Category Archives: Genetic Therapy

By using the herpes simplex virus (HSV) as a helper for its adeno-associated viral (AAV) platform, Applied Genetic Technologies Corporation (AGTC) created AAVs that are more robust, purer and lower cost than any of the other methods.

Its gene therapy program for X-linked retinitis pigmentosa (XLRP) is a case in point. By using its herpes-assisted vector expansion (HAVE) methodology, we are now achieving finished product specifications that demonstrate nearly 90% full capsids with extremely low residuals, many of which fall below the level of detection, resulting in purity levels exceeding 97%, said Dave Knop, Ph.D., head of process development at AGTC. This is in addition to yields that are more than 10-fold higher than what we achieved in our Phase I/II manufacturing campaigns.

Still in the midst of trials, the company can produce AAVs at commercial scale using 40L bioreactors.

Thats particularly notable because of the challenges associated with manufacturing AAVs. The overarching problem is complexity. AAV vectors require simultaneously introducing DNA encoding the AAV replication and capsid genes, a therapeutic gene and a helper-function gene. Too often, some but not all of the elements are introduced successfully.

AGTCs HAVE method uses recombinant, replication-incompetent herpes simplex virus vectors to introduce the rep and cap genetic sequences as well as the therapeutic gene into baby hamster kidney (BHK) cells grown in suspension.

We further adapted the BAK cell to serum-free media, making the process scalable, Knop said.

Compared to transient transfection, the HAVE method is 50-fold more productive.

This method is more productive (than transfection) because the virus does what its meant to do naturally, Knop told BioSpace.

Benefits include high levels of infectivity and lower cost of goods.

We see a very good infectivity ratios in the final purified virus, Knop said.

A one-to-one ratio, in which it takes one vector to infect one cell, is ideal. The ratios reported in the literature are 50 or 100 to one. AGTCs ratio is about ten to one.

AGTC also has experienced a 90-fold reduction in the cost of goods benchmarked against traditional transfection in cell culture, Knop added. Thats possible because the HSV method allows scale-up rather than merely scale-out. Scale-out breaks down with larger markets. With our process, we can scale to one larger, single-use stir tank bioreactor, rather than adding many smaller bioreactors.

That allows a smaller footprint and tighter control of the process, resulting in reduced risk of contamination and processing errors. During scaleup, it creates greater consistency while increasing quantities are manufactured for clinical trials and, ultimately, for commercialization.

AGTC doesnt begin with this system, though.

Typically, for very early, non-clinical work, researchers use the most flexible, readily available systems they can, Knop said. The resulting vectors typically produce a relatively low ratio of fully-loaded vectors, making them inadequate for manufacturing materials for late-stage clinical trials.

We use transfection until we narrow down the options, and then port the work to our system, testing and adjusting as needed, he said. Our process is more involved than transfection, so we use it for programs that are earmarked for formal toxicological or bio-distribution studies for FDA submissions for clinical trials.

To ensure robustness, AGTC isolates individual cells, expands them into small cell banks and screens them for productivity and quality. Then the company develops a robust downstream process for further separation. That results in a capsid fill rate of about 90%. Continued screening allows the company to meet its quality and purity needs and to increase the effective filled percentage to about 95%.

The HAVE manufacturing approach has provided materials for six successful investigational new drug (IND) applications without any clinical holds, and has been transferred successfully to industry partners and contract manufacturing organizations, according to an article by Knop and AGTC President and CEO Sue Washer.

Currently, AGTC is using HAVE to manufacture materials targeting XLRP, a rare, inherited condition that causes progressive vision loss and leads to blindness in boys and young men. It is caused by mutations in the RPGR gene. As of yet, there is no specific treatment. The drug was granted orphan status by both the FDA and the EMA. This is one of several programs AGTC has advanced to clinical trials for people with rare and debilitating ophthalmic, otologic and central nervous system (CNS) diseases.

Going forward, were continuing to refine the system and partner with those who need assistance where our manufacturing capabilities may be useful, Knop said. We have active, ongoing research for every element of the process. Almost every step is being reexamined to find additional ways to produce additional and better cell lines, improve purification processes and outcomes and lower the cost of goods.

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AGTC Boosts AAV Manufacturing Productivity with Herpes Simplex Virus - BioSpace

SAN RAFAEL, Calif., June 17, 2020 /PRNewswire/ --BioMarin Pharmaceutical Inc.(NASDAQ: BMRN) announced today additional data from its previously reported four-year update of an open-label Phase 1/2 study of valoctocogene roxaparvovec, an investigational gene therapy treatment for severe hemophilia A. The results were presented during a late-breaking oral presentation at the World Federation of Hemophilia (WFH) Virtual Summit by Professor John Pasi, M.B., Ch.B., Ph.D., from Barts and the London School of Medicine and Dentistry and Chief Investigator for this Phase 1/2 study.

"With four years of data, this study represents the longest duration of clinical experience for any gene therapy in hemophilia A. It is exciting to observe that all study participants remain off Factor VIII prophylaxis therapy, while also experiencing a greater than 90 percent reduction in bleeding episodes from a single administration of valoctocogene roxaparvovec," said Professor Pasi. "These data demonstrate the very real potential of a paradigm shift in the treatment of hemophilia A and that ongoing research into gene therapies could represent an entirely new way to approach meeting the high unmet need in patients with severe hemophilia A."

"BioMarin is committed to the bleeding disorders community with the most robust and advanced clinical development program for a potential first gene therapy in severe hemophilia A," said Hank Fuchs, M.D., President, Global Research and Development at BioMarin. "We are pleased to share these data at WFH. Demonstrating a 96% reduction in exogenous Factor VIII usage as patients are now producing their own endogenous factor VIII is a potential benefit that we hope to be able to offer as we work closely with regulators to seek approval and work to reduce the burden of hemophilia."

The data presented at WFH is the most current data (April 8, 2020, cut off) and includes four years of data for the 6e13 vg/kg cohort and three years of data for the 4e13 vg/kg cohort.

Annualized Bleed Rate and Factor VIII Use in 6e13 vg/kg Cohort

In the six study participants who were previously on Factor VIII prophylaxis in the 6e13 vg/kg cohort, the data showed substantial and sustained reductions in bleeding that required Factor VIII infusions. In the year prior to treatment with valoctocogene roxaparvovec, the mean Annualized Bleed Rate (ABR) was 16.3 and the median was 16.5. During the four years following treatment with valoctocogene roxaparvovec, the cumulative mean ABR was 0.8, which represents a 95% reduction from baseline. In the fourth year, the mean ABR was 1.3 and the median was zero (see Table 1). There was a 96% reduction in mean Factor VIII usage to 5.4 infusions per year cumulatively over four years from the baseline of 135.6 infusions per year.

Among all seven study participants in the 6e13 vg/kg cohort, 86% or six out of seven were bleed-free in the fourth year. All participants remain off Factor VIII prophylaxis therapy (see Table 1).

Annualized Bleed Rate and Factor VIII Use in 4e13 vg/kg Cohort

Similarly, in the six study participants in the 4e13 vg/kg cohort, the data showed substantial and sustained reductions in bleeding requiring Factor VIII infusions following treatment with valoctocogene roxaparvovec. All participants remain off Factor VIII prophylaxis therapy.

In the year prior to treatment with valoctocogene roxaparvovec, the mean ABR was 12.2 and the median was 8.0. The cumulative mean ABR was reduced by 93% to 0.9 with continued absence of target joint bleeds in 5 of 6 subjects during the three years observed, which represents a 93% reduction from baseline. During the thirdyear of follow-up, the mean ABR was 0.5 and the median was zero (0), and 67% or four out of six study participants were bleed-free. Five out of six participants had no spontaneous bleeds. There was a 96% reduction in mean Factor VIII usage to 5.7 infusions per year cumulatively over three years from the baseline of 142.8 infusions per year. (see Table 1)

Factor VIII Activity Levels for 6e13 vg/kg and 4e13 vg/kg Cohorts

For the 6e13 vg/kg and 4e13 vg/kg cohorts, mean Factor VIII activity levels over four and three years, respectively, support the observed reductions in bleed rates and annualized Factor VIII usage. All study participants had severe hemophilia A at baseline, defined as less than or equal to 1 IU/dL of Factor VIII activity.

At the end of the fourth-year post-infusion with valoctocogene roxaparvovec, all patients continue to produce their own endogenous factor with the mean Factor VIII activity level of the 6e13 vg/kg cohort at 24.2 IU/dL as measured by the chromogenic substrate (CS) assay and at 35.4 IU/dL as measured by the One-Stage (OS) assay. The median Factor VIII activity levels at the end of the fourth year was 16.4 IU/dL as measured by the CS assay and 23.4 IU/dL as measured by the OS assay. These measurements are based on six of the seven participants, as an evaluable sample for the seventh study participant was not available.

Mean Factor VIII activity levels over three years similarly support the observed reductions in bleed rates and annualized Factor VIII usage for the 4e13 vg/kg cohort. At the end of the third year post-infusion with valoctocogene roxaparvovec, mean Factor VIII activity level of the 4e13 vg/kg cohort was 9.9 IU/dL as measured by the CS assay and 14.9 IU/dL as measured by the OS assay. The median Factor VIII activity levels at the end of the third year was 7.9 IU/dL as measured by the CS assay and 12.3 IU/dL as measured by the OS assay (see Tables 2 and 3 for graphics of data results).

Webinar with BioMarin and Study Investigators, Today at 5:00 PM ET

At 5pm ET, BioMarin management will host a webinar with key clinical investigators, Professor John Pasi and Dr. Steve Pipe, to discuss results from the Phase 1/2 Study of valoctocogene roxaparvovec gene therapy for severe hemophilia Apresented at the WFH Virtual Summit today. Interested parties may access a live video webinar that will include audio and slides at: https://bmrn.zoom.us/j/94005113278

For access to the audio portion only, please use a dial-in number in your region for the highest quality connection:

U.S. Dial-in Numbers: +1 669 900 6833 (Bay Area); +1 253 215 8782 (Washington); +1 346 248 7799 (Houston): +1 929 205 6099 (New York); +1 301 715 8592 (Maryland); +1 312 626 6799 (Chicago)

International Dial-in Numbers Available at: https://bmrn.zoom.us/u/acdpx0wbxX

Webinar ID: 940 0511 3278

Safety Summary

Overall, the safety profile of valoctocogene roxaparvovec remains consistent with previously reported data with no delayed-onset, treatment-related events. No participants developed inhibitors to Factor VIII, and no participants withdrew from the study. No participants have developed thrombotic events. The most common adverse events associated with valoctocogene roxaparvovec occurred early and included transient infusion-associated reactions and transient, asymptomatic, and mild to moderate rise in the levels of certain proteins and enzymes measured in liver function tests with no long-lasting clinical sequelae.

Robust Clinical Program

The global Phase 3 study of valoctocogene roxaparvovec at the 6e13 vg/kg dose (GENEr8-1) evaluates superiority of valoctocogene roxaparvovec to the current standard of care, FVIII prophylactic therapy. The sample size of the GENEr8-1 study is approximately 130 total participants. Enrollment is completed and the data from this study is expected in the fourth quarter of 2020 or the first quarter of 2021.

BioMarin has five clinical studies underway in its comprehensive gene therapy program for the treatment of severe hemophilia A. In addition to the global Phase 3 study GENEr8-1, the Company is running a Phase 1/2 Study with the 6E13kg/vg dose of valoctocogene roxaparvovec in approximately 10 participants with pre-existing AAV5 antibodies. The Company is also running two additional and separate studies, one to study AAV seroprevalence in people with severe hemophilia A and one non-interventional study to determine baseline characteristics in people with hemophilia A. Participants in the Phase 1/2 dose escalation study will continue to be monitored as part of the global program underway.

Regulatory Status

The Food and Drug Administration (FDA) is reviewing the biologics license application, under Priority Review, for valoctocogene roxaparvovec with a PDUFA action date of August 21, 2020. The FDA also granted valoctocogene roxaparvovec Breakthrough Therapy designation.

The European Medicines Agency (EMA) validated the Company's Marketing Authorization Application (MAA) for valoctocogene roxaparvovec, which has been in review under accelerated assessment since January. Recognizing valoctocogene roxaparvovec for its potential to benefit patients with unmet medical needs, EMA granted access to its Priority Medicines (PRIME) regulatory initiative. Although the MAA remains under accelerated assessment at this time, the Company expects the review procedure to be extended by at least three months due to COVID-19 delays. Further, the Company believes there is a high possibility that the MAA will revert to the standard review procedure, as is the case with most filings that initially receive accelerated assessment. Because of the combination of these events, the Company expects an opinion from the Committee for Medicinal Products for Human Use (CHMP) in late 2020/early 2021.

BioMarin's valoctocogene roxaparvovec has also received orphan drug designation from the FDA and EMA for the treatment of severe hemophilia A.The Orphan Drug Designation program is intended to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions.

The Company believes that both submissions represent the first time a gene therapy product for any type of hemophilia indication is under review for marketing authorization by health authorities.

About Hemophilia A

People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A (FVIII levels <1%) often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. People with hemophilia A with moderate (FVIII 1-5%) or mild (FVIII 5-40%) disease show a much-reduced propensity to bleed. The standard of care for individuals with severe hemophilia A is a prophylactic regimen of replacement Factor VIII infusions administered intravenously up to two to three times per week or 100 to 150 infusions per year. Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have Hemophilia A.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for serious and life-threatening rare and ultra-rare genetic diseases. The Company's portfolio consists of six commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visitwww.biomarin.com. Information on BioMarin's website is not incorporated by reference into this press release.

Forward Looking Statements

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including without limitation, statements about: (i) the development of BioMarin's valoctocogene roxaparvovec program generally, (ii) the impact of valoctocogene roxaparvovec gene therapy for treating patients with severe hemophilia A, (iii) the 4-year data demonstrating the very real potential of a paradigm shift in the treatment of hemophilia A and that ongoing research into gene therapies could represent an entirely new way to approach meeting the high unmet need in patients with severe hemophilia A, (iv) the data from the Company's Phase 3 study expected in the fourth quarter of 2020 or the first quarter of 2021, (v) that Factor VIII activity levels over four years supporting reductions in bleed rates and Factor VIII usage, and (vi) the potential approval and commercialization of valoctocogene roxaparvovec for the treatment of severe hemophilia A, including timing of such approval decisions.These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of valoctocogene roxaparvovec, including final analysis of the above interim data; any potential adverse events observed in the continuing monitoring of the patients in the Phase 1/2 trial; the content and timing of decisions by the FDA, the European Commission and other regulatory authorities, including the potential impact of the COVID-19 pandemic on the regulatory authorities' abilities to issue such decisions and the timing of such decisions; the content and timing of decisions by local and central ethics committees regarding the clinical trials; BioMarin's ability to successfully manufacture valoctocogene roxaparvovec; and those other risks detailed from time to time under the caption "Risk Factors" and elsewhere in BioMarin's Securities and Exchange Commission (SEC) filings, including BioMarin's Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, and future filings and reports by BioMarin. BioMarin undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events or changes in its expectations.

BioMarin is a registered trademark of BioMarin Pharmaceutical Inc.

Contacts:

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BioMarin Pharmaceutical Inc.

BioMarin Pharmaceutical Inc.

(415) 455-7558

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BioMarin Provides Additional Data from Recent 4 Year Update of Ongoing Phase 1/2 Study of Valoctocogene Roxaparvovec Gene Therapy for Severe...

INTRODUCTION Over the last few years, the exponential growth in the pipeline of nucleic acid based therapies has led to the escalating interest of pharmaceutical industry in this domain.

New York, June 18, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Non-Viral Transfection Reagents and Systems Market, 2020-2030" - https://www.reportlinker.com/p05915358/?utm_source=GNW Presently, more than 2,000 trials evaluating different types of gene therapies are underway. Moreover, according to experts at the US FDA, around 40 new gene therapies are likely to be approved by 2022. In this context, it is worth highlighting that viral vectors are a crucial element in gene therapy development and manufacturing. Although, viral vectors have shown significant success in R&D, their applications are limited due to immunogenicity and toxicity related concerns, high development costs and the limitation on amount of genomic material that they can carry. Excessively high price tags associated with viral-based therapies, such as Zolgensma (USD 2.1 million) and Luxtruna (USD 850,000), have led to several reimbursement challenges, thereby decreasing patient access. Owing to the aforementioned concerns related to viral vectors, therapy developers are evaluating a variety of non-viral methods of gene delivery.

In the present scenario, non-viral transfection systems are not yet widely used in therapy development and clinical studies, primarily due to their relatively low efficiency compared to viruses. The applications of these methods are largely restricted to fundamental research, including protein and gene expression, and cell line development. However, there are a number of companies that have developed proprietary technologies and products to facilitate physical (electroporation, gene gun, microinjection and sonoporation), chemical (transfection reagents) and other non-viral methods of transfection (transposon based systems, piggyBac and magnetofection). We believe that, as the demand for advanced therapy medicinal products, which require genetic engineering, the opportunity for non-viral transfection system developers is also likely to grow.

SCOPE OF THE REPORTThe Non-Viral Transfection Reagents and Systems Market, 2020-2030 report features an extensive study of the various systems and technologies available for non-viral transfection, in addition to the current market landscape and future potential of product developers.

Amongst other elements, the report features: A detailed assessment of the competitive landscape of various types of non-viral transfection systems, including transfection reagents, electroporation-based transfection systems and other non-viral transfection systems, featuring product specific information, such as type of carrier used, type of molecule delivered, recommended cell type and price of the system (if available). Additionally, the chapter includes information on non-viral transfection system developers, including information on year of establishment, company size and geographical location. An insightful 2X2 representation, highlighting the competitiveness analysis of non-viral transfection system developers captured in our database, taking into consideration supplier power (based on company size) and service strength (based on strength of product portfolio, years of experience and type of molecule delivered). An analysis highlighting potential strategic partners segregated based on likelihood of entering into collaboration with non-viral transfection system developers. The analysis takes into consideration multiple relevant parameters, such as type of therapy, pipeline strength, pipeline maturity, type of vector and company size. An analysis of the big pharma players engaged in this domain, featuring a heat map based on parameters, such as type of initiative, type of therapy and target therapeutic area. An analysis of completed, ongoing and planned clinical studies related to non-viral transfection systems, featuring details on registration year, trial phase, trial status, type of sponsor, type of therapy, target therapeutic area, trial design, type of patient allocation model used, type of trial masking adopted, type of intervention, trial purpose, geographical location of trial and enrolled patient population. An in-depth analysis of close to 14,000 patents related to non-viral transfection systems that have been filed / granted since 2017, highlighting key trends associated with these patents, across type of patents, publication year, geographical location, type of applicants, issuing authority / patent offices involved, CPC symbols, emerging focus areas, leading players (in terms of number of patents granted / filed in the given time period), patent characteristics and geography. It also includes a detailed patent benchmarking and an insightful valuation analysis. A detailed publication analysis of more than 1,100 peer-reviewed, scientific articles that have been published since 2014, highlighting the key trends associated with these publications, across year of publication, focus area, type of molecule delivered, target therapeutic area, important cells and cell lines evaluated, leading players across different geographies and key journals (in terms of number of articles published in the given time period) within this domain.

One of the key objectives of the report was to understand the primary growth drivers and estimate the future opportunity within the market. Based on several parameters, such as annual number of transfections, cost per transfection, share of non-viral systems within the transfections market and expected annual growth rate across various geographies, we have provided an informed estimate of the likely evolution of the market, in the mid to long term, for the period 2020-2030. The chapter features the likely distribution of the future opportunity across [A] non-viral transfection systems (non-viral transfection reagents, electroporation-based transfection systems and other non-viral transfection systems), [B] end-users (academic and research institutions, pharmaceutical companies and other end-users), [C] area of application (clinical application and research application) and [D] geographical regions (North America, Europe, Asia-Pacific and rest of the world).

In order to account for future uncertainties and to add robustness to our model, we have provided three forecast scenarios, portraying the conservative, base and optimistic tracks of the markets evolution. The opinions and insights presented in this study were influenced by discussions conducted with multiple stakeholders in this domain. In addition, the report features detailed transcripts of interviews held with the following individuals (in alphabetical order of company names): George Eastwood (Vice-President of Business Development, Kytopen) Claudia Andretta (Global Business Development Manager, Clinical, Polyplus-transfection)

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

RESEARCH METHODOLOGYThe research, analysis and insights presented in this report are backed by a deep understanding of insights gathered from both secondary and primary sources. For all our projects, we conduct interviews with experts in the area (academia, industry 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 till 2030, the report also provides our independent view on various non-commercial trends emerging 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.

CHAPTER OUTLINESChapter 2 is an executive summary of the insights captured in our research. It offers a high-level view on the likely evolution of the non-viral transfection systems market in the mid to long term.

Chapter 3 provides an overview of transfection and its applications, such as advanced therapy medicinal product development, gene silencing, bioproduction of therapeutic protein and stem cell engineering. It highlights different methods of transfection (such as viral and non-viral), with a brief outline of various viral vectors (AAV, adenoviral, lentiviral, retroviral and others), chemical methods (lipoplexes, polyplexes, lipoplexes and others) and physical methods (electroporation, gene gun, sonoporation, magnetofection and others) used in transfection.

Chapter 4 provides an overview of various types of non-viral transfection systems including transfection reagents, electroporation-based transfection systems and other non-viral transfection systems, featuring product specific information, such as type of carrier used, type of molecule delivered, recommended cell type and price of the system (if available). Additionally, the chapter includes information on non-viral transfection system developers, including information on year of establishment, company size and geographical location.

Chapter 5 provides a detailed competitiveness analysis of the companies offering non-viral transfection systems, taking into consideration supplier power (based on company size) and service strength (based on strength of product portfolio, years of experience and type of molecule delivered).

Chapter 6 includes detailed profiles of prominent transfection reagent developers, electroporation-based transfection system developers and other non-viral delivery system developers, featuring a brief overview of the company, its financial information (if available), recent developments and an informed future outlook.

Chapter 7 features an insightful analysis, highlighting potential strategic partners, based on likelihood of entering into collaboration with non-viral transfection system developers, taking into account several parameters, such as type of therapy, pipeline strength, pipeline maturity, company size and type of vector.

Chapter 8 highlights the activity of top ten big pharma players in this domain, featuring a heat map based on parameters, such as such as type of initiative, type of therapy and target therapeutic area.

Chapter 9 provides an analysis of completed, ongoing and planned clinical studies related to non-viral transfection systems, featuring details on registration year, trial phase, trial status, type of sponsor, type of therapy, target therapeutic area, trial design, type of patient allocation model used, type of trial masking adopted, type of intervention, trial purpose, geographical location of trial and enrolled patient population.

Chapter 10 provides an in-depth patent analysis to provide an overview of how the industry is evolving from the R&D perspective. For this analysis, we considered those patents that have been filed / granted related to non-viral transfection systems, since 2017, highlighting key trends associated with these patents, across type of patents, publication year, geographical location, type of applicants, issuing authority / patent offices involved, CPC symbols, emerging focus areas, leading players (in terms of number of patents granted / filed in the given time period), patent characteristics and geography. It also includes a detailed patent benchmarking and an insightful valuation analysis.

Chapter 11 presents a detailed publication analysis of more than 1,100 peer-reviewed, scientific articles that have been published since 2014, highlighting the key trends associated with these publications, across year of publication, focus area, type of molecule delivered, target therapeutic area, important cells and cell lines evaluated, leading players across different geographies and key journals (in terms of number of articles published in the given time period) within this domain.

Chapter 12 presents a detailed market forecast, highlighting the future potential of the non-viral transfection systems market till the year 2030. The chapter features the likely distribution of the opportunity across different [A] non-viral transfection methods (non-viral transfection reagents, electroporation-based transfection systems and other non-viral transfection systems), [B] end-users (academic and research institutions, pharmaceutical companies and other end-users), [C] area of application (clinical application and research application) and [D] geographical regions (North America, Europe, Asia-Pacific and rest of the world).

Chapter 13 is a collection of executive insights of the discussions that were held with various key stakeholders in this market. The chapter provides a brief overview of the companies and details of interviews held with George Eastwood (Vice-President of Business Development, Kytopen) and Claudia Andretta (Global Business Development Manager, Clinical, Polyplus-transfection).

Chapter 14 summarizes the entire report. It presents a list of key takeaways and offers our independent opinion on the current market scenario. Further, it summarizes the various evolutionary trends that are likely to influence the future of this market.

Chapter 15 is an appendix, which provides tabulated data and numbers for all the figures included in the report.

Chapter 16 is an appendix, which contains the list of companies and organizations mentioned in the report.Read the full report: https://www.reportlinker.com/p05915358/?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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Non-Viral Transfection Reagents and Systems Market, 2020-2030 - Yahoo Sport UK

BETHESDA, Md.--(BUSINESS WIRE)--Today the Cystic Fibrosis Foundation announced an investment of up to $14 million in 4D Molecular Therapeutics (4DMT) to develop a customized vehicle to deliver a healthy cystic fibrosis transmembrane conductance regulator (CFTR) gene into the lung cells of people with cystic fibrosis (CF). The delivery of genetic-based therapies is one of the key hurdles to developing an effective therapy for the more than 1,700 different mutations that cause CF, including nonsense and rare mutations.

This industry award is part of the CF Foundations $500 million Path to a Cure challenge to accelerate treatments for the underlying cause of CF and develop a cure. Current therapies have significantly improved the lives of many people living with CF, but there are still people who do not have an effective treatment for their CF mutations. Developing a way of delivering genetic-based approaches, including gene therapy and gene editing, is critical to finding a cure.

Todays announcement reaffirms our commitment to invest aggressively to draw the best scientific minds and technology into CF and deliver the next generation of transformative therapies for people with CF, said Michael P. Boyle, MD, President and Chief Executive Officer. Despite decades of progress in gene therapy, delivery to the lung remains a key challenge and one we are committed to solving.

4DMTs gene delivery vehicle, known as 4D-710, is a customized adeno-associated virus (AAV) vector designed to deliver a healthy CFTR gene specifically to cells in the lungs of people with CF. The vehicle was selected by 4DMT from their proprietary library of over one billion different AAVs based on its particular ability to target cells in the lung. One of the challenges that needs to be addressed is countering the lungs aggressive protection against foreign intruders including vehicles designed to deliver a healthy CFTR gene.

With this funding, 4DMT will explore whether an inhaled version of 4D-710 will restore CFTR protein levels to improve lung function. This includes developing manufacturing processes and assessing the safety and tolerability of this potential new CF treatment. If successful, 4DMT plans to advance 4D-710 into early stage clinical trials for CF.

The Foundation previously awarded 4DMT more than $3 million in funding to expand its preclinical development of viral gene delivery in the lung.

Path to a Cure

The CF Foundation launched its $500 million Path to a Cure initiative in October 2019. This initiative centers around three core strategies to address the underlying cause of CF: repairing broken CFTR protein, restoring CFTR protein when none exists, and fixing or replacing the underlying genetic mutation to address the root cause of CF. Each approach requires a different set of scientific tools and knowledge, leading the Foundation to bring together researchers and industry leaders from a range of disciplines to advance multiple areas of research in parallel, driving progress toward our goal to make CF stand for Cure Found. Innovators who are interested in pursuing programs in cystic fibrosis can learn about our specific funding opportunities here cff.org/PathtoaCure.

About the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization, and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The CF Foundation is a donor-supported nonprofit organization. For more information, visit cff.org.

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CF Foundation Invests up to $14M in Effort to Solve Key Challenges to Gene Delivery in Cystic Fibrosis - Business Wire

MENLO PARK, Calif. , June 17, 2020 (GLOBE NEWSWIRE) -- Orca Bio, a clinical-stage biotechnology company developing high precision allogeneic cell therapies, today announced a Series D financing that brings its total capital raised since its 2016 launch to nearly $300 million. The company creates precisely controlled cell therapies by building each dose cell-by-cell from another persons blood. Each therapy is constructed by formulating a proprietary mixture of cells that aims to cure the patients disease and eliminate dangerous side effects.

Orca Bios $192 million Series D financing was co-led by Lightspeed Venture Partners and an undisclosed investor. Other new and existing blue-chip investors also participated in the latest round, including 8VC, DCVC Bio, ND Capital, Mubadala Investment Company, Kaiser Foundation Hospitals, Kaiser Permanente Group Trust and IMRF.

The financing will support the continued advancement of Orca Bios cell therapy pipeline and its novel manufacturing platform, which sorts blood with single-cell precision and a high level of purity and speed to create optimal therapeutic mixtures of immune and stem cells. These proprietary mixtures have the potential to revolutionize allogeneic cell therapy for hematological and other cancers, as well as many other diseases and disorders.

A conventional bone marrow transplant relies on naturally occurring T cells. However, the uncontrolled cellular composition often results in life-threatening complications. The companys most advanced program, TRGFT-201, is evaluating a highly controlled formulation of T cells that includes subsets of regulatory T cells, in a Phase I/II clinical study in patients with certain blood cancers. The companys second program, OGFT-001, is evaluating a fully controlled cell product candidate that contains a next-generation formulation of T cells, in a Phase I study, also in patients with blood cancers. Orca Bios two ongoing clinical studies are among the largest Phase I cell therapy trials ever conducted. Each product candidate has the potential to deliver curative outcomes for the initial indications Orca Bio is pursuing, as well as the promise to significantly expand the eligible patient population by substantially reducing the severe toxicities associated with conventional bone marrow transplants.

The capital we have raised has formed the launch pad for a world-class, fully integrated allogeneic cell therapy company differentiated from all others, said Ivan Dimov, PhD, Co-founder and Chief Executive Officer of Orca Bio. Replacing bone marrow transplants is a logical first step in next-generation allogeneic cell therapy. While a conventional bone marrow transplant administers an uncontrolled cell product, Orca Bio has been the first to deliver a high precision cell therapy. We are initially focused on advancing two clinical programs in patients with blood cancers and have successfully treated the largest-ever number of patients with a high precision cell therapy. We believe our approach has the potential to transform allogeneic cell therapy, and thus the treatment of not only blood cancer, but also many other diseases with significant unmet need, such as a variety of genetic diseases and autoimmune disorders.

With precise reconstitution using highly defined cell preps and a swift reboot of the patients immune system, Orca Bios product candidates have the potential to eliminate fatal side effects, such as graft-versus-host disease, and infections commonly associated with bone marrow transplants while maintaining or enhancing anti-tumor efficacy, said Rick Klausner, MD, an investor and member of Orca Bios advisory board. The possibility of improving cure rates and minimizing toxicity holds the promise of expanding the eligible patient population for successful bone marrow transplantation in cancer.

Orca Bios visionary leadership team, seasoned advisors, solid financial foundation and novel technology make the company uniquely suited to develop truly differentiated, scalable allogeneic cell therapies, said Jonathan MacQuitty, PhD, Venture Partner at Lightspeed Venture Partners. I look forward to the Orca Bio teams continued development and commercialization of revolutionary allogeneic cell therapies.

Internationally Recognized Experts and Leaders

Orca Bios leadership, Ivan Dimov, PhD, Chief Executive Officer, Nate Fernhoff, PhD, Chief Scientific Officer, and Jeroen Bekaert, PhD, Chief Operating Officer, met at Stanford University and launched the company in 2016. Orca Bios board of directors and advisory board are comprised of renowned scientific leaders and seasoned biotech executives with extensive experience in drug discovery and cell-based therapeutics, including:

About Orca Bio

Established in 2016, Orca Bio is a clinical-stage biotechnology company developing a pipeline of high precision allogeneic cell therapy products that are designed to safely and effectively replace a patients blood and immune system with a healthy one. The companys proprietary therapeutic and manufacturing platforms are exclusively licensed from Stanford University. The manufacturing platform sorts donor blood with single-cell precision and a high level of purity and speed, enabling the creation of proprietary, optimal therapeutic mixtures of immune and stem cells that have the potential to transform allogeneic cell therapy. The companys lead product candidate is being evaluated in a multi-center Phase I/II clinical trial in patients with blood cancers. For more information, please visit http://www.orcabio.com.

Media Contact: media@orcabio.com

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Orca Bio Emerges With Nearly $300 Million to Transform Allogeneic Cell Therapy - BioSpace

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) today announced that new data from ongoing Phase 3 studies of betibeglogene autotemcel (beti-cel; formerly LentiGlobin for -thalassemia gene therapy) show pediatric, adolescent and adult patients with a range of genotypes of transfusion-dependent -thalassemia (TDT) achieve and maintain transfusion independence with hemoglobin (Hb) levels that are near-normal (10.5 g/dL). These data are being presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.

With more than a decade of clinical experience evaluating gene therapy in patients with transfusion dependent -thalassemia across a wide range of ages and genotypes, we have built the most comprehensive understanding of treatment outcomes in the field, said David Davidson, M.D., chief medical officer, bluebird bio. Seeing patients achieve transfusion independence and maintain that positive clinical benefit over time with robust hemoglobin levels reflects our initial vision of the potential of beti-cel. The accumulating long-term data demonstrating improvements in bone marrow histology, iron balance and red cell biology support the potential of beti-cel to correct the underlying pathophysiology of transfusion-dependent -thalassemia.

A total of 60 pediatric, adolescent and adult patients across genotypes of TDT have been treated with beti-cel in the Phase 1/2 Northstar (HGB-204) and HGB-205 studies, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies as of March 3, 2020. In studies of beti-cel, transfusion independence is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

TDT is a severe genetic disease caused by mutations in the -globin gene that results in significantly reduced or absent adult hemoglobin (HbA). In order to survive, people with TDT maintain Hb levels through lifelong, chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Patients with transfusion-dependent -thalassemia do not make enough healthy red blood cells and cannot live without chronic transfusions; for patients that means a lifetime of necessary visits to a hospital or clinic and reliance on an often unreliable blood supply, which compounds the challenges of managing this disease, said presenting study author Professor John B. Porter, MA, M.D., FRCP, FRCPath, University College London Hospital, London, UK. These results showing patients free from transfusions and maintaining near-normal hemoglobin levels after treatment with beti-cel is a positive outcome for people living with transfusion-dependent -thalassemia. In addition, we now have more data that provide further evidence that most of these patients have a measurable improvement in markers of healthy red blood cell production.

Beti-cel is a one-time gene therapy designed to address the underlying genetic cause of TDT by adding functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). This means there is no need for donor HSCs from another person, as is required for allogeneic HSC transplantation (allo-HSCT). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived Hb, at levels that eliminate or significantly reduce the need for transfusions.

Northstar-2 (HGB-207) Efficacy

As of March 3, 2020, all 23 patients in HGB-207 were treated and have been followed for a median of 19.4 months. These patients ranged in age from four to 34 years, including eight pediatric (<12 years of age) and 15 adolescent/adult (>12 years of age) patients. Only 19 patients were evaluable for transfusion independence; four additional patients do not yet have sufficient follow-up to be assessed for transfusion independence.

Eighty-nine percent of evaluable patients (17/19) achieved transfusion independence, with median weighted average total Hb levels of 11.9 g/dL (min-max: 9.4 12.9 g/dL) over a median of 19.4 months of follow-up to date (min-max: 12.3 31.4 months). These 17 patients previously required a median of 17.5 transfusions per year (min-max: 11.5 37 transfusions per year).

Improved iron levels, as measured by serum ferritin and hepcidin levels (proteins involved in iron storage and homeostasis), were observed and trends toward improved iron management were seen. Over half of patients stopped chelation therapy, which is needed to reduce excess iron caused by chronic blood transfusions. Seven out of 23 patients began using phlebotomy for iron reduction.

Analysis of Healthy Red Blood Cell Production

In exploratory analyses, biomarkers of ineffective erythropoiesis (red blood cell production) were evaluated in patients who achieved transfusion independence in HGB-207.

The myeloid to erythroid (M:E) ratio in bone marrow from patients who achieved transfusion independence increased from a median of 1:3 (n=17) at baseline to 1:1.2 (n=16) at Month 12. Improvement of the M:E ratio, the ratio of white blood cell and red blood cell precursors in the bone marrow, suggests an improvement in mature red blood cell production. Images illustrating the bone marrow cellularity at baseline, Month 12 and Month 24 are available in the EHA25 presentation (abstract #S296): Improvement in erythropoiesis in patients with transfusion-dependent -thalassemia following treatment with betibeglogene autotemcel (LentiGlobin for -thalassemia) in the Phase 3 HGB-207 study.

Additionally, biomarkers of erythropoiesis continue to demonstrate a trend toward normalization in patients who achieved transfusion independence, including improved levels over time of erythropoietin, a hormone involved in red blood cell production; reticulocytes, immature red blood cells; and soluble transferrin receptor, a protein measured to help evaluate iron status. The continued normalization of red blood cell production over time among some patients who achieved transfusion independence supports the disease-modifying potential of beti-cel in patients with TDT.

Northstar-3 (HGB-212) Efficacy

As of March 3, 2020, 15 patients (genotypes: 9 0/0, 3 0/ +IVS1-110, 3 homozygous IVS-1-110 mutation) were treated and had a median follow-up of 14.4 months (min-max: 1.124.0 months). Median age at enrollment was 15 (min-max: 4 33 years).

Six of eight evaluable patients achieved transfusion independence, with median weighted average total Hb levels of 11.5 g/dL (min-max: 9.5 13.5 g/dL), and continued to maintain transfusion independence for a median duration of 13.6 months (min-max: 12.2 21.2 months) as of the data cutoff.

Eighty-five percent of patients (11/13) with at least seven months of follow-up had not received a transfusion in more than seven months at time of data cutoff. These 11 patients previously required a median of 18.5 transfusions per year (min-max: 11.0 39.5 transfusions per year). In these patients, gene therapy-derived HbAT87Q supported total Hb levels ranging from 8.814.0 g/dL at last visit.

Betibeglogene autotemcel Safety

Non-serious adverse events (AEs) observed during the HGB-207 and HGB-212 trials that were considered related or possibly related to beti-cel were tachycardia, abdominal pain, pain in extremities, leukopenia, neutropenia and thrombocytopenia. One serious event of thrombocytopenia was considered possibly related to beti-cel.

In HGB-207, serious events post-infusion in two patients included three events of veno-occlusive liver disease and two events of thrombocytopenia. In HGB-212, serious events post-infusion in two patients included two events of pyrexia.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

In both Phase 3 studies, there have been no deaths, no graft failure, no cases of vector-mediated replication competent lentivirus or clonal dominance, no leukemia and no lymphoma.

The presentations are now available on demand on the EHA25 website:

About betibeglogene autotemcel

The European Commission granted conditional marketing authorization (CMA) for betibeglogene autotemcel (beti-cel; formerly LentiGlobin gene therapy for -thalassemia), marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent -thalassemia (TDT) who do not have a 0/0 genotype, for whom hematopoietic stem cell (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 ZYNTEGLO, supported by data from 32 patients treated with ZYNTEGLO, including three patients with up to five years of follow-up.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Beti-cel adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity and non-cardiac chest pain. Two serious adverse events (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration (FDA) granted beti-cel orphan drug designation and Breakthrough Therapy designation for the treatment of transfusion-dependent -thalassemia. Beti-cel is not approved in the U.S.

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 http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207) and NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of betibeglogene autotemcel or LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene 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 including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

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

bluebird bio Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the COVID-19 pandemic and resulting impact on our operations and healthcare systems will affect the execution of our development plans or the conduct of our clinical studies; the risk that the efficacy and safety results observed in the patients treated in our prior and ongoing clinical trials of beti-cel may not persist; and the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated with additional patients in our ongoing or planned clinical trials or in the commercial context; the risk that the FDA will require additional information regarding beti-cel, resulting in a delay to our anticipated timelines for regulatory submissions, including submission of our BLA. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Majority of Evaluable Patients Across Genotypes Achieve Transfusion Independence and Maintain It with Near-Normal Hemoglobin Levels in Phase 3 Studies...