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.

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

ALISO VIEJO, Calif.--(BUSINESS WIRE)--As gene therapies and editing technologies rapidly advance, it is more urgent than ever to provide updates and information to the rare disease community on how these technologies can be applied across multiple diseases. Global Genes, a leading rare disease patient advocacy organization, is pleased to announce they will be publishing a multimedia series, titled Platforms of Hope: Advances in Gene Therapy and Gene Editing, throughout 2021 regarding upcoming data announcements and information on gene therapy and editing technology advances with thought leaders from the National Center for Advancing Translational Sciences (NCATS), the NIH Common Funds Somatic Cell Genome Editing (SCGE) program and other leading voices in these fields.

In addition to ongoing coverage through Global Genes videos, online publication RARE Daily and RARECast podcast, the organization will be publishing a special report at the end of 2021 on gene therapy and gene editing innovation. This will address a wide range of topics, with a focus on efforts to accelerate the translation of discoveries into genetic medicines that benefit patients with rare diseases.

With more than 7,000 rare diseases, there is an urgent need to keep the rare disease community abreast of developments in the rapidly changing fields of gene therapy and genome editing, said P.J. Brooks, program director at the Office of Rare Diseases Research at the NCATS. In this collaboration, NIH will help Global Genes identify the ideas, technologies and advances that have broad implications for many patients and families affected by rare diseases and provide information that could positively impact their lives and care in the future.

This collaboration will bring visibility into cutting-edge science at the frontier of genetic medicines and provide the rare disease community with insights into emerging technologies and therapies in development for rare diseases, said Christian Rubio, vice president, strategic advancement at Global Genes. Its critically important to educate the rare disease community on these rapidly evolving events.

For more information, visit http://www.globalgenes.org/media-hub.

About Global Genes

Global Genes is a 501(c)(3) nonprofit organization dedicated to eliminating the burdens and challenges of rare diseases for patients and families globally. In pursuit of our mission, we connect, empower, and inspire the rare disease community to stand up, stand out, and become more effective on their own behalf -- helping to spur innovation, meet essential needs, build capacity and knowledge, and drive progress within and across rare diseases. We serve the more than 400 million people around the globe and nearly one in 10 Americans affected by rare diseases. If you or someone you love has a rare disease, or are searching for a diagnosis, contact Global Genes at 949-248-RARE, or visit our resource hub.

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Global Genes Announces New Multimedia Series Focused on Advances in Gene Therapy and Editing, in Collaboration with the National Institutes of Health...

New York, Feb. 10, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Europe Cell and Gene Therapy Market - Industry Outlook and Forecast 2021-2026" - https://www.reportlinker.com/p06021776/?utm_source=GNW

The global cell and gene therapy market is observing significant mergers and acquisition activities, product sales, and new market authorizations. In 2026, the market is expected to grow almost four times more than the current value, with new product approvals expected annually. Although initial product approvals have been for relatively small patient groups, the significant pipeline of cell & gene therapy studies for diseases such as hemophilia and various forms of blindness will significantly expand. In addition, the Europe market is witnessing steady growth due to the increased availability of funds from several public and private institutes. There is increased support from regulatory bodies for product approvals and fast-track product designations, which encourage vendors to manufacture products at a fast rate. Moreover, with over 237 regenerative medicines companies headquartered in Europe, the region is seen as the favorite destination for cell and gene therapy manufacturing.

The following factors are likely to contribute to the growth of the Europe cell and gene therapy market during the forecast period: CMOs Offering Vector Manufacturing Services for Cell and Gene Therapy Companies Robust Cell & Gene Therapies in the Pipeline Increase in Strategic Acquisitions Regulatory Support for Cell and Gene Therapy Products

The study considers the present scenario of the Europe cell and gene therapy market and its market dynamics for the period 2020?2026. It covers a detailed overview of several market growth enablers, restraints, and trends. The report offers both the demand and supply aspects of the market. It profiles and examines leading companies and other prominent ones operating in the market.

Europe Cell and Gene Therapy Market Segmentation The Europe cell and gene therapy market research report includes a detailed segmentation by product, end-user, application, geography. A high potential to treat several chronic diseases, which cannot be effectively treated/cured through conventional methods otherwise, is propelling the growth of gene therapies. Gene therapies are regarded as a potential revolution in the health sciences and pharmaceutical fields. The number of clinical trials investigating gene therapies is increasing in Europe, despite the limited number of products that have successfully reached the market. However, gene therapies show slow progress and promising prospect in terms of treatments. High support from regulatory bodies to commercialize these products and make them affordable to patients is another important factor contributing the market growth.

Delivering cell and gene therapies requires specialized facilities, capabilities, and clinician skills. Therefore, manufacturers are working in tandem with chosen treatment centers (hospitals) to establish the protocols and procedures necessary to receive the product and therapies. While cell therapies represent a paradigm shift in the treatment of several incurable, chronic diseases, with durable responses and long-term disease control measures, hospitals appear an ideal location to carry out these procedures. Hospitals are growing at a significant rate due to the increasing target population in Europe. Tier-I hospitals are proving to be sought-after network partners for cell and gene therapy developers. They tend to be in major population centers, have adequate financial and personnel resources, and value the prestige that comes with being the first movers in an innovative treatment area.

Oncology accounted for a share of over 30% in 2020. While cancer treatments have evolved and undergone massive developments in recent years, it continues to be one of the deadliest diseases confronted by humans. Traditional cancer therapies have a curative effect in the short term; however, they have side effects, thereby decreasing the patients quality of life. Cell and gene therapies for certain types of cancers have been promising results. The chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. CAR-T cell therapies are developing rapidly, and many clinical trials have been established on a global scale, which has high commercial potential for the treatment of cancer. Immunotherapies based on CAR-T cells go one step further, engineering the T cells themselves to enhance the natural immune response against a specific tumor antigen. CAR-T clinical trials have shown high remission rates, up to 94%, in severe forms of blood cancer, thereby increasing the market growth.

Product Cell Therapies Gene Therapies End-user Hospitals Cancer Care Centers Wound Care Centers Others Application Oncology Dermatology Musculoskeletal Others

INSIGHTS BY GEOGRAPHY Germany, France, the UK, Italy, and Spain play a significant role in the Europe cell and gene therapy market. Clinical trials and the number of manufacturing facilities are increasing slowly in the European region. The region has become a major R&D destination for several vendors as the funding for cell & gene therapies is increasing. Europe has supported collaborative efforts in gene transfer and gene therapy research. In addition, the target patient population is increasing across Europe; there were an estimated 3.9 million new cases of cancer and 1.9 million cancer deaths in Europe in 2018. In addition, the prevalence surveys in the UK and Denmark indicate that there are 34 people with one or more wounds per 1,000 people. Favorable government support in terms of product approvals, reimbursement and coverage, and high R&D funding to academic institutes that are involved in the development of cell and gene therapies are expected to boosting the market in Europe.

Geography Europe o UK o Germany o France o Italy o Spain o Switzerland o Netherlands

INSIGHTS BY VENDORS Novartis, Spark Therapeutics, Amgen, Gilead Sciences, and Organogenesis are the leading players in the Europe cell and gene therapy market. The market offers tremendous growth opportunities for existing and future/emerging players on account of the presence of a large pool of target patient population with chronic diseases such as cancer, wound disorders, diabetic foot ulcer, CVDs, and other genetic disorders. Recent approvals have prompted an unprecedented expansion among vendors. While a few vendors are opting for in-house production of cell and gene therapies, a substantial number of vendors are preferring third-party service providers, including CMOs.

Prominent Vendors Novartis Spark Therapeutics Amgen Gilead Sciences Organogenesis

Other Prominent Vendors APAC Biotech AVITA Medical bluebird bio CHIESI Farmaceutici CollPlant CO.DON Human Stem Cells Institute PJSC (HSCI) Medipost NuVasive Nipro Orchard Therapeutics RMS Regenerative Medical System Orthocell Osiris Therapeutics Sibino GeneTech Shanghai Sunway Biotech Takeda Pharmaceutical Company Terumo Vericel

Emerging Investigational Vendors In Europe Adaptimmune Therapeutics AgenTus Therapeutics Autolus Cellecits Celyad CombiGene EUKARS Freeline Therapeutics Innoskel PsiOxus Therapeutics Ltd SparingVision uniQure

KEY QUESTIONS ANSWERED 1. What is the Europe cell and gene therapy market size and growth rate during the forecast period? 2. What are the factors driving the demand for CAR-T therapy in the European region? 3. How are strategic acquisitions aiding in market growth of cell and gene therapy products? 4. Which segments are expected to generate the highest revenues during the forecast period? 5. Who are the leading vendors in the European cell and gene therapy market?Read the full report: https://www.reportlinker.com/p06021776/?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.

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The Europe cell and gene therapy market by revenue is expected to grow at a CAGR of over 23% during the period 20212026 - GlobeNewswire

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.

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

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.

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

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.

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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.

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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.

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

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.

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