NEW YORK / ACCESSWIRE / November 11, 2019 / Kadmon Holdings, Inc. (KDMN) today announced positive topline results from the planned interim analysis of ROCKstar (KD025-213), the fully enrolled pivotal trial evaluating KD025 in patients with chronic graft-versus-host disease (cGVHD) who have received at least two prior lines of systemic therapy. The trial met the primary endpoint of Overall Response Rate (ORR) at the interim analysis, which was conducted as scheduled two months after completion of enrollment.

KD025 showed statistically significant ORRs of 64% with KD025 200 mg once daily (QD) (95% Confidence Interval (CI): 51%, 75%; p<0.0001) and 67% with KD025 200 mg twice daily (BID) (95% CI: 54%, 78%; p<0.0001). KD025 has been well tolerated and adverse events have been consistent with those expected in the patient population.

"We are extremely pleased with the outcomes of the interim analysis, which showed that KD025 has already greatly exceeded the threshold for success in this pivotal trial," said Harlan W. Waksal, M.D., President and CEO of Kadmon. "We look forward to sharing these results with the FDA at a pre-NDA meeting, where we will also discuss the timing for a regulatory filing for KD025 in cGVHD, which we expect to occur in 2020, subject to FDA input."

"KD025 was shown to be a highly active and well-tolerated therapy across the spectrum of this complex, multi-organ disease," said Corey Cutler, MD, MPH, FRCPC, Associate Professor of Medicine, Harvard Medical School; Medical Director, Adult Stem Cell Transplantation Program, Dana-Farber Cancer Institute and a KD025-213 study investigator and Steering Committee member. "The response rates observed are particularly impressive since this study is being conducted in a real-world population with severe disease, supporting the potential role of KD025 in cGVHD patients who are in need of effective and well-tolerated therapies."

"It is highly encouraging to see the positive results from the pivotal trial are in line with those observed in the earlier Phase 2 study of KD025 in this difficult-to-treat disease," said Madan Jagasia, MD, Vanderbilt University, an investigator of the KD025-208 and KD025-213 studies and the KD025-213 Steering Committee chair. "These latest KD025 data continue to underscore the value that KD025 may offer to cGVHD patients."

KD025-213 is an ongoing open-label trial of KD025 in adults and adolescents with cGVHD who have received at least two prior lines of systemic therapy. Patients were randomized to receive KD025 200 mg QD or KD025 200 mg BID, enrolling 66 patients per arm. Statistical significance is achieved if the lower bound of the 95% CI of ORR exceeds 30%, which was achieved in both arms of the trial at the interim analysis.

While the ORR endpoint was met at the interim analysis, the primary analysis of the KD025-213 study will occur in the first quarter of 2020, six months after completion of enrollment. This analysis will include updated safety data and efficacy data, including ORRs and secondary endpoints, such as duration of response, changes in corticosteroid dose and changes in quality of life. Kadmon plans to submit results from the KD025-213 study for presentation at an upcoming scientific meeting.

Conference Call and Webcast

Kadmon will host a conference call and webcast on Monday, November 11, 2019, at 5:00 p.m., Eastern time, to discuss the topline results of the interim analysis of the KD025-213 study.

To participate in the conference call, please dial (866) 762-3021 (domestic) or (703) 925-2661 (international) and reference the conference ID: 6468498. The accompanying slides will be available for download on Kadmon's website beginning at 5:00 p.m. Eastern time.

To listen online via webcast, please visit: https://edge.media-server.com/mmc/p/9b9w8p38. The webcast will be archived and will be available at http://investors.kadmon.com/presentations-and-events.

About KD025

KD025 is a selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates inflammatory response. In addition to cGVHD, KD025 is being studied in an ongoing Phase 2 clinical trial in adults with diffuse cutaneous systemic sclerosis (KD025-209). KD025 was granted Breakthrough Therapy Designation and Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD who have received at least two prior lines of systemic therapy.

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About cGVHD

cGVHD is a common and often fatal complication following hematopoietic stem cell transplantation. In cGVHD, transplanted immune cells (graft) attack the patient's cells (host), leading to inflammation and fibrosis in multiple tissues, including skin, mouth, eye, joints, liver, lung, esophagus and gastrointestinal tract. Approximately 14,000 patients in the United States are currently living with cGVHD, and approximately 5,000 new patients are diagnosed with cGVHD per year.

About Kadmon

Kadmon is a biopharmaceutical company developing innovative products for significant unmet medical needs. Our product pipeline is focused on inflammatory and fibrotic diseases as well as immuno-oncology.

Forward Looking Statements

This press release contains forward-looking statements. Such statements may be preceded by the words "may," "will," "should," "expects," "plans," "anticipates," "could," "intends," "targets," "projects," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. Forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. We believe that these factors include, but are not limited to, (i) the initiation, timing, progress and results of our preclinical studies and clinical trials, including KD025-213, and our research and development programs; (ii) our ability to advance product candidates into, and successfully complete, clinical trials; (iii) our reliance on the success of our product candidates, including KD025; (iv) the timing or likelihood of regulatory filings and approvals, including in connection with KD025-213; (v) our ability to expand our sales and marketing capabilities; (vi) the commercialization of our product candidates, if approved; (vii) the pricing and reimbursement of our product candidates, if approved; (viii) the implementation of our business model, strategic plans for our business, product candidates and technology; (ix) the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and technology; (x) our ability to operate our business without infringing the intellectual property rights and proprietary technology of third parties; (xi) costs associated with defending intellectual property infringement, product liability and other claims; (xii) regulatory developments in the United States, Europe and other jurisdictions; (xiii) estimates of our expenses, future revenues, capital requirements and our needs for additional financing; (xiv) the potential benefits of strategic collaboration agreements and our ability to enter into strategic arrangements; (xv) our ability to maintain and establish collaborations or obtain additional grant funding; (xvi) the rate and degree of market acceptance of our product candidates; (xvii) developments relating to our competitors and our industry, including competing therapies; (xviii) our ability to effectively manage our anticipated growth; (xix) our ability to attract and retain qualified employees and key personnel; (xx) our ability to achieve cost savings and other benefits from our efforts to streamline our operations and to not harm our business with such efforts; (xxi) the use of proceeds from our recent public offerings; (xxii) the potential benefits of any of our product candidates being granted orphan drug designation; (xxiii) the future trading price of the shares of our common stock and impact of securities analysts' reports on these prices; and/or (xxiv) other risks and uncertainties. More detailed information about Kadmon and the risk factors that may affect the realization of forward-looking statements is set forth in Kadmon's filings with the U.S. Securities and Exchange Commission (the "SEC"), including Kadmon's Annual Report on Form 10-K for the fiscal year ended December 31, 2018 and subsequent Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SEC's website at http://www.sec.gov. Kadmon assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise.

Contact Information

Ellen Cavaleri, Investor Relations646.490.2989ellen.cavaleri@kadmon.com

SOURCE: Kadmon Holdings, Inc.

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Kadmon Announces that KD025 Met Primary Endpoint at Interim Analysis of Pivotal Trial in Chronic Graft-Versus-Host Disease - Yahoo Finance

Skin Stem Cells Comments Off on Kadmon Announces that KD025 Met Primary Endpoint at Interim Analysis of Pivotal Trial in Chronic Graft-Versus-Host Disease – Yahoo Finance | November 11th, 2019

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Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

Know the Growth Opportunities in Emerging Markets

Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

The regional analysis covers:

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Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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Stem Cell Therapy Market Poised to Expand at a Robust Pace Over 2025 - Tech Admirers

Cardiac Stem Cells Comments Off on Stem Cell Therapy Market Poised to Expand at a Robust Pace Over 2025 – Tech Admirers | November 11th, 2019

US Stem Cell (OTCMKTS:USRM) and Auxly Cannabis Group (OTCMKTS:CBWTF) are both small-cap medical companies, but which is the superior business? We will contrast the two businesses based on the strength of their risk, earnings, analyst recommendations, valuation, profitability, dividends and institutional ownership.

Valuation & Earnings

This table compares US Stem Cell and Auxly Cannabis Groups gross revenue, earnings per share (EPS) and valuation.

US Stem Cell has higher revenue and earnings than Auxly Cannabis Group.

Risk & Volatility

US Stem Cell has a beta of 5.05, suggesting that its stock price is 405% more volatile than the S&P 500. Comparatively, Auxly Cannabis Group has a beta of 0.62, suggesting that its stock price is 38% less volatile than the S&P 500.

Analyst Ratings

This is a summary of current ratings for US Stem Cell and Auxly Cannabis Group, as provided by MarketBeat.com.

Institutional and Insider Ownership

0.0% of Auxly Cannabis Group shares are held by institutional investors. 16.7% of US Stem Cell shares are held by company insiders. Strong institutional ownership is an indication that large money managers, endowments and hedge funds believe a company will outperform the market over the long term.

Profitability

This table compares US Stem Cell and Auxly Cannabis Groups net margins, return on equity and return on assets.

Summary

US Stem Cell beats Auxly Cannabis Group on 6 of the 9 factors compared between the two stocks.

US Stem Cell Company Profile

U.S. Stem Cell, Inc., a biotechnology company, focuses on the discovery, development, and commercialization of autologous cellular therapies for the treatment of chronic and acute heart damage, and vascular and autoimmune diseases in the United States and internationally. Its lead product candidates include MyoCell, a clinical therapy designed to populate regions of scar tissue within a patient's heart with autologous muscle cells or cells from a patient's body for enhancing cardiac function in chronic heart failure patients; and AdipoCell, a patient-derived cell therapy for the treatment of acute myocardial infarction, chronic heart ischemia, and lower limb ischemia. The company's product development pipeline includes MyoCell SDF-1, an autologous muscle-derived cellular therapy for improving cardiac function in chronic heart failure patients. It is also developing MyoCath, a deflecting tip needle injection catheter that is used to inject cells into cardiac tissue in therapeutic procedures to treat chronic heart ischemia and congestive heart failure. In addition, the company provides physician and patient based regenerative medicine/cell therapy training, cell collection, and cell storage services; and cell collection and treatment kits for humans and animals, as well operates a cell therapy clinic. The company was formerly known as Bioheart, Inc. and changed its name to U.S. Stem Cell, Inc. in October 2015. U.S. Stem Cell, Inc. was founded in 1999 and is headquartered in Sunrise, Florida.

Auxly Cannabis Group Company Profile

Auxly Cannabis Group Inc. operates as a cannabis streaming company. It provides funding for cannabis production; and holds contractual rights and minority equity interest relating to the operation of cannabis facilities. The company was formerly known as Cannabis Wheaton Income Corp. and changed its name to Auxly Cannabis Group Inc. in June 2018. Auxly Cannabis Group Inc. was incorporated in 1987 and is headquartered in Vancouver, Canada.

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Reviewing US Stem Cell (OTCMKTS:USRM) and Auxly Cannabis Group (OTCMKTS:CBWTF) - Riverton Roll

Cardiac Stem Cells Comments Off on Reviewing US Stem Cell (OTCMKTS:USRM) and Auxly Cannabis Group (OTCMKTS:CBWTF) – Riverton Roll | November 11th, 2019

Scientists from Dystrogen Therapeutics Corp. published data supporting cardioprotective effects of the Companys therapy for muscular dystrophy disorders. Cardiomyopathy is the most devastating cause of morbidity and mortality in Duchenne Muscular Dystrophy (DMD) patients and affects 30% of patients by 14years of age and 50% of patients by 18years of age. Heart failure in these patients is the result of cardiac myocyte death and fibrosis, leading to both diastolic and systolic dysfunction.

Dystrogen Therapeutics Corp has developed an engineered chimeric cell therapy which has been previously shown to restore muscle function in pre-clinical studies. For Duchennes muscular dystrophy, the company has developed dystrophin expressing chimeras DECs. Using the companys proprietary technology, DECs are created by an ex vivo fusion of allogeneic human myoblast from a healthy donor with autologous human myoblast received from DMD patient. DECs have been shown to maintain the ability to express normal dystrophin protein in previously published pre-clinical studies.

The new study published in theOctober 15th, 2019online edition of the journalStem Cell Reports and Reviewsconfirmed the protective effect of DEC on cardiac function after intraosseous delivery shown by increased values of both ejection fraction and fractional shortening, which at 90days revealed a rebound effect when compared to the vehicle injected controls and mice receiving not-chimeric cell therapy. Moreover, these functional improvements correlated with restoration of dystrophin expression in cardiac muscle at 90days post-DEC treatment.

These findings are potentially significant for the treatment of DMD, said Dr. Maria Siemionow, MD, PhD Dystrogen Therapeutics Corp chief scientific officer and the therapys inventor. This study establishes DEC as a promising new option for cardiac protection and potential amelioration of DMD related cardiac pathology.

These data add to the growing body of literature supporting the potential of our chimeric cell platform to restore systemic muscle function, with less potential side effects then gene therapy-based approaches, said Dr. Kris Siemionow, MD, PhD Dystrogen Therapeutics Corp CEO. We are very pleased to have these data published in a highly relevant journal for the field and look forward to further exploring this opportunity.

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Dystrogen Therapeutics Announces That Treatment With DEC Cells Improves Cardiac Function Cardiology2.0 - Cardiology2.0

Cardiac Stem Cells Comments Off on Dystrogen Therapeutics Announces That Treatment With DEC Cells Improves Cardiac Function Cardiology2.0 – Cardiology2.0 | November 11th, 2019

Another seminar is again advertised in The Union. I first thought it might help my wife with neuropathy until I did some extensive research.

First off, Medicare does not cover stem cell injections. Bone marrow stem cell injections range from $2,000 to $5,000 or more. Read Consumer Research report at: https://www.consumerreports.org/medical-treatments-procedures/trouble-with-stem-cell-therapy.

Stem cell treatments are widely accepted only for two broad medical indications: to help treat a handful of blood disorders including leukemia and some forms of anemia and in some cases to help burn victims. Ask questions. Any doctor who offers stem cell therapy should be able to explain where the cells will come from, what will be done to them before theyre injected into your body, and how, exactly, they will resolve your illness or injury. He or she should also be able to offer you proof of safety and efficacy, even for experimental treatments. Dont rely on patient testimonials.

Stem cells survive much longer than ordinary cells, increasing the chance that they might accumulate genetic mutations. It might take only a few mutations for one cell to lose control over its self-renewal and growth and become the source of cancer. Please do your own research.

Gary Pesselt

Grass Valley

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Gary Pesselt: Vitality Healthcare is it worth the cost? - The Union of Grass Valley

Bone Marrow Stem Cells Comments Off on Gary Pesselt: Vitality Healthcare is it worth the cost? – The Union of Grass Valley | November 10th, 2019

Whoever saves a single life is considered by the Talmud to have saved the whole world.

In August 2013, Jeffrey Altadonna, who was on a Birthright trip, was tested at a bone marrow testing drive at the Jerusalem Gate Hotel.

It was perfectly ordinary summer day when the 29-year-old accountant from Sherman Oaks, California received the fateful phone call.

A 77-year-old woman from Los Angeles was the perfect stranger that he was deemed to save.

Diane Gebel, a widow from Cyprus, California was diagnosed with Acute Myeloid Leukemia (AML). Her husband had passed away right before she was diagnosed with cancer.

For an entire year, the donor and recipient need to remain anonymous to each other, but last week, the time came for the two to finally meet.

The two were honored at the Los Angeles One Huge Night Gala event hosted by Gift of Life.

In a statement, Birthright Israel explained that the gala also celebrated the successful 15-year partnership of Birthright Israel and Gift of Life.

This partnership has so far resulted in 83,000 Birthright donors joining the registry, with 1,900 matches made between patients and Birthright donors, and 241 life-saving transplants to date.

Prior to the meeting, Altadonna recalled his Birthright trip explaining that it was really great to see that part of the world, to go to where its our given right to visit.

It had a profound effect on my friendships and cultural Jewish identity to see that Jewish people are one people, and we have each others backs, he said. It left me with the feeling that I had backing in anything that I wanted to do in my life. It really felt like a family.

He recalled that after being swabbed at the drive, he didnt really think too much of it because everyone did it.

I got the donation call 15 months ago, he explained, adding that he immediately decided to donate. I find it very bizarre, that everyone is telling me Its such a great thing that you are doing. For me, it wasnt an option to say yes or no, its just, Okay, lets do this, Im a match. Im surprised that more people dont donate.

After doing preliminary tests, he took the plunge and donated.

I had to do it early in the morning, it lasted 6-8 hours a marathon blood donation and it was finished,Altadonna continued. It didnt seem all that hard to me.

He made it clear that this opportunity to help only came about because of the Birthright Israel and Gift of Life collaboration.

It wasnt a mission of mine. I wouldnt have gone out of my way to get swabbed, so it only happened as a result of their collaboration, he said.

In an emotional meeting, the two finally met. Of the meeting, Gebel stressed that she is here because of my selfless and generous donor.

For me, it was easy, I just had an infusion, but for him it was hard, she said. It takes a very special person to do that, to actually give the gift of life.

Gebel said she had been waiting to meet him.

I didnt know he was such a good looking guy, Gebel joked. Im here because of him. I was not ready to die. I had too much to live for.

She stressed that she has changed because of my new life.

I take risks, I live my life fully, she explained. My motto has always been that I want to go through life with a Cosmopolitan in one hand and a travel book in the other. Because of my donor, I can do that, so I thank him from the bottom of my heart.

Altadonna called on others to also take the plunge by getting tested and donating.

I stand here for my recipients valor, for her victory. I ask you to do the same: sit and swab today, so someone can swim and live tomorrow, he said.

Birthrights International CEO Gidi Mark said he was proud of our participants who register as donors and the powerful impact of such a simple choice when they get the call that they are the perfect match for a perfect stranger.

It is a great honor that Birthright Israel is able to assist in this mission, he added.

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Perfect match: How Birthright alumni saved the lives of 100s of strangers - The Jerusalem Post

Bone Marrow Stem Cells Comments Off on Perfect match: How Birthright alumni saved the lives of 100s of strangers – The Jerusalem Post | November 10th, 2019

Home News Going into Space Changes the Human Heart Cells, but What Happens When They Get Back on Earth?

Commonly, astronauts stay in space for a more extended period of time, and NASA is planning longer missions to the Moon and Mars. Researchers say that we need to understand better the effects that microgravity has on the heart.

Studies have shown that spaceflight can reduce heart rate and the lower arterial pressure, and can also increase cardiac output. However, new research shows how microgravity zero gravity has an impact on the human heart when it comes to the cellular level.

Scientists have been able to check the health of astronauts while they were in space, which was a great way to understand the molecular cell changes. This comes from Joseph C. Wu, from Stanford Universitys School of Medicine. He is the author of the study.

The health of humans can be sustained for about a year in space, says NASA. When trying to answer this, researchers from Stanford University have taken a look at the cardiac function and at the gene expression in the human heart cells from three people. The cells did not come from biopsies, but they were made by reprogramming a sample of blood into the human stem cells. Then, the heart cells were cultured abroad the International Space Station for around 5 weeks. This is the first study of this kind.

Scientists found that the exposure to microgravity changed the expression of 2.635 genes, which was a temporary change in the RNA, that is made from DNA. Most of them returned to the normal patterns of gene expression in about 10 days after coming back to Earth. RNA is a temporary and handwritten copy of the DNA. So the gene expression was temporarily changed by the environment microgravity. The changes were subtle, but they were still significant.

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Going into Space Changes the Human Heart Cells, but What Happens When They Get Back on Earth? - Henri Le Chat Noir

Cardiac Stem Cells Comments Off on Going into Space Changes the Human Heart Cells, but What Happens When They Get Back on Earth? – Henri Le Chat Noir | November 10th, 2019

When Nicky Turkoz (aboveleft) was diagnosed with leukaemia, her only hope was an anonymous stem-cell donation. That donor was Annette Hamson (above right) and the two, once strangers, now share an unbreakable bond

I was wrestling the Christmas decorations down from the loft when I got the call. I can remember hearing the landline ring and telling my daughter, Meltem, who was steadying the ladder, to leave it. They can call back if its urgent, I said. My mobile rang and we left that too, but the landline went again. I better get it, Mum, said Meltem. Someone clearly wants to talk to you. She answered it as I was hauling the last of the decorations down. Its the surgery, she said, passing the phone to me.

That morning Id had a blood test. Id been feeling strange for months and had finally made an appointment to see the GP. I told her I was feeling lethargic and depressed, which was very unlike me, but Id put it down to ageing and a spot of empty-nest syndrome, as my youngest daughter Zeynep had just left home to work abroad. Odd things, such as a recurring gum infection, were making me wonder if something else was going on. My GP seemed unconcerned but sent me for blood tests anyway. A few hours later she was telling me to pack an overnight bag and get to hospital. Your results show youre very anaemic, she said. Theyll need to do some more tests. You might be there a while.

She never used the word cancer. Looking back, I think she knew then but was sugar- coating it for me. We left the decorations.

Three hours later, after more prodding and poking, a consultant told me I had acute myeloid leukaemia, a blood cancer. It seems unbelievable now but I can remember thinking, Well, thank goodness theyve found something wrong with me, I knew I wasnt feeling great. I had no idea, of course, what was coming down the track.

It was a Wednesday evening and I was told they would start my chemotherapy on the Friday, but Id need to stay in hospital in the meantime. So while I was being installed on a ward, my poor daughter was handed a leaflet about myeloid leukaemia and drove home to our undecorated tree.

The first round of chemo lasted 10 days, which meant I had to miss Meltems 23rd birthday on 21 December. Zeynep left Gran Canaria, where she had just started working as a holiday rep, and flew home to be with us. It has always been just the three of us, ever since they were tiny. Im a very can-do sort of person and have always just got on with life whatever it has thrown at us. I couldnt bear it when my girls suddenly had to look after me. It all just seemed so unfair. I suppose everyone feels like that though.

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'I've become best friends with the woman who saved my life' - Telegraph.co.uk

Bone Marrow Stem Cells Comments Off on ‘I’ve become best friends with the woman who saved my life’ – Telegraph.co.uk | November 9th, 2019

Scientists at Harvard-affiliated Massachusetts General Hospital (MGH) have identified a previously unknown biological pathway that promotes chronic inflammation and may help explain why sedentary people have an increased risk for heart disease and strokes.

In a study to be published in the November issue ofNature Medicine, MGH scientists and colleagues at several other institutions found that regular exercise blocks this pathway. This discovery could aid the development of new therapies to prevent cardiovascular disease.

Regular exercise protects the cardiovascular system by reducing risk factors such as cholesterol and blood pressure. But we believe there are certain risk factors for cardiovascular disease that are not fully understood, said Matthias Nahrendorf of the Center for Systems Biology at MGH. In particular, Nahrendorf and his team wanted to better understand the role of chronic inflammation, which contributes to the formation of artery-clogging blockages called plaques.

Nahrendorf and colleagues examined how physical activity affects the activity of bone marrow, specifically hematopoietic stem and progenitor cells (HSPCs). HSPCs can turn into any type of blood cell, including white blood cells called leukocytes, which promote inflammation. The body needs leukocytes to defend against infection and remove foreign bodies.

When these [white blood] cells become overzealous, they start inflammation in places where they shouldnt, including the walls of arteries.

Matthias Nahrendorf

But when these cells become overzealous, they start inflammation in places where they shouldnt, including the walls of arteries, said Nahrendorf.

Nahrendorf and his colleagues studied a group of laboratory mice that were housed in cages with treadmills. Some of the mice ran as much as six miles a night on the spinning wheels. Mice in a second group were housed in cages without treadmills. After six weeks, the running mice had significantly reduced HSPC activity and lower levels of inflammatory leukocytes than the mice that simply sat around their cages all day.

Nahrendorf explains that exercising caused the mice to produce less leptin, a hormone made by fat tissue that helps control appetite, but also signaled HSPCs to become more active and increase production of leukocytes. In two large studies, the team detected high levels of leptin and leukocytes in sedentary humans who have cardiovascular disease linked to chronic inflammation.

This study identifies a new molecular connection between exercise and inflammation that takes place in the bone marrow and highlights a previously unappreciated role of leptin in exercise-mediated cardiovascular protection, said Michelle Olive, program officer at the National Heart, Lung, and Blood Institute Division of Cardiovascular Sciences. This work adds a new piece to the puzzle of how sedentary lifestyles affect cardiovascular health and underscores the importance of following physical-activity guidelines.

Reassuringly, the study found that lowering leukocyte levels by exercising didnt make the running mice vulnerable to infection. This study underscores the importance of regular physical activity, but further focus on how exercise dampens inflammation could lead to novel strategies for preventing heart attacks and strokes. We hope this research will give rise to new therapeutics that approach cardiovascular disease from a completely new angle, said Nahrendorf.

The primary authors of theNature Medicinepaper are Nahrendorf, who is also a professor of radiology at Harvard Medical School; Vanessa Frodermann, a former postdoctoral fellow at MGH who is now a senior scientist at Novo Nordisk; David Rohde, a research fellow in the Department of Radiology at MGH; and Filip K. Swirski, an investigator in the Department of Radiology at MGH.

The work was funded bygrantsHL142494 andHL139598from the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

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Exercise found to block chronic inflammation in mice - Harvard Gazette

Bone Marrow Stem Cells Comments Off on Exercise found to block chronic inflammation in mice – Harvard Gazette | November 9th, 2019

Doris A. Taylors so-called replacement ghost heart suggests something otherworldly, but the eerie-looking form is far from an apparition. Its an innovative approach to organ transplantation that has inspired many in the medical community and at least one artist.

The Texas researchers process piggybacks on natures sophisticated design. Together she and a team of researchers strip cells off human and animal cadaver hearts with a soapy solution, leaving ghostly white protein shells that retain the form of the organ. They inject them with a patients blood or bone-marrow stem cells, and the ghost hearts act as scaffolding on which the newly introduced cells can slowly transform into a beating muscle.

What we said was, Wouldnt it be really cool if we could wash the sick cells out and put the healthy cells back in? said Taylor, director of Regenerative Medicine Research and director of the Center for Cell and Organ Biotechnology at the Texas Heart Institute, during a recent talk at the Radcliffe Institute for Advanced Study.

The hope is that one day these regenerated hearts will resolve the most challenging issues transplant patients currently face: the lack of a permanent artificial replacement, concerns about rejection, and the shortage of viable donor hearts.

Taylors efforts are driving what could become a revolution in organ transplants, and they have sparked the creativity of transdisciplinary artist Dario Robleto, whose latest work, on view at the Johnson-Kulukundis Family Gallery in Radcliffes Byerly Hall, recreates in images and sounds the original pulse wave of the heart first captured in visual form by scientists in the 1900s. Robleto and Taylor, longtime friends and Texas residents, explored those connections during Mondays Radcliffe discussion, which was moderated by Jennifer Roberts, Elizabeth Cary Agassiz Professor of the Humanities.

Robletos exhibit, Unknown and Solitary Seas, touches on the overlap between the medical mysteries and workings of the vascular pump, and the metaphor for the heart as the emotional center of the soul. It includes a video installation that features recreated sounds of a beating heart from the 19th century, reconstructed images of how the earliest pulse waves first appeared on the page, and a series of heart waveform sculptures in brass-plated stainless steel.

Roberts said that with his work, Robleto acknowledges the pulse waves promise, their profundity, their scientific value, but he also reclaims some of their ambiguity and asks us to wonder whether we can or should accept that these waveforms have escaped the realms of art, culture, and emotional communication.

Taylor similarly views her work as a blend of the scientific and the human. It transcends complicated, complex science, she says, in that her ghost hearts require a kind of passion, commitment, care, attention, and nurturing similar to whats required by a small child. Its really about building hearts at the emotional, mental, spiritual, and physical level that I think is going to get them to work, she said.

For Robleto, big ideas, like the creation of a new human heart, require multiple perspectives.

The artist called Taylors work one of the most fascinating and definitely one of the most emotional things Ive ever seen. As an object, he added, the ghost heart is stunningly beautiful but it also raises questions about the self, identity, emotion, the notions of form and where memory is truly held, questions he thinks artists can help address. He cited two of the nations earliest heart transplants, after which the patients wives asked their husbands, who had received donor hearts, if they still loved them.

Taylors work, Robleto said, is right at the edge of identity and materiality and so when the day comes when someone says the first ghost heart transplant I think we will have a similar moment where perhaps we will be forced to re-evaluate what we ask from our heart metaphor.

Dario Robletos Unknown and Solitary Seas is on view in Byerly Halls Johnson-Kulukundis Family Gallery through Jan. 18, 2020.

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An artist and a transplant researcher discuss the heart - Harvard Gazette

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Ambrosia Health is back.

Following a brief shuttering and then a rebranding effort during which it was known as Ivy Plasma the young blood clinic has gone back to its roots: selling plasma sourced from the blood of 16- to 25- year-olds to healthy patients who believe the transfusions can give them ill-defined health benefits.

People really like the Ambrosia name and brand, so Ambrosia is going to continue, Ambrosia founder and young blood advocate Jesse Karmazin told OneZero. The resounding response from people wanting to sign up was, keep things the same. So thats what were going to do.

With the return to its original branding, Ambrosia is also embracing a new business model.

When it was Ivy Plasma, the clinic offered transfusions in San Francisco and Tampa. It since shuttered the clinic in Tampa, but Karmazin told Futurism that Ambrosia will ship plasma directly to any customers doctor so they can get their dose of young blood without having to fly to California.

We use overnight shipping to deliver the plasma to patients doctors offices, and provide training for the doctors to infuse it, Karmazin told Futurism last month. This way, the number of patients we are able to serve has increased dramatically. I dont operate a blood bank.

Ambrosias checkered, on-again-off-again status was spurred by an FDA statement issued in February in which the regulatory agency warned that transfusions of young blood didnt have any of the health benefits especially enhanced youthfulness, improved longevity, or reversedmemory loss that advocates claimed it did.

In slightly more words, the FDA essentially called young blood transfusions dangerous scams.

Because of the FDA warning, Karmazins clinic offered off-label treatments when it resurfaced as Ivy Plasma. That meant that customers could get their treatments if they desired, but they did so at their own risk and then-Ivy Plasma wasnt legally permitted to claim it would do them any good.

That practice continues today in the newly rebranded Ambrosia, according to OneZero. But the clinics updated website includes more details about the treatment.

Our treatment has been found to produce statistically significant improvements in biomarkers related to Alzheimers disease, cancer, inflammation, and stem cells in our clinical trial, the website reads. Patients have reported subjective improvements in athletics, memory, skin quality, sleep, and other areas.

When asked whether the FDAs rules had grown more lenient, Karmazin told Futurism he had consulted with the agency as well as a number of lawyers and wasnt worried about the claims made on his website.

Im comfortable with going ahead and offering this treatment commercially to patients, he told OneZero.

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Since 2006, when Shinya Yamanaka, now the director of the Center for iPS Cell Research and Application at Kyoto University, discovered a method that could guide fully differentiated cells back to their pluripotent state, scientists have been using his recipe to produce induced pluripotent stem cells. The protocol relies on overexpressing the so-called Yamanaka factors, which are four transcription factors: Oct4, Sox2, Klf4, and cMyc (OSKM). While the technique reliably creates iPS cells, it can cause unintended effects, some of which can lead to cells to become cancerous. So researchers have worked to adjust the cocktail and understand the function of each factor.

No one had succeeded in creating iPS cells without forcing the overexpression of Oct4. It was thought that this was the most crucial factor of the four. At least until now.

If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

Shinya Yamanaka, Kyoto University

Four years ago, Sergiy Velychko, a graduate student at the Max Planck Institute for Molecular Biomedicine in Hans Schlers lab, and his team were studying the role of Oct4 in creating iPS cells from mouse embryonic fibroblasts. He used vectors to introduce various mutations of the gene coding for Oct4 to the cells he was studying, along with a negative controlone that didnt deliver any Oct4. He was shocked to discover that even using his negative control, he was able to generate iPS cells.

Velychkos experiment was suggesting that it is possible to develop iPS cells with only SKM.

We just wanted to publish this observation, Velychko tells The Scientist, but he knew hed need to replicate it first because reviewers wouldnt believe it.

He and his colleagues, including Guangming Wu, a senior scientist in the lab, repeated the experiment several times, engineering vectors with different combinations of the four factors. SKMthe combination that didnt include Oct4was able to induce pluripotency in the cells with about 30 percent of the efficiency of OSKM, but the cells were of higher quality, meaning that the researchers didnt see evidence of common off-target epigenetic effects. They reported their results yesterday (November 7) in Cell Stem Cell.

Efficiency is not important. Efficiency means how many colonies do you get, explains Yossi Buganim, a stem cell researcher at the Hebrew University of Jerusalem, who was not involved in the study. If the colony is of low quality, the chances that eventually the differentiated cells will become cancerous is very high.

Finally, the team employed the ultimate test, the tetraploid complementation assay, in which iPS cells are aggregated with early embryos that otherwise would not have been able to form a fully functional embryo on their own. These embryos grew into mouse pups, meaning that the iPS cells the team created were capable of maturing into every type of cell in the animal.

Whats more is they found that the SKM iPS cells could develop into normal mouse pups 20 times more often than the OSKM iPS cells, suggesting that the pluripotency of iPS cells can be greatly improved by omitting Oct4 from the reprogramming factor cocktail.

The results will need to be verified in human cells, Buganim cautions. His team has developed methods for creating iPSCs that worked well in mouse cells only to be completely ineffective in humans.

Yamanaka himself was enthusiastic about the results, telling The Scientist in an email that his team would definitely try the method in other cell types, especially adult human blood cells and skin fibroblasts. If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

S.Velychkoet al.,Excluding Oct4 from Yamanaka cocktail unleashes the developmental potential of iPSCs,Cell Stem Cell,doi:10.1016/j.stem.2019.10.002,2019.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

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The recent release of Terminator: Dark Fate saw both Arnold Schwarzenegger and Linda Hamilton reprise their iconic roles and James Cameron's return as a writer and producer. While the sentient killing machines depicted in the Terminator franchise are comprised of CGI and Hollywood special effects, plenty of real world research is going into developing robots with similar capabilities, just without the murderous intent (we hope).

This research spans academia, militaries (though it can be difficult to suss out the actual breakthroughs from government propaganda), and private enterprise. Perhaps the most well known privately-owned robotics developer is Boston Dynamics, makers of the Atlas. You may remember this bipedal robot from September when it showed off its uncanny parkour abilities, which the robot can pull off 80 percent of the time. The Atlas is able to move so fluidly thanks to a novel optimization algorithm that breaks down complex movements into smaller reference motions for its arms, torso, and legs. The Atlas then utilizes a model predictive controller to chain each appendages movements into smoothly flowing movements. However, while Boston Dynamics' Big Dog was developed as a quadrupedal cargo carrier for military operations, the Atlas is strictly for use as an emergency first responder.

But for all of Atlas' fancy footwork, it doesn't look or work very much like the humans it aims to imitate. But, then again, neither did the T-800 from The Terminator and T2: Judgement Day -- at least once stripped of its biological covering. As you can see in the clip below, the T-800's muscles don't operate like a human's. Instead of bundles of contracting fibers, it utilized a complex series of delicate pneumatic compressors to manipulate its movements.

However, building bundles of synthetic muscles is exactly what a number of researchers are currently attempting. These fibers can be made from a variety of materials, from carbon fiber to nylon to exotic polyethylenes. When activated, these materials are capable of lifting up to 1,000 times their own mass (far more than we can) as well as retain a "memory" of their previous shape.

For example, a team of researchers from MIT developed a polymer that can expand 1,000 times its original length and pick up 650 times its own mass. It does this by bonding high-density polyethylene (the stuff used to make recyclable soda bottles) and a stretchy elastomer. This bonded pair naturally coils, like a bedspring. But when heat or cold is applied, the HDPE expands or contracts at five times the rate of the elastomer which lengthens or shortens the coil by as much as 50 percent of its original length.

Similarly, a team from Columbia Engineering recently developed a 3D printed synthetic muscle that not only expands and contracts but also bends, and even twists, on command -- while hauling 1000 times its own mass. This is a big deal because, like the T-800, today's robots are mostly driven by pneumatics, which severely restricts their applications and their overall size. This material, however, can be activated with just 8V of current.

"We've been making great strides toward making robots minds, but robot bodies are still primitive," lead scientist Hod Lipson said in a 2017 statement. "This is a big piece of the puzzle and, like biology, the new actuator can be shaped and reshaped a thousand ways. We've overcome one of the final barriers to making lifelike robots."

Electricity isn't the only potential source of power for these synthetic fibers. Human muscles run on glucose and oxygen, so why not a robot's as well? A research team from Linkping University, Sweden recently did just that and published their findings in the journal, Advanced Materials, this past June.

Their muscle consists of two electroactive polymer sheets sandwiching a non-conductive central membrane. When a positive current is applied to one side (causing it to contract) and a negative current is applied to the other (causing it to expand), the entire thing bends towards the positive charge. But rather than use an electrical current, the Linkping team integrated a naturally occurring enzyme capable of converting chemical energy into electrical energy.

"These enzymes convert glucose and oxygen, in the same way as in the body, to produce the electrons required to power motion in an artificial muscle made from an electroactive polymer. No source of voltage is required: it's enough simply to immerse the actuator into a solution of glucose in water", Edwin Jager, senior lecturer at Linkping University, said in a June statement.

Skin is another sticking point for the T-800 -- it can't travel back in time without an "Edgar Suit" after all -- but modern research is already hard at work on growing human skin in the lab. Don't worry, we're not bringing back Leatherface. It's actually to help eliminate the need for animal testing in the cosmetics industry.

In 2015, cosmetics giant L'Oreal teamed up with 3D printing startup Organovo to begin bioprinting human skin, in half-centimeter square patches. Similarly in 2016, the RIKEN Center for Developmental Biology paired with Tokyo University to grow a nearly complete epidermis -- down to the hair follicles -- that could be transplanted onto live subjects and actually work. The team took cells from the gums of mice and reset them to their stem cell-like iPS state before culturing and then implanting them on other mice, where they grew into integumentary tissue -- that's the layer of cells between the outer and inner skin layers where hairs are developed.

But the skin suit does not make the man -- sit down, Buffalo Bill -- at least when it comes to Terminators. It's their big beautiful AI brains. Obviously, we don't have anything as capable as what sits between the T-800's audio inputs, but that doesn't mean we're not trying. Many of the biggest names in Silicon Valley, including Apple, Huawei, Qualcomm and Alphabet, are racing to develop a new generation of processors specifically designed to handle machine learning tasks. Similar to ARM chips, which pair slower-performing but less energy-intensive cores with more powerful cores with a bigger current draw, the latest generation of "AI chips" integrate cores dedicated to machine learning functions. Image recognition and those sorts of applications -- looking at you Apple Face ID -- are instead routed to the GPU's neural engine.

The T-1000 (portrayed by Robert Patrick in T2 and Byung-hun Lee in Genisys) conveniently didn't require a flesh jacket to get back through time on account of its mimetic poly-alloy "liquid metal" construction. In the movies, these poly-alloys enabled the T-1000 to shrug off immense amounts of damage and change its shape at will. Real-life liquid metals like gallium offer some unique properties of their own like high electrical conductivity and deformability. But there are drawbacks. Most magnetic liquid metals suffer from a high surface tension, limiting their stretchiness to just the horizontal plane. Plus, they typically have to be submerged lest they become a sticky paste when exposed to atmosphere.

To get around these issues, a team of researchers submerged a droplet of gallium-indium-tin alloy in a hydrochloric acid bath. The gallium alloy reacted to the acid, forming a gallium oxide skin on the droplet, which drastically lowered its surface tension and allowed the droplet to be stretched both horizontally and vertically. The results of the team's experiments were published in the journal Applied Materials & Interfaces this past March. But don't worry about getting a finger needle through the eye anytime soon. This research is still in very early development, though it could one day find use in flexible electronics and soft robots.

We're also not likely to see robots melting through gates in the near future, but plenty of robots can already modify their shapes in response to environmental changes. NASA, for example, is working on the Shapeshifter ahead of a proposed expedition to Saturn's moon, Titan.

"We have very limited information about the composition of the surface. Rocky terrain, methane lakes, cryovolcanoes - we potentially have all of these, but we don't know for certain," JPL Principal Investigator Ali Agha said in a statement. "So we thought about how to create a system that is versatile and capable of traversing different types of terrain but also compact enough to launch on a rocket."

The team's answer is a gang of up to 12 small robots, dubbed "cobots," that can Voltron themselves into various configurations depending on the challenge at hand. Each would be capable of autonomous flight. Together they'd be able to daisy chain themselves across gaps or combine into a large wheel for faster overland travel. The team plans to submit their proposal in 2020 for consideration ahead of the next scheduled mission to Titan in 2026.

It may not be able to fully recombine on the other side of a security gate, this tendril-like robot developed by UCSB and Stanford researchers can easily make it between the bars. Taking inspiration from the movements of plant and fungal roots, the inflatable robot can extend up to 72 meters in length. Think of it as one of those balloons that clowns twist into animals, just 236 feet long. By incorporating specialized "control chambers" the robo-tube can also change direction, manipulate objects and even form its own tools, like hooks.

In the third Terminator, T3, Skynet has improved upon the T-1000's poly-alloy design -- this time using it as a protective coating over a super strong endoskeleton -- to create the T-X model. It doesn't just hunt humans, the T-X is a Terminator-killer to boot.

Unfortunately, plenty of research has already been sunk into developing autonomous war machines. In 2016 the US Navy and DARPA collaborated on the Sea Hunter, an autonomous anti-sub system, the US Army is currently accepting proposals for its Advanced Targeting and Lethality Automated System (ATLAS), an AI-powered system able to "acquire, identify, and engage targets at least 3X faster than the current manual process," per the solicitation notice. The Air Force is also exploring the idea of fully autonomous drones as part of its Skyborg project. And those are just a few of the programs we know about.

Whether these systems ever see the light of day -- at least publicly -- remains to be seen given the tremendous public outcry against autonomous weapons. Human Rights Watch is a founding member of the Campaign to Stop Killer Robots and calls for a "preemptive ban on the development, production, and use of fully autonomous weapons." In 2015, robotics researchers and tech luminaries like Steve Wozniak and Stephen Hawking penned an open letter arguing against their development.

"You can't have machines deciding whether humans live or die," Toby Walsh, a professor at the University of New South Wales, told the NYT in July. "It crosses new territory. Machines don't have our moral compass, our compassion and our emotions. Machines are not moral beings."

These pleas have not gone unnoticed. Earlier this month, the Pentagon released draft guidelines regarding AI development. The guidelines demand that AI systems be accountable, avoid bias and be "governable." That is, the systems use an inhibitor function to stop themselves before causing unnecessary harm or damage. Then again, on November 5th, the bipartisan National Security Commission on Artificial Intelligence called for the rapid development and deployment of autonomous weapon systems -- ethical concerns be damned.

"In light of the choices being made by our strategic competitors, the United States must also examine AI through a military lens, including concepts for AI-enabled autonomous operations," the commission's interim report reads.

What could possibly be more terrifying than an unstoppable killing machine? An unstoppable killing machine that can step out of its own skin to become a pair of unstoppable killing machines, that's what. And that's exactly what Sarah Connor has to defeat in Dark Fate. The Rev-9 Terminator builds off of the T-X's endoskeleton-wrapped-in-liquid-metal design except it can separate its halves and fight like those freaky blonde twins from Matrix Reloaded. Our current state of the art swarm technology can't coordinate at that level just yet, but it's getting close.

Drone swarms can actually be quite useful by splitting sensory and processing functions across a group of robots. Lady Gaga would never have been able to pull off her 2017 Super Bowl Halftime Show were it not for a swarm of 300 Intel drones.

This technology has also caught the attention of the US military. The Army, for example, has developed the Perdix system, a hoard of more than 100 microdrones which are launched from a trio of F/A-18 Super Hornets and provide low-altitude surveillance for troops on the ground. The US Navy is developing a similar system, dubbed "swarmbots." These autonomous patrol boats coordinate with one another to investigate suspicious vessels that enter their domain (in this case Chesapeake Harbor) and then relay that information back to a human supervisor. But not all drone swarms wear capes. In 2018, a kidnapping ring leveraged a swarm of drones to buzz an FBI hostage team in the middle of their operation and keep tabs on the Feds' movements.

So even as the military and private enterprises continue to slog towards a future filled with autonomous weapons of war, we can take comfort in knowing that at the current rate of development, we likely won't face a Terminator uprising in our lifetimes. Then again, those maniacal mechanical bastards can time travel.

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Humanity is well on its way to a real-life Terminator uprising - Yahoo Lifestyle

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Hormonal changes can play havoc with our skin as we get older, especially in the perimenopause and menopause years.

These changes aren't the same for every woman, and they don't all begin at once.

During the perimenopause and menopause, the most notable hormonal change is a decline of oestrogen levels.

Oestrogen affects every tissue and organ of the human body, skin included, so the decline of oestrogen in perimenopause and menopause can cause the following symptoms:

Dermatologist and founder of Meder Beauty Science Dr Tiina Meder explained the best way to look after your skin during perimenopause and menopause is a "considered daily skincare routine".

"Using a gentle cleanser will help preserve the skins barrier function and prevent dryness and sensitivity," she said.

"Antioxidant-rich moisturisers, packed with prebiotics, will help keep skin hydrated and protected, simultaneously restoring and preserving the skins microbiome.

"Facial oils will also help to compensate lipid deficiency, while weekly exfoliation will help stimulate skin renewal.

Perimenopausal and menopausal skin is more sensitive to sun exposure.

"The maintenance of melanocytes the cells that manufacture the pigment melanin - is controlled by oestrogen," said Dr Meder.

"During the perimenopause and menopause, the number of melanocytes in your skin reduces andoestrogenlevels decline. As a result, less protective melanin is produced, making the skin appear lighter.

"As melanin helps protect the skin from the environmental damage and sun exposure, a decline in the production of melanin results in skin that is more prone to damage from sun exposure.

"As a consequence, it is very important to protect the skin regularly and correctly the second these hormonal changes appear."

When choosing skincare products thatll protect and repair skin during the perimenopause and menopause, Dr Meder recommends looking out for the following ingredients:

Moisturisers- hyaluronic acid, glycerine, carrageenan, chondrus crispus extract, gluconolactone and others.

Fatty acids and lipids- primrose, apricot, olive, macadamia, sweet almond, argan, borago, canola, meadowfoam, sunflowers, and sesame oil, as well as shea butter, squalane, cacao and, in some cases, coconut butter.

Prebiotics and probiotics- alpha-glucan oligosaccharide, inulin, and others, including some bacterial ferments and lysates (alteromonas filtrate, lactobacillus lysate, and saccharomyces).

Antioxidants- resveratrol, green tea, aloe barbadensis, rosemary and wild carrot extracts, vitamin E and C, and beta-carotene.

Remodelers- EGF (Epidermal Growth Factor) and others growth factors, plant stem cells, and peptides (Matrixyl-3000, Rigin, Syn-Tack and others).

Anti-inflammatories- centella asiatica, aloe barbadensis, green tea, calendula officinalis and chamomilla recutita extracts, panthenol, peptide skinasensyl, and albatrellus ovinus.

Microcirculation and capillary strengtheners- niacinamide (vitamin B3), caffeine, horse chestnut extract, and escin.

"Some ingredients - such as retinol or hydroxyl acids - can potentially increase the sensitivity of the skin, cause dryness, or increase ultraviolet sensitivity during the perimenopause and menopause," she went on.

"Sadly, many of these ingredients can actually help perimenopausal andmenopausal skin in many ways by improving the renewal process, lightening pigmentation, decreasing the appearance of wrinkles, and helping restore skin elasticity.

"Luckily, there are some great alternatives to these more aggressive ingredients. For example, retinol and retinol derivatives can be replaced with bakuchiol a natural ingredient that acts in a similar way to retinol - promoting the same benefits but with no side effects."

"Studies have found that HRT can provide several benefits to the skin. The reduction of oestrogen levels during the menopause has a detrimental effect on the skin, so it can be corrected, at least in part, through the early use of HRT in perimenopause.

"When HRT is introduced in the perimenopause period, skin dryness and sensitivity have been shown to be prevented. In addition, long-term use of HRT has been shown to restore the skins water-holding capacity and barrier function of the epidermis.

"Some studies have also found that HRT can control, in part, the dermal thickness and laxity, collagen content and density, as well as the skins mechanical properties and stress reaction."

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Science Foundation Ireland 2019 Science Awards recognise key leaders in the Irish Research Community

Associate Professor Dr Eilish McLoughlin has been honoured with a prestigious 2019 Science Foundation (SFI) award announced today at the annual SFI Science Summit in Athlone attended by over 300 leading members of Irelands research community who gathered to celebrate the significant contributions made over the past year to Science, Technology, Engineering and Maths (STEM) in Ireland.

Dr McLoughlin was presented with the SFI Outstanding Contribution to STEM Communication in recognition of her incredible contribution to the popularisation of science and her sterling efforts in raising public awareness of the value of science to human progress.

Dr McLoughlin is Director of the Research Centre for the Advancement of STEM Teaching and learning (CASTeL) at DCU. She obtained her BSc in Applied Physics and PhD in Surface Physics from DCU.

A firm believer in the mantra that science is for all, she has led several large-scale national initiatives to widen participation in STEM including Physics Busking, Science on Stage, Improving Gender Balance (all 3 have been funded by SFI) and the STEM Teacher Internship.

Her significant contributions to STEM engagement have resulted in many awards, especially the prestigious Institute of Physics Lise Meitner Medal in 2018 and the DCU President's Award for Engagement in 2017.

She has led several EU collaborations in STEM Education including coordinator of ESTABLISH, Co-Coordinator SAILS and is currently National Coordinator of the H2020 Open Schools for Open Societies project.

Speaking about her award Dr McLoughlin said:

I would like to thank Science Foundation Ireland for presenting me with this award.

I really appreciate their on-going support for STEM education and public engagement activities that allow me to engage with members of the public and teachers and students in schools across Ireland and share my passion for physics.

I hope that my interaction with young people and their parents will encourage more students to choose physics and follow a career in STEM.

Young girls need role models to encourage them to follow their interests and achieve their potential in physics. I hope by winning this award, more young people will realise that physics is a rewarding pathway to follow.

Dr McLoughlin was among ten award winners including a new award for Mentorship which was introduced to celebrate the important role mentors play in providing guidance, motivation and emotional support in our research system.

Acknowledging the award winners, Minister for Training, Skills, Innovation and Research and Development, John Halligan TD, said:

The Science Foundation Ireland Awards recognise the breadth and depth that research encompasses from industry collaborations to public engagement and the innovative breakthroughs that are leading research globally in the areas of Immunology, Biomaterials, Cancer research and much more.

I would like to congratulate each awardee on their achievements, which illustrate the invaluable knowledge and resource that Irelands research community offers.

I am also pleased to see mentorship amongst the awards this year, highlighting the importance of supporting the next generation of researchers and enriching our growing research community.

Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, also congratulated the award winners, saying:

On behalf of Science Foundation Ireland, I would like to congratulate the award winners on their success and recognise their dedication in realising their ambitions and in doing so, building Irelands reputation as a global research leader.

We are very proud of the excellent quality of research that our funding enables, and the SFI Awards are an important acknowledgement of the collective achievements of the Irish research community, which continue to be impactful, inspirational and world-leading.

The 2019 Recipients are as follows:

SFI Researcher of the Year 2019

The SFI Researcher of the Year Award recognises the accomplishments of an SFI funded researcher who has contributed significantly to the Irish research community in the year of the award and/or throughout their career.

The successful researcher has achieved exceptional scientific and engineering research outputs combined with a clear demonstration of the ability to communicate their research.

Recipient: Professor Kevin OConnor, Director of the BEACON SFI Bioeconomy Research Centre, University College Dublin

Professor Kevin OConnor received his BSc degree and PhD from University College Cork.

He is a Professor of Microbial biotechnology in the School of Biomolecular and Biomedical Science at UCD and an investigator in the UCD Earth Institute.

As Director of the BEACON SFI Bioeconomy Research Centre, Professor OConnor is leading blue skies and industry focused research to build and support the development of Irelands bioeconomy.

He is shaping the European Bioeconomy Strategy through his chairmanship of the Scientific Committee for the Bio-based Industries Joint Undertaking (BBIJU), a 3.7 billion Public-Private Partnership.

His research work is seminal in the area of circular economy (plastics to biodegradable plastics), circular bioeconomy (dairy processing by-product to value-added chemical) and biotechnology (hydroxytyrosol production by a biocatalyst).

Collaborating with industry, Professor OConnor developed technology to convert a dairy by-product into an organic acid, which was patented and licensed to industry.

It is now being scaled and implemented in a world first second generation dairy biorefinery, which has received over 30 million in EU funding.

He has published extensively and patented technologies on the conversion of waste plastics to biodegradable plastic and the biotechnological production of hydroxytyrosol (a health promoting molecule) and founded two spin-out companies Bioplastech and Nova Mentis.

Commenting on receiving the Award Professor Kevin OConnor stated:

I am delighted and honoured to receive this prestigious SFI award.

It is a recognition of the dedication of the many researchers and industry partners with whom I work and collaborate with, across multiple scientific fields and sectors, at UCD, across Ireland and internationally.

Through these collaborations we are creating knowledge and translating this knowledge into innovative technological solutions to address global and societal bioeconomy challenges.

I would especially like to acknowledge and thank SFI for their funding, and UCD, BEACON centre members and my wife and family for all their support.

SFI Early Career Researcher of the Year

The SFI Early Career Researcher Award recognises outstanding early career research talent and in recognition of the high calibre of nominations in 2019, there are two individual recipients of the Early Career Researcher of the Year Award:

Recipient: Associate Professor Lydia Lynch, Trinity College Dublin

An Associate Professor at Trinity College Dublin (TCD), in the School of Biochemistry and Immunology, Dr Lydia Lynch established and runs the Lynch Laboratory.

She graduated from University College Dublin with a BSc in Cell Biology and Genetics and a PhD in Immunology and went onto receive a Newman Fellowship for her early post-doctoral studies in St. Vincents University Hospital, where she helped establish the Immunology and Obesity Lab.

Here she discovered adipose iNKT cells and demonstrated that their activation could help manage obesity and metabolic disease.

Dr Lynch is also the recipient of the prestigious LOreal-UNESCO International Women in Science Award and a Marie Curie International Fellowship, which allowed her to move to Harvard Medical School in 2013 and continue studying immunometabolism.

Whilst at Harvard, she was a recipient of the inaugural Innovation Evergreen Fund award. She is also the holder of an American Diabetes Association Award and a Cancer Research Institute Award as well as a European Research Council (ERC) Starting grant and SFI President of Ireland Future Research Leader Award and currently leads an international team in immunometabolism at TCD.

Recipient: Dr Orla OSullivan, APC Microbiome Ireland SFI Research Centre and Vistamilk SFI Research Centre, Teagasc

Dr Orla OSullivan completed her degree in Biochemistry and PhD in Bioinformatics in UCC. She went on to complete a postdoctoral fellowship at the Conway Institute UCD and then joined Teagasc, where she focuses on profiling the microbiome and where she has worked on the ELDERMET project amongst many others.

Dr OSullivan is a funded investigator within the APC Microbiome Ireland SFI Research Centre and Vistamilk SFI Research Centre.

In 2014, Dr OSullivan was awarded an SFI Starting Investigator Research Grant to allow her to establish herself as an independent scientist.

In the same year she was awarded the APC Junior Scientist of the Year.

She is committed to communicating science to all and actively participates in a number of outreach programmes such as BIG STEM communicators, BT Young Scientist, Fota Mad Scientist and World Microbiome Day.

Her research focuses on the microbiome and her studies have established that healthy and protein-rich athlete diets result in a more diverse gut microbiota than standard diets.

She aims to utilise outputs from this research to holistically manage chronic illnesses associated with the gut microbiome, thereby addressing a number of critical societal health challenges.

In 2018, Dr OSullivan was named by Clarivate Analytics as a Highly Cited Researcher placing her in the top 1% of researchers worldwide.

SFI Industry Partnership Award

The SFI Industry Partnership Award celebrates a collaboration between an SFI-funded academic research group and industry.

Recipient: Professor Danny Kelly, AMBER SFI Research Centre for Advanced Materials and BioEngineering Research, Trinity College Dublin, for collaboration with Johnson & Johnson Services, Inc.

Professor Danny Kelly is a Professor of Biomedical Engineering and is Director of the Trinity Centre for Biomedical Engineering where he leads a large multidisciplinary orthopaedic tissue engineering group.

He holds the Chair of Tissue Engineering at TCD and has received three prestigious European Research Council (ERC) awards. Professor Kelly is at the forefront of tissue regeneration using 3D bioprinting strategies.

Through his position at AMBER he has led the Johnson & Johnson partnership on the TRANSITION programme, funded under SFIs Spokes programme to develop a new class of 3D-printed biological implants that will regenerate, rather than replace, diseased joints.

TRANSITION is a shared vision and expands upon AMBERs long-standing collaboration with DePuy Ireland Unlimited Company.

TRANSITION, led by Professor Danny Kelly, brings together Principal Investigators and researchers from four AMBER partners (DCU, RCSI, TCD & UCD) and scientists and engineers from Johnson & Johnsons 3D Printing Centre of Excellence and DePuy Synthes.

A significant milestone was realised earlier this year with the establishment of the Collaborative Bioprinting Laboratory in TCDs Trinity Biomedical Sciences Institute, which co-locates researchers from both sides of the partnership.

SFI Best International Engagement Award

This award recognises the accomplishments of a Science Foundation Ireland-funded researcher/group specifically in the context of their international activities.

Recipient: Professor Abhay Pandit, Scientific Director, CRAM SFI Research Centre for Medical Devices, NUI Galway

Professor Abhay Pandit is Professor of Biomaterials at NUI Galway and Scientific Director of CRAM SFI Research Centre for Medical Devices.

Professor Pandit has been an elected member on the Council for both the Tissue Engineering and Regenerative Medicine International Society and European Society for Biomaterials Society.

He was the first Irish academic to be inducted as an International Fellow in Biomaterials Science and Engineering by the International Union of Societies for Biomaterials Science and Engineering and elected as a Fellow of the Tissue Engineering and Regenerative International Society.

He was also elected to the American Institute of Medical and Biological Engineering (AIMBE) College of Fellows.

Professor Pandit has published more than 250 papers in peer-reviewed journals, filed numerous patent applications and has licensed four technologies to medical device companies.

He has coordinated four EU grants to date and has generated research contracts from industry and government funding agencies totalling 90 million.

Throughout his career, his work has been outward facing, from engaging in international collaborations and hosting international conferences, to supporting trade missions and championing residency programs for leaders in the community (artists, filmmakers, teachers) to empower them with the STEM message.

SFI Entrepreneurship Award

The SFI Entrepreneurship Award celebrates an entrepreneurial achievement by SFI supported researchers.

Recipient: Professor William Gallagher, University College Dublin

Professor William Gallagher is Director of the UCD Conway Institute of Biomolecular and Biomedical Research and Professor of Cancer Biology in the UCD School of Biomolecular & Biomedical Science at University College Dublin.

He was also the Director of the first Irish Cancer Society Collaborative Cancer Research Centre, BREAST-PREDICT, which completed its ground-breaking six year programme in September 2019. Professor Gallagher co-founded the molecular diagnostics company OncoMark in 2007 and is currently its Chief Scientific Officer.

OncoMark focuses on the development and application of biomarker panels which address critical unmet needs for cancer patients.

A major focus of Professor Gallaghers research work is the identification and validation of candidate biomarkers of breast and other cancers, particularly those which guide treatment decision making.

He has received a number of awards to date, including the BACR/AstraZeneca Young Scientist Frank Rose Award in 2004, the St. Luke's Silver Medal Award in 2008, the NovaUCD Innovation Award in 2011 and the inaugural IACR Award for 'Outstanding Contribution to Cancer Medicine and Research' in 2017.

Professor Gallagher has led multiple EU networks under EU programmes, he has had many collaborations with a variety of industrial partners throughout his research, and has filed multiple patents.

SFI Outstanding Contribution to STEM Communication (There are two recipients of this award, including Dr McLoughlin)

Recipient: Dr Muriel Grenon, NUI Galway

Dr Muriel Grenon is a lecturer in Biochemistry, School of Natural Sciences, NUI Galway and the founding Director of the Cell EXPLORERS science outreach programme.

Dr Grenon started out the programme in 2012 with a team of 10 undergraduate science students in NUI Galway and has built Cell EXPLORERS into a national network comprising 13 partner teams with members from 15 Higher Education Institutions in Ireland.

Between 2012 and 2018 Cell EXPLORERS involved 1,187 team members, visited 471 classrooms in 280 schools and reached 32,000 members of the public.

Cell EXPLORERS has also successfully integrated science outreach projects into the final year of the Biochemistry undergraduate course at NUI Galway allowing the creation of potential novel science outreach resources each semester.

Dr Grenon is also involved in driving science communication internationally: Cell EXPLORERS is part of Scientix, the community for Science Education in Europe.

The programme has also started a collaboration with the University of Kwatzulu-Natal in South Africa, where a team is currently piloting the Fantastic DNA school visits.

Dr Grenons contribution and dedication to the popularisation of STEM has been recognised by the Outstanding Contribution to STEM award at the 2013 Galway Science and Technology Festival, the 2017 NUI Galway President Award for Societal Impact and being made Knight of the Order of the Palmes Acadmiques by the French Ministry of Education in 2019.

SFI Mentorship Award

This inaugural award recognises outstanding mentorship provided by a researcher funded by Science Foundation Ireland.

Recipient: Dr Fatima Gunning, IPIC SFI Research Centre and Tyndall National Institute

Dr Fatima Gunning completed her BSc in Physics and PhD in Optoelectronics from Pontifcia Universidade Catlica do Rio de Janeiro (PUC-Rio), Brazil before joining IPIC SFI Research Centre, hosted by Tyndall National Institute after a brief two year period at Corning.

Currently serving as Head of Graduate Studies at Tyndall National Institute and a PI at IPIC SFI Research Centre, she is looking at novel photonics technologies for the Internet of the future.

She has also led many diversity and inclusion programmes that are directly targeted at improving the deficit of diverse talent and gender balance in the field including Empowering Women@Tyndall and being a key advocate for Tyndall to apply for Athena SWAN by 2020.

Dr Gunning has been selected to become Vice President of Membership and Outreach of the IEEE Photonics Society starting January 2020 to expand the diversity, inclusion and mentorship efforts to an international scale.

Dr Gunning believes that all students are different, are driven by different motivations and develop their research in different ways.

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Dr Eilish McLoughlin honoured by SFI for Outstanding Contribution to STEM Communication - Dublin City University

Cardiac Stem Cells Comments Off on Dr Eilish McLoughlin honoured by SFI for Outstanding Contribution to STEM Communication – Dublin City University | November 9th, 2019

The thought of spaceflight may make the heart skip a beat, but actually travelling beyond Earth could alter the organs cells.

With extended stays aboard the International Space Station (ISS) commonplace, and the likelihood of humans spending longer periods in space increasing, there is a need to better understand the effects of micro-gravity on cardiac function.

New research suggests heart muscle cells derived from stem cells have a remarkable ability to adapt to their environment during and after spaceflight.

Scientists examined cell-level cardiac function and gene expression in human heart cells cultured aboard the International Space Station for five-and-a-half weeks.They found that exposure to micro-gravity changed the expression of thousands of genes, but largely normal patterns reappeared within 10 days after returning to Earth.

Read more about the body in space:

Senior study author, Joseph Wu, of Stanford University School of Medicine, said: Our study is novel because it is the first to use human induced pluripotent stem cells to study the effects of spaceflight on human heart function.

Micro-gravity is an environment that is not very well understood, in terms of its overall effect on the human body, and studies like this could help shed light on how the cells of the body behave in space, especially as the world embarks on more and longer space missions such as going to the Moon and Mars.

Until now, most studies on how the heart reacts to micro-gravity have been conducted in either non-human models or at tissue, organ or systemic level.To address this, the beating cells were launched to the ISS aboard a SpaceX spacecraft as part of a commercial resupply service mission.Simultaneously, they were also cultured on Earth for comparison purposes.

When they returned to the planet, the cells showed normal structure and morphology.However, they did adapt by modifying their beating pattern and calcium recycling patterns.

Immunofluorescence imaging of the cells grown in micro-gravity aboard the International Space Station Joseph Wu lab, Stanford University School of Medicine/PA

Researchers sequenced the cells harvested at four-and-a-half weeks aboard the ISS, and 10 days after returning to Earth.Results showed that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples.

Most notably, gene pathways related to mitochondrial function were expressed more in the space-flown cells, according to the research published in the Stem Cells Reports journal.

A comparison of the samples revealed the space cells adopted a unique gene expression pattern during spaceflight, which reverted to one that is similar to ground-side controls upon return to normal gravity.

Dr Wu added: Were surprised about how quickly human heart muscle cells are able to adapt to the environment in which they are placed, including micro-gravity.

These studies may provide insight into cellular mechanisms that could benefit astronaut health during long-duration spaceflight, or potentially lay the foundation for new insights into improving heart health on Earth.

See the rest here:
Space travel affects heart cells, but only temporarily - BBC Focus Magazine

Cardiac Stem Cells Comments Off on Space travel affects heart cells, but only temporarily – BBC Focus Magazine | November 9th, 2019

JERUSALEM & PARSIPPANY, N.J. & INCHEON, South Korea--(BUSINESS WIRE)--Teva Pharmaceuticals USA, Inc., a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), Celltrion, Inc., (KRX KRX:068270) and Celltrion Healthcare, Co., Ltd. (KRX KOSDAQ:091990), today announced that TRUXIMA (rituximab-abbs) injection is the first biosimilar to the reference product Rituxan1 (rituximab) now available in the United States with a full oncology label. TRUXIMA is currently indicated for the treatment of adult patients with non-Hodgkins Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL):

We are excited about the first FDA-approved biosimilar to rituximab in the U.S., stated Brendan OGrady, Executive Vice President and Head of North America Commercial at Teva. Tevas commitment to biosimilars is focused on the potential to create lower healthcare costs and increased price competition. This focus is consistent with Tevas mission of making accessible medications to help improve the lives of patients.

TRUXIMA was approved by the U.S. Food and Drug Administration (FDA) as the first rituximab biosimilar. The approval was based on a review of a comprehensive data package inclusive of foundational and extensive analytical characterization, nonclinical data, clinical pharmacology, immunogenicity, clinical efficacy, and safety data. In May 2019, the FDA approved TRUXIMA to match all of the reference products oncology indications for NHL and CLL. In light of a patent settlement with Genentech, Celltrion and Teva have a pending FDA submission for rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA), and a license from Genentech to expand the TRUXIMA label to include these indications in Q2 2020.

We are pleased to announce the launch of the first rituximab biosimilar, TRUXIMA, with our marketing partner Teva in the U.S. said Mr. Hyoung-Ki Kim, Vice Chairman at Celltrion Healthcare. We believe that the introduction of TRUXIMA into the U.S. market will contribute to addressing unmet needs of U.S. patients as well.

The Wholesale Acquisition Cost (WAC or list price) for TRUXIMA will be 10 percent lower than the reference product. TRUXIMA is being made available through primary wholesalers at a WAC of $845.55 for 100mg vial and $4227.75 for 500mg vial. Actual costs to individual patients and providers for TRUXIMA are anticipated to be lower than WAC because WAC does not account for additional rebates and discounts that may apply. Savings on out-of-pocket costs may vary depending on the patients insurance payer and eligibility for participation in the assistance program.

Dedicated patient support services are also available from Teva through the Comprehensive Oncology Reimbursement Expertise (CORE) program. CORE is available to help eligible patients, caregivers and healthcare professionals navigate the reimbursement process. CORE offers a range of services, including benefits verification and coverage determination, support for precertification and prior authorization, assistance with coverage guidelines and claims investigation, and support through the claims and appeals process. A savings program is also available for eligible commercially insured patients. To learn more, please visit TevaCORE.com. For healthcare professionals seeking additional information, there is also a dedicated site at TRUXIMAhcp.com.

Celltrion and Teva Pharmaceutical Industries Ltd. entered into an exclusive partnership in October 2016 to commercialize TRUXIMA in the U.S. and Canada.

Please see the Important Safety Information below including the Boxed Warning regarding fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation and progressive multifocal leukoencephalopathy. For more information, please visit the full prescribing information.

Important Safety Information

WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Infusion-Related Reactions - Administration of rituximab products, including TRUXIMA, can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first infusion. Monitor patients closely. Discontinue TRUXIMA infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions

Severe Mucocutaneous Reactions - Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products

Hepatitis B Virus (HBV) Reactivation - HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with TRUXIMA. Discontinue TRUXIMA and concomitant medications in the event of HBV reactivation

Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab products

Warnings and Precautions

Infusion-Related Reactions - Rituximab products can cause severe, including fatal, infusion-related reactions. Severe reactions typically occurred during the first infusion with time to onset of 30-120 minutes. Rituximab product-induced infusion-related reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.

Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion-related reactions as needed. Depending on the severity of the infusion-related reaction and the required interventions, temporarily or permanently discontinue TRUXIMA. Resume infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (>25,000/mm3)

Severe Mucocutaneous Reactions - Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab products. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has been variable and includes reports with onset on the first day of rituximab exposure. Discontinue TRUXIMA in patients who experience a severe mucocutaneous reaction. The safety of re-administration of rituximab products to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus Reactivation - Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab products. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive and hepatitis B surface antibody [anti-HBs] positive).

HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels. In severe cases increase in bilirubin levels, liver failure, and death can occur.

Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with TRUXIMA. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during TRUXIMA treatment.

Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following TRUXIMA therapy. HBV reactivation has been reported up to 24 months following completion of rituximab therapy.

In patients who develop reactivation of HBV while on TRUXIMA, immediately discontinue TRUXIMA and any concomitant chemotherapy, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming TRUXIMA treatment in patients who develop HBV reactivation. Resumption of TRUXIMA treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

Progressive Multifocal Leukoencephalopathy (PML) - JC virus infection resulting in PML and death can occur in rituximab product-treated patients with hematologic malignancies. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab.

Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture.

Discontinue TRUXIMA and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Tumor Lysis Syndrome (TLS) - Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of rituximab products in patients with NHL. A high number of circulating malignant cells (>25,000/mm3) or high tumor burden, confers a greater risk of TLS.

Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated.

Infections - Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure). New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue TRUXIMA for serious infections and institute appropriate anti-infective therapy. TRUXIMA is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions - Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of TRUXIMA for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina.

Renal Toxicity - Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and TRUXIMA is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue TRUXIMA in patients with a rising serum creatinine or oliguria.

Bowel Obstruction and Perforation - Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1-77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization - The safety of immunization with live viral vaccines following rituximab product therapy has not been studied and vaccination with live virus vaccines is not recommended before or during treatment.

Embryo-Fetal Toxicity - Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving TRUXIMA and for 12 months following the last dose of TRUXIMA.

Most common adverse reactions in clinical trials of NHL (>25%) were: infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia

Most common adverse reactions in clinical trials of CLL (>25%) were: infusion-related reactions and neutropenia

Nursing Mothers - There are no data on the presence of rituximab in human milk, the effect on the breastfed child, or the effect on milk production. Since many drugs including antibodies are present in human milk, advise a lactating woman not to breastfeed during treatment and for at least 6 months after the last dose of TRUXIMA due to the potential for serious adverse reactions in breastfed infants.

About TRUXIMA

TRUXIMA (rituximab-abbs) is a U.S. Food and Drug Administration (FDA)-approved biosimilar to RITUXAN (rituximab) for the treatment of adult patients with CD20-positive, B-cell NHL to be used as a single agent or in combination with chemotherapy or CLL in combination with fludarabine and cyclophosphamide (FC).

TRUXIMA has the same mechanism of action as Rituxan and has demonstrated biosimilarity to Rituxan through a totality of evidence.

About Celltrion Healthcare, Co. Ltd.

Celltrion Healthcare conducts the worldwide marketing, sales and distribution of biological medicines developed by Celltrion, Inc. through an extensive global network that spans more than 120 different countries. Celltrion Healthcares products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US Food and Drug Administration (FDA) cGMP guidelines and the EU GMP guidelines.

About Celltrion, Inc.

Headquartered in Incheon, Korea, Celltrion is a leading biopharmaceutical company, specializing in research, development and manufacturing of biosimilar and innovative drugs. Celltrion strives to provide more affordable biosimilar mAbs to patients who previously had limited access to advanced therapeutics. Celltrion received FDA approval for TRUXIMA (rituximab-abbs) and HERZUMA (trastuzumab-pkrb) in 2018.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve peoples lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com.

Teva's Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding TRUXIMA, which are based on managements current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

and other factors discussed in our Quarterly Reports on Form 10-Q for the first and second quarter of 2019 and in our Annual Report on Form 10-K for the year ended December 31, 2018, including in the sections captioned "Risk Factors and Forward Looking Statements. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

1 RITUXAN is a registered trademark of Genentech and Biogen.

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Teva and Celltrion Announce the Availability of TRUXIMA (rituximab-abbs) Injection, the First Biosimilar to Rituxan (rituximab) in the United States -...

Cardiac Stem Cells Comments Off on Teva and Celltrion Announce the Availability of TRUXIMA (rituximab-abbs) Injection, the First Biosimilar to Rituxan (rituximab) in the United States -… | November 8th, 2019

CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) today announced that it will present a total of 29 company-sponsored abstracts at the 61st American Society of Hematology (ASH) Annual Meeting on December 7-10, 2019 in Orlando, FL, highlighting the companys commitment to advancing the treatment of hematologic cancers and bleeding disorders.

Pursuing Breakthrough, Patient-Centric Innovation in Oncology and Bleeding Disorders

Takeda will present 29 scientific updates on the companys investigational and early-stage therapies, which demonstrates its investment in new compounds to address patient needs, as well as data from Phase 3 trials and real-world evidence findings, in disease states including multiple myeloma, lymphoma and leukemia.

We are presenting notable data on several clinical programs at ASH, highlighting our deep oncology pipeline and our commitment to developing innovative therapies that may address unmet needs for blood cancer patients, said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. In particular we look forward to sharing data from the Phase 3 clinical trial of ixazomib in amyloidosis patients, data from the US MM-6 study, which evaluates an in-class transition from parenteral bortezomib to oral ixazomib in multiple myeloma, further analyses from the Phase 3 ECHELON-2 trial of ADCETRIS in peripheral T-cell lymphoma, as well as early stage data from several of our pipeline programs.

In hematology, Takeda will present real-world evidence from studies of its portfolio of treatments across bleeding disorders, including hemophilia A, hemophilia B and von Willebrand disease. The company will also present scientific updates related to its hemophilia A and hemophilia B gene therapy programs and adeno-associated virus (AAV) gene therapy platform.

Understanding real-world evidence is critical as Takeda continues to provide patients with innovative therapies for hemophilia A and hemophilia B while broadening our research and development efforts in von Willebrand disease and other bleeding disorders, said Daniel Curran, M.D., Head, Rare Diseases Therapeutic Area Unit, Takeda. Also at ASH, we look forward to providing an update on our gene therapy programs in hemophilia and the optimization of Takedas AAV gene therapy platform, particularly for patients with pre-existing immunity to AAV serotypes.

Accepted oncology abstracts include:

Note: all times listed are in Eastern Standard Time

NINLARO (ixazomib) and Multiple Myeloma

ADCETRIS (brentuximab vedotin) and Lymphoma

ICLUSIG (ponatinib)

Pipeline (multiple myeloma, lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia)

Accepted hematology abstracts include:

Note: all times listed are in Eastern Standard Time

ADYNOVATE (Antihemophilic Factor (Recombinant), PEGylated) and Hemophilia A

FEIBA (Anti-Inhibitor Coagulant Complex)

von Willebrand Disease

Pipeline (hemophilia A, hemophilia B and gene therapies)

About ADCETRISADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics' proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, and for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD.

ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Important Safety Information (European Union)Please refer to Summary of Product Characteristics (SmPC) before prescribing.

CONTRAINDICATIONS

ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin causes pulmonary toxicity.

SPECIAL WARNINGS & PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.

Closely monitor patients for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established Hold dosing for any suspected case of PML and permanently discontinue ADCETRIS if a diagnosis of PML is confirmed.

Be alert to PML symptoms that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).

Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Closely monitor patients for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. Hold ADCETRIS for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.

Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. Promptly evaluate and treat new or worsening pulmonary symptoms (e.g., cough, dyspnoea) appropriately. Consider holding dosing during evaluation and until symptomatic improvement.

Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Carefully monitor patients during treatment for emergence of possible serious and opportunistic infections.

Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS. Carefully monitor patients during and after an infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS and administer appropriate medical therapy. If an IRR occurs, interrupt the infusion and institute appropriate medical management. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. Monitor these patients closely and manage according to best medical practice.

Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically an effect of cumulative exposure to ADCETRIS and is reversible in most cases. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.

Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Monitor complete blood counts prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Closely monitor patients for fever and manage according to best medical practice if febrile neutropenia develops.

When ADCETRIS is administered in combination with AVD, primary prophylaxis with G-CSF is recommended for all patients beginning with the first dose.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs and administer appropriate medical therapy.

Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, have been reported with ADCETRIS. Promptly evaluate and treat patients if new or worsening GI symptoms occur.

Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Test liver function prior to treatment initiation and routinely monitor during treatment. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. Closely monitor serum glucose for patients who experiences an event of hyperglycemia. Administer anti-diabetic treatment as appropriate.

Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations.

CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Szary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Carefully consider the benefit-risk per patient and use with caution in other CD30+ CTCL patient types.

Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

INTERACTIONSPatients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia. If neutropenia develops, refer to dosing recommendations for neutropenia (see SmPC section 4.2). Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS, but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.

PREGNANCY: Advise women of childbearing potential to use two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. Do not use ADCETRIS during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus.

LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.

FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Advise men being treated with ADCETRIS not to father a child during treatment and for up to 6 months following the last dose.

Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines.

UNDESIRABLE EFFECTS

Monotherapy: The most frequent adverse reactions (10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnoea, weight decreased, myalgia and abdominal pain. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was 1%. Adverse events led to treatment discontinuation in 24% of patients.

Combination Therapy: In the study of ADCETRIS as combination therapy with AVD in 662 patients with previously untreated advanced HL, the most common adverse reactions ( 10%) were: neutropenia, nausea, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhoea, pyrexia, alopecia, peripheral motor neuropathy, decreased weight, abdominal pain, anaemia, stomatitis, febrile neutropenia, bone pain, insomnia, decreased appetite, cough, headache, arthralgia, back pain, dyspnoea, myalgia, upper respiratory tract infection, alanine aminotransferase increased. Serious adverse reactions occurred in 36% of patients. Serious adverse reactions occurring in 3% of patients included febrile neutropenia (17%), pyrexia (6%), and neutropenia (3%). Adverse events led to treatment discontinuation in 13% of patients.

ADCETRIS (brentuximab vedotin) Important Safety Information (U.S.)

BOXED WARNINGPROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Most Common (20% in any study) Adverse ReactionsPeripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug InteractionsConcomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific PopulationsModerate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

For additional Important Safety Information, including BOXED WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com or http://www.ADCETRIS.com.

ADYNOVATE Professional Important Information

ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] Important Information

Indications and Limitation of UseADYNOVATE is a human antihemophilic factor indicated in children and adults with hemophilia A (congenital factor VIII deficiency) for:

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONSPrior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE [Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONSHypersensitivity ReactionsHypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing AntibodiesFormation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONSThe most common adverse reactions (1% of subjects) reported in the clinical studies were headache and nausea.

Click here for Full Prescribing Informationhttps://www.shirecontent.com/PI/PDFs/ADYNOVATE_USA_ENG.pdf

FEIBA [Anti-Inhibitor Coagulant Complex] Indications and Detailed Important Risk Information

Indications for FEIBA

FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:

FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX.

Detailed Important Risk Information for FEIBA

WARNING: EMBOLIC AND THROMBOTIC EVENTS

CONTRAINDICATIONS

FEIBA is contraindicated in patients with:

WARNINGS AND PRECAUTIONS

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur, particularly following the administration of high doses (>200 units/kg/day) and/or in patients with thrombotic risk factors.

Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulopathy. Potential benefit of treatment should be weighed against potential risk of these thromboembolic events.

Infusion should not exceed a single dose of 100 units/kg and daily doses of 200 units/kg. Maximum injection or infusion rate must not exceed 2 units/kg/minute. Monitor patients receiving >100 units/kg for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue FEIBA and initiate appropriate diagnostic and therapeutic measures.

Safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established. Cases of thrombotic microangiopathy (TMA) were reported in a clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding following emicizumab treatment. Consider the benefits and risks with FEIBA if considered required for patients receiving emicizumab prophylaxis. If treatment with FEIBA is required for patients receiving emicizumab, the hemophilia treating physician should closely monitor for signs and symptoms of TMA. In FEIBA clinical studies TMA has not been reported.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur. Symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. Reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

FEIBA contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may interfere with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).

ADVERSE REACTIONS

Most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting.

Serious adverse reactions seen are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

DRUG INTERACTIONS

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Takeda to Highlight Expanded Portfolio of Products Across Oncology and Hematology at 61st American Society of Hematology (ASH) Annual Meeting -...

Cardiac Stem Cells Comments Off on Takeda to Highlight Expanded Portfolio of Products Across Oncology and Hematology at 61st American Society of Hematology (ASH) Annual Meeting -… | November 8th, 2019

In Brazil, scientists affiliated with the Human Genome and Stem Cell Research Center (HUG-CELL) at the University of So Paulo (USP) have identified a molecule capable of reducing the aggressiveness of embryonal central nervous system tumors. These are malignant tumors that start in fetal cells in the brain and mainly affect children up to four years old.

The results arepublishedin the journalMolecular Oncology.HUG-CELLis one of the Research, Innovation and Dissemination Centers (RIDCs) supported by So Paulo Research Foundation - FAPESP. Its principal investigator isMayana Zatz, Professor of Human and Medical Genetics at USP's Institute of Biosciences (IB).

The approach proposed by the group can be classified as a type of microRNA-based therapy. A microRNA is a small RNA molecule that does not encode protein but plays a regulatory role in the genome. In this study, researchers used a synthetic version of an inhibitor of microRNA-367 (miR-367) with anti-tumor activity.

"We demonstrated in an animal model of a central nervous system tumor that treatment with a microRNA inhibitor attenuates properties of tumor stem cells and prolongs survival," saidOswaldo Keith Okamoto, a professor at IB-USP and the principal investigator for the study.

Okamoto explained that embryonal central nervous system tumors such as medulloblastomas and atypical teratoid/rhabdoid tumors (AT/RTs) tend to contain cells with characteristics similar to those of stem cells, which boosts their tumorigenic potential and capacity to invade tissue while also making them more resistant to cell death.

These tumors are caused by genetic or epigenetic aberrations in stem cells and neural progenitors when the nervous system is being formed during embryonic development. The neural stem cells that undergo these alterations later give rise to tumor cells. They form aggressive, fast-growing tumors that may appear shortly after birth, in later childhood or in adolescence.

In a previous study, the group tested an approach that used the Zika virus to destroy tumor stem cells (read more atagencia.fapesp.br/27677).

Expression and inhibition

A more recent study was led byCarolini Kaid, a postdoctoral researcher at IB-USP with a scholarship fromFAPESP.

Previous research has already shown that OCT4A, one of the genes that encode pluripotency factors, is overexpressed in aggressive medulloblastomas and that this overexpression is associated with an unfavorable prognosis. During hermaster's research, Kaid detected the expression of miR-367, a gene that promotes stem-like traits in tumor cells, in parallel with overexpression of OCT4A (read more atagencia.fapesp.br/21959).

The researchers then tested a specific synthetic inhibitor of miR-367 containing minor chemical alterations that make it more stable in cells. A patent application has been filed for the invention.

After inducing the formation of central nervous system tumors in mice using three different strains of tumor cells, the researchers injected the miR-367 inhibitor into the brain's right lateral ventricle, a pathway to the cerebrospinal fluid that surrounds the brain and spinal cord. From there, the miR-367 inhibitor was able to access the tumor cells.

Tumor size was reduced considerably, and survival improved in all groups of mice. The results confirmed what had previously been observed in cell cultures.

In this model, the researchers noted that when the synthetic molecule interacted with miR-367 in tumor cells, it prevented this microRNA from affecting the levels of proteins it normally regulates, such as ITGAV and SUZ12.

The latter is known to be involved in silencing pluripotency-related genes in embryonic stem cells.

While the role of ITGAV in embryonal central nervous system tumors is not fully understood, ITGAV is known to participate in the renewal of both normal and tumor stem cells.

"When miR-367 is inhibited in cancer cells, it stops regulating several proteins. This molecular alteration eventually affects the properties of these cells, resulting in an attenuation of the tumor's aggressiveness. This is what makes the strategy interesting," Kaid said.

The researchers believe that in humans, the synthetic molecule alone may be capable of at least containing the development of these tumors and improving survival. Even so, they are testing combinations of the molecule with drugs currently used to treat the tumors. They want to find out whether the approaches could be combined using lower doses of chemotherapy drugs.

Before clinical trials can be performed, however, pharmacology and toxicity studies will be necessary, as will pharmacokinetic testing to show how the molecule is metabolized and how long it stays in the organism (its half-life).

When embryonal central nervous system tumors are conventionally treated with surgery, chemotherapy and/or radiotherapy, morbidity and mortality rates for these patients are high. These tumors correspond to 10% of all central nervous system cancer cases in children.

Even patients who survive longer than most may suffer from permanent treatment-related sequelae that impair their quality of life, such as problems with development, cognition, locomotion and speech.

Reference: Kaid et al. 2019.miR367 as a therapeutic target in stemlike cells from embryonal central nervous system tumors. Molecular Oncology. DOI: https://doi.org/10.1002/1878-0261.12562.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Novel Molecule Reduces the Aggressiveness of Pediatric Cancer - Technology Networks

Spinal Cord Stem Cells Comments Off on Novel Molecule Reduces the Aggressiveness of Pediatric Cancer – Technology Networks | November 8th, 2019

NEW YORK--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket), a leading U.S.-based multi-platform clinical-stage gene therapy company, today announces presentations at the upcoming 61st American Society of Hematology (ASH) Annual Meeting being held December 7-10, 2019 in Orlando, Florida. The two poster presentations will highlight clinical data from the Phase 1 study of RP-L102 utilizing Process B for the treatment of Fanconi Anemia (FA), as well as long-term follow-up data from the Phase 1/2 EUROFANCOLEN trial.

Details for Rockets poster presentations are as follows:Title: Changing the Natural History of Fanconi Anemia Complementation Group-A with Gene Therapy: Early Results of U.S. Phase I Study of Lentiviral-Mediated Ex-Vivo FANCA Gene Insertion in Human Stem and Progenitor CellsSession Title: Gene Therapy and Transfer: Poster IIPresenter: Sandeep Soni, M.D.Session Date: Sunday, December 8, 2019Session Time: 6:00 p.m. 8:00 p.m. ESTLocation: Orange County Convention Center, Hall B

Title: Hematopoietic Engraftment of Fanconi Anemia Patients through 3 Years after Gene TherapySession Title: Gene Therapy and Transfer: Poster IIIPresenter: Paula Ro, Ph.D.Session Date: Monday, December 9, 2019Session Time: 6:00 p.m. 8:00 p.m. ESTLocation: Orange County Convention Center, Hall B

The Sunday poster session will be followed by a breakout session to give investors and analysts the opportunity to ask questions and discuss the data. The breakout session, hosted by Rocket management, will be held on Sunday, December 8th at 8:30 p.m. EST, directly after Dr. Sonis presentation. At the event, Dr. Soni, Clinical Associate Professor of Stem Cell Transplantation and Regenerative Medicine at the Stanford University School of Medicine and principal investigator of the U.S. Phase 1 trial of RP-L102 and Paula Ro, Ph.D., Senior Scientist, Divisin de Terapias Innovadoras en el Sistema Hematopoytico, CIEMAT/CIBERER Unidad Mixta de Terapias Avanzadas CIEMAT/IIS Fundacin Jimnez Daz will be participating in a Q&A panel. For further information, please contact investors@rocketpharma.com.

About Fanconi Anemia

Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a FANC-A gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANC-A gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Chromosome fragility induced by DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is the gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natures gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells1.

1Soulier, J.,et al. (2005) Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 105: 1329-1336

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket) is an emerging, clinical-stage biotechnology company focused on developing first-in-class gene therapy treatment options for rare, devastating diseases. Rockets multi-platform development approach applies the well-established lentiviral vector (LVV) and adeno-associated viral vector (AAV) gene therapy platforms. Rocket's clinical programs using LVV-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rockets first clinical program using AAV-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. Rockets pre-clinical pipeline program is for Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements

Various statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to successfully demonstrate the efficacy and safety of such products and pre-clinical studies and clinical trials, its gene therapy programs, the pre-clinical and clinical results for its product candidates, which may not support further development and marketing approval, the potential advantages of Rocket's product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's and its licensors ability to obtain, maintain and protect its and their respective intellectual property, the timing, cost or other aspects of a potential commercial launch of Rocket's product candidates, Rocket's ability to manage operating expenses, Rocket's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Annual Report on Form 10-K for the year ended December 31, 2018. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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Rocket Pharmaceuticals to Present Preliminary Phase 1 Data of RP-L102 Process B for Fanconi Anemia at the 61st American Society of Hematology Annual...

Bone Marrow Stem Cells Comments Off on Rocket Pharmaceuticals to Present Preliminary Phase 1 Data of RP-L102 Process B for Fanconi Anemia at the 61st American Society of Hematology Annual… | November 8th, 2019