapy, without differing in its fundamental enzymatic parameter KM.

In the third poster, the researchers showed a custom in vitro phage display library against the enzyme -galactosidase A (GLA) to screen and develop a unique GLA neutralizing IgG4 antibody.

The Future

Freeline is expecting to initiate the first in-human dose finding studies of FLT201 by late 2021.

FLT201 data suggest that our gene therapy candidate for Gaucher disease is capable of delivering -glucocerebrosidase variant85 to tissues not sufficiently addressed by standard-of-care enzyme replacement therapy, said Theresa Heggie, Chief Executive Officer of Freeline, in a statement. In addition, we believe steady delivery of enzyme into target tissues to enable sustained clearance of pathologic substrate has the potential to offer significant improvements in clinical outcomes over existing standard of care.

Link:

FLT201 Shows Promise as a Gene Therapy for Gaucher Disease - MD Magazine

Feb. 11, 2021 16:00 UTC

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dyno Therapeutics, a biotech company applying artificial intelligence (AI) to gene therapy, today announced a publication in Nature Biotechnology that demonstrates the use of artificial intelligence to generate an unprecedented diversity of adeno-associated virus (AAV) capsids towards identifying functional variants capable of evading the immune system, a factor that is critical to enabling all patients to benefit from gene therapies. The research was conducted in collaboration with Google Research, Harvards Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School laboratory of George M. Church, Ph.D., a Dyno scientific co-founder. The publication is entitled Deep diversification of an AAV capsid protein by machine learning.

It is estimated that up to 50-70% of the human population have pre-existing immunity to natural forms of the AAV vectors currently being using to deliver gene therapies. This immunity renders a large portion of patients ineligible to receive gene therapies which rely upon these capsids as the vector for delivery. Overcoming the challenge of pre-existing immunity to AAV vectors is therefore a major goal for the gene therapy field.

The approach described in the Nature Biotechnology paper opens a radically new frontier in capsid design. Our study clearly demonstrates the potential of machine learning to guide the design of diverse and functional sequence variants, far beyond what exists in nature, said Eric Kelsic, Ph.D., Dynos CEO and co-founder. We continue to expand and apply the power of artificial intelligence to design vectors that can not only overcome the problem of pre-existing immunity but also address the need for more effective and selective tissue targeting. At Dyno, we are making rapid progress to design novel AAV vectors that overcome the limitations of current vectors, improving treatments for more patients and expanding the number of diseases treatable with gene therapies.

The Nature Biotechnology paper describes the rapid production of a large library of distinct AAV capsid variants designed by machine learning models. Nearly 60% of the variants produced were determined to be viable, a significant increase over the typical yield of <1% using random mutagenesis, a standard method of generating diversity.

The more we change the AAV vector from how it looks naturally, the more likely we are to overcome the problem of pre-existing immunity, added Sam Sinai, Ph.D., Dyno co-founder and Machine Learning Team Lead. Key to solving this problem, however, is also ensuring that capsid variants remain viable for packaging the DNA payload. With conventional methods, this diversification is time- and resource-intensive, and results in a very low yield of viable capsids. In contrast, our approach allows us to rapidly unlock the full potential diversity of AAV capsids to develop improved gene therapies for a much larger number of patients.

This research builds upon previous work published in Science in which a complete landscape of single mutations around the AAV2 capsid was generated followed by evaluation of the functional properties important for in vivo delivery. In parallel with these works, Dyno has established collaborations with leading gene therapy companies Novartis, Sarepta Therapeutics, Roche and Spark Therapeutics to develop next-generation AAV gene therapy vectors with a goal of expanding the utility of gene therapies for ophthalmic, muscle, central nervous system (CNS) and liver diseases.

About CapsidMap for Designing Optimized AAV Gene Therapies

By designing capsids that confer improved functional properties to Adeno-Associated Virus (AAV) vectors, Dynos proprietary CapsidMap platform overcomes the limitations of todays gene therapies on the market and in development. Todays treatments are primarily confined to a small number of naturally occurring AAV vectors that are limited by delivery efficiency, immunity, payload size, and manufacturing challenges. CapsidMap uses artificial intelligence (AI) technology to engineer capsids, the cell-targeting protein shell of viral vectors. The CapsidMap platform applies leading-edge DNA library synthesis and next generation DNA sequencing to measure in vivo gene delivery properties in high throughput. At the core of CapsidMap are advanced search algorithms leveraging machine learning and Dynos massive quantities of experimental data, that together build a comprehensive map of sequence space and thereby accelerate the design of novel capsids optimized for gene therapy.

About Dyno Therapeutics

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative high-throughput in vivo experiments to gene therapy. The companys proprietary CapsidMap platform rapidly discovers and systematically optimizes Adeno-Associated Virus (AAV) capsid vectors that significantly outperform current approaches for in vivo gene delivery, thereby expanding the range of diseases treatable with gene therapies. Dyno was founded in 2018 by experienced biotech entrepreneurs and leading scientists in the fields of gene therapy and machine learning. The company is located in Cambridge, Massachusetts. Visit http://www.dynotx.com for additional information.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210211005156/en/

Read more here:

Dyno Therapeutics Announces Publication in Nature Biotechnology Demonstrating Use of Artificial Intelligence to Generate Unprecedented Diversity of...

The Telegraph

A detained Saudi womens rights activist had electrodes fixed to her head during phone calls with her family to prevent her speaking of the torture she suffered in prison, her sister said on Thursday after her release. Loujain al-Hathoul was released to her familys home in Riyadh on Wednesday after 1,001 days in prison on charges related to her activism. Under her probation she is unable to travel, use social media or speak to the media. Her sisters, who live abroad, announced Thursday that Ms al-Hathoul will seek legal redress in Saudi Arabia for torture she said she suffered in detention. She was tortured and she cannot forget this, her sister Lina said, during an online press conference. The family have previously claimed Ms al-Hathoul was tortured which Saudi authorities deny but gave new details Thursday, including that the threat of electrocution stopped her speaking out. If I complained about anything they were ready to electrocute me, Lina said her sister told the family on Wednesday of her early months in detention. It was months later that we found out about the torture when Ms al-Hathoul was moved to another prison, Lina said. Ms al-Hathoul has identified one of her torturers as Saud Al Qahtani, a top adviser to the Saudi crown prince until he was sanctioned by the US over his role in the murder of journalist Jamal Khashoggi. Hes the only person that we know the name of who was present at the torture sessions, Lina said. Mr Qahtani is notorious in Saudi Arabia, sometimes called the lord of the flies for his army of Twitter trolls used for attacking dissidents. Loujain recognised him, hes a public figure, said her older sister Alia. Ms al-Hathoul now hopes to use the Saudi justice system to prove she was tortured and seek justice. The torturers must be sentenced, Lina said. In December, Ms al-Hathoul was sentenced to nearly six years imprisonment over her activism, which included demanding the right for women to drive and calling for the abolition of Saudi Arabias male guardianship system. The decades old driving ban was lifted weeks after her arrest, with Crown Prince Mohammed bin Salman eager to claim the credit for the reform. The 35-year-old prince muscled his way to become next in line to the throne in 2015, partly by projecting an image as a dynamic young reformer who could modernise the conservative kingdom. But the sisters believe that any reforms under Mohammed bin Salman are illusory. MBS is far from being a reformer, hes an oppressor, said Lina, referring to him by his initials. Womens empowerment is a lie in Saudi Arabia, there are no real reforms, she said. Lina said she was choosing her words carefully to avoid further negative repercussions for her family still in Saudi Arabia: Theres really an atmosphere of fear under MBS. The family believe Ms al-Hathouls early release was timed by the Saudi government to impress new US President Joe Biden, who has promised closer scrutiny of his close allys human rights record. Saudi Arabias situation is tightly connected with whats going on in the US, Alia said. The Biden administration made clear that they care about human rights.

View post:

Breakthrough gene therapy helps Utah boy thrive - Yahoo News

Bloomberg

(Bloomberg) -- Stefan Qin was just 19 when he claimed to have the secret to cryptocurrency trading.Buoyed with youthful confidence, Qin, a self-proclaimed math prodigy from Australia, dropped out of college in 2016 to start a hedge fund in New York he called Virgil Capital. He told potential clients he had developed an algorithm called Tenjin to monitor cryptocurrency exchanges around the world to seize on price fluctuations. A little more than a year after it started, he bragged the fund had returned 500%, a claim that produced a flurry of new money from investors.He became so flush with cash, Qin signed a lease in September 2019 for a $23,000-a-month apartment in 50 West, a 64-story luxury condo building in the financial district with expansive views of lower Manhattan as well as a pool, sauna, steam room, hot tub and golf simulator.In reality, federal prosecutors said, the operation was a lie, essentially a Ponzi scheme that stole about $90 million from more than 100 investors to help pay for Qins lavish lifestyle and personal investments in such high-risk bets as initial coin offerings. At one point, facing client demands for their money, he variously blamed poor cash flow management and loan sharks in China for his troubles. Last week, Qin, now 24 and expressing remorse, pleaded guilty in federal court in Manhattan to a single count of securities fraud.I knew that what I was doing was wrong and illegal, he told U.S. District Judge Valerie E. Caproni, who could sentence him to more than 15 years in prison. I deeply regret my actions and will spend the rest of my life atoning for what I did. I am profoundly sorry for the harm my selfish behavior has caused to my investors who trusted in me, my employees and my family.Eager InvestorsThe case echoes similar cryptocurrency frauds, such as that of BitConnect, promising people double-and triple-digit returns and costing investors billions. Ponzi schemes like that show how investors eager to cash in on a hot market can easily be led astray by promises of large returns. Canadian exchange QuadrigaCX collapsed in 2019 as a result of fraud, causing at least $125 million in losses for 76,000 investors.While regulatory oversight of the cryptocurrency industry is tightening, the sector is littered with inexperienced participants. A number of the 800 or so crypto funds worldwide are run by people with no knowledge of Wall Street or finance, including some college students and recent graduates who launched funds a few years ago.Qins path started in college, too. He had been a math whiz who planned on becoming a physicist, he told a website, DigFin, in a profile published in December, just a week before regulators closed in on him. He described himself on his LinkedIn page as a quant with a deep interest and understanding in blockchain technology.In 2016, he won acceptance into a program for high-potential entrepreneurs at the University of New South Wales in Sydney with a proposal to use blockchain technology to speed up foreign exchange transactions. He also attended the Minerva Schools, a mostly online college based in San Francisco, from August 2016 through December 2017, the school confirmed.Crypto BugHe got the crypto bug after an internship with a firm in China, he told DigFin. His task had been to build a platform between two venues, one in China and the other in the U.S., to allow the firm to arbitrage cryptocurrencies.Convinced he had happened upon a business, Qin moved to New York to found Virgil Capital. His strategy, he told investors, would be to exploit the tendency of cryptocurrencies to trade at different prices at various exchanges. He would be market-neutral, meaning that the firms funds wouldnt be exposed to price movements.And unlike other hedge funds, he told DigFin, Virgil wouldnt charge management fees, taking only fees based on the firms performance. We never try to make easy money, Qin said.By his telling, Virgil got off to a fast start, claiming 500% returns in 2017, which brought in more investors eager to participate. A marketing brochure boasted of 10% monthly returns -- or 2,811% over a three-year period ending in August 2019, legal filings show.His assets got an extra jolt after the Wall Street Journal profiled him in a February 2018 story that touted his skill at arbitraging cryptocurrency. Virgil experienced substantial growth as new investors flocked to the fund, prosecutors said.Missing AssetsThe first cracks appeared last summer. Some investors were becoming increasingly upset about missing assets and incomplete transfers, the former head of investor relations, Melissa Fox Murphy, said in a court declaration. (She left the firm in December.) The complaints grew.It is now MID DECEMBER and my MILLION DOLLARS IS NOWHERE TO BE SEEN, wrote one investor, whose name was blacked out in court documents. Its a disgrace the way you guys are treating one of your earliest and largest investors.Around the same time, nine investors with $3.5 million in funds asked for redemptions from the firms flagship Virgil Sigma Fund LP, according to prosecutors. But there was no money to transfer. Qin had drained the Sigma Fund of its assets. The funds balances were fabricated.Instead of trading at 39 exchanges around the world, as he had claimed, Qin spent investor money on personal expenses and to invest in other undisclosed high-risk investments, including initial coin offerings, prosecutors said.So Qin tried to stall. He convinced investors instead to transfer their interests into his VQR Multistrategy Fund, another cryptocurrency fund he started in February 2020 that used a variety of trading strategies -- and still had assets.Loan SharksHe also sought to withdraw $1.7 million from the VQR fund, but that aroused suspicions from the head trader, Antonio Hallak. In a phone call Hallak recorded in December, Qin said he needed the money to repay loan sharks in China that he had borrowed from to start his business, according to court filings in a lawsuit filed by the Securities and Exchange Commission. He said the loan sharks might do anything to collect on the debt and that he had a liquidity issue that prevented him from repaying them.I just had such poor cash flow management to be honest with you, Qin told Hallak. I dont have money right now dude. Its so sad.When the trader balked at the withdrawal, Qin attempted to take over the reins of VQRs accounts. But by now the SEC was involved. It got cryptocurrency exchanges to put a hold on VQRs remaining assets and, a week later, filed suit.Asset RecoveryBy the end, Qin had drained virtually all of the money that was in the Sigma Fund. A court-appointed receiver who is overseeing the fund is looking to recover assets for investors, said Nicholas Biase, a spokesman for Manhattan U.S. Attorney Audrey Strauss. About $24 million in assets in the VQR fund was frozen and should be available to disperse, he said.Stefan He Qin drained almost all of the assets from the $90 million cryptocurrency fund he owned, stealing investors money, spending it on indulgences and speculative personal investments, and lying to investors about the performance of the fund and what he had done with their money, Strauss said in a statement.In South Korea when he learned of the probe, Qin agreed to fly back to the U.S., prosecutors said. He surrendered to authorities on Feb. 4, pleaded guilty the same day before Caproni, and was freed on a $50,000 bond pending his sentencing, scheduled for May 20. While the maximum statutory penalty calls for 20 years in prison, as part of a plea deal, prosecutors agreed that he should get 151 to 188 months behind bars under federal sentencing guidelines and a fine of up to $350,000.That fate is a far cry from the career his parents had envisioned for him -- a physicist, he had told DigFin. They werent too happy when I told them I had quit uni to do this crypto thing. Who knows, maybe someday Ill complete my degree. But what I really want to do is trade crypto.The case is U.S. v Qin, 21-cr-75, U.S. District Court, Southern District of New York (Manhattan)(Updates with comment from prosecutor and case caption)For more articles like this, please visit us at bloomberg.comSubscribe now to stay ahead with the most trusted business news source.2021 Bloomberg L.P.

Read more from the original source:

Global Adeno-Associated Virus (AAV) Vectors in Gene Therapy Market to 2030 - Insight, Epidemiology and Forecasts - ResearchAndMarkets.com - Yahoo...

Bloomberg

(Bloomberg) -- Stefan Qin was just 19 when he claimed to have the secret to cryptocurrency trading.Buoyed with youthful confidence, Qin, a self-proclaimed math prodigy from Australia, dropped out of college in 2016 to start a hedge fund in New York he called Virgil Capital. He told potential clients he had developed an algorithm called Tenjin to monitor cryptocurrency exchanges around the world to seize on price fluctuations. A little more than a year after it started, he bragged the fund had returned 500%, a claim that produced a flurry of new money from investors.He became so flush with cash, Qin signed a lease in September 2019 for a $23,000-a-month apartment in 50 West, a 64-story luxury condo building in the financial district with expansive views of lower Manhattan as well as a pool, sauna, steam room, hot tub and golf simulator.In reality, federal prosecutors said, the operation was a lie, essentially a Ponzi scheme that stole about $90 million from more than 100 investors to help pay for Qins lavish lifestyle and personal investments in such high-risk bets as initial coin offerings. At one point, facing client demands for their money, he variously blamed poor cash flow management and loan sharks in China for his troubles. Last week, Qin, now 24 and expressing remorse, pleaded guilty in federal court in Manhattan to a single count of securities fraud.I knew that what I was doing was wrong and illegal, he told U.S. District Judge Valerie E. Caproni, who could sentence him to more than 15 years in prison. I deeply regret my actions and will spend the rest of my life atoning for what I did. I am profoundly sorry for the harm my selfish behavior has caused to my investors who trusted in me, my employees and my family.Eager InvestorsThe case echoes similar cryptocurrency frauds, such as that of BitConnect, promising people double-and triple-digit returns and costing investors billions. Ponzi schemes like that show how investors eager to cash in on a hot market can easily be led astray by promises of large returns. Canadian exchange QuadrigaCX collapsed in 2019 as a result of fraud, causing at least $125 million in losses for 76,000 investors.While regulatory oversight of the cryptocurrency industry is tightening, the sector is littered with inexperienced participants. A number of the 800 or so crypto funds worldwide are run by people with no knowledge of Wall Street or finance, including some college students and recent graduates who launched funds a few years ago.Qins path started in college, too. He had been a math whiz who planned on becoming a physicist, he told a website, DigFin, in a profile published in December, just a week before regulators closed in on him. He described himself on his LinkedIn page as a quant with a deep interest and understanding in blockchain technology.In 2016, he won acceptance into a program for high-potential entrepreneurs at the University of New South Wales in Sydney with a proposal to use blockchain technology to speed up foreign exchange transactions. He also attended the Minerva Schools, a mostly online college based in San Francisco, from August 2016 through December 2017, the school confirmed.Crypto BugHe got the crypto bug after an internship with a firm in China, he told DigFin. His task had been to build a platform between two venues, one in China and the other in the U.S., to allow the firm to arbitrage cryptocurrencies.Convinced he had happened upon a business, Qin moved to New York to found Virgil Capital. His strategy, he told investors, would be to exploit the tendency of cryptocurrencies to trade at different prices at various exchanges. He would be market-neutral, meaning that the firms funds wouldnt be exposed to price movements.And unlike other hedge funds, he told DigFin, Virgil wouldnt charge management fees, taking only fees based on the firms performance. We never try to make easy money, Qin said.By his telling, Virgil got off to a fast start, claiming 500% returns in 2017, which brought in more investors eager to participate. A marketing brochure boasted of 10% monthly returns -- or 2,811% over a three-year period ending in August 2019, legal filings show.His assets got an extra jolt after the Wall Street Journal profiled him in a February 2018 story that touted his skill at arbitraging cryptocurrency. Virgil experienced substantial growth as new investors flocked to the fund, prosecutors said.Missing AssetsThe first cracks appeared last summer. Some investors were becoming increasingly upset about missing assets and incomplete transfers, the former head of investor relations, Melissa Fox Murphy, said in a court declaration. (She left the firm in December.) The complaints grew.It is now MID DECEMBER and my MILLION DOLLARS IS NOWHERE TO BE SEEN, wrote one investor, whose name was blacked out in court documents. Its a disgrace the way you guys are treating one of your earliest and largest investors.Around the same time, nine investors with $3.5 million in funds asked for redemptions from the firms flagship Virgil Sigma Fund LP, according to prosecutors. But there was no money to transfer. Qin had drained the Sigma Fund of its assets. The funds balances were fabricated.Instead of trading at 39 exchanges around the world, as he had claimed, Qin spent investor money on personal expenses and to invest in other undisclosed high-risk investments, including initial coin offerings, prosecutors said.So Qin tried to stall. He convinced investors instead to transfer their interests into his VQR Multistrategy Fund, another cryptocurrency fund he started in February 2020 that used a variety of trading strategies -- and still had assets.Loan SharksHe also sought to withdraw $1.7 million from the VQR fund, but that aroused suspicions from the head trader, Antonio Hallak. In a phone call Hallak recorded in December, Qin said he needed the money to repay loan sharks in China that he had borrowed from to start his business, according to court filings in a lawsuit filed by the Securities and Exchange Commission. He said the loan sharks might do anything to collect on the debt and that he had a liquidity issue that prevented him from repaying them.I just had such poor cash flow management to be honest with you, Qin told Hallak. I dont have money right now dude. Its so sad.When the trader balked at the withdrawal, Qin attempted to take over the reins of VQRs accounts. But by now the SEC was involved. It got cryptocurrency exchanges to put a hold on VQRs remaining assets and, a week later, filed suit.Asset RecoveryBy the end, Qin had drained virtually all of the money that was in the Sigma Fund. A court-appointed receiver who is overseeing the fund is looking to recover assets for investors, said Nicholas Biase, a spokesman for Manhattan U.S. Attorney Audrey Strauss. About $24 million in assets in the VQR fund was frozen and should be available to disperse, he said.Stefan He Qin drained almost all of the assets from the $90 million cryptocurrency fund he owned, stealing investors money, spending it on indulgences and speculative personal investments, and lying to investors about the performance of the fund and what he had done with their money, Strauss said in a statement.In South Korea when he learned of the probe, Qin agreed to fly back to the U.S., prosecutors said. He surrendered to authorities on Feb. 4, pleaded guilty the same day before Caproni, and was freed on a $50,000 bond pending his sentencing, scheduled for May 20. While the maximum statutory penalty calls for 20 years in prison, as part of a plea deal, prosecutors agreed that he should get 151 to 188 months behind bars under federal sentencing guidelines and a fine of up to $350,000.That fate is a far cry from the career his parents had envisioned for him -- a physicist, he had told DigFin. They werent too happy when I told them I had quit uni to do this crypto thing. Who knows, maybe someday Ill complete my degree. But what I really want to do is trade crypto.The case is U.S. v Qin, 21-cr-75, U.S. District Court, Southern District of New York (Manhattan)(Updates with comment from prosecutor and case caption)For more articles like this, please visit us at bloomberg.comSubscribe now to stay ahead with the most trusted business news source.2021 Bloomberg L.P.

Go here to see the original:

Taysha Gene Therapies Announces Participation in Upcoming Investor Healthcare Conferences - Yahoo Finance

Amicus Optimized Transgene Show Greater Substrate Reduction than Wild Type Construct Across All Tissues and Doses

Further Validates Combining Amicus-Engineered Transgenes with Penns AAV Gene Therapy Technologies to Develop Next Generation Gene Therapies

PHILADELPHIA, Feb. 08, 2021 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD) today announced initial preclinical data from its investigational adeno-associated viral (AAV) gene therapy program for Fabry disease in mice. The results are featured in a virtual poster presentation at the 17th Annual WORLDSymposium 2021, being held February 8-12, 2021. The poster is also available in the Events and Presentations section of the Amicus Therapeutics corporate website.

Fabry disease is an inherited lysosomal disorder caused by deficiency of the enzyme alpha-galactosidase A (GLA). Reduced or absent levels of GLA lead to accumulation of disease substrate leading to cellular disfunction and organ damage, which results in the clinical manifestations of Fabry disease. Amicus, in collaboration with the Gene Therapy Program of the Perelman School of Medicine at the University of Pennsylvania (Penn), is developing a novel gene therapy for Fabry disease that combines the Amicus protein-engineering expertise and deep knowledge and experience in Fabry disease with Penns adeno associated virus (AAV) gene transfer technologies.

This initial preclinical study assessed a range of single doses of AAV in Gla knockout (KO) mice with either natural unmodified hGLA (wildtype hGLA) or Amicus/Penn engineered hGLA transgenes (engineered hGLA). The Amicus/Penn engineered hGLAs are designed for improved stability which is believed to provide a larger window for the enzyme to stay active while in circulation prior to being taken up into the target tissues and for additional stabilization after cell uptake. The lead Amicus/Penn engineered hGLA declared as an IND candidate is designated as AT-GTX-701.

Preclinical Poster Highlights for Amicus/Penn AAV Gene Therapy for Fabry Disease:

Hung Do, Ph.D., Chief Science Officer of Amicus Therapeutics, stated, These very important preclinical results validate our capabilities to develop engineered proteins via a gene therapy that can result in superior substrate reduction compared with a wildtype transgene. This is the second program in our collaboration with Penn that has demonstrated the potential advantages of optimizing the target protein in these disorders, and may be applicable to other lysosomal disorders as we continue to combine our understanding of the molecular basis of these diseases and expertise in protein engineering, together with Penns vector engineering expertise, to develop novel gene therapies.

Amicus is currently developing AAV gene therapies in collaboration with Penn for Pompe disease, Fabry disease, CDD, CLN1, MPS IIIB, a next generation program in MPS IIIA, as well as Angelman Syndrome. The agreement between Amicus and Penn is a Research, Collaboration and License Agreement, providing funding to Penn to advance the preclinical research programs in the Wilson Lab and to license certain technologies invented under the funded Research Collaboration.

About Fabry DiseaseFabry disease is an inherited lysosomal disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A), which is the result of mutations in the GLA gene. The primary biological function of alpha-Gal A is to degrade specific lipids in lysosomes, including globotriaosylceramide (referred to here as GL-3 and also known as Gb3). Lipids that can be degraded by the action of alpha-Gal A are called "substrates" of the enzyme. Reduced or absent levels of alpha-Gal A activity lead to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. Progressive accumulation of GL-3 is believed to lead to the morbidity and mortality of Fabry disease, including pain, kidney failure, heart disease, and stroke. The symptoms can be severe, differ from patient to patient, and begin at an early age. All Fabry disease is progressive and may lead to irreversible organ damage regardless of the time of symptom onset.

About Amicus Therapeutics Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare metabolic diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a robust pipeline of cutting-edge, first- or best-in-class medicines for rare metabolic diseases. For more information please visit the companys website at http://www.amicusrx.com, and follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to initial preclinical data from its investigational adeno-associated viral (AAV) gene therapy program for Fabry disease in mice and the potential implications of these data for the future advancement and development of a gene therapy for Fabry disease and other lysosomal disorders and development of potential platform technologies. Words such as, but not limited to, look forward to, believe, expect, anticipate, estimate, intend, "confidence," "encouraged," potential, plan, targets, likely, may, will, would, should and could, and similar expressions or words identify forward-looking statements. The forward looking statements included in this press release are based on management's current expectations and belief's which are subject to a number of risks, uncertainties and factors, including that the preliminary data reported before completion of the study will not be predictive of future results, that results of additional preliminary data or data from the completed study or any future study will not yield results that are consistent with the preliminary data presented, that later study results will not support further development, or even if such later results are favorable, that the Company will not be able to successfully complete the development of, obtain regulatory approval for, or successfully commercialize. In addition, all forward looking statements are subject to the other risks and uncertainties detailed in our Annual Report on Form 10-K for the year ended December 31, 2019 and the Quarterly Report filed on Form 10-Q for the quarter ended September 30, 2020. As a consequence, actual results may differ materially from those set forth in this press release. You are cautioned not to place undue reliance on these forward looking statements, which speak only of the date hereof. All forward looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise this press release to reflect events or circumstances after the date hereof.

CONTACTS:

Investors:Andrew FaughnanSr. Director, Investor Relationsafaughnan@amicusrx.com(609) 662-3809

Media:Diana MooreHead of Global Corporate Communicationsdmoore@amicusrx.com(609) 662-5079

FOLDG

Read the original here:

Amicus Therapeutics Presents Positive Preclinical Fabry Disease Gene Therapy Data at the 17th Annual WORLDSymposium 2021 - GlobeNewswire

Paragon Biosciences, a life science innovator that creates, invests in and builds life science companies in biopharmaceuticals, cell and gene therapy and synthetic biology utilizing artificial intelligence, has launched CiRC Biosciences, a cell therapy company developing treatments for serious diseases with high, unmet needs with an initial focus on the eye."The addition of CiRC Biosciences to our portfolio builds upon our cell and gene therapy platform, an area that has tremendous potential to address serious genetic diseases," said Jeff Aronin, founder, chairman and chief executive officer, Paragon Biosciences. "CiRC Biosciences gives us the science to target retinal diseases that could lead to vision restoration with numerous other applications in the years ahead."CiRC Biosciences is currently advancing pre-clinical development of chemically induced retinal cells for vision restoration in Geographic Atrophy Age-Related Macular Degeneration (Dry AMD), which is the most common cause of irreversible vision loss over the age of 65, and advanced Retinitis Pigmentosa (RP), a genetic disorder that causes tunnel vision and eventual blindness. There are no U.S. Food & Drug Administration (FDA) approved treatments to restore vision loss in Dry AMD or RP.The company's novel mechanism of action is designed for direct chemical conversion of fibroblasts into other cell types using a cocktail of small molecules in an 11-day chemical conversion process. Pre-clinical studies have shown efficacy in blind mice that demonstrated vision restoration. CiRC Biosciences has provisional patent applications to protect its platform."Our technology transforms ordinary skin cells into specialized retinal cells using a cocktail of small molecules," said Sai Chavala, M.D., co-founder and chief scientific officer, CiRC Biosciences. "This process is potentially safer, quicker, more cost effective and easier to manufacturer than using traditional stem cells. Working with Paragon Biosciences to build and advance CiRC Biosciences provides us the opportunity to efficiently progress this technology through research and development stages.CiRC Biosciences first reported its discovery in the highly respected scientific journal Nature (April 15, 2020). A recently published New England Journal of Medicine article (Nov. 5, 2020) discussed CiRC's technology of using chemically induced cells to restore retinal function. The article concluded, "The new and emerging strategies for the rescue, regeneration, and replacement of photoreceptors suggest a bright future in the fight to preserve and restore vision in blinding eye diseases."The abstract in Nature is available here.Access to the NEJM article is available here.

Continue reading here:

Paragon Biosciences Expands Cell And Gene Therapy Platform - Contract Pharma

New York, Feb. 05, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Gene Therapy Market by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of Administration, and Key Geographical Regions: Industry Trends and Global Forecasts, 2020-2030" - https://www.reportlinker.com/p06020737/?utm_source=GNW Considering the current pace of research and product development activity in this field, experts believe that the number of clinical research initiatives involving gene therapies are likely to grow by 17% annually. In this context, the USFDA released a notification, mentioning that it now expects to receive twice as many gene therapy applications each year, starting 2020. Despite the ongoing pandemic, it is worth highlighting that gene therapy companies raised approximately USD 5.5 billion in capital investments, in 2020 alone. This is indicative of the promising therapeutic potential of this emerging class of pharmacological interventions, which has led investors to bet heavily on the success of different gene therapy candidates in the long term.

Several technology platforms are currently available for discovery and development of various types of gene therapies. In fact, advances in bioanalytical methods (such as genome sequencing), and genome editing and manipulation technologies (such as molecular switches), have enabled the development of novel therapy development tools / platforms. In fact, technology licensing is a lucrative source of income for stakeholders in this industry, particularly for those with proprietary gene editing platforms. Given the growing demand for interventions that focus on the amelioration of the underlying (genetic) causes of diseases, it is expected that the gene therapy pipeline will continue to steadily expand. Moreover, promising results from ongoing clinical research initiatives are likely to bring in more investments to support therapy product development initiatives in this domain. Therefore, we are led to believe that the global gene therapy market is poised to witness significant growth in the foreseen future.

SCOPE OF THE REPORT The Gene Therapy Market (4th Edition) by Therapeutic Approach (Gene Augmentation, Oncolytic Viral Therapy, Immunotherapy and Others), Type of Gene Therapy (Ex vivo and In vivo), Type of Vectors used (Adeno Associated Virus, Adenovirus, Herpes Simplex Virus, Lentivirus, Plasmid DNA, Retrovirus and Others), Target Therapeutic Areas (Autoimmune Disorders, Cardiovascular Diseases, Dermatological Disorders, Genetic Disorders, Hematological Disorders, Metabolic Disorders, Muscle-related Diseases, Oncological Disorders, Ophthalmic Diseases and Others), Route of Administration (Intraarticular, Intracerebellar, Intradermal, Intramuscular, Intratumoral, Intravenous, Intravesical, Intravitreal, Subretinal and Others), and Key Geographical Regions (US, EU5 and rest of the world): Industry Trends and Global Forecasts, 2020-2030 report features an extensive study of the current market landscape of gene therapies, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, immunotherapies and gene editing therapies. The study also features an elaborate discussion on the future potential of this evolving market.

Amongst other elements, the report features: - A detailed review of the overall market landscape of gene therapies and gene editing therapies, including information on phase of development (marketed, clinical, preclinical and discovery) of pipeline candidates, key therapeutic areas (autoimmune disorders, cardiovascular diseases, dermatological disorders, genetic disorders, hematological disorders, immunological disorders, infectious diseases, inflammatory disorders, liver diseases, metabolic disorders, muscle-related diseases, nervous system disorders, oncological disorders, ophthalmic diseases and others), target disease indication(s), type of vector used, type of gene, therapeutic approach (gene augmentation, oncolytic viral therapy and others), type of gene therapy (ex vivo and in vivo), route of administration and special drug designation(s) awarded (if any). - A detailed review of the players engaged in the development of gene therapies, along with information on their year of establishment, company size, location of headquarters, regional landscape and key players engaged in this domain. - An elaborate discussion on the various types of viral and non-viral vectors, along with information on design, manufacturing requirements, advantages and limitations of currently available gene delivery vectors. - A discussion on the regulatory landscape related to gene therapies across various geographies, namely North America (the US and Canada), Europe and Asia-Pacific (Australia, China, Hong Kong, Japan and South Korea), providing details related to the various challenges associated with obtaining reimbursements for gene therapies. - Detailed profiles of marketed and late stage (phase II/III and above) gene therapies, including development timeline of the therapy, information on the current development status, mechanism of action, affiliated technology, strength of patent portfolio, dosage and manufacturing details, as well as details related to the developer company. - An elaborate discussion on the various commercialization strategies that can be adopted by drug developers across different stages of therapy development, including prior to drug launch, at / during drug launch and post-marketing. - A review of the various emerging technologies and therapy development platforms that are being used to design and manufacture gene therapies, featuring detailed profiles of technologies that were / are being used for the development of four or more products / product candidates. - An in-depth analysis of various patents that have been filed / granted related to gene therapies and gene editing therapies, since 2016. The analysis assesses several relevant parameters associated with the patents, including type of patent (granted patents, patent applications and others), publication year, regional applicability, CPC symbols, emerging focus areas, leading industry players (in terms of the number of patents filed / granted), and patent valuation. - A detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2020, based on several relevant parameters, such as year of agreement, type of deal, geographical location of the companies involved, key value drivers, highest phase of development of the acquired company product and target therapeutic area. - An analysis of the investments made at various stages of development in companies that are focused in this area, between 2015-2020, including seed financing, venture capital financing, IPOs, secondary offerings, debt financing, grants and other equity offerings. - A detailed geographical clinical trial analysis of completed, ongoing and planned studies of numerous gene therapies, based on various relevant parameters, such as trial registration year, trial status, trial phase, target therapeutic area, geography, type of sponsor, prominent treatment sites and enrolled patient population. - An analysis of the various factors that are likely to influence the pricing of gene therapies, featuring different models / approaches that may be adopted by manufacturers to decide the prices of these therapies. - An analysis of the big biopharma players engaged in this domain, featuring a heat map based on parameters, such as number of gene therapies under development, funding information, partnership activity and strength of patent portfolio. - An informed estimate of the annual demand for gene therapies, taking into account the marketed gene-based therapies and clinical studies evaluating gene therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength. - A case study on the prevalent and emerging trends related to vector manufacturing, along with information on companies offering contract services for manufacturing vectors. The study also includes a detailed discussion on the manufacturing processes associated with various types of vectors. - A discussion on the various operating models adopted by gene therapy developers for supply chain management, highlighting the stakeholders involved, factors affecting the supply of therapeutic products and challenges encountered by developers across the different stages of the gene therapy supply chain.

One of the key objectives of the report was to estimate the existing market size and the future opportunity associated with gene therapies, for the next decade. Based on multiple parameters, such as target patient population, likely adoption rates and expected pricing, we have provided informed estimates on the evolution of the market for the period 2020-2030. The report also features the likely distribution of the current and forecasted opportunity across [A] therapeutic approach (gene augmentation, oncolytic viral therapy, immunotherapy and others), [B] type of gene therapy (ex vivo and in vivo), [C] type of vectors used (adeno associated virus, adenovirus, herpes simplex virus, lentivirus, plasmid DNA, retrovirus and others), [D] target therapeutic areas (autoimmune disorders, cardiovascular diseases, dermatological disorders, genetic disorders, hematological disorders, metabolic disorders, muscle-related diseases, oncological disorders, ophthalmic diseases and others), [E] route of administration (intraarticular, intracerebellar, intradermal, intramuscular, intratumoral, intravenous, intravesical, intravitreal, subretinal and others), and [F] key geographical regions (US, EU5 and rest of the world). In order to account for future uncertainties and to add robustness to our model, we have provided three market forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industrys growth.

The opinions and insights presented in this study were influenced by discussions conducted with multiple stakeholders in this domain. The report features detailed transcripts of interviews held with the following individuals: - Adam Rogers (CEO, Hemera Biosciences) - Al Hawkins (CEO, Milo Biotechnology) - Buel Dan Rodgers (Founder & CEO, AAVogen) - Christopher Reinhard (CEO and Chairman, Gene Therapeutics (previously known as Cardium Therapeutics)) - Michael Triplett (CEO, Myonexus Therapeutics) - Robert Jan Lamers (CEO, Arthrogen) - Ryo Kubota (CEO, Chairman & President, Acucela) - Tom Wilton (CBO, LogicBio Therapeutics) - Jeffrey Hung (CCO, Vigene Biosciences) - Cedric Szpirer (Executive & Scientific Director, Delphi Genetics) - Marco Schmeer (Project Manager) & Tatjana Buchholz (Marketing Manager, PlasmidFactory) - Molly Cameron (Corporate Communications Manager, Orchard Therapeutics)

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

RESEARCH METHODOLOGY The data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market will evolve across different regions and technology segments. Where possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include - Annual reports - Investor presentations - SEC filings - Industry databases - News releases from company websites - Government policy documents - Industry analysts views

While the focus has been on forecasting the market over the coming decade, the report also provides our independent view on various emerging trends in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market, gathered from various secondary and primary sources of information.

KEY QUESTIONS ANSWERED - Who are the leading industry players engaged in the development of gene therapies? - How many gene therapy candidates are present in the current development pipeline? Which key disease indications are targeted by such products? - Which types of vectors are most commonly used for effective delivery of gene therapies? - What are the key regulatory requirements for gene therapy approval, across various geographies? - Which commercialization strategies are most commonly adopted by gene therapy developers, across different stages of development? - What are the different pricing models and reimbursement strategies currently being adopted for gene therapies? - What are the various technology platforms that are either available in the market or are being designed for the development of gene therapies? - Who are the key CMOs / CDMOs engaged in supplying viral / plasmid vectors for gene therapy development? - What are the key value drivers of the merger and acquisition activity in the gene therapy industry? - Who are the key stakeholders that have actively made investments in the gene therapy domain? - Which are the most active trial sites (in terms of number of clinical studies being conducted) related to this domain? - How is the current and future market opportunity likely to be distributed across key market segments?

CHAPTER OUTLINES Chapter 2 provides an executive summary of the key insights captured in our research. It offers a high-level view on the current state of the market for gene therapies and its likely evolution in the short-mid term and long term.

Chapter 3 provides a general overview of gene therapies, including a discussion on their historical background. It further highlights the different types of gene therapies (namely somatic and germline therapies, and in vivo and ex vivo therapies), potential application areas of such products and route of administration of these therapeutic interventions. In addition, it provides information on the concept of gene editing, highlighting key historical milestones, applications and various techniques used for gene editing. The also chapter includes a discussion on the advantages and disadvantages associated with gene therapies. Further, it features a brief discussion on the ethical and social concerns related to gene therapies, while highlighting future constraints and challenges related to the manufacturing and commercial viability of such product candidates.

Chapter 4 provides a general introduction to the various types of viral and non-viral gene delivery vectors. It includes a detailed discussion on the design, manufacturing requirements, advantages and limitations of currently available vectors.

Chapter 5 features a detailed discussion on the regulatory landscape related to gene therapies across various geographies, such as the US, Canada, Europe, Australia, China, Hong Kong, Japan and South Korea. Further, it highlights an emerging concept of reimbursement which was recently adopted by multiple gene therapy developers, along with a discussion on several issues associated with reimbursement of gene therapies.

Chapter 6 includes information on over 800 gene therapies and gene editing therapies that are currently approved or are in different stages of development. It features a detailed analysis of pipeline molecules, based on several relevant parameters, such as key therapeutic areas (autoimmune disorders, cardiovascular diseases, dermatological disorders, genetic disorders, hematological disorders, immunological disorders, infectious diseases, inflammatory disorders, liver diseases, metabolic disorders, muscle-related diseases, nervous system disorders, oncological disorders, ophthalmic diseases and others), target disease indication(s), phase of development (marketed, clinical, preclinical and discovery), type of vector used, type of gene, type of gene therapy (ex vivo and in vivo), therapeutic approach (gene augmentation, oncolytic viral therapy and others), route of administration and special drug designation (if any). Further, we have presented a grid analysis of gene therapies based on phase of development, therapeutic area and therapeutic approach.

Chapter 7 provides a detailed review of the players engaged in the development of gene therapies, along with information on their year of establishment, company size, location of headquarters, regional landscape and key players engaged in this domain. Further, we have presented a logo landscape of product developers in North America, Europe and the Asia-Pacific region on the basis of company size.

Chapter 8 provides detailed profiles of marketed gene therapies. Each profile includes information about the innovator company, its product pipeline (focused on gene therapy only), development timeline of the therapy, its mechanism of action, target indication, current status of development, details related to manufacturing, dosage and sales, the companys patent portfolio and collaborations focused on its gene therapy product / technology.

Chapter 9 features an elaborate discussion on the various strategies that can be adopted by therapy developers across key commercialization stages, including prior to drug launch, during drug launch and post-launch. In addition, it presents an in-depth analysis of the key commercialization strategies that have been adopted by developers of gene therapies approved during the period 2015-2020.

Chapter 10 provides detailed profiles of drugs that are in advanced stages of clinical development (phase II/III and above). Each drug profile provides information on the current developmental status of the drug, its route of administration, developers, primary target indication, special drug designation received, target gene, dosage, mechanism of action, technology, patent portfolio, clinical trials and collaborations (if any).

Chapter 11 provides a list of technology platforms that are either available in the market or in the process of being designed for the development of gene therapies. In addition, it features brief profiles of some of the key technologies. Each profile features details on the various pipeline molecules that have been / are being developed using the technology, its advantages and the partnerships that have been established related to the technology platform. Further, the chapter includes detailed discussions on various novel and innovative technologies, along with brief information about key technology providers.

Chapter 12 highlights the potential target indications (segregated by therapeutic areas) that are currently the prime focus of companies developing gene therapies. These include genetic disorders, metabolic disorders, nervous system disorders, oncological disorders and ophthalmic diseases.

Chapter 13 provides an overview of the various patents that have been filed / granted in relation to gene therapy and gene editing technologies. It also features a detailed analysis, highlighting the prevalent trends related to type of patent, publication year, regional applicability, CPC symbols, emerging areas and leading industry players (in terms of number of patents filed). In addition, it features a competitive benchmarking analysis of the patent portfolios of leading industry players and patent valuation. For the purpose of this analysis, we have taken into consideration patents that have been filed / granted since 2016.

Chapter 14 features a detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2020, based on several relevant parameters, such as year of agreement, type of deal, geographical location of the companies involved, key value drivers, highest phase of development of the acquired company product and target therapeutic area.

Chapter 15 presents details on various funding instances, investments and grants reported within the gene therapy domain. The chapter includes information on various types of investments (such as venture capital financing, debt financing, grants, capital raised from IPO and subsequent offerings) received by the companies between 2015 and 2020, highlighting the growing interest of the venture capital community and other strategic investors in this market.

Chapter 16 presents a detailed, geographical clinical trial analysis of completed, ongoing and planned studies focused on gene therapies, based on various relevant parameters, such as trial registration year, trial status, trial phase, target therapeutic area, geography, type of sponsor, prominent treatment sites and enrolled patient population.

Chapter 17 highlights our views on the various factors that may be taken into consideration while deciding the price of a gene therapy. It features discussions on different pricing models / approaches, based on the size of the target population, which a pharmaceutical company may choose to adopt in order to decide the price of its proprietary products.

Chapter 18 highlights top big biopharma players engaged in the field of gene therapy, featuring a heat map analysis based on several parameters, including therapeutic area, type of vector used, therapeutic approach and type of gene therapy.

Chapter 19 features an informed estimate of the annual demand for gene therapies, taking into account the marketed gene-based therapies and clinical studies evaluating gene therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength.

Chapter 20 presents an elaborate market forecast analysis, highlighting the future potential of the market till the year 2030. It also includes future sales projections of gene therapies that are either marketed or in advanced stages of clinical development (phase II/III and above). Sales potential and growth opportunity were estimated based on the target patient population, likely adoption rates, existing / future competition from other drug classes and the likely price of products. The chapter also presents a detailed market segmentation on the basis of [A] therapeutic approach (gene augmentation, oncolytic viral therapy, immunotherapy and others), [B] type of gene therapy (ex vivo and in vivo), [C] type of vector used (adeno associated virus, adenovirus, herpes simplex virus, lentivirus, plasmid DNA, retrovirus and others), [D] target therapeutic area (autoimmune disorders, cardiovascular diseases, dermatological disorders, genetic disorders, hematological disorders, metabolic disorders, muscle-related diseases, oncological disorders, ophthalmic diseases and others), [E] route of administration (intraarticular, intracerebellar, intradermal, intramuscular, intratumoral, intravenous, intravesical, intravitreal, subretinal and others), and [F] key geographical regions (US, EU5 and rest of the world).

Chapter 21 provides insights on viral vector manufacturing, highlighting the steps and processes related to manufacturing and bioprocessing of vectors. In addition, it features the challenges that exist in this domain. Further, the chapter provides details on various players that offer contract manufacturing services for viral and plasmid vectors.

Chapter 22 provides a glimpse of the gene therapy supply chain. It discusses the steps for implementing a robust model and provides information related to the global regulations for supply chain. Moreover, the chapter discusses the challenges associated with supply chain of gene therapies. In addition, it features the technological solutions that can be adopted for the management of gene therapy supply chain.

Chapter 23 summarizes the overall report, wherein we have mentioned all the key facts and figures described in the previous chapters. The chapter also highlights important evolutionary trends that were identified during the course of the study and are expected to influence the future of the gene therapy market.

Chapter 24 is a collection of interview transcripts of the discussions that were held with key stakeholders in this market. The chapter provides details of interviews held with Adam Rogers (CEO, Hemera Biosciences), Al Hawkins (CEO, Milo Biotechnology), Buel Dan Rodgers (Founder & CEO, AAVogen), Christopher Reinhard (CEO & Chairman, Gene Therapeutics (previously known as Cardium Therapeutics)), Michael Triplett (CEO, Myonexus Therapeutics), Robert Jan Lamers (CEO, Arthrogen), Ryo Kubota (CEO, Chairman & President, Acucela), Tom Wilton (CBO, LogicBio Therapeutics), Jeffrey Hung (CCO, Vigene Biosciences), Cedric Szpirer (Executive & Scientific Director, Delphi Genetics), Marco Schmeer (Project Manager) & Tatjana Buchholz (Marketing Manager, PlasmidFactory) and Molly Cameron (Corporate Communications Manager, Orchard Therapeutics). In addition, a brief profile of each company has been provided.

Chapter 25 is an appendix, which provides tabulated data and numbers for all the figures included in the report.

Chapter 26 is an appendix, which contains a list of companies and organizations mentioned in this report.Read the full report: https://www.reportlinker.com/p06020737/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

__________________________

Read more:

Gene Therapy Market by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of Administration, and Key...

DetailsCategory: DNA RNA and CellsPublished on Monday, 08 February 2021 16:09Hits: 438

- Phase 1/2 trial expected to commence in first half of 2021

- Company has three INDs cleared for rare monogenic CNS disorders

PHILADELPHIA, PA, USA I February 08, 2021 I Passage Bio, Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare monogenic central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for PBKR03, an adeno-associated virus (AAV)-delivery gene therapy being studied for the treatment of early infantile Krabbe disease (Globoid Cell Leukodystrophy). Currently, there are no approved disease-modifying therapies available for Krabbe disease, a rare lysosomal storage disease that most often presents early in a childs life, resulting in rapid progressive damage to both the brain and peripheral nervous system and mortality by two years of age. Underscoring the urgent medical need in the patient population, the FDA has previously granted Passage Bio both Orphan Drug and Rare Pediatric Disease designations for PBKR03 for treatment in Krabbe disease.

As part of our commitment to deliver a transformative, one-time gene therapy to the children and their families who suffer from the devastating effects of Krabbe disease, we are excited to advance toward clinically evaluating the potential life-changing benefits of PBKR03, said Bruce Goldsmith, Ph.D., chief executive officer of Passage Bio. The FDA clearance of our IND for PBKR03 is an important milestone for Passage Bio, paving the way for the start of our third clinical program in rare monogenic CNS disorders in the first half of 2021. Having solidified our clinical trial preparedness and manufacturing readiness during the past year, we are well-positioned to move with urgency to advance PBKR03 into the clinic.

PBKR03 utilizes a next-generation proprietary AAV capsid to deliver, through intra-cisterna magna (ICM) administration, a functional GALC gene to Krabbe patients with mutations in the gene that codes for galactosylceramidase (GAL-C). Low GAL-C activity results in accumulation of psychosine which is toxic to the myelin-producing oligodendrocytes of the CNS and Schwann cells in the periphery, resulting in damage to both the central and peripheral nervous systems. PBKR03 has the potential to treat both the central nervous system and peripheral nerve manifestations observed in Krabbe disease patients.

Compelling preclinical data support advancement into clinical trials

PBKR03 is supported by extensive preclinical studies, conducted by our collaborator, the University of Pennsylvanias Gene Therapy Program, showing meaningful transduction of both the central and peripheral nervous system in animal models, with restoration of myelination in the brain and peripheral nerves. In a naturally occurring Krabbe animal model, a single ICM injection of an AAVhu68 capsid containing the normal canine GALC gene showed normalization of GALC activity, reduction of cerebral spinal fluid psychosine levels, normalization of peripheral nerve conduction velocity, improvement in brain myelination, reduction in brain inflammation and increased survival.

Phase 1/2 study anticipated for 1H21

Passage Bio expects to initiate a Phase1/2 clinical trial for PBKR03 in the first half of 2021. The trial is designed as a dose escalation study of a single ICM dose of PBKR03 in pediatric subjects with early infantile Krabbe disease. The primary endpoint of the Phase 1/2 study is safety and tolerability; secondary endpoints include CSF and serum GALC levels, disease biomarkers, and clinical outcome measures. Initial data from the trial is anticipated to potentially readout in late 2021 or early 2022, depending on the timing of when the first patient is treated in the study.

PENN Financial Disclosure

The University of Pennsylvania (Penn) and its Gene Therapy Program receives sponsored research funding from Passage Bio, and Penn has licensed intellectual property to Passage Bio that may result in future financial returns to Penn.

About Krabbe Disease

Krabbe disease is a rare and often life-threatening lysosomal storage disease caused by mutations in the GALC gene, which encodes galactosylceramidase, an enzyme that breaks down galactosylceramide and psychosine. Without adequate levels of galactosylceramidase, psychosine accumulates, causing widespread death of myelin-producing cells and progressive damage to nerves in both the brain and peripheral tissues. The early infantile form of the disease is the most severe and common, typically manifesting before six months of age and accounting for 60 percent to 70 percent of diagnoses. In these patients, the disease course is highly predictable and rapidly progresses to include loss of acquired milestones, staring episodes, apnea, peripheral neuropathy, severe weakness, unresponsiveness to stimuli, seizures, blindness, deafness and eventual death by two years of age. Late infantile patients, defined by onset between seven to twelve months of age, present similar symptoms and have a median survival of approximately five years from onset of symptoms. The estimated worldwide incidence of Krabbe disease is 2.6 in 100,000 births, which is higher than reported due to lack of adequate screening at birth.

About Passage Bio

At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvanias Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with enhanced access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at http://www.passagebio.com.

SOURCE: Passage Bio

Go here to read the rest:

FDA Clears IND Application for Passage Bio's Gene Therapy Candidate PBKR03 for Treatment of Patients with Early Infantile Krabbe Disease, A Rare...

Breyanzi (lisocabtagene maraleucel) was approved on the 54 percent complete remission rate achieved in diffuse large B-cell lymphoma trials.

Breyanzi (lisocabtagene maraleucel), a chimeric antigen receptor (CAR) T cell-based gene therapy to treat adult patients with certain types of large B-cell lymphoma who have not responded to, or relapsed, after at least two other types of systemic treatment has been approved by the US Food and Drug Administration (FDA).

According to the agency, Breyanzi is the third gene therapy approved in the US for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Todays approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes, commented Dr Peter Marks, director of the FDAs Center for Biologics Evaluation and Research. Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens.

DLBCL is the most common type of non-Hodgkin lymphoma in adults. Approximately 77,000 new cases of non-Hodgkin lymphoma are diagnosed in the US each year, with DLBCL accounting for around a third of newly diagnosed cases.

Breyanzi is customised for each patient; their T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates targeting and killing of the lymphoma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of the treatment were established in a multi-centre clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54 percent.

The treatment can cause severe side effects, including cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities. Both CRS and neurological events can be life-threatening, so the therapy is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU).

The requirements include, among other things, that healthcare facilities that dispense Breyanzi be specially certified, with staff involved in the prescribing, dispensing or administering of the treatment being trained to recognise and manage the risks of CRS and neurologic toxicities.

Other side effects include hypersensitivity reactions, serious infections, low blood cell counts and a weakened immune system. According to the FDA, side effects generally appear within the first one to two weeks following treatment, but some side effects may occur later.

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Breyanzi.

The approval was granted to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.

Read more from the original source:

FDA approves third gene therapy for large B-cell lymphoma - European Pharmaceutical Review