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Archive for the ‘Stem Cell Negative’ Category

Second patient cured of HIV using stem cell transplant treatment – The Japan Times

Wednesday, March 11th, 2020

PARIS A second patient has been cured of HIV after undergoing stem cell transplant treatment, doctors said Tuesday, after finding no trace of infection 30 months after he stopped traditional treatment.

The London Patient, a cancer sufferer originally from Venezuela, made headlines last year when researchers at the University of Cambridge reported they had found no trace of the AIDS-causing virus in his blood for 18 months.

Ravindra Gupta, lead author of the study published in The Lancet HIV, said the new test results were even more remarkable and likely demonstrated the patient was cured.

Weve tested a sizeable set of sites that HIV likes to hide in and they are all pretty much negative for an active virus, Gupta told AFP.

The patient, who revealed his identity this week as Adam Castillejo, 40, was diagnosed with HIV in 2003 and had been on medication to keep the disease in check since 2012.

Later that year, he was diagnosed with advanced Hodgkins lymphoma, a deadly cancer.

In 2016 he underwent a bone marrow transplant to treat blood cancer, receiving stem cells from donors with a genetic mutation present in less than 1 percent of Europeans that prevents HIV from taking hold.

He becomes only the second person to be cured of HIV after American Timothy Brown, known as the Berlin Patient, recovered from HIV in 2011 following similar treatment.

Viral tests of Castillejos cerebral fluid, intestinal tissue and lymphoid tissue more than two years after stopping retroviral treatment showed no active infection.

Gupta said the tests uncovered HIV fossils fragments of the virus that were now incapable of reproducing, and were therefore safe.

Wed expect that, he said.

Its quite hard to imagine that all trace of a virus that infects billions of cells was eliminated from the body.

Researchers cautioned that the breakthrough did not constitute a generalized cure for HIV, which leads to nearly 1 million deaths every year.

Castillejos treatment was a last resort as his blood cancer would likely have killed him without intervention, according to Gupta.

The Cambridge doctor said that there were several other patients who had undergone similar treatment but who were less far along in their remission.

There will probably be more but they will take time, he said.

Researchers are currently weighing up whether or not patients suffering from drug-resistant forms of HIV might be eligible for stem cell transplants in future, something Gupta said would require careful ethical consideration.

Youd have to weigh up the fact that theres a 10 percent mortality rate from doing a stem-cell transplant against what the risk of death would be if we did nothing, he said.

Commenting on The Lancet study, Sharon Lewin, an infectious disease expert at the University of Melbourne, said the findings could provide comfort to patients.

But she advised caution.

Given the large number of cells sampled here and the absence of any intact virus, is the London patient cured? she said.

Unfortunately in the end, only time will tell.

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Forty Seven and Rocket Pharmaceuticals Announce Research Collaboration for Fanconi Anemia – BioSpace

Wednesday, March 11th, 2020

MENLO PARK, Calif. and NEW YORK, March 11, 2020 (GLOBE NEWSWIRE) -- Forty Seven Inc. (Nasdaq: FTSV) and Rocket Pharmaceuticals Inc. (Nasdaq: RCKT) announced today that they have entered into a research collaboration to pursue clinical proof-of-concept for Forty Sevens novel antibody-based conditioning regimen, FSI-174 (anti-cKIT antibody) plus magrolimab (anti-CD47 antibody), with Rockets ex vivo lentiviral vector hematopoietic stem cell (LVV HSC) gene therapy, RP-L102. The initial collaboration will evaluate this treatment regimen in Fanconi Anemia (FA), a genetic disease that affects patients capacity to produce blood cells and is associated with an increased risk of leukemia and other neoplasms. RP-L102, Rockets gene therapy approach for FA, involves treatment with patients own gene-corrected blood forming stem cells (hematopoietic stem cells, or HSCs).

Gene therapies for monogenic blood disorders have broad potential. One concern associated with these treatments is the toxicity of pre-therapy conditioning regimens that utilize cytotoxic chemotherapy and/or radiation to destroy existing HSCs and facilitate engraftment of gene-corrected HSCs. Forty Sevens all-antibody based conditioning regimen is designed to address the limitations of current pre-treatment conditioning therapies. These regimens are often associated with serious side effects, including severe infection, cognitive impairment, infertility, endocrine dysfunction, secondary malignancies and organ damage. These toxicities are especially difficult for pediatric patients and are particularly severe for patients with FA, who are more sensitive to the DNA-damaging effects of traditional conditioning agents. Preliminary data demonstrate that RP-L102 may confer efficacy without pre-treatment conditioning. The combination of RP-L102 with Forty Sevens all-antibody conditioning regimen may provide patients an alternate treatment option in situations where conditioning may be advantageous.

We are pleased to enter into this collaboration with Forty Seven, said Jonathan Schwartz, M.D., Chief Medical Officer and Senior Vice President of Rocket. RP-L102 Process B is currently being evaluated in a registrational trial without the use of conditioning. In parallel, we are assessing incorporation of a non-genotoxic conditioning regimen as a part of Rockets life-cycle management strategy. Forty Sevens novelall-antibodyconditioning regimen could also beapplied to Rockets other lentiviral programs, in which conditioning is more integral to the gene therapy approach.

We are initiating our first in human healthy volunteer study of FSI-174 in the first quarter this year, and are excited to enter into a partnership with Rocket at this time. Rocket is at the forefront of developing gene therapies for high unmet-need diseases, and this collaboration will provide an opportunity to evaluate the benefit of Forty Sevens novel conditioning regimen with Rockets RP-L102 to help FA patients, says Jens-Peter Volkmer, VP of Research at Forty Seven.

This collaboration is in line with our strategy to study our anti-cKIT and anti-CD47, all-antibody conditioning regimen in combination with several different gene therapies, and to establish clinical proof-of-concept in a broad range of transplant indications, said Mukul Agarwal, VP of Corporate Development at Forty Seven.

Maria Grazia Roncarolo, M.D., Scientific Advisor to Forty Seven, commented, The goal of my lifes work is to bring pediatric patients transformative therapies for currently incurable diseases. We believe Rocket Pharmaceuticals commitment to devastating diseases, such as FA, addresses a critical unmet need and Forty Sevens antibody conditioning creates an alternative avenue to deliver this therapy to those patients. We look forward to seeing how this collaboration may help patients in need.

Under the terms of the agreement, Rocket will provide its ex vivo LVV HSC gene therapy platform and Forty Seven will contribute its innovative antibody-based conditioning regimen for the collaboration.

About FSI-174 and MagrolimabFSI-174 is a humanized monoclonal antibody targeting cKIT, which is a receptor that is highly expressed on hematopoietic stem cells. Magrolimab is a humanized monoclonal antibody targeting CD47, which is a dont eat me signal to macrophages and is expressed on all cells. Magrolimab is currently being investigated in Phase 2 clinical trials to treat cancer and has established clinical efficacy in four indications, including myelodysplastic syndrome, acute myeloid leukemia, diffuse large B cell lymphoma and follicular lymphoma, with a favorable safety profile in over 400 patients treated, including some patients treated continuously for over two years. When combined, FSI-174 sends a positive signal to macrophages to target blood forming stem cells for removal and magrolimab disengages inhibitory signals that block phagocytosis. Combination of these antibodies has shown efficient removal of blood forming stem cells, allowing for transplantation in pre-clinical models.

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 aFANC-Agene mutation, which encodes for a protein essential for DNA repair. Mutation in theFANC-Agene 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 natural 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 advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients contending with rare genetic diseases. Rocket's clinical programs using lentiviral vector (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 adeno-associated virus (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 visitwww.rocketpharma.com.

For more information, please visit http://www.rocketpharma.com or contact info@rocketpharma.com

About Forty Seven, Inc.Forty Seven, Inc.is a clinical-stage immuno-oncology company that is developing therapies targeting cancer immune evasion pathways based on technology licensed fromStanford University. Forty Sevens lead program, magrolimab, is a monoclonal antibody against the CD47 receptor, a dont eat me signal that cancer cells commandeer to avoid being ingested by macrophages. This antibody is currently being evaluated in multiple clinical studies in patients with myelodysplastic syndrome, acute myeloid leukemia, and non-Hodgkins lymphoma.

For more information, please visitwww.fortyseveninc.comor contactinfo@fortyseveninc.com.

Follow Forty Seven on social media:@FortySevenInc,LinkedIn

Rocket Cautionary Statement Regarding Forward-Looking StatementsVarious 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 preclinical 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, 2019, filed March 6, 2020 with the SEC. 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.

Forty Seven Cautionary Statement Regarding Forward-Looking StatementsStatements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as will, may, assess, could, believe, and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those related to the research and development plans for Rockets and Forty Sevens respective platforms and product candidates, the timing and success of Forty Sevens collaboration with Rocket, Forty Sevens plans to pursue clinical proof-of-concept for FSI-174 plus magrolimab with the LVV HSC gene therapy platform, the focus on diseases that have the potential to be corrected with the combination of RP-L102 and Forty Sevens all-antibody conditioning regimen, the tolerability and efficacy of RP-L102, FSI-174 and magrolimab, the timing and success of any future collaborations between Forty Seven and Rocket, Forty Sevens plans to continue development of FSI-174 plus magrolimab, as well as related timing for clinical trials of the same.

Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The product candidates that Forty Seven develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all.In addition, clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release. Such product candidates may not be beneficial to patients or successfully commercialized. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Forty Seven's stock price. Additional information concerning these and other risk factors affecting Forty Seven's business can be found in Forty Seven's periodic filings with theSecurities and Exchange Commissionatwww.sec.gov. These forward-looking statements are not guarantees of future performance and speak only as of the date hereof, and, except as required by law, Forty Seven disclaims any obligation to update these forward-looking statements to reflect future events or circumstances.

Forty SevenInvestors:Hannah Deresiewicz, (212) 362-1200hannah.deresiewicz@sternir.com

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Media:Sarah Plumridge, (312) 506-5218fortyseven@hdmz.com

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Forty Seven and Rocket Pharmaceuticals Announce Research Collaboration for Fanconi Anemia - BioSpace

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Researcher Calls on Others Worldwide to Join Efforts to Understand Role of Sleep in Pediatric Cancer – Rutgers-Camden NewsNow

Wednesday, March 11th, 2020

By Tom McLaughlin

Lauren Daniel recalls that, as a clinical psychologist working with pediatric cancer patients at the Childrens Hospital of Philadelphia (CHOP), she would often arrive in the mornings to do therapy sessions and find that her patients were still sleeping.

It was then difficult for her to sit down with them, she remembers, but the predicament was understandable, since they were frequently woken up throughout the night for a variety of reasons, including vital checks, to urinate, and to get pumps and other medical equipment serviced.

For someone to wake them up during the day, it was torture for them, says the assistant professor of psychology at Rutgers UniversityCamden. They dont want to talk to you at that point.

Daniels understanding and concern would spark a career research interest in the sleep patterns of children with cancer and the connection to patients psychosocial health outcomes.

The RutgersCamden researcher is now leading an international team of sleep researchers to establish research priorities for better understanding the role of sleep in pediatric cancer. The team calls on other researchers to join them in their collaborative efforts in their paper, A call to action for expanded sleep research in pediatric oncology: A position paper on behalf of the International Psycho-Oncology Society Pediatrics Special Interest Group, in the journal Psycho-Oncology.

We are excited to put the call out there, says Daniel, who notes that three of the participating researchers spoke at the 2019 International Psycho-Oncology Society World Congress.

Daniel explains that the pediatric cancer population is thankfully small at any one center, so it is incredibly valuable for researchers to collaborate in pooling data across multiple centers.

The RutgersCamden researcher notes that research on adult cancer patients shows a bidirectional relationship linking negative health outcomes with disrupted sleep and circadian rhythms, as well as compelling evidence showing that improved sleep improves health outcomes in adults. However, she says, little is known about these effects on pediatric cancer patients.

It is essential to increase our understanding because sleep and circadian rhythms are vital components of health and quality of life, write the researchers in their paper. In children without cancer, sleep and circadian disturbances respond well to intervention, suggesting that they may also be modifiable in children with cancer.

In addition to Daniels work with the research group, she recently received a $50,000 grant from the New Jersey Commission on Cancer Research to lead the pilot program Disrupted Sleep and its Association with Symptom Burden and Reduced Engagement in Supportive Care in Pediatric Stem Cell Transplant Patients.

Daniel will work with medical professionals and psychologists on the study at CHOP to collect data on an intervention to improve sleep in pediatric cancer patients undergoing stem cell transplants.

Lauren Daniel

I am grateful for the opportunity to branch out into a new area of research and continue the work that we are doing for patients at CHOP, says Daniel.

The researchers are currently studying how sleep affects the day-to-day symptoms and coping abilities of patients in the peritransplant period, the early stage when cells are starting to graft and grow. The researchers ultimately hope to determine what they can alter to improve sleep patterns of patients and encourage changes in nursing practices accordingly in order to improve psychosocial outcomes.

Even if we can make modest gains, we hope to improve the psychosocial health outcomes in addition to medical outcomes for patients, says Daniel, who adds that there isnt a lot of psychosocial research on these patients, in part because these children are already going through intensive research.

Daniel notes an earlier study found that patients need to be woken up an average of 12 times per night.

In their forthcoming study, says the RutgersCamden researcher, pediatric patients will wear a wristwatch to measure their motion for a two-week period after receiving transplant cells and be asked to complete daily surveys on what their sleep experience was like the night before. Their symptoms, such as nausea, fatigue, anxiety, and depression, will then be assessed every five days. Researchers will also extend the intervals between vital checks and determine the effects on their symptoms.

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Single-Cell Analysis of Ovarian Cortex Fails to Find Stem Cells – The Scientist

Wednesday, March 11th, 2020

The first single-cell analysis of the human ovarian cortex revealed six main types of cells, but none of the oogonial stem cells that other researchers say they have isolated, according to a study published earlier this week (March 2) in Nature Communications. These findings are backed by the most advanced technologies, the authors say, and could put to rest a heated debate about the properties of the adult ovary that has raged for more than a decade.

The results of the experiment dont leave a lot of space for different interpretations, says Susana Chuva de Sousa Lopes, a developmental biologist at Leiden University Medical Center in the Netherlands who served on the PhD dissertation committee of coauthor Sarita Panula but was not involved in the research. It seems, she says, that cells previously identified as ovarian stem cells are in fact perivascular cells, which support blood vessel structure and help regulate blood flow.

But the discoverers of ovarian stem cells in adult mammals and other proponents of the cells existence are not convinced, citing methodological weaknesses of the new study.

Until relatively recently, scientific consensus was that a female mammals oocyte pool is fixed at birth. Adult ovaries, it was assumed, are simply unable to generate new eggs. But in 2004, Northeastern University reproductive biologist Jonathan Tilly and colleagues published findings that appeared to upend this understanding of oocyctes by presenting evidence of ovarian stem cells in adult mice.

A few years later, scientists in China claimed to have also found such germ line stem cells in the ovaries of adult mice, and showed that these cells could differentiate into functional eggs that gave rise to viable mouse pups. And in 2012, Tillys group reported the existence of germ cells in samples of human ovarian tissue, claiming that these cells could similarly generate oocytes in vitro and in vivo when injected into mice.

These findings generated a lot of publicity because they suggested that human fertility wasnt fixed after all. But the data has always been criticized, says Fredrik Lanner, an embryonic stem cell researcher at the Karolinska Institute and a coauthor on the newly published study that failed to find such stem cells.

We quite feel certain to say that in the human adult ovary in this cortex region, there is no cell that would be the oogonial stem cell.

Pauliina Damdimopoulou, Karolinska Institute

While some groups have been able to reproduce the results, others have tried and failed. Debates have erupted over methods, techniques, and protocols, and Tilly and his colleagues have published lengthy replies to those who have challenged their work. Today, the field is more or less divided into two camps regarding the existence of ovarian stem cells, says Chuva de Sousa Lopes.

To try to get to the bottom of the issue, Lanner and his collaborators harvested high-quality ovarian tissue samples from 21 healthy patients of reproductive age and isolated the ovarian cortex, the outer layer of the ovary where researchers claim to have found the elusive stem cells. The team used enzymes to break down the ovarian tissues, yielding 24,000 individual cells in total, then performed single-cell transcriptome and cell surface marker profiling, revealing six main cell types: oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. None of the single-cell profiles matched those of reported ovarian stem cells.

When Lanner and colleagues stained the cells with an antibody against DDX4, a germ cell marker that is reported to select for oogonial stem cells, they found that they had instead isolated perivascular cells. The team then stained intact ovarian tissue and saw that the antibody similarly identifies perivascular cells. A comparison of the 24,000 cells to existing transcriptome data from both human fetal ovaries and the ovarian medulla, the inner region of the ovary, also failed to reveal any oogonial stem cells.

We quite feel certain to say that in the human adult ovary in this cortex region, there is no cell that would be the oogonial stem cell, says coauthor Pauliina Damdimopoulou, a cell biologist at the Karolinska Institute. She believes that other researchers have succeeded in using the DDX4 isolation technique to select and culture cells, but that what they have found are in fact perivascular cells and not oogonial stem cells.

This study again highlights that the DDX4 isolation technique is not something that can be used to isolate oogonial stem cells, University of Adelaide cell biologist Keith Jones, who was not involved in the work but coauthored a 2016 papersuggesting that the same antibody does not isolate DDX4 positive cells, writes in an email to The Scientist. It brings into question the existence of such stem cells, and leads us back to the dogma that prevailed previously in the fieldthe adult ovary does not contain oogonial stem cells.

Damdimopoulou also notes that she and her colleagues found that small, mature oocytes can slip through the filtration process, and when cultured, may appear as if they had been generated from stem cells. We think [the oocytes] were there all along from the beginning, she says. The formation of new vasculature by perivascular cells surrounding these oocytes, Chuva de Sousa Lopes suspects, could trigger dormant egg cells to become active and then mature, which might explain the results published by other labs.

Perivascular cells dont undergo meiosis, perivascular cells dont express meiotic genes, perivascular cells dont express germ cell genes.

Jonathan Tilly, Northeastern University

Others are not ready to give up on the idea of ovarian stem cells just yet. Deepa Bhartiya, a stem cell biologist at the National Institute for Research in Reproductive Health in India who was not involved with the research, has been working with ovarian stem cells since 2010 and says that they can be easily detected. Research with sheep ovarian tissues has shown that simple scraping of [the] ovary surface can show the presence of stem cells amongst the ovary surface epithelial cells, she writes in an email to The Scientist. The problem with the new study out of Sweden, Bhartiya says, is the speed at which the researchers spun their cellsmuch too slow to isolate the stem cells, which due to their small size do not pellet down at lower speeds and are therefore unknowingly discarded. Bhartiya writes that the study used novel techniques, but revealed nothing new: if sample preparation is not properone will get negative data.

Tilly argues that there are numerous methodological problems with the study. He says that at this point four independent groups have reported on the existence of oogonial stem cells, showing that the cells can generate new oocytes in both somatic ovarian tissue and outside the body in culture, and that they can undergo complete meiosis, a germ cell-specific event. Perivascular cells dont undergo meiosis, perivascular cells dont express meiotic genes, perivascular cells dont express germ cell genes, he says.

What the field really needs, says Chuva de Sousa Lopes, is more communication among researchers. The scientists that claim there are stem cells in the ovary and the scientists that are against that are somehow not really talking to each other, she says. I wish there would be more open dialogue, because sooner or later all these populations [of cells] will be clarified . . . and things will be more clear.

M. Wagner et al., Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells,Nat Commun,doi:10.1038/s41467-020-14936-3, 2020.

Amy Schleunes is an intern atThe Scientist. Email her ataschleunes@the-scientist.com.

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6Ways to Tackle Coronavirus Related Stress and Anxiety – TheHealthMania

Wednesday, March 11th, 2020

As coronavirus (SARS-CoV-2) continues to infect more people worldwide, it has also increased the cases of stress and anxiety caused by a coronavirus. People are so scared of going to public places and if someone sneezes near to them, it gives them a little panic attack.

Considering the fast and uncontrollable spread of coronavirus, it is justified that people are under stress. Psychologist finds the occurrence of stress and anxiety in response to any threat as a normal human reaction. But this added stress is extremely harmful to people who are already at risk of certain diseases i.e. heart patients, blood pressure patients, stress and anxiety patients, pregnant women, and immunocompromised patients.

Here are a few suggestions for people, written as per psychological science to deal with the coronavirus related stress and anxiety.

It is a proven scientific fact that the US is going through a rapid increase in intolerance., which makes it difficult for people to cope up with stress. A study based on the H1N1 pandemic of 2009 shows that it was extremely hard for the people to accept the uncertainty of this pandemic situation and as a result that they experience anxiety.

The solution to this problem is by changing the behavior towards small things in routine. Building the patience level is something that not only helps to overcome the anxiety of coronavirus but helps a person to tackle all uncertain situations in life.

Also read- Can Scientists Cure HIV With Stem Cell Therapy?

Although it might not be the first thing that a stressed person would like to hear it is necessary to keep up the struggle in all forms. Distract yourself and involve in various activities that would keep you busy. Watch Netflix, read a book, write something, experiment with cooking, play with your pets, or anything that you like. Engaging yourself in an activity that you like is much likely to reduce the tress and pressure created by anything including the coronavirus outbreak.

One way to overcome the coronavirus related stress is by connecting to the goodness in life and finding meaning in it. Be it relationships, spirituality or anything, focus on what makes you happy and how you have given years to something. It would help you to feel important and life would suddenly look worth it.

It is understandable if someone is fearing what to do if coronavirus shows up in his town. Ending up at quarantine for days doesnt seem like a very good idea but human minds typically estimate the worst situation out of everything. There is plenty of research that explains peoples behavior as they overestimate their conditionsin event of any negative thing. Also, they underestimate their own responsesthat how would they adjust to any difficult situation. But mind it that you are way more resilient than you consider yourself, do not let the anxiety of it shaken you.

Also read- What does Your Period Blood Color Show?

In addition to the common psychological conditioning, you must remember that its a virus-borne disease that could be avoided if you follow a good self-care practice. Follow personal hygiene practices as prescribed by the CDC. Eat healthily, sleep regularly and spend time in exercise. Avoid meeting people unnecessarily and stay away from a person who exhibits any signs of flu or cold.

Prioritizing your behavior with others during this coronavirus outbreak. The coronavirus related stress could be tackled with a combination of psychological and practical approaches together.

It is normal to feel stressed because of the coronavirus outbreak. Disease in all forms is fearful and it is risky for people who are weak or already suffering from a disease. If you think that self-help plans are not working on you, it is better to get professional help. Contact your nearest mental health professional. He might prescribe you with Cognitive behavioral therapyand/orcertain medicines after evaluating your case. All in all, it would lead to successful anxiety treatment.

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Indonesian scientists want government to get professional help in fighting COVID-19 – The Jakarta Post – Jakarta Post

Wednesday, March 11th, 2020

The government has stepped up its efforts to contain the coronavirus disease 2019 (COVID-19) by tightening health screenings at borders and testing more people after confirming two cases in a Jakarta suburb over the weekend.

Scientists, however, say there is still a crucial element lacking in the war against the virus: transparency.

A number of scientists have highlighted the importance of involving more people, including independent scientists, in the handling of the virus outbreak, saying it is essential that health authorities work effectively and scientifically.

Ahmad Utomo, a principal investigator at the Stemcell and Cancer Institute in Jakarta, has said that how the authorities are conducting testing is not transparent and not helping the public understand the situation.

The government, he said, needed to write in detail about the sample collection, preservation, transport and quality control.

And if they are going to write a [scientific] paper [on the issue], they must disclose what brand they are using for the PCR testing, he toldThe Jakarta Poston Wednesday, adding that China's Centers for Disease Control and Prevention had done exactly that.

Paper publications like the ones in China showed the details of the outbreak, complete with molecular genetic data of the virus.

The Health Ministry has posted updates about the COVID-19 situation atinfeksiemerging.kemkes.go.id. In its latest update, posted on March 4, the ministry mostly explains the global situation of the outbreak and only spares one paragraph (or one pointer) to explain the domestic situation.

The links to the previous updates are all broken.

Indonesia has reported two confirmed cases in the country, even though the government itself has admitted that it was unable to detect infected people since they showed no symptoms and that the incubation period had been extended to more than 14 days.

Critics have said Indonesia should have reported more cases but the government, which claims to have conducted the lab tests according to the WHO standards, has insisted that the number of confirmed cases has not changed.

Achmad Yurianto, a government spokesman for the handling of the virus outbreak, said Indonesia had tested 168 samples as of Wednesday. Two of them, case one and case two, came back positive with COVID-19. We are still studying the 10 other samples. The rest are negative, he said.

When asked about the Polymerase Chain Reaction (PCR) test equipment, Yurianto said: I will not tell you the name of the brand.

Utomo deplored Yuriantos response, saying that information regarding the test kit was critical to allow independent parties review its reliability. Some test kits, he said, could be faulty, referring to the ones used by the US Centers for Disease Control.

After insisting that its Jakarta laboratory alone could conduct testing, the ministry decided to let local laboratories in 10 major cities conduct throat swab tests for COVID-19. However, it has yet to allow other scientific organizations, including from universities, conduct testing.

The government argued that such a policy was redundant, saying that scientists had been consulted with in the formulation of the governments policy, including the testing system. It doesnt matter where the testing is conducted, he said, adding that what mattered was the scientists contribution to the crisis management system.

Read also: Calls mount for revival of national outbreak committee over coronavirus fears

The building of Eijkman Institute in Jakarta (Eijkman Institute/File)

Herawati, the deputy for fundamental research at Eijkman Institute, said the institution had all the equipment needed to conduct testing but the government had yet to seek its assistance with the testing of the suspected coronavirus patients.

When the avian influenza outbreak occurred, the government immediately asked Eijkman to also help with the testing of samples from suspected patients, she claimed.

Indonesia, she said, should follow Singapore, where the government and universities are working together to conduct testing for COVID-19.

Indonesia, she said, might be underreporting confirmed cases.

[The two positive cases] I think are just the tip of the iceberg. We have to do more tests. Not because we want to get more patients but we have to make sure that we are ready, our abilities, facilities and everything for pandemic preparation, Hera said.

When asked about whether having local labs do the testing was enough, Hera said: The key is to have an independent laboratory under the command of the Health Ministry for comparison. This is to strengthen transparency, Hera added.

Ahmad concurred with Hera, saying that the government needed to get professional help. At least seek help to conduct supervision. We have many world-class virologists.

Bayu Krisnamurthi, who headed the National Committee for Avian Flu Control and Pandemic Preparedness (Komnas Flu Burung) between 2006 and 2010, also highlighted the importance of an independent laboratory for testing.

"It is important to confirm. This examination laboratory has two critical functions, to identify whether the patient is indeed infected with the virus and whether the virus is still the same, or has it mutated and even to trace the origin of the virus," he said.

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Indonesian scientists want government to get professional help in fighting COVID-19 - The Jakarta Post - Jakarta Post

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Spectrum Pharmaceuticals, Inc. (NASDAQ:SPPI) Forecasted to Earn FY2024 Earnings of $1.59 Per Share – Redmond Register

Wednesday, March 11th, 2020

Spectrum Pharmaceuticals, Inc. (NASDAQ:SPPI) Equities research analysts at Jefferies Financial Group issued their FY2024 earnings estimates for shares of Spectrum Pharmaceuticals in a research report issued to clients and investors on Wednesday, March 4th. Jefferies Financial Group analyst M. Raycroft anticipates that the biotechnology company will post earnings per share of $1.59 for the year.

Several other equities analysts also recently commented on SPPI. HC Wainwright assumed coverage on shares of Spectrum Pharmaceuticals in a research note on Thursday, December 26th. They issued a buy rating and a $11.00 price objective for the company. B. Riley dropped their price objective on shares of Spectrum Pharmaceuticals from $11.00 to $8.00 and set a buy rating for the company in a research note on Monday, March 2nd. Zacks Investment Research downgraded shares of Spectrum Pharmaceuticals from a buy rating to a hold rating and set a $3.75 price objective for the company. in a research note on Friday, January 3rd. Cantor Fitzgerald reissued a neutral rating and issued a $4.00 price objective (down previously from $17.00) on shares of Spectrum Pharmaceuticals in a research note on Thursday, December 26th. Finally, BidaskClub downgraded shares of Spectrum Pharmaceuticals from a hold rating to a sell rating in a research note on Thursday, January 23rd. One research analyst has rated the stock with a sell rating, three have issued a hold rating and four have issued a buy rating to the company. The stock has a consensus rating of Hold and an average target price of $11.13.

Spectrum Pharmaceuticals (NASDAQ:SPPI) last issued its quarterly earnings data on Thursday, February 27th. The biotechnology company reported ($0.35) EPS for the quarter, missing the Thomson Reuters consensus estimate of ($0.33) by ($0.02). The companys revenue was up NaN% on a year-over-year basis. During the same quarter last year, the company earned ($0.30) EPS.

In other Spectrum Pharmaceuticals news, COO Thomas J. Riga sold 11,381 shares of the companys stock in a transaction that occurred on Thursday, January 16th. The shares were sold at an average price of $3.37, for a total value of $38,353.97. Following the completion of the transaction, the chief operating officer now directly owns 246,678 shares in the company, valued at approximately $831,304.86. The sale was disclosed in a filing with the SEC, which is available at this hyperlink. Over the last 90 days, insiders sold 40,764 shares of company stock valued at $123,463. Corporate insiders own 4.17% of the companys stock.

A number of hedge funds and other institutional investors have recently made changes to their positions in SPPI. Nisa Investment Advisors LLC increased its position in Spectrum Pharmaceuticals by 1,280.0% in the 4th quarter. Nisa Investment Advisors LLC now owns 6,900 shares of the biotechnology companys stock valued at $25,000 after acquiring an additional 6,400 shares during the period. Clear Harbor Asset Management LLC acquired a new position in Spectrum Pharmaceuticals in the 4th quarter valued at approximately $36,000. Tower Research Capital LLC TRC increased its position in Spectrum Pharmaceuticals by 251.3% in the 4th quarter. Tower Research Capital LLC TRC now owns 10,346 shares of the biotechnology companys stock valued at $38,000 after acquiring an additional 7,401 shares during the period. Los Angeles Capital Management & Equity Research Inc. acquired a new position in Spectrum Pharmaceuticals in the 4th quarter valued at approximately $55,000. Finally, Bank of Montreal Can increased its position in Spectrum Pharmaceuticals by 27.7% in the 4th quarter. Bank of Montreal Can now owns 18,412 shares of the biotechnology companys stock valued at $67,000 after acquiring an additional 3,989 shares during the period. Hedge funds and other institutional investors own 68.53% of the companys stock.

About Spectrum Pharmaceuticals

Spectrum Pharmaceuticals, Inc develops and commercializes oncology and hematology drug products. The company offers KHAPZORY, a novel folate analog and the pharmacologically active levo-isomer of d, and 1-leucovorin; FOLOTYN, a folate analogue metabolic inhibitor for peripheral T-cell lymphoma (PTCL); ZEVALIN injection to treat non-Hodgkin's lymphoma; MARQIBO for adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia; BELEODAQ, a histone deacytelase, or HDAC, inhibitor for the treatment of patients with relapsed or refractory PTCL; and EVOMELA for use as a conditioning treatment prior to autologous stem cell transplant in multiple myeloma patients.

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Spectrum Pharmaceuticals, Inc. (NASDAQ:SPPI) Forecasted to Earn FY2024 Earnings of $1.59 Per Share - Redmond Register

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TO YOUR HEALTH: Inflammation can drive triple-negative breast cancer – Dover Post

Saturday, February 29th, 2020

Study at ChristianaCare Cawley Center for Translational Cancer Research

While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCares Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types.

Sims-Mourtadas latest study, Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells, brings scientists closer to understanding the mechanisms behind this aggressive and hard-to-treat cancer. It shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem breast cancer cells.

This is the good and the bad of radiation, Sims-Mourtada said. We know radiation induced inflammation can help the immune system to kill tumor cells thats good but also it can protect cancer stem cells in some cases, and thats bad.

She added, Whats exciting about these findings is were learning more and more that the environment the tumor is in its microenvironment is very important. Historically, research has focused on the genetic defects in the tumor cells. Were now also looking at the larger microenvironment and its contribution to cancer.

The term triple-negative breast cancer refers to the fact that the cancer cells dont have estrogen or progesterone receptors and also dont make too much of the protein called HER2. The cells test negative on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation.

My work focuses on cancer stem cells and their origination, Sims-Mourtada said. They exist in many cancers, but theyre particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth.

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. As yet unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.

For women living in Delaware, Sims-Mourtadas research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

At ChristianaCare, we are advancing cancer research to help people in our community today, while we also advance the fight against cancer nationwide, said Dr. Nicholas J. Petrelli, Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. Dr. Sims-Mourtadas research is a dramatic step toward better treatments for triple-negative breast cancer.

To advance her research on inflammation, last year Sims-Mourtada received a $659,538 grant from the Lisa Dean Moseley Foundation. The three-year grant will enable her and her team at the Cawley Center for Translational Cancer Research to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible therapy for this particularly difficult cancer.

Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing, Sims-Mourtada said.

Sims-Mourtadas research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

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TO YOUR HEALTH: Inflammation can drive triple-negative breast cancer - Dover Post

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A new approach to both high safety and high performance of lithium-ion batteries – Science Advances

Saturday, February 29th, 2020

RESULTS

As a proof of concept, we prepare a baseline cell composed of a standard electrolyte, 1 M LiPF6 in ethylene carbonate (EC)/ethyl methyl carbonate (EMC) (3/7 wt) + 2 weight % (wt %) vinylene carbonate (VC), and a graphite anode and an NCM622 cathode. Protective layers of solid electrolyte interphase (SEI) on graphite and cathode electrolyte interphase (CEI) are formed during initial charge/discharge cycles. To yield low DCR and hence high power, these interfacial layers are usually thin, lacking sufficient density and resilience to resist decomposition under abuse conditions, to suppress continuous reaction of the solvent EC in the SEI, or to hinder continuous oxidation of EC with oxygen released from cathode materials in the CEI, thereby leading to Li consumption and loss of cell capacity. In contrast, in SEB cells, we create highly stable, flame-retardant EEIs through the addition of a small amount of TAP in the standard electrolyte. This electrolyte modification is accompanied by the simultaneous reduction of EC content, i.e., EC/EMC (1/9 wt) + 2 wt % VC, intended for further reduction in gas production via side reactions. In this work, we present results for three prototype SEB cells, identified as SEB-1, SEB-2, and SEB-3 and corresponding to 0.5, 1, and 1.5 wt % TAP, respectively. The charge-transfer resistance of the SEB cells, measured by electrochemical impedance spectroscopy (EIS), increases by 3 to 5 as compared to the baseline cell without the electrolyte additives, as shown in Fig. 2A. The high impedance comes from the polymerization of TAP molecules that form thick and dense interfacial films at the surfaces of both the anode and cathode (2). On the anode side, the film serves as an enhanced SEI layer to stabilize further growth. On the cathode side, the film hinders EC in the electrolyte from reacting with lattice oxygen on the NCM surface at high temperature or high voltage (3), as shown schematically in Fig. 2B.

(A) Nyquist plots showing measured charge-transfer resistances of SEB cells versus the baseline LIB cell. (B) Schematic showing the in situ formed interfacial layers on the surface of graphite and NCM particles. The enhanced SEI layer on graphite slows down EC transport though the film and suppresses further SEI growth. The CEI layer hinders EC oxidation with lattice oxygen over the NCM surface at high temperatures or high voltages. (C and D) Cell voltage and temperature evolutions during nail penetration of a SEB cell and the baseline LIB cell along with qualitative temperature distributions. Both cells are 2.8-Ah pouch cells composed of the same graphite anode and NMC622 cathode materials. The baseline LIB cell is filled with a standard electrolyte: 1 M LiPF6 in EC/EMC (3/7 wt) + 2 wt % VC. The SEB cell has the electrolyte of 1 M LiPF6 in EC/EMC (1/9 wt) + 2 wt % VC with TAP as electrolyte additive. RT, room temperature.

PolyTAP and its composites are flame-retardant materials. In addition, the PolyTAP has electrically insulative properties and stability at elevated temperatures (4). All these properties make PolyTAP well suited to enhance the safety of SEB cells under abuse conditions. This is confirmed by nail penetration tests shown in Fig. 2C, where the temperature rise is only 100C (without cell deformation, smoking, or fire) versus almost 1000C (catching fire) in the baseline case (Fig. 2D). The superior safety performance of the SEB cell is further illustrated by the electrical performance of the cell during nail penetration. For the baseline cell, the cell voltage decreases to 0.1 V within 5 s after the nail penetration. The sharp voltage drop indicates that the shorting current is extremely high due to low internal resistance of the baseline cell. In contrast, the voltage of the SEB cell drops from 4.171 to 3.085 V within 5 s after penetration, showing a slow and controlled discharge due to the high internal resistance of the SEB cell. The substantially higher resistance in the SEB cell than the baseline is caused by the electrically nonconductive layers formed on the surface of the graphite and NCM particles, as schematically shown in Fig. 2B.

The stability and safety of SEB cells are further evident in high-voltage charge and high-temperature calendar life tests (figs. S1 and S2). The SEB cells can undergo 1254 exposures to high-voltage abuse [constant current (CC) charge to 4.4 V, constant voltage (CV) to C/20] at 40C with a capacity retention of 80%, whereas the baseline cell sustains only 40 cycles at the same capacity loss and operating temperature, indicating that the SEB cell is >30 more stable and hence safer than the baseline cells under high-voltage charging conditions. Calendar life testing further shows that the passivated SEB cells can effectively suppress self-discharge. The self-discharge current is measured by holding the cell voltage constant at a required value, such as 4.187 V for 100% state of charge (SOC). Both baseline and SEB cells display a fast decrease of self-discharge current density in the beginning of calendar aging due to anode SEI layer growth. Fresh SEB cells show self-discharging currents ~5 lower than the baseline cell at room temperature and 50% SOC, 6 lower at room temperature and 100% SOC, and ~7 lower at 60C at both 50 and 100% SOC. After 60 days of storage, the self-discharge current begins to plateau; however, the self-discharge current in the SEB cell is still 2 lower than that in the baseline cell at room temperature and 50% SOC and 3 lower at room temperature and 100% SOC. The self-discharge becomes 4 lower at high temperature (60C) at both 50 and 100% SOC, indicating that at elevated temperatures, the SEB cells maintain superiority in calendar life over the baseline cell.

A distinctive feature of SEB cells is high power on demand. When batteries are not in operation, SEB cells are left idle at room temperature, exhibiting high stability and safety. However, upon operation, a SEB cell switches to high-reactivity conditions through rapid thermal stimulation. This can be illustrated through DCR, which is inversely proportional to power performance. Here, DCRs upon discharge and charge for SEB and baseline LIB cells are measured at 50% SOC by a 10-s hybrid pulse power characterization (HPPC) method. As expected, the DCR values increase substantially by adding a small amount of TAP in the electrolyte, as shown in Fig. 3 (A and B), which also demonstrates that adding more TAP in SEB-3 (e.g., 1.5 wt %) results in a further increase in DCR, owing to the formation of thicker protective layers.

(A and B) DCRs of discharge and charge, respectively, at 50% SOC for SEB cells versus the baseline LIB cell. (C) Relative discharge power (DCRbaseline@RT/DCR) of a SEB cell versus the baseline LIB cell. (D) Relative reactivity (Rct,baseline@RT/Rct) of a SEB cell versus the baseline LIB cell, showing that SEB cells operated at appropriate elevated temperatures, e.g., SEB-3 at 50C, can deliver sufficient power at all ambient temperatures (labeled as line a), that SEB cells are 5 safer and less aging at room temperature (labeled as line b), and that SEB cells are 2.6 less prone to thermal runaway at 60C (labeled as line c).

Figure 3C shows the relative power of SEB cells versus the baseline LIB, where the power of the baseline cell at room temperature is normalized to be unity, thus demonstrating that SEB cells can provide sufficient, higher power by operating at higher temperatures. At 50% SOC, SEB-1 operated at 29.2C provides the same power as the baseline cell at room temperature. The safest cell, SEB-3, with 1.5 wt % TAP additive requires an operation temperature of 44.6C to deliver the same power as the baseline cell at room temperature. The baseline cell has a narrow temperature window of 15 to 35C, whereas the SEB cells have much higher maximum operating temperature without becoming excessively reactive. Thus, the necessity of higher temperature operation for power recovery does not pose an issue for SEB cells. At 50% SOC, the discharge power boost over the baseline Li-ion cell is 2.05, 1.81, and 1.39 for the SEB-1, SEB-2, and SEB-3, respectively (Fig. 3C). Moreover, at the ambient temperature of 0C, the baseline LIB cell has a relative power of 0.38, while SEB-2 has a relative power of 1.81 when operated at 60C [it takes 30 s to heat up a cell from 0 to 60C at a speed of 2C/s, typical of the self-heating structure of Wang et al. (1)]. This is ~5 boost in power over the LIB cell for SEB cells working in the freezing environments. Generally, SEB cells perform independent of ambient temperatures or weather, as they are always heated up in a matter of seconds and operate at a constant elevated temperature. Although heating a cell to an elevated temperature consumes cell energy, the total deliverable energy of a cell, counterintuitively, is not reduced. As shown in fig. S3, the C/3 discharge energy was 9.62 watt-hours (Wh) for the baseline cell at room temperature and 10.15 Wh for the SEB-3 cell at 60C. According to our previous work (1), it takes ~1% cell energy for a 10C temperature rise, meaning that the SEB-3 cell needs 3.5% of its energy for heating from 25 to 60C; the remaining discharge energy is thus 9.79 Wh, which is 2% higher than that of the baseline cell at room temperature.

As mentioned, such rapid heating is achieved through the insertion of a micrometer-thick nickel sheet. The impact of this additional component on cell power density can be evaluated through Eq. 1, where m is the mass of the given cell and the ratio of discharge power evaluated through HPPC is inversely proportional to the ratio of DCRs(Power Density)SEB(Power Density)baseline@RT=(DCRbaseline@RTDCRSEB@60C)(mbaselinemSEB)(1)

The addition of the nickel foil increases cell mass by 1.3%, while the ratio of DCRs in Eq. 1 is the relative power presented in Fig. 3C at 60C. On the basis of these values, the power density is not reduced but rather increased by a factor of 2.02, 1.79, and 1.37 in the case of SEB-1, SEB-2, and SEB-3, respectively. Thus, in the case of SEB-3 with the highest internal resistance, the power density is still 37% higher than the baseline cell operated at room temperature.

Figure 3D presents the relative interfacial reactivity as derived from the charge-transfer resistance of EIS results. This further confirms that increased operational temperature effectively decreases the charge-transfer resistance of SEB cells and consequently increases the cell reactivity and power. The reactivity boost over the baseline LIB cell is 2.06 for SEB-2. Overall, both relative power and relative reactivity illustrate the ability of SEB cells to achieve high power on demand. On the other hand, the values of relative reactivity of these two cells shown in Fig. 3D indicate that the SEB cell will be 5 safer and undergo 5 less aging at room temperature, which is supported by self-discharge and capacity retention tests displayed in fig. S2. Furthermore, the comparison of relative reactivity for the two cell types at 60C indicates that the SEB cell is more than 2 less prone to thermal runaway.

Beyond safety and high power, there is an ever-increasing need for long cycle life of LIBs. Low-reactivity SEB cells built with highly stable materials offer longer calendar life (fig. S2), evident from the slow capacity fade when the battery is in idle conditions at room temperature. At elevated temperatures, cycling of SEB cells is also stable. Figure 4A compares capacity retention of the baseline cell with SEB cells during cycling at 60C of 1C CC charge to 4.2 V CV charge till C/20 and then 1C discharge to 2.8 V. Clearly, the SEB cells outperform the baseline cell as evidenced by a 20% capacity loss at 481 cycles with visible signs of cell deformation due to gas evolution and graphite anode swelling for the baseline cell, while SEB-3 can achieve 2821 cycles before reaching 20% capacity loss. This corresponds to ca. 6 improvement in cycle life. In addition, SEB-3 achieves 4014 cycles at 75% capacity retention while still showing signs of a healthy cell capable of cycling stably (no perceptible gassing or lithium plating). The average discharge capacity of these 4014 cycles is 84.2% of an equivalent full cycle (EFC). Assuming a 153-mile driving range per EFC for an electric vehicle (e.g., 2019 BMW i3), the 4014 cycles mean >517,000 miles of lifetime. That is more than 5 the warranty for commercial electric cars (e.g., BMW i3, 70% capacity for 8 years or 100,000 miles). Improvement of cell lifetime can be further demonstrated by considering the rate of capacity fade during calendar aging at room temperature (i.e., the stable state), which is 7 lower than that at 60C (the reactive state). The SEB cell will only be heated to the reactive state for situations requiring high power or fast charging. The greater part of its lifetime (>90%) would be spent in idle conditions (the stable state). Therefore, in the field, the SEB cycle life is expected to extend much beyond 4014 cycles before reaching 25% capacity loss.

(A and B) Capacity retention and DCR of the SEB cells versus the baseline LIB cell during cycling at 60C. The cells are charged with CCCV protocol at 1 C to 4.2 V with a cutoff current of C/20 and then discharged at 1 C to 2.8 V. (C and D) Discharge curves of the fresh SEB cell versus aged cell.

The tremendous extension of cycle life of the SEB over the baseline cell may stem from the denser and more stabilized SEI layer formed on graphite particles and CEI layer on NCM622 particles in the presence of the electrolyte additives. For the baseline cell, the nickel-rich NCM particles are prone to microcracks along grain boundaries (5, 6) that provide gaps for electrolyte penetration and lead to more severe electrolyte oxidation and rock salt formation (7). Particle cracking also sets free new, fresh surface area from which oxygen can be released (8). The microcracks on NCM622 particles for the baseline cell are observed after only 50 cycles (Fig. 5D). The formation of cracks becomes much more notable throughout the micrograph domain after 956 cycles (Fig. 5F). For the SEB cells, cracks on NCM particles are not observed at 50 cycles, and a small amount of cracks are observed after 4021 cycles (Fig. 5J). The presence of microcracks not only causes a loss of contact but also accelerates NCM capacity fade. For the SEB cells, the polymer coating from TAP likely forms a robust CEI, reducing formation of microcracks (Fig. 2B). This is also evidenced by optical images (fig. S4) and no observable cell deformation or swelling after 4021 cycles even at an elevated temperature of 60C.

(A) Pristine anode. (B) Pristine cathode. (C) Baseline anode after 50 cycles. (D) Baseline cathode after 50 cycles. (E) Baseline anode after 956 cycles. (F) Baseline cathode after 956 cycles. (G) SEB-3 anode after 50 cycles. (H) SEB-3 cathode after 50 cycles. (I) SEB-3 anode after 4021 cycles. (J) SEB-3 cathode after 4021 cycles. ETD, Everhart-Thornley Detector; HV, electron accelerating voltage; WD, working distance; HFW, horizontal field width.

The use of the TAP additives altered the EEI compositions markedly. We performed x-ray photoelectron spectroscopy (XPS) on the graphite and NCM electrodes after 4021 cycles and compared the EEI structure of the samples from the baseline cell after 956 cycles. At the graphite anode, the TAP-containing electrolyte-derived SEI contains high concentrations of C, O, and P elements, compared to the control sample of the baseline cell (Fig. 6 and fig. S5). In addition, a higher content of CC species in the entire C-containing species was also found in the TAP-containing electrolyte-derived SEI, suggesting the decomposition of the TAP at the anode (fig. S5). Meanwhile, the composition of the cathode CEI was also changed. With the TAP additive, the SEI layer has more C, P, and F and less Li and O, compared to the baseline SEI (Fig. 6 and fig. S5). High contents of LiF and P-containing species (OPO, LixPyOFz, and LixPyFz) (9) were found in the cathode CEI layer, owing to the use of the TAP additive (Fig. 6). A detailed peak interpretation is as follows: peaks at 284.6, 286.1, 288.8, and 290.1 eV in the C 1s spectrum are attributed to CC, CO, OCO, and poly(OCO) (10), respectively; peaks at 684.6 eV in the F 1s spectrum are attributed to LiF; peaks at 686.9 eV in the F 1s spectrum and 136.7 eV in the P 2p spectrum are attributed to OPO and LixPyOFz; and peaks at 686.3 eV in the F 1s spectrum and 134.5 eV in the P 2p spectrum are attributed to LixPyFz. In comparing O 1s spectrum of the aged baseline (956 cycles) and SEB-3 electrodes (4021 cycles), the peak at 529.2 eV for SEB-3 cathode is effectively eliminated in comparison to that for the baseline cathode (Fig. 6). This indicates that less lattice oxygen of NCM622 is detected for SEB-3 cathode attendant to a relatively thicker CEI layer. This is consistent with the thicker CEI layer detected by Xia et al. (2) on the coated NMC442 surface in the presence of TAP additive. Thus, the XPS result confirms that the TAP additive leads to a thick CEI layer and, in consequence, slower crack evolution, less gas generation, and longer cycle life.

The graphite and NCM622 electrodes are taken from the baseline cell after 956 cycles and the SEB-3 cell after 4021 cycles.

The three SEB cells show very close rates of capacity fade within 1000 cycles (Fig. 4A). Beyond 1000 cycles, SEB-3 shows a much lower rate of capacity fade than the other two SEB cells, as expected from its lowest reactivity. In comparison with the baseline cell, the stability and long cycle life of SEB cells are clearly evident, the reasons of which can be delineated from the differences in the capacity retention trend at various stages of aging. For the baseline cell, we see a sharp decrease in C/3 capacity retention during the initial stage and a slow decrease in the secondary stage. This is primarily attributed to the loss of lithium inventory during the quick and slow growth of the SEI layer. For the SEB cells, the capacity fade is linear with cycle number, indicating that there is no quick growth in the initial stage of aging as SEI layer growth is suppressed by in situ formation of the flame-retardant protective layer. Moreover, a sharp, nonlinear capacity loss due to lithium plating can usually be observed in the baseline cell at room temperature and at low temperatures in final stages of cell aging (11). In all SEB cells operated at 60C, this lithium plating-induced capacity loss is, however, absent, indicative of no lithium plating in SEB cells. The SEB cell free of Li plating offers a significant improvement in safety over conventional LIB cells.

There is another advantage of SEB cells promising for ultralong cycle life when deployed in the field. While conventional LIB cells undergo a large environmental temperature swing, the SEB cells almost always operate at a single, constant temperature (say 60C) regardless of ambient temperatures and after an extremely short period of initial transition by self-heating (on the order of tens of seconds). The latter feature guarantees minimal damage of battery materials in SEB cells caused by wide temperature variations.

For the baseline cell, the capacity loss at elevated temperatures is mainly due to SEI growth on the anode side and solvent oxidation on the cathode side. As a consequence, the DCR increases markedly with cycle number (Fig. 4B). In the case of SEB cells, the DCR of the fresh cell is initially much larger than the baseline cell; however, its rate of increase is much slower due to the protective coating on both the anode and cathode (Fig. 2B). Figure 4 (C and D) shows discharge curves of the fresh SEB cell versus the aged cell, respectively. Because of its DCR increase with cycle number, SEB-3 shows slight power fade after 2821 cycles at 60C. In contrast, the baseline cell shows a drastic DCR increase and, hence, substantial power loss within only 556 cycles (fig. S6). For all the SEB cells with TAP additive, their DCRs increase linearly and increased additive content leads to higher DCR in fresh cells but slower DCR evolution with cycle number (Fig. 4B). The SEB cells do not produce gas during cycling tests, yielding more safety than the baseline cell. In addition, cells containing TAP produce less gas during formation than the baseline cell (2, 12).

Because of the high-voltage tolerance of SEB cells, when charged to a high voltage of 4.4 V as compared to 4.2 V, the SEB cell discharge capacity increases 12.7%, and its discharge energy increases 14.5% (fig. S1B). Thus, the high-voltage tolerance can be used to increase cell energy density.

The electrolytes for SEB cells were formulated by reducing EC content and adding TAP as an additive. Although EC is an essential solvent for SEI layer formation, it also leads to gas generation, especially at high voltage (13). Calendar aging testing shows that high-temperature and high-SOC conditions accelerate capacity fade and increase in internal resistance while also promoting gas generation. SEB cells initially contains 10 wt % EC in the electrolyte. Some EC is consumed during the formation cycle, resulting in an EC content much less than 10% in formed SEB cells. This is advantageous since the rate of gas generation in an EC-less electrolyte would be lower than that in an electrolyte with high EC content.

With the introduction of new materials into the electrolyte, the effect on cell cost, weight, and fabrication should be evaluated. The electrolyte additive, TAP, has a comparable price and density when compared to current standard solvents; thus, no notable material cost difference is expected with the introduction of SEB electrolytes. Unlike superconcentrated electrolytes (14), the electrolytes with TAP do not increase the viscosity compared to the standard electrolyte. From a fabrication perspective, the SEB electrolytes will also add no additional cost due to the similarity in processing during and after introduction into a cell.

Last, the SEB cells offer an important benefit associated with thermal management of a battery pack. When high power is required, the SEB cells are to be heated internally (1) and operated at elevated temperatures. Assuming the environmental temperature is 25C, and the SEB and baseline cells operate at 60 and 30C, respectively, the SEB provides a temperature difference driving heat dissipation that is 7 larger than the baseline case. Further, the SEB cell has lower DCR at its operational temperature of 60C (17.1 ohmcm2 for SEB with 1 wt % TAP) than the baseline cell at 30C (25.3 ohmcm2), indicating ~1.5 lower heat generation at the same current. The combination of these two factors eases the burden of thermal management by a factor of approximately 10 for SEB cells.

We fabricated 2.8-Ah pouch cells using LiNi0.6Co0.2Mn0.2O2 (Umicore) for cathodes and graphite (Nippon Carbon) for anodes. The capacity ratio of negative to positive electrode, or NP ratio, was designed at 1.2. The 2.8-Ah pouch cell contains a stack of 20 anode and 19 cathode layers. A Celgard-2325 separator of 25 m in thickness was used. The loadings of NMC622 on the positive electrode and graphite on the negative electrode were 10.5 and 6.6 mg/cm2, respectively.

The cathodes were prepared by coating an N-methyl-2-pyrrolidone-basedbased slurry onto 15-m-thick Al foil, whose dry material consists of NCM622 (91.5 wt %), Super-P (TIMCAL) (4.1 wt %), and polyvinylidene fluoride (Arkema) (4.4 wt %) as a binder. The anodes were prepared by coating deionized waterbased slurry onto 10-m-thick Cu foil, whose dry material consists of graphite (95.4 wt %), Super-P (1.0 wt %), styrene-butadiene rubber (Zeon) (2.2 wt %), and carboxymethyl cellulose (Dai-Ichi Kogyo Seiyaku) (1.4 wt %).

One molar of LiPF6 dissolved in EC/EMC (3:7 by wt) + 2 wt % VC was used as control electrolyte (BASF). One molar of LiPF6 dissolved in a mixture of EC/EMC + 2 wt % VC was mixed in-house. To build SEB cells, 0.5 to 1.5 wt % TAP were mixed into the conventional electrolyte as additives.

Each pouch cell has a 110 mm 56 mm footprint area, weighs 63 g, and has 2.8-Ah nominal capacity with a specific energy of 166 Wh/kg and an energy density of 310 Wh per liter. Discharge performance of the baseline and SEB cells at room temperatures is shown in fig. S7 as a function of C-rate.

Cycle aging tests of the pouch cells were performed using a Land instrument battery testing system (Model CT2001B, Land Instruments). A forced-air oven was used to control different ambient temperatures. For each aging cycle, the cell was charged to 4.2 V at a constant current of 2.8 A (1C-rate) and then charged at a constant voltage of 4.2 V until the current decreased to 0.14 A (C/20). After resting for 5 min, the cell was discharged to 2.8 V at a constant current of 2.8 A (1C-rate) followed by a final rest period of 5 min. When the aging cycle number reached a specific value (e.g., 403, 1006 cycles), the cell was cycled at a charge and discharge rate of C/3 to determine the capacity (designated as C/3 capacity) of the cell. For impedance tests at different temperatures, the cells were fully charged and then discharged at a rate of C/3 to 90% SOC. Impedance testing was performed with an AC voltage amplitude of 5 mV in the frequency range of 50 kHz to 0.005 Hz. For DCR test, the cells were fully charged and then discharged to 50% SOC at C/3-rate. A discharge rate of 5C and a charge rate of 3.75C were used to determine the value of DCRDischarge and DCRCharge.

Calendar aging tests were performed at different ambient temperatures and SOCs. The forced-air oven was used to control different ambient temperatures. The cell voltage was kept constant, and the current was collected. When the calendar aging time reached a specific value (e.g., 25, 60, 120, and 180 days), the cell was cycled at a charge and discharge rate of C/3 to determine capacity of the cell. Then, impedance and DCR tests were conducted under the same conditions as that for the cycle-aged cells.

For the nail penetration test, the cell was fully charged (1C CCCV charge with a cutoff voltage of 4.2 V and a cutoff current of C/20). Thermocouples were placed at 10 mm to the geometry center of the cell and at the negative tab of the cell. The nail diameter is 5 mm, made of heat-resisting steel (point angle of the nail is 60; nail surface is clean, without rust or oil). Rate of penetration was at 30 mm/s; the nail penetrated through the geometrical center of the electrode plane perpendicularly and stayed inside the cell. The observation time was 1 hour until the cell cooled down and the cell voltage dropped to nearly zero.

The SEM and XPS analyses were performed by first extracting the electrode samples from the fully discharged graphite/NCM622 pouch cells after cycling and washing 3 with EMC. XPS tests were conducted on a PHI VersaProbe II Scanning XPS Microprobe. The samples were loaded in a glove box and transferred into the instrument through a vacuum transfer vessel. SEM imaging was performed on an FEI Nova NanoSEM 630 SEM instrument.

Acknowledgments: Funding: This work was partially supported by U.S. Department of Energys Office of Energy Efficiency and Renewable Energy under award number DE-EE0008447. Author contributions: S.G. and C.-Y.W. developed the concept and wrote the manuscript. S.G. and R.S.L. designed and built the cells. S.G. built the test stand and carried out the performance characterization. T.L. carried out the nail penetration test. Y.L. performed the impedance analysis. Y.G. and Daiwei Wang carried out the XPS and SEM analysis. All authors contributed to development of the manuscript and to discussions as the project developed. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Car T-cell therapy: The future fifth pillar of cancer treatment – The Irish Times

Thursday, February 27th, 2020

Revolutionary Car T-cell therapy is set to become the fifth pillar of cancer treatment and is already showing dramatic results in the successful treatment of blood cancers.

Prof Owen Smith is a consultant paediatric haematologist who has dedicated his 35-year career to researching and treating cancer in children and young adolescents. Smith, who is based at Childrens Health Ireland at Crumlin hospital, is a specialist in stem cell transplantation. Over the years, he has seen big advances in cancer treatments but few have excited him as much as Car T-cell therapy which is showing huge potential as a pioneering treatment for blood and other challenging cancers.

In a nutshell, Car (chimeric antigen receptor) T-cell therapy is a form of immunotherapy that uses the patients own immune cells to recognise and attack cancer. It involves drawing blood from the patient, isolating the T-cells within it and genetically altering and multiplying them in a lab. The end product is transfused back into the patient where the Car T-cells bind to an antigen or structural molecule on the cancer cells and kills them.

Car T-cells or Cars for short, are like sniper fire that target the cancer rather than blanket bombing it, explains Prof Smith. They cause much less toxicity than chemotherapy and have much better results and remission rates.

Cars therapy has been in gestation since the early 1980s with the first-generation treatment becoming available around 2010.

To date, about 2,200 Cars have been completed in the US, while in Europe the number is about 800 and growing fast. There are now two second generation Car T products licensed for three types of blood cancer and Prof Smith says: We now have hope with these relapse/refractory blood cancers where only a few years ago, we had none.

Prof Smith was working in Royal Free Hospital in London (one of the UKs major Car T therapy centres today) in the 1980s when the therapeutic potential of T-cells, which was initially discovered in Israel, was first being realised. It became clear through some good connected thinking that it was the T-cells that were having a very important effect on cure in patients with CML (chronic myeloid leukaemia), he says. Around the same time there were papers coming in from the States with similar results so the concept was beginning to gather momentum.

The question became: could you take T-cells from a donor and give them to people who were relapsing and put them into remission? Things began to crystallise in the late 80s/early 90s as T cells were recognised as immune effector cells that were very good at killing cancer, especially in patients with CML who were relapsing after stem cell transplantation.

Then people began wondering if we could use the end of the molecule the so-called antigen binding part of an antibody and link it to the T-cell receptor and put it into T-cells to see if that would give an even better result. What eventually followed between 2010 and 2014 were a number of first generation Car T-cell studies that showed it was very effective in some patients with haematological malignancies and in those with acute lymphoblastic and chronic lymphocytic leukaemia in particular. Since then there have been 10 big studies with second generation Cars that have also proved its efficacy, says Prof Smith.

Acute lymphoblastic leukaemia is the most common form of blood cancer in children and Prof Smith sees about 50 cases a year here. Unfortunately, if this cancer relapses, particularly during or shortly after chemotherapy, it usually becomes resistant to further treatment and the children can also no longer tolerate it. The only option up to now has been palliative care, but Cars is a lifeline that can alter this outcome.

Second generation Car T-cell activity can push around 90 per cent of children into remission and once you get them into remission you have time to get them into prime clinical condition to give them a stem cell transplant and cure them that way, says Prof Smith. In the adult population, about 20 cases a year of non-Hodgkins lymphoma would be suitable for this therapy.

Weve known for a long time that the immune system is important in someone developing cancer, Prof Smith adds. So, for example when a persons T-cells are knocked out by something like HIV, they typically have an increased risk of developing lymphoid malignancies. The immune system can also be tricked into not recognising when a cancer develops and undergoes metastatic spread. This immune activation therapy can unmask this camouflaging of the cancer resulting in regression.

One of the challenges with the Cars is that they can become lost in the body and lose their persistence. When this happens the person usually relapses. We are now looking at different combinations of Cars and using two or three of them on the one cell to prevent relapse, says Prof Smith.

This is a massively evolving field and one of these exponential technologies you hear about from time to time. Whats really encouraging it that its now being pushed out to treat other types of high-risk solid tumours that currently have dismal survival rates such as metastatic non-small cell lung cancer, pancreatic cancer, triple negative breast cancer, ovarian cancer, brain tumours and neuroblastomas in children. Its opening up a totally different treatment pathway for cancer.

Prof Smith acknowledges that Cars, like many innovative cancer treatments, is expensive at about 300,000 per commercially produced treatment. But he points out that as its use becomes more widespread prices will drop and that if the total costs of conventional treatments are added up the economic argument for its use is compelling. Yes, its costly but some recent health economic data from the USA is suggesting it may not be as costly as it first appears, he says. Specifically, repeated chemotherapy, the cost of regular hospital admissions due to relapse, trips to intensive care, blood product support and anti-bacterial, anti-fungal and anti-viral therapies all with very little return in terms of clinical outcome.

Prof Smith adds that Car T therapy is set to become the fifth pillar of cancer treatment alongside surgery, chemotherapy, radiation and targeted therapy and that whats happening now is just the start of the Car T revolution. The next phase will be using them in combination with checkpoint inhibitors (another arm of immunotherapy) and the third generation of Cars will have greater efficacy and less toxicity, he says.

Prof Smith is low key about his personal achievements but in addition to saving the lives of countless children under his care, he also has a distinguished research record and his work has been widely published and acknowledged internationally. He was to the forefront of a major breakthrough in the intervention and treatment of meningitis in the 1980s and he is a strong believer in robust peer-reviewed clinical trials, which he believes are one of the most effective ways of establishing a cure for any disease.

Owen Smith is professor of Paediatric and Adolescent Medicine at UCD, honorary Regius Professor of Physic (1637) at Trinity College and academic lead to the Childrens Hospital Group. He is also a principal investigator at the National Childrens Research Centre and Systems Biology Ireland at University College Dublin and national clinical programme lead for children and adolescents/young adults with cancer. In 2015 he was awarded a CBE by Queen Elizabeth for his life-long dedication to treating cancer in children.

Prof Smith is a speaker at the international BioPharma Ambition 2020 event which is being held in Dublin Castle on March 3rd and 4th.

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Policy and public health: all the decisions we can’t see – PMLiVE

Thursday, February 27th, 2020

Lets be honest, January was a bad month for healthcare news coming out of China.

For starters, at the end of December, a Chinese court sentenced He Jiankui to three years in prison for operating an illegal medical practice, which includes using a fake ethical review certificate and misleading participants about a studys risks, and also violating an ethics guidance from 2003 that barred the reproductive use of research embryos.

You may remember Dr Jiankui as the individual who made the worlds first genetically edited babies by recruiting couples in which the man was HIV positive but the woman was not, as part of an effort to create embryos with a genetic mutation that made the couples offspring protected from the virus.

Esteemed bioethicists and scholars, such as Josephine Johnston from the Hastings Center that produces books, articles and other publications on ethical questions in medicine, science and technology that help inform policy, practice and public understanding, as well as Robin Lovell-Badge, a stem cell biologist at the Francis Crick Institute, have both acknowledged that He Jiankuis work straddled a line that might have got them in hot water in both the US and the UK.

In fact, Lovell-Badge said in a statement distributed by the United Kingdoms Science Media Centre that both prison and a fine would have been the likely penalties if someone had done what [He Jiankui] did in the UK.

And then, in early January, China informed the world about a deadly new coronavirus that has been causing severe respiratory illness and death among its citizens.

As of 6 February, in China there were over 28,000 confirmed cases and 565 people have died there; in addition there were more than 220 confirmed cases outside China and there has been one death in the Philippines.

On 26 January, the New York Times wrote: The outbreak has drawn fresh attention to Chinas animal markets, where the sale of exotic wildlife has been linked to epidemiological risks. The Wuhan virus is believed to have spread from one such market in the city. The SARS outbreak nearly two decades ago was also traced back to the wildlife trade.

These two scenarios highlight an important aspect of public health and health policy: complex decisions that require almost real-time response are only as good as the information upon which those decisions are based.

In the case of He Jiankui, many countries have policies and laws in place against germline gene editing. But because the court proceedings, documentation and testimony in this case have not been made public, it is impossible to know the details surrounding the events that may have facilitated this rogue scientists behaviour.

And because we dont have those details, implementing new health policy to prevent recurrences of this situation remains difficult. Not impossible, but difficult. Some will argue that US and UK laws are expansive enough and the penalties imposing enough on their own merits that we need not fret about a single scientists actions in a universally agreed upon opaque scientific ecosystem.

Others will argue that the scientific communitys overwhelmingly negative response and outrage will discourage this from happening again. I disagree.

And in the coronavirus situation, the same New York Times article went on to say: Conclusive evidence about how this outbreak started is lacking. Although officials in Wuhan first traced it to a seafood market, some who have fallen ill never visited the market.

'Researchers have also offered disparate explanations about which animals may have transmitted the virus to humans. Chinas record doesnt help. During the SARS epidemic in 2002 and 2003, officials covered up the extent of the crisis, delaying the response. The Chinese government has promised far more transparency this time, and the World Health Organization (WHO) has praised its cooperation with scientists.

Im sure we all feel better that a non-partisan agency like the WHO has authenticated the cooperation of the Chinese scientific community in 2020 but the issue is far more complex.

We need to understand the larger social and cultural issues that may be driving the underlying causes of these deadly illnesses. And in order to do that, the Chinese governments openness to the rest of the worlds questions and, ultimately, its willingness to revise public policy to reflect a greater harmonisation for global public health will be put to the test.

This is not a China issue. Its a transparency issue. Whether its the reporting of a measles outbreak in America or the promulgationof information on Ebola cases in West Africa, we are all responsible because the world needs more transparency.

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Kadmon Announces Expanded Results of Interim Analysis of Pivotal Trial of KD025 in cGVHD – Yahoo Finance

Thursday, February 27th, 2020

Patient Analyses and Safety Data Continue to Underscore Positive Impact of KD025 in cGVHD

Pre-NDA Meeting with FDA Planned for March 2020; Topline Results of Primary Analysis to be Announced in Q2 2020

NEW YORK, NY / ACCESSWIRE / February 23, 2020 / Kadmon Holdings, Inc. (KDMN) today announced expanded results from the previously reported interim analysis of ROCKstar (KD025-213), its ongoing pivotal trial of KD025 in chronic graft-versus-host disease (cGVHD). The data were presented today in the oral latebreaker session at the 2020 Transplantation & Cellular Therapy (TCT) Meetings.

As announced in November 2019, KD025 met the primary endpoint of Overall Response Rate (ORR) at the study's planned interim analysis, two months after completion of enrollment. KD025 showed statistically significant and clinically meaningful ORRs of 64% with KD025 200 mg once daily (95% Confidence Interval (CI): 51%, 75%; p<0.0001) and 67% with KD025 200 mg twice daily (95% CI: 54%, 78%; p<0.0001). In the expanded KD025-213 dataset presented today, ORRs were consistent with the previously reported interim analysis across key subgroups, including in patients with four or more organs affected by cGVHD (n=69; 64%), patients who had prior treatment with ibrutinib (n=45; 62%) and patients who had prior treatment with ruxolitinib (n=37; 62%). Three patients achieved a Complete Response. Responses were observed in all affected organ systems, including in organs with fibrotic disease. KD025 has been well tolerated: adverse events were consistent overall with those expected to be observed in cGVHD patients receiving corticosteroids, and no apparent increased risk of infection was observed. Additional secondary endpoints, including duration of response, corticosteroid dose reductions, Failure-Free Survival, Overall Survival and Lee Symptom Scale reductions continue to mature and will be available later in 2020.

"KD025 has been well tolerated and has already demonstrated high response rates in patients with severe and complex cGVHD after a median of five months of follow-up," 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.

"We are extremely pleased with the interim outcomes of this pivotal trial of KD025 in cGVHD, which track closely our findings from our earlier Phase 2 study. KD025 achieved robust response rates across all subgroups of this difficult-to-treat patient population, who had a median of four prior lines of therapy, and 73% of whom had no response to their last line of treatment," said Harlan W. Waksal, M.D., President and CEO of Kadmon. "We plan to meet with the FDA for a pre-NDA meeting in March 2020 and to announce topline results from the primary analysis of this trial in Q2 2020."

At the TCT Meetings, Kadmon also presented long-term follow-up data from KD025-208, its ongoing Phase 2 study of KD025 in cGVHD (Abstract #15205). These data were recently presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in December 2019.

About the ROCKstar (KD025-213) Trial

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 once daily or KD025 200 mg twice daily, enrolling 66 patients per arm. Statistical significance is achieved if the lower bound of the 95% CI of ORR exceeds 30%.

While the ORR endpoint was met at the interim analysis, which was conducted as scheduled two months after completion of enrollment, topline data from the primary analysis of the KD025-213 study, six months after completion of enrollment, will be reported in Q2 2020. Full data from the primary analysis will be submitted for presentation at an upcoming scientific meeting.

About KD025

KD025 is a selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates immune response as well as fibrotic pathways. 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 clinical-stage biopharmaceutical company that discovers, develops and delivers transformative therapies for unmet medical needs. Our clinical pipeline includes treatments for immune and fibrotic diseases as well as immuno-oncology therapies.

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, 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; (iv) the timing or likelihood of regulatory filings and approvals; (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, China, Japan 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) the potential benefits from any of our product candidates being granted orphan drug or breakthrough designation; (xxi) the future trading price of the shares of our common stock and impact of securities analysts' reports on these prices; and/or (xxii) 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 the Company's filings with the U.S. Securities and Exchange Commission (the "SEC"), including the Company'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. The Company 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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Radiation, Inflammation and Triple-Negative Breast Cancer: A Study – OncoZine

Wednesday, February 26th, 2020

Although radiation is successfully used to treat breast cancer, inflammation caused as a side-effect of radiation may have an adverse effect, promoting the survival of triple-negative breast cancer cells.

This is the conclusion of a study by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCares Helen F. Graham Cancer Center & Research Institute, published online in the International Journal of Radiation Biology.[1]

Triple-negative breast cancer is cancer that tests negative for estrogen receptors, progesterone receptors, and excess human epidermal growth factor receptor 2 (HER2) protein. As a result, the growth of this cancer is not fueled by the hormones estrogen and progesterone, or by the HER2 protein. These cancers tend to be more common in women under age 40, who are African-American, Latina, or who carry a mutated BRCA1 gene.

Triple-negative breast cancer accounts for 15-20% of all breast cancers and is faster growing than other types of breast cancers.

Sims-Mourtadas latest study helps scientists to better understand the mechanisms behind the development of this aggressive and hard-to-treat cancer. It shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem breast cancer cells.[1]

The good and the badThis is the good and the bad of radiation, Sims-Mourtada noted. We know radiation-induced inflammation can help the immune system to kill tumor cells thats good but also it can protect cancer stem cells in some cases, and thats bad.

Whats exciting about these findings is were learning more and more that the environment the tumor is in its microenvironment is very important. Historically, research has focused on the genetic defects in the tumor cells. Were now also looking at the larger microenvironment and its contribution to cancer, she added.

My work focuses on cancer stem cells and their origination. [These cells] exist in many cancers, but theyre particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth, Sims-Mourtada explained.

The researchers applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation-induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. As yet unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.

DelawareFor women living in Delaware, Sims-Mourtadas research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

At ChristianaCare, we are advancing cancer research to help people in our community today, while we also advance the fight against cancer nationwide, said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute.

Sims-Mourtadas research is a dramatic step toward better treatments for triple-negative breast cancer, Petrelli concluded.

To advance her research on inflammation, last year Sims-Mourtada received a US $ 659,538 grant from the Lisa Dean Moseley Foundation. The three-year grant will enable her and her team at the Cawley Center for Translational Cancer Research to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and possible therapy for this particularly difficult to treat cancer.

Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing, Sims-Mourtada said.

The researchers previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

Reference[1] Arnold KM, Opdenaker LM, Flynn NJ, Appeah DK, Sims-Mourtada J. Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells [published online ahead of print, 2020 Jan 6]. Int J Radiat Biol. 2020;114. doi:10.1080/09553002.2020.1705423 [Pubmed][Article]

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Magenta Therapeutics to Participate in Cowen Health Care Conference on Monday, March 2nd in Boston – Yahoo Finance

Wednesday, February 26th, 2020

Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that the company is scheduled to participate in a fireside chat at the 40th annual Cowen Health Care Conference on Monday, March 2nd, 2020, at 4:10 p.m. ET at the Boston Marriott Copley Place.

A live webcast of the fireside chat can be accessed on the Magenta Therapeutics website at https://investor.magentatx.com/events-and-presentations. The webcast replay will be available for 90 days following the event.

About Magenta TherapeuticsMagenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking StatementThis press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as "may," "will," "could", "should," "expects," "intends," "plans," "anticipates," "believes," "estimates," "predicts," "projects," "seeks," "endeavor," "potential," "continue" or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption "Risk Factors" in Magentas Registration Statement on Form S-1, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200226005256/en/

Contacts

Manisha Pai, Vice President, Communications & Investor Relations617-510-9193mpai@magentatx.com

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Top 5 AJMC Stories of the Week: February 22, 2020 – AJMC.com Managed Markets Network

Wednesday, February 26th, 2020

The most popular stories of the week onAJMC.

The journalOncogenerecently publishedresultsof an investigation into the drivers behind triple-negativebreast cancer. Because the disease has such high recurrence and low survival rates, investigators from Manchester, Glasgow, and Sheffield universities sought to better understand what triggers, and arrests, the growth of this subtype of breast cancer.

Stem Cells Prove Effective in Treating MS Neural Damage

Several clinical trials have found mesenchymal stem cell therapy effective in treating neural damage in patients with multiple sclerosis (MS), according to a review published inStem Cell Investigation.

Youth Newly Diagnosed With HIV Have Advanced Infection, Higher Viral Loads

Close to 80% of HIV-positive individuals are shown to be virally suppressed through their most recent test results, according to data from 2016 through 2018, as well as 32% to 63% of adults older than 24 years. Youth with a new HIV diagnosis, however, come in at only 12%.

DC Circuit Panel Rejects Arkansas Medicaid Work Rules

Writing for the panel, Judge David Sentelle said HHS Secretary Alex Azar ignored predictions that thousands of people would lose their healthcare coverage.

Much of MS Cost Burden Falls on Patients' Shoulders

A British study shows nonmedical costs make up a significant portion of the annual expense generated by MS. Most of those nonmedical costs are not covered by insurance.

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Analysts Estimate Fate Therapeutics (FATE) to Report a Decline in Earnings: What to Look Out for – Yahoo Finance

Wednesday, February 26th, 2020

The market expects Fate Therapeutics (FATE) to deliver a year-over-year decline in earnings on higher revenues when it reports results for the quarter ended December 2019. This widely-known consensus outlook is important in assessing the company's earnings picture, but a powerful factor that might influence its near-term stock price is how the actual results compare to these estimates.

The stock might move higher if these key numbers top expectations in the upcoming earnings report. On the other hand, if they miss, the stock may move lower.

While management's discussion of business conditions on the earnings call will mostly determine the sustainability of the immediate price change and future earnings expectations, it's worth having a handicapping insight into the odds of a positive EPS surprise.

Zacks Consensus Estimate

This clinical-stage biotech company that develops stem cell treatments is expected to post quarterly loss of $0.39 per share in its upcoming report, which represents a year-over-year change of -56%.

Revenues are expected to be $1.84 million, up 10.8% from the year-ago quarter.

Estimate Revisions Trend

The consensus EPS estimate for the quarter has remained unchanged over the last 30 days. This is essentially a reflection of how the covering analysts have collectively reassessed their initial estimates over this period.

Investors should keep in mind that an aggregate change may not always reflect the direction of estimate revisions by each of the covering analysts.

Price, Consensus and EPS Surprise

Earnings Whisper

Estimate revisions ahead of a company's earnings release offer clues to the business conditions for the period whose results are coming out. Our proprietary surprise prediction model -- the Zacks Earnings ESP (Expected Surprise Prediction) -- has this insight at its core.

The Zacks Earnings ESP compares the Most Accurate Estimate to the Zacks Consensus Estimate for the quarter; the Most Accurate Estimate is a more recent version of the Zacks Consensus EPS estimate. The idea here is that analysts revising their estimates right before an earnings release have the latest information, which could potentially be more accurate than what they and others contributing to the consensus had predicted earlier.

Thus, a positive or negative Earnings ESP reading theoretically indicates the likely deviation of the actual earnings from the consensus estimate. However, the model's predictive power is significant for positive ESP readings only.

A positive Earnings ESP is a strong predictor of an earnings beat, particularly when combined with a Zacks Rank #1 (Strong Buy), 2 (Buy) or 3 (Hold). Our research shows that stocks with this combination produce a positive surprise nearly 70% of the time, and a solid Zacks Rank actually increases the predictive power of Earnings ESP.

Please note that a negative Earnings ESP reading is not indicative of an earnings miss. Our research shows that it is difficult to predict an earnings beat with any degree of confidence for stocks with negative Earnings ESP readings and/or Zacks Rank of 4 (Sell) or 5 (Strong Sell).

How Have the Numbers Shaped Up for Fate Therapeutics?

For Fate Therapeutics, the Most Accurate Estimate is the same as the Zacks Consensus Estimate, suggesting that there are no recent analyst views which differ from what have been considered to derive the consensus estimate. This has resulted in an Earnings ESP of 0%.

Story continues

On the other hand, the stock currently carries a Zacks Rank of #3.

So, this combination makes it difficult to conclusively predict that Fate Therapeutics will beat the consensus EPS estimate.

Does Earnings Surprise History Hold Any Clue?

Analysts often consider to what extent a company has been able to match consensus estimates in the past while calculating their estimates for its future earnings. So, it's worth taking a look at the surprise history for gauging its influence on the upcoming number.

For the last reported quarter, it was expected that Fate Therapeutics would post a loss of $0.38 per share when it actually produced a loss of $0.40, delivering a surprise of -5.26%.

The company has not been able to beat consensus EPS estimates in any of the last four quarters.

Bottom Line

An earnings beat or miss may not be the sole basis for a stock moving higher or lower. Many stocks end up losing ground despite an earnings beat due to other factors that disappoint investors. Similarly, unforeseen catalysts help a number of stocks gain despite an earnings miss.

That said, betting on stocks that are expected to beat earnings expectations does increase the odds of success. This is why it's worth checking a company's Earnings ESP and Zacks Rank ahead of its quarterly release. Make sure to utilize our Earnings ESP Filter to uncover the best stocks to buy or sell before they've reported.

Fate Therapeutics doesn't appear a compelling earnings-beat candidate. However, investors should pay attention to other factors too for betting on this stock or staying away from it ahead of its earnings release.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free reportFate Therapeutics, Inc. (FATE) : Free Stock Analysis ReportTo read this article on Zacks.com click here.

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Meet 20 European Immuno-Oncology Companies that are Fighting… – Labiotech.eu

Wednesday, February 26th, 2020

With the success of CAR T-cell therapies and other innovative medicines in this area, immuno-oncology has become a buzzword in biotech, with more and more companies starting up in Europe and elsewhere. With so many players involved, it can be hard to know who is doing what. Here are 20 European companies we think stand out and are leading the revolution in cancer medicine.

Although immunotherapies to treat cancer have been around for decades, new approaches are popping up every other day. After all, enlisting the immune system to fight cancer remains an extremely promising therapeutic strategy. There are so many companies focusing on different kinds of immunotherapies that it was quite a challenge to choose our favorites. We therefore enlisted the help of experts in the industry to select the following 20 immuno-oncology companies in Europe as our top picks. As ever, these are in no particular order.

Founded in Abingdon, UK, in 2008, Adaptimmune develops enhanced T-cell therapies that support the immune system in detecting and targeting cancer cells. Interestingly, its SPEAR T cell technology can target a variety of solid tumors a feat that is not easy to achieve, as solid tumors have a highly complex tumor microenvironment that many immunotherapies find difficult to penetrate.

The companys technology can identify and select T cell receptors (TCRs) that are more likely to improve the patients immune response and result in the effective binding of cancer cells. In January 2020, Adaptimmune and Japanese company Astellas agreed to co-develop and co-commercialize stem-cell-derived allogeneic chimeric antigen receptor (CAR)-T and TCR T cell therapies, which means that they not only treat one specific patient but a large number of patients with a particular cancer type. The deal was worth 806M.

ADC Therapeutics works in the area of antibody-drug conjugates (ADCs). Since being founded in 2011 in Lausanne, Switzerland, ADC Therapeutics has raised 514M ($558M) to advance its immuno-oncology therapies. The companys proprietary ADCs combine monoclonal antibodies that are specific to targets on the surface of tumor cells with a specific class of toxins called pyrrolobenzodiazepine (PBD) dimers.

The PBD dimer is released inside the tumor cells and binds to the tumor DNA, which blocks the division of the tumor cells and eventually kills them. ADC Therapeutics currently has two ADCs for liquid tumors in pivotal phase II studies, and one ADC targeting solid tumors in phase Ib. In January 2020, the company announced the positive results of its phase II trial of its leading ADC in patients with relapsed or refractory diffuse large B cell lymphoma.

Yet another direction in the treatment of cancer via the immune system is taken by Heidelberg-based company Affimed Therapeutics. Founded in 2000, the company focuses on the innate immune system. Using its ROCK platform, Affimed develops multi-specific antibodies called cell engagers.

Innate cell engagers can bind to the patients innate immune cells, including natural killer cells and macrophages, while simultaneously binding to specific tumor cells. As a result, the patients own immune systems can attack and kill the cancer cells. The companys lead candidate is currently in phase II for a number of liquid tumors.

Based in London, UK, and founded in 2014 as a spin-out from the University College London, Autolus Therapeutics uses CARs and TCRs to reprogram T cells so they recognize and consequently kill tumor cells. In January 2020, the company revealed the closure of its public offering on the Nasdaq with net proceeds of 68.4M ($74.2M).

Autolus other news in January was the announcement of the clinical progress of its next-generation programmed T cell therapy. It is currently in Phase I/II for the treatment of adults with relapsed or refractory diffuse large B cell lymphoma. The results showed no neurotoxicity and a manageable safety profile.

BioNTech has a much larger pipeline that contains CARs, TCRs, recombinant cytokines, and optimized mRNA. Founded in Mainz, Germany, in 2008, the company is one of the largest biotechs in Europe. Its pipeline is full to bursting with a variety of immuno-oncology therapies based on mRNA, antibodies, and CAR-T cells.

In July 2019, BioNTech raised one of the biggest ever funding rounds of a European biotech with a whopping 290M Series B. However, in October of that same year, the companys Nasdaq IPO, which was initially estimated to raise around 725M, resulted in pricing at only 141M due to poor market conditions in the US.

Based in Paris, France, and founded in 1999, Cellectis is also focusing on CART-cell therapy. It is working on a novel type of CART therapy known as Universal CARTs (UCARTs). Unlike the two approved CAR-T therapies, Novartis Kymriah and Gileads Yescarta, UCARTs are allogeneic so rather than being personalized, they can treat a large number of patients with a particular cancer type.

In November 2019, Cellectis announced that it had won the European patent challenge for the use of CRISPR-Cas9 for gene editing T cells. This process will help the company further develop its UCART platform. To date, six of its main UCART product candidates are in Phase I clinical trials. For three of these programs, Cellectis has partnered with Servier and Allogene.

As another biotech giant, Celyad is also working in the field of CART-cell therapies but is focusing on the NKG2D receptor. Founded in 2004 in Mont-Saint Guibert, Belgium, the companys lead immuno-oncology candidate uses the NKG2D receptor. NKG2D can bind to eight different ligands that are naturally found on cancer cells present in 80% of solid and liquid malignancies.

Something cool about NKG2D is that the ligands that it recognizes are also expressed by the tumor microenvironment, which comprises the blood vessels that support the tumor and the cells that make sure the tumor can evade the immune system. As a result, the lead candidate can target and kill the tumor as well as cleaning up its microenvironment. The candidate is currently in phase I.

Spun-off from the Babraham Institute in Cambridge, UK, in 2007, Crescendo Biologics develops targeted T-cell enhancing therapeutics with the aim of tackling difficult-to-treat cancers. The companys Humabody therapies are small, multi-specific antibody fragments that can penetrate tumor tissue in a way that conventional antibodies cannot.

Crescendo Biologics lead proprietary candidate is a bispecific T-cell engager targeting the prostate-specific membrane antigen. It can selectively activate tumor-specific T cells within the tumor microenvironment. It is currently advancing towards clinical development.

As a spring chicken among other European immuno-oncology companies, we felt Ervaxx deserved a mention here because it develops cancer vaccines and cell therapies targeting dark antigens normally silent genes that are expressed in cancer cells. Founded in 2017 in London, UK, Ervaxx recently made headlines when it got its hands on the license of an exciting new preclinical stage universal cancer immunotherapy.

In early January 2020, a group of researchers at Cardiff University discovered a new type of T cells that have the potential to attack a wide range of cancers, such as leukemia and melanoma. Ervaxx is continuously expanding its repertoire of Dark Antigens. Using these, the company is working on a pipeline of off-the-shelf cancer vaccines and TCR-based therapies.

Founded in 2008 in Copenhagen, Denmark, Evaxion takes a very different approach to fighting cancer: using artificial intelligence (AI) to develop immunotherapies. The company has developed two AI platforms that can identify and optimize epitopes and antigens that are capable of eliciting strong immune responses against cancer and infectious diseases.

The companys PIONEER platform is used for the development of personalized cancer immunotherapies. In April 2019, it announced the beginning of phase I with the dosing of the first patient with its lead candidate, a therapeutic vaccine. Evaxion closed the year by successfully raising 16M ($17M).

GammaDelta Therapeutics, founded in 2016, takes another approach to immuno-oncology therapies. The London-based company focuses on gamma delta T cells. Unlike alpha beta T cells which are commonly used in CAR-T therapy, gamma delta T cells are a part of the innate immune system. In short, this means that gamma delta T cells are already pre-programmed to identify and kill cells that are modified by cancer. The company is currently advancing its allogeneic gamma delta T cell therapies through preclinical development.

In October 2019, GammaDelta Therapeutics announced the formation of the spinout company Adaptate Biotherapeutics. Adaptate will be developing therapeutic antibodies that can modulate the activity of gamma delta T cells with the aim of triggering an immune response to fight cancer.

Danish biotech Genmab had an exciting start to the new year. In January 2020, one of the companys lead candidates daratumumab, a monoclonal antibody, received marketing authorization by the EMA. Marketed as DARZALEX, it can be used in combination with bortezomib, thalidomide, and dexamethasone to treat multiple myeloma.

Founded in Copenhagen in 1999, Genmab focuses on the development of antibody therapies against cancer. In December 2019, Genmab signed a deal with German biotech CureVac to develop mRNA drugs that can produce antibodies within the patient, which is an exciting development.

Heidelberg Pharma, formerly known as Wilex, was founded in 1997 in Heidelberg, Germany. The company focuses on ADCs. It has an exclusive license agreement with the Max Delbrck Center for Molecular Medicine in the Helmholtz Association in Berlin that includes a number of surface proteins found in multiple myeloma cells called B cell maturation antigen (BCMA).

Heidelberg Pharmas lead candidate targets BCMA and is currently advancing through the preclinical stage. It is an ADC that consists of a BCMA antibody, a specific linker, and the toxin amanitin, one of the deadliest toxins found in several mushroom species.

Founded in 2011, Austrian company Hookipa Pharma engineers arenaviruses to deliver tumor-specific genes to dendritic cells. Dendritic cells naturally activate killer T cells by delivering the tumor-specific antigens to them, which triggers an immune response. HOOKIPA Pharmas co-founder, Rolf Zinkernagel, actually received the Nobel Prize for Physiology or Medicine in 1996 for his work on how killer T cells can recognize virus-infected cells.

Hookipas leading immuno-oncology therapy is currently progressing through phase I. In February 2019, the company closed a Series D financing round for 33.2M ($37.4M). The funding is being used to boost the clinical development of its immunotherapies for cancer and infectious diseases based on its proprietary arenavirus platform.

This French company develops antibody therapies to fight cancer. Marseille-based ImCheck has developed a pipeline of monoclonal antibodies that target specific checkpoint molecules of the butyrophilin (BTN) family, which engage gamma delta T cells. As part of the innate immune system, gamma delta T cells fight cancer cells naturally.

ImChecks lead drug candidate, an anti-BTN3 antibody that targets solid tumors, is expected to enter phase I in 2020. In order to fund this trial and further boost the development of immunotherapies, ImCheck closed a series B funding round in December 2019 worth 48M.

Immatics was founded in 2000 in Tbingen, Germany. The company develops personalized immuno-oncology therapies by engineering patient T cells to express TCRs, which specifically target the patients cancer. Unlike CAR-T therapies that generally target surface proteins, Immatics immunotherapy can also target proteins within cancer cells, which makes the cancer cells more vulnerable and accessible to the immune system.

In August 2019, American company Celgene and Immatics signed a deal worth more than 1.35B ($1.5B) to further develop its immuno-oncology therapies. In three cancer immunotherapy programs, Immatics will develop leading cell immunotherapy candidates for solid tumors, while Celgene has the option to co-develop the candidates or take over the development altogether.

Based in Oxfordshire, UK, and founded in 2008, Immunocore also focuses on TCRs. Its ImmTAC (immune mobilizing monoclonal TCRs against cancer) technology is based on a new class of bi-specific biologics that can activate a specific T cell response in cancer cells.

In December 2019, Immunocore announced the start of the first-in-human clinical trial of its third bispecific, which was developed using the ImmTAC technology platform. Immunocore has collaborations with a number of partners, including AstraZeneca, Genentech, GSK, and Eli Lilli.

Medigene also focuses on TCRs. However, this company develops modified TCRs called TCR-Ts, as well as dendritic cell vaccines (DCs), and T cell-specific antibodies (TABs).

In January 2020, Medigene announced positive results after a two-year phase I/II for its DC vaccine in patients with acute myeloid leukemia (AML). Moreover, its leading TCR-T candidate is currently being prepared for phase II clinical trials. Medigene was founded in 1994 in Martinsried, Germany.

As a neighbor of Medigene, MorphoSys is also based in Martinsried, Germany. It was founded in 1992. The company is one of the very few European biotechs valued at over 1B. MorphoSys develops antibody therapies for numerous conditions.

The companys lead immuno-oncology candidate tafasitamab is a humanized monoclonal antibody that targets CD19, an antigen mainly expressed by various B cell-derived blood cancers, such as non-Hodgkins lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia. This candidate is being co-commercialized by Incyte. Other partners of MorphoSys include Novartis, Roche, GSK, and Roche.

Another company focusing on ADCs is NBE Therapeutics. This companys goal is to target solid tumors. Based in Basel, Switzerland, and founded in 2012, NBE Therapeutics has developed a technology that uses an enzyme to attach small molecule drugs to monoclonal antibodies. This approach is different from conventional ADCs that are usually generated using a chemical junction, which can be unstable at times.

The companys lead candidate, an ADC for the treatment of triple-negative breast cancer, lung, and ovarian cancer, is expected to reach phase I in 2020.

Images via Elena Resko & Shutterstock.com

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Cell Analysis Market is Expected to See Growth Rate of 6.96% – Nyse Nasdaq Live

Wednesday, February 26th, 2020

Cells constitute discrete units of biological function and serve as starting points in a myriad of studies to identify and map many of the basic biochemical and physical processes of life. Cell analysis is a wide term that can be applied to a range of different technologies, the technology used depends on experimental needs. Compiling data sets from multiple cell analysis investigations allows scientists to better understand, predict, and ultimately influence the factors that underlie cell health, function, death, and proliferation.

This intelligence report provides a comprehensive analysis of the Global Cell Analysis Market. This includes Investigation of past progress, ongoing market scenarios, and future prospects. Data True to market on the products, strategies and market share of leading companies of this particular market are mentioned. Its a 360-degree overview of the global markets competitive landscape. The report further predicts the size and valuation of the global market during the forecast period. Some of the key players profiled in the study are Thermo Fisher Scientific, Inc. (United States), Danaher Corporation (United States), The Merck KGaA Group (Germany), Becton, Dickinson and Company (United States), GE Healthcare (United States), Agilent Technologies, Inc. (United States), Olympus Corporation (Japan), PerkinElmer, Inc. (United States), Promega Corporation (United States), Sysmex Corporation (Japan) and AbbVie, Inc.(United States) are some of the key players profiled in the study. Additionally, the Players which are also part of the research are Lonza Group (Switzerland), Tecan Group (Switzerland), Miltenyi Biotec (Germany), Stemline Therapeutics, Inc.(United States), Fujifilm Irvine Scientific (United States), STEMCELL Technologies Inc. (Canada), Sino Biological Inc. (United States), BIOTIME, Inc. (United States), Miltenyi Biotec (Germany), PromoCell GmbH (Germany), Carl Zeiss (Germany), Bio-Rad Laboratories Inc (United States), MacroGenics, Inc. (United States), OncoMed Pharmaceuticals, Inc. (United States) and Bionomics (Australia).

Free Sample Report + All Related Graphs & Charts @: https://www.advancemarketanalytics.com/sample-report/124696-global-cell-analysis-market

Market Trend

Market Drivers

Restraints

Opportunities

Each segment and sub-segment is analyzed in the research report. The competitive landscape of the market has been elaborated by studying a number of factors such as the best manufacturers, prices and revenues. Global Cell Analysis Market is accessible to readers in a logical, wise format. Driving and restraining factors are listed in this study report to help you understand the positive and negative aspects in front of your business.

This study mainly helps understand which market segments or Region or Country they should focus in coming years to channelize their efforts and investments to maximize growth and profitability. The report presents the market competitive landscape and a consistent in depth analysis of the major vendor/key players in the market.Furthermore, the years considered for the study are as follows:Historical year 2013-2017Base year 2018Forecast period** 2019 to 2025 [** unless otherwise stated]

**Moreover, it will also include the opportunities available in micro markets for stakeholders to invest, detailed analysis of competitive landscape and product services of key players.The Global Cell Analysis segments and Market Data Break Down are illuminated below:Type (Flow Cytometry Products (Reagents and Consumables, Instruments, Accessories, and Software), QPCR Products (Reagents and Consumables, and Instruments), Cell Microarrays (Consumables, and Instruments), Microscopes (Electron, Inverted, Stereo, and Near-field Scanning Optical), Spectrophotometers (Single-mode Readers, and Multi-mode Readers), Cell Counters (Automated Cell Counters, Hemocytometers, and Manual Cell Counters), HCS Systems, Others)

Application (Cell Culture, Cell Imaging, Cell Isolation and Expansion, Cell Signaling Pathways, Cell Structure, Cell Tracing & Tracking, Cell Function Assays, Stem Cell Research, Others), End Use Verticals (Hospitals and Diagnostic Laboratories, Pharmaceutical & Biotechnology Companies, Research Institutes, Cell Culture Collection Repositories, Others), Process (Cell Identification, Cell Viability, Cell Signaling Pathways/Signal Transduction, Cell Proliferation, Cell Counting and Quality Control, Cell Interaction, Target Identification and Validation, Single-cell Analysis)

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Enquire for customization in Report @ https://www.advancemarketanalytics.com/enquiry-before-buy/124696-global-cell-analysis-marketRegion Included are: North America, Europe, Asia Pacific, Oceania, South America, Middle East & Africa

Country Level Break-Up: United States, Canada, Mexico, Brazil, Argentina, Colombia, Chile, South Africa, Nigeria, Tunisia, Morocco, Germany, United Kingdom (UK), the Netherlands, Spain, Italy, Belgium, Austria, Turkey, Russia, France, Poland, Israel, United Arab Emirates, Qatar, Saudi Arabia, China, Japan, Taiwan, South Korea, Singapore, India, Australia and New Zealand etc.

Objectives of the Study

Read Detailed Index of full Research Study at @ https://www.advancemarketanalytics.com/reports/124696-global-cell-analysis-market

Strategic Points Covered in Table of Content of Global Cell Analysis Market:

Chapter 1: Introduction, market driving force product Objective of Study and Research Scope the Cell Analysis market

Chapter 2: Exclusive Summary the basic information of the Cell Analysis Market.

Chapter 3: Displaying the Market Dynamics- Drivers, Trends and Challenges of the Cell Analysis

Chapter 4: Presenting the Cell Analysis Market Factor Analysis Porters Five Forces, Supply/Value Chain, PESTEL analysis, Market Entropy, Patent/Trademark Analysis.

Chapter 5: Displaying the by Type, End User and Region 2013-2018

Chapter 6: Evaluating the leading manufacturers of the Cell Analysis market which consists of its Competitive Landscape, Peer Group Analysis, BCG Matrix & Company Profile

Chapter 7: To evaluate the market by segments, by countries and by manufacturers with revenue share and sales by key countries in these various regions.

Chapter 8 & 9: Displaying the Appendix, Methodology and Data SourceKey questions answered

Definitively, this report will give you an unmistakable perspective on every single reality of the market without a need to allude to some other research report or an information source. Our report will give all of you the realities about the past, present, and eventual fate of the concerned Market.

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Asia.

About Author:

Advance Market Analytics is Global leaders of Market Research Industry provides the quantified B2B research to Fortune 500 companies on high growth emerging opportunities which will impact more than 80% of worldwide companies revenues.

Our Analyst is tracking high growth study with detailed statistical and in-depth analysis of market trends & dynamics that provide a complete overview of the industry. We follow an extensive research methodology coupled with critical insights related industry factors and market forces to generate the best value for our clients. We Provides reliable primary and secondary data sources, our analysts and consultants derive informative and usable data suited for our clients business needs. The research study enable clients to meet varied market objectives a from global footprint expansion to supply chain optimization and from competitor profiling to M&As.

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Cell Analysis Market is Expected to See Growth Rate of 6.96% - Nyse Nasdaq Live

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Device inspired by mangroves could help clear up flood water – The Guardian

Wednesday, February 26th, 2020

A novel approach to removing salt from water, inspired by mangrove trees, has been revealed by researchers who say the system could offer an unusual approach to clearing up flood water.

Mangroves, like other trees, employ a system of water transport: it is thought evaporation of moisture from their leaves produces a negative pressure in their water-conducting tissues that helps to draw water into their roots and up their trunks.

This transport relies on surface tension, the fact that water molecules like to interact with the walls of the tissues, and that water molecules exert a tug on each other.

Salty water can damage most plants, but mangroves can thrive in salty conditions because they have adaptations including cell membranes that prevent salts from passing through in an uncontrolled manner, as well as cell walls that contain a waxy substance.

The upshot is that a mangrove essentially desalinates the water from its surroundings.

Now, writing in the journal Science Advances, researchers say they have reproduced this process in a synthetic system, using a polymer membrane that filters out salts as the root, a finely porous silica filter as the stem, and leaves based on either a hydrogel-filled membrane or aluminium oxide featuring tiny pores.

In our particular demonstration, through simple evaporation, a huge negative pressure was generated to drive water flow through a semi-permeable, reverse-osmosis membrane, thereby desalinating the water, said Dr Jay Werber and Dr Jongho Lee, co-authors of the study, who carried out the work at Yale University. In the industrial process, large, high-pressure pumps and loads of electricity are required to generate these high pressures to drive flow and desalination.

Importantly, they note, their system works without the production of air-bubbles which can block the flow thanks to the use of the membrane and tiny pores in the silica stem.

The team add that replicating the natural process adds support to the theory of how water transport in mangrove trees occurs.

However, they note that the system is not a practical way to desalinate water, not least since a large amount of heat would be needed.

The energy that drives desalination in our device is absorbed from the environment: basically, heat is absorbed to drive evaporation, said Werber and Lee. In a small-scale device, this energy is essentially free, meaning that it isnt provided as electricity or generated heat, similar to how drying clothes on a clothes line doesnt take added energy. However, trying to scale this up to large volumes would be very challenging.

But they offer an alternative suggestion: incorporate the system into buildings to turn them into giant sponges, offering a novel way to handle stormwater and reduce flood damage.

In this scenario, the buildings themselves would soak up excess groundwater and evaporate the water from their walls and roofs, the authors write.

And there is a bonus: The evaporation of water from the building walls would additionally provide passive cooling, the team write.

Prof Marc-Olivier Coppens, director of the UCL Centre for Nature-Inspired Engineering, who was not involved in the study, described the teams synthetic mangrove device as remarkable, but said further developments would be needed.

The proposed device is a creative, exciting development; however, the application of this principle is still early stages, he said. Higher stability for longer times than those tested here, with less salt build-up, but also the possibility to be used for real seawater, containing more [chemical] species, would be necessary for practical use.

He added that the idea of using such synthetic mangroves for stormwater management was exciting. He said: It remains to be seen whether sufficient fluxes and total flows can be achieved for this application, but it is a compelling application.

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Device inspired by mangroves could help clear up flood water - The Guardian

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TG Therapeutics Edges Closer To Commercialization And Potential Share Price Gain – Seeking Alpha

Wednesday, February 26th, 2020

Investment Thesis

I last posted about TG Therapeutics (TGTX) in November last year after the company published long-awaited positive trial data concerning flagship drugs umbralisib and ublituximab, which caused a small uptick in the share price from ~$5 to ~$9.

I felt that TG was edging closer to commercialising its first drug and recommended its stock as a speculative investment - since then the share price has continued to grow and has reached $16 at the time of posting this update on further positive news flow. The next few months promise to be a critical period for the company.

Data is expected in the coming days from a pivotal trial - UNITY CLL - in which umbralisib and ublituximab are being used in combination (referred to as "U2") to treat chronic lymphocytic leukemia ("CLL"). The randomised trial - which began in November 2015 and has enrolled ~420 patients - compares U2 against a combination of Obinutuzumab and Chlorambucil with the primary outcome measure being progression-free survival ("PFS") assessed over 3 years and the secondary outcome being overall response rates ("ORR"). The company is waiting for the PFS data before deciding whether to push for accelerated approval from the FDA for the treatment.

What makes the data from this trial all the more significant is the impact it will have on a phase 1/2a triple combination trial TG is conducting where U2 is being combined with a third indication targeting CLL, venetoclax. Early data from this trial released in December suggested ORR of 87% after U2 induction and before the use of venetoclax, and the U2 induction was also shown to reduce risk of tumor lysis syndrome. After venetoclax was introduced a 100% ORR was achieved as well as a 44% complete response ("CR"). After 12 cycles of therapy 7 of 9 patients tested had undetectable minimal residue disease and stopped therapy.

According to a recent TG coporate presentation 115,000 Americans are affected by CLL with 20,000 patients being diagnosed with the disease every year. The size of the treatment market for CLL is estimated to reach ~$10bn by 2025 growing at a CAGR of 15%. TG believes that there is significant unmet need in this market and therefore should U2 receive approval as a stand-alone treatment for relapsed patients who have not responded to prior treatment or in combination with other drugs such as venetoclax as a first line treatment then TG's share price is likely to soar on the prospect of global drug sales in the triple-digit millions.

Besides U2 TG is progressing ublituximab through phase 3 trials as a potential treatment for multiple sclerosis ("MS") compared with oral teriflunomide with top line data expected sometime in 2020, and through phase 3 trials in combination with ibrutinib for treatment of high-risk CLL. Umbrasilib could soon win approval as a stand-alone treatment for MZL and FL after management submitted a joint NDA to the FDA in January. Other promising candidates are also in the early phases of clinical testing.

The company recently completed a $50m direct public offering of common stock to a single investor which has eased perennial fears over TG's precarious funding runway, and as such, a stellar 2020 could conceivably be in prospect.

It's worth remembering however that 1 bad trial result could seriously undermine TG's progress and decimate the share price. The fact that TG does not have any development partners for its drug candidates programs in the US and does not seem to be an acquisition target at present can be read either as an encouraging sign (TG can go it alone and earn bigger profits) or as slightly suspicious (do pharma insiders know something investors don't?).

On balance however, just as I did in November, I am prepared to give management the benefit of the doubt. One thing that is for certain is that the company's fortunes (and share price) are about to change significantly whether for better or for worse. After taking a deep breath, I remain bullish.

TG Therapeutics has a somewhat unique approach to drug discovery - founded in 2012 the company is focused on B-cell mediated diseases. B-cells are produced by hematopoietic stem cells in bone marrow from where they migrate to the spleen, lymph nodes or other tissues forming immunocompetent B-cells capable of initiating an immune response when activated by cell antigens. B-cells however can become cancerous causing diseases such as non-Hodgkin's lymphoma ("NHL") or CLL, or become aberrant causing auto-immune diseases such as MS, rheumatoid arthritis ("RA") or systemic lupus erythematosus ("SLE").

TG's strategy is to identify validated targets against B-cell mediated diseases and then conduct global searches for and acquire "best-in-class" drug candidates in early stages of development - preferably with human clinical proof-of-concept ("POC") from a network of academic research centres or biotech drug development companies. Having acquired a candidate the company then looks to use its proprietary technology platform to develop multiple complementary candidates that can be used either as single treatments or in combination.

The 2 drugs are TG's most advanced candidates. Ublituximab is an anti-CD20 monoclonal antibody, similar to commercialised drugs such as Rituximab, Ofatumumab or Obinutuzumab. CD20 tends to be over-expressed in cancerous or malignant B-cells - anti CD20 antibodies can attach themselves to these cells and trigger immune reactions - such as antibody dependent cellular cytotoxicity or phagocytosis - that result in the death of the malignant cell.

TG has bioengineered ublituximab using a process known as glyco-engineering so that certain naturally occurring sugar molecules have been removed from the antibody which the company says increases its potency and shortens drug-infusion times.

Umbralisib is a PI3K delta and CK1 epsilon inhibitor taken orally once a day. PI3K delta is part of a family of enzymes involved in various cell processes such as proliferation and immunity which tends to be implicated in B-cell related lymphomas, whilst inhibiting CK1 epsilon is also suggested to have anti-cancer effects and modulate adverse T-cell activity.

TG initiated this in January after data from a phase 2b study - Unity-NHL - of 72 patients with MZL and 118 with FL showed that the number of positive responses to umbrailsib as a single treatment was above the study threshold of 40%. Preliminary efficacy data from the first 42 patients with MZL also showed 52% of patients who had failed to respond to prior treatment responded to umbralisib and an additional 36% attained stable disease. Overall, umbralisib was well tolerated by patients - 10 patients discontinued treatment due to adverse events ("AEs") possibly related to the drug's side-effects, no deaths were reported and only 3 patients demonstrated grade 3 infections.

A rolling submission allows TG to file sections of the NDA on an ongoing basis, which is an unusual concession from the FDA, as is the permission to file one NDA for 2 separate indications (MZL and FL) - but umbralisib's prior breakthrough drug designation seems to have made this possible. The NDA should be submitted during the first half of 2020 moving the company one step closer to commercialisation.

The data behind TG's NDA submission for umbralisib. Source: TG Therapeutics analyst day presentation Jan 2020.

22,500 new cases of MZL or FL are diagnosed per annum (according to the American Cancer Society, quoted in TG's JPM Healthcare conference presentation), with ~6,000 - 10,000 relapsed indolent patients needing treatment per annum.

Ublituximab is now progressing through 2 fully-enrolled (500 patients) randomised phase 3 trials - ULTIMATE 1 and ULTIMATE 2 - where the drug is being evaluated against oral treatment Teriflunomide (marketed by Sanofi as Aubagio, Teriflunomide makes sales of ~$430m per quarter) with topline data expected in 2H 2020. During its phase 2 MS trials ublituximab patients' annualized relapse rates of 0.05 were favourably comparable to treatments Ocrelizumab (0.13), Rebif (0.36) and the placebo (0.64), whilst no T1 GD-enhancing lesions were present at weeks 24 and 48 of the trial compared to a baseline of 3.63.

TG estimates the global market for MS treatment will exceed $30bn by 2025 with the only other anti-CD20 approved treatment, Ocrelizumab (marketed as Ocrevus by Roche) currently making more than $2bn in annual sales (and on track to reach $4bn by 2025). Should approval be granted to ublituximab the drug will compete in a crowded field (as shown by the table below) but TG management believes that the convenience of the bi-annual, one-hour duration infusion, efficacy and pricing will translate to a $1 - $2bn market opportunity.

MS treatment options. Source: TG Therapeutics analyst day presentation Jan 2020.

TG Therapeutics drug candidate pipeline. Source: TG Website.

TG is progressing a number of other candidates with similar indications to umbrasilib and ublituximab.

TG 1701 is a novel covalent Brutons tyrosine kinase ("BTK") inhibitor that targets the B-cell receptor signalling pathway that helps to proliferate and protect B-lymphocytes. The drug has entered a phase 1 trial where it will be evaluated both as a single agent and in triple combination alongside U2, an interesting prospect for the company since success would enable them to provide an entirely in-house triple combination therapy.

TG-1501, a monoclonal antibody that attaches to Programmed Death-Ligand 1 (PD-L1) blocking the signals that cancerous cells use to protect themselves from the body's natural immune system. Similarly to TG-1701 the drug is in single agent and combination trials with other TG candidates.

Finally, TG-1801 is an ANTI-CD47/CD19 monoclonal antibody. CD47, is expressed by cancerous cells in order to express a "don't eat me" signal to avoid elimination through phagocytosis whilst CD19 is used by B-tumor cells to make up for a loss of CD20 and continue to resist treatment. TG-1801 has also entered a phase 1 trial.

In Q319 TG made a loss of $59.9m compared to a net loss of $34m over the same period in 2018. The difference was put down to manufacturing and CMC costs but the company says they decreased trial costs by $3.8m in the quarter and expect this reduction to continue into 2020. CFO Sean Power told analysts on the Q3 earnings call that management expects to reduce cash burn from Q3's $33m to $25m - $30m per quarter going forward, and that the cash position (at the time) of $96m would be sufficient to see the company through 2020 and the conclusion of the critical ongoing phase 3 trials.

The $50m raise completed in December will probably be viewed by investors as good business since the share price has subsequently risen and therefore the effects of dilution have been minimised. Still management has made repeated use of at-the-market offerings ("ATMs") with the most recent being a $24m raise at the end of Q319 - and further use of their mixed shelf offering may start to try backers' patience.

The upside for investors is that, besides several minor licensing agreements TG has resisted the temptation to enter into collaboration agreements with big-pharma concerns based on development milestones and post commercialisation revenue sharing, and therefore retains exclusive rights to all of its drug candidates.

TG clearly believes that commercialisation is imminent having appointed a new Chief Commercial Officer, Adam Waldman, who joins from Celgene where he was Head of Hematology-Oncology Marketing. Waldman has extensive experience building sales and marketing teams and will be expected to deliver the launch programs that TG will hope are initiated before the end of this year.

The upcoming results, firstly from the UNITY-CLL trial, and subsequently from ublituximab's MS trial will dictate whether or not TG proves to be a good investment or whether investors who have endured years of frustration will have to accept further short-to-medium term disappointment.

Management has done well in my view to progress different drug candidates to the near-conclusion of pivotal trials, win breakthrough drug designations and submit NDAs to the FDA that stand a good chance of success. It has taken time admittedly and the share price has suffered but it feels to me as though the company now has some momentum.

In my view, the signs are promising enough to suggest that TG will have a commercialised drug - and possibly 2 - by the end of the year. Should they be approved both drugs - perhaps ublituximab for MS more so than Umbrasilib for MZL and FL - will have sizeable addressable markets, and the prospect of an approval for treatment of CLL (U2 + venetoclax or even U2 + proprietary TG-1701) is a juicy one given the size of the market.

If the upcoming UNITY-CLL data is positive TG will surely make an attractive acquisition target for a big pharma - and the figures involved could be large - witness the $9.7bn Novartis recently paid Medicines Company for a single RNA therapy. Therefore I would put at least a 25-50% premium on TG's current price and look at a price of $21+, which is below analyst consensus targets of ~$25, and significantly below what TG could achieve if the market, as expected, reacts buoyantly to good news. With more candidates in development and because the company addresses a range of indications, the worst case scenario (in the event of poorly received data) is not catastrophic either.

Long-term, management will have to prove it has what it takes to successfully commercialise an approved drug and generate sales volumes that justify the high cash burn investors have endured for years. But that is for a different day. In the short term I remain bullish and see this as a potentially exciting time to be holding TG stock, although the usual biotech investing caveats still apply. Things can de-escalate quickly when data is not up to scratch.

Disclosure: I am/we are long TGTX. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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TG Therapeutics Edges Closer To Commercialization And Potential Share Price Gain - Seeking Alpha

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