Archive for May, 2020

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PRATTELN, Switzerland I May06, 2020 I Santhera Pharmaceuticals (SIX: SANN) announces the signing of two agreements with Rutgers, The State University of New Jersey as part of its program to advance gene therapy research for the treatment of LAMA2-deficient congenital muscular dystrophy (LAMA2MD or MDC1A). Under the agreements, Santhera gains rights to intellectual property developed at Rutgers on certain gene constructs that will be further studied under a collaboration agreement.

Santhera has entered into a license agreement with Rutgers, The State University of New Jersey and a collaboration with Prof. Peter Yurchenco, a pioneer in a novel gene therapy approach for the treatment of LAMA2MD. These agreements complement the ongoing collaboration of Santhera with Prof. Markus Regg from the Biozentrum of the University of Basel [1]. Previous collaborative work by Prof. Regg and Prof. Yurchenco has established the potential of this approach in animal models.

The novel gene therapy strategy developed by these leading experts uses two linker proteins that are composed of domains derived from extracellular matrix proteins agrin, laminin and nidogen [2-5]. In animal models for LAMA2MD, this approach has led to restoration of muscle fiber basement membranes, recovery of muscle force and size, increased overall body weight and markedly prolonged survival thus demonstrating strong evidence for disease modifying potential [2].

The coordinated work of both collaborations will further advance Santheras effort to bring this innovative gene therapy approach to patients with LAMA2MD.

Gene replacement is a promising therapeutic option for the treatment of LAMA2MD, said Peter D. Yurchenco, MD, PhD, Professor at Rutgers Robert Wood Johnson Medical School, USA. We have been working on continuously optimizing linker proteins engineered from extracellular matrix proteins which will aid in advancing such gene therapy approach towards clinical use.

Santhera is excited to extend its collaborative network for this therapeutic approach, now including experts from Rutgers University, added Kristina Sjblom Nygren, MD, Chief Medical Officer and Head of Development of Santhera. This will add value to our gene therapy program for LAMA2MD and complements the work already under way with the Biozentrum at the University of Basel, which was awarded a grant by Innosuisse in 2019. Both of our collaboration partners have pioneered this field and will work closely with Santhera, clinical experts and the patient community to establish the best way to bring this approach to clinical use.

About LAMA2MD (CMD Type 1A or MDC1A) and Emerging Therapy Approaches

Congenital muscular dystrophies (CMDs) are inherited neuromuscular diseases characterized by early-onset weakness and hypotonia alongside associated dystrophic findings in muscle biopsy. Progressive muscle weakness, joint contractures and respiratory insufficiency characterize most CMDs. Laminins are proteins of the extracellular matrix that help maintain muscle fiber stability by binding to other proteins. LAMA2-related muscular dystrophy (LAMA2MD, also called MDC1A), is one of the most common forms of CMD. It is caused by mutations in the LAMA2 gene encoding the alpha2 subunit of laminin-211. Most LAMA2MD patients show complete absence of laminin-alpha 2, are hypotonic (floppy) at birth, fail to ambulate, and succumb to respiratory complications.

Previous work has demonstrated that two linker proteins, engineered with domains derived from the extracellular matrix proteins agrin, laminin and nidogen, could compensate for the lack of laminin-alpha2 and restore the muscle basement membrane [2-5]. Through simultaneous expression of artificial linkers (SEAL), this gene therapy approach aims to overcome the genetic defect by substituting laminin-alpha2 deficiency with small linker proteins containing necessary binding domains to re-establish muscle fiber integrity. In a transgenic mouse model, the linker expression increased the lifespan of LAMA2-deficient mice 5-fold to a median of 81 weeks compared to 15.5 weeks in the disease model without the therapeutic linker expression [2]. Recently, it was demonstrated that such linker constructs could be applied by standard adeno-associated virus (AAV) vectors [6, 7]. First results using the AAV technology have been presented by Prof Regg [8].

References

[1] Santhera press release on gene collaboration with Biozentrum Basel (May 21, 2019), accessible here

[2] Reinhard et al. (2017). Sci Transl Med 9, eaal4649

[3] Moll et al. (2001). Nature 413, 302-307.

[4] Meinen et al. (2007) J. Cell Biol. 176, 979-993.

[5] McKee et al. (2017) J. Clin. Invest. 127, 1075-1089.

[6] Qiao et al. (2018) Mol Ther Methods Clin Dev 9, 47-56.

[7] Qiao et al. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 11999-12004.

[8] Reinhard, J. et al. (2019) Neuromuscular Disorders, Volume 29, S164

About Rutgers, The State University of New Jersey

Rutgers, The State University of New Jersey, is a leading national research university and the state of New Jerseys preeminent, comprehensive public institution of higher education. Established in 1766, the university is the eighth-oldest higher education institution in the United States. More than 71,000 students and 23,000 faculty and staff learn, work and serve the public at Rutgers University-New Brunswick, Rutgers University-Newark, Rutgers University-Camden, and Rutgers Biomedical and Health Sciences.

About Santhera

Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. Santhera is building a Duchenne muscular dystrophy (DMD) product portfolio to treat patients irrespective of causative mutations, disease stage or age. A marketing authorization application for Puldysa (idebenone) is currently under review by the European Medicines Agency. Santhera has an option to license vamorolone, a first-in-class anti-inflammatory drug candidate with novel mode of action, currently investigated in a pivotal study in patients with DMD to replace standard corticosteroids. The clinical stage pipeline also includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases, as well as omigapil and an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone (idebenone), for the treatment of Leber's hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit http://www.santhera.com.

SOURCE: Santhera Pharmaceuticals

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Santhera Signs Agreements in Gene Therapy Research for Congenital Muscular Dystrophy with Rutgers University | More News | News Channels -...

WORCESTER, Mass., May 12, 2020 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, today announced two poster presentations at the virtual 23rd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), being held May 12-15, 2020.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, We are extremely pleased with the strides forward that our researchers have made in gaining greater insights into our innovative CS1 chimeric antigen receptor (CAR) T cell therapy (MB-104), which we previously licensed from City of Hope. We commend them on their poster presentations at ASGCT and look forward to learning more as they continue their research to optimize our clinical trials.

Details on the poster presentations are as follows:

Title: CS1 Targeted CAR-T Cells (MB-104) for the Treatment of Multiple Myeloma Shows Antitumor Activity Sparing Normal T-Cells Despite the Common Expression of CS1Session: Cell TherapiesAbstract number: 421Date and Time: Tuesday, May 12, 2020, 5:30 PM-6:30 PM ETRoom: Exhibit Hall C & DAuthors: Nathan Gumlaw, Aviva Joseph, James Edinger, Ekta Patel, Research and Translational Sciences, Mustang Bio, Worcester, MA

This poster describes researchers investigation into the impact of MB-104 on CS1 positive and negative cells in vitro, as well as T cells due to shared CS1 antigen expansion. The researchers demonstrated MB-104 does not confer biologically significant fratricide and can be successfully manufactured as evident by viability, growth kinetics and fold expansion, despite the shared antigen expression between tumor cells and T cells. CS1 positive T cells are present in culture during the expansion of MB-104, suggesting absence of fratricide. Finally, MB-104 can induce potent anti-tumor cell lysis and proliferates in response to tumor cells but not primary T cells expressing CS1. Taken together, their results demonstrate MB-104 is a novel CS1-targeting CAR T that shows potent anti-tumor cell lysis but spares normal T cells, despite the shared CS1 antigen expression.

Title: Development of an Immunohistochemistry Assay for the Detection of CS-1 Expression in Multiple Myeloma PatientsSession: Pharmacology/Toxicology Studies or Assay DevelopmentAbstract number: 897Date and Time: Wednesday, May 13, 2020, 5:30 PM-6:30 PM ETRoom: Exhibit Hall C & DAuthors: Bethany Biron Girard, James Edinger, Ekta Patel, Translational Sciences, Mustang Bio, Worcester, MA

This poster details a study in which researchers evaluated commercially available CS1 antibodies for IHC and identified the best clone with high specificity for CS1 to improve screening subjects for CS1 positive tumor expression prior to treatment and correlate efficacy with antigen expression. The researchers, for the first time, developed and optimized a robust immunohistochemistry assay for the assessment of CS1 expression in bone marrow core biopsy samples and plasmacytoma solid tumor samples from multiple myeloma (MM) patients, which can be used for enrollment into Mustangs CS1 CAR T clinical trials.

For more information, including abstracts, please visit the ASGCT meeting website at https://annualmeeting.asgct.org/am20/.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (SEC). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements

This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contacts:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Mustang Bio Announces Presentations at 23rd Annual Meeting of the American Society of Gene & Cell Therapy - GlobeNewswire

The latest report pertaining to The Future of Gene Therapy Market collated by Market Study Report, LLC, provides a detailed analysis regarding market size, revenue estimations and growth rate of the industry. In addition, the report illustrates the major obstacles and newest growth strategies adopted by leading manufacturers who are a part of the competitive landscape of this market.

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According to a new report, the global gene therapy market is anticipated to reach USD 4,300 million by 2021. The demand for gene therapy is primarily driven by continuous technological advancements and successful progression of several clinical trials targeting treatments with strong unmet need. Moreover, rising R&D spend on platform technologies by large and emerging biopharmaceutical companies and favorable regulatory environment will accelerate the clinical development and the commercial approval of gene therapies in the foreseeable future. Despite promise, the high cost of gene therapy represents a significant challenge for commercial adoption in the forecast period.

Gene therapy offers promise in the treatment of range of indications in cancer and genetic disorders. Large Pharmaceuticals and Biotechnology companies exhibit strong interest in this field and key among them include Allergan, Shire, Biomarin, Pfizer and GSK. The gene therapy space is witnessing a wave of partnerships and alliances. Pfizer has recently expanded its presence in gene therapy with the acquisition of Bamboo Therapeutics and Allergan entered the field, with the acquisition of RetroSense and its Phase I/II optogenetic program.

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North America holds a dominating position in the global gene therapy market which is followed by Europe and the Asia Pacific. The U.S. has maximum number of clinical trials ongoing followed by Europe. Moreover, the field of gene therapy in the U.S. and Europe continues to gain investor attention driven by success of high visible clinical programs and the potential of gene therapy to address strong unmet need with meaningful commercial opportunity. Moreover, the increasing partnerships and alliances and the disruptive potential of gene therapy bodes well for the sector through the forecast period.

Gene therapy involves inactivating a mutated gene that is not functioning properly and introducing a new gene to assist in fighting a disease. Overall, the field of gene therapy continues to mature and advance with many products in development and nearing commercialization. For instance, Spark Therapeutics received approval of Luxturna, a rare form inherited blindness in December 2017. Gene therapy market in late 2017 also witnessed the approvals of Gilead/Kite Pharmas Yescarta and Novartis Kymriah in the cancer therapeutic area.

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Key Findings from the study suggest products accessible in the market are much competitive and manufacturers are progressively concentrating on advancements to pick up an aggressive edge. Companies are in a stage of development of new items in order to guarantee simple implementation and connection with the current gene. The hospatility segment is anticipated to grow at a high growth rate over the forecast period with the expanding utilization of smart locks inferable from expanding security-related worries among clients amid their stay at the hotels. North America is presumed to dominate the global smart locks market over the forecast years and Asia Pacific region shows signs of high growth owing to the booming economies of India, and China.

The Future of Gene Therapy Market share byMajor regions included:

United StatesNorth AmericaAsia PacificEuropeMiddle East & Africa

Table of Contents

1.Gene Therapy Overview1.1.History and Evolution of Gene Therapies1.2.What is Gene Therapy1.3.Types of Gene Therapy1.4.Ex vivo and in vivo Approaches of Gene Therapy1.5.RNAi Therapeutics1.6.CAR-T Technology based Gene Therapy1.7.Types of Vectors used for Gene Therapy1.7.1.Viral1.7.2.Non-Viral2.Historical Marketed Gene Therapies [2003-2012]2.1.Rexin-G (Epeius Biotechnologies Corporation)2.2.Gendicine (SiBiono GeneTech Co., Ltd)2.3.Neovasculgen [Human Stem Cells Institute (HSCI))2.4.Glybera (UniQure Biopharma B.V.)3.First Countries to get an access to Gene Therapies3.1.Philippines for Rexin-G [2003]3.2.China for Gendicine [2003]3.3.Russia for Neovasculgen [2011]3.4.Selected European Countries for Glybera [2012]4.Marketed Gene Therapies [Approved in Recent Years]4.1.KYMRIAH (tisagenlecleucel)4.1.1.Therapy Description4.1.2.Therapy Profile4.1.2.1.Company4.1.2.2.Approval Date4.1.2.3.Mechanism of Action4.1.2.4.Researched Indication4.1.2.5.Vector Used4.1.2.6.Vector Type4.1.2.7.Technology4.1.2.8.Others Development Activities4.1.3.KYMRIAH Revenue Forecasted till 20214.2.YESCARTA (axicabtagene ciloleucel)4.2.1.Therapy Description4.2.2.Therapy Profile4.2.2.1.Company4.2.2.2.Approval Date4.2.2.3.Mechanism of Action

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Global and Regional The Future of Gene Therapy Market Research 2018 Report | Growth Forecast 2026 - Jewish Life News

MEMPHIS, Tenn. and BOTHELL, Wash., May 12, 2020 /PRNewswire/ -- Key Biologics and Astarte Biologics, together the leading provider of research- and clinical-grade human immune cells, blood products, and related services to the biopharmaceutical industry, today announced its rebranding to Cellero. The new Cellero brand better reflects the full capabilities of the organization, which serves customers across the entire cell and gene therapy lifecyclefrom concept to cure. In 2018, Key Biologics and Astarte Biologics merged to establish a comprehensive product and service offering that provides researchers critical access to biomaterial products, and the new Cellero brand represents the synergy and broad capabilities of the combined organizations.

"We are very excited to announce the launch of Cellero and the comprehensive, end-to-end product and service line we offer to our customers," said Jeffrey Allen, CEO. "Regardless of where organizations are in the continuum of discovery through cure, they can trust Cellero to recruit common and hard-to-find blood donors, isolate and characterize specific immune cells, deliver high-volume pure blood products, execute early-stage contract research and discovery projects, and collect from patients for autologous and allogeneic therapies."

In conjunction with the launch of the new brand, Cellero has also announced the grand opening of its new, state-of-the-art cell collection and CLIA-laboratory facility in Lowell, MA. The new facility, combined with the doubling of the company's capacity for collections at its Memphis site in late 2019, represent the completion of Phase One of Cellero's multi-year $50 million plan to invest in new facilities and capabilities to meet the growing demand for human cells for biopharmaceutical R&D and clinical development.

Allen continued, "Our mission is to fuel and accelerate advancements in the discovery, development, and administration of new treatments and cures. Our new facility in Lowell represents one of several steps to execute on this vision and meet the growing demand of our clinical and R&D customers for high-quality cell-based products. This new facility supports our commitment to sourcing and delivering a full range of fresh and frozen GMP-grade biomaterials to some of the most cutting-edge biopharmaceutical companies in Massachusetts, Europe, and elsewhere around the world. Even more exciting is that our new location will also provide apheresis collections for patients in the greater New England area, establishing Cellero as a critical player in the local community supporting patients receiving innovative, life-changing cell therapies."

The new 5,000 square foot facility in Lowell boasts state of the art collection stations utilizing TerumoBCT Spectra Optias for optimal blood collection and superior donor/patient safety and comfort. In addition to the collection suites, a CLIA-licensed laboratory is situated onsite to ensure the highest quality, most efficient operations for Cellero's donors, patients, and customers.

With locations in Seattle, Memphis, and Lowell, Cellero is able to quickly and reliably supply fresh and frozen leukapheresis products to customers across North America, Europe, and Asia. In addition to research and clinical leukapheresis products, the company offers cell characterization and processing services to support cell therapy manufacturers as well as cell-based research tools and services for drug discovery.

Get to know Cellero!

ABOUT CELLEROCellero is the most comprehensive end-to-end provider of donor and patient collection services, biomaterials, characterized immune cells, and custom research and clinical laboratory services for companies developing new drugs and therapies.

Cellero leverages immunology research expertise and coast-to-coast collection facilities and distribution centers to service academic and biopharmaceutical researchers around the world. Visit http://www.cellero.comto learn how Cellero can be your partner in discovery and development.

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Key Biologics and Astarte Biologics Rebrand as Cellero and Announce Completion of Phase One of $50 Million Multi-Year Expansion Plan - NBC Right Now

GERMANTOWN, Md., May 11, 2020 (GLOBE NEWSWIRE) -- Orgenesis Inc. (NASDAQ: ORGS) (Orgenesis or the Company), a pioneering, global biotech company committed to accelerating commercialization and transforming the delivery of cell and gene therapies (CGTs) while lowering costs, today reported financial results for the first quarter ended March 31, 2020.

First Quarter 2020 Financial Highlights:

Vered Caplan, CEO of Orgenesis, commented, Step by step, our CGT Biotech Platform is gaining traction within the market, as illustrated by the year-over-year growth. In the first quarter of 2020, revenue increased to $1.9 million, or nearly an $8 million revenue run rate compared to $3.1 million for all of 2019. We believe our CGT Biotech Platform is poised for growth this year through industry partnerships that are currently underway with leading research institutes and hospitals around the world.

Earlier this year, we entered into a collaboration agreement with two of the leading healthcare research institutes in the U.S., whereby we plan to utilize our POCare Network to support their growing development and processing needs in order to advance and accelerate cell and gene-based clinical therapeutic research. We believe these collaborations with such high-profile institutions in the field of cell and gene therapy further validate the significant value proposition of our platform.

In addition to our POCare Network, we are building our pipeline of POCare Therapeutics and Technologies, with an ultimate goal of providing life-changing treatments to large numbers of patients at reduced costs within the point-of-care setting. Specifically, we are focusing on immuno-oncology, metabolic and autoimmune diseases, as well as anti-viral therapies. Most recently, we completed the acquisition of Tamir Biotechnology, Inc., including ranpirnase, a broad spectrum anti-viral platform. Ranpirnase has demonstrated clinical efficacy against HPV and other hard to target viruses based on its unique mechanism of action of killing the virus and modulating the immune system. Having demonstrated clinical activity against human papillomavirus, as well as preclinical activity against some of the worlds most persistent viral threats, we plan to aggressively pursue a number of complementary approaches with a goal to maximize the potential of ranpirnase.

We have received approval from regulators to continue working in our research and development labs during the current COVID-19 pandemic, and we are leveraging all our knowledge and expertise in the field of cell and gene therapy, including anti-viral technologies, in an attempt to find potential COVID-19 cures and therapies. Importantly, we have a strong balance sheet and are strategically positioned to bring a variety of therapies to market in a cost-effective, high-quality and scalable manner.

We also announced a joint venture agreement with RevaTis S.A. to advance the development of autologous therapies utilizing and banking muscle-derived mesenchymal stem cells (mdMSC) as a source of exosomes and other cellular products. Our plan is to combine RevaTis patented technique to obtain mdMSCs through a minimally invasive muscle micro-biopsy with our own automated/closed-systems, 3D printing, and bioreactor technologies. The goal of this JV is to lower the costs and accelerate the timeline of bringing these innovative therapies through the clinic and into commercialization.

The Companys complete financial results are available in the Companys Form 10-Q filed with the Securities and Exchange Commission on May 8, 2020 which is available at http://www.sec.gov and on the Companys website.

About Orgenesis

Orgenesis is a pioneering global biotech company which is unlocking the full potential of personalized therapies and closed processing systems through its Cell & Gene Therapy Biotech Platform, with the ultimate aim of providing life changing treatments at the Point of Care to large numbers of patients at low cost. The Platform consists of: (a) POCare Therapeutics, a pipeline of licensed cell and gene therapies (CGTs), and proprietary scientific knowhow; (b) POCare Technologies, a suite of proprietary and in-licensed technologies which are engineered to create customized processing systems for affordable point of care therapies; and (c) POCare Network, a collaborative, international ecosystem of leading research institutes and hospitals committed to clinical development and supply of CGTs at the point of care. By combining science, technologies and a collaborative network, Orgenesis is able to identify the most promising new therapies and provide a pathway for them to reach patients more quickly, more efficiently and at scale, thereby unlocking the power of cell and gene therapy for all. Additional information is available at: http://www.orgenesis.com.

Notice Regarding Forward-Looking Statements

This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended. These forward-looking statements involve substantial uncertainties and risks and are based upon our current expectations, estimates and projections and reflect our beliefs and assumptions based upon information available to us at the date of this release. We caution readers that forward-looking statements are predictions based on our current expectations about future events. These forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Our actual results, performance or achievements could differ materially from those expressed or implied by the forward-looking statements as a result of a number of factors, including, but not limited to, the risk that the acquisition of Tamirs assets will not be successfully integrated with our technologies or that the potential benefits of the acquisition will not be realized, our ability to further develop ranpirnase following the acquisition, our reliance on, and our ability to grow, our point-of-care cell therapy platform, our ability to effectively use the net proceeds from the sale of Masthercell, our ability to achieve and maintain overall profitability, the development of our POCare strategy, the sufficiency of working capital to realize our business plans, the development of our trans-differentiation technology as therapeutic treatment for diabetes which could, if successful, be a cure for Type 1 Diabetes; our technology not functioning as expected; our ability to retain key employees; our ability to satisfy the rigorous regulatory requirements for new procedures; our competitors developing better or cheaper alternatives to our products and the risks and uncertainties discussed under the heading "RISK FACTORS" in Item 1A of our Annual Report on Form 10-K for the fiscal year ended December 31 2019, and in our other filings with the Securities and Exchange Commission. We undertake no obligation to revise or update any forward-looking statement for any reason.

Contact for Orgenesis:David WaldmanCrescendo Communications, LLCTel: 212-671-1021ORGS@crescendo-ir.com

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Orgenesis First Quarter 2020 Revenue Increases 348% to $1.9 Million Reflecting Success of CGT Biotech Platform - GlobeNewswire

Abstract

Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Follistatin (FST), a protein that binds myostatin and activin, may have the potential to enhance muscle formation while inhibiting inflammation. Here, we hypothesized that adeno-associated virus 9 (AAV9) delivery of FST enhances muscle formation and mitigates metabolic inflammation and knee OA caused by a high-fat diet in mice. AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid. Regardless of diet, mice receiving FST gene therapy were protected from post-traumatic OA and bone remodeling induced by joint injury. Together, these findings suggest that FST gene therapy may provide a multifactorial therapeutic approach for injury-induced OA and metabolic inflammation in obesity.

Osteoarthritis (OA) is a multifactorial family of diseases, characterized by cartilage degeneration, joint inflammation, and bone remodeling. Despite the broad impact of this condition, there are currently no disease-modifying drugs available for OA. Previous studies demonstrate that obesity and dietary fatty acids (FAs) play a critical role in the development of OA, and metabolic dysfunction secondary to obesity is likely to be a primary risk factor for OA (1), particularly following joint injury (2, 3). Furthermore, both obesity and OA are associated with a rapid loss of muscle integrity and strength (4), which may contribute directly and indirectly to the onset and progression of OA (5). However, the mechanisms linking obesity, muscle, and OA are not fully understood and appear to involve interactions among biomechanical, inflammatory, and metabolic factors (6). Therefore, strategies that focus on protecting muscle and mitigating metabolic inflammation may provide an attractive target for OA therapies in this context.

A few potential interventions, such as weight loss and exercise, have been proposed to reverse the metabolic dysfunction associated with obesity by improving the quantity or quality of skeletal muscle (7). Skeletal muscle mass is modulated by myostatin, a member of the transforming growth factor (TGF-) superfamily and a potent negative regulator of muscle growth (8), and myostatin is up-regulated in obesity and down-regulated by exercise (9). While exercise and weight loss are the first line of therapy for obesity and OA, several studies have shown difficulty in achieving long-term maintenance of weight loss or strength gain, particularly in frail or aging populations (10). Thus, targeted pharmacologic or genetic inhibition of muscle-regulatory molecules such as myostatin provides a promising approach to improving muscle metabolic health by increasing glucose tolerance and enhancing muscle mass in rodents and humans (8).

Follistatin (FST), a myostatin- and activin-binding protein, has been used as a therapy for several degenerative muscle diseases (11, 12), and loss of FST is associated with reduced muscle mass and prenatal death (13). In the context of OA, we hypothesize that FST delivery using a gene therapy approach has multifactorial therapeutic potential through its influence on muscle growth via inhibition of myostatin activity (14) as well as other members of the TGF- family. Moreover, FST has been reported to reduce the infiltration of inflammatory cells in the synovial membrane (15) and affect bone development (16), and pretreatment with FST has been shown to reduce the severity of carrageenan-induced arthritis (15). However, the potential for FST as an OA therapy has not been investigated, especially in exacerbating pathological conditions such as obesity. We hypothesized that overexpression of FST using a gene therapy approach will increase muscle mass and mitigate obesity-associated metabolic inflammation, as well as the progression of OA, in high-fat diet (HFD)induced obese mice. Mice fed an HFD were treated with a single dose of adeno-associated virus 9 (AAV9) to deliver FST or a green fluorescent protein (GFP) control, and the effects on systemic metabolic inflammation and post-traumatic OA were studied (fig. S1).

Dual-energy x-ray absorptiometry (DXA) imaging of mice at 26 weeks of age (Fig. 1A) showed significant effects of FST treatment on body composition. Control-diet, FST-treated mice (i.e., Control-FST mice) exhibited significantly lower body fat percentages, but were significantly heavier than mice treated with a GFP control vector (Control-GFP mice) (Fig. 1B), indicating that increased muscle mass rather than fat was developed with FST. With an HFD, control mice (HFD-GFP mice) showed significant increases in weight and body fat percentage that were ameliorated by FST overexpression (HFD-FST mice).

(A) DXA images of mice at 26 weeks of age. (B) DXA measurements of body fat percentage and bone mineral density (BMD; 26 weeks) and body weight measurements over time. (C) Serum levels for adipokines (insulin, leptin, resistin, and C-peptide) at 28 weeks. (D) Metabolite levels for glucose, triglycerides, cholesterol, and FFAs at 28 weeks. (E) Serum levels for cytokines (IL-1, IL-1, MCP-1, and VEGF) at 28 weeks. (F) Fluorescence microscopy images of visceral adipose tissue with CD11b:Alexa Fluor 488 (green), CD11c:phycoerythrin (PE) (red), and 4,6-diamidino-2-phenylindole (DAPI; blue). Scale bars, 100 m. Data are presented as mean SEM; n = 8 to 10; two-way analysis of variance (ANOVA), P < 0.05. Groups not sharing the same letter are significantly different with Tukey post hoc analysis. For IL-1 and VEGF, P < 0.05 for diet effect and AAV effect. For MCP-1, P < 0.05 for diet effect.

In the HFD group, overexpression of FST significantly decreased serum levels of several adipokines including insulin, leptin, resistin, and C-peptide as compared to GFP-treated mice (Fig. 1C). HFD-FST mice also had significantly lower serum levels of glucose, triglycerides, cholesterol, and free FAs (FFAs) (Fig. 1D), as well as the inflammatory cytokine interleukin-1 (IL-1) (Fig. 1E) when compared to HFD-GFP mice. For both dietary groups, AAV-FST delivery significantly increased circulating levels of vascular endothelial growth factor (VEGF) while significantly decreasing IL-1 levels. Furthermore, obesity-induced inflammation in adipose tissue was verified by the presence of CD11b+CD11c+ M1 pro-inflammatory macrophages or dendritic cells (Fig. 1F).

To determine whether FST gene therapy can mitigate injury-induced OA, mice underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed 12 weeks after surgery. Cartilage degeneration was significantly reduced in DMM joints of the mice receiving FST gene therapy in both dietary groups (Fig. 2, A and C) when compared to GFP controls. FST overexpression also significantly decreased joint synovitis (Fig. 2, B and D) when compared to GFP controls. To evaluate the local influence of pro-inflammatory cytokines to joint degeneration and inflammation, synovial fluid (SF) was harvested from surgical and ipsilateral nonsurgical limbs and analyzed using a multiplexed array. The DMM joints from mice with FST overexpression exhibited a trend toward lower levels of pro-inflammatory cytokines, including IL-1, IL-1, and IL-6, and a higher level of interferon- (IFN-)induced protein (IP-10) in the SF of DMM joints as compared to contralateral controls (Fig. 2E).

(A) Histologic analysis of OA severity via Safranin O (glycosaminoglycans) and fast green (bone and tendon) staining of DMM-operated joints. (B) Histology [hematoxylin and eosin (H&E) staining] of the medial femoral condyle of DMM-operated joints. Thickened synovium (S) from HFD mice with a high density of infiltrated cells was observed (arrows). (C) Modified Mankin scores compared within the diet. (D) Synovitis scores compared within the diet. (E) Levels of proinflammatory cytokines in the SF compared within the diet. (F) Hot plate latency time and sensitivity to cold plate exposure, as measured using the number of jumps in 30 s, both for non-operated algometry measurements of pain sensitivity compared within the diet. Data are presented as mean SEM; n = 5 to 10 mice per group; two-way ANOVA, P < 0.05. Groups not sharing the same letter are significantly different with Tukey post hoc analysis.

To investigate the effect of FST on pain sensitivity in OA, animals were subjected to a variety of pain measurements including hot plate, cold plate, and algometry. Obesity increased heat withdrawal latency, which was rescued by FST overexpression (Fig. 2F). Cold sensitivity trended lower with obesity, and because no significant differences in heat withdrawal latency were found with surgery (fig. S2), no cold sensitivity was measured after surgery. We found that FST treatment protected HFD animals from mechanical algesia at the knee receiving DMM surgery, while Control-diet DMM groups demonstrated increased pain sensitivity following joint injury.

A bilinear regression model was used to elucidate the relationship among OA severity, biomechanical factors, and metabolic factors (table S1). Factors significantly correlated with OA were then selected for multivariate regression (Table 1). Both multivariate regression models revealed serum tumor necrosis factor- (TNF-) levels as a major predictor of OA severity.

, standardized coefficient. ***P < 0.001.

We analyzed the effects of FST treatment on muscle structure and mass, and performance measures were conducted on mice in both dietary groups. Both Control-FST and HFD-FST limbs exhibited visibly larger muscles compared to both AAV-GFP groups (Fig. 3A). In addition, the muscle masses of tibialis anterior (TA), gastrocnemius, and quadriceps increased significantly with FST treatment (Fig. 3B). Western blot analysis confirmed an increase in FST expression in the muscle at the protein level in FST-treated groups compared to GFP-treated animals in Control and HFD groups (Fig. 3C). Immunofluorescence labeling showed increased expression of FST in muscle (Fig. 3D) and adipose tissue (Fig. 3E) of the AAV-FST mice, with little or no expression of FST in control groups.

(A) Photographic images and (B) measured mass of tibialis anterior (TA), gastrocnemius (GAS), and quadriceps (QUAD) muscles; n = 8, diet and AAV effects both P < 0.05. (C) Western blot showing positive bands of FST protein only in FST-treated muscles, with -actin as a loading control. Immunolabeling of (D) GAS muscle and (E) adipose tissue showing increased expression of FST, particularly in skeletal muscle. (F) H&E-stained sections of GAS muscles were measured for (G) mean myofiber diameter; n = 100 from four mice per group, diet, and AAV effects; both P < 0.05. (H) Oil Red O staining was analyzed for (I) optical density values of FAs; n = 6. (J) Second-harmonic generation imaging of collagen in TA sections was quantified for intensity; n = 6. (K) Western blotting showing the level of phosphorylation markers of protein synthesis in GAS muscle. (L) Functional analysis of grip strength and treadmill time to exhaustion; n = 10. Data are presented as mean SEM; two-way ANOVA, P < 0.05. Groups not sharing the same letter are significantly different with Tukey post hoc analysis. Photo credit: Ruhang Tang, Washington University.

To determine whether the increases in muscle mass reflected muscle hypertrophy, gastrocnemius muscle fiber diameter was measured in H&E-stained sections (Fig. 3F) at 28 weeks of age. Mice with FST overexpression exhibited increased fiber diameter (i.e., increased muscle hypertrophy) relative to the GFP-expressing mice in both diet treatments (Fig. 3G). Oil Red O staining was used to determine the accumulation of neutral lipids in muscle (Fig. 3H). We found that HFD-FST mice were protected from lipid accumulation in muscles compared to HFD-GFP mice (Fig. 3I). Second-harmonic generation imaging confirmed the presence of increased collagen content in the muscles of HFD mice, which was prevented by FST gene therapy (Fig. 3J). We also examined the expression and phosphorylation levels of the key proteins responsible for insulin signaling in muscles. We observed increased phosphorylation of AktS473, S6KT389, and S6RP-S235/2369 and higher expression of peroxisome proliferatoractivated receptor coactivator 1- (Pgc1-) in muscles from FST mice compared to GFP mice, regardless of diet (Fig. 3K). In addition to the improvements in muscle structure with HFD, FST-overexpressing mice also showed improved function, including higher grip strength and increased treadmill running endurance (Fig. 3L), compared to GFP mice.

Because FST has the potential to influence cardiac muscle and skeletal muscle, we performed a detailed evaluation on the effect of FST overexpression on cardiac function. Echocardiography and short-axis images were collected to visualize the left ventricle (LV) movement during diastole and systole (fig. S3A). While the Control-FST mice had comparable LV mass (LVM) and left ventricular posterior wall dimensions (LVPWD) with Control-GFP mice (fig. S3, B and C), the HFD-FST mice have significantly decreased LVM and trend toward decreased LVPWD compared to HFD-GFP. Regardless of the diet treatments, FST overexpression enhanced the rate of heart weight/body weight (fig. S3D). Although Control-FST mice had slightly increased dimensions of the interventricular septum at diastole (IVSd) compared to Control-GFP (fig. S3E), there was significantly lower IVSd in HFD-FST compared to HFD-GFP. In addition, we found no difference in fractional shortening among all groups (fig. S3F). Last, transmitral blood flow was investigated using pulse Doppler. While there was no difference in iso-volumetric relaxation time (IVRT) in Control groups, HFD-FST mice had a moderate decrease in IVRT compared to HFD-GFP (fig. S3G). Overall, FST treatment mitigated the changes in diastolic dysfunction and improved the cardiac relaxation caused by HFD.

DXA demonstrated that FST gene therapy improved bone mineral density (BMD) in HFD compared to other groups (Fig. 1B). To determine the effects of injury, diet intervention, and overexpression of FST on bone morphology, knee joints were evaluated by microcomputed tomography (microCT) (Fig. 4A). The presence of heterotopic ossification was observed throughout the GFP knee joints, whereas FST groups demonstrated a reduction or an absence of heterotopic ossification. FST overexpression significantly increased the ratio of bone volume to total volume (BV/TV), BMD, and trabecular number (Tb.N) of the tibial plateau in animals, regardless of diet treatment (Fig. 4B). Joint injury generally decreased bone parameters in the tibial plateau, particularly in Control-diet mice. In the femoral condyle, BV/TV and Tb.N were significantly increased in mice with FST overexpression in both diet types, while BMD was significantly higher in HFD-FST compared to HFD-GFP mice (Fig. 4B). Furthermore, AAV-FST delivery significantly increased trabecular thickness (Tb.Th) and decreased trabecular space (Tb.Sp) in the femoral condyle of HFD-FST compared to HFD-GFP animals (fig. S4).

(A) Three-dimensional (3D) reconstruction of microCT images of non-operated and DMM-operated knees. (B) Tibial plateau (TP) and femoral condyle (FC) regional analyses of trabecular bone fraction bone volume (BV/TV), BMD, and trabecular number (Tb.N). Data are presented as mean SEM; n = 8 to 19 mice per group; two-way ANOVA. (C) 3D microCT reconstruction of metaphysis region of DMM-operated joints. (D) Analysis of metaphysis BV/TV, Tb.N, and BMD. (E) 3D microCT reconstruction of cortical region of DMM-operated joints. (F) Analysis of cortical cross-sectional thickness (Ct.Cs.Th), polar moment of inertia (MMI), and tissue mineral density (TMD). (D and F) Data are presented as mean SEM; n = 8 to 19 mice per group; Mann-Whitney U test, *P < 0.05.

Further microCT analysis was conducted on the trabecular (Fig. 4C) and cortical (Fig. 4E) areas of the metaphyses. FST gene therapy significantly increased BV/TV, Tb.N, and BMD in the metaphyses regardless of the diet (Fig. 4D). Furthermore, FST delivery significantly increased the cortical cross-sectional thickness (Ct.Cs.Th) and polar moment of inertia (MMI) of mice on both diet types, as well as tissue mineral density (TMD) of cortical bones of mice fed control diet (Fig. 4F).

To elucidate the possible mechanisms by which FST mitigates inflammation, we examined the browning/beiging process in subcutaneous adipose tissue (SAT) with immunohistochemistry (Fig. 5A). Here, we found that key proteins expressed mainly in brown adipose tissue (BAT) (PGC-1, PRDM16, thermogenesis marker UCP-1, and beige adipocyte marker CD137) were up-regulated in SAT of the mice with FST overexpression (Fig. 5B). Increasing evidence suggests that an impaired mitochondrial oxidative phosphorylation (OXPHOS) system in white adipocytes is a hallmark of obesity-associated inflammation (17). Therefore, we further examined the mitochondrial respiratory system in SAT. HFD reduced the amount of OXPHOS complex subunits (Fig. 5C). We found that proteins involved in OXPHOS, including subunits of complexes I, II, and III of mitochondria OXPHOS complex, were significantly up-regulated in AAV-FSToverexpressing animals compared to AAV-GFP mice (Fig. 5D).

(A) Immunohistochemistry of UCP-1 expression in SAT. Scale bar, 50 m. (B) Western blotting of SAT for key proteins expressed in BAT, with -actin as a loading control. (C) Western blot analysis of mitochondria lysates from SAT for OXPHOS proteins using antibodies against subunits of complexes I, II, III, and IV and adenosine triphosphate (ATP) synthase. (D) Change of densitometry quantification normalized to the average FST level of each OXPHOS subunit. Data are presented as mean SEM; n = 3. *P < 0.05, t test comparison within each pair.

Our findings demonstrate that a single injection of AAV-mediated FST gene therapy ameliorated systemic metabolic dysfunction and mitigated OA-associated cartilage degeneration, synovial inflammation, and bone remodeling occurring with joint injury and an HFD. Of note, the beneficial effects were observed across multiple tissues of the joint organ system, underscoring the value of this potential treatment strategy. The mechanisms by which obesity and an HFD increase OA severity are complex and multifactorial, involving increased systemic metabolic inflammation, joint instability and loss of muscle strength, and synergistic interactions between local and systemic cytokines (4, 6). In this regard, the therapeutic consequences of FST gene therapy also appear to be multifactorial, involving both direct and indirect effects such as increased muscle mass and metabolic activity to counter caloric intake and metabolic dysfunction resulting from an HFD while also promoting adipose tissue browning. Furthermore, FST may also serve as a direct inhibitor of growth factors in the TGF- family that may be involved in joint degeneration (18).

FST gene therapy showed a myriad of notable beneficial effects on joint degeneration following joint injury while mitigating HFD-induced obesity. These data also indirectly implicate the critical role of muscle integrity in the onset and progression of post-traumatic OA in this model. It is important to note that FST gene therapy mitigated many of the key negative phenotypic changes previously associated with obesity and OA, including cartilage structural changes as well as bone remodeling, synovitis, muscle fibrosis, and increased pain, as compared to GFP controls. To minimize the number of animals used, we did not perform additional controls with no AAV delivery; however, our GFP controls showed similar OA changes as observed in our previous studies, which did not involve any gene delivery (2). Mechanistically, FST restored to control levels a number of OA-associated cytokines and adipokines in the serum and the SF. While the direct effects of FST on chondrocytes remains to be determined, FST has been shown to serve as a regulator of the endochondral ossification process during development (19), which may also play a role in OA (20). Furthermore, previous studies have shown that a 2-week FST treatment of mouse joints is beneficial in reducing infiltration of inflammatory cells into the synovial membrane (15). Our findings suggest that FST delivery in skeletally mature mice, preceding obesity-induced OA changes, substantially reduces the probability of tissue damage.

It is well recognized that FST can inhibit the activity of myostatin and activin, both of which are up-regulated in obesity-related modalities and are involved in muscle atrophy, tissue fibrosis, and inflammation (21). Consistent with previous studies, our results show that FST antagonizes the negative regulation of myostatin in muscle growth, reducing adipose tissue content in animals. Our observation that FST overexpression decreased inflammation at both serum systemic and local joint inflammation may provide mechanistic insights into our findings of mitigated OA severity in HFD-fed mice. Our statistical analysis implicated serum TNF- levels as a major factor in OA severity, consistent with previous studies linking obesity and OA in mice (22). Although the precise molecular mechanisms of FST in modulating inflammation remain unclear, some studies postulate that FST may act like acute-phase protein in lipopolysaccharide-induced inflammation (23).

In addition to these effects of skeletal muscle, we found that FST gene therapy normalized many of the deleterious changes of an HFD on cardiac function without causing hypertrophy. These findings are consistent with previous studies showing that, during the process of aging, mice with myostatin knockout had an enhanced cardiac stress response (24). Furthermore, FST has been shown to regulate activin-induced cardiomyocyte apoptosis (1). In the context of this study, it is also important to note that OA has been shown to be a serious risk factor for progression of cardiovascular disease (25), and severity of OA disability is associated with significant increases in all-cause mortality and cardiovascular events (26).

FST gene therapy also rescued diet- and injury-induced bone remodeling in the femoral condyle, as well as the tibial plateau, metaphysis, and cortical bone of the tibia, suggesting a protective effect of FST on bone homeostasis of mice receiving an HFD. FST is a known inhibitor of bone morphogenetic proteins (BMPs), and thus, the interaction between the two proteins plays an essential role during bone development and remodeling. For example, mice grown with FST overexpression via global knock-in exhibited an impaired bone structure (27). However, in adult diabetic mice, FST was shown to accelerate bone regeneration by inhibiting myostatin-induced osteoclastogenesis (28). Furthermore, it has been reported that FST down-regulates BMP2-driven osteoclast activation (29). Therefore, the protective role of FST on obesity-associated bone remodeling, at least in part, may result from the neutralizing capacity of FST on myostatin in obesity. In addition, improvement in bone quality in FST mice may be explained by their enhanced muscle mass and strength, as muscle mass can dominate the process of skeletal adaptation, and conversely, muscle loss correlates with reduced bone quality (30).

Our results show that FST delivery mitigated pain sensitivity in OA joints, a critical aspect of clinical OA. Obesity and OA are associated with both chronic pain and pain sensitization (31), but it is important to note that structure and pain can be uncoupled in OA (32), necessitating the measurement of both behavioral and structural outcomes. Of note, FST treatment protected only HFD animals from mechanical algesia at the knee post-DMM surgery and also rescued animals from pain sensitization induced by HFD in both the DMM and nonsurgical limb. The mitigation in pain sensitivity observed here with FST treatment may also be partially attributed to the antagonistic effect of FST on activin signaling. In addition to its role in promoting tissue fibrosis, activin A has been shown to regulate nociception in a manner dependent on the route of injection (33, 34). It has been shown that activin can sensitize the transient receptor potential vanilloid 1 (TRPV1) channel, leading to acute thermal hyperalgesia (33). However, it is also possible that activin may induce pain indirectly, for example, by triggering neuroinflammation (35), which could lead to sensitization of nociceptors.

The earliest detectable abnormalities in subjects at risk for developing obesity and type 2 diabetes are muscle loss and accumulation of excess lipids in skeletal muscles (4, 36), accompanied by impairments in nuclear-encoded mitochondrial gene expression and OXPHOS capacity of muscle and adipose tissues (17). PGC-1 activates mitochondrial biogenesis and increases OXPHOS by increasing the expression of the transcription factors necessary for mitochondrial DNA replication (37). We demonstrated that FST delivery can rescue low levels of OXPHOS in HFD mice by increasing expression PGC-1 (Fig. 3H). It has been reported that high-fat feeding results in decreased PGC-1 and mitochondrial gene expression in skeletal muscles, while exercise increases the expression of PGC-1 in both human and rodent muscles (38, 39). Although the precise molecular mechanism by which FST promotes PGC-1 expression has not been established, the infusion of lipids decreases expression of PGC-1 and nuclear-encoded mitochondrial genes in muscles (40). Thus, decreased lipid accumulation in muscle by FST overexpression may provide a plausible explanation for the restored PGC-1 in the FST mice. These findings were further confirmed by the metabolic profile, showing reduced serum levels of triglycerides, glucose, FFAs, and cholesterol (Fig. 1D), and are consistent with previous studies, demonstrating that muscles with high numbers of mitochondria and oxidative capacity (i.e., type 1 muscles with high levels of PGC-1 expression) are protected from damage due to an HFD (4).

In addition, we found increased phosphorylation of protein kinase B (Akt) on Ser473 in the skeletal muscle of FST-treated mice as compared to untreated HFD counterparts (Fig. 3K), consistent with restoration of a normal insulin response. A number of studies have demonstrated that the serine-threonine protein kinase Akt1 is a critical regulator of cellular hypertrophy, organ size, and insulin signaling (41). Muscle hypertrophy is stimulated both in vitro and in vivo by the expression of constitutively active Akt1 (42, 43). Furthermore, it has been demonstrated that constitutively active Akt1 also promotes the production of VEGF (44).

BAT is thought to be involved in thermogenesis rather than energy storage. BAT is characterized by a number of small multilocular adipocytes containing a large number of mitochondria. The process in which white adipose tissue (WAT) becomes BAT, called beiging or browning, is postulated to be protective in obesity-related inflammation, as an increase in BAT content positively correlates with increased triglyceride clearance, normalized glucose level, and reduced inflammation. Our study shows that AAV-mediated FST delivery serves as a very promising approach to induce beiging of WAT in obesity. A recent study demonstrated that transgenic mice overexpressing FST exhibited an increasing amount of BAT and beiging in subcutaneous WAT with increased expression of key BAT-related markers including UCP-1 and PRDM16 (45). In agreement with previous reports, our data show that Ucp1, Prdm16, Pgc1a, and Cd167 are significantly up-regulated in SAT of mice overexpressing FST in both dietary interventions. FST has been recently demonstrated to play a crucial role in modulating obesity-induced WAT expansion by inhibiting TGF-/myostatin signaling and thus promoting overexpression of these key thermogenesis-related genes. Together, these findings suggest that the observed reduction in systemic inflammation in our model may be partially explained by FST-mediated increased process of browning/beiging.

In conclusion, we show that a single injection of AAV-mediated FST, administered after several weeks of HFD feeding, mitigated the severity of OA following joint injury, and improved muscle performance as well as induced beiging of WAT, which together appeared to decrease obesity-associated metabolic inflammation. These findings provide a controlled model for further examining the differential contributions of biomechanical and metabolic factors to the progression of OA with obesity or HFD. As AAV gene therapy shows an excellent safety profile and is currently in clinical trials for a number of conditions, such an approach may allow the development of therapeutic strategies not only for OA but also, more broadly, for obesity and associated metabolic conditions, including diseases of muscle wasting.

All experimental procedures were approved by and conducted in accordance with the Institutional Animal Care and Use Committee guidelines of Washington University in Saint Louis. The overall timeline of the study is shown in fig. S1A. Beginning at 5 weeks of age, C57BL/6J mice (The Jackson Laboratory) were fed either Control or 60% HFD (Research Diets, D12492). At 9 week of age, mice received AAV9-mediated FST or GFP gene delivery via tail vein injection. A total of 64 mice with 16 mice per dietary group per AAV group were used. DMM was used to induce knee OA in the left hind limbs of the mice at the age of 16 weeks. The non-operated right knees were used as contralateral controls. Several behavioral activities were measured during the course of the study. Mice were sacrificed at 28 weeks of age to evaluate OA severity, joint inflammation, and joint bone remodeling.

Mice were weighed biweekly. The body fat content and BMD of the mice were measured using a DXA (Lunar PIXImus) at 14 and 26 weeks of age, respectively.

Complementary DNA synthesis for mouse FST was performed by reverse transcriptase in a reverse transcription quantitative polymerase chain reaction (RT-qPCR) ( Invitrogen) mixed with mRNAs isolated from the ovary tissues of C57BL/6J mouse. The PCR product was cloned into the AAV9-vector plasmid (pTR-UF-12.1) under the transcriptional control of the chicken -actin (CAG) promoter including cytomegalovirus (CMV) enhancers and a large synthetic intron (fig. S1B). Recombinant viral vector stocks were produced at Hope Center Viral Vectors Core (Washington University, St. Louis) according to the plasmid cotransfection method and suspension culture. Viral particles were purified and concentrated. The purity of AAV-FST and AAV-GFP was evaluated by SDSpolyacrylamide gel electrophoresis (PAGE) and stained by Coomassie blue. The results showed that the AAV protein components in 5 1011 vector genomes (vg) are only stained in three major protein bands: VR1, 82 kDa; VR2, 72 kDa; and VR3, 62 kDa. Vector titers were determined by the DNA dot-blot and PCR methods and were in the range of 5 1012 to 1.5 1013 vector copies/ml. AAV was delivered at a final dose of 5 1011 vg per mouse by intravenous tail injection under red light illumination at 9 weeks of age. This dose was determined on the basis of our previous studies showing that AAV9-FST gene delivery by this route resulted in a doubling of muscle mass at a dose of 2.5 1011 vg in 4-week-old mice or at 5 1011 vg in 8-week-old mice (46).

At 16 weeks of age, mice underwent surgery for the DMM to induce knee OA in the left hindlimb as previously described (2). Briefly, anesthetized mice were placed on a custom-designed device, which positioned their hindlimbs in 90 flexion. The medial side of the joint capsule was opened, and the medial meniscotibial ligament was transected. The joint capsule and subcutaneous layer of the skin were closed with resorbable sutures.

Mice were sacrificed at 28 weeks of age, and changes in joint structure and morphology were assessed using histology. Both hindlimbs were harvested and fixed in 10% neutral-buffered formalin (NBF). Limbs were then decalcified in Cal-Ex solution (Fisher Scientific, Pittsburgh, PA, USA), dehydrated, and embedded in paraffin. The joint was sectioned in the coronal plane at a thickness of 8 m. Joint sections were stained with hematoxylin, fast green, and Safranin O to determine OA severity. Three blinded graders then assessed sections for degenerative changes of the joint using a modified Mankin scoring system (2). Briefly, this scoring system measures several aspects of OA progression (cartilage structure, cell distribution, integrity of tidemark, and subchondral bone) in four joint compartments (medial tibial plateau, medial femoral condyle, lateral tibial plateau, and lateral femoral condyle), which are summed to provide a semiquantitative measure of the severity of joint damage. To assess the extent of synovitis, sections were stained with H&E to analyze infiltrated cells and synovial structure. Three independent blinded graders scored joint sections for synovitis by evaluating synovial cell hyperplasia, thickness of synovial membrane, and inflammation in subsynovial regions in four joint compartments, which were summed to provide a semiquantitative measure of the severity of joint synovitis (2). Scores for the whole joint were averaged among graders.

Serum and SF from the DMM and contralateral control limbs were collected, as described previously (2). For cytokine and adipokine levels in the serum and SF fluid, a multiplexed bead assay (Discovery Luminex 31-Plex, Eve Technologies, Calgary, AB, Canada) was used to determine the concentration of Eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), IFN-, IL-1, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IP-10, keratinocyte chemoattractant (KC), leukemia inhibitory factor (LIF), liposaccharide-induced (LIX), monocyte chemoattractant protein-1 (MCP-1), M-CSF, monokine induced by gamma interferon (MIG), macrophage inflammatory protein1 (MIP-1), MIP-1, MIP-2, RANTES, TNF-, and VEGF. A different kit (Mouse Metabolic Array) was used to measure levels for amylin, C-peptide, insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, glucagon, insulin, leptin, protein phosphatase (PP), peptide yy (PYY), and resistin. Missing values were imputed using the lowest detectable value for each analyte.

Muscles were cryopreserved by incubation with 2-methylbutane in a steel beaker using liquid nitrogen for 30 s, cryoembedded, and cryosectioned at 8 m thickness. Tissue sections were stained following standard H&E protocol. Photomicrographs of skeletal muscle fiber were imaged under brightfield (VS120, Olympus). Muscle slides fixed in 3.7% formaldehyde were stained with 0.3% Oil Red O (in 36% triethyl phosphate) for 30 min. Images were taken in brightfield (VS120, Olympus). The relative concentration of lipid was determined by extracting the Oil Red O with isopropanol in equally sized muscle sections and quantifying the OD500 (optical density at 500 nm) in a 96-well plate.

To determine spatial expression of FST in different tissues, cryosections of gastrocnemius muscles and adipose tissue were immunolabeled for FST. Tissue sections were fixed in 1.5% paraformaldehyde solution, and primary anti-FST antibody (R&D Systems, AF-669, 1:50) was incubated overnight at 4C after blocking with 2.5% horse serum (Vector Laboratories), followed by labeling with a secondary antibody (Alexa Fluor 488, Invitrogen, A11055) and with 4,6-diamidino-2-phenylindole (DAPI) for cell nuclei. Sections were imaged using fluorescence microscopy.

Second-harmonic generation images of TA were obtained from unstained slices using backscatter signal from an LSM 880 confocal microscope (Zeiss) with Ti:sapphire laser tuned to 820 nm (Coherent). The resulting image intensity was analyzed using ImageJ software.

To measure bone structural and morphological changes, intact hindlimbs were scanned by microCT (SkyScan 1176, Bruker) with an 18-m isotropic voxel resolution (455 A, 700-ms integration time, and four-frame averaging). A 0.5-mm aluminum filter was used to reduce the effects of beam hardening. Images were reconstructed using NRecon software (with 10% beam hardening and 20 ring artifact corrections). Subchondral/trabecular and cortical bone regions were segmented using CTAn automatic thresholding software. Tibial epiphysis was selected using the subchondral plate and growth plate as references. Tibial metaphysis was defined as the 1-mm region directly below the growth plate. The cortical bone analysis was performed in the mid-shaft (4 mm below the growth plate with a height of 1 mm). Hydroxyapatite calibration phantoms were used to calibrate bone density values (mg/cm3).

Fresh visceral adipose tissues were collected, frozen in optimal cutting temperature compound (OCT), and cryosectioned at 5-m thickness. Tissue slides were then acetone-fixed followed by incubation with Fc receptor blocking in 2.5% goat serum (Vector Laboratories) and incubation with primary antibodies cocktail containing anti-CD11b:Alexa Fluor 488 and CD11c:phycoerythrin (PE) (BioLegend). Nuclei were stained with DAPI. Samples were imaged using fluorescence microscopy (VS120, Olympus).

Adipose tissues were fixed in 10% NBF, paraffin-embedded, and cut into 5-m sections. Sections were deparaffinized, rehydrated, and stained with H&E. Immunohistochemistry was performed by incubating sections (n = 5 per each group) with the primary antibody (antimUCP-1, U6382, Sigma), followed by a secondary antibody conjugated with horseradish peroxidase (HRP). Chromogenic substrate 3,3-diaminobenzidine (DAB) was used to develop color. Counterstaining was performed with Harris hematoxylin. Sections were examined under brightfield (VS120, Olympus).

Proteins of the muscle or fat tissue were extracted using lysis buffer containing 1% Triton X-100, 20 mM tris-HCl (pH 7.5), 150 mM NaCl, 1 mm EDTA, 5 mM NaF, 2.5 mM sodium pyrophosphate, 1 mM -glycerophosphate, 1 mM Na3VO4, leupeptin (1 g ml1), 0.1 mM phenylmethylsulfonyl fluoride, and a cocktail of protease inhibitors (Sigma, St. Louis, MO, USA, catalog no. P0044). Protein concentrations were measured with Quick Start Bradford Dye Reagent (Bio-Rad). Twenty micrograms of each sample was separated in SDS-PAGE gels with prestained molecular weight markers (Bio-Rad). Proteins were wet-transferred to polyvinylidene fluoride membranes. After incubating for 1.5 hours with a buffer containing 5% nonfat milk (Bio-Rad #170-6404) at room temperature in 10 mM tris-HCl (pH 7.5), 100 mM NaCl, and 0.1% Tween 20 (TBST), membranes were further incubated overnight at 4C with antiUCP-1 rabbit polyclonal antibody (1:500, Sigma, U6382), anti-PRDM16 rabbit antibody (Abcam, ab106410), anti-CD137 rabbit polyclonal antibody (1:1000, Abcam, ab203391), total OXPHOS rodent western blot (WB) antibodies (Abcam, ab110413), anti-actin (Cell Signaling Technology, 13E5) rabbit monoclonal antibody (Cell Signaling Technology, 4970), followed by HRP-conjugated secondary antibody incubation for 30 min. A chemiluminescent detection substrate (Clarity, Western ECL) was applied, and the membranes were developed (iBrightCL1000).

The effects of HFD and FST gene therapy on thermal hyperalgesia were examined at 15 weeks of age. Mice were acclimatized to all equipment 1 day before the onset of testing, as well as a minimum of 30 min before conducting each test. Thermal pain tests were measured in a room set to 25C. Peripheral thermal sensitivity was determined using a hot/cold analgesia meter (Harvard Apparatus, Holliston, MA, USA). For hot plate testing, the analgesia meter was set to 55C. To prevent tissue damage, a maximum cutoff time of 20 s was established a priori, at which time an animal would be removed from the plate in the absence of pain response, defined as paw withdrawal or licking. Animals were tested in the same order three times, allowing each animal to have a minimum of 30 min between tests. The analgesia meter was cleaned with 70% ethanol between trials. The average of the three tests was reported per animal. To evaluate tolerance to cold, the analgesia meter was set to 0C. After 1-hour rest, animals were tested for sensitivity to cold over a single 30-s exposure. The number of jumps counted per animal was averaged within each group and compared between groups.

Pressure-pain tests were conducted at the knee using a Small Animal Algometer (SMALGO, Bioseb, Pinellas Park, FL, USA). Surgical and nonsurgical animals were evaluated over serial trials on the lateral aspect of the experimental and contralateral knee joints. The average of three trials per limb was calculated for each limb. Within each group, the pain threshold of the DMM limb versus non-operated limb was compared using a t test run on absolute values of mechanical pain sensitivity for each limb, P 0.05.

To assess the effect of HFD and AAV-FST treatments on neuromuscular function, treadmill running to exhaustion (EXER3, Columbus Instruments) was performed at 15 m/min, with 5 inclination angle on the mice 4 months after gene delivery. Treadmill times were averaged within groups and compared between groups.

Forelimb grip strength was measured using Chatillon DFE Digital Force Gauge (Johnson Scale Co.) for front limb strength of the animals. Each mouse was tested five times, with a resting period of 90 s between each test. Grip strength measurements were averaged within groups and compared between groups.

Cardiac function of the mice was examined at 6 months of age (n = 3) using echocardiography (Vevo 2100 High-Resolution In Vivo Imaging System, VisualSonics). Short-axis images were taken to view the LV movement during diastole and systole. Transmitral blood flow was observed with pulse Doppler. All data and images were performed by a blinded examiner and analyzed with an Advanced Cardiovascular Package Software (VisualSonics).

Detailed statistical analyses are described in methods of each measurement and its corresponding figure captions. Analyses were performed using GraphPad Prism, with significance reported at the 95% confidence level.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: Funding: This study was supported, in part, by NIH grants AR50245, AR48852, AG15768, AR48182, AG46927, AR073752, OD10707, AR060719, AR074992, and AR75899; the Arthritis Foundation; and the Nancy Taylor Foundation for Chronic Diseases. Author contributions: R.T. and F.G. developed the concept of the study; R.T., N.S.H., C.-L.W., K.H.C., and Y.-R.C. collected and analyzed data; S.J.O. analyzed data; and all authors contributed to the writing of the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

Link:
Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat dietinduced obesity - Science Advances

BOSTON--(BUSINESS WIRE)--Decibel Therapeutics, a clinical-stage biotechnology company developing novel gene therapeutics for restoration of hearing loss and balance disorders, today announced that it will present new findings on its pipeline and platform at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), which will be held virtually from May 1215.

Decibels platform utilizes leading single-cell genomics and bioinformatics capabilities to enable AAV-based gene therapy to restore functionality of cochlear and vestibular hair cells in multiple forms of hearing loss and balance disorders. The company has used its platform to identify a suite of genetic control elements enabling cell-specific expression in each of the key cell types of the inner ear. Decibel is further identifying key reprogramming factors to regenerate hair cells in the inner ear by gene therapy or small molecules.

Decibel will deliver three presentations:

The research our team will share at ASGCT represents the progress we have made in developing our precision AAV platform to deliver genes that can restore hearing and balance function, said John Lee, CSO of Decibel. Our AAV platform, combined with our single-cell genomics and bioinformatics capabilities, is driving our progress to create transformative therapeutics for people who are living with severe hearing loss and balance disorders.

The three presentations the Decibel team will share during the conference are the following:

Dual AAV Delivery of Otoferlin Durably Rescues Hearing in Congenitally Deaf Preclinical ModelsPresenter: Jonathon Whitton, Au.D., Ph.D. Session Title: Gene Therapy for the Special Senses Date & Time: Tuesday, May 12, 11:15 a.m.

Tailored AAV-Based Transgene Expression in the Inner Ear with Cell Type-Specific PromotersPresenter: Adam Palermo, Ph.D. Session Title: Controlling AAV Gene Expression: Shifting Paradigms Date & Time: Wednesday, May 13, 4:45 p.m.

A Transient Burst of Transgene Expression Promotes Regeneration of Mature Vestibular Hair CellsPresenter: Joseph Burns, Ph.D. Session Title: AAV Vectors Preclinical and Proof-of-Concept Studies in CNS Disorders Date & Time: Friday, May 15, 10:45 a.m.

About Decibel Therapeutics, Inc.

Decibel Therapeutics, a clinical-stage biotechnology company, has established the worlds first comprehensive drug discovery, development and translational research platform for hearing loss and balance disorders. Decibel is advancing a portfolio of discovery-stage programs aimed at restoring hearing and balance function to further our vision of a world in which the benefits and joys of hearing are available to all. Decibels lead therapeutic candidate, DB-020, is being investigated for the prevention of ototoxicity associated with cisplatin chemotherapy. For more information about Decibel Therapeutics, please visit decibeltx.com or follow @DecibelTx.

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Decibel Therapeutics to Present at the 23rd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) - Business Wire

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Size & Share Of Cell and Gene Therapy Consumables Market 2020 Report Including COVID-19 Impact Analysis And Forecast Till 2026 - Bandera County...

Merck is moving its global headquarters slightly.

After five years at Schering-Ploughs old 100-acre campus in Kenilworth, the company announced plans to transition its base to its 210-acre site in Rahway. The two New Jersey towns are less than 10 miles apart. The move, quietly announced in the companys Q1 and reported on by ROINJ, is slated to be completed by 2023.

The shift will not only mean moving the headquarters but also consolidating the offices scattered across New Jersey, including inMadison, Whitehouse West and Branchburg. No employees are expected to be laid off, the company said.

We announced our intention to consolidate our New Jersey campuses into a single New Jersey location in Rahway, the company said in an emailed statement. Rahway, the birthplace of lifechanging scientific breakthroughs that have improved human health over the last century, will once again be Mercks global headquarters by the end of 2023. We remain committed to New Jersey and invested in the state as the home of our global headquarters.

The move to Rahway is something of a homecoming for Merck. The pharma giant was based in Rahway until 1992, until it moved to Whitehouse Station in Readington, a small town in rural western New Jersey. The company hired a legendary architectural firm to build what became known as the Merck Headquarters Building on woods and old farmland, a jagged hexagon, circumscribed by trees, with trees nestled in the center.

In 2012, Merck said they would shutter the campus and, after a shakeup that saw the closing of the would-be new headquarters in Summit, NJ and the layoff of 8,500 employees worldwide, moved their base to Kenilworth. The Merck Headquarters Building has since been purchased by UNICOM and renamed UNICOM Science and Technology Park.

Although originally established in 1889 in New York City then as the US subsidiary of the German Merck Merck built a manufacturing facility in Rahway in 1902, and, with the addition of research facilities, the site became the headquarters until the 1992 move.

See the article here:
UPDATED: Merck to move global headquarters, returning to an old home - Endpoints News

Image source: The Motley Fool.

Sangamo Therapeutics Inc(NASDAQ:SGMO)Q12020 Earnings CallMay 11, 2020, 5:00 p.m. ET

Operator

Good afternoon, and welcome to the Sangamo Therapeutics Teleconference to discuss First Quarter 2020 Financial Results. This call is being recorded.

I will now pass you over to the coordinator of this event, McDavid Stilwell, Senior Vice President of Corporate Communications and Investor Relations.

McDavid Stilwell -- Senior Vice President of Corporate Communications and Investor Relations

Good afternoon, and thank you for joining us today. With me this afternoon on this call are several members of the Sangamo senior management team, including Sandy Macrae, Chief Executive Officer; Sung Lee, Chief Financial Officer; Stephane Boissel, Head of Corporate Strategy; Adrian Woolfson, Head of Research and Development; Mark McClung, Chief Business Officer; and Bettina Cockroft, Chief Medical Officer.

Slides from our corporate presentation can be found in our website sangamo.com under the Investors and Media section in the Events and Presentations page.

This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to our pipeline of genomic medicine product candidates, our ability to develop, obtain regulatory approval for and commercialize therapies to treat certain diseases and the timing, availability and costs of such therapies, plans and timelines for Sangamo and our collaborators to conduct clinical trials and share clinical data and the potential for these trials to provide clinical benefit to patients, the potential to use certain technologies to develop our therapies, the financial and operational impacts of our collaboration, plans and timelines for building and opening manufacturing facilities, the evolving COVID-19 pandemic and our expectations regarding our financial performance and resources. Actual results may differ substantially from what we discuss today. In addition, these statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed in documents that we file with the Securities and Exchange Commission. Specifically in our most recent quarterly report on Form 10-Q filed today and our annual report on Form 10-K. The forward-looking statements stated today are made as of this date and we undertake no duty to update such information, except as required under applicable law.

On this call, we discuss the non-GAAP financial measure. We believe this measure is helpful in understanding our past financial performance and our potential future results. This is not meant to be considered in isolation or as a substitute for the comparable GAAP measure. The comparable GAAP measure and reconciliations of GAAP to the non-GAAP measure discussed on this call are included in today's press release, which is available on our website.

And now, I'd like to turn the call over to Sandy.

Sandy Macrae -- President and Chief Executive Officer

Thank you, McDavid, and good afternoon to everyone on the call. Typically, when I come together with the Sangamo executive team to talk to you about our business every quarter, we are in the boardroom of the headquarters in Brisbane, California. Today, due to the COVID-19 pandemic, we're all in our home offices. One of the many adaptations we've all had to make in these unprecedented circumstances.

At Sangamo, over the last two months, we've worked together to minimize any impact of the pandemic on our business, and I believe that we are in a very strong position. Last month, we were very pleased to announce the closing of our collaboration agreement with Biogen to develop gene regulation therapies for Alzheimer's disease, Parkinson's disease, neuromuscular and other neurological diseases. We have received from Biogen $225 million in proceeds from the sale of stock and an additional $125 million upfront license fee payment. With this $350 million received from Biogen and in addition to the $363 million in cash resources that we reported on our March 31 balance sheet, we believe we have the financial strength to execute on our wholly owned and partnered development programs beyond multiple important milestones, including the potential filing of the BLA for SB-525 for hemophilia A.

In response to COVID-19, Sangamo has prioritized employee safety, and welfare, while responsibly advancing the business. Following the shelter-in-place guidance from government authorities in the middle of March, we asked all non-lab employees to work from home. We also implemented modified labs operations and updated safety protocols to continue critical research and manufacturing work while protecting employee safety and adhering to social distance guidelines. In the labs, we are strategically prioritizing projects to keep our business on track, including focusing on research activities for partnered programs. We are also conducting clinical activities cautiously, so as not to contribute unnecessarily to the current stream in the healthcare system, while seeing close communication with trial sites to protect the safety of the patients in our trial.

We continue to be optimistic that our AAV manufacturing facility in our Brisbane headquarters will be operational by the end of this year. We also expect our cell therapy manufacturing units in Brisbane, California and in Valbonne, France to be opened by the end of 2021. Furthermore, we are keeping in regular contact with our CDMO partners and as of now, do not anticipate any COVID-19-related manufacturing delays with our activities.

Despite the challenges of the current environment, we continue to actively pursue new partnerships both inbound to access new technology, as well as out-licensing deals such as established ones that we already have with Pfizer, Gilead, Sanofi, Biogen and Takeda. An important example of an inbound partnership is our recently announced collaboration and exclusive license with Mogrify, a Cambridge UK company developing novel cell conversion technology that has the potential to serve as a renewable cell source. Under the terms of this agreement, Sangamo aim to use Mogrify's proprietary cell conversion technology to develop allogeneic, zinc finger protein gene-engineered CAR-Treg cell therapies using iPSC-derived regulatory T-cells. This license agreement will diversify our options and complement our current efforts as we develop off-the-shelf allogeneic CAR-Treg cell therapies. We believe that this exciting collaboration has the potential to accelerate the development and manufacturing of novel renewable cell source, Treg therapies.

We are also continuing our discussions on out-licensing opportunities. As a reminder, our strategy for collaborations is to advance select development programs in partnership with biopharmaceutical companies in situations where we believe that our partners' financial resources or clinical and therapeutic area expertise may enable more rapid development and availability of new treatment to patients.

Before I turn the call over to the team, I want to update you on some recent transitions among my direct reports that are natural part of Sangamo's evolution, as we advance our clinical development and strategic partnering. Over the last three years, we've added Executive Vice Presidents to lead manufacturing, legal, finance and R&D. In our latest executive appointment, as we look to the future and perceive the need for commercial development expertise and capabilities, Mark McClung has joined Sangamo as Chief Business Officer and now leads commercial strategic planning, alliance management and corporate and business development. Mark has a distinguished career leading commercial organizations, including GSK, Onyx and Amgen in highly competitive therapeutic areas that require a deep scientific knowledge and where innovative products have disrupted the standards of care and where successful product development occurs as a result in a tightly integrating patient and physician insights into late stage clinical development programs.

Stephane Boissel, our EVP of Corporate Strategy will leave Sangamo at the end of in July and plans to return to an entrepreneurial project. Stephane joined Sangamo in 2018 after we acquired TxCell, now Sangamo France, which Stephane lead as CEO. His energy and vision resulted in our recent Biogen transaction, which is one of the largest pre-clinical collaboration deals ever in the biopharmaceutical industry. Stephane's impactful contribution to Sangamo will endure for many years.

With that, I will turn the call over to our Chief Medical Officer, Bettina.

Bettina Cockroft -- Senior Vice President and Chief Medical Officer

Good afternoon. In light of the COVID-19 pandemic, Sangamo is working very closely with all our clinical trial site partners to devise individualized plans to protect the safety of every patient enrolled in our studies, as well as the continued integrity of our trial data. After we have established a plan for each patient, we work with sites and IRBs to establish appropriate procedures. In some cases, trial site partners have been reducing or pausing clinical trial work to redirect capacity and resources to COVID-19 patients. At other sites, clinical trial patients are still being screened and enrolled, but may not be dosed until an appropriate time is identified.

In addition to adopting our clinical operations to this new situation, we are implementing procedures now, so that as the COVID-19 crisis subsides, we'll be able to resume operations as quickly and as efficiently as possible. To do this, we are keeping close contact with our trial site partners and continuing to identify potential patients that may be suitable for enrollment. In some cases, we're also using this time to further optimize clinical operations, processes and engage with regulatory agencies. We're also working closely with our collaboration partners to track the status of our joint development programs.

Turning now to some clinical updates commencing with SB-525 or PF-07055480, hemophilia A gene therapy. We transferred operations of the fully enrolled Phase 1/2 ALTA Study to Pfizer along with the IND at the end of last year. We're working closely together with Pfizer to identify an appropriate opportunity this year to provide an update on the results that we shared at ASH 2019 from the high-dose expansion cohort. Pfizer continues to target dosing the first patient in the Phase 3 study in H2 2020. Pfizer is working to minimize any potential disruptions to the schedule, due to the ongoing COVID-19 pandemic and continues to recruit patients into the Phase 3 lead-in study. Pfizer recently updated clinicaltrials.gov with the Phase 3 study protocol and have informed us that they plan to provide additional updates on the Phase 3 trial in due course.

Moving now to our wholly owned gene therapy, ST-920 for Fabry disease. We have successfully screened and enrolled patients into the STAAR study and we are awaiting for a safe and appropriate time to initiate dosing the first patient.

In conjunction with our partner Sanofi, we're evaluating gene-edited cell therapies for two hemoglobinopathies, ST-400 for beta thalassemia and BIVV003 for sickle cell disease. ST-400 and BIVV003 are both designed to induce the synthesis of fetal hemoglobin. This is achieved by gene-edited knock out of the erythroid-specific enhancer of the BCL11a gene, which encodes a strong repressor of the gamma globin gene. In beta thalassemia, if fetal hemoglobin is expressed at high enough levels, it may substitute for patients absent or impaired levels of beta globin. We have enrolled and dosed five patients into the THALES Study evaluating ST-400 for beta thalassemia.

In sickle cell disease, increased fetal hemoglobin synthesis may provide the patient with functional hemoglobin and help down regulate the abnormal sickle hemoglobin that results in painful sickle cell crisis and other disease features. Sanofi has also been enrolling patients into the PRECIZN-1 study evaluating BIVV003 in sickle cell disease and dosed the first patient last year. New analysis of the study's data will be shared when the two studies have accumulated a sufficient number of the patients and follow up. No additional beta thalassemia patients in the THALES Study will be treated until the data from both studies has been collected and analyzed. Sanofi, will in the meantime, continue enrolling sickle cell patients into the PRECIZN-1 study. We will look for an appropriate time to present data from both these studies at a future date.

I'd like to conclude by addressing a few programs that we are monitoring closely with regard to potential impact by COVID-19. We continue to make progress with additional regulatory approvals for the Phase 1/2 STEADFAST study, evaluating our first in human CAR-Treg cell therapy, TX200, in HLA-A2 mismatched kidney transplantation. We expect to dose the first patient in this study in 2021.

Moving on now to KITE-037, an allogeneic anti-CD19 CAR-T cell product being developed by Kite, a Gilead company. Kite has informed us that there is a potential for a COVID-related delay to the initiation of the KITE-037 clinical trial.

I will now turn the call over to Sung for an overview of the financial results. Sung?

Sung Lee -- Executive Vice President and Chief Financial Officer

Thank you, Bettina, and good afternoon, everyone. We're pleased to share our financial results for the first quarter of 2020. We reported a net loss of $42.9 million, or $0.37 per share, compared to a net loss of $42.2 million, or $0.41 per share for the same period in 2019. The revenues were $13.1 million, compared to $8.1 million for the same period in 2019.

Turning to expenses, non-GAAP operating expenses, which excludes stock compensation, were $52 million, compared to $47.4 million in 2019. The increase in operating expenses was primarily related to the Company's overall headcount growth and facilities expansion to support the advancement of Sangamo's therapeutic pipeline and manufacturing capabilities.

Moving to the balance sheet. We ended the quarter with $363 million in cash, cash equivalents and marketable securities. Following the end of Q1, we received $350 million from Biogen from the sale of stock and the upfront license fee. As Sandy mentioned earlier, we believe we have the balance sheet strength to take us through important R&D milestones, including the first potential filing of the BLA for SB-525 for hemophilia A.

Turning to 2020 full-year guidance. We are reiterating our previously shared financial guidance and anticipate non-GAAP operating expense, which excludes estimated stock compensation expense of $25 million to be in the range of $245 million to $260 million in 2020. At this time, we do not expect any material negative financial impact from COVID-19 to our operating expense guidance. We will continue to monitor the situation and provide an update in the future. In the meantime, we will continue to be good stewards of capital.

I will now turn it back to Sandy for closing remarks.

Sandy Macrae -- President and Chief Executive Officer

Thank you, Sung. This quarter marked an important milestone with the closing of the Biogen agreement, which will significantly strengthened our balance sheet and represents yet another vote of confidence in our highly differentiated zinc finger protein genomic medicine platform from a top biopharmaceutical company.

In these unprecedented times, I've observed tremendous resilience and adaptiveness from our employees. And this has kept our business moving forward, including ongoing business development discussions, continued research and technical operations in our laboratories and continued partnerships with our clinical trial sites. We feel a great sense of confidence in our business and in our ability to weather the COVID-19 crisis, due to our balance sheet strength, strategic investments in infrastructure, and to the prudent plans that we have established to facilitate our rapid return to more normal operations, as this crisis subsides.

Operator, we are ready for questions?

Operator

Thank you. [Operator Instructions] Our first question comes from Maury Raycroft with Jefferies. Your line is open.

Maury Raycroft -- Jefferies LLC -- Analyst

Hi, everyone. Thanks for taking my questions. First question is just on hemophilia A. So, with the Phase 3 trial posted to clinicaltrials.gov. Can you talk more about the design at this time, including dose, steroid use and what estimates are on how long it's going to take to enroll the study?

Sandy Macrae -- President and Chief Executive Officer

Maury, thanks for your question. As you can imagine that the Phase 3 trial is under the control and communication of Pfizer, and they will give all announcements about the design of the trial, and we want to respect that relationship with them. Everything they have told us so far guides to the trial moving ahead as planned. One of the advantages of our partnership with Pfizer is, they are a global organization that can take the trial to where the patients are available and where the COVID impact is less. So, we look forward to them sharing more information with you as the year progresses.

Maury Raycroft -- Jefferies LLC -- Analyst

Understood. Understood. And then, for Fabry, you guys have mentioned before that you had more patients screen failures than you initially expected. Just wondering if you've implemented enrollment criteria changes and have those been helping.

Sandy Macrae -- President and Chief Executive Officer

Bettina, would you be able to talk to that?

Bettina Cockroft -- Senior Vice President and Chief Medical Officer

Yes, of course. Hi, there. So, we have been looking at implementing some changes. And, as you will have noted from the communication today, we have actually enrolled patients into the Fabry study. Now, of course, during the COVID pandemic, we are being very cautious as to assessing the best timing for dosing the first subject. But we have had an uptick and that has resulted in inclusion of patients into the study.

Sandy Macrae -- President and Chief Executive Officer

And Bettina, you feel that the changes you made to the protocol have permitted that or facilitated that?

Bettina Cockroft -- Senior Vice President and Chief Medical Officer

Exactly. Absolutely, absolutely.

Maury Raycroft -- Jefferies LLC -- Analyst

Great. Okay. And then last quick one was just on, wondering if you have formalized plans to conduct a renal biopsy for Gb3 reduction in this initial part of the study. Or could that come in later on, maybe if you could just talk more about the plans are?

Sandy Macrae -- President and Chief Executive Officer

We haven't discussed our plans for the Gb3 and for renal biopsy. As you can imagine, that is a complex issue about patient benefit and the risk of a renal biopsy. We are very appreciative of the FDA trying to make medicines for Fabry, get to patients as quickly as possible by allowing registration quicker with the renal biopsy and are very aware of that and are incorporating it into our plans.

Maury Raycroft -- Jefferies LLC -- Analyst

Got it. Thank you for taking my questions.

Sandy Macrae -- President and Chief Executive Officer

Thanks, Maury. Do well.

Operator

Thank you. Our next question comes from Gena Wang of Barclays. Your line is open.

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. I have two questions. The first is regarding hemophilia A update, and second question is regarding Fabry disease. First, hemophilia A update, I understand Pfizer emphasized the importance of 18-month data. Given follow-up from last ASH, is it fair to say 4Q this year likely would be a good timing to show data? And for the Fabry disease, you did mention you enrolled several patients. Just wondering how many patients. And also, is this still possible to present initial data beginning of next year? Also, can you remind us the first dose for Fabry disease?

Sandy Macrae -- President and Chief Executive Officer

So, I'll let me take the first question before passing you on to Bettina, but warning you that we haven't talked about the first dose yet. But if I could do the hemophilia A, unfortunately, the world time moves at just the same rate, and patients are only now coming out of their 18-month point and that's very weak patients and it will take throughout the rest of the -- this and the next quarter for the majority of patients to reach their 18-month point. So, Pfizer will lead all communications as part of the deal for transition like this. You agree which company will lead all communications, and that is in Pfizer's hands and they will decide when they have data that they will share with you all. I know this is frustrating, but it's -- it has to be a single company that leads that.

And Bettina, can you talk about our enrollment in Fabry, please?

Bettina Cockroft -- Senior Vice President and Chief Medical Officer

Yes, absolutely. So, as far as Fabry is concerned, to address your last question first, we're going to be showing data after we've completed dose escalation across the three cohorts that we have in our protocol. We want to make sure that we present a mature dataset that can represent safety and efficacy of ST-920. And in terms of which doses we were planning to test, we have said low, medium and high. We will disclose specific doses at an appropriate point in the future. What I can say is, we've learned a lot about AAV6 through our SB-525 hemophilia A program and we've made protocol amendments to the Fabry program to take those learnings and also FDA guidance into account. So, we look forward to updating further on this in the future.

Gena Wang -- Barclays -- Analyst

Okay. How many patient already have enrolled?

Bettina Cockroft -- Senior Vice President and Chief Medical Officer

[Speech Overlap] I think we've not disclosed...

Sandy Macrae -- President and Chief Executive Officer

Yeah, exactly. We're not disclosing that. But we have patients enrolled. We have interest from sites and it's just a matter of us choosing when to dose the first patient. I'm sure you would agree that we need to choose wisely, because the patients will have to come in for monitoring and we want to make sure that they are safe and that their health service is not overstressed.

Gena Wang -- Barclays -- Analyst

Thank you.

Operator

Thank you. Our next question comes from Whitney Ijem of Guggenheim. Your line is open.

Whitney Ijem -- Guggenheim Securities -- Analyst

Hey, guys. Thanks for taking the questions. Wanted to follow up on Fabry. So, I guess, first, can you give us any color on the entry criteria that were adjusted, that kind of facilitated enrollment, just curious if we could learn more there?

And then the second question is on the endpoints, you mentioned you won't present data until you have a complete dataset. I guess, what does that mean in terms of follow-up and kind of what endpoints are you tracking? Or is that the 12-month kind of safety follow-up that's reflected on clin-trials? Thanks.

Sandy Macrae -- President and Chief Executive Officer

So, Whitney, thank you for your question. The criteria that we adjusted were not things about antibody criteria like gene therapy things. They were more our understanding of what Fabry patients look like onboard, the right patients to put into the study. Each time, a company like our goes into a new disease, we learn from the first few patients and Bettina and her team done an excellent job in simply understanding what patients are available.

When we say we won't talk about the study until it's complete, what we mean is that, we've gone through the -- each of the dose cohorts. And as soon as we have biochemistry data from each of the dose cohorts, the low, medium and high as Bettina has said, we will share them with you. You're absolutely right that there will be follow-on data that will look at additional parameters, including in some patients' biopsy. But we hope to be able to share the biochemistry initially and talk to you about the results of our intervention.

Whitney Ijem -- Guggenheim Securities -- Analyst

Got it. And just a quick follow-up, in terms of the biochemistry what particular endpoints, I guess, are you looking at there and what's the cut-off? I guess, is it like three months or six months of biochemistry you want to have at that higher dose to kind of be the threshold for announcing the data?

Sandy Macrae -- President and Chief Executive Officer

We haven't described that. We -- you've been with us for a long time and you understand our cautiousness in speaking too soon and waiting for the results to stabilize. So, as we can most inform you and most inform the patient community.

Whitney Ijem -- Guggenheim Securities -- Analyst

Understood. Thanks very much.

Sandy Macrae -- President and Chief Executive Officer

Thank you.

Operator

Thank you. [Operator Instructions] Our next question comes from Ritu Baral of Cowen. Your line is open.

Originally posted here:
Sangamo Therapeutics Inc (SGMO) Q1 2020 Earnings Call Transcript - The Motley Fool

Global Gene Therapy Marketis a comprehensive study that presents forecasted market size and trends based on past and present status of the industry. The report encompasses top manufacturers, prospective market share, revenue, purchaser volume with respect to dealing volume and global segmentation of the globalGene Therapymarket. The report explains complicated data in simple language. The report comprises market classification and definitions, product and industry overview, manufacturing specifications, and cost structure. The research offers the current technological innovations affecting the growth of the market during the forecast period from 2020 to 2025.

NOTE: Our final report will be revised to address COVID-19 effects on the specific market.

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The report additionally reviews the market key drivers, restraints, growth signs, challenges, market dynamics, aggressive landscape, and different key aspects related to the globalGene Therapymarket. The report presents a top to bottom illumination of the markets past, current, and future status. It offers an analysis of emerging market sectors and development opportunities in the market. Market structure is described by analyzing the segments such as product type, application, end-users, key regions, and key companies. Further, the report gives in detailed information about the players on the basis of type, financial position, price, growth strategies, product portfolio, and regional presence of the players in the market.

Regional Spectrum:

This section contains regional segmentation which describes the regional aspects of the globalGene Therapymarket. This chapter explains the framework that is expected to affect the entire market. It covers the scenario of the market and anticipates its impact on the market. Main region market conditions are assessed with respect to the product price, profit, capacity, production, supply, demand, and market growth rate and forecast, etc. Key regions analyzed in the market are:North America, Europe, Asia Pacific, South America, and the Middle East and Africa.

The global market report offers in-depth information about the major market players:Spark Therapeutics LLC, Bluebird Bio, UniQure N.V., Juno Therapeutics, GlaxoSmithKline, Chiesi Farmaceutici S.p.A., Bristol Myers Squibb, Celgene Corporation, Human Stem Cell Institute, Voyager Therapeutics, Shire Plc, Sangamo Biosciences, Dimension Therapeutics and others.

The report delivers the industrial chain analysis, downstream buyers, and raw material sources along with the accurate insights of market dynamics. Major insights and statistical details are provided in terms of demand and supply, cost structure, barriers and challenges, product type, key market players, technology, regions, and applications. Further, the report evaluates upstream and downstream raw materials, present globalGene Therapymarket dynamics, and offers subsequent consumer analysis.

Demand and uptake patterns in key industries of the market are analyzed. The research report covers product innovation, market strategies of the key players, market share, the latest research and development, revenue generation, and market expert views. In the end, the report delivers a conclusion which includes breakdown and data triangulation, consumer needs/customer preference change, research findings, globalGene Therapymarket size estimation, data source.

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Global Gene Therapy Market 2020 Key Factors and Emerging Opportunities with Current Trends Analysis 2025 - NJ MMA News

(Inside Science) Early in the 1960s, a group of enthusiasts advanced the concept of freezing humans as soon as they die, in hopes of reviving them after the arrival of medical advances able to cure the conditions that killed them. The idea went into practice for the first time 50 years ago.

On Jan. 12, 1967, James Bedford, an emeritus professor of psychology at the University of California, became the first person to be "cyropreserved." A small team of doctors and other enthusiasts froze him a few hours after he died from liver cancer that had spread to his lungs.

A few days later the team placed the body into an insulated container packed with dry ice. Later still, Bedford was immersed in liquid nitrogen in a large Dewar container. Fifteen years on, after a series of moves from one cryopreservation facility to another, his body found a home at the Alcor Life Extension Foundation in Scottsdale, Arizona, where it still resides.

By current standards of cryonics, the procedure was remarkably untidy and disorganized. Nevertheless, a visual evaluation of Bedford's condition in 1991 found that his body had remained frozen and suffered no obvious deterioration.

"There's no date set for another examination," said R. Michael Perry, care services manager at Alcor.

Related: Life-Saving Drones Promise Revolution in Emergency Care

But as promoters of cryopreservation celebrate the 50th anniversary of Bedford's death and freezing known to some as "Bedford Day" they emphasize improvements to the freezing and preservation procedures that Bedford's experiences advanced.

The community is also undergoing a significant change in its expectations for reviving frozen patients. Rather than planning for a Lazarus-like resuscitation of the entire body, some proponents of the technology focus more on saving individuals' stored memories, and perhaps incorporating them into robots.

Beyond the cryopreservation community, however, an aura of scientific suspicion that surrounded Bedford's freezing remains.

"Reanimation or simulation is an abjectly false hope that is beyond the promise of technology and is certainly impossible with the frozen, dead tissue offered by the 'cryonics' industry," neuroscientist Michael Hendricks of McGill University in Montreal, Canada, wrote in Technology Review.

Scientists aren't the industry's only critics.

Families of individuals designated for freezing including Bedford's own family have gone to court to protest or defend loved ones' decisions to undergo freezing.

Related: This App is Revolutionizing Diagnoses of Rare Diseases

In a more recent case, in 2011, a Colorado probate judge upheld a contract that Mary Robbins had signed with Alcor over objections from Robbins' children. And last year the High Court of England upheld a mother's right to seek cryonic treatment of her terminally ill 14-year-old daughter after her death, despite the father's wishes.

Public reaction to the technology reached its nadir in New England in 2002, when court documents revealed that Boston Red Sox baseball icon Ted Williams was frozen in the Alcor facility, with his head severed from his body. Williams' son John Henry, who arranged the process, was himself frozen after he died of leukemia.

Politics has also impacted the technology's progress. In 2004, for example, Michigan's state government voted to license a facility called the Cryonics Institute, located in Clinton, as a cemetery. That move, reversed eight years later, prevented the institute from preparing bodies for cryopreservation on its own, because applying such procedures to a dead body required the services of a licensed funeral director.

The cryonics industry flatly disagrees with its critics.

Alcor asserts on its website that "[t]here are no known credible technical arguments that lead one to conclude that cryonics, carried out under good conditions today, would not work." The company adds: "Cryonics is a belief that no one is really dead until the information content of the brain is lost, and that low temperatures can prevent this loss."

Related: How Computers are Learning to Predict the Future

Certainly the controversies have not discouraged candidates for cryopreservation.

Worldwide, more than 250 individuals are now housed in cryonic facilities, at a minimum per-person cost of about $28,000 in the U.S.

Russia's KrioRus company offers a cut-rate level starting at $12,000, with the condition that it stores several human bodies and assorted pets and other animals in communal Dewar containers. Individual contracts can specify the length of storage. At present, the U.S. and Russia are the only countries with facilities that offer human cryopreservation.

The first attempt at cryopreservation did not go particularly smoothly.

Bedford died before all preparations for his cryopreservation were complete. So instead of draining his blood and replacing it with a customized antifreeze solution to protect the body's tissues from freezing damage, the team simply injected the antifreeze into Bedford's arteries without removing the blood.

The team then surrounded the body in dry ice, and started it on a series of transfers from one container to another that ended up in a Dewar container in Alcor's facility.

Because of those difficulties, cryonics experts feared that the body had suffered serious damage. But the examination in 1991 quelled those concerns.

"We were really relieved that he was not discolored," Perry recalled. "And corners of the ice cubes [around him] were still sharp; he had stayed frozen all the time."

Related: The Hunt For Alien Megastructures Is On

In recent years, cryonics promoters have borrowed from medical advances in such fields as cryobiology and nanobiology.

To prevent ice crystals from damaging cell walls in the frozen state, cryopreservationists replace the body's blood supply with mixtures of antifreeze compounds and organ preservatives a technique developed to preserve frozen eggs for fertility treatments.

Another emerging approach accounts for the separation of Ted Williams' head and body. Based on studies of roundworms, promoters of cryonics argue that freezing can preserve the contents of individuals' brains even if their bodies can't be revived. That opens the possibility of downloading cryopreserved personalities into a robotic future body.

Hendricks disagrees. "While it may be possible to preserve these features in dead tissue, that is certainly not happening now," he pointed out in Technology Review.

Scientists such as Barry Fuller, a professor of surgical science and low temperature medicine at England's University College, London, emphasize that even preserving body parts in such a way that they remain viable on thawing remains a distant dream.

"There is ongoing research into these scientific challenges, and a potential future demonstration of the ability to cryopreserve human organs for transplantation would be a major first step into proving the concept," he told The Guardian. "But at the moment we cannot achieve that."

Nevertheless, Perry expresses optimism about a timeline for the revival of frozen humans.

"We think in terms of decades," he said. "Sometimes we say fifty to a hundred years."

David Gorski, a surgeon at Wayne State University Medical Center in Michigan, takes a darker view.

"Fifty years from now," he said, "it's likely that all that will remain of my existence will be some scientific papers and a faint memory held by my nieces and nephews and maybe, if I'm lucky, a few of my youngest readers."

Reprinted with permission from Inside Science, an editorially independent news product of the American Institute of Physics, a nonprofit organization dedicated to advancing, promoting and serving the physical sciences.

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Here's How Far Cryonic Preservation Has Come in the 50 ...

InForGrowth Market Research offers a most recent distributed report on Global Cryonics Technology industry examination and figure 2019-2025 conveying key bits of knowledge and giving an upper hand to customers through a point by point report. The report contains XX pages which profoundly displays on current market investigation situation, up and coming just as future chances, income development, evaluating and gainfulness. The Global pandemic of COVID19 calls for redefining of business strategies. This Cryonics Technology Market report includes the impact analysis necessary for the same

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Worldwide Cryonics Technology Market inspect reports consolidate market designs nuances, genuine scene, feature assessment, cost structure, capability, bargains, net advantage, and movement and measuring of business.

Major Key players covered in this report:Praxair, Cellulis, Cryologics, Cryotherm, KrioRus, VWR, Thermo Fisher Scientific, Custom Biogenic Systems, Oregon Cryonics, Alcor Life Extension Foundation, Osiris Cryonics, Sigma-Aldrich, Southern Cryonics.

Cryonics Technology Market Potential

The overall market is set up for energetic advancement with progressively moving of various gathering methodology to more affordable objectives in rising economies. Another factor booked to altogether bolster the market is fused programming game plans disposing of the prerequisite for different models and thing survey concerns.Premium Insights on Cryonics Technology Market 2020 with Market Players Positioning; Download Free Sample Copy: https://inforgrowth.com/sample-request/5557682/cryonics-technology-market

The Worldwide Market forGlobal Cryonics Technology marketis relied upon to develop at a CAGR of generally xx% throughout the following five years, will arrive at xx million US$ in 2026, from xx million US$ in 2019, as per another research.

This report focuses around the Cryonics Technology Market in the worldwide market, particularly in North America, Europe and Asia-Pacific, South America, Middle East, and Africa. This Cryonics Technology Market report sorts the market dependent on the manufacturer, region, type, and application.

Major Classifications of Cryonics Technology Market:

By Product Type: Slow freezing, Vitrification, Ultra-rapid

By Applications: Animal husbandry, Fishery science, Medical science, Preservation of microbiology culture, Conserving plant biodiversity

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Regional Analysis of Cryonics Technology Market:

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FOR ALL YOUR RESEARCH NEEDS, REACH OUT TO US AT:Address: 6400 Village Pkwy suite # 104, Dublin, CA 94568, USAContact Name: Rohan S.Email:[emailprotected]Phone: +1-909-329-2808UK: +44 (203) 743 1898Website: http://www.inforgrowth.com

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Latest Update 2020: Cryonics Technology Market by COVID19 Impact Analysis And Top Manufacturers: Praxair, Cellulis, Cryologics, Cryotherm, KrioRus,...

Ted Williams was one of the greatest hitters in MLB history. The two-time Triple Crown winner and 17-time All-Star remains the last batter to finish a season with an average above .400. Sadly, since the Hall of Famer died in July 2002, his name is associated more with the things done to his body after death than his innumerable baseball accomplishments. Why was Ted Williams decapitated after his death?

The list of accomplishments in Ted Williams 19-year career is long. He won six batting titles and led the American League in home runs and RBIs four times. In 1941, the 22-year-old Williams hit .406 for the season and that included 37 home runs and 120 RBIs. He was the last hitter to ever hit above .400.

Williams followed up in 1942 with another stellar performance becoming the first-ever player to win the Triple Crown leading the league with a .356 average, hitting 36 homers, and driving in 137 RBIs. Unbelievably, he finished second in MVP voting that season.

After three years of military service in World War II, Williams returned to baseball and resumed right where he left off. He finished the 1946 season with a .342 average and won the first of two MVPs in his career. He also played in his only World Series that season. He won the Triple Crown for a second time in 1947 and retired in 1960 with a lifetime average of .344.

Williams was inducted into the Baseball Hall of Fame in 1966.

When Ted Williams died in Florida on July 5, 2002 at age 83, things got weird fast. Despite his wishes to be cremated and his ashes scattered in the Florida Keys, his son John Henry and youngest daughter Claudia opted to have his body sent to Scottsdale, Arizona to be frozen at the Alcor cryonics facility.

Cryonics is a process done with the hope that someday scientists will be able to bring the subjects back to life. The heads and bodies are stored in stainless steel containers at extremely cold temperatures.

When Williams oldest daughter, Bobby-Jo Ferrell learned about the plan of her siblings, she sued. John Henrys lawyer produced a family pact signed by Ted, Claudia, and John Henry, where the three agreed to be placed into biostasis after death. While there was legal wrangling back and forth between the siblings questioning the authenticity of Williams signature, Ferrell eventually dropped her lawsuit due to a lack of funds.

Several months later his death made headlines for a second time when it was discovered that Williams head had been decapitated by surgeons and stored separately from his body at the Alcor facility.

In 2009, the bizarre circumstances of the Splendid Splinters death and actions that followed took an even stranger twist with the release of a book from a former Alcor employee. In Larry Johnsons book Frozen: My Journey Into the World of Cryonics, Deception and Death, he offered up details on how employees at Alcor allegedly mistreated the Hall of Famers body.

Johnson wrote in one incident where an empty tuna can was used as a pedestal to support the batters head and had stuck to it during transportation from one container to another. An Alcor employee allegedly decided to use a monkey wrench in an attempt to dislodge the can from the head.

Then he grabbed a monkey wrench, heaved a mighty swing, missing the tuna can completely but hitting the head dead center, Johnson wrote. Tiny pieces of frozen head sprayed around the room. The author detailed how a second swing knocked the can loose.

Alcor denied all allegations that there was any mistreatment of Ted Williams. John Henry died just two years later in 2004 from leukemia. His body was transported to Alcor.

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Why Was Baseball Hall of Famer Ted Williams Decapitated? - Sportscasting

DALLAS, May 12, 2020 /PRNewswire/ --Jacobs (NYSE:J) was selected by Radioactive Waste Management Ltd (RWM), a subsidiary of the U.K. Government's Nuclear Decommissioning Authority, to study the release of radioactivity from irradiated graphite sampled from reactor cores at the U.K.'s nuclear power stations. This research will support RWM in their analysis of graphite behavior and the options for graphite waste management in the future.

"We're combining our leading graphite knowledge from our Integrated Waste Management team at Harwell, our role as designer and architect engineer of the Advanced Gas Reactor (AGR) and Magnox reactors, and our work on operational support and life extension," said Jacobs Critical Mission Solutions Senior Vice President Clive White. "Our Technology and Innovation Centre at Birchwood Park, Warrington, is applying this graphite knowledge to work through options for safe and timely characterization, retrieval, treatment and storage solutions to meet the growing global decommissioning market."

RWM has commissioned Jacobs to measure and characterize releases of the radioactive isotope carbon-14 and compare it with releases from irradiated graphite in earlier reactor types, including the U.K.'s first generation of Magnox civil nuclear power stations.

This research will have a significant bearing on the safe management and disposal of graphite wastes arising from the decommissioning of 14 advanced gas-cooled reactors (AGR), which generate nearly 20% of the country's electricity but are due to be phased out over the next 10 years.

The contract has an initial duration of two years. Subject to experimental program results, it may be extended by an additional two years.

At Jacobs, we're challenging today to reinvent tomorrow by solving the world's most critical problems for thriving cities, resilient environments, mission-critical outcomes, operational advancement, scientific discovery and cutting-edge manufacturing, turning abstract ideas into realities that transform the world for good. With $13 billion in revenue and a talent force of more than 55,000, Jacobs provides a full spectrum of professional services including consulting, technical, scientific and project delivery for the government and private sector. Visitjacobs.comand connect with Jacobs on Facebook, Instagram,LinkedInand Twitter.

Certain statements contained in this press release constitute forward-looking statements as such term is defined in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such statements are intended to be covered by the safe harbor provided by the same. Statements made in this release that are not based on historical fact are forward-looking statements. We base these forward-looking statements on management's current estimates and expectations as well as currently available competitive, financial and economic data. Forward-looking statements, however, are inherently uncertain. There are a variety of factors that could cause business results to differ materially from our forward-looking statements. For a description of some additional factors that may occur that could cause actual results to differ from our forward-looking statements see our Annual Report on Form 10-K for the year ended September 27, 2019, and in particular the discussions contained under Item 1 - Business; Item 1A - Risk Factors; Item 3 - Legal Proceedings; and Item 7 - Management's Discussion and Analysis of Financial Condition and Results of Operations, as well as the Company's other filings with the Securities and Exchange Commission. The Company is not under any duty to update any of the forward-looking statements after the date of this press release to conform to actual results, except as required by applicable law.

For press/media inquiries:Kerrie Sparks214.583.8433

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Jacobs Selected by Radioactive Waste Management Ltd to Study Radioactivity in Graphite Nuclear Reactor Cores - Tyler Morning Telegraph

Back in the pre-pandemic era, I was really looking forward to April 8. On that date,Carl Zimmerwas going to give a talk at my school, Stevens Institute of Technology, about his latest book,She Has Her Mothers Laugh. For decades, Zimmer has reported on biology in The New York Times and other publications and in books,13 so far.Mothers Laughtells the epic tale of our attempts to plumb the mysteries of heredity and to improve ourselves with that knowledge. The book is a marvelous work of historyZimmers account of the early days of eugenics in the U.S. is especially grippingas well as a detailed, up-to-date report on CRISPR and other advances that add urgency to old debates about human enhancement. Zimmer is an engaging story-teller and insatiable reporter, who visits scientists in their labs and even volunteers to be a subject. As a result, while discussing the remarkable diversity of creatures dwelling on and in our bodies, he can tell you that his own bellybutton harbors a bacterium,Marimonas, also found in the Mariana Trench. In lieu of Carls April 8 talk, here he answers questions about genetics and related topics. John Horgan

Horgan:How did you end up in the science-writing racket, anyway? Any regrets?

Zimmer:I feel incredibly lucky to have this job. It wasn't anything I thought about with any foresight. I loved to write, and I loved science. A couple years out of college, I got a job as an assistant copy editor at the science magazineDiscover. There, I got a great training in how to fact-check and report on science. I stayed there for ten years before heading out on my own.

Horgan:Why the focus on biology? When you started out, wasnt physics going to solve everything?

Zimmer:As a junior reporter atDiscover, I had to write about all sorts of stuff--astronomy, geoscience, physics, technology, and so on. But I found that biology was always the field that managed to surprise me the most. Evolution has gone off in such crazy directions in the past four billion years, and the tools biologists have to study life have grown incredibly powerful over the past few decades.

Horgan:I sometimes worry Im too mean to scientists. Do you ever worry youre too nice?

Zimmer:As a fact-checker, you learn that no one should be given a pass. When I report on a story, I talk with outside experts to see if researchers I'm writing about are really delivering on what they claim. And it's also important to keep up with what social scientists and philosophers have to say--because science doesn't happen in a vacuum and can have dangerous consequences.

Horgan:Whats the biggest thing thats happened in science since you started writing about it?

Zimmer:DNA sequencing. It changed everything, from the study of Neanderthals to tracking the covid-19 pandemic.

Horgan:In 2009you quit the online chat show Bloggingheads.tv, on whichwe once spoke, because it gave a platform to creationists. Have your feelings about creationism evolved over the past decade?

Zimmer:No. Creationists have not done any good science since then, while evolutionary biology has leapt forward in dramatic fashion.

Horgan:Whenever I criticize scientificracism, orsexism, people call me an unscientific social justice warrior. I knowthis happens to you, too. How do you deal with these people?

Zimmer:People try to deflect from weak arguments by accusing their opponents of being contemptible.

Horgan:Is CRISPR living up to its hype? If so, will it help gene therapy, finally, take off?

Zimmer:CRISPR is already a mainstay of scientific research, for testing how genes work and how mutations affect health. It's already into clinical trials for diseases like sickle cell anemia just few years after its invention. We have yet to see how well it will work in those applications. But it's unquestionably one of the most important advances in the history of biology.

Horgan:By the time I reached the end ofShe Has Her Mothers Laugh, I wasnt sure whether you think genetic enhancement of humans is feasible, or desirable. Could you clarify?

Zimmer:I think anyone who pretends to have a simple answer is wrong. The answer depends not only on the complexity of biology, but also on what we really want from genetic enhancement. We are already carrying out genetic enhancement when parents with Huntington's disease pick embryos for IVF without the mutation. But I'm skeptical that any manipulation will affect, say, intelligence--certainly not more than what a decent education and a healthy childhood can offer.

Horgan:Will there be any more revolutions in our understanding of heredity?

Zimmer:It's not possible to predict revolutions that haven't happened. But I think that scientists will learn a lot about how epigenetic changes can be carried down through generations--if not in humans, then in other animals and plants.

Horgan:Will our knowledge ever be so complete that the nature/debate finally ends?

Zimmer:I can't rule it out, but it won't be easy. It's relatively easy to study how genes influence variation, but the environment is so vast and complex it may not submit to simple experiments with clear results. Still, there are some very impressive experiments that are grappling with these challenges.

Horgan:Are radical life extension, and possibly immortality, feasible?

Zimmer:I'm not holding my breath. Aging is the result of so many factors that it's hard to see how any simple intervention can change it much. Immortality just seems biologically silly to me.

Horgan:I cant resist asking: what do you think of the U.S. response to the coronavirus?

Zimmer:A disaster.

Further Reading:

Was Darwin Wrong?

How Can We Curb the Spread of Scientific Racism?

Should Research on Race and IQ Be Banned?

My Problem with Taboo Behavioral Genetics? The Science Stinks!

Quest for Intelligence Genes Turns Out More Dubious Results

Have Researchers Really Discovered Any Genes for Behavior?

Defending Stephen Jay Goulds Crusade Against Biological Determinism

Darwin Was Sexist, and So Are Many Modern Scientists

Do Women Want to be Oppressed?

Google Engineer Fired for Sexist Memo Isnt a Hero

See also my free, online bookMind-Body Problems: Science, Subjectivity & Who We Really Are, also available as a Kindle e-book and paperback.

Go here to read the rest:
Will the Nature/Nurture Debate Ever End? - Scientific American

Global Cryonics Technology Market 2020 to 2026, is a comprehensive report which provides a detailed overview of the major driver, opportunities, challenges, current market trends and strategies impacting the global Cryonics Technology market in conjunction with calculation and forecast of size, share, and growth rate analysis. Combining the analysis capabilities and knowledge integration with the relevant findings, the report has foretold the robust future growth of the Cryonics Technology market all told its geographical and merchandise segments.

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Key Players of the Global Cryonics Technology Market

Praxair, Cellulis, Cryologics, Cryotherm, KrioRus, VWR, Thermo Fisher Scientific, Custom Biogenic Systems, Oregon Cryonics, Alcor Life Extension Foundation, Osiris Cryonics, Sigma-Aldrich, Southern Cryonics.

Segmentation by product type

Slow freezingVitrificationUltra-rapid

Segmentation by application

Animal husbandryFishery scienceMedical sciencePreservation of microbiology cultureConserving plant biodiversity

Market Segment by Regions, regional analysis covers 2019-2025:

North America(United States, Canada and Mexico)Europe(Germany, France, UK, Russia and Italy)Asia-Pacific(China, Japan, Korea, India and Southeast Asia)South America(Brazil, Argentina, Colombia etc.)Middle East and Africa(Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

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Market Overview:The report begins with this section where product overview and highlights of product and application segments of the global Cryonics Technology Market are provided. Highlights of the segmentation study include price, revenue, sales, sales growth rate, and market share by product.

Competition by Company:Here, the competition in the global Cryonics Technology Market is analyzed, taking into consideration price, revenue, sales, and market share by company, market concentration rate, competitive situations and trends, expansion, merger and acquisition, and market shares of top 5 and 10 companies.

Company Profiles and Sales Data:As the name suggests, this section gives the sales data of key players of the global Cryonics Technology Market as well as some useful information on their business. It talks about the gross margin, price, revenue, products and their specifications, applications, competitors, Manufacturing base, and the main business of players operating in the global Cryonics Technology Market.

Market Status and Outlook by Region:In this section, the report discusses about gross margin, sales, revenue, production, market share, CAGR, and market size by region. Here, the global Cryonics Technology Market is deeply analyzed on the basis of regions and countries such as North America, Europe, China, India, Japan, and the MEA.

Application or End User:This part of the research study shows how different application segments contribute to the global Cryonics Technology Market.

Market Forecast:Here, the report offers complete forecast of the global Cryonics Technology Market by product, application, and region. It also offers global sales and revenue forecast for all years of the forecast period.

Research Findings and Conclusion:This is one of the last sections of the report where the findings of the analysts and the conclusion of the research study are provided.

Appendix:Here, we have provided a disclaimer, our data sources, data triangulation, market breakdown, research programs and design, and our research approach.

The research includes historic data from 2015 to 2020 and forecasts until 2026 which makes the reports an invaluable resource for industry executives, marketing, sales and product managers, consultants, analysts, and other people looking for key industry data in readily accessible documents with clearly presented tables and graphs.

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Research Report, Growth Trends and Competitive Analysis 2020-2026 Cole Reports - Cole of Duty

The Department of Defense has begun to ratchet up spending to recapitalize the U.S. strategic nuclear triad and its supporting infrastructure, as several programs move from research and development into the procurement phase. The projected Pentagon expenditures are at least $167 billion from 2021-2025. This amount does not include the large nuclear warhead sustainment and modernization costs funded by the Department of Energy, projected to cost $81 billion over the next five years.

Nuclear forces require modernization, but that will entail opportunity costs.In a budget environment that offers little prospect of greater defense spending, especially in the COVID19 era, more money for nuclear forces will mean less funding for conventional capabilities.

That has potentially negative consequences for the security of the United States and its allies.While nuclear forces provide day-to-day deterrence, the Pentagon leadership spends most of its time thinking about how to employ conventional forces to manage security challenges around the world.The renewed focus on great power competition further elevates the importance of conventional forces.It is important to get the balance between nuclear and conventional forces right, particularly as the most likely path to use of nuclear arms would be an escalation of a conventional conflict.Having robust conventional forces to prevail in or deter a conventional conflict in the first place could avert a nuclear crisis or worse.

Nuclear Weapons and Budgets

For the foreseeable future, the United States will continue to rely on nuclear deterrence for its security and that of its allies (whether we should be comfortable with that prospect is another question).Many U.S. nuclear weapons systems are aging, and replacing them will cost money, lots of money.The Pentagons five-year plan for its nuclear weapons programs proposes $29 billion in fiscal year 2021, rising to $38 billion in fiscal year 2025, as programs move from research and development to procurement.The plan envisages a total of $167 billion over five years.And that total may be understated; weapons costs increase not just as they move to the procurement phase, but as cost overruns and other issues drive the costs up compared to earlier projections.

The Pentagon knew that the procurement bow wave of nuclear weapons spending would hit in the 2020s and that funding it would pose a challenge.In October 2015, the principal deputy undersecretary of defense said Were looking at that big bow wave and wondering how the heck were going to pay for it and probably thanking our stars that we wont be here to have to answer the question.

The Pentagons funding request for fiscal year 2021 includes $4.4 billion for the new Columbia-class ballistic missile submarine that will replace Ohio-class submarines, which will begin to be retired at the end of the decade; $1.2 billion for the life extension program for the Trident II submarine-launched ballistic missile (SLBM); $1.5 billion for the Ground Based Strategic Deterrent, an intercontinental ballistic missile (ICBM) to replace the Minuteman III ICBM; $2.8 billion for the B-21 stealth bomber that will replace the B-1 and B-2 bombers; $500 million for the Long-Range Standoff Missile that will arm B-52 and B-21 bombers; and $7 billion for nuclear command, control and communications systems.

The Pentagon funds primarily go to delivery and command and control systems for nuclear weapons.The National Nuclear Security Administration at the Department of Energy bears the costs of the warheads themselves. It seeks $15.6 billion for five nuclear warhead life-extension and other infrastructure programs in fiscal year 2021, the first year of a five-year plan totaling $81 billion.The fiscal year 2021 request is nearly $3 billion more than the agency had earlier planned to ask, which suggests these programs are encountering significant cost growth.

Some look at these figures and the overall defense budget (the Pentagon wants a total of $740 billion for fiscal year 2021) and calculate that the cost of building and operating U.S. nuclear forces will amount to only 6-7 percent of the defense budget.That may be true, but how relevant is that figure?

By one estimate, the cost of building and operating the F-35 fighter program for the U.S. Air Force, U.S. Navy and U.S. Marines over the programs lifetime will be $1 trillion.Amortized over 50 years, that amounts to $20 billion per year or only 2.7 percent of the Defense Departments fiscal year 2021 budget request.The problem is that these percentages and lots of other small percentages add up.When one includes all of the programs, plus personnel and readiness costs as well as everything else that the Pentagon wants, the percentages will total to more than 100 percent of the figure that Congress is prepared to appropriate for defense.

Opportunity Costs

The defense budget is unlikely to grow.Opportunity costs represent the things the Pentagon has to give up or forgo in order to fund its nuclear weapons programs.The military services gave an indication of these costs with their unfunded priorities lists, which this year total $18 billion.These show what the services would like to buy if they had additional funds, and that includes a lot of conventional weapons.

The Air Force, for example, would like to procure an additional twelve F-35 fighters as well as fund advance procurement for an additional twelve F-35s in fiscal year 2022.It would also like to buy three more tanker aircraft than budgeted.

The Army is reorienting from counter-insurgency operations in places such as Afghanistan and Iraq to facing off against major peer competitors, that is, Russia and China.Its wish list includes more long-range precision fires (artillery and short-range surface-to-surface missiles), a new combat vehicle, helicopters and more air and missile defense systems.

The Navy would like to add five F-35s to its aircraft buy, but its bigger desire is more attack submarines and warships, given its target of building up to a fleet of 355 ships. The Navy termed a second Virginia-class attack submarine its top unfunded priority in fiscal year 2021.It has set a requirement for 66 attack submarines and currently has about 50.However, as older Los Angeles-class submarines retire, that number could fall to 42. Forgoing construction of a Virginia-class submarine does not help to close that gap.

Moreover, the total number of Navy ships, now 293, will decline in the near term, widening the gap to get to 355.The Navys five-year shipbuilding program cut five of twelve planned Arleigh Burke-class destroyers, and cost considerations have led the Navy to decide to retire ten older Burke-class destroyers rather than extend their service life for an additional ten years.This comes when China is rapidly expanding its navy, and Russian attack submarines are returning on a more regular cycle to the Atlantic Ocean.

The Navy has said that funding the first Columbia-class ballistic missile submarine forced a cut-back in the number of other ships in its fiscal 2021 shipbuilding request.The decision not to fund a second Virginia-class attack submarine appears to stem directly from the unexpected $3 billion plus-up in funding for the National Nuclear Security Administrations fiscal year 2021 programs.

These are the opportunity costs of more nuclear weapons:fewer dollars for aircraft, ships, attack submarines and ground combat equipment for conventional deterrence and defense.

Nuclear War and Deterring Conventional Conflict

The principal driving factor behind the size of U.S. nuclear forces comes from Russian nuclear forces and doctrine.Diverse and effective U.S. nuclear forces that can deter a Russian nuclear attack should suffice to deter a nuclear attack by any third country.In contrast to the Cold War, the U.S. military no longer seems to worry much about a bolt from the bluea sudden Soviet or Russian first strike involving a massive number of nuclear weapons designed to destroy the bulk of U.S. strategic forces before they could launch.That is because, under any conceivable scenario, sufficient U.S. strategic forcesprincipally on ballistic missile submarines at seawould survive to inflict a devastating retaliatory response.

The most likely scenario for nuclear use between the United States and Russia is a regional conflict fought at the conventional level in which one side begins to lose and decides to escalate by employing a small number of low-yield nuclear weapons, seeking to reverse battlefield losses and signal the strength of its resolve.Questions thus have arisen about whether Russia has an escalate-to-deescalate doctrine and whether the 2018 U.S. nuclear posture review lowers the threshold for use of nuclear weapons.

If the United States and its allies have sufficiently robust conventional forces, they can prevail in a regional conflict at the conventional level and push any decision about first use of nuclear weapons onto the other side (Russia, or perhaps China or North Korea depending on the scenario).The other side would have to weigh carefully the likelihood that its first use of nuclear weapons would trigger a nuclear response, opening the decidedly grim prospect of further nuclear escalation and of things spinning out of control.The other sides leader might calculate that he/she could control the escalation, but that gamble would come with no guarantee. It would appear a poor bet given the enormous consequences if things go wrong.Happily, the test has never been run.

This is why the opportunity costs of nuclear weapons programs matter.If those programs strip too much funding from conventional forces, they weaken the ability of the United States and its allies to prevail in a conventional conflictor to deter that conflict in the first placeand increase the possibility that the United States might have to employ nuclear weapons to avert defeat.

Read the original:
Weapons, Opportunity Costs, COVID19 and Avoiding Nuclear War - The National Interest

Adeles significant slim down has been credited to a combination of exercise and eating sirtfoods. So what is the sirt diet and could it work for you?

COVID-19 may still be daily overwhelming the internet, but for a few hours last week all the talk on social mediturned to just how singer Adele could havelost so much weight.

And the answer? Apparently (allegedly) shes been following the sirtfood diet, detailed in a book of the same name written by Aidan Goggins and Glen Matten.

The sirt in sirtfood stands for sirtuins a group of genes and the proteins they encode that play a key role in cellular homeostasis. Sirtuins have been implicated in the stress response, DNA repair and energy metabolism, but the area where they've whipped up more scientific interest (and hype) than any other isin relation to extending lifespan.

The finding that sirtuins were linked to longevity in yeast led to an explosion of research that has yielded ambiguous results. There have been some signs of life extension and improved long-term health, including an anti-diabetic potential in laboratory animals, but nothing thats been reliably shown to extend life in mammals.

The central tenet of the sirtfood diet is that eating certain polyphenol-rich foods red wine and dark chocolate are frequently citedas examples to make the diet seem sexier can stimulate sirtuins (coined your skinny genes by the authors) and create weight loss.

Activating sirtuins through diet is an intriguing theory, but theres little evidence to support it, and even less evidence that doing so would lead to significant weight loss in practice.

The diet promises a weight loss of 7 pounds in 7 days and that longer-term you will improve your resistance to disease while gaining incredible energy and glowing health.

If you dont gnaw off your arm in hunger before you get slim that is.

Phase one of the diet is three miserable days of consuming just 1000 calories including three green juices, followed by four more days when youre permitted 1500 calories but still have to gag on drink green juice.

Phase two lasts for two weeks and isn't a whole lot more appealing, while longer-term you have to continue consuming the same list of foods repeatedly.

Polyphenol-rich food such as apples and citrus, green leafy vegetables, berries and olive oil are all perfectly healthy but having to focus on them at every meal is faddish and restrictive.

And thats the real reason the sirt diet works for those that do stick to it despite sounding seductively sciencey the restraints mean its just another not-particularly-well-disguised route to cutting calories.

If it works for you and it worked for Adele, then great. But lets not pretend sirt diet success stories are down to anything other than eating less.

Excerpt from:
Eat Like a Bird and Weight Loss Will Be a Dead Sirt - American Council on Science and Health

The exploration drive approval allows for development within a nominated corridor as it is recognised that the exact location will vary as the mineralisation is further identified.

Alkane Resources Limited () has received approval from the NSW Government Resources Regulator to develop an exploration drive from theexisting Wyoming One underground operations at Tomingley Gold Project to Roswell and San Antonio deposits, around four kilometres to the south.

The company believes this is an important milestone towards a future potential underground mine at Roswell and San Antonio that could be developed independently of an open cut operation.

While being an exploration drive, itwill be sized such that it could also accommodate production in the future.

Alkane managing director Nic Earner said: Alkane has the equipment purchased, personnel recruited and land acquired to allow this development to proceed and we will now incorporate the timing of the drive development into the Tomingley Gold Operations budget schedules, as well as our regional exploration plans.

Given the prospectivity of the region around our existing operations, this approval provides Alkane with all the exploration and, in time, production options, to extend the life of mine at Tomingley well into the future.

The Tomingley Gold Project (TGP) in Central West NSW contains Alkanes Tomingley Gold Operations (TGO), an open pit mine with a 1 million tonnes per annum processing facility that is transitioning to underground.

Over the past two years, Alkane has conducted an extensive regional exploration program around the TGP with the objective of defining additional resources that have the potential to be mined either via open pit or underground operations and fed to the TGO processing facility.

Thisprogram has yielded broad, shallow, high-grade intercepts that demonstrate potential for material project life extension in excess of 10 years, and show that a return to open pit mining and/or underground extension is possible with appropriate resource confirmation, landholder agreement and regulatory approvals.

The drive is conceptual in nature to allow visualisation of the potential development.

At both the Roswell and San Antonio prospects, inferred resources have been defined of 7.02 million tonnes at 1.97 g/t gold for 445,000 ounces and 7.92 million tonnes at 1.78 g/t for 453,000 ounces respectively.

The resources are now being prepared into conceptual mine plans that can be used to progress NSW Government mining approvals.

Development of the underground exploration drive will allowdrilling positions, bulk-samplingand assessment of the corridor between the existing operations, as the Roswell and San Antonio deposits are not as readily accessible from surface.

Visit link:
Alkane Resources gets green light for underground exploration drive to reach new gold deposits - Proactive Investors Australia

Complete study of the global Reishi Mushroom Supplements market is carried out by the analysts in this report, taking into consideration key factors like drivers, challenges, recent trends, opportunities, advancements, and competitive landscape. This report offers a clear understanding of the present as well as future scenario of the global Reishi Mushroom Supplements industry. Research techniques like PESTLE and Porters Five Forces analysis have been deployed by the researchers. They have also provided accurate data on Reishi Mushroom Supplements production, capacity, price, cost, margin, and revenue to help the players gain a clear understanding into the overall existing and future market situation.

Key companies operating in the global Reishi Mushroom Supplements market include ,Natures Way Reishi,Solaray Reishi Mushroom,Life Extension Reishi Extract,Host Defense Reishi,Terrasoul Superfoods,Swanson Reishi Mushroom,Aloha Medicinals,Mushroom Science,Planetary Herbals

Get PDF Sample Copy of the Report to understand the structure of the complete report: (Including Full TOC, List of Tables & Figures, Chart) :

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Segmental Analysis

The report has classified the global Reishi Mushroom Supplements industry into segments including product type and application. Every segment is evaluated based on growth rate and share. Besides, the analysts have studied the potential regions that may prove rewarding for the Reishi Mushroom Supplements manufcaturers in the coming years. The regional analysis includes reliable predictions on value and volume, thereby helping market players to gain deep insights into the overall Reishi Mushroom Supplements industry.

Global Reishi Mushroom Supplements Market Segment By Type:

,Organic Reishi Mushroom Supplements,Inorganic Reishi Mushroom Supplements Reishi Mushroom Supplements

Global Reishi Mushroom Supplements Market Segment By Application:

,Online Sales,Offline Sales

Competitive Landscape

It is important for every market participant to be familiar with the competitive scenario in the global Reishi Mushroom Supplements industry. In order to fulfil the requirements, the industry analysts have evaluated the strategic activities of the competitors to help the key players strengthen their foothold in the market and increase their competitiveness.

Key companies operating in the global Reishi Mushroom Supplements market include ,Natures Way Reishi,Solaray Reishi Mushroom,Life Extension Reishi Extract,Host Defense Reishi,Terrasoul Superfoods,Swanson Reishi Mushroom,Aloha Medicinals,Mushroom Science,Planetary Herbals

Key questions answered in the report:

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TOC

1 Study Coverage1.1 Reishi Mushroom Supplements Product Introduction1.2 Market Segments1.3 Key Reishi Mushroom Supplements Manufacturers Covered: Ranking by Revenue1.4 Market by Type1.4.1 Global Reishi Mushroom Supplements Market Size Growth Rate by Type1.4.2 Organic Reishi Mushroom Supplements1.4.3 Inorganic Reishi Mushroom Supplements1.5 Market by Application1.5.1 Global Reishi Mushroom Supplements Market Size Growth Rate by Application1.5.2 Online Sales1.5.3 Offline Sales1.6 Coronavirus Disease 2019 (Covid-19): Reishi Mushroom Supplements Industry Impact1.6.1 How the Covid-19 is Affecting the Reishi Mushroom Supplements Industry

1.6.1.1 Reishi Mushroom Supplements Business Impact Assessment Covid-19

1.6.1.2 Supply Chain Challenges

1.6.1.3 COVID-19s Impact On Crude Oil and Refined Products1.6.2 Market Trends and Reishi Mushroom Supplements Potential Opportunities in the COVID-19 Landscape1.6.3 Measures / Proposal against Covid-19

1.6.3.1 Government Measures to Combat Covid-19 Impact

1.6.3.2 Proposal for Reishi Mushroom Supplements Players to Combat Covid-19 Impact1.7 Study Objectives1.8 Years Considered 2 Executive Summary2.1 Global Reishi Mushroom Supplements Market Size Estimates and Forecasts2.1.1 Global Reishi Mushroom Supplements Revenue 2015-20262.1.2 Global Reishi Mushroom Supplements Sales 2015-20262.2 Reishi Mushroom Supplements Market Size by Region: 2020 Versus 20262.2.1 Global Reishi Mushroom Supplements Retrospective Market Scenario in Sales by Region: 2015-20202.2.2 Global Reishi Mushroom Supplements Retrospective Market Scenario in Revenue by Region: 2015-2020 3 Global Reishi Mushroom Supplements Competitor Landscape by Players3.1 Reishi Mushroom Supplements Sales by Manufacturers3.1.1 Reishi Mushroom Supplements Sales by Manufacturers (2015-2020)3.1.2 Reishi Mushroom Supplements Sales Market Share by Manufacturers (2015-2020)3.2 Reishi Mushroom Supplements Revenue by Manufacturers3.2.1 Reishi Mushroom Supplements Revenue by Manufacturers (2015-2020)3.2.2 Reishi Mushroom Supplements Revenue Share by Manufacturers (2015-2020)3.2.3 Global Reishi Mushroom Supplements Market Concentration Ratio (CR5 and HHI) (2015-2020)3.2.4 Global Top 10 and Top 5 Companies by Reishi Mushroom Supplements Revenue in 20193.2.5 Global Reishi Mushroom Supplements Market Share by Company Type (Tier 1, Tier 2 and Tier 3)3.3 Reishi Mushroom Supplements Price by Manufacturers3.4 Reishi Mushroom Supplements Manufacturing Base Distribution, Product Types3.4.1 Reishi Mushroom Supplements Manufacturers Manufacturing Base Distribution, Headquarters3.4.2 Manufacturers Reishi Mushroom Supplements Product Type3.4.3 Date of International Manufacturers Enter into Reishi Mushroom Supplements Market3.5 Manufacturers Mergers & Acquisitions, Expansion Plans 4 Breakdown Data by Type (2015-2026)4.1 Global Reishi Mushroom Supplements Market Size by Type (2015-2020)4.1.1 Global Reishi Mushroom Supplements Sales by Type (2015-2020)4.1.2 Global Reishi Mushroom Supplements Revenue by Type (2015-2020)4.1.3 Reishi Mushroom Supplements Average Selling Price (ASP) by Type (2015-2026)4.2 Global Reishi Mushroom Supplements Market Size Forecast by Type (2021-2026)4.2.1 Global Reishi Mushroom Supplements Sales Forecast by Type (2021-2026)4.2.2 Global Reishi Mushroom Supplements Revenue Forecast by Type (2021-2026)4.2.3 Reishi Mushroom Supplements Average Selling Price (ASP) Forecast by Type (2021-2026)4.3 Global Reishi Mushroom Supplements Market Share by Price Tier (2015-2020): Low-End, Mid-Range and High-End 5 Breakdown Data by Application (2015-2026)5.1 Global Reishi Mushroom Supplements Market Size by Application (2015-2020)5.1.1 Global Reishi Mushroom Supplements Sales by Application (2015-2020)5.1.2 Global Reishi Mushroom Supplements Revenue by Application (2015-2020)5.1.3 Reishi Mushroom Supplements Price by Application (2015-2020)5.2 Reishi Mushroom Supplements Market Size Forecast by Application (2021-2026)5.2.1 Global Reishi Mushroom Supplements Sales Forecast by Application (2021-2026)5.2.2 Global Reishi Mushroom Supplements Revenue Forecast by Application (2021-2026)5.2.3 Global Reishi Mushroom Supplements Price Forecast by Application (2021-2026) 6 North America6.1 North America Reishi Mushroom Supplements by Country6.1.1 North America Reishi Mushroom Supplements Sales by Country6.1.2 North America Reishi Mushroom Supplements Revenue by Country6.1.3 U.S.6.1.4 Canada6.2 North America Reishi Mushroom Supplements Market Facts & Figures by Type6.3 North America Reishi Mushroom Supplements Market Facts & Figures by Application 7 Europe7.1 Europe Reishi Mushroom Supplements by Country7.1.1 Europe Reishi Mushroom Supplements Sales by Country7.1.2 Europe Reishi Mushroom Supplements Revenue by Country7.1.3 Germany7.1.4 France7.1.5 U.K.7.1.6 Italy7.1.7 Russia7.2 Europe Reishi Mushroom Supplements Market Facts & Figures by Type7.3 Europe Reishi Mushroom Supplements Market Facts & Figures by Application 8 Asia Pacific8.1 Asia Pacific Reishi Mushroom Supplements by Region8.1.1 Asia Pacific Reishi Mushroom Supplements Sales by Region8.1.2 Asia Pacific Reishi Mushroom Supplements Revenue by Region8.1.3 China8.1.4 Japan8.1.5 South Korea8.1.6 India8.1.7 Australia8.1.8 Taiwan8.1.9 Indonesia8.1.10 Thailand8.1.11 Malaysia8.1.12 Philippines8.1.13 Vietnam8.2 Asia Pacific Reishi Mushroom Supplements Market Facts & Figures by Type8.3 Asia Pacific Reishi Mushroom Supplements Market Facts & Figures by Application 9 Latin America9.1 Latin America Reishi Mushroom Supplements by Country9.1.1 Latin America Reishi Mushroom Supplements Sales by Country9.1.2 Latin America Reishi Mushroom Supplements Revenue by Country9.1.3 Mexico9.1.4 Brazil9.1.5 Argentina9.2 Central & South America Reishi Mushroom Supplements Market Facts & Figures by Type9.3 Central & South America Reishi Mushroom Supplements Market Facts & Figures by Application 10 Middle East and Africa10.1 Middle East and Africa Reishi Mushroom Supplements by Country10.1.1 Middle East and Africa Reishi Mushroom Supplements Sales by Country10.1.2 Middle East and Africa Reishi Mushroom Supplements Revenue by Country10.1.3 Turkey10.1.4 Saudi Arabia10.1.5 U.A.E10.2 Middle East and Africa Reishi Mushroom Supplements Market Facts & Figures by Type10.3 Middle East and Africa Reishi Mushroom Supplements Market Facts & Figures by Application 11 Company Profiles11.1 Natures Way Reishi11.1.1 Natures Way Reishi Corporation Information11.1.2 Natures Way Reishi Description, Business Overview and Total Revenue11.1.3 Natures Way Reishi Sales, Revenue and Gross Margin (2015-2020)11.1.4 Natures Way Reishi Reishi Mushroom Supplements Products Offered11.1.5 Natures Way Reishi Recent Development11.2 Solaray Reishi Mushroom11.2.1 Solaray Reishi Mushroom Corporation Information11.2.2 Solaray Reishi Mushroom Description, Business Overview and Total Revenue11.2.3 Solaray Reishi Mushroom Sales, Revenue and Gross Margin (2015-2020)11.2.4 Solaray Reishi Mushroom Reishi Mushroom Supplements Products Offered11.2.5 Solaray Reishi Mushroom Recent Development11.3 Life Extension Reishi Extract11.3.1 Life Extension Reishi Extract Corporation Information11.3.2 Life Extension Reishi Extract Description, Business Overview and Total Revenue11.3.3 Life Extension Reishi Extract Sales, Revenue and Gross Margin (2015-2020)11.3.4 Life Extension Reishi Extract Reishi Mushroom Supplements Products Offered11.3.5 Life Extension Reishi Extract Recent Development11.4 Host Defense Reishi11.4.1 Host Defense Reishi Corporation Information11.4.2 Host Defense Reishi Description, Business Overview and Total Revenue11.4.3 Host Defense Reishi Sales, Revenue and Gross Margin (2015-2020)11.4.4 Host Defense Reishi Reishi Mushroom Supplements Products Offered11.4.5 Host Defense Reishi Recent Development11.5 Terrasoul Superfoods11.5.1 Terrasoul Superfoods Corporation Information11.5.2 Terrasoul Superfoods Description, Business Overview and Total Revenue11.5.3 Terrasoul Superfoods Sales, Revenue and Gross Margin (2015-2020)11.5.4 Terrasoul Superfoods Reishi Mushroom Supplements Products Offered11.5.5 Terrasoul Superfoods Recent Development11.6 Swanson Reishi Mushroom11.6.1 Swanson Reishi Mushroom Corporation Information11.6.2 Swanson Reishi Mushroom Description, Business Overview and Total Revenue11.6.3 Swanson Reishi Mushroom Sales, Revenue and Gross Margin (2015-2020)11.6.4 Swanson Reishi Mushroom Reishi Mushroom Supplements Products Offered11.6.5 Swanson Reishi Mushroom Recent Development11.7 Aloha Medicinals11.7.1 Aloha Medicinals Corporation Information11.7.2 Aloha Medicinals Description, Business Overview and Total Revenue11.7.3 Aloha Medicinals Sales, Revenue and Gross Margin (2015-2020)11.7.4 Aloha Medicinals Reishi Mushroom Supplements Products Offered11.7.5 Aloha Medicinals Recent Development11.8 Mushroom Science11.8.1 Mushroom Science Corporation Information11.8.2 Mushroom Science Description, Business Overview and Total Revenue11.8.3 Mushroom Science Sales, Revenue and Gross Margin (2015-2020)11.8.4 Mushroom Science Reishi Mushroom Supplements Products Offered11.8.5 Mushroom Science Recent Development11.9 Planetary Herbals11.9.1 Planetary Herbals Corporation Information11.9.2 Planetary Herbals Description, Business Overview and Total Revenue11.9.3 Planetary Herbals Sales, Revenue and Gross Margin (2015-2020)11.9.4 Planetary Herbals Reishi Mushroom Supplements Products Offered11.9.5 Planetary Herbals Recent Development11.1 Natures Way Reishi11.1.1 Natures Way Reishi Corporation Information11.1.2 Natures Way Reishi Description, Business Overview and Total Revenue11.1.3 Natures Way Reishi Sales, Revenue and Gross Margin (2015-2020)11.1.4 Natures Way Reishi Reishi Mushroom Supplements Products Offered11.1.5 Natures Way Reishi Recent Development 12 Future Forecast by Regions (Countries) (2021-2026)12.1 Reishi Mushroom Supplements Market Estimates and Projections by Region12.1.1 Global Reishi Mushroom Supplements Sales Forecast by Regions 2021-202612.1.2 Global Reishi Mushroom Supplements Revenue Forecast by Regions 2021-202612.2 North America Reishi Mushroom Supplements Market Size Forecast (2021-2026)12.2.1 North America: Reishi Mushroom Supplements Sales Forecast (2021-2026)12.2.2 North America: Reishi Mushroom Supplements Revenue Forecast (2021-2026)12.2.3 North America: Reishi Mushroom Supplements Market Size Forecast by Country (2021-2026)12.3 Europe Reishi Mushroom Supplements Market Size Forecast (2021-2026)12.3.1 Europe: Reishi Mushroom Supplements Sales Forecast (2021-2026)12.3.2 Europe: Reishi Mushroom Supplements Revenue Forecast (2021-2026)12.3.3 Europe: Reishi Mushroom Supplements Market Size Forecast by Country (2021-2026)12.4 Asia Pacific Reishi Mushroom Supplements Market Size Forecast (2021-2026)12.4.1 Asia Pacific: Reishi Mushroom Supplements Sales Forecast (2021-2026)12.4.2 Asia Pacific: Reishi Mushroom Supplements Revenue Forecast (2021-2026)12.4.3 Asia Pacific: Reishi Mushroom Supplements Market Size Forecast by Region (2021-2026)12.5 Latin America Reishi Mushroom Supplements Market Size Forecast (2021-2026)12.5.1 Latin America: Reishi Mushroom Supplements Sales Forecast (2021-2026)12.5.2 Latin America: Reishi Mushroom Supplements Revenue Forecast (2021-2026)12.5.3 Latin America: Reishi Mushroom Supplements Market Size Forecast by Country (2021-2026)12.6 Middle East and Africa Reishi Mushroom Supplements Market Size Forecast (2021-2026)12.6.1 Middle East and Africa: Reishi Mushroom Supplements Sales Forecast (2021-2026)12.6.2 Middle East and Africa: Reishi Mushroom Supplements Revenue Forecast (2021-2026)12.6.3 Middle East and Africa: Reishi Mushroom Supplements Market Size Forecast by Country (2021-2026) 13 Market Opportunities, Challenges, Risks and Influences Factors Analysis13.1 Market Opportunities and Drivers13.2 Market Challenges13.3 Market Risks/Restraints13.4 Porters Five Forces Analysis13.5 Primary Interviews with Key Reishi Mushroom Supplements Players (Opinion Leaders) 14 Value Chain and Sales Channels Analysis14.1 Value Chain Analysis14.2 Reishi Mushroom Supplements Customers14.3 Sales Channels Analysis14.3.1 Sales Channels14.3.2 Distributors 15 Research Findings and Conclusion 16 Appendix16.1 Research Methodology16.1.1 Methodology/Research Approach16.1.2 Data Source16.2 Author Details

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Originally posted here:
Reishi Mushroom Supplements Market Research Report: Probable Key Development To Be Observed Market States And Outlook Across By 2026 - Weekly Wall

Several accidents at the power station reveal serious issues in maintenance, safety systems

In the past five years, two major accidents and a minor accident occurred at the Neyveli Lignite Thermal Power Station (NLTPS) a lignite-based thermal power station located near the lignite mines of Neyveli in Tamil Nadus Cuddalore district.

Another accident at the plant owned by Neyveli Lignite Corporation (NLC), an undertaking of the Union government revealed serious issues in maintenance and safety systems in the old units running at NLTPS, for which the senior management should be held responsible.

NLC has a history of management issues. There have been frequent strikes by workers over several issues over the years. These strikes may be one of the reasons for poor operational practices at NLTPS.

Continuous delays in the commissioning of new units forced NLTPS to run its old units, scheduled to retire between 2011-15. Efficient and safe operating life of thermal power plant is considered to be around 25 years. At NLTPS, however, a large number of units are 25-57 years old.

Unit 6, where the incident occurred, is more than 26 years old and is to be retired due to unavailability of space for pollution control technologies, according to the National Electricity Plan, 2018.

NLTPS has distinct phases, where new units are usually commissioned, with auxillary utilities (like coal handling, water treatment etc) being common for different units in each phase.Phase one consists of units 1-6 (50 x 6 megawatts or MW) and 7-9 (100 x 3 MW), commissioned during 1962-70. All these units were scheduled to be retired between 2011-15.

This plan, however, could not be executed due to a continuous delay in commissioning of the new capacity.

The present total capacity of the first stage is 500 MW (unit 7, with a capacity of 100 MW, was retired in 2019). The expansion of phase one included two units of 210 MW capacity each.

NLTPS phase two has units 1-7 (210 x 7 MW) commissioned during 1988-93. Stage two expansion has two units of 250 MW capacity, each commissioned in 2014-15.

Two new units of 500 MW each, that were scheduled to arrive in 2014-15, were continuously delayed. One of them was added in 2019 and the other is yet to come.

These two units were critical as retirement of the old plant was based on the commissioning of these units. The retirement of old units (40-50-years-old) was continuously delayed due to delay in the commissioning of new units.

Source: CSE

History of disorder

2011:It was planned for NLTPS phase one to be decommissioned between 2011 and 2014. In 2011, however, the period of operations was extended for five years and still has not been retired.

2013-17: Frequent strikes in NLC on dilution of stakes and wages issues, with the matter in court till February, 2020.

May 20, 2014: Blast at a pipeline of a boiler in NLTPS phase one unit seven (100 MW) killed two people and injured four others. An NLC probe committee blamed an engineer for the incident and said it was satisfied with the built-in safety protection available in the scheme. It was claimed that a life extension programme and periodical residual life assessment studies were conducted to ensure safe operation of the plant.

June 2019:One person was killed and two others seriously injured in an explosion of the safety valve at one of the units in NLTPS phase two.

May 5, 2020: Minor fire incident at the conveyor belt in NLTPS phase two.

May 7, 2020: The incident occurred in the NLTPS phase two, unit 6 boiler of NLC India's second thermal power station. The pressure build-up inside the boiler caused the blast. Eight people, who were working in the area, were injured and taken to NLC's hospital.

There may be many technical reasons including excessive accumulation of ash and improper fuel combustion for a blast in a boiler, caused by uneven heat transfer at certain locations, said Ashu Gupta, a former general manager at National Thermal Power Corporation Limited.

All these issues are handled by power plants in day-to-day operations andmaintenance, he said. This blast is clearly a result of a failure of built-in checks and safety systems that are in place in all the power plants, Gupta added.

Such incidents are the blatant failure of maintenance and operational safety interlocks and should not be linked to the novel coronavirus disease (COVID-19) outbreak, according to Amit Kumar Singh, a power sector consultant.

There might be various technical reasons for the blast, but the real reasons will be revealed after the investigation report comes out, according to several experts.

Over the years, Delhi-based non-profit Centre for Science and Environment (CSE) has been pushing hard to expedite the retirement of old units.

The execution of government plans for the retirement of old plants are continuously delayed. These old plants require significant investment for operation and safety, with poor management at the plant level making these units prone to such serious incidents.

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All is not well at the Neyveli thermal power station in Cuddalore - Down To Earth Magazine

CAMBRIDGE, Mass., May 12, 2020 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology bothin vivoandex vivo,is presenting three oral presentations and two poster presentations at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), taking place virtually from May 12-15, 2020. Intellia researchers are presenting new data in support of NTLA-5001, the companys engineered cell therapy candidate for the treatment of acute myeloid leukemia (AML). Intellia is also providing an update on NTLA-2002, its newest development candidate for the treatment of hereditary angioedema (HAE).

At Intellia, we are applying our CRISPR/Cas9 technology to develop new processes that can produce enhanced engineered cell therapies to treat severe cancers, such as AML, that traditional approaches cannot address. Our proprietary platform provides a powerful tool to generate more potent TCR-directed cells, that can treat blood cancers initially and potentially solid tumors. The data being presented today validate Intellias approach of reducing AML tumor cell blasts, and our plans to enter the clinic with NTLA-5001 next year, said Intellia President and CEO John Leonard, M.D. We are also pleased to present data that support our recently announced HAE development candidate, NTLA-2002, Intellias second systemic therapy employing our in vivo knockout approach and modular delivery platform.

Data Presentations on Intellias First Engineered Cell Therapy Development Candidate, NTLA-5001 for the Treatment of AML, and Proprietary Cell Engineering Process

NTLA-5001 is Intellias first engineered T cell receptor (TCR) T cell therapy development candidate, which targets the Wilms Tumor 1 (WT1) intracellular antigen for the treatment of AML. NTLA-5001 is being developed in collaboration with Chiara Boninis team at IRCCS Ospedale San Raffaele to treat AML patients regardless of the genetic subtype of a patients leukemia. AML is a cancer of the blood and bone marrow that is rapidly fatal without immediate treatment and is the most common type of acute leukemia in adults(Source:NIH SEER Cancer Stat Facts: Leukemia AML).

Intellias proprietary process is a significant improvement over standard engineering processes commonly used to introduce nucleic acids into cells. Intellias process enabled multiple gene edits using CRISPR/Cas9, while maintaining cell products with high expansion potential and minimal undesirable chromosomal translocations. CRISPR/Cas9 was used to insert a WT1-directed TCR in locus, while eliminating the expression of the endogenous TCRs, with the goal of producing homogeneous T cell therapies like NTLA-5001.

Intellias novel approach with NTLA-5001 can overcome the challenges of standard T cell therapy, including risks of reduced specificity associated with mixed expression and mispairing of endogenous and transgenic TCRs (tgTCRs); graph-versus-host disease (GvHD) risks, which could lead to an attack on the patients healthy cells; and reduced efficacy tied to lower tgTCR expression per T cell. Intellias unprecedented process is expected to streamline cell engineering and manufacturing, yielding a homogenous product comprising WT1-targeted T cells with high anti-tumor activity. Data highlights from todays presentation include the following:

Intellias cell engineering efforts are focused on its initial clinical investigation of NLTA-5001 on AML, while continuing preclinical studies exploring the potential for targeting WT1 in solid tumors. The company confirmed plans last week to submit an IND or IND-equivalent for NTLA-5001 for the treatment of AML in the first half of 2021.

The presentation titled, Enhanced tgTCR T Cell Product Attributes Through Process Improvement of CRISPR/Cas9 Engineering, will be made today by Aaron Prodeus, Ph.D., senior scientist, Cell Therapy, and can be found here, on the Scientific Publications & Presentations page of Intellias website. These data were a follow-on to the study presented at Keystone Symposias Engineering the Genome Conference from this past February.

In Vivo Data Supports Intellias Novel TCR Candidate

A second presentation on engineered cell therapy progress, in collaboration with IRCCS Ospedale San Raffaele, showed in vivo data demonstrating the potential of TCR-edited T cells to effectively target WT1 tumor cells in AML. In addition to the previously disclosed results of effective in vitro recognition of primary AML tumor cells by edited WT1-specific cytotoxic T cells (CD8 T cells), new data indicate that the selected TCR also enables T helper cells (CD4 T cells) to react to WT1-expressing tumor cells, providing cytokine support. This distinguishes Intellias TCR from other therapeutic TCR candidates, which either exclusively activate toxic CD8 T cells or require the co-transfection of CD8 into CD4 T cells to render them functional.

Using a mouse model carrying disseminated human primary AML, researchers observed a significant therapeutic effect, including decreased AML tumor burden. In addition, no signs of GvHD were observed in mice treated with the WT1-specific T cells. The data show that tgTCR-engineered cells have targeted anti-cancer activity in a challenging model of systemic AML, demonstrating the therapeutic potential of Intellias engineered TCR T cell approach.

The presentation titled, Exploiting CRISPR-Genome Editing and WT1-Specific T Cell Receptors to Redirect T Lymphocytes Against Acute Myeloid Leukemia, will be given today by Eliana Ruggiero, Ph.D., Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Italy. Notably, ASGCT meeting organizers selected this presentation as one of six to receive the ASGCT Excellence in Research Award this year.

Continued Progress on Intellias Second In Vivo Development Candidate, NTLA-2002 for the Treatment of HAE

Intellia is presenting development data updates on its potential HAE therapy, NTLA-2002, which utilizes the companys systemic in vivo knockout approach, including its proprietary lipid nanoparticle (LNP) system. HAE is a rare genetic disorder characterized by recurring and unpredictable severe swelling attacks in various parts of the body, and is significantly debilitating or even fatal in certain cases. NTLA-2002 aims to prevent unregulated production of bradykinin by knocking out the prekallikrein B1 (KLKB1) gene through a single course of treatment to ameliorate the frequency and intensity of these swelling attacks.

The KLKB1 gene knockout in an ongoing non-human primate (NHP) study resulted in a sustained 90% reduction in kallikrein activity, a level that translates to a therapeutically meaningful impact on HAE attack rates(Source: Banerji et al., NEJM, 2017). This kallikrein activity reduction was sustained for at least six months, demonstrating the same high level of efficacy and durability seen in earlier rodent studies.

The short talk titled, CRISPR/Cas9-Mediated Gene Knockout of KLKB1 to Treat Hereditary Angioedema, will be given by Jessica Seitzer, director, Genomics, Intellia on Fri., May 15, 2020, when it will be made available here, on the Scientific Publications & Presentations page of Intellias website. The presented data include results from ongoing collaborations with researchers at Regeneron, and the program is subject to an option by Regeneron to enter into a Co/Co agreement, in which Intellia would remain the lead party. Intellia expects to submit an IND or IND-equivalent to initiate a Phase 1 trial for NTLA-2002 in the second half of 2021.

About Intellia Therapeutics

Intellia Therapeuticsis a leading genome editing company focused on developing proprietary, curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by permanently editing disease-associated genes in the human body with a single treatment course, and through improved cell therapies that can treat cancer and immunological diseases, or can replace patients diseased cells. The combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts Intellia in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create a new class of therapeutic products. Learn more aboutIntellia Therapeuticsand CRISPR/Cas9 atintelliatx.comand follow us on Twitter @intelliatweets.

Forward-Looking Statements

This press release contains forward-looking statements of Intellia Therapeutics, Inc. (Intellia or the Company) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias beliefs and expectations regarding its: planned submission of an investigational new drug (IND) application or similar clinical trial application for NTLA-2001 for the treatment of transthyretin amyloidosis (ATTR) in mid-2020 and its planned dosing of first patients in the second half of 2020; plans to submit an IND application for NTLA-5001, its first T cell receptor (TCR)-directed engineered cell therapy development candidate for its acute myeloid leukemia (AML) program in the first half of 2021; plans to submit an IND or similar clinical trial application for its hereditary angioedema (HAE) program in the second half of 2021; plans to advance and complete preclinical studies, including non-human primate studies for its ATTR program and HAE programs, and other animal studies supporting other in vivo and ex vivo programs, including its AML program; development of a proprietary LNP/AAV hybrid delivery system, as well as its modular platform to advance its complex genome editing capabilities, such as gene insertion; further development of its proprietary cell engineering process for multiple sequential editing; presentation of additional data at upcoming scientific conferences, and other preclinical data in 2020; advancement and expansion of its CRISPR/Cas9 technology to develop human therapeutic products, as well as its ability to maintain and expand its related intellectual property portfolio; ability to demonstrate its platforms modularity and replicate or apply results achieved in preclinical studies, including those in its ATTR, AML, and HAE programs, in any future studies, including human clinical trials; ability to develop other in vivo or ex vivo cell therapeutics of all types, and those targeting WT1 in AML in particular, using CRISPR/Cas9 technology; ability to optimize the impact of its collaborations on its development programs, including but not limited to its collaborations with Novartis or Regeneron Pharmaceuticals, Inc., and Regenerons ability to enter into a co-development and co-promotion agreement for the HAE program; statements regarding the timing of regulatory filings regarding its development programs.

Any forward-looking statements in this press release are based on managements current expectations and beliefs 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: risks related to Intellias ability to protect and maintain its intellectual property position; risks related to Intellias relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Intellias product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and the risk that Intellias collaborations with Novartis or Regeneron or its other ex vivo collaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Intellias other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

Intellia Contacts:

Media:Lynnea OlivarezDirectorExternal Affairs & Communications+1 956-330-1917 lynnea.olivarez@intelliatx.com

Investors:Lina LiAssociate DirectorInvestor Relations+1 857-706-1612lina.li@intelliatx.com

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Intellia Therapeutics Reports Progress on CRISPR/Cas9 AML Cancer Therapy Using Proprietary Cell Engineering Process at the 23rd Annual Meeting of the...

ZUG, Switzerland and CAMBRIDGE, Mass. and BOSTON, May 11, 2020 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX001, an investigational, autologous, gene-edited hematopoietic stem cell therapy, for the treatment of severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).

RMAT designation is another important regulatory milestone for CTX001 and underscores the transformative potential of a CRISPR-based therapy for patients with severe hemoglobinopathies, said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. We expect to share additional clinical data on CTX001 in medical and scientific forums this year as we continue to work closely with global regulatory agencies to expedite the clinical development of CTX001.

The first clinical data announced for CTX001 late last year represented a key advancement in our efforts to bring CRISPR-based therapies to people with beta thalassemia and sickle cell disease and demonstrate the curative potential of this therapy, said Bastiano Sanna, Ph.D., Executive Vice President and Chief of Cell and Genetic Therapies at Vertex. We are encouraged by these recent regulatory designations from the FDA and EMA, which speak to the potential impact this therapy could have for patients.

Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising pipeline products, including genetic therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition. Similar to Breakthrough Therapy designation, RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the biologics license application (BLA) and other opportunities to expedite development and review.

In addition to RMAT designation, CTX001 has received Orphan Drug Designation from the U.S. FDA for TDT and from the European Commission for TDT and SCD. CTX001 also has Fast Track Designation from the U.S. FDA for both TDT and SCD.

About CTX001CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patients hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients. CTX001 is the most advanced gene-editing approach in development for beta thalassemia and SCD.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.

About the CRISPR-Vertex CollaborationCRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding CRISPR Therapeutics expectations about any or all of the following: (i) the status of clinical trials (including, without limitation, the expected timing of data releases) and discussions with regulatory authorities related to product candidates under development by CRISPR Therapeutics and its collaborators, including expectations regarding the benefits of RMAT designation; (ii) the expected benefits of CRISPR Therapeutics collaborations; and (iii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential impacts due to the coronavirus pandemic, such as the timing and progress of clinical trials; the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients (as is the case with CTX001 at this time) not to be indicative of final trial results; the potential that CTX001 clinical trial results may not be favorable; that future competitive or other market factors may adversely affect the commercial potential for CTX001; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

About VertexVertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London, UK. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 10 consecutive years on Science magazine's Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Vertex Special Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, the information provided regarding the status of, and expectations with respect to, the CTX001 clinical development program and related global regulatory approvals, and expectations regarding the RMAT designation. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the development of CTX001 may not proceed or support registration due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

CRISPR Therapeutics Investor Contact:Susan Kim, +1 617-307-7503susan.kim@crisprtx.com

CRISPR Therapeutics Media Contact:Rachel EidesWCG on behalf of CRISPR+1 617-337-4167 reides@wcgworld.com

Vertex Pharmaceuticals IncorporatedInvestors:Michael Partridge, +1 617-341-6108orZach Barber, +1 617-341-6470orBrenda Eustace, +1 617-341-6187

Media:mediainfo@vrtx.com orU.S.: +1 617-341-6992orHeather Nichols: +1 617-961-0534orInternational: +44 20 3204 5275

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CRISPR Therapeutics and Vertex Pharmaceuticals Announce FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX001 for the...

Treatment of metastatic hormone receptor (HR)-positive, HER2-negative breast cancer is traditionally executed with the use of endocrine therapy. With the emergence of targeted therapies for the treatment of this disease, however, the landscape is rapidly shifting, and more therapies are under active research.

In the current landscape, oncologists have made room for CDK4/6 inhibition in combination with endocrine therapy, a combination that has been proven to improve upon progression-free and overall survival in this patient population.

At this point in time, we're grateful to have CDK4/6inhibition as our standard of care, but there is so much work going on and so many exciting new agents. What I what to think about is what lies ahead in the next decade in terms of the introduction of a lot of these newer agents into our clinics, Erica Mayer, MD, toldTargeted Oncology.

A new clinical trial is underway (PACE, NCT03147287) to further investigate CDK4/6 inhibition in combination with endocrine therapy after chemotherapy. In 3 arms of fulvestrant monotherapy, fulvestrant plus palbociclib, and fulvestrant plus palbociclib with avelumab (Bavencio), the study is primarily assessing progression-free survival (PFS), with overall response rate and treatment-emergent adverse events as secondary end points.

In an interview withTargeted Oncology, Mayer, senior medical oncologist, Breast Oncology Center, Dana-Farber Cancer Institute, discussed advances in the treatment landscape of HR-positive, HER2-negative breast, primarily with endocrine therapy and CDK4/6 inhibition.

TARGETED ONCOLOGY: Can you discuss advances in endocrine therapy in recent years and explain what you see for the future of endocrine therapy in advanced HR+, HER-negative breast cancer?

Mayer: Over the past several decades, we have primarily been using endocrine monotherapy to treat metastatic hormone receptor positive breast cancer. However, over the past several years weve had the introduction of new targeted therapies that we used in combination with an endocrine back bone, and the introduction of these agents has substantially improved progression free and overall survival for patients with metastatic hormone receptor positive HER2-negative disease. We had the introduction of the mTOR inhibitor everolimus, and the CDK4/6 inhibitors, palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio), as well as the most recent from 2019, a PI3 kinase inhibitor, alpelisib (Piqray).

At this point in time, there are at least 8 large randomized studies that have looked at the addition of a CDK4/6 inhibitor to back on endocrine therapy, either in the first- or second-line settings. There are trials that have used all 3 available agents and the diversity of endocrine back bone. Importantly and consistently, there is a substantial improvement in hazard ratio across the board of 0.5 to .055,which suggests a doubling and PFS with the addition of the CDK4/6 inhibitor, and that has become our standard of care for the majority of patients in the first-line or second-line settings.

In the past year, weve seen overall survival (OS) data from these agents and again, suggesting that there may be an OS advantage from the use CDK4/6 inhibitors and supporting the upfront use of these agents. The big question that has come up, though, is after a CDK4/6 inhibitor, if the cancer is progressing, what do we give next? What are our next best strategies? Should we be continuing on a CDK4/6 inhibitor like we would do with trastuzumab in HER2-positive breast cancer, or should we be switching to a different endocrine therapy with a new targeted partner? Also, how can we best select that targeted partner?

In terms of the idea of maintaining CDK4/6 inhibition, there are multiple studies ongoing trying to address this question. We are fortunate to lead a study called PACE, which is a randomized study open throughout the United States, in which patients who have progressed on a CDK4/6 inhibitor are then randomized to 1 of 3 arms, fulvestrant alone, which could be standard of care and many patients, fulvestrant with the CDK4/6 inhibitor, palbociclib, or a triplet combination of fulvestrant, palbociclib, and avelumab, which is an immunotherapy agent. This study is based off of some strong preclinical data and is actively accruing. Were hoping that will help address this question.

Beyond that, there has been research to understand mechanisms of resistance to CDK4/6 inhibitors and dissect that from known mechanisms of resistance to endocrine therapy. Ideally, we would love to think of a framework where we could, in real time, test the tumor or even test circulating tumor DNA to identify the mutation that is the cause of the resistance. Then we can apply a new targeted therapy with the next line of endocrine treatment to overcome that resistance. There are several candidates, therapies, and mechanisms which have been identified.

At this point in time, were grateful to have CDK4/6 inhibition as our standard of care, but there is so much work going on and so many exciting new agents. What I what to think about is what lies ahead in the next decade in terms of the introduction of a lot of these newer agents into our clinics.

TARGETED ONCOLOGY: With all the different agents that are available in the space, how do you determine which patients are eligible for which therapies?

Mayer: The paradigm of which treatment we give at which step in time has been something that's been changing a bit recently. As I mentioned, the first line of therapy that most patients will now be receiving would be in endocrine therapy with a CDK4/6 inhibitor, and I think it is important to note that in years past when patients showed evidence of what we think of as visceral disease, there may have been a tendency to start those patients with chemotherapy. Thats not necessary. We can give them endocrine therapy with a CDK4/6 inhibitor, which has a high response rate and a very favorable PFS and is much better tolerated than chemotherapy. This needs to be the standard of care for the vast majority of patients.

Following that, we're increasingly going to see the introduction of tumor genomics to help us identify mutations. We have 1 actionable mutation right now, which is a mutation in PIK3CA. For patients who have that mutation, the use of alpelisib may be an attractive way to go. However, for those who don't have a PIK3CA mutation, at this point in time, we have our standard endocrine therapies, and we also have everolimus. With ongoing trials were going to start to see some interesting new options for the other categories of mutations.

TARGETED ONCOLOGY: What is the key takeaway?

Mayer: The key takeaway is that none of these advances could have happened without laboratory discovery, translation to the clinic, and the completion of clinical trials. I think that for us to move as a field we need to help design the best possible trials. We need to support them all by structuring and running the trials. Importantly, all providers and patients need to work together to enter these trials and complete them and get answers these questions.

TARGETED ONCOLOGY: What accessible are some of these available agents?

Mayer: The majority of agents that I have discussed in the standard setting are FDA-approved.

These drugs that should be available to any patient, wherever they are in the United States. The availability outside the United States varies depending on each country's approval status.

Clinical trials are a challenge that our community needs to work on. Many clinical trials are available at the large academic medical centers and increasingly, trials could be open through our cooperative networks at community cancer centers or at satellite hospitals close to the larger centers. We still have many patients in this country who live very far away from institutions that have trials available for them, and I think we need to work harder to community oncologists and every breast cancer patient.

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Improving Upon Treatment Standards in HR+ Breast Cancer - Targeted Oncology