StemCell Therapy

Penn Medicine researchers have developed a new targeted approach to prevent a toxicity seen in the sensory neurons of dorsal root ganglia after gene therapy to treat neurological disorders. It's an important hurdle to clear, as the field works toward more safe and effective gene therapies for patients with disorders like spinal muscular atrophy.

"We believe that this new approach could improve safety in gene therapy universally," said first author Juliette Hordeaux, DVM, PhD, senior director of Translational Research in Penn's Gene Therapy Program.

The findings were reported online this week in theScience Translational Medicine.

The toxicity has not been reported in humans, but studies in nonhuman primates using adeno-associated viral (AAV) vectors to deliver corrected genes via the spinal cord fluid and intravenously have revealed problems of axonal degeneration in some tracts of the spinal cord and peripheral nerves. The cause was traced back to the dorsal root ganglion, or DRG, a cluster of neural cells on the outside of the spinal cord responsible for transmission of sensory messages.

This toxicity stems from the overexpression of an introduced gene, known as a transgene, in cells in the DRG, researchers from Penn's Gene Therapy Program found in the study. To correct that, they modified a transgene with a microRNA target designed to reduce the level of the transgene expression in the DRG. That alteration eliminated more than 80 percent of the transgene expression and reduced the toxicity in primates, the researchers report.

"We believe it is a safe, straightforward way to ameliorate the safety of AAV therapy for the central nervous system," said first author Juliette Hordeaux, DVM, PhD, senior director of Translational Research in Penn's Gene Therapy Program. "This approach could be used to design other gene therapy vectors to repress transgene expression in the cell types that are affected by the toxicity and not others, which is critical, because you need the expression everywhere else to effectively treat the disorder."

Gene transfer expert James M. Wilson, MD, PhD, director of the Gene Therapy Program, and professor of Medicine and Pediatrics in Penn's Perelman School of Medicine, served as the senior author of the paper.

After Penn researchers documented DRG toxicity in nonhuman primates, they began devising a way to overcome it. Though its asymptomatic in primates, the damage became clear under close study of histopathology in the CNS. Damage to the DRG in humans, researchers know, can lead to the breakdown of axons responsible for delivering impulses from nerves to the brain. Numbness and weakness in limbs, among other side effects, follow suit.

The observed toxicity in past animal studies was enough for the U.S. Food and Drug Administration to recently place a partial hold on human trials administering a gene therapy vector into the spinal cord to treat spinal muscular atrophy, the genetic disease that severely weakens muscles and causes problems with movement. In the new study, the researchers injected vectors with and without an microRNA target, first in mice and then primates. microRNA regulates gene expression and makes for an ideal target in the cells. microRNA-183 was chosen specifically because it is largely restricted to the neurons in the DRG.

Administering unmodified AAV vectors resulted in robust delivery of the new gene into target tissue and toxicity in DRG neurons. Vectors with the miRNA target, on the other hand, reduced transgene expression significantly, as well as the toxicity of DRG neurons, without affecting transduction elsewhere in the primate's brain, histological analyses of the specimens up to 90 days later showed. An immune response was first believed to be causing the toxicity; however, the researchers debunked that hypothesis through experiments that showed how immunosuppressants and steroids were unsuccessful at alleviating the toxicity.

According to the authors, toxicity of DRGs is likely to occur in any gene therapy that relies on high doses of a vector or direct delivery of a vector into the spinal cord fluid. This latest study paves a path forward to prevent that damage.

"We were concerned about the DRG pathology that was observed in most of our NHP studies," Wilson said. "This modified vector shows great promise to reduce DRG toxicity and should facilitate the development of safer AAV-based gene therapies for many CNS diseases."

Reference: Hordeaux J, Buza EL, Jeffrey B, et al. MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates. Science Translational Medicine. 2020;12(569). doi:10.1126/scitranslmed.aba9188

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New Approach Reduces the Toxicity of Brain-Targeted Gene Therapy - Technology Networks

First look at preclinical data in frontotemporal dementia with progranulin mutations (GRN-FTD) and new amyotrophic lateral sclerosis (ALS) program

NOD2 mutation revealed as Crohns disease (CD) genetic target, associated with 7-10% of all CD cases in the U.S. and Europe

Deep dive on transduction enhancers and stable cell line technology innovations that support manufacturing for larger indications

BOSTON and LONDON, Nov. 12, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today previewed details on its investigational hematopoietic stem cell (HSC) gene therapy research programs in GRN-FTD and NOD2-CD in advance of an upcoming virtual R&D investor event. The company also disclosed a new research program in ALS. A live webcast of the presentation will be available in the Investors & Media section of the companys website at http://www.orchard-tx.com starting Friday, November 13, 2020 at 9:00 a.m. ET.

We are excited to draw back the curtain at tomorrows event on our work in larger indications that form an important part of Orchards evolution as a company, including a new program in ALS, in addition to our work in genetic subsets of FTD and Crohns disease, said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. These research programs have been established using a scientific approach that has resulted in more than 160 patients being treated across multiple rare diseases and a recent positive CHMP opinion in the EU for Libmeldy. We believe that HSC gene therapy has the power to transform lives, and we are excited about the possibilities for Orchard and patients with its expanded application.

OTL-204 for GRN-FTD and new ALS research program

The GRN-FTD and ALS programs are based on the same HSC gene therapy approach that has been clinically validated with Libmeldy (OTL-200), Orchards program for metachromatic leukodystrophy, and is under clinical evaluation in the OTL-203 and OTL-201 programs for mucopolysaccharidosis type I and mucopolysaccharidosis type IIIA, respectively. Development work in GRN-FTD and ALS will be undertaken as part of a collaboration with Boston Childrens Hospital (BCH), the University of Padua (UNIPD) and Prof. Alessandra Biffi, chair of the Pediatric Hematology, Oncology and Stem Cell Transplant Division at UNIPD and co-director of the Gene Therapy Program at BCH.

Prof. Biffi commented, The ability of HSC gene therapy to restore healthy microglia function supports the use of this technology for the development of treatments for a variety of diseases with central nervous system involvement. In GRN-FTD, initial in vitro data shows progranulin expression and secretion in culture and uptake indicative of cross-correction. My previous work at BCH researching ALS supports the novel approach of treating this severe neurodegenerative condition by targeting the NOX2 pathway.

OTL-104 for NOD2-CD

Orchards preclinical program in CD targets mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene, which plays a role in immune cell response to bacterial peptides in the gastrointestinal (GI) tract. The companys proposed approach leverages this link, using gene modified HSC-derived cells (monocytes) to replace GI resident macrophages, thus potentially correcting the inflammation and colitis associated with NOD2-CD.

Manufacturing Innovations to Support Work in Larger IndicationsTransduction enhancers (TEs) and stable cell line technology (SCLT)

Orchard has completed a thorough TE screening process and identified and validated several novel TE compounds, which in combination, facilitate lentiviral vector entry into HSCs and have shown a greater than 50% reduction in vector requirements. The enhancers mode of action is expected to be effective in each of Orchards HSC gene therapy programs. An evaluation of enhancer-treated HSC engraftment potential in mice is currently underway.

The company has worked extensively with SCLT, including the technology licensed from GSK for certain programs, to both develop processes to efficiently create SCLs for new vectors and scale up the production of SCLs to clinical grade. Results have delivered consistent levels of high-titer lentiviral production comparable to those seen using conventional methods. Selection of single high-titer clones for new vectors using this method has been achieved within three months. Work at Orchard is ongoing to develop upstream and downstream processes to further improve productivity and scalability.

We have a clear roadmap for Orchards future that prioritizes strategic growth and draws on the many synergies across our scientific, manufacturing and emerging commercial platforms, said Frank Thomas, president and chief operating officer. Over the next 12 months we have an array of exciting commercial, regulatory and clinical milestones that will continue to showcase the breadth and depth of our advanced HSC gene therapy portfolio.

Webcast Information

A live webcast of the presentation New Horizons in Gene Therapy will be available under Events in the Investors & Media section of the companys website at http://www.orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation.

About Orchards Research Collaborations

In connection with its previously disclosed collaboration with Prof. Alessandra Biffi, Orchard has signed agreements with Boston Childrens Hospital and the University of Padua to develop and exclusively license new ex vivo HSC gene therapy programs, patents and technologies for the treatment of neurodegenerative disorders. As part of the collaboration, Orchard has initiated sponsored research agreements and obtained exclusive options to license multiple new preclinical programs, including frontotemporal dementia with progranulin mutations (GRN-FTD), amyotrophic lateral sclerosis (ALS) and other rare and less rare indications.Orchard continues to support Professor Biffis labs in the development of new proprietary technology focused on enhancing the application of gene-modified HSC therapy for CNS disorders.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, plans, intends, projects, and future or similar expressions that are intended to identify forward-looking statements.Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including with respect to its manufacturing strategy, expected future milestones, and its plans and expectations for the development of its product candidates, including the product candidates referred to in this release, and the therapeutic and commercial potential of its product candidates.These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials of Orchards product candidates will not be repeated or continue in ongoing or future studies or trials involving its product candidates; the risk that the market opportunity for its product candidates may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on preclinical and clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading Risk Factors in Orchards quarterly report on Form 10-Q for the quarter ended September 30, 2020, as filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

1Knopman DS, Roberts RO. J Mol Neurosci. 2011, Onyike CU, Diehl-Schmid J. Int Rev Psychiatry. 2013 and Riedl L, et al Neuropsychiatr Dis Treat. 20142 Centers for Disease Control and Prevention; European Crohns and Colitis Organisation (ECCO); Ashton, James J et al.Clin Transl Gastroenterol. 2020 Feb

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Orchard Therapeutics Unveils Details on New HSC Gene Therapy Research Programs as Part of R&D Investor Event Tomorrow at 9:00 a.m. ET - GlobeNewswire

Belgium-headquartered UCB has strengthened its gene therapy capabilities with a pair of deals a collaboration agreement with Lacerta Therapeutics and the acquisition of Handl Therapeutics.

Handl Therapeutics based in Leuven, Belgium specialises in adeno-associated virus (AAV) capsid technology and has a focus on developing disease modifying gene therapies to treat neurodegenerative diseases.

In addition to its own capabilities, Handl has built an international network to access expertise from a number of institutions. This includes platforms licensed from KU Leuven in Belgium, the Centre for Applied Medical Research in Spain, the University of Chile and Kings College London in the UK.

UCBs global footprint and scientific expertise in neurodegenerative diseases, coupled with our shared cultures of scientific advancement and commitment to patients, creates an exceptional environment in which we can accelerate the development of gene therapies and change patients lives, said Florent Gros, founder and chief executive officer of Handl Therapeutics.

UCB did not disclose the financial terms of the acquisition, although it did add in a statement that the Handl team will continue to be based in Handl and will work closely with UCBs international research team.

The Lacerta deal is focused on developing AAV-based therapies for patients with a central nervous system disease with a high unmet need. Like the Handl acquisition, UCB did not offer the financial details of the Lacerta research collaboration and licensing agreement.

Lacerta is set to lead research and preclinical activities as well as the early manufacturing process development, with UCB planning to lead IND-enabling studies, manufacturing and clinical development.

UCBs ambition for patients relies on our ability to innovate and deliver highly differentiated medicines, said Dhavalkumar Patel, chief scientific officer of UCB.

The acquisition of Handl Therapeutics and the new partnership with Lacerta Therapeutics offers us the potential to drive a fundamental change in how diseases are treated, by moving us from treating symptoms to disease modification and eventually towards a cure. he added.

The Handl and Lacerta deals build on UCBs previous acquisition of Element Genomics in 2018.

UCB paid $30m to access Elements platform of technologies aimed at improving the understanding of genome structure and function including CRISPR editing technologies used for genomic and epigenomic regulatory region analysis and modulation.

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UCB boosts gene therapy offering with a pair of new deals - PMLiVE

Researchers from Penn Medicine have developed a new targeted approach that modifies viral vectors and inhibits toxicities in the sensory neurons of dorsal root ganglia (DRG) that commonly occur following the use of gene therapy for neurological diseases.

This strategy will likely have several important research and clinical implications, as investigators in the field have worked tirelessly for years to develop safer and more effective gene therapies for neurological disorders. We believe that this new approach could improve safety in gene therapy universally, said lead author Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penns Gene Therapy Program, in a statement.

Many gene therapies use viral vectors, but these vectors can have adverse neurological effects. While these toxicities have not yet been observed in humans, nonhuman primate studies using adeno-associated viral (AAV) vectors to deliver corrected genes via the spinal cord fluid have shown issues of axonal degeneration in spinal cord and peripheral nerve tracts. In these studies, the cause of the issues led back to the DRG, comprising a cluster of neural cells found on the outside of the spinal cord that are responsible for delivering sensory messages.

In a recent paper published in Science Translational Medicine, Dr. Hordeaux and colleagues found a way of modifying these vectors so they ultimately avoid these dangerous side effects. They first found that the toxicities appear to come from overexpression of a transgene in cells in the DRG.

The researchers altered a transgene with a microRNA target that was designed to reduce transgene expression levels in the DRG. Ultimately, this modification eliminated over 80% of the transgene expression and resulted in drastic toxicity reduction in the studied primates

We believe it is a safe, straightforward way to ameliorate the safety of AAV therapy for the central nervous system, said Hordeaux about the studied modification. This approach could be used to design other gene therapy vectors to repress transgene expression in the cell types that are affected by the toxicity and not others, which is critical, because you need the expression everywhere else to effectively treat the disorder.

Senior author of the paper was gene transfer expert James M. Wilson, MD, Ph.D., professor of Medicine and Pediatrics in Penns Perelman School of Medicine. Dr. Wilson, who left Solid Biosciences two years ago. Dr. Wilson has been discussing the potential adverse neurological effects of AAV vectors for several years.

Drs. Hordeaux and Wilson injected vectors with and without a microRNA target miRNA183 in mice and primates in the new study. The administration of unaltered AAV vectors led to robust delivery of the gene into target tissue as well as toxicities in DRG neurons. These effects occurred without impacting transduction in elsewhere in the brain, according to histological analyses conducted up to 90 days later.

The authors of the study suggest the toxicity of DRGs likely occur in a gene therapy relying on high vector doses or direct vector delivery into the fluid of the spinal cord. We were concerned about the DRG pathology that was observed in most of our nonhuman primate studies, noted Wilson. This modified vector shows great promise to reduce DRG toxicity and should facilitate the development of safer AAV-based gene therapies for many central nervous system diseases.

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New Targeted Approach Could Prevent Toxicities Associated with Neurological Gene Therapies - BioSpace

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced positive new data across its clinical programs in Gaucher disease type 1, Fabry disease and cystinosis, further reinforcing the potential of ex vivo lentiviral gene therapy for lysosomal disorders. Additionally, AVROBIO is further expanding its lysosomal disorder pipeline with a new program in Gaucher disease type 3, which joins the recently announced program in Hunter syndrome in a synergistic portfolio of six programs designed to prevent, halt or reverse genetic disease.

Were delighted to report substantial new data across our three clinical programs. Three months post-gene therapy infusion, the first Gaucher disease patients levels of the toxic metabolite plasma lyso-Gb1, as well as plasma chitotriosidase, were lower than the baseline levels when the patient was still on enzyme replacement therapy (ERT). With our Fabry disease data continuing to reflect sustained and durable results, with our first patient now out 3.5 years from dosing, we are planning our strategy to seek accelerated approvals in one or more major markets, said Geoff MacKay, president and CEO of AVROBIO. Additionally, the first patient in the investigator-sponsored trial for cystinosis, now out one year, remains off both oral and eye drop cysteamine and we are thrilled to announce that a third patient has been dosed.

As we move into the next stage of company growth, were expanding our lysosomal disorder pipeline with a new program for Gaucher disease type 3 and we plan to dose the first Hunter syndrome patient next year. We expect to be the first lentiviral gene therapy to the clinic across all six of these indications and in some cases, the first to be in the clinic with an investigational gene therapy of any type. We believe the new data weve announced today help de-risk our portfolio which leverages the same lentiviral gene therapy approach across indications, MacKay added. With strong clinical trial enrollment momentum coming out of the COVID-19-related slowdown, we anticipate dosing, enrolling or consenting five patients across our clinical trials this quarter, and dosing a total of 30 patients cumulatively across our clinical programs by the end of 2021.

Positive clinical data out as far as 3.5 years across a broad lysosomal disorder gene therapy pipeline

New clinical updates announced today include:

At three months post-gene therapy, no unexpected safety events or trends have been identified in the trial, with no serious adverse events related to AVR-RD-02 reported in the first patient dosed as of the safety data cut-off date, Nov. 3, 2020.

The company reported durable and sustained response in enzyme activity, substrate levels and VCN across patients in both the Phase 1 and Phase 2 trials as of the data cut-off date, indicating successful engraftment of genetically modified cells and endogenous production of the functional enzyme needed to break down toxic substrate and metabolites in patients. Updated biomarker data on kidney function show generally stable estimated glomerular filtration rate (eGFR) in both Phase 1 and Phase 2 patients. Historically, people living with Fabry disease experience a progressive, faster-than-normal rate of decline in kidney function, as measured by eGFR, whether or not they are on ERT, the current standard of care. AVROBIO believes the stability in eGFR for patients in its clinical trials to be clinically significant and relevant.

No unexpected safety events or trends have been identified in the trials as of the safety data cut-off date, Oct. 8, 2020. The eight serious adverse events reported in the two Fabry disease trials have been consistent with the conditioning regimen, stem cell mobilization, underlying disease or pre-existing conditions. Pre-existing low anti-AGA antibody titers have been detected in four patients in the Fabry Phase 1 trial and a transient low titer was observed but not detectable in subsequent measures in one patient in the Fabry Phase 2 trial.

No unexpected safety events or trends have been identified in the trial, with no serious adverse events reported as of the Nov. 2, 2020, safety data cut-off date.

Pioneering approach to personalized conditioning to leverage advantages of busulfan

The company also shared new data on the safety and tolerability profile of precision conditioning with busulfan prior to gene therapy administration. AVROBIO is pioneering a new approach called targeted concentration intervention (TCI) that enables precise dosing designed to optimize engraftment durability and head-to-toe reach of ex vivo lentiviral gene therapies. TCI aims to maximize the likelihood of engraftment while minimizing the risk of out-of-range side effects by targeting busulfan exposure to an area under the curve of 90 mg x hr/L over four days, called Bu90-TCI.

In AVROBIOs clinical trials to date, data suggest that side effects from its single-agent, single-cycle approach to Bu90-TCI conditioning may be predictable, manageable and transient. The side effects have tended to be mild to moderate in nature and typically presented one week after dosing and peak over three to four days before quickly subsiding. Unlike other conditioning agents, Bu90-TCI is lymphocyte sparing, meaning that important components of the adaptive immune system, B and T cells, are expected to be minimally affected.

Strategic pipeline expansion into relentlessly progressive lysosomal disorders

AVROBIO announced the addition of Gaucher disease type 3 to its pipeline, following the recent addition of Hunter syndrome, which is planned to enter the clinic next year. Together with the existing program in Pompe disease, these make up AVROBIOs second wave of clinical programs focused on life-threatening lysosomal disorders, with the goals of preventing the central nervous system and systemic deterioration that make lysosomal disorders so devastating, normalizing lifespan and lifting the burden of chronic treatment with ERT. New preclinical data suggest that AVROBIOs proprietary tagging technology, part of its industry-leading plato gene therapy platform toolbox, further enhances the potential of its investigational gene therapies in these disorders.

We believe that all six of our pipeline programs share tremendous synergies in clinical development, manufacturing, regulatory processes and commercialization. This second wave of programs will evaluate our promising investigational therapies in diseases with high unmet medical need for patients and families, said Chris Mason, M.D., Ph.D., chief scientific officer at AVROBIO. We believe the opportunity we have to potentially prevent patients, especially children, from developing the disabilities that would otherwise result from their inherited genetic code to perhaps give them the possibility of a full and healthy life is humbling. That is our purpose; it drives all of us at AVROBIO every day.

Preclinical updates include:

End-to-end plato platform ready to enable global commercialization

AVROBIO also presented data on its industry-leading plato platform highlighting advances in chemistry, manufacturing and controls (CMC) to prepare for planned upcoming trials and potential global commercialization.

The optimized processes embedded in plato are designed to enable robust product characterization and efficient production of potent, consistent drug product on two continents, with a third site slated to become operational in Europe in 2021. New advances include:

R&D Day webcast information

A live webcast of Virtual R&D Day and accompanying slides will be available under Events and Presentations in the Investors section of the companys website at http://www.avrobio.com. An archived webcast recording of the event will be available on the website for approximately 30 days.

About AVROBIO

Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene therapy designed to drive durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our ex vivo lentiviral gene therapy pipeline includes clinical programs in Fabry disease, Gaucher disease type 1 and cystinosis, as well as preclinical programs in Hunter syndrome, Gaucher disease type 3 and Pompe disease. AVROBIO is powered by its industry leading plato gene therapy platform, our foundation designed to deliver gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking Statement

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, results of preclinical studies, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, and the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, including the use of a personalized and ultra-precision busulfan conditioning regimen. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

1 Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to UCSD from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).

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AVROBIO Announces New Positive Clinical Data and Preclinical Data, as Well as Expanded Leading Lysosomal Disorder Gene Therapy Pipeline - Business...

People with blood cancers and rare genetic diseases in NSW may benefit from a $50 million funding boost for innovative cell and gene therapies.

Treasurer Dominic Perrottet said the funding allocated in Tuesday's budget would provide better access to cutting-edge and lifesaving treatments, including CAR T-cell therapy.

"This funding offers real hope to the families of children suffering from rare and often fatal diseases by opening the door to new, innovative therapies," Mr Perrottet said.

"This is an exciting time in medicine. There is a wave of cell and gene therapies now available for rare, previously untreatable, often fatal conditions."

Health Minister Brad Hazzard said NSW had played a leading role in global research in the development of novel cell and gene therapies to treat rare, fatal conditions.

"This investment will help ensure NSW children with these rare and life-threatening conditions are given every chance possible at a longer, happier and healthier life."

The funding will give more access to CAR T-cell therapy which modifies a person's own immune cells to attack cancer, offering hope for remission and long-term survival for children and young adults with acute lymphoblastic leukaemia and adults with diffuse large B-cell lymphoma.

It will also provide potentially sight-saving gene therapy for children with the genetic blinding eye disease, retinitis pigmentosa.

Also available would be monoclonal antibody therapy for neuroblastoma, which vastly improves the outcomes for children with that type of cancer.

The funding would also provide gene-based therapies for spinal muscular atrophy, a fatal condition with few treatment options until recently.

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NSW boost for new cell and gene therapies - Yahoo News Australia

PHILADELPHIA, Nov. 11, 2020 (GLOBE NEWSWIRE) -- Passage Bio Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system (CNS) disorders, today commends the newly published research of the University of Pennsylvanias (Penn) Gene Therapy Program (GTP) regarding a novel targeted approach to prevent a selective neurotoxicity seen in the sensory neurons of dorsal root ganglia (DRG) after gene therapy treatment. As previously published, this DRG toxicity has been observed after both systemic and central nervous system (CNS) delivery of gene therapy and across a variety of vectors in pre-clinical models, but clinical manifestations have not been observed.1

As part of its unique collaboration agreement with Penn, Passage Bio has certain rights to this novel DRG technology for the indications the company progresses with Penn.

Although our safety studies for our programs have not shown any clinical manifestations of DRG toxicity, we are excited about the promising approach developed by Penns GTP, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. As part of our mission to develop transformative therapies for patients, we remain committed to advancing the field of gene therapy. If in the future this new approach shows clinical benefit for patients, we will be in a strong position to incorporate it into our programs. Our relationship with Penns GTP is an important distinguishing characteristic of Passage Bio. Through our collaboration, we have ready access to world-class expertise and groundbreaking research that we can rapidly apply, if appropriate, to our therapeutic programs.

GTPs research on preventing DRG toxicity published online this week in Science Translational Medicine. According to the researchers, DRG toxicity is the result of over expression of an introduced gene, known as a transgene, in cells in the DRG, a cluster of neural cells on the outside of the spinal cord responsible for transmission of sensory messages. To correct this over expression, the GTP research team modified a transgene with a microRNA target designed to reduce the level of the transgene expression in DRG neurons as well as toxicity in DRG neurons, without affecting transduction elsewhere in the brain. That alteration eliminated more than 80 percent of the transgene expression in DRG neurons and reduced the related DRG toxicity in preclinical studies with primates.

James M. Wilson, M.D., Ph.D., director of Penns GTP and a chief scientific advisor at Passage Bio, served as a senior author of the published manuscript. Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penns GTP is first author. They reported that their microRNA target approach may be a straightforward way to potentially make AAV therapy for the central nervous system more safe.

As previously reported, results from preclinical toxicology studies for Passage Bios lead therapeutic programs, PBGM01 (GM1 gangliosidosis), PBKR03 (Krabbe disease), PBFT02 (FTD-GRN), were consistent with this overall AAV platform observation, and showed no clinical manifestations in detailed neurological examinations or daily observations. To proactively determine whether there is appearance of clinical signs of DRG toxicity in our clinical programs, Passage Bio will implement monitoring of patients, consisting of both nerve-conduction studies and neurological exams focused on sensory and peripheral nerve functions.

Passage Bio is advancing six programs, which include the lead programs for GM1 gangliosidosis (GM1), Krabbe disease, and frontotemporal dementia (FTD), as well as three additional programs for amyotrophic lateral sclerosis (ALS), metachromatic leukodystrophy (MLD) and Charcot-Marie-Tooth disease Type 2a (CMT2a). The company anticipates that the initial three clinical candidates will be in clinical trials in 2021. Through its collaboration agreement with Penn, Passage Bio has the option to license a total of 17 programs focused on rare, monogenic disorders of the CNS.

About Passage Bio

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

Penn Financial Disclosure

Dr. Wilson is a Penn faculty member and also a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the Company, receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, he may receive additional financial benefits under the license in the future. The University of Pennsylvania also holds equity and licensing interests in Passage Bio.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabe and Zofia MitaStern Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.comZofia.mita@sternir.com

Media:Gwen FisherPassage Bio215-407-1548gfisher@passagebio.com

1 Juliette Hordeaux, Elizabeth L. Buza, et al. Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology, Human Gene Therapy, published online June 25, 2020.

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Passage Bio Highlights University of Pennsylvania's Gene Therapy Program's Newly Published Research to Prevent Toxicity Associated with Gene Therapy -...

The global stem cell therapy market is estimated to surpass $18,391.9 million by 2027, exhibiting a CAGR of 10.0% from 2020 to 2027.

The report aims to offer a clear picture of the current scenario and future growth of the global Stem Cell Therapy market. The report provides scrupulous analysis of global market by thoroughly reviewing several factors of the market such as vital segments, regional market condition, market dynamics, investment suitability, and key players operating in the market. Besides, the report delivers sharp insights into present and forthcoming trends & developments in the global market.

The report articulates the key opportunities and factors propelling the global Stem Cell Therapy market growth. Also, threats and limitations that have the possibility to hamper the market growth are outlined in the report. Further, Porters five forces analysis that explains the bargaining power of suppliers and consumers, competitive landscape, and development of substitutes in the market is also sketched in the report.

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The report reveals various statistics such as predicted market size and forecast by analyzing the major factors and by assessing each segment of the global Stem Cell Therapy market. Regional market analysis of these segments is also provided in the report. The report segments the global market into four main regions including Asia-Pacific, Europe, North America, and LAMEA. Moreover, these regions are sub-divided to offer an exhaustive landscape of the Stem Cell Therapy market across key countries in respective regions. Furthermore, the report divulges some of the latest advances, trends, and upcoming opportunities in every region.

Furthermore, the report profiles top players active in the global Stem Cell Therapy market. A comprehensive summary of 10 foremost players operating in the global market is delivered in the report to comprehend their position and footmark in the industry. The report highlights various data points such as short summary of the company, companys financial status and proceeds, chief company executives, key business strategies executed by company, initiatives undertaken & advanced developments by the company to thrust their position and grasp a significant position in the market.

RESEARCH METHODOLOGY

The research report is formed by collating different statistics and information concerning the Stem Cell Therapy market. Long hours of deliberations and interviews have been performed with a group of investors and stakeholders, including upstream and downstream members. Primary research is the main part of the research efforts; however, it is reasonably supported by all-encompassing secondary research. Numerous product type literatures, company annual reports, market publications, and other such relevant documents of the leading market players have been studied, for better & broader understanding of market penetration. Furthermore, medical journals, trustworthy industry newsletters, government websites, and trade associations publications have also been evaluated for extracting vital industry insights.

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KEY MARKET BENEFITS

KEY MARKET SEGMENTS

The global Stem Cell Therapy market is segmented on the basis of the following:

Global Stem Cell Therapy Market By Product Type:

Global Stem Cell Therapy Market By Applications:

Global Stem Cell Therapy Market By Regions:

Top Leading key players stated in Global Stem Cell Therapy Market report are:

Astellas Pharma Inc., Capricor Therapeutics, Cellectis, Cellular Dynamics, Celyad, CESCA Therapeutic, DiscGenics, Gamida Cell, Mesoblast Ltd, Novadip Biosciences, OxStem.

The report also summarizes other important aspects including financial performance, product portfolio, SWOT analysis, and recent strategic moves and developments of the leading players.

Contact Us:

Mr. Abhishek PaliwalResearch Dive30 Wall St. 8th Floor, New YorkNY 10005 (P)+ 91 (788) 802-9103 (India)+1 (917) 444-1262 (US) TollFree : +1 -888-961-4454Email:support@researchdive.comLinkedIn:https://www.linkedin.com/company/research-diveTwitter:https://twitter.com/ResearchDiveFacebook:https://www.facebook.com/Research-DiveBlog:https://www.researchdive.com/blogFollow us on:https://covid-19-market-insights.blogspot.com

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Competitive Landscape: What Are the Manufacturers Evolving In the Growth of the Stem Cell Therapy Market? - Illadel Graff Supply

A succinct analysis of market size, regional growth and revenue projections for the coming years is presented in GlobalStem Cells Marketreport. The study further sheds light on major issues and the new growth strategies implemented by manufacturers that are part ofcompetitive landscape of the studied market.Thereport offers key trends, investment opportunities and drivers in Global Stem Cells Marketwith the latest market intelligence by adopting primary and secondary research methods. It also includes strategies adopted in the context of acquisitions and mergers, and business footprint extensions.

In order to provide more exactmarket forecast, the report comprises a complete research study and analysis ofCOVID-19 impact on the Global Stem Cells market. It also considers the strategies that can be adopted to deal with the situation.

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Competitive Landscape and Stem Cells Market Share Analysis:

The competitive landscape of the Stem Cells market provides data about the players operating in the studied market. The report includes a detailed analysis and statistics onprice, revenue and market share of the playersfor the period 2020-2025. The major players covered are as follows:

Thermo Fisher Scientific Inc.

Cellular Engineering Technologies Inc

Qiagen N.V

Sigma Aldrich Corporation

Becton, Dickinson and Company

Miltenyi Biotec

International Stem Cell Corporation

Stem Cell Technologies Inc.

Pluristem Therapeutics Inc

Medtronic, Inc

Zimmer Holdings, Inc.

Bio Time Inc

Zimmer Holdings, Inc

Orthofix, Inc.

Osiris Therapeutics Inc

Others Prominent Players

Key segments covered:

By Product

Adult Stem Cells

Neural Stem Cells

Hematopoietic Stem Cells

Mesenchymal Stem Cells

Umbilical Cord Stem Cells

Epithelial Stem cells and Skin Stem Cells

Others

Human Embryonic Stem Cells

Induced Pluripotent Stem Cells

Others

By Application

Regenerative Medicine

Neurology Regenerative Medicine

Oncology Regenerative Medicine

Myocardial Infraction Regenerative Medicine

Diabetes Regenerative Medicine

Hematology & Immunology Regenerative Medicine

Orthopedics Regenerative Medicine

Other Regenerative Medicine

Drug Discovery and Development

Other Applications

By Technology

Cell Acquisition

Bone Marrow Harvest

Umbilical Blood Cord

Apheresis

Others

Cell Production

Therapeutic Cloning

In-vitro Fertilization

Cell Culture

Isolation

Cryopreservation

Expansion and Sub-Culture

By End-User

Biopharmaceutical

Biotechnology Industry

Research Institutes

By Treatment Type

Allogeneic Stem Cell Therapy

Auto logic Stem Cell Therapy

Syngeneic Stem Cell Therapy

By Banking Type

Public

Private

By Region:

North America (U.S. & Canada)

Europe (Germany, United Kingdom, France, Italy, Spain, Russia, and Rest of Europe)

Asia Pacific (China, India, Japan, South Korea, Indonesia, Taiwan, Australia, New Zealand, and Rest of Asia Pacific)

Latin America (Brazil, Mexico, and Rest of Latin America)

Middle East & Africa (GCC, North Africa, South Africa, and Rest of Middle East & Africa)

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Some Important Highlights from the Report include:

Market CAGR during the 2020-2025 forecast period.

Comprehensive analysis on factors that will speed up the growth of Stem Cells marketover the next five years.

Precise estimates about the market size of global Stem Cells market and itscontribution to the parent market.

Precise forecasts for future developments in the Stem Cells industry and shifts in consumer behavior.

The growth of the Stem Cells Market across the Americas, APAC, Europe and MEA.

A detailed analysis of the industry competition and quantitative data on various vendors.

Comprehensive information on variables that will impede the growth of Stem Cells companies.

The Following are the Key Features of Global Stem Cells Market Report:

Market Overview, Industry Development, Market Maturity, PESTLE Analysis, Value Chain Analysis

Growth Drivers and Barriers, Market Trends & Market Opportunities

Porters Five Forces Analysis & Trade Analysis

Market Forecast Analysis for 2020-2025

Market Segments by Geographies and Countries

Market Segment Trend and Forecast

Market Analysis and Recommendations

Price Analysis

Key Market Driving Factors

Stem Cells Market Company Analysis: Company Market Share & Market Positioning, Company Profiling, Recent Industry Developments etc.

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Provides accurate data and best-in class solutions to our clients.

Offers optimal market predictions and analysis of the business.

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Stem Cells Market Detailed Analysis by On-going Trends, Prominent Size, Share, Sales and Forecast to 2025 - PRnews Leader

Final Report will add the analysis of the impact of COVID-19 on this industry.

November 2020:

A new report by CMI takes a deep dive into the Stem Cell Therapy after conducting meticulous research, assessing each microscopic aspect of the market. The researches have connected the dots with minuscule details that shape into an intricate, immaculate yet elucidate study. The report presents a thoroughly scrutinized study of the Stem Cell Therapy Market, leaving no stone unturned in offering market players a valuable and constructive tool that navigates them in the profitable path with the right set of objectives.

This is the most recent report that includes the effects of COVID-19 on the functioning of the market. It is well known that some changes, for the worse, were managed by the pandemic in all industries. The current scenario of the business sector and the impact of the pandemic on the industrys past and future are addressed in this report.

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The researchers have studied the factors that are expected to drive the growth of the Stem Cell Therapy by creating revenue opportunities, directly and indirectly. Similarly, the emerging trends, both long-term and short-term, present factors that are likely to impact the markets growth and project the direction the whole market is moving. Economical, technological, or any other trend that could bestow opportunities, have been studied. Moreover, the researchers have expanded the analysis beyond growth prospects and analyzed the possible restraining factors to the growth of the Stem Cell Therapy Market, thus enabling market players to foresee the likely challenges and emerge successful through the forecast period 2020-2027.

In the market segmentation by manufacturers, the report covers the following companies:

Magellan, Medipost Co., Ltd, Osiris Therapeutics, Inc., Kolon TissueGene, Inc., JCR Pharmaceuticals Co., Ltd., Anterogen Co. Ltd., Pharmicell Co., Inc., and Stemedica Cell Technologies, Inc.

The report covers exhaustive analysis on:

Stem Cell Therapy Market Segments

Stem Cell Therapy Market Dynamics

Stem Cell Therapy Market Size

Supply & Demand

Current Trends/Issues/Challenges

Competition & Companies involved

Value Chain

Stem Cell Therapy Market regional analysis includes:

Asia-Pacific (Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia and Australia)

Europe (Turkey, Germany, Russia, United Kingdom, Italy, France, etc.)

North America (United States, Mexico and Canada).

South America (Brazil etc.)

Middle East and Africa (GCC countries and Egypt).

The report assesses key players in the Stem Cell Therapy Market, studying their services, strategies, landmarks, growth plans, and recent developments. By studying multiple organizations covering small, medium, and large players the report enables emerging players to equip themselves with knowledge of competition scenarios. The most critical aspect in the competitive landscape individual growth strategy is studied extensively by dwelling into the foregoing growth trajectory of the organization. Moreover, the study paints a picture of the individual standpoints of the players in the years to come, considering the drivers and trends.

To breakdown the vast study that spreads through geographies, products, and end-use segments, among other market-specific segments, the authors present CAGR (Compound Annual Growth Rate) of each segment throughout the years of forecast. CAGR is a simplistic representation of growth that clearly projects which segment registered the highest/least growth through the forecast period 2020-2027. Moreover, each segment is analyzed on the basis of volume and volume, also projected with year-on-year growth and CAGR.

Researchers also present production and consumption analysis, key findings, important suggestions and recommendations, and other aspects, thus offering a comprehensive picture of the Stem Cell Therapy Market to bolster market players in planning their strategies in the years to come.

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Important Questions Answered

What is the growth potential of the Stem Cell Therapy market?

Which company is currently leading the Stem Cell Therapy market? Will the company continue to lead during the forecast period 2020-2027?

What are the top strategies that players are expected to adopt in the coming years?

Which regional market is anticipated to secure the highest market share?

How will the competitive landscape change in the future?

What do players need to do to adapt to future competitive changes?

What will be the total production and consumption in the Stem Cell Therapy Market by 2027?

Which are the key upcoming technologies? How will they impact the Stem Cell Therapy Market?

Which product segment is expected to show the highest CAGR?

Which application is forecast to gain the biggest market share?

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Highlights of TOC:

Overview: Presents a broad overview of the Stem Cell Therapy Market, acting as a snapshot of the elaborate study that follows.

Market Dynamics: A straight-forward discussion about key drivers, restraints, challenges, trends, and opportunities of the Stem Cell Therapy Market.

Product Segments: Explores the market growth of the wide variety of products offered by organizations, and how they fare with end-users.

Application Segments: This section studies the key end-use applications that contribute to the market growth and the emerging opportunities to the Stem Cell Therapy Market.

Geographical Segments: Each regional market with a region-specific study of each segment- is carefully assessed for understanding its current and future growth scenarios.

Company Profiles: Leading and emerging players of the Stem Cell Therapy Market are thoroughly profiled in the report based on their market share, market served, products, applications, regional growth, and other factors.

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Impact Analysis of Covid-19 On Global Stem Cell Therapy Market Continues to Expand to Support Development and Top Players: Magellan, Medipost Co.,...

Malaysia Animal Stem Cell Therapy Market Overview

The Global Malaysia Animal Stem Cell Therapy Market is showing positive signs of growth. With the current COVID-19 pandemic scenario, new business opportunities are sprouting in the market. Organizations must explore new markets to expand their business globally and locally. For getting a deeper understanding of the emerging trends, the Global Malaysia Animal Stem Cell Therapy Market report showcases various factors that drive the economy worldwide. Moreover, the companies will get to know the market landscape for the next decade 2020-2027.

The Global Malaysia Animal Stem Cell Therapy Market report has been uniquely designed to cater to the needs of the businesses of the 21st century. Going digital is the new normal. Moreover, companies can get to understand their strengths and weaknesses after assessing the market. The next decade is going to be ruled by customer-centric services. To align the business operations, the management team can utilize the actionable recommendations offered at the end of the Global Malaysia Animal Stem Cell Therapy Market report. Factors that can lift or reduce the business are termed as the external factors that also govern the functioning of the market or industries as a whole.

Before designing the blueprint, every business group can go through the Global Malaysia Animal Stem Cell Therapy Market report to understand the key business areas. For shaping a new business venture or expanding into a new market, every company must look into the opportunities and threats that are lurking in the current market. To make an efficient business plan, corporations need to understand the market dynamics that will shape the market in the forecast period (2020-2027).

Following key players have been profiled with the help of proven research methodologies:

Malaysia Animal Stem Cell Therapy Market: Competitive Landscape

To get a head start in a new market, every enterprise needs to understand the competitive landscape and the basic rules that have kept the specific market afloat. The global Malaysia Animal Stem Cell Therapy Market report unravels the secret ingredients used by competitors to meet the demands of their target audience. For specifically understanding the need to balance the capital invested with profits, organizations must use specific indicators. These indicators will not only help in pointing towards growth but also act as an alert to the upcoming threats in the near future. A proper business plan and approach can guarantee a smooth path ahead for every organization.

If the firms believe in offering a memorable experience to their prospective customers, the Global Malaysia Animal Stem Cell Therapy Market report is going to be very useful. Facts and figures are churned into this investigative report to share the strengths and weaknesses of the company. With new technologies being introduced every day, many new entrants have started their business in the market. So, to understand their approach towards the market, the Global Malaysia Animal Stem Cell Therapy Market report has a dedicated section. From the financial aspect to legal, the market report covers all the major things required to study the market and put the business plan in action. Not only this, the competitors added in the report can be altered as per the clients needs and expectations. Furthermore, the companies get a basic outline of moves, in the Global Malaysia Animal Stem Cell Therapy Market report, that can push the business to emerald heights, both in terms of sales and customer generation for the estimated time frame (2020-2027).

Malaysia Animal Stem Cell Therapy Market Segmentation:

The Malaysia Animal Stem Cell Therapy Market has been examined into different global market segments such as type, applications, and global geographies. Each and every global market segment has been studied to get informative insights into various global regions.

Malaysia Animal Stem Cell Therapy Market Segment by Type:

Malaysia Animal Stem Cell Therapy Market Segment by Application:

Malaysia Animal Stem Cell Therapy Market Segment by Global Presence:

North America Latin America Middle East Asia-Pacific Africa Europe

The report has been aggregated by using a couple of research methodologies such as primary and secondary research techniques. It helps in collecting informative pieces of professional information for deriving effective insights into the market. This informative report helps in making well informed and strategic decisions throughout the forecast period.

Malaysia Animal Stem Cell Therapy Market: Scope of the Report

To properly get a deeper understanding of the Global Malaysia Animal Stem Cell Therapy Market, this detailed report is the best choice for businesses. To boost the business along with gaining an edge over the competition, every enterprise needs to focus on the pain points of the market (under investigation). Our experienced professionals have collated facts and figures.

This in-depth analysis has revealed many fascinating facts for organizations. For smooth functioning, every business needs to be flexible towards the latest market trends. For this, the framework must be designed to adapt to the trends running at the moment. An end-to-end examination done on the target crowd helped in building the fundamental segment of the investigation, namely the external factors. These have a high tendency to push or pull the industries. Entire industries can either flourish or wipe out due to these uncontrollable factors. Global Malaysia Animal Stem Cell Therapy market report shows the most affordable options for new as well as established business players to gain market share.

With the highly experienced and motivated team at your service, the team also provides the impact of major factors such as Porters five forces. In the Global Malaysia Animal Stem Cell Therapy Market, every business runs on the image that is generated digitally in the current decade. Hence, companies need to understand the legal hurdles also. Moreover, with the in-depth study conducted across the various market verticals, it is crystal clear that stakeholders also play a significant role in running the business. Get all the details in the Global Malaysia Animal Stem Cell Therapy Market report and understand your competitors.

Key questions answered through this analytical market research report include:

What are the latest trends, new patterns and technological advancements in the Malaysia Animal Stem Cell Therapy Market? Which factors are influencing the Malaysia Animal Stem Cell Therapy Market over the forecast period? What are the global challenges, threats and risks in the Malaysia Animal Stem Cell Therapy Market? Which factors are propelling and restraining the Malaysia Animal Stem Cell Therapy Market? What are the demanding global regions of the Malaysia Animal Stem Cell Therapy Market? What will be the global market size over the coming future? What are the different effective business strategies followed by global companies?

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Malaysia Animal Stem Cell Therapy Market Size 2020 | Opportunities, Regional Overview, Top Leaders, Revenue and Forecast to 2027 - Eurowire

CARLSBAD, Calif.--(BUSINESS WIRE)--Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, strongly endorses the recent passing of Proposition 14 in California. This bill will enhance patients access to groundbreaking stem cell therapy treatments by authorizing the California Institute for Regenerative Medicine (CIRM) the ability to fund up to $5.5 billion in grants to support therapeutic development, medical research, and facilities based on stem cell technologies. This initiative builds upon the success of Proposition 71, which issued approximately $3 billion for the funding of stem cell research and led to important medical advances, including functional cures in some patients receiving cell therapy treatments. The development of Lineages OPC1 oligodendrocyte progenitor cell therapy for the treatment of acute spinal cord injury (SCI), was one of the first clinical trials supported by CIRM and has showed durable and encouraging results in some patients.

At Lineage, the patients and their families inspire us to advance cell therapy products and this recent approval of Proposition 14 ensures that access to cutting edge cell-based therapies can continue from companies like ours, stated Brian M. Culley, Lineage CEO. Cell therapy has the ability to make a profound impact on millions of lives and the passage of Proposition 14 reflects Californias serious commitment to supporting innovative local companies through the expensive and time-consuming process required to discover and test new cell-based therapies and will drive further innovation in stem cell development and research. Of note, our clinical study of OPC1 for the treatment of acute spinal cord injury was one of the first cell therapy clinical trials supported by CIRM under Prop 71. It was tremendously meaningful for some of our patients success stories to be featured in the Prop 14 campaign this year, along with others who have experienced life-changing benefits from stem cell therapy innovation in California. We are extremely thankful to CIRM for their partnership and valuable contributions, not only to Lineage, but also for other companies working in this exciting and rapidly growing field. We believe that all three of our clinical-stage programs could be considered for future grant funding under this new initiative.

About OPC1

OPC1 is an oligodendrocyte progenitor cell (OPC) transplant therapy designed to provide clinically meaningful improvements to motor recovery in individuals with acute spinal cord injuries (SCI). OPCs are naturally occurring precursors to the cells which provide electrical insulation for nerve axons in the form of a myelin sheath. SCI occurs when the spinal cord is subjected to a severe crush or contusion injury and typically results in severe functional impairment, including limb paralysis, aberrant pain signaling, and loss of bladder control and other body functions. There are approximately 18,000 new spinal cord injuries annually in the U.S. and there currently are no FDA-approved drugs specifically for the treatment of SCI. The OPC1 program has been partially funded by a $14.3 million grant from the California Institute for Regenerative Medicine. OPC1 has received Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug designation from the U.S. Food and Drug Administration (FDA).

About the OPC1 Clinical Study

The SCiStar Study of OPC1 is an open-label, 25-patient, single-arm trial testing three sequential escalating doses of OPC1 which was administered 21 to 42 days post-injury, at up to 20 million OPC1 cells in patients with subacute motor complete (AIS-A or AIS-B) cervical (C-4 to C-7) acute spinal cord injuries (SCI). These individuals had experienced severe paralysis of the upper and lower limbs. The primary endpoint in the SCiStar study was safety as assessed by the frequency and severity of adverse events related to OPC1, the injection procedure, and immunosuppression with short-term, low-dose tacrolimus. Secondary outcome measures included neurological functions measured by upper extremity motor scores (UEMS) and motor level on International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examinations through 365 days post-treatment. Enrollment is complete in this study; patients will continue to be evaluated on a long-term basis.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include three allogeneic (off-the-shelf) product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; and (iii) VAC, an allogeneic dendritic cell therapy platform for immuno-oncology and infectious disease, currently in clinical development for the treatment of non-small cell lung cancer. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as believe, may, will, estimate, continue, anticipate, design, intend, expect, could, plan, potential, predict, seek, should, would, contemplate, project, target, tend to, or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to Lineages expected eligibility for grants. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including risks and uncertainties inherent in Lineages business and other risks in Lineages filings with the Securities and Exchange Commission (the SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading Risk Factors in Lineages periodic reports with the SEC, including Lineages Annual Report on Form 10-K filed with the SEC on March 12, 2020 and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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Lineage Cell Therapeutics Proudly Supports Patients' Access to Innovative Cell Therapy Treatments and Research Through Passage of Proposition 14 -...

SAN DIEGO, Nov. 11, 2020 /PRNewswire/ -- Angiocrine Bioscience Inc., a clinical-stage biopharmaceutical company today announced that the U.S. Food and Drug Administration (FDA) granted the Regenerative Medicine Advanced Therapy (RMAT) designation for AB-205, for "the treatment of organ vascular niche injuries to prevent or reduce severe regimen-related toxicities (SRRT) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) undergoing high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation".Based on its Phase 2 trial results, Angiocrine expects to initiate a single pivotal registration Phase 3 trial in 2021 involving leading cancer centers in North America and Europe.

Angiocrine Bioscience Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to AB-205

"The RMAT designation speaks to the clinical meaningfulness and the promising efficacy data and safety profile of AB-205 based on our Phase 1b/2 study.This is an important step in accelerating the development of AB-205 towards its first market approval," commented Paul Finnegan, MD, Angiocrine's CEO."We appreciate the thorough assessment provided by the FDA reviewers and the support from our partner, the California Institute for Regenerative Medicine."Angiocrine was awarded a $6 million grant from CIRM in 2019 for the clinical development of AB-205.

About Regenerative Medicine Advanced Therapy (RMAT) DesignationEstablished under the 21st Century Cures Act, the RMAT designation was established to facilitate development and expedite review of cell therapies and regenerative medicines intended to treat serious or life-threatening diseases or conditions. Advantages include the benefits of the FDA's Fast Track and Breakthrough Therapy Designation programs, such as early interactions with the FDA to discuss potential surrogate or intermediate endpoints to support accelerated approval.

About HDT-AHCT High-dose therapy and autologous hematopoietic cell transplantation (HDT-AHCT) is considered a standard-of-care therapy for patients with aggressive systemic Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).Although efficacious and considered a potential cure, HDT-AHCT is associated with severe regimen-related toxicities (SRRT) that increase patient morbidity and risk for mortality, especially in the aging population. Effective prevention of SRRT may lead to more patients being eligible for a potential cure through HDT and stem cell transplantation.

About SRRT Consequences of Diffuse Injury to the Organ Vascular NichesThe human body is capable of renewing, healing and restoring organs.For example, the human oral-GI tract renews its lining every 3 to 7 days. Both the organ renewal and healing processes are dependent on organ stem cell vascular niches made up of stem cells, endothelial cells (cells that line blood vessels) and supportive cells.When tissues are injured, the vascular niche endothelial cells direct the stem cells, via angiocrine factor expression, to repair and restore the damaged tissue. This restorative capacity is most active during childhood and youth but starts to diminish with increasing age.HDT provided to eradicate cancer cells also cause diffuse, collateral damage to vascular niches of multiple healthy organs. In particular, the organs with the highest cell turnover (ones with most active vascular niches) are severely affected.Specifically, the oral-GI tract, dependent on constant renewal of its mucosal lining, starts to break down upon vascular niche injury.The mucosal breakdown can cause severe nausea, vomiting and diarrhea. In addition, the bacteria in the gut may escape into the circulation, resulting in patients becoming ill with endotoxemia, bacteremia or potentially lethal sepsis.HDT-related vascular niche damage can also occur in other organs resulting in severe or life-threatening complications involving the lung, heart, kidney, or the liver.Collectively, these complications are known as severe regimen-related toxicities or SRRT.SRRT can occur as frequently as 50% in lymphoma HDT-AHCT patients, with increased rate and severity in older patients.

About AB205AB-205 is a first-in-class engineered cell therapy consisting of proprietary 'universal' E-CEL (human engineered cord endothelial) cells.The AB-205 cells are intravenously administered after the completion of HDT on the same day as when the patient's own (autologous) blood stem cells are infused. AB-205 acts promptly to repair injured vascular niches of organs damaged by HDT.By repairing the vascular niches, AB-205 restores the natural process of tissue renewal, vital for organs such as oral-GI tract and the bone marrow. Successful and prompt organ restoration can prevent or reduce SRRT, an outcome that is beneficial to quality of life and cost reductive to the healthcare system.

About CIRMThe California Institute for Regenerative Medicine (CIRM) was established in November, 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The statewide ballot measure provided $3 billion in funding for California universities and research institutions.With over 300 active stem cell programs in their portfolio, CIRM is the world's largest institution dedicated to stem cell research. For more information, visit http://www.cirm.ca.gov.

About Angiocrine Bioscience Inc.Angiocrine Bioscience is a clinical-stage biotechnology company developing a new and unique approach to treating serious medical conditions associated with the loss of the natural healing and regenerative capacity of the body.Based on its novel and proprietary E-CEL platform, Angiocrine is developing multiple therapies to address unmet medical needs in hematologic, musculoskeletal, gastrointestinal, soft-tissue, and degenerative/aging-related diseases.A Phase 3 registration trial is being planned for the intravenous formulation of AB-205 for the prevention of severe complications in lymphoma patients undergoing curative HDT-AHCT.This AB-205 indication is covered by the Orphan Drug Designation recently granted by the US FDA.In addition, Angiocrine is conducting clinical trials of local AB-205 injections for the treatment of: (1) rotator cuff tear in conjunction with arthroscopic repair; and, (2) non-healing perianal fistulas in post-radiation cancer patients.

For additional information, please contact:

Angiocrine Bioscience, Inc.John R. Jaskowiak(877) 784-8496IR@angiocrinebio.com

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Angiocrine Bioscience Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to AB-205 (Universal E-CEL Cell Therapy) to...

First Approval for KEYTRUDA in the Breast Cancer Setting

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score [CPS] 10) as determined by an FDA-approved test. The approval is based on results from the Phase 3 KEYNOTE-355 trial, where KEYTRUDA in combination with chemotherapy paclitaxel (pac), paclitaxel protein-bound (commonly known as nab-paclitaxel) or gemcitabine (gem) and carboplatin (carbo) significantly reduced the risk of disease progression or death by 35% for patients whose tumors express PD-L1 (CPS 10) versus the same chemotherapy regimens alone (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012). Events were observed in 62% (n=136220) of these patients receiving KEYTRUDA in combination with pac, nab-paclitaxel or gemcarbo versus 77% (n=79103) with the same chemotherapy regimens alone. In the trial, 38% of patients had tumors expressing PD-L1 with CPS 10. This indication is approved under accelerated approval based on progression-free survival (PFS); continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Approximately 15-20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer, said Dr. Hope Rugo, director of Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. Notably, in KEYNOTE-355, KEYTRUDA was combined with three different chemotherapy regimens: paclitaxel, nab-paclitaxel or gemcitabine and carboplatin. The approval of KEYTRUDA in combination with chemotherapy gives physicians an important new option for appropriate patients.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

Todays approval is a significant milestone, as it represents the first approval for KEYTRUDA in the breast cancer setting, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. In the study supporting this approval, KEYTRUDA in combination with paclitaxel, nab-paclitaxel or gemcitabine and carboplatin significantly improved progression-free survival for patients with advanced triple-negative breast cancer whose tumors express PD-L1 with CPS greater than or equal to 10 compared with the same chemotherapy regimens alone.

Data Supporting the Approval

The accelerated approval was based on data from KEYNOTE-355 (ClinicalTrials.gov, NCT02819518 ), a multicenter, double-blind, randomized, placebo-controlled trial conducted in 847 patients with locally recurrent unresectable or metastatic TNBC, regardless of tumor PD-L1 expression, who had not been previously treated with chemotherapy in the metastatic setting. Patients were randomized (2:1) to receive either KEYTRUDA (200 mg on Day 1 every three weeks) or placebo (on Day 1 every three weeks) in combination with the following chemotherapy; all medications were administered via intravenous infusion:

Randomization was stratified by chemotherapy treatment (pac or nab-paclitaxel vs. gem and carbo), tumor PD-L1 expression (CPS 1 vs. CPS

The study population characteristics were: median age of 53 years (range, 22 to 85), 21% age 65 or older; 100% female; 68% White, 21% Asian and 4% Black; 60% ECOG PS of 0 and 40% ECOG PS of 1; and 68% were post-menopausal. Seventy-five percent of patients had tumor PD-L1 expression CPS 1 and 38% had tumor PDL1 expression CPS 10.

In KEYNOTE-355, efficacy results were in patients who were PDL1 positive with a CPS 10 (n=323) and randomized to receive KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo compared with the same chemotherapy regimens alone. KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo (n=220) reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012), with a median PFS of 9.7 months (95% CI, 7.6, 11.3) versus 5.6 months (95% CI, 5.3, 7.5) with the same chemotherapy regimens alone (n=103). For PFS, 62% (n=136) of patients experienced an event with KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo versus 77% (n=79) with the same chemotherapy regimens alone. For patients who received KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo, the ORR was 53% (95% CI, 46, 60), with a complete response rate of 17% and a partial response rate of 36%. For patients treated with the same chemotherapy regimens alone, the ORR was 40% (95% CI, 30, 50), with a complete response rate of 13% and a partial response rate of 27%. Median DOR was 19.3 months (95% CI, 9.9, 29.8) with KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo versus 7.3 months (95% CI, 5.3, 15.8) with the same chemotherapy regimens alone.

In the study, the median duration of exposure to KEYTRUDA was 5.7 months (range, 1 day to 33.0 months). Fatal adverse reactions occurred in 2.5% of patients (n=596) receiving KEYTRUDA in combination with chemotherapy, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with pac, nab-paclitaxel, or gem/carbo. Serious adverse reactions observed in 2% of patients were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued for adverse reactions in 11% of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (1%) were increased alanine aminotransferase (ALT) (2.2%), increased aspartate aminotransferase (AST) (1.5%), and pneumonitis (1.2%). Adverse reactions leading to the interruption of KEYTRUDA occurred in 50% of patients. The most common adverse reactions leading to interruption of KEYTRUDA (2%) were neutropenia (22%), thrombocytopenia (14%), anemia (7%), increased ALT (6%), leukopenia (5%), decreased white blood cell count (3.9%), and diarrhea (2%). The most common adverse reactions (all grades 20%) for KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo were: fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

About Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,300 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

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FDA Approves Merck's KEYTRUDA in Combination With Chemotherapy for Patients With Locally Recurrent Unresectable or Metastatic Triple?Negative Breast...

This article was originally published here

Stem Cells Transl Med. 2020 Nov 14. doi: 10.1002/sctm.20-0385. Online ahead of print.

ABSTRACT

Anti-inflammatory and immune-modulatory therapies have been proposed for the treatment of COVID-19 and its most serious complications. Among others, the use of mesenchymal stromal cells (MSCs) is under investigation given their well-documented anti-inflammatory and immunomodulatory properties. However, some critical issues regarding the possibility that MSCs could be infected by the virus have been raised. Angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) entry but so far it is unclear if human MSCs express or do not these two proteins. To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS-CoV-2. We evaluated human MSCs derived from amnios, cord blood, cord tissue, adipose tissue and bone marrow. ACE2 and TMPRSS2 were expressed by the SARS-CoV-2-permissive human pulmonary Calu-3 cell line but not by all the MSCs tested. MSCs were then exposed to SARS-CoV-2 wild strain without evidence of cytopathic effect. Moreover, we also excluded that the MSCs could be infected without showing lytic effects since their conditioned medium after SARS-CoV-2 exposure did not contain viral particles. Our data, demonstrating that MSCs derived from different human tissues are not permissive to SARS-CoV-2 infection, support the safety of MSCs as potential therapy for COVID-19. AlphaMed Press 2020 SIGNIFICANCE STATEMENT: Human mesenchymal stromal cells (hMSCs) are currently under investigation for the treatment of COVID-19. However, the potential safety profile of hMSCs in this context has never been defined since none has described if they express ACE2 and TMPRSS2, the main host cell factors for SARS-CoV-2 entry, and if they can be infected by SARS-CoV-2. We provide the first evidence that ACE2 and TMPRSS2 are not expressed in hMSCs derived from both adult and fetal human tissues and, most importantly, that hMSCs are not permissive to SARS-CoV-2 infection. These results support the safety of MSCs as potential therapy for COVID-19.

PMID:33188579 | DOI:10.1002/sctm.20-0385

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Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection - DocWire News

The idea of repurposingexisting medicines as a fast approach to containing COVID-19 is still popular, even as vaccines and antibodies designed to combat the disease are starting to gain steam. Scientists at the Cleveland Clinic are among those examining existing compounds as possible treatments for the coronavirus, and now they're suggesting that the popular over-the-counter sleep aid melatonin may be a possible option in treating the disease.

The researchers used an artificial intelligence tool to analyze data from 26,779 individuals in the Cleveland Clinics COVID-19 registry, of whom 8,274 tested positive for SARS-CoV-2, the novel coronavirus that causes COVID-19.

They found that people who were taking melatonin were 28% less likely to test positive for SARS-CoV-2, after adjusting for factors such as age, sex and underlying diseases, according to results published in the journal PLOS Biology.

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The melatonin effect was more pronounced in African Americans, with a reduction of 52%. In White Americans, the number was 23%.

Melatonin is a hormone released by the body that regulates the sleep-wake cycle. As a dietary supplement, its commonly used to help manage insomnia andjet lag.

Besides melatonin, the Cleveland Clinic team also found that the beta-blocker carvedilol, sold under the brand Coreg for high blood pressure and other heart diseases, was associated with a 26% reduction in a persons chance of testing positive for SARS-CoV-2.

RELATED:Melatonin? Stem cells? Researchers step up with unconventional approaches to COVID-19

Some members of the same Cleveland Clinic team previously pinpointed melatonin among a group of drugs they suggested might work for COVID. They showed that melatonin and mercaptopurine might work as a good combo for COVID. Those findings came from a pharmacology-based platform that used a technique called network proximity analysis. It was based on the idea that some proteins involved in other diseases might hold proximity to a virus interaction with the host.

The researchersapplied the same method in the current study to shed a light on clinical manifestations and pathologies common between COVID-19 and 64 other diseases. Closer proximity would mean a higher likelihood of pathological associations between the diseases.

They found that proteins involved in respiratory distress syndrome and sepsis were highly connected with SARS-CoV-2. That wasnt a surprise given that the two disorders can also cause death in patients with severe COVID-19.

This signals to us that a drug already approved to treat these respiratory conditions may have some utility in also treating COVID-19 by acting on those shared biological targets, Feixiong Cheng, Ph.D., the studys senior author, said in a statement.

Overall, they identified close network proximity to SARS-CoV-2 proteins from inflammatory bowel disease, attention deficit hyperactivity disorder, as well as pulmonary diseases such as COPD. Using a computational model, they identified 34 drugs that were significantly proximal to two or more SARS-CoV-2 host protein sets.

RELATED:COVID-19: Bio researchers race to repurpose everything from antiviral to anticancer discoveries

A team at Columbia University has also linked melatonin with increased likelihood of clinical improvement among critically ill COVID-19 patients on intubation or mechanical ventilation.

The sleep-promoting supplement was also reportedly used by President Donald Trump during his COVID-19 infection, though its not clear if he was taking it specifically to treat the disease or as part of his daily nutrition routine.

Despite melatonin emerging as a top pick from the Cleveland Clinic registry, Cheng cautioned that larger, randomized control trials would be needed before the supplement could be widely adopted in the treatment of COVID-19.

Cheng added that AI-based approaches to analyzing COVID-19 patient registries should be embraced in the effort to find effective treatments for the disease.Recent studies suggest that COVID-19 is a systematic disease impacting multiple cell types, tissues and organs, so knowledge of the complex interplays between the virus and other diseases is key to understanding COVID-19-related complications and identifying repurposable drugs, Cheng said. Our study provides a powerful, integrative network medicine strategy to predict disease manifestations associated with COVID-19 and facilitate the search for an effective treatment.

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Cleveland Clinic team draws a link between COVID-19 protection and the sleep aid melatonin - FierceBiotech

Big Market Research, one of the worlds prominent market research firms has released a new report on GlobalAnimal Stem Cell Therapy Market, The report expertise includes assessing new opportunities & sizing, identifying and evaluating complex global value chains (including key drivers, restraints and winning strategies). The report will help the vendor to strategize its positioning in the Animal Stem Cell Therapy Market projects around the globe. The detailed competitor profiling helped identify and understand the key strategies and growth drivers of its competitors. The report includes detailed profile of key competitors, pre/post launch surveys, go-to-market research, supplier selection surveys, industry demand/pain point surveys, pricing analysis, product testing, effectiveness studies, and product positioning studies.

The Animal Stem Cell Therapy Market research report includes:

The Animal Stem Cell Therapy Market report explore:

The Animal Stem Cell Therapy Market includes identification of important potential market demand, expected sale of these devices in the next 5 years, various price and demand sensitive scenarios were built to ascertain on the profitability of investing, customer analysis, and future price analysis.

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The Animal Stem Cell Therapy Market is also characterized by a highly complex value chain involving product manufacturers, material suppliers, technology developers, and manufacturing equipment developers. Partnerships between research organizations and the industry players help in streamlining the path from the lab to commercialization. In order to also leverage the first mover benefit, companies need to collaborate with each other so as to develop products and technologies that are unique, innovative and cost effective.

Several existing Animal Stem Cell Therapy Industry manufacturers, new start-ups as well as research organizations and universities are constantly coming up with innovative ideas. The Animal Stem Cell Therapy Market is expected to grow exponentially over the next five years with the emergence of new applications and cost competitive products.

Market players have been discussed and profiles of leading players including Top Key Companies:Medivet Biologics LLCVETSTEM BIOPHARMAJ-ARMU.S. Stem Cell, IncVetCell TherapeuticsCelavet Inc.Magellan Stem CellsKintaro Cells PowerAnimal Stem CareAnimal Cell TherapiesCell Therapy SciencesAnimacel

Animal Stem Cell Therapy Market By Product Type 2019-2025:DogsHorsesOthers

Based on type, the global market is segmented into the following sub-markets with annual revenue for 2015-2025 (historical and forecast) included in each section.

Animal Stem Cell Therapy Market By Application 2019-2025:Veterinary HospitalsResearch Organizations

Based on application, the global market is segmented into the following sub-markets with annual revenue for 2019-2025 (historical and forecast) included in each section.

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The comprehensive competitive landscape section of the report contains detailed analysis of the trends in mergers and acquisitions, agreements and partnerships, new product launches and so on in the Animal Stem Cell Therapy Market. This information will be very useful for existing players as well as new entrants in any market.

Geographically,Animal Stem Cell TherapyMarket is further analyzed into regions and country level analysis:North America, Europe, Asia-Pacific, Latin America, Middle East & Africa

Conclusively, this report is a one stop reference point for the industrial stakeholders to get Animal Stem Cell Therapy market forecast of till 2025. This report helps to know the estimated market size, market status, future development, growth opportunity, challenges, and growth drivers of by analyzing the historical overall data of the considered market segments.

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Animal Stem Cell Therapy Market Projected to Witness Vigorous Expansion by 2027 - re:Jerusalem

Rheumatoid arthritis refers to an inflammatory disease of the supportive tissues of the body and the condition generally affects fingers and toes of human beings. This inflammation is caused by an abnormal response of the body to the normal functioning tissues. This leads to acute pain and malformed joints. Novel cells that are produced by regenerative centers of the body are called stem cells. These cells can be changed into any other type of cell in the body with just the right kind of stimulant. The growth of the global rheumatoid arthritis stem cell therapy market is likely to observe growth in its ability to demonstrate profound healing activity. It also helps in checking the arthritic condition. In addition to that, this therapy is capable of regenerating and reversing joint tissue in many cases, which is likely to pave way for rapid growth of the global rheumatoid arthritis stem cell therapy market in the years to come.

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Ability to Diminish Pain and Inflammation to Bolster Demand in the Market

In present times, human umbilical cord tissue (allogeneic mesenchymal stem cells), fat-derived or adipose stem cells, and bone marrow transplant are utilized for the purpose of the rheumatoid arthritis stem cell therapy. As the condition becomes worse, the body starts autoimmune response and keeps on attacking the cells of the body. The global rheumatoid arthritis stem cell therapy market is estimated to gather momentum from its growing importance and popularity in specialty clinics, ambulatory surgical centers, and hospitals. This therapy comes with the excellent healing capabilities that can treat the entire system causing inflammation and joint pain.

Extensive growth opportunities of the global rheumatoid arthritis stem cell therapy market are likely to be influenced by the multiple benefits offered by this therapy. However, this therapy comes with its own share of disadvantages as well and is not an infallible method for healing arthritis. All though, this therapy is capable of assisting in the stabilization of the body immune system and diminish inflammation.

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Rheumatoid Arthritis Stem Cell Therapy Market to Ride on Increased Prevalence of Rheumatoid Arthritis - TMR Research Blog

A team of UB researchers has published a paper in Nature Communications that is helping to define the best time to give a specific treatment to infants born with Krabbe disease (KD). This treatment has been found to prolong life for these infants for as long as a few years.

The paper was published online in Nature Communication Oct. 23.

Daesung Shin, assistant professor in the Department of Biotechnical and Clinical Laboratory Sciences and the Neuroscience Program, both in the Jacobs School of Medicine and Biomedical Sciences at UB, is the lead investigator. He also conducts research at UBs Hunter James Kelly Research Institute.

KD is an inherited disorder that destroys myelin, the protective coating of nerve cells in the brain and throughout the nervous system. In most cases, signs and symptoms of Krabbe disease develop in babies before 6 months of age, and the disease usually results in death by age 2. When it develops in older children and adults, the course of the disease can vary greatly.

The progressive neurologic disorder is caused by a deficiency of galactosylceramidase (GALC). GALC is an enzyme that breaks down galactosylceramide, an important component of myelin, which ensures the rapid transmission of nerve impulses.

Although there is no cure for KD, hematopoietic stem cell therapy (HSCT), a therapy that makes blood cells, reduces neurologic deterioration and improves developmental advances. These benefits are dependent on the severity of the disease at the time the stem cells are transplanted, and are only beneficial if delivered at a clinically defined pre-symptomatic time point before symptoms appear.

Even though it is widely accepted that early treatment is essential for the most positive outcome, the precise therapeutic window for treatment and what happens during this early time have never been elucidated, Shin says.

To address that issue, his team used mutations to create a novel mouse model of KD.

We engineered an inducible knockout mouse for the GALC gene deletion in specific cells at specific times, which provided us with the opportunity to directly ask when and where GALC enzyme is required for brain development, Shin explains.

We were particularly interested in the role of early developmental GALC function, he says. Our study not only revealed a key developmental process that requires GALC in the perinatal period, but also demonstrated that temporal GALC expression is likely a major contributor to brainstem development.

The researchers found that by increasing GALC levels at or before this newly defined perinatal period they could improve the effectiveness of therapeutic interventions for KD.

For the first time, our work showed the mechanistic evidence to explain why treatment must occur so early, with the defined critical postnatal period at days 4-6 in mice, and demonstrated that temporal GALC expression during this time is a major contributor to brainstem development, Shin says. Augmenting GALC levels at or prior to this newly defined period would likely improve the efficacy of therapeutic interventions for Krabbe patients.

While the time scale between mice and humans is considerably different, the sequence of key events in brain maturation between the two is consistent, he notes. It was estimated that the mouse nervous system at postnatal days 4-6 corresponds to a gestational age of 32 weeks in humans. Therefore, we anticipate that if our result is correct, then in utero treatments at, or prior to, 32 weeks should have better outcomes than conventional postnatal treatment for Krabbe babies.

Shin says his team will further identify which cell type needs to be targeted with therapy.

This work will directly impact the design of novel treatment options for KD patients, he says, noting that KD studies are at the basis of research on other, more common neurodegenerative diseases, such as multiple sclerosis and Parkinsons disease. Therefore, the teams work will have implications beyond KD.

Co-authors on the research were Nadav I. Weinstock, MD-PhD student, and Conlan Kreher, former masters student, both of the HJKRI and the Department of Biochemistry in the Jacobs School; Jacob Favret, research technician in the Department of Biotechnical and Clinical Laboratory Sciences; Lawrence Wrabetz and M. Laura Feltri, both co-directors of the HJKRI and members of the departments of Biochemistry and Neurology, as well as the Neuroscience Program.

Duc Nguyen and Ernesto R. Bongarzone of the Department of Anatomy and Cell Biology in the College of Medicine at the University of Illinois at Chicago also participated in the research.

The project was initiated with the support from Empire State development fund for HJKRI, and further developed and finalized by the R01, R56 and R03 grants from National Institutes for Health-National Institute for Neurological Disorders and Stroke awarded to Shin.

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UB researcher narrows time window for administering specific treatment to infants with Krabbe disease - UB Now: News and views for UB faculty and...

BOSTON & LOUISVILLE, Ky.--(BUSINESS WIRE)--Talaris Therapeutics, Inc., a privately held biotechnology company developing transformative cell therapies that have the potential to induce durable immune tolerance across a range of indications, today announced the expansion of its senior leadership team with the appointments of Michael Zdanowski as Chief Technology Officer, Farah Natoli as Head of Portfolio and Program Management and Mary West as Vice President, Clinical Operations.

The appointments of Michael, Farah and Mary build on our recently announced Series B financing to position Talaris for long-term success, as we advance our ongoing Phase 3 trial in living donor kidney transplant, prepare for additional Phase 2 trials next year and further realize the pipeline in a product potential of our unique cell therapy. Their accomplished and diverse backgrounds in manufacturing, portfolio strategy and clinical operations will be key assets guiding our future strategic direction, said Scott Requadt, Chief Executive Officer of Talaris. We are excited to welcome them to the Talaris team and look forward to their important contributions to Talaris continued success.

Mr. Zdanowski, Chief Technology Officer, is an accomplished leader in cell therapy manufacturing with over 25 years of experience. He has led manufacturing, logistics, quality and analytical development groups for stem cell organizations, and led design, construction and validation of facilities for commercial manufacturing for such firms as Pfizer Pharmaceuticals, Bayer Pharmaceuticals and Regeneron Pharmaceuticals. He was most recently Senior Vice President of BioPharmaceutical Operations for Medeor Therapeutics. Previously, Mr. Zdanowski was Vice President of GMP Operations for the New York Stem Cell Foundation and Vice President of Manufacturing for Mesoblast. Mr. Zdanowski has prepared FDA & EU CMC submissions for several late-stage stem cell products, including the BLA supporting FDA approval for the first allogeneic stem cell therapy product, HemaCord. He received his MBA from Columbia University and degrees in mechanical engineering and philosophy from the University of Pennsylvania.

Ms. Natoli, Head of Portfolio and Program Management, brings deep expertise in strategic direction and operational oversight of program advancement. She served most recently as Vice President, Program Management at Imara, in which capacity she provided strategic and operational leadership for Imaras global programs in sickle cell anemia and beta-thalassemia. Previously, Ms. Natoli served as the Executive Director, Program and Alliance Leadership at Bioverativ, a Sanofi Company; prior to that she held roles at AMAG Pharmaceuticals and FORUM Pharmaceuticals. Ms. Natoli holds an M.S. in natural sciences from the Roswell Park Cancer Institute, a division of State University of New York at Buffalo, and graduated with a B.S. in biology-chemistry and medical technology from Elmira College.

Ms. West, Vice President, Clinical Operations, brings an extensive background in complex clinical trial execution and team leadership. Most notably, she led all clinical operations at Boston-based Alnylam Pharmaceuticals for their lead product, Onpattro, in a successful registration trial that recruited over 220 patients globally and led to the historic approval of the product in late 2018. Ms. West previously served in clinical operations leadership roles at Paratek Pharmaceuticals, Momenta Pharmaceuticals, Acambis Pharmaceuticals, Millennium Pharmaceuticals and Pfizer Pharmaceuticals. Until recently, she was Head of Clinical Operations at BlueRock Therapeutics, where she implemented all of their GCP quality systems and laid the operational groundwork for their first IND. Ms. West received her M.S. in project management from Boston University and her B.S. in dietetics from Michigan State University.

About Talaris Therapeutics

Talaris Therapeutics, Inc. is a late-clinical stage biotechnology company that is developing transformative cell therapies with the potential to eliminate the burden of chronic immunosuppression for organ transplant recipients as well as induce durable remissions in patients with severe autoimmune and immune-mediated disorders. Talaris is backed by a number of leading life sciences investors and maintains corporate offices in Boston, Mass., and its cell processing facility in Louisville, Ky. http://www.TalarisTx.com.

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Talaris Therapeutics Expands Leadership Team With Appointments of Accomplished Executives in Manufacturing, Portfolio Strategy and Clinical Operations...