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Bayer Launches Cell and Gene Therapy Platform to Maximize Recent Acquisitions – BioSpace

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Less than two months after life sciences giant Bayer acquired N.C.-based AskBio, a gene therapy company, the healthcare giant launched a cell and gene therapy platform within its pharmaceutical division.

This morning, Bayer said the launch of the new platform is a deeply transformative move for its business. Stefan Oelrich, a member of Bayers Board of Management and president of the companys Pharmaceuticals Division, pointed to the impact cell and gene therapies have made in treating diseases and said the companys goal is to be at the forefront of this revolution in science. The company tapped Wolfram Carius, its current vice president of Pharmaceuticals Product Supply, to head the new program.

The C> field is growing at an unprecedented pace. With the establishment of Bayers own C> Platform our company will propel its presence in this area. This will complement our existing C> pipeline which already includes five advanced assets with at least three investigational new drugs annually for the next years, Oelrich said in a statement.

To boost its cell and gene therapy presence, Bayer said it is strengthening its internal capabilities and will also pursue external strategic collaborations, technology acquisitions and licensing. In October, the company acquired AskBio's AAV-based gene therapy pipeline of treatments and its Pro10 AAV manufacturing process, which has become something of a standard across the industry. The Pro10 AAV process is used by multiple companies, including Pfizer, Takeda and Viralgen Vector Core SA.Bayer now owns AskBios pipeline of treatments for Pompe disease, Parkinsons disease, as well as therapies for neuromuscular, central nervous system, cardiovascular and metabolic diseases.

The addition of AskBio complements Bayers other cell and gene therapy company, BlueRock Therapeutics, which itacquired last year. BlueRock is developing induced pluripotent stem cells (iPSC), with its most advanced program aimed at Parkinsons disease. In addition to the two companies, Bayer also acquired a contract manufacturing organization that specializes in gene therapy. Bayer said it has established a C> pipeline that includes five advanced assets and more than fifteen preclinical candidates.

The new C> Platform will combine multiple functions by providing support across the entire value chain for the research and development of cell and gene therapies, the company said. This includes support in preclinical development, CMC, clinical programs, project management and more. The platform will guide projects form concept through commercial launch. The goal is to build robust platforms with broad application across different therapeutic areas, the company said.

The emerging bio revolution represents a once-in-a-lifetime opportunity and a new era for Bayer, said Carius said in a statement. A dedicated C> Platform is vital to accelerate innovation at its source, and to ensure its translation into tangible therapies for patients who have no time to wait.

The C> Platform will allow its partners to operate autonomously to develop and progress their portfolio and technology. The role of Bayers C> Platform is to serve as a strategic guide to ensure the different parts of the organization complement each other and combine the best in Biotech and Pharma know-how.

The formation of the C> Platform comes one day after Bayer and Blackford Analysis entered into a development and license agreement to establish an artificial intelligence (AI) platform for medical imaging. The platform will enable the integration of AI applications into the medical imaging workflow which can support the complex decision-making process of radiologists and is intended to enhance diagnostic confidence, the companies said.

Also this week, Bayer sold most of its stake in Elanco Animal Health for $1.6 billion to cover legal bills from ongoing litigation over the weedkiller Roundup and its alleged role as a carcinogen. Bayer owned approximately 15.5% of Elanco, but faces nearly $11 billion in potential damages related to Roundup lawsuits. In June, the company proposed a $12 billion agreement to resolve Roundup litigation.

Last week, a federal judge rejected a $650 million settlement claim for pollution related to polychlorinated biphenyl, or PCB, which is used to cool heavy-duty electrical equipment.

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Chrysalis BioTherapeutics Receives $10.4 Million From BARDA to Continue Development of TP508 as a Nuclear Countermeasure – Business Wire

GALVESTON, Texas--(BUSINESS WIRE)--Chrysalis BioTherapeutics, Inc., a clinical-stage biotechnology company focused on the development of regenerative medicines to save lives, announced today that the Biomedical Advanced Research and Development Authority (BARDA) part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services executed options to add $10.4 million under contract # HHSO100201900016C with the Company to develop TP508 (ChrysalinTM ) as a nuclear medical countermeasure.

Chrysalis will conduct safety studies and additional options required to achieve Emergency Use Authorization and Animal Rule approval for TP508 as a medicinal treatment for acute and delayed effects of ionizing radiation exposure. TP508 mechanism of action represents a potential first in class countermeasure to mitigate radiation-induced vascular damage, reduce inflammation, prevent hemorrhage, and restore tissue function.

The decision of BARDA to further support the development of TP508 is evidence of successful milestones achieved under the original contract and emphasizes the potential of TP508 to save lives as an effective stand-alone post-exposure countermeasure or as a valuable therapeutic for use in combination with other countermeasure agents, said Chrysalis CEO, Dr. Darrell Carney.

This contract modification includes options to initiate nonclinical and human clinical safety/PK studies, assay development, large scale manufacturing, and clinical formulation development. This increases the total BARDA funding for this contract to over $21 million.

Our hope is that TP508 will never have to be used as a nuclear countermeasure, said Executive VP, Dr. Laurie Sower, But results show that if needed, a single injection of TP508 given 24 hours after a nuclear event may increase survival and prevent delayed radiation effects throughout the body.

About TP508

TP508 is a regenerative peptide drug representing a natural part of human thrombin that is released upon tissue injury to stimulate vascular and stem cell repair and to regenerate damaged tissue. TP508 has demonstrated safety and potential efficacy in non-clinical and in human clinical tissue repair trials, but it is not yet FDA-approved and only available for investigational use. TP508 is also in development as a potential solution to prevent thrombosis and systemic vascular damage caused by SARS-CoV-2 infection.

Chrysalis BioTherapeutics, Inc. is a biopharmaceutical company located in Galveston, TX. TP508 (rusalatide acetate) is licensed from The University of Texas Medical Branch Galveston, TX. For additional information, contact Dr. Darrell Carney, CEO, at dcarney@chrysbio.com or visit http://www.chrysbio.com.

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Chrysalis BioTherapeutics Receives $10.4 Million From BARDA to Continue Development of TP508 as a Nuclear Countermeasure - Business Wire

Reversing vision loss by turning back the aging clock – FierceBiotech

Aging has implications for a wide range of diseases. Researchers have been looking for ways to halt the aging process for millennia, but such methods remain elusive. Scientists at Harvard Medical School have now offered a glimmer of hope that the aging clock in the eye could be reversedat least in animals.

By reprogramming the expression of three genes, the Harvard team successfully triggered mature nerve cells in mice eyes to adopt a youthful state. The method reversed glaucoma in the mice and reversed age-related vision loss in elderly mice, according to results published in Nature.

GenScript ProBio is the bio-pharmaceutical CDMO segment of the worlds leading biotech company GenScript, proactively providing end-to-end service from drug discovery to commercialization with professional solutions and efficient processes to accelerate drug development for customers.

If further studies prove out the concept, they could pave the way for therapies that employ the same approach to repair damagein other organs and possibly treat age-related diseases in humans, the team said.

The researchers focused on the Yamanaka factors, which are four transcription factorsOct4, Sox2, Klf4 and c-Myc. In a Nobel Prize-winning discovery, Shinya Yamanaka found that the factors can change the epigenomehow genes are turned on or offand can thereby transform mature cellsback to a stem cell-like state. It has been hypothesized that changes to the epigenome drive cell aging, especially a process called DNA methylation, by which methyl groups are tagged onto DNA.

Past researches have tried to use the four Yamanaka factorsto turn back the age clock in living animals, but doing so caused cells to adopt unwanted new identities and induced tumor growth.

RELATED:Restoring eyesight with genetically engineered stem cells

To test whether the approach works in living animals, the scientists used adeno-associated virus to deliver the three genes into the retina of mice with optic nerve injuries. The treatment led to a two-fold increase in the number of retinal ganglion cells, which are neurons responsible for receiving and transmitting visual information. Further analysis showed that the injury accelerated DNA methylation age, while the gene cocktail counteracted that effect.

Next the scientists tested whether the gene therapy could also work in disease settings. In a mouse model of induced glaucomawhich is a leading cause of age-related blindness in peoplethe treatment increased nerve cell electrical activity and the animals visual acuity.

But can the therapy also restore vision loss caused by natural aging? In elderly, 12-month-old mice, the gene therapy also restored ganglion cells electrical activity as well as visual acuity, the team reported.

By comparing cells from the treated micewith retinal ganglion cells from young, 5-month-old mice, the researchers found that mRNA levels of 464 genes were altered during aging, and the gene therapy reversed 90% of those changes. The scientists also noticed reversed patterns of DNA methylation, which suggests that DNA methylation is not just the marker but rather the driver behind aging.

What this tells us is the clock doesn't just represent timeit is time. If you wind the hands of the clock back, time also goes backward, the studys senior author, David Sinclair, explained in a statement.

The study marks the first time that glaucoma-induced vision loss was reversednot just slowedin living animals, according to the team.

RELATED:Reprogrammed skin cells restore sight in mouse models of retinal disease

Other researchers are also studying regenerative approaches to treating eye diseases. A research group at the Centre for Genomic Regulation in Barcelona just showed that by modifying mesenchymal stem cells to express chemokine receptors Ccr5 and Cxcr6, retinal tissue could be saved from degeneration.

The idea of reversing age-related decline in humans by epigenetic reprogramming with a gene therapy is exciting, Sinclair said. The Harvard researchers intend to do more animal work that could allow them to start clinical trials in people with glaucoma in about two years.

Our study demonstrates that it's possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function, Sinclair said. If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large.

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Clinical Trials Offer Opportunities to Change Practice to Improve Prevention and Treatment of Blood Disorders – PRNewswire

WASHINGTON, Dec. 4, 2020 /PRNewswire/ --Four studies being presented during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition present opportunities to improve care for patients with a variety of blood disorders. Together, the studies provide support for new clinical approaches such as alternate treatment delivery methods, updated uses for existing therapies, and earlier referrals to specialty care.

"These are very practical trials with real-world implications," said press briefing moderator Lisa Hicks, MD, of St. Michael's Hospital and the University of Toronto. "They address important questions relevant to everyday practice in the clinic."

The first study supports administering the monoclonal antibody daratumumab for multiple myeloma via a quick injection instead of an intravenous infusion, an approach that could save significant time for patients and clinics.

The second study found that, despite being routinely used in practice, the clot stabilizer tranexamic acid does not prevent bleeding when used prophylactically for patients undergoing treatment for blood cancers, although it leaves open the possibility that the drug may be an effective treatment for these patients when bleeding occurs.

The third study reports the drug ruxolitinib can offer relief for patients with chronic graft-versus-host disease (GVHD) after a stem cell transplant, suggesting ruxolitinib is a viable second-line treatment for patients whose symptoms are not fully resolved with corticosteroids.

Finally, the fourth study supports referring older patients with myelodysplastic syndromes to transplant centers for allogeneic hematopoietic cell transplantation, an important shift from current practice that could offer many more patients the potential for a cure.

This press briefing will take place on Friday, December 4, at 9:30 a.m. Pacific time on the ASH annual meeting virtual platform.

Study Bolsters Case for Delivering Daratumumab Subcutaneously for Multiple Myeloma412: Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)

A new study suggests the monoclonal antibody daratumumab has similar benefits when delivered via subcutaneous injection as it does when delivered intravenously to individuals with multiple myeloma which persists or recurs after first-line treatments. Patients given subcutaneous daratumumab along with the immunomodulator pomalidomide and the anti-inflammatory steroid dexamethasone were 37% less likely to die or have their disease worsen compared to patients who received pomalidomide and dexamethasone alone in the phase III trial.

"This is an effective combination with a predictable safety profile that allows for the use of subcutaneous daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide and a proteasome inhibitor," said senior study authorMeletios A. Dimopoulos, MD,of National and Kapodistrian University of Athens in Athens, Greece. "Subcutaneous daratumumab is much easier for the patient and reduces the time they need to spend at the outpatient chemotherapy unit."

The combination of intravenous daratumumab and pomalidomide with dexamethasone has been widely adopted in the U.S. as a second-line therapy for patients whose multiple myeloma does not respond durably to lenalidomide and proteasome inhibitors. However, delivering daratumumab intravenously typically requires patients to spend a full day at the clinic for each infusion. Administering the therapy via a five-minute subcutaneous injection can substantially reduce the burden for patients and clinics, Dr. Dimopoulos said.

The researchers enrolled 304 patients in 12 European countries. Half were randomly assigned to receive daratumumab plus pomalidomide with dexamethasone and half only received pomalidomide with dexamethasone. Patients underwent 28-day treatment cycles until their disease worsened or they experienced unacceptable side effects.

About one-third of patients died during the trial's median follow-up period of about 17 months. The study met its primary endpoint, showing a significantly higher rate of progression-free survival at 12 months among patients receiving the combination therapy. Participants receiving the daratumumab-pomalidomide combination were treated for a median of nearly 12 months, substantially longer than the median treatment duration of less than seven months among those receiving pomalidomide alone.

Patients receiving daratumumab experienced adverse events at a rate consistent with previous studies, raising no new safety concerns. Dr. Dimopoulos said the findings suggest the combination therapy can be a good option for patients who have not experienced lasting benefits from lenalidomide and proteasome inhibitors, particularly those whose cancer is resistant to lenalidomide. He noted that the study suggested a slight trend toward increased survival in the daratumumab arm, but additional follow-up is necessary to assess any survival benefit.

Meletios A. Dimopoulos, MD,National and Kapodistrian University of Athens, will present this study in an oral presentation on Sunday, December 6, at 12:00 noon Pacific time on the ASH annual meeting virtual platform.

Tranexamic Acid Not Found to Prevent Bleeding in Patients with Blood Cancers 2: Effects of Tranexamic Acid Prophylaxis on Bleeding Outcomes in Hematologic Malignancy: The A-TREAT Trial

The clot stabilizer tranexamic acid performed no better than placebo when administered prophylactically to prevent bleeding in patients with blood cancers who also received routine prophylactic platelet transfusions. Researchers cautioned that the study's focus is different from other situations in which tranexamic acid has been found effective, such as its use in treating bleeding related to childbirth, surgery, or inherited blood disorders.

"Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery," said senior study author Terry B. Gernsheimer, MD, of the University of Washington School of Medicine. "Their bleeding likely is due to endothelial damage damage to the lining of blood vessels that tranexamic acid would not treat. To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-versus-host disease in patients receiving a transplant."

Between 48% and 70% of patients undergoing treatment for blood cancers experience bleeding complications of World Health Organization grade 2 or higher. Though not life-threatening, grade 2 bleeding for example, a nosebleed lasting more than 30 minutes can be concerning. Bleeding of grade 3 or 4 can be life-threatening and warrant blood transfusions. Most patients undergoing treatment for blood cancers are routinely given platelet transfusions to prevent bleeding, but many continue to experience bleeding episodes, nevertheless.

Tranexamic acid works by slowing the process by which blood clots naturally break down. To determine whether tranexamic acid could help to further reduce bleeding in these patients, the researchers enrolled 327 patients undergoing treatment for blood cancers at three U.S. medical centers. Half were randomly assigned to receive tranexamic acid and half received a placebo, administered either orally or intravenously three times a day until they recovered their platelet count, or for up to 30 days. Researchers regularly followed up with participants to assess bleeding events both in and outside of the hospital.

The results revealed no significant differences among the study groups in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions patients required during the treatment period and for up to 14 days afterward. Patients receiving tranexamic acid had a significantly higher rate of occlusions in their central venous line (a catheter placed in a large vein commonly used for delivering cancer drugs) which required clearing with a clot-dissolving drug, but there was no difference in the occurrence of clots in patients' veins or arteries.

Dr. Gernsheimer noted that other studies could help elucidate whether the drug may be helpful for specific subgroups of patients with blood cancers or as a treatment for bleeding, rather than as a preventive measure in these patients. It may also be useful to prevent or treat bleeding in patients with other causes of low platelet counts.

Terry B. Gernsheimer, MD, University of Washington School of Medicine, will present this study in a plenary presentation on Sunday, December 6, 2020 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

Researchers Report First Successful Second-Line Treatment for Chronic Graft-Versus-Host Disease77: Ruxolitinib (RUX) Vs Best Available Therapy (BAT) in Patients with Steroid- Refractory/Steroid-Dependent Chronic Graft-Vs-Host Disease (cGVHD): Primary Findings from the Phase 3, Randomized REACH3 Study

The drug ruxolitinib brought relief from the debilitating effects of chronic graft-versus-host disease (GVHD) at twice the rate of the best available therapy in a phase III trial. The findings represent a major step forward for patients with chronic GVHD that is not resolved by taking corticosteroids, said researchers. There is currently no approved second-line therapy for chronic forms of the disease.

"This is the first multicenter randomized controlled trial for chronic, steroid-refractory or steroid-dependent GVHD that is positive," said senior study authorRobert Zeiser, PhD,of University Medical Center, Freiburg Im Breisgau, Germany. "It shows a significant advantage for ruxolitinib. It is likely that this trial will lead to approval for this indication and change the guidelines for the treatment of this disease."

GVHD is a complication of allogeneic hematopoietic (stem) cell transplantation, a therapy used to treat blood cancers. It occurs when T cells (the graft) received from a donor through the transplant see the patient's healthy cells and tissue (the host) as foreign and start to attack them. Roughly half of patients undergoing a stem cell transplant develop GVHD. About half of these patients are able to resolve their symptoms with a temporary course of corticosteroids, a class of drugs that lower inflammation in the body. The remaining patients either do not respond to steroids, cannot take them, or must take them continuously to stave off symptoms.

Ruxolitinib is designed to block a molecular signal involved in triggering inflammation. A previous trial, REACH2, found that ruxolitinib offered benefits for patients with acute GVHD, a severe form of GVHD with a mortality rate of 80%. The new trial, REACH3, aimed to determine whether the drug could bring similar benefits for the much larger number of patients affected by chronic GVHD. While chronic GVHD is not nearly as deadly as acute GVHD, its symptoms, which include weight loss, skin stiffness, and multiple disabilities, can severely and permanently affect patients' quality of life.

Researchers enrolled 329 patients with moderate-to-severe chronic GVHD. Half were randomly assigned to receive ruxolitinib for six 28-day cycles. The other half received one of nine alternative treatments, representing the best available therapy, at the discretion of their physician. At the end of the six treatment cycles, researchers assessed symptoms of 125 patients who had completed the full course of treatment to which they were assigned.

The trial met its primary endpoint, showing a clear and substantial improvement in the overall response to treatment among patients taking ruxolitinib. Of the 125 patients assessed, 50% of those receiving ruxolitinib had at least some reduction in symptoms, compared to only 25% among those receiving best available therapy. Seven percent of those taking ruxolitinib saw their symptoms resolve completely, compared to only 3% among those receiving best available therapy.

Participants in both arms of the study experienced similar rates of adverse events, which aligned with the health challenges commonly faced by patients with chronic GVHD, suggesting ruxolitinib has an acceptable safety profile in these patients, according to Dr. Zeiser.

Robert Zeiser, PhD, University Medical Center, Freiburg Im Breisgau, Germany, will present this study in an oral presentation on Saturday, December 5, at 8:00 a.m. Pacific time on the ASH annual meeting virtual platform.

Curative Transplant Improves Survival for Older Adults with Myelodysplastic Syndrome75: A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

Allogeneic hematopoietic cell transplantation nearly doubled the rate of survival among patients 50 to 75 years old with myelodysplastic syndrome (MDS) in a trial conducted by the Blood and Marrow Transplant Clinical Trials Network. Despite being the only known cure for MDS, this therapy is typically only offered to younger patients because its benefits for older adults have not previously been proven. Researchers say the study offers the most definitive evidence to date that this type of stem cell transplantation significantly improves the outlook for older adults who would otherwise face a high likelihood of dying.

"Transplantation has been underutilized, historically, in this patient group," said senior study author Corey Cutler, MD, MPH,of Dana-Farber Cancer Institute. "Based on our findings, all patients should at least be referred to a transplant center so that those who are eligible and who have a suitable donor can undergo transplant and have better survival. It is important to refer these patients early so that the transplant center can work on finding an optimal donor right from the get-go."

Allogeneic hematopoietic (stem) cell transplantation is a process to replace a recipient's stem cells and immune system with cells from a healthy donor. It is the only known method to cure patients with MDS. The Centers for Medicare and Medicaid Services (CMS) covers transplantation for MDS as part of a Coverage with Evidence Development program. CMS approved the design of the trial and is expected to consider the findings when determining future payment policies.

Researchers from the Blood and Marrow Transplant Clinical Trials Network enrolled 384 patients treated for MDS at 34 U.S. medical centers. Patients were referred to transplant centers, which searched for suitable stem cell donors. The 260 patients who were matched with a donor within 90 days were assigned to receive a stem cell transplant; the other 124 patients with no suitable donor received standard supportive care. Participants were followed for roughly three years from their date of enrollment.

Overall survival was much higher in patients assigned to receive a stem cell transplant (47.9%) compared to those who were not (26.6%) at three years from treatment assignment. Leukemia-free survival was also higher in those assigned to receive a transplant (35.8%) than those who were not (20.6%). The researchers observed no significant differences among subgroups and no differences in quality of life between the two study arms.

Dr. Cutler noted that starting the transplantation process as early as possible can increase a patient's chance of finding a suitable donor and successfully proceeding with a transplant.

This study was co-funded by the National, Heart, Lung and Blood Institute (NHLBI) and the National Cancer Institute (NCI), both part of the National Institutes of Health.

Corey Cutler, MD, MPH, Dana-Farber Cancer Institute, will present this study in an oral presentation on Saturday, December 5, at 7:30 a.m. Pacific time on the ASH annual meeting virtual platform.

Additional press briefings will take place throughout the meeting on health disparities, genome editing and cellular therapy, COVID-19, and late-breaking abstracts. For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

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http://www.hematology.org

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Clinical Trials Offer Opportunities to Change Practice to Improve Prevention and Treatment of Blood Disorders - PRNewswire

Researchers make ‘exciting first step’ to better understanding development and treatment of autism – BioPharma-Reporter.com

The authors of a paper, published in the journalScience, in an attempt tostudy the function of genes implicated in autism spectrum disorders (ASDs), applied a gene-editing and single-cellsequencing system, Perturb-Seq, to knock out 35 ASD candidate genes in multiple mice embryos.

They described how the Perturb-Seq method they developed can investigate the function of many different genes in many different cell types at once.

Directing the large-scale method to the study of dozens of genes that are associated with ASD, they identified how specific cell types in the developing mouse brain are impacted by mutations.

"The field has been limited by the sheer time and effort that it takes to make one model at a time to test the function of single genes. Now, we have shown the potential of studying gene function in a developing organism in a scalable way, which is an exciting first step to understanding the mechanisms that lead to autism spectrum disorder and other complex psychiatric conditions, and to eventually develop treatments for these devastating conditions," co-senior author Paola Arlotta, the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard.

The method is also broadly applicable to other organs, enabling scientists to better understand a wide range of disease and normal processes, she said.

The study was also led by co-senior authors Aviv Regev, who was a core member of the Broad Institute during the study and is currently executive vice president of Genentech research and early development, and Feng Zhang, a core member of the Broad Institute and an investigator at MIT's McGovern Institute.

"Through genome sequencing efforts, a very large number of genes have been identified that, when mutated, are associated with human diseases. Traditionally, understanding the role of these genes would involve in-depth studies of each gene individually. By developing Perturb-seq for in vivo applications, we can start to screen all of these genes in animal models in a much more efficient manner, enabling us to understand mechanistically how mutations in these genes can lead to disease," said Zhang, who is also the James and Patricia Poitras Professor of Neuroscience at MIT and a professor of brain and cognitive sciences and biological engineering at MIT.

According to the World Health Organization (WHO), the global burden of ASD is continuously growing, with a current prevalence rate of 1 in 160 children.

Reported prevalence rates vary widely from country to country though, according to apaper published in Nature.

Data from the US Centers for Disease Control and Prevention shows that about 1 in 68 children in the US had been identified with some form of ASD, with more than 3 million people affected.A study referenced in the Nature report estimates that the prevalence of ASD in the US in 20142016 was 2.47% among adolescents and children, while in the UK, the annual prevalence rate for children aged 8 years between 2004 and 2010 was 3.8/1000 for boys and 0.8/1000 for girls.

That paper also indicated recent studies showing the pooled ASD prevalence estimate in Asia is 0.36%, including data from nine countries: China, Korea, India, Bangladesh, Lebanon, Iran, Israel, Nepal and Sri Lanka, while the prevalence of ASD in the Middle East region was documented to be 1.4 per 10,000 children in Oman, 4.3 per 10,000 children in Bahrain, and 1/167 in Saudi Arabia.

Moreover, ASD incidence is four to five times greater in males than in females, according to the Nature report.

To investigate gene function at a large scale, the researchers said they combined two powerful genomic technologies. They used CRISPR-Cas9 genome editing to make precise changes, or perturbations, in 35 different genes linked to autism spectrum disorder risk. Then, they analyzed changes in the developing mouse brain using single-cell RNA sequencing, which allowed them to see how gene expression changed in over 40,000 individual cells.

By looking at the level of individual cells, the researchers could compare how the risk genes affected different cell types in the cortex - the part of the brain responsible for complex functions including cognition and sensation. They analyzed networks of risk genes together to find common effects.

"We found that both neurons and glia - the non-neuronal cells in the brain - are directly affected by different sets of these risk genes," said Xin Jin, lead author of the study and a Junior Fellow of the Harvard Society of Fellows. "Genes and molecules don't generate cognition per se - they need to impact specific cell types in the brain to do so. We are interested in understanding how these different cell types can contribute to the disorder."

To get a sense of the model's potential relevance to the disorder in humans, the researchers compared their results to data from post-mortem human brains. In general, they found that in the post-mortem human brains with autism spectrum disorder, some of the key genes with altered expression were also affected in the Perturb-seq data.

"We now have a really rich dataset that allows us to draw insights, and we're still learning a lot about it every day," Jin said. "As we move forward with studying disease mechanisms in more depth, we can focus on the cell types that may be really important."

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Research Antibodies and Reagents Market to Reach $6.32 Billion by 2027 With COVID-19 Impact, at a CAGR of 5.6% from 2020- Meticulous Research Analysis…

December 01, 2020 05:00 ET | Source: Meticulous Market Research Pvt. Ltd.

London, Dec. 01, 2020 (GLOBE NEWSWIRE) -- In its latest publication, titled Research Antibodies and Reagents Market by Product {Antibodies [Type (Primary, Secondary), Production, Source, Research Area (Oncology, Neurology)], Reagents}, Technology (ELISA, Western Blot), Application, End User (Pharma, Academia) - Global Forecast to 2027, Meticulous Research analyses that the research antibodies and reagents market is expected to grow at a CAGR of 5.6% from 2020 to reach $6.32 billion by 2027.

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Traditionally, antibodies were obtained from blood and serum. However, these antibodies were produced in a limited number and may cause cross-reactivity. This led to an increase in their cost, along with decreasing use in basic research. To overcome these drawbacks and decrease the outgrowth of various diseases, researchers developed different types of antibodies using sophisticated technologies that can produce a large number of antibodies within less time with high specificity and affinity than traditional ones. Thus, to promote research activities, advanced technologies using research antibodies and reagents products are widely used by various end-users.

Factors such as the increasing proteomics and genomics research studies, increased funding for research activities, and growing industry-academia collaborations are majorly driving the research antibodies and reagents market. Also, growing economies, rising protein-based research, and increasing biomarker discovery provide opportunities for the growth of the market. In addition, the growing growing number of research activities due to increasing COVID-19 cases all over the globe is further driving the adoption of research antibodies and reagents by various end-users.

To provide efficient analysis, Meticulous Research has segmented this market by product {antibodies [type (primary antibody, secondary antibody), production type (monoclonal antibody, polyclonal antibody, and antibody fragments), source (mouse, rabbit, and others), research area (oncology, cardiovascular disease, infectious diseases, immunology, neurology, stem cell research, and others)], reagents [sample preparation reagents (media and serum, stain and dyes, probes, buffers, and solvents), antibody production reagents (enzymes and proteins), other research reagents}, technology (western blot, immunofluorescence, ELISA, multiplex immunosorbent assay, flow cytometry, immunohistochemistry, immunoprecipitation, and others), application (proteomics, drug discovery and development, and genomics), end user (pharmaceutical and biotechnology industry, academic and research institutes, and contract research organizations), and geography (Asia-Pacific, Europe, North America, the Middle East & Africa, and Latin America).

Wish to customize this report or get any additional specific information of your interest? Let us know here-https://www.meticulousresearch.com/custom-research.php

In 2020, geographically, North America is projected to command the largest share of the research antibodies and reagents market, closely followed by Europe and Asia-Pacific. However, Asia-Pacific region is expected to grow at the fastest rate due to growing R&D investment in proteomics research, rising middle-income people, growing focus on the pharma sector, and improving healthcare industry.

Based on product, the reagents segment is projected to grow at the fastest growth rate of the overall research antibodies and reagents market due to increasing focus on understanding the molecular basis of diseases and routine use in target-based assays during the basic research and huge demand for various reagents in many routine assays.

In 2020, the flow cytometry segment is expected to command the largest share of the overall research antibodies and reagents market. Growing focus on biomedical research for improving diagnosis and therapy developments and growing focus on biomarker discovery and cell-based research are the key factors driving the growth of this segment.

In 2020, on the basis of application, the proteomics segment is poised to command the largest share of the overall research antibodies and reagents market. The upsurge in proteomics research is attributed to the rising need to design more effective drugs through protein-based disease profiling, rising uptake of research antibodies in the significantly growing proteomics market, and increasing public & private sector spending on proteomic research.

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On the basis of end user, in 2020, the pharmaceutical and biotechnology industry segment is estimated to command the largest share of the research antibodies and reagents market due to the highest adoption of antibodies and reagents by this end-user for increasing research activities.

The report includes a competitive landscape based on an extensive assessment of the product portfolio offerings, geographic presence, and key strategic developments adopted by leading market players in the industry over the past four years (2016-2019). The key players profiled in the research antibodies and reagents market are GE Healthcare (U.S.), Merck KGaA (Germany), Thermo Fisher Scientific Inc. (U.S.), F. Hoffmann La-Roche AG (Switzerland), Rockland Immunochemicals Inc. (U.S.), Johnson & Johnson (U.S.), Agilent Technologies, Inc. (U.S.), Eli Lily and Company (U.S.), Becton Dickinson and Company (U.S.), Danaher Corporation (U.S.), PerkinElmer, Inc. (U.S.), GenScript Biotech Corporation (U.S.), Lonza (Switzerland), Bio-Techne Corporation (U.S.), Bio-Rad Laboratories, Inc. (U.S.), Teva Pharmaceutical Industries Limited (Israel), Santa Cruz Biotechnology, Inc. (U.S.), and BioLegend, Inc. (U.S.) among others.

To gain more insights into the market with a detailed table of content and figures, click here:https://www.meticulousresearch.com/product/research-antibodies-reagents-market-5055/

Scope of the Report:

Research Antibodies And Reagents Market, by Product Type

Research Antibodies And Reagents Market, by Technology

Research Antibodies And Reagents Market, by Application

Research Antibodies And Reagents Market, by End User

Research Antibodies And Reagents Market, by Geography

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Research Antibodies and Reagents Market to Reach $6.32 Billion by 2027 With COVID-19 Impact, at a CAGR of 5.6% from 2020- Meticulous Research Analysis...

Nobel Prize history from the year you were born – Morganton News Herald

Nobel Prize history from the year you were born

Since 1901, Nobel Prizes have honored the worlds best and brightest and showcased the work of brilliant and creative minds, thanks to Swedish businessman Alfred Nobel, who made his fortune with the invention of dynamite.

The Prize in Physiology or Medicine often honors those whose discoveries led to medical breakthroughs, new drug treatments, or a better understanding of the human body that benefit us all.

The Prize in Literature celebrates those skilled in telling stories, creating poetry, and translating the human experience into words. The Prizes in Chemistry and Physics remind most of us how little we understand of genetics, atomic structures, or the universe around us, celebrating the scientists who further knowledge. A later addition to the award roster, the Nobel Memorial Prize in Economic Sciences is not an original Prize, but was established by the Central Bank of Sweden in 1968 as a memorial to Alfred Nobel. It applauds those who can unravel the mysteries of markets, trade, and money.

The Peace Prize celebrates, in Nobels words, the person who shall have done the most or the best work for fraternity between nations, the abolition or reduction of standing armies and for the holding and promotion of peace congresses, sometimes risking their lives to do so.

So precious are the awards that the medals of German physicists Max von Laue and James Franck, stored away for safekeeping in Copenhagen during World War II, were dissolved in acid to keep them away from approaching Nazi troops. After the war, the gold was reconstituted from the acid and recast into new medals.

But Nobel history has not been entirely noble. In 1939, British Prime Minister Neville Chamberlain, known for his policy of appeasement toward Nazi Germany, was nominated for the Peace Prize. In an act of irony and protest, members of the Swedish Parliament nominated Adolf Hitler. That nomination was withdrawn. Some recipients have ordered oppressive crackdowns on their own people or ignored genocides, either before or after receiving the Prize. The 1918 Nobel Prize in Chemistry was given to Germanys Fritz Haber, who invented a method of producing ammonia on a large scale, which was helpful in making fertilizer. But the same chemist helped develop the chlorine gas that was used as a chemical weapon in World War I.

Stacker looked at facts and events related to the Nobel Prizes each year from 1931 to 2020, drawing from the Nobel Committees recollections and announcements, news stories, and historical accounts.

Take a look, and see what was happening with the Nobel Prizes the year you were born.

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Erik Axel Karlfeldt was the first Nobel winner to be awarded posthumously. The Swedish poet was alive during the nomination and deliberation process but died six months before the Literature Prize was announced. As of 1974, the rules were changed so that awards can only be given posthumously if the winner dies after the announcement but before the formal award is bestowed.

John Galsworthy, author of The Forsyte Saga, was awarded the Nobel Prize in Literature. The chronicle of English life became a hugely popular miniseries in 1967 on American public television.

Ivan Bunin, the first Russian writer to win the Nobel Prize in Literature, departed Russia after the 1917 revolution and settled in France as a permanent exile. His books were banned by Soviet authorities due to his anti-Bolshevik writing. To accept his Nobel Prize in Stockholm, Bunin had to travel through Germany, where he was arrested by the Nazis and falsely accused of smuggling jewels. The Nazis forced him to drink a bottle of castor oil before letting him go.

Three Americans shared the Nobel Prize in Physiology or Medicine for their research into anemia, when the bodys red blood cell count is low. George Whipple found dogs formed new blood cells by eating diets of liver, kidney, meat, and apricots, and George Minot and William Murphy applied those findings to humans with pernicious anemia. They also delved into the cause of pernicious anemia: a shortage of vitamin B12.

The 1935 Peace Prize was awarded to Carl von Ossietzky, a journalist and critic of Nazi Germany who was being held in a concentration camp. Hitler would not allow him to accept the prize. He died in 1938 in a prison hospital. Also in 1935, married couple Frdric Joliot and Irne Joliot-Curie won the Nobel Prize in Chemistry. Joliot-Curie was the daughter of Marie Curie and Pierre Curie, also Nobel Prize winners.

The Norwegian royal family chose not to attend the Nobel ceremony following the controversial choice of German pacifist Carl von Ossietzky to win the Peace Prize. Critics said the prize decision would provoke Germany. The royal family offered no official explanation for skipping the ceremony, but it was widely believed that Norway wanted to distance itself from the prize selection.

Contributions to understanding how the human eye functions earned the Nobel Prize in Physiology or Medicine for a scientific trio. Finnish scientist Ragnar Granit researched the types of cones responsible for seeing color; American Keffer Hartline analyzed how the eye processes contrasts; and American George Wald studied the role of light in visual impressions.

The Nobel Memorial Prize in Economic Sciences was established in 1968 by Sveriges Riksbank, the central bank of Sweden. It was created to mark the banks 300th anniversary. The first recipients would be awarded in 1969.

The first Nobel Memorial Prize in Economic Sciences was shared by Norwegian economist Ragnar Frisch and Dutch economist Jan Tinbergen, who helped develop the study of economics based upon mathematics. Tinbergen created a model of macroeconomics, placing economic variables in mathematical relationships to each other. His younger brother, Nikolaas Tinbergen, was one of three scientists awarded the 1973 Nobel Prize in Physiology or Medicine for their studies of animal behavior, particularly how animals communicate and care for their young.

Swedens Ulf von Euler discovered the bodys neurotransmitter norepinephrine, which is involved in the fight-or-flight process, and was awarded the Nobel Prize in Physiology or Medicine. His father, Hans von Euler-Chelpin, won the Nobel Prize in Chemistry in 1929 for his research in the fermentation of sugar and the enzymes involved in the process.

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Physicist Dennis Gabor won the Nobel Prize in Physics for inventing the holograph, and German Chancellor Willy Brandt won the Peace Prize for helping ease relations between East and West Germany. Under his administration, West Germany signed a nuclear weapons non-proliferation treaty, reached a nonviolence deal with the Soviet Union, and laid the groundwork for making family visits easier in the divided city of Berlin.

In a controversial decision, the 1973 Nobel Peace Prize was awarded jointly to U.S. Secretary of State Henry Kissinger and Le Duc Tho of North Vietnam for the Vietnam ceasefire negotiations. But the North Vietnamese leader refused to accept the prize, on grounds that the war was ongoing and the United States violated terms of the agreement. Kissinger did not travel to Norway to accept the prize and said he wanted to return it but was told he could not do so.

Free-market economist Friedrich von Hayek, a critic of central planning, shared the Nobel Prize with Swedish economist Gunnar Myrdal. Hayek argued for a decentralized market system with open competition and disagreed with the use of government fiscal policy to moderate movements of the economy as promoted by economist John Maynard Keynes.

Danish physicist Aage Bohr won the Nobel Prize for his experiments on the structure of atoms. His father, Niels Bohr, won the Nobel Prize in Physics in 1922, also for work on atomic structure. The elder Bohr created a theory that explained how moving electrons cause atoms to emit light.

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American economist Milton Friedman was awarded the Nobel Memorial Prize in Economic Sciences for his work on monetarypolicy. Friedman advocated for free markets and opposed government economic intervention. His views influenced the conservative fiscal policies of U.S. President Ronald Reagan and British Prime Minister Margaret Thatcher. He was a major proponent of school vouchersusing public tax funds to pay for students to attend private schoolsa system that remains hugely controversial to this day.

The Camp David Agreement, which laid out a framework for peace in the Middle East, earned the Nobel Peace Prize for Egyptian President Mohamed Anwar al-Sadat and Israeli Prime Minister Menachem Begin. U.S. President Jimmy Carter was to have been a third recipient, but a technicality prevented him from being nominated within the Committees deadline. But he won the Peace Prize nevertheless in 2002.

Mother Teresa of the Missionaries of Charity was given the Nobel Peace Prize for her work assisting the poor in Kolkata, especially its orphans, lepers, and terminally ill. Pope Francis declared the Albanian nun a saint in 2016. She started the Missionaries of Charity with a dozen nuns and it had nearly 5,000 at the time of her death in 1997.

Britains Frederick Sanger won his second Nobel Prize in Chemistry, having won his first in 1958. The first prize honored his research in the composition of insulin molecules, and the second prize recognized his work in mapping human genomes and developing a method used in DNA sampling and identification.

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The Office of the United Nations High Commissioner for Refugees won its second Nobel Peace Prize. It was awarded its first Peace Prize in 1954 for its relief to refugees in post-war Europe. The Nobel Committee noted that more recently, refugees were coming from developing countries, especially Vietnam, Afghanistan, and Ethiopia, and that the UNHCR accomplished its humanitarian work despite political obstacles and challenges.

Alva Myrdal, along with Mexicican diplomat Alfonso Garca Robles, won the Nobel Peace Prize for working toward nuclear disarmament. Myrdal was a Swedish scientist, government official, and diplomat, and she was married to Gunnar Myrdal, a Swedish economist who was awarded an Economics Nobel in 1974.

Best known for Lord of the Flies, British author William Golding won the Nobel Prize in Literature. The Nobel Committee said his novels, with the perspicuity of realistic narrative art and the diversity and universality of myth, illuminate the human condition in the world of today."

The Nobel Peace Prize was given to Desmond Tutu for his role in ending apartheid in South Africa. The Nobel Committee said it selected the Anglican bishop for his advocacy of using non-violence to counter the system of racial separation. The award to Tutu was influential in the global advocacy for the economic sanctions that pressured South Africa to dismantle its brutal system.

In awarding the Peace Prize to the International Physicians for the Prevention of Nuclear War, the Nobel Committee singled out its Soviet founder Yevgeny Chazov and American founder Bernard Lown to accept the award because of their cooperative influence. The IPPNW consists of tens of thousands of medical professionals, now in 64 countries, who banded together in hopes of preventing and averting nuclear war.

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Holocaust survivor, activist, and author Elie Wiesel won the Nobel Peace Prize for his message of peace, atonement and dignity, the Nobel Committee said. At 16, Wiesel was imprisoned in Buchenwald. His mother, father, and younger sister were killed in the camps.

Costa Rican President Oscar Arias Snchez is credited for his leadership in encouraging five presidents in Central America to sign a peace agreement ending the regions civil wars. The peace plan signed by Costa Rica, Guatemala, El Salvador, Honduras, and Nicaragua called for human rights safeguards, free elections, and an end to interference by other countries.

The winners of the Prize in Physiology or Medicine brought relief to millions with their drug discoveries. The work of Sir James Black led to the use of receptor-blocking drugs to treat heart disease, hypertension, and peptic ulcers, and collaborators Gertrude Elion and George Hitchings made discoveries that led to drugs for the treatment of leukemia, malaria, gout, and herpes virus infections.

Marking the end of the Cold War, the Nobel Committee presented the Peace Prize to Soviet President Mikhail Gorbachev. It honored Gorbachev for his efforts at economic and political reform known as perestroika and dtente with the United States. In a speech delivered by an aide sent to accept the prize, the Soviet leader said it was a recognition of what we call perestroika and innovative political thinking, which is of vital significance for human destinies all over the world.

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Myanmars human rights activist Aung San Suu Kyi was under house arrest when she was awarded the Peace Prize. In 2015 she was released and elected to national office, but she has come under strong criticism for her countrys treatment of its Muslim Rohingya minority and its possible genocide. Calls were made for her Nobel Prize to be revoked, but the head of the Nobel Foundation said it would not be withdrawn for events that took place after it was awarded.

Marking the 500th anniversary of Christopher Columbus landing in the Americas, Mayan Rigoberta Mench Tum of Guatemala was hailed for her campaign for human and Indigenousrights. Taking a global approach, she facilitated the use of international intermediaries in negotiations between guerrilla forces and the government, culminating in a 1996 peace agreement that ended a 36-year civil war.

South Africa took the spotlight when the Nobel Peace Prize was awarded to Nelson Mandela and Frederik Willem de Klerk for their roles in ending the apartheid system of racial separation. Mandela was imprisoned 27 years for his political activism, and de Klerk, the president of South Africa, released him in 1990. They went on to work together to end apartheid and design a new constitution that allowed universal voting rights, regardless of race.

American John Nash was one of three winners of the Nobel Memorial Prize in Economic Sciences for his work on game theory. Nashs struggle with schizophrenia was portrayed in the 2001 Academy Award-winning film A Beautiful Mind, starring Russell Crowe as the Princeton-educated mathematician. His work, which became known as the Nash equilibrium, is used in understanding the processes of chance and decision-making.

Joseph Rotblat, a physicist and longtime opponent of nuclear weapon development, won the Nobel Peace Prize 50 years after atom bombs were dropped on Hiroshima and Nagasaki. He withdrew in 1943 from the Manhattan Project, which was producing nuclear weapons. He worked with the anti-nuclear Pugwash movement, a series of conferences with which he shared the Peace Prize.

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Southeast Asias East Timor was highlighted when the Peace Prize was awarded to Carlos Belo and Jos Ramos-Horta. Ramos-Horta was a leader of resistance in East Timor to the occupation by Indonesia and helped build international support for self-determination, and Belo, a Roman Catholic bishop, demanded the United Nations and the United Nations Commission on Human Rights take notice. The Peace Prize is considered a major factor in East Timor achieving independence in 2002.

Citing the more than 100 million anti-personnel landmines estimated to be strewn around the world, the Nobel Committee gave the Peace Prize to the International Campaign to Ban Landmines and to its coordinator Jody Williams for their accomplishments in banning and clearing mines. Their work culminated in the United Nations Mine Ban Convention, adopted in 1997, that prohibited the stockpiling and use of landmines and required countries to clear mines.

Two political leadersDavid Trimble and John Humein Northern Ireland shared the Peace Prize for helping bring about the Good Friday Agreement that laid out plans for governance of Northern Ireland. Key to the agreement were the Protestant Ulster Unionist Party, led by Trimble, and the Catholic Social Democratic and Labour Party, led by Hume.

The Nobel Committee applauded Mdecins Sans Frontires, known as Doctors without Borders in English, for its extensive humanitarian work across several continents. It said the organization maintained a high degree of independence, helped build public opinion in opposition to humanitarian abuses, and helped forge contacts between sides in conflicts.

Understanding our relation to money earned the Nobel Prize for two American economists. James Heckman researched factors that affect statistical sampling, and his findings have been used to understand how early life experiences influence earnings potential and economic status. Daniel McFadden studied how people make decisions, developing so-called discrete choice models that can explain and predict behavior and are applied to such real-life uses as public transportation systems and senior housing.

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Americans George Akerlof, Michael Spence, and Joseph Stiglitz were awarded the Nobel Memorial Prize in Economics for their work on markets with asymmetric informationmarkets in which one side has better information than the other. Akerlof looked at the consequences of such markets in areas like developing world lending and medical insurance, Spence demonstrated how market participants convey information, and Stiglitz showed how asymmetric markets work in areas like unemployment and credit.

Jimmy Carter was commended for decades of untiring effort to find peaceful solutions to international conflicts, to advance democracy and human rights, and to promote economic and social development. The Committee cited his foreign policy achievements including the Panama Canal treaties, Camp David Middle Eastern accord, and SALT II treaty with the Soviet Union as well as his founding afterward of The Carter Center, which specialized in international conflict mediation and election monitoring.

The creators of magnetic resonance imagining, or MRI, took home the Nobel Prize in Physiology or Medicine. Paul Lauterbur of the United States and Britains Sir Peter Mansfield researched the behavior of atoms and molecules in a magnetic field to develop interior imagery of the human body.

Wangari Maathai, the first female professor in Kenya, became the first African woman to win the Nobel Peace Prize. Already active in the nations democratic movement, Maathai launched a grassroots movement that mobilized women to plant trees to fight deforestation. Called the Green Belt Movement, it spread elsewhere in Africa and led to the planting of more than 30 million trees.

Winners of the Nobel Prize in Physiology or Medicine, Australians J. Robin Warren and Barry Marshall discovered the bacterium that causes gastritis and peptic ulcer disease. Their discovery ran counter to the commonly held belief that peptic ulcer disease was caused by lifestyle and stress. The revelation influenced research into the causes of other chronic inflammatory conditions and the links between chronic infection, inflammation, and cancer.

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The winner of the Nobel Prize in Chemistry, American Roger Kornberg, researched the structure and role of an enzyme called RNA polymerase in a genetic process essential to building and maintaining molecular and cell structure. His father Arthur Kornberg won the 1959 Prize in Physiology or Medicine for his pioneering work in genetics.

Doris Lessing, author of dozens of books including the novel The Golden Notebook, became the oldest winner of the Nobel Prize in Literature at age 88. She told reporters from her doorstep in London that she was not that surprised because her name had been under consideration for decades. Either they were going to give it to me sometime before I popped off or not at all, she said.

The New York Times columnist Paul Krugman won the Nobel memorial Prize in Economic Sciences for his work in international trade patterns and economic geography. Krugman was instrumental in the development of New Trade Theory, which concerns factors in international market patterns such as economies of scale and the network effect, when goods become more valuable with wider use.

Sir John Gurdon of England and Shinya Yamanaka of Japan, winners of the Nobel Prize in Physiology or Medicine, researched the way cells and organisms develop. They discovered how mature specialized cells could be reprogrammed to become immature cells, a major medical breakthrough applicable to stem cell research.

The three American economists who shared the Nobel Prize made discoveries that help predict the long-term prices of stocks and bonds. Eugene Famas research was used in the development of stock index funds, Robert Shiller discovered certain dynamics about stock prices and dividends, and Lars Hansen looked at theories of risks and returns that are used in asset pricing.

At age 17, Malala Yousafzai was the youngest Nobel Laureate when she was awarded the 2014 Peace Prize. Yousafzai, an outspoken advocate for girls education and rights, survived an attempted assassination in 2012 by the Taliban in Pakistan. She shared the Peace Prize with Indian activist Kailash Satyarthi, who was honored for his work fighting child labor.

American physicist Clinton Davisson won the Nobel Prize partly by accident. When he was testing the hypothetical relation between particle velocity and wavelength, he bombarded a nickel block with electrons and measured how they scattered. But when the nickel was baked at high heat after accidental contamination, the structure of its atoms changed, as did the patterns of the electrons, proving the hypothesis.

Germanys Adolf Butenandt won the Nobel Prize in Chemistry for his research into sex hormones that would be used in the development of oral contraception. Like Richard Kuhn in 1938, he was forced by the Nazis to decline the prize but was able to accept the certificate and medal in 1949. Germanys Gerhard Domagk, whose research led to the development of antibiotics, also had to turn down the Nobel Prize in Physiology or Medicine but got it after the war.

No Nobel prizes were awarded in 1940 due to World War II. Norway was occupied by German forces, and Adolf Hitler was angry about the 1936 Peace Prize awarded to Carl von Ossietzky, a journalist who disclosed that Germany had been secretly rearming, a violation of the Treaty of Versailles that ended World War I. Ossietzky was tried and convicted of treason.

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Not only were no Nobel Prizes awarded while the world was locked in war, but a significant brain drain was underway that would see Europe lose many of its brilliant thinkers. By 1941, a dozen Nobel-winning scientists had left for England and the United States, including physicists Niels Bohr, a winner in 1922, Albert Einstein, who won in 1921, and Enrico Fermi, who won in 1938.

While no Nobel Prizes were awarded, 1942 was the year that the name United Nations was coined by President Franklin Roosevelt in a declaration by 26 nations to stand together against the Axis powers. Founded three years later, the United Nations, along with its agencies, programs, and staff, has been awarded the Nobel Peace Prize a dozen times. The U.N.s High Commissioner for Refugees (UNHCR) has won it twice, and most recently, the U.N.s World Food Programme won in 2020.

Henrik Dam and Edward Doisy shared the Nobel Prize in Physiology or Medicine for their work in the discovery of vitamin K, which the human body uses for clotting and healing. Dam determined that Vitamin K is needed for blood to coagulate, and Doisy found ways to produce it artificially, which was useful in stopping bleeding in small children.

The Nobel Peace Prize was awarded to the International Committee of the Red Cross for the work it had done during the war on behalf of humanity. It was the first Peace Prize bestowed in five years; the prizes were not given out from 1939, the year Germany invaded Poland at the start of World War II, to 1943.

Two American activists shared the Nobel Peace Prize. One was Emily Greene Balch, co-founder of the Womens International League for Peace and Freedom and a professor at Wellesley College for 22 years until she was fired for her activism. John Raleigh Mott, head of the Young Mens Christian Association, promoted international youth programs, worked with relief programs for prisoners of war, and was an outspoken critic of colonial oppression and race discrimination.

Gerty Cori, the first woman to win the Nobel Prize in Physiology or Medicine, was honored with her husband Carl Cori for their work in understanding the metabolism process. When the couple moved to America in 1922 from Austria, Carl Cori was hired as a biochemist at a New York research institute. Gerty Cori could only find work as an assistant pathologist, despite having the same degrees and research experience, because she was a woman. She was finally allowed a position equal with her talent and experience at Washington University in St. Louis in 1938.

Indian leader Mahatma Gandhi was nominated five times for the Nobel Peace Prize, the final time being in 1948 not long before he was assassinated. That year, the Nobel Committee chose not to bestow any award, declaring there was no suitable living candidate.

The winner of the Nobel Prize in Medicine, Portugals Egas Moniz, invented the lobotomy. He discovered how a surgical incision into the brains prefrontal lobe could alter behavior. Lobotomies were used widely to treat mental illness in the 1940s and 1950s until they were widely recognized as dangerous, and medication for mental illness became more commonly prescribed.

Ralph Bunche was principal secretary of the United Nations Palestine Commission when he was awarded the Peace Prize for his role in mediating the 1949 cease-fires between Israel and Arab states after the partition of Palestine. Bunche, an academic and U.S. State Department advisor, was the first Black person to receive a Nobel Prize.

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Max Theiler of South Africa was honored for his research on yellow fever, a deadly disease found in subtropical and tropical South America and Africa and spread primarily by mosquitoes. Theiler discovered how to transmit the yellow fever virus to mice, helping produce weaker forms of the virus that could be used as a vaccine for humans.

For his role in the discovery of streptomycin, Selman Waksman was awarded the Nobel Prize in Physiology or Medicine. Streptomycin was the first antibiotic found to be effective against tuberculosis. Waksman studied how the bacteria that causes tuberculosis interacted with microorganisms in soil and found that a bacterium called Streptomyces griseus blocked its growth.

British Prime Minister Winston Churchill won the Nobel Prize in Literature for his works that included an autobiography, several volumes about the First and Second World Wars, and his notable speeches during World War II. From 1946 to 1953, Churchill was nominated in seven years for the Literature Prize and twice for the Nobel Peace Prize.

Although the Nobel Prize in Literature is considered to honor a writers body of work, the Nobel Academy singled out The Old Man and the Sea when it chose American author Ernest Hemingway. It said the novel demonstrated his mastery of the art of narrative.

The winner of the Chemistry Prize, Vincent du Vigneaud, studied biochemical sulphur compounds, including oxytocin, a hormone involved in sexual intimacy and reproduction. Sometimes called the cuddle or love hormone, it is released when people bond, including as couples or parents with children. Vigneaud isolated oxytocin, calculated its chemical composition, and determined how to produce it artificially.

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The king of Sweden goodnaturedly reprimanded John Bardeen for leaving most of his family homehis children were in schoolwhen he was awarded the Nobel Prize in Physics. The American physicist told the king he would bring his family the next time. Sure enough, Bardeen won a second Nobel Prize in 1972, and he took his whole family to theceremony.

Ending conflict in the Middle East was the focus of Canadian historian and diplomat Lester Pearson, who won the Peace Prize for his role in ending violence that erupted in 1956 over control of the Suez Canal. The conflict among the major superpowers could have had severe global consequences. Thanks to Pearsons efforts, a United Nations Emergency Force was dispatched to oversee a cease-fire.

Russias Boris Pasternak was awarded the Nobel Prize in Literature, which he at first accepted but later was forced to turn down by Soviet authorities who banned his novel Doctor Zhivago. The only novel the poet wrote, Dr. Zhivago was deemed to be anti-Soviet and remained forbidden until the late 1980s.

Biochemists Severo Ochoa and Arthur Kornbergs work on DNA and RNA earned them the Nobel Prize in Physiology or Medicine. Ochoa discovered how to create RNA, and Kornberg, formerly a student of Ochoas, found ways of making DNA. Kornbergs son, Roger, a chemical physicist, also conducted genetic research and won the Nobel Prize in Chemistry in 2006.

The awarding of the Peace Prize to Dag Hammarskjld, the second Secretary-General of the United Nations, was only the second time a Nobel was given posthumously. The first occasion was the posthumous literature prize awarded to Erik Axel Karlfeldt in 1931. The rules were changed in 1974 so that prizes could not be awarded posthumously unless the winner dies after the announcement but before the award ceremony.

The winner of the Nobel Prize in Physiology or Medicine, to American James Watson, would later sell it at auction at Christies in 2014 to raise money for charity. Russian tycoon Alisher Usmanov paid $4.7 million, then said he was returning the award to the scientist. Watson won for discovering the structure of DNA along with Francis Crick.

Frances Jean-Paul Sartre was awarded, and declined, the Nobel Prize in Literature.He explained that he always declined official honors and that as a writer, he felt he should remain distinct from any institution.

The United Nations Childrens Fund, better known as UNICEF, was awarded the Nobel Peace Prize. UNICEF started out in 1946 providing food, clothes, and medicine to children and mothers but expanded to promote nutrition, school attendance, and health care in developing countries. The Nobel Committee honored UNICEF for its effort to enhance solidarity between nations and reduce the difference between rich and poor states.

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Peyton Rous won the Nobel Prize in Physiology or Medicine when he was 87, the oldest winner ever in the category. The American studied the role of viruses in cancer cells and transmission. His work was based on research begun in the early 1910s.

In awarding the Prize in Literature, the Nobel Committee honored German writer Heinrich Bll, saying his a broad perspective on his time and a sensitive skill in characterization has contributed to a renewal of German literature." After World War II, Bll was part of the Gruppe 47, a number of influential writers who would meet over the course of three decades as they dealt with the wars destruction and the aftermath of the Holocaust.

Winners of the Nobel Prize in Physiology or Medicine, Roger Guillemin and Andrew Schally used pig brains and lamb brains in their research on hormonal roles and structure. They shared the prize with Rosalyn Yalow, a nuclear physicist who developed radioimmunoassay, a method that can measure extremely small amounts of bodily substances. It was used in helping determine the cause of type 2 diabetes.

When the 14th Dalai Lama was awarded the Nobel Peace Prize, he was living in exile for his opposition to the Chinese occupation of Tibet. Chinese authorities said the award was an act of interference in its internal affairs and that it hurt the Chinese peoples feelings. The Dalai Lama used the occasion to present a plan for Tibet to be a demilitarized zone, an idea the Chinese government rejected.

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Nobel Prize history from the year you were born - Morganton News Herald

Environmental Factor – December 2020: Aging and cancer interplay explored at NIH workshop – Environmental Factor Newsletter

Researchers discussed how aging influences cancer progression and how cancer accelerates aging, at National Institutes of Health event.

By Arif Rahman

The population of older individuals is increasing globally, and most cancers arise as people age, according to experts at an Oct. 26-27 National Institutes of Health (NIH) virtual conference: Age-Dependent Changes in Cancer Biology. NIEHS, the National Cancer Institute (NCI), and National Institute on Aging (NIA) jointly organized the meeting.

Invited speakers discussed common ground in the biology of cancer and aging and identified areas for further research efforts.

Cancer is rare among people younger than 45. There is a sharp rise after that, peaking between 65 to 74 years, according to NCI Director Ned Sharpless, M.D.

Among the possible explanations for this association, one factor stands out. It is becoming increasingly clear that time itself is a potent mutagen, he said. Mutagens promote errors in DNA replication that can lead to cancer.

Sharpless discussed key causes of age-related cancers, including the following.

He pointed to two critical areas that need more attention from researchers in basic science. The first issue is that many cancer drugs contribute to aging directly, he said. Secondly, therapies that are beneficial in young adults can be difficult to use in older adults because of the age-associated reduced resilience of the host.

NIA Scientific Director Luigi Ferrucci, M.D., Ph.D., echoed Sharpless during his keynote talk. Nearly half of the cancer risk factors are unknown to this day, Ferrucci said. He suggested that studying the role of aging in cancer development would significantly fill that knowledge gap.

Les Reinlib, Ph.D., moderated a session on the overlap between environmental carcinogens and gerontogens, or agents that quicken the aging process. Reinlib is a health scientist administrator in the NIEHS Exposure, Response, and Technology Branch.

Studies suggest that gerontogens such as air pollutants, cigarette smoke, and arsenic may cause cancer by promoting cellular senescence, or cell death. Although senescence gets rid of old or damaged cells, it also promotes cancer development by changing the cellular microenvironment.

Susan Neuhausen, Ph.D., from the City of Hope Comprehensive Cancer Center, noted that the U.S. Environmental Protection Agency has registered approximately 85,000 synthetic chemicals for commercial use, only 10% of which have been tested for effects on human health.

She emphasized the need for more human-relevant testing of these chemicals.

One unifying theme among the talks was that aging and cancer share common biological mechanisms.

By slowing down the aging process, it should be possible to reduce cancer incidence. One way to do that is to promote a healthy cellular microenvironment via proper nutrition, according to Trygve Tollefsbol, Ph.D., from the University of Alabama at Birmingham.

Tollefsbol said that certain dietary guidelines could help curb the high prevalence of cancer, as well as obesity, in developed countries.

Due to the rapid global rise in the population of older adults, experts at the meeting expressed the belief that it is more cost effective to prevent diseases like cancer in the elderly population than to manage them.

(Arif Rahman, Ph.D., is a visiting fellow in Division of the National Toxicology Program Toxicoinformatics Group.)

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Environmental Factor - December 2020: Aging and cancer interplay explored at NIH workshop - Environmental Factor Newsletter

CURE Media Group Announces the 2020 MPN Heroes Winners – Business Wire

CRANBURY, N.J.--(BUSINESS WIRE)--CURE Media Group, the industry-leading multimedia platform devoted to cancer updates and research that reaches more than one million patients, has named the winners of the MPN Heroes Recognition Program. The virtual celebration will take place tonight from 6 to 7:30 p.m. CST.

Keynote speaker Devon Still, former professional athlete, entrepreneur, motivational speaker, author and advocate for childhood cancer awareness, will join in this years annual evening of gratitude and celebration honoring these eight remarkable heroes who have gone above and beyond, making a difference in the field of rare blood cancers known as myeloproliferative neoplasms (MPNs).

The following individuals will be recognized in the Commitment to the Individual category:

The second category honors MPN specialists whose efforts have helped the broader MPN community:

These incredible heroes have truly dedicated themselves to improving the lives of people with myeloproliferative neoplasms, said Mike Hennessy Jr., president and CEO of MJH Life Sciences, parent company of CURE Media Group. This year marks the eighth anniversary of the MPN Heroes Recognition Program, and we look forward to an amazing celebration this evening recognizing these champions who have made a difference in MPN care.

The MPN Heroes Recognition Program is sponsored by Incyte and CURE Media Group, publishers of CURE magazine. Incyte partners with CURE Media Group to support the program, with CURE hosting the annual MPN Heroes Celebration Event. The honorees were nominated by colleagues, patients and caregivers for their heroic contributions and dedication. The selected MPN Heroes were chosen by an independent judging panel comprised of patient advocates and healthcare professionals. Individuals or entities supported through funding or directed by Incyte were not eligible for consideration or recognition. Supporting the MPN community is an ongoing priority for Incyte, a global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development, and commercialization of proprietary therapeutics.

About CURE Media Group

CURE Media Group is the leading resource for cancer updates, research, and education. It features a full suite of media products, including the industry-leading website CUREtoday.com; innovative video programs such as CURE Connections; a series of widely attended live events; CURE magazine, which reaches more than 1 million readers; and the dynamic website for oncology nurses, OncNursingNews.com, and its companion publication, Oncology Nursing News. CURE Media Group is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in North America, dedicated to delivering trusted health care news across multiple channels.

About Incyte

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

MPN Heroes is a registered trademark of Incyte. Other trademarks are the property of their respective owners.

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CURE Media Group Announces the 2020 MPN Heroes Winners - Business Wire

John Theurer Cancer Center (JTCC) Researchers to Present 52 Abstracts across Hematological Malignancies at the 2020 American Society of Hematology…

Newswise December 4th, 2020 Hackensack, NJClinical investigators from Hackensack MeridianHealthJohn Theurer Cancer Center (JTCC), amember of the Georgetown Lombardi Comprehensive Cancer Center consortium, are to present updates on treatment advances in multiple myeloma (MM), mantle cell lymphoma (MCL), and other types of B-cell lymphoma (BCL) as well as leukemia at the 62ndAmerican Society of Hematology (ASH) Annual Meeting and Exposition, to be held virtually from December 5-8, 2020.

Once again, and despite COVID, our team has a full presence at ASH 2020, being part of 52 abstracts. This shows our commitment to clinical science and collaboration with other leading institutions, from new studies on CAR-T cells, bispecific T cell engager antibodies, and other new small molecules in leukemia, lymphoma, and myeloma, said Andre Goy, MD, MS, Chairman and Director of John Theurer Cancer Center (JTCC) at Hackensack University Medical Center. It is not just a requirement for our patients but a privilege to contribute to the phenomenal acceleration of cancer medicine.

The 51 abstracts (listed in the table below) cover three of the main themes of ASH this year:

CAR-T cells have emerged over the last few years as a game-changing therapy for patients withhematologicmalignancies. Anti-CD19 CAR-T cells are approved for use in adults with aggressive B-cell non-Hodgkin lymphoma (NHL) or MCL,but also in B-cell acute lymphocytic leukemia (ALL, up to 25years ofage). At ASH,JTCC is part of the team presenting an update from the ZUMA 2 pivotal trial in MCL, in which CAR-T therapy was associated with a durable response (40% of the first28patients still in remission at 32 months follow-up), an unprecedented response in that setting.(Abstract 1120; Dr. AndreGoy).Also, there was a consistent benefitacross all patients with relapsed/refractory MCL, even in those with high-risk features such as blastoid variant or with a high proliferation rate(Abstract 1126; Dr.AndreGoy).

CAR-T cell therapy is also being tested in other blood cancers and will be featured in other presentations at ASH focusing onMM and indolent BCL.

CAR-T cell therapy directed against B-cell maturation antigen (BCMA) has shown promising results in the treatment of relapsed/refractory multiple myeloma (RRMM), with very high response rates (>90%), but unfortunately a significant proportion of patientshave relapsed, potentially due to the lack of sustainability of CAR-T cells over time. To address this, bb21217 is an anti-BCMA CAR-T cell therapy that uses the same CAR molecule as idecabtagene vicleucel (called bb2121; see below) but adds the PI3K inhibitor molecule bb007 during theex vivomanufacture/T cells culture to enrich the drug product for memory-like T cells, thereby reducing the proportion of highly differentiated or senescent T cells. The rationale is to make CAR-T cells more sustainable and to help prolong treatment responses. The results from a Phase I dose-escalation trial of bb21217(Abstract 130; Dr. DavidSiegel)in which patients with RRMM had received 3 prior regimens, are promising, with no added toxicity. The presence of T cell markers associated with memory-like T cells and the absence of T cell markers associated with differentiation/senescence correlated positively with the T cells peak expansion in the patients and the duration of response, consistent with the investigators hypothesis.

Also, an update on BCMA CAR-T therapy(Abstract 131; Dr.DavidSiegel)confirmed a high response rate of 76% (39% with a complete response [CR]) and a median duration of response of 10.3 months. Similarly, a BCMA CAR-T update from the KarMMA trial (NEJM 2019) showed the same benefit in older patients(65-70 years old), even in those who were heavily pretreated(Abstract 1367; Dr. DavidSiegel)or presenting very high-risk features(Abstract 3234; Dr.DavidSiegel).

Finally, JTCC will be a co-presenter of the ZUMA-5 trial, providing the firstCAR-T therapy data in indolent BCL (146 patients), using an anti-CD19 CAR-T and showing a very high response rate (>90% overall response rate [ORR] and >80% CR).These data are very impressive based on the efficacy -- even in double-refractory patients -- but also because of the favorable toxicity profile(Abstract 700; Dr. Lori Leslie).

Alternative options to generate cell therapies are emerging, including natural killer (NK) cell therapygenerated from a pluripotent stem cell (iPSC) line, which can be used as a renewable source for the mass production of off-the-shelf NK cells for broad patient access.Early data on FT538, an investigational, first-of-its-kind, multiplexed engineered NK cell therapy, will be presented in both myeloma and acute myeloid leukemia (AML) at ASH(Abstract 1449; Dr. David Siegel).

The BITE antibodieshelp force the normal immune system to reengage and to fight cancer cells. They are definitely a big topic at ASH, as they continue to show great activity and unlike CAR-T cells, do not necessitate a complex process of cell collection and manufacturing. They may thus offer a form of off-the shelf cell therapy. However, as with CAR-T cell therapy, BITE antibodies can be associated as in CAR-T cells therapy - with cytokine release syndrome (CRS) and/or neurotoxicity both related to the rapid activation and amplification of T cells in patients after infusion. In order to address this, JTCC investigators and colleagues explored the subcutaneous (SC) administration of mosunetuzumab a lead product among BITEs (targeting anti CD3 and CD20) to patients with B-cell relapsed/refractory lymphomas. Results showed an ORR of 60% in heavily pretreated patients with aggressive lymphoma (DLBCL), including in patients who failed prior CAR-T therapy. In addition,researchers observed much less toxicity andhigh bioavailability (>75%), supporting the use of SC dosing for CRS mitigation(Abstract 2096; Dr. AndreGoy).

Usage of both CAR-T cells and BITEs will expand dramatically in the future across many cancers and JTCC has a robust ongoing comprehensive portfolio of CAR-T cells and BITE-based trials, including, off-the shelf CAR-T cells and NK cells, dual/multi-target CAR-T cells, as well as combinations with small molecules to enhance the activity and/or durability of these modifiedT cells.

Another emerging form of immunotherapy involvescheckpoint inhibitors,which also help unleash the immune system and have been approved in many cancers. At ASH a new study using an anti-CD47 checkpoint inhibitor showed very promising results(Abstract 646; Dr. TatyanaFeldman).CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRP) and delivers a"do not eat"signal to suppress macrophage phagocytosis. Overexpression of CD47 can allow tumor cells to escape immune surveillance. TTI-621 (SIRPFc) is a fusion protein consisting of the CD47 binding domain of human SIRP linked to the Fc region of human immunoglobulin G1 (IgG1), designed to enhance phagocytosis and antitumor activity by blocking the CD47-SIRP interaction between malignant cells and macrophages.

Finally, the standard of care of patientswith relapsed Hodgkin disease is salvage with high-dose therapy, followed by stem cell transplantation. A subset of these patientsstill relapse and experience a poor outcome. The ability to use immunotherapy as consolidation post-transplantation (brentuximab + nivolumab) was illustrated in a study presented at ASH(Abstract 472; Dr. TatanyaFeldman), in whichonly one of 59 enrolled patientsrelapsed, leading to a remarkable 98% survival rate and no major toxicity issues.

A number of presentations at ASH will focus on novel emerging agents in several diseases with persistent unmet need, including the following examples.

Acute myeloid leukemia (AML):

The FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib (Gilt) improves survival compared with standard salvage chemotherapy in relapsed/refractory (R/R)FLT3-mutated (FLT3mut+) AML. However, relapses are common and long-term survival remains poor. Combination therapies of FLT3 inhibitors with agents that induce apoptosis have demonstrated preclinical activity and synergy againstFLT3mut+clones and may delay or prevent drug resistance. This was the subject of a study of Gilt + venetoclax (Ven) in patients with refractory AML, with most having previously failed FLT3 inhibitor therapy (Abstract 333; Dr. JamesMcCloskey),suggesting substantially greater antileukemic activity from Gilt + Ven than with single-agent Gilt in a very difficult-to-treat patient population.

Chronic myeloid leukemia (CML):

CML is a disease literally transformed by kinase inhibitors (TKIs)over the last 20 years.However, patients can develop resistance against these targeted therapies, leading to the development of second-, third-, and fourth-generation kinase inhibitors, offering new options, albeit often with new or different toxicities encountered over time. The OPTIC trial was a randomized Phase 2 trial evaluating different dosing schedules of ponatinib in patients with CP-CML who were resistant/intolerant to 2 TKIs or with a T315I mutation. The results of this large landmark trial will help refine dosing in this population, while minimizing toxicities(Abstract 48; Dr. JamesMcCloskey).

B-cell lymphoma (BCL)

CA-4948 is a novel oral small molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 is part of the Myddosome signaling pathway (a group of proteins forming a complex involved in innate immunity) and is essential for downstream signaling of tolllike receptors (TLRs) and the interleukin-1 receptor (IL-1R) family in immune cells including B lymphocytes. Dysregulated signaling in these pathways is frequently observed in certain types of BCL, particularly in ABC-subtype of DLBCL and Waldenstrm macroglobulinemia (WM). In this early trial CA-4948 demonstrated a good safety profile, desirable pharmacokinetic properties, and preliminary clinical activity. This offers a new venue to target B-cell signaling in BCLs and provides a rationale for combination therapy with BTK and/or BCL2 inhibitors, expanding the portfolio of emerging non-chemotherapy options for these patients(Abstract 703;Dr. LoriLeslie).

Epstein-Barr virus (EBV) can play a role in several subtypes of lymphoma including Hodgkin, B and T cell lymphomas. EBV-positive (EBV+) lymphomas are generally associated with poor clinical outcomes, particularly for patientswho have relapsed or are refractory (R/R) to standard therapies. Targeting EBV by using the antiviral valganciclovir and the histone deacetylase (HDAC) inhibitorNstat showed promising results, with an ORR up to 80% (50% CR) in T/NK cell lymphoma (a very difficult-to-treat subtype) and 60% in aggressive BCL, providing a potential new approach, as there are currently no approved therapies for these EBV+lymphomas(Abstract 1154; Dr. TatyanaFeldman).

Multiple myeloma (MM):

Proteasome inhibitors were the firstnew class of drugs approved in myeloma; they typically disrupt the system responsible for protein recycling inside the cells and have become the backbone of MM therapy. Attempts to refine these drugs have led to new compounds including IBER, an oral, potent novel cereblon E3 ligase modulator (CELMoD) agent, which has shown marked synergistic tumoricidal and immune-stimulatory effects in combination with bortezomib or daratumumab in preclinical models.CC-220-MM-001 is a phase 1/2 study evaluating dose escalations of IBER with different treatment combinations in independent cohorts in patients with RRMM, expanding the combination of biological agents and providing new options in this population(Abstract 724; Dr. DavidSiegel).

Selinexor (SEL) is a novel, first-in-class oral selective inhibitor of nuclear export (SINE), which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, ultimately causing apoptosis in cancer cells.STOMP is a multicenter, open-label, phase 1b/2 study ofcombination therapy with SEL, pomalidomide, and dexamethasone in patients with RRMM who previously failed lenalidomide and proteasome inhibitor therapy, two of the key therapies in myeloma. This combination almost doubled the response rate (58% vs 31%) and led to a durable response in these heavily pretreated patients(Abstract 726; Dr. NoaBiran).

Stem cell transplantation:

Despite prophylaxis, graft versus host disease (GVHD) remains a significant cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation (HCT). ITA is a potent, selective Janus kinase (JAK) 1 inhibitor that has been combined safely with steroids in patients with acute GVHD. Results from a proof-of-concept study evaluating ITA + a calcineurin inhibitor (CNI) for GVHD prophylaxis, co-presented by the JTCC Bone Marrow Transplantation team, were promising, showing reduced incidence of severe GVHD, a crucial complication post-transplantation(Abstract 356; Dr. ScottRowley).

Clinical trials help move the field and establish new standards with more and more options for multiple cancer types, raising the complexity of treatment decisions. Real-world evidence (RWE) can help confirm a clinical benefit observed in a given trial and refine potential toxicities but also can help inform the best sequence of care among the many available options -- one of the biggest current challenges in oncology. Several abstracts at ASH report on this specific issue.

JTCC was part of the largest series to date comparing the first-line use of chemoimmunotherapy (CIT) to targeted therapy (e.g., ibrutinib [IBR]) in more than 500 high-risk patients with chronic lymphocytic leukemia (CLL) (Abstract 372, Dr. LoriLeslie). Results showed that patients treated with single-agentIBRtherapy had significantly longer responses and longer time to next therapy than those treated with CIT, despite similar demographics and clinical characteristics. This RWE study also demonstrated that IBR therapy provided sustained clinical benefit regardless of risk status and supports the use of IBR in the first-line setting.

JTCCs Euro-oncology group was part of a RWE study in patients with primary central nervous system lymphoma (PCNSL). Thetreatment of older patients with PCNSL is challenging due to the prevalence of comorbidities, frailty, and complexities with delivery of chemotherapy (CT). Investigators from this large series showed that outcomes in these older patients are suboptimal, and the use -- when possible -- of high-dose methotrexate truly makes a difference (as in younger patients)(Abstract 476, Dr. SamuelSinger),helping guide oncologists in this rare disease.

Burkitt lymphoma is a rare lymphoma which carries the most aggressive features and requires very intensive therapy. Authors from several institutions including JTCC reported on a new prognostic model and its impact of modern therapy(Abstract 706; Dr. TatanyaFeldman)as well as the outcome in HIV-infected patients where this lymphoma subtype is more common(Abstract 705; Dr. TatanyaFeldman).

Finally, JTCC was part of two studies reported at ASH on the impact of COVID-19 on cancer patients. The first, a global observation of more than 400 patients with CLL who were hospitalized with COVID, which showed that advanced age was the highest risk factor for mortality(Abstract 1590, Dr.LoriLeslie andDr.Michael Koropsac), while CLL treatment did not seem to have a consistent impact across cohorts. Another study looked at 89 evaluable BCL patients with COVID, with the goal of determining the impact of immunosuppression due to the lymphoma itself and/or therapies received.Survival was poor in lymphoma patients with hypertension, diabetes, or age 70 years. Interestingly, the rate of seropositivity (i.e., developing antibodies to COVID) in patients treated with monoclonal CD20 antibody therapy was significantly lower (12.5% vs 55%). Patients exposed to anti-CD20 therapy also required significantly more days to clear viral shedding (median 56 days vs 14 days). Such patientsmight be candidates for plasma therapy to help control virus expansion and induce its clearance(Abstract 2553; Dr. AndrewIp and Dr. TatanyaFeldman).

The full set of ASH data presentations by JTCC researchers is as follows:

Abstract #

Type

Title of Abstract

Authors

Presenting (PST)

48

Oral

Outcome By Mutation Status and Line of Treatment in Optic, a Dose-Ranging Study of 3 Starting Doses of Ponatinib in Patients with CP-CML

James K. McCloskey, MD

Saturday, December 5, 2020: 8:15 AM

130

Oral

Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes

David S. Siegel, MD

Saturday, December 5, 2020: 9:45 AM

131

Oral

Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401 Study

David S. Siegel, MD

Saturday, December 5, 2020: 10:00 AM

333

Oral

Efficacy and Safety of Venetoclax in Combination with Gilteritinib for Relapsed/RefractoryFLT3-Mutated Acute Myeloid Leukemia in the Expansion Cohort of a Phase 1b Study

James K. McCloskey, MD

Sunday, December 6, 2020: 10:15 AM

356

Oral

A Single-Arm, Open-Label Phase 1 Study of Itacitinib (ITA) with Calcineurin Inhibitor (CNI)Based Interventions for Prophylaxis of Graft-Versus-Host Disease (GVHD; GRAVITAS-119)

Scott D. Rowley, MD

Sunday, December 6, 2020: 10:15 AM

372

Oral

Clinical Outcomes Among Real-World Patients with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line Ibrutinib or Chemoimmunotherapy (CIT) Stratified By Risk Status: Results from a US Retrospective Chart Review Study

Lori A. Leslie, MD

Sunday, December 6, 2020: 10:00 AM

472

Oral

Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

Tatyana A. Feldman, MD

Sunday, December 6, 2020: 2:30 PM

476

Oral

Real World (RW) Outcomes and Prognostication of Older Patients with Primary Central Nervous System Lymphoma (PCNSL) in the Contemporary Era

Samuel Singer, MD,

Samuel Goldlust, MD

Sunday, December 6, 2020: 2:00 PM

646

Oral

Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies

Tatyana A. Feldman, MD

Monday, December 7, 2020: 12:00 PM

677

Oral

Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Stacey Rifkin-Zenenberg, DO

Monday, December 7, 2020: 1:30 PM

700

Oral

Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Lori A. Leslie, MD

Monday, December 7, 2020: 1:30 PM

703

Oral

Safety, Pharmacokinetics and Activity of CA-4948, an IRAK4 Inhibitor, for Treatment of Patients with Relapsed or Refractory Hematologic Malignancies: Results from the Phase 1 Study

Lori A. Leslie, MD

Monday, December 7, 2020: 2:15 PM

705

Oral

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John Theurer Cancer Center (JTCC) Researchers to Present 52 Abstracts across Hematological Malignancies at the 2020 American Society of Hematology...