Category Archives: Molecular Medicine

The United States is purchasing an additional10 million courses of Pfizer's COVID-19 treatment Paxlovid, the company said Tuesday, bringing the total U.S. order to 20 million.

The move comes as the Biden administration seeks to ramp up the treatments available as another tool to battle the virus.

Pfizer also said Tuesday that the delivery of the first 10 million courses has been accelerated to June, with the following 10 million coming by September.

Experts have been pushing the White House to do more to ramp up production of the treatment given that it can play a major role in defanging the virus, but it is expected to be in shortage in the near term.

The White House previously said that just 265,000 courses of the treatment would be available in January, amid a major surge of COVID-19.

Officials have pointed to a complex manufacturing process as posing hurdles to getting doses sooner.

"Its still way too small and too late to meet the anticipated needs," Eric Topol, professor of molecular medicine at Scripps Research, wrote in an email after the announcement of the new order.

President BidenJoe BidenTrump blasts 'low-life Twitter' after Greene's account suspended Jill Biden to visit Kentucky to see tornado damage On The Money Biden's beef with the meat industry MORE is set to give remarks on the omicron variant and the latest in the response to the surge later Tuesday afternoon.

Pfizer did not give a price for the latest order of its treatment. The U.S. paid$5.295 billion for the original 10 million courses.

Trials showed that the pill is highly effective, reducing the risk of hospitalization or death by 89 percent in high-risk patients. It is intended to be taken within five days of the onset of symptoms.

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US orders another 10 million courses of Pfizer COVID-19 treatment | TheHill - The Hill

Irvine, Calif., Jan. 4, 2022 For the first time, University of California, Irvine researchers in collaboration with the Max-Planck Institute of Biochemistry have revealed at a molecular level, key structural determinants of the highly specialized rod outer segment (ROS) membrane architecture of the eye, which is instrumental to vision.

Published in eLife, the study, titled Determinants shaping the nanoscale architecture of the mouse rod outer segment, provides an understanding of the mechanisms underlying the pathologies of certain gene mutations. These mutations, found within genes encoding the key structural proteins in the ROS membrane, have been shown to lead to blindness.

Our findings indicate that these gene mutations could impede or completely prevent disk morphogenesis which, in turn, would disrupt the structural integrity of ROS, compromise the viability of the retina and ultimately lead to blindness, said Krzysztof Palczewski, Ph.D., Donald Bren Professor of Ophthalmology at the UCI School of Medicine and corresponding author. This study gives us insight into how the viability of the retina is compromised by diseases, like retinitis pigmentosa and Stargardt disease, that affect structural proteins including peripherin of ABCA4. Armedwith this data, we can now target new therapeutic approaches aimed at treating or potentially curing blindness.

The highly ordered ultrastructure of ROS was described more than five years ago, however its organization on the molecular level remained poorly understood, until now. Utilizing cryo-electron tomography (cryo-ET) and a new sample preparation method, the UCI-led team was able to obtain molecular resolution images of ROS.

Cryo-ET enabled us to image rim disc structures and to quantitatively assess the connectors between disks revealing the molecular landscape in ROS, including connectors between ROS disk membranes, explained Palczewski. With this information, we are able to address open questions regarding the close disk stacking and the high membrane curvature at disk rims, which are specialized and essential structural characteristics of ROS.

Ongoing research, including studies involving humans, is necessary to test these new findings. However, preliminary indications are that new therapeutic approaches will most likely involve gene editing technologies, rather than gene augmentation or pharmacological interventions.

This research was supported by grants from the CIFAR program Molecular Architecture of Life, the National Institutes of Health and the Research to Prevent Blindness organization.

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and masters students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and masters degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/masters in public health, or an MD/masters degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

About the University of California, Irvine:Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities and is ranked among the nations top 10 public universities byU.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys largest employer, contributing $7 billion annually to the local economy and $8 billion statewide.For more on UCI, visitwww.uci.edu.

About the UCIs Brilliant Future campaign:Publicly launched on October 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UCI. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UCI seeks to reach new heights of excellence instudent success,health and wellness, research and more. TheSchool of Medicine plays a vital role in the success of the campaign. Learn more by visitinghttps://brilliantfuture.uci.edu/uci-school-of-medicine/.

Media access:Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visitwp.communications.uci.edu. Additional resources for journalists may be found atcommunications.uci.edu/for-journalists.

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UCI researchers reveal molecular mechanisms underlying mutations within the eye that lead to blindness - UCI News

SOUTH SAN FRANCISCO, Calif., Jan. 4, 2022 /PRNewswire/ -- Molecular Stethoscope, a leading Precision Medicine biotechnology company pioneering the next-generation cf-mRNA Liquid Biopsy, announced today that it has joined Verily Life Sciences ("Verily") partnered laboratory ecosystem in South San Francisco and appointed Gajus Worthington to its Board of Directors. The Company is now positioned to accelerate the translation of its proprietary cf-mRNA Liquid Biopsy Technology Platform to develop products and services for Precision Medicine clinical practice and biopharma R&D.

Circulating cell-free RNA in the blood provides a window into patient health, phenotype and developmental programs of a variety of human organs.

"We are excited and energized to establish our new corporate headquarters and expand our R&D laboratories in South San Francisco, which positions us to attract and retain the best talent, grow our clinical and academic collaborations, expand our commercial partnerships, and drive the development of our clinical-grade cf-mRNA liquid biopsy pipeline infrastructure to support our roadmap of products and services," stated Guillermo Elias, Ph.D., Chief Executive Officer at Molecular Stethoscope. "This new phase of our growth in Silicon Valley will significantly build upon our foundational cell-free RNA biology research and development work in San Diego and will leverage our recently completed and published human proof-of-concept studies in transplant oncology, Alzheimer's and liver disease" added Dr. Elias, CEO.

Molecular Stethoscope also announced the appointment of Gajus Worthington as Executive Chairman of its Board of Directors. "I've been a fan of Molecular Stethoscope's cf-mRNA technology for years," said Gajus. "I believe this company is positioned to lead the next generation of liquid biopsy development, and I'm very excited to be part of it."

"We are delighted to welcome Gajus to our company. I have known Gajus for many years and admire his passion for translating cutting-edge technologies into game-changing products and building successful companies. Gajus brings a wealth of significant leadership experience to our Board of Directors to guide and support the continued growth of our enterprise," commented Dr. Elias, CEO.

Story continues

Mr. Worthington has been Chief Operating Officer of the Chan Zuckerberg Biohub (CZ Biohub) since May of 2017, where he has worked with the CZ Biohub leadership to set strategy, build and oversee much of the organization. Prior to the CZ Biohub, Mr. Worthington served as Chief Executive Officer of Fluidigm Corporation (NASDAQ:FLDM), a company he co-founded. During his 17-year tenure at Fluidigm, he led the development and commercialization of Fluidigm's pioneering microfluidics technology with applications in single-cell genomics, agriculture, and diagnostic testing and raised over $500M in private and public funding. Mr. Worthington earned a Bachelor's degree in physics and a Master's degree in electrical engineering from Stanford University. He is an elected fellow of the American Institute for Medical and Biological Engineering.

About Molecular Stethoscope

Molecular Stethoscope is a Precision Medicine biotechnology company pioneering a Next-Generation cf-mRNA Liquid Biopsy AI/ML Technology Platform. The Company is focused on discovering, developing and commercializing non-invasive and dynamic products for the early detection, diagnosis and treatment-response monitoring of chronic diseases starting with the liver (NAFLD/NASH) and the central nervous system (Alzheimer's Disease and Multiple Sclerosis). Molecular Stethoscope was co-founded by Dr. Stephen Quake, Professor of Bioengineering at Stanford University, and co-President of the Chan Zuckerberg Biohub, and Dr. Eric Topol, Director and Founder, Scripps Research Translational Institute, and Chair of Innovative Medicine at Scripps. The Company's proprietary Next-Generation cf-mRNA Liquid Biopsy Technology Platform integrates cell-free mRNA (cf-mRNA) with RNA-Seq, clinical information, and purpose-built bioinformatics, machine learning and artificial intelligence to generate clinically actionable, dynamic information to significantly improve the health of patients. The Company's novel Technology Platform harnesses with unprecedented precision the dynamic information from biological processes underlying chronic diseases in biopsy-accessible (e.g., liver) and biopsy-inaccessible (e.g., brain) organ systems, thus enabling early, non-invasive, longitudinal and serial diagnosis and monitoring of diseases - while avoiding costly and invasive biopsies which can have adverse effects - to fundamentally change how healthcare is delivered at scale.

Forward Looking Statement

This press release contains forward-looking statements including, but not limited to statements about the Company's expectations regarding its proprietary Technology Platform. Forward looking statements are subject to uncertainties that could cause actual performance or results to differ materially from those expressed in the forward-looking statements.

Additional information and inquiries

Investor Relations: investorrelations@molecularstethoscope.com

Public and Media Relations: publicrelations@molecularstethoscope.com

SOURCE Molecular Stethoscope, Inc.

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Molecular Stethoscope, Inc. establishes new Corporate Headquarters and Research & Development Laboratories in South San Francisco and appoints...

Welcome toTuesdaysOvernight Health Care, where were following the latest moves on policy and news affecting your health.Subscribe here:thehill.com/newsletter-signup.

An untreated,frozenroad trappedriversovernight on I-95in Virginia, including Sen.Tim KaineTimothy (Tim) Michael KaineSchumer vows Senate rules change vote by Jan. 17 if GOP blocks voting rights Democratsreturn with lengthy to-do list Biden, lawmakers mourn Harry Reid MORE(D-Va.), who arrived at the Capitol nearly 27 hours after he left home.

President BidenJoe BidenTrump blasts 'low-life Twitter' after Greene's account suspended Jill Biden to visit Kentucky to see tornado damage On The Money Biden's beef with the meat industry MORE addressed the nation on Tuesday attemptingto alleviate concerns about the omicron variant ascases have spiked nationwide.

For The Hill, were Peter Sullivan (psullivan@thehill.com), Nathaniel Weixel (nweixel@thehill.com)andJustine Coleman (jcoleman@thehill.com). Write to us with tips and feedback, and follow us on Twitter:@PeterSullivan4,@NateWeixeland@JustineColeman8.

Lets get started.

Bideneases omicron alarm, urges vaccinations

President Bidenon Tuesday sought to tamp down worries about the omicron coronavirus variant, underscoring that COVID-19 vaccines protect against severe illness from the virus.

Speaking before a briefing with his COVID-19 advisers at the White House, Biden said that the U.S. has the tools to protect Americans from severe illness from the virus.

If you are vaccinated and boosted you are highly protected, Biden said Tuesday, noting that those who are vaccinated can still contract COVID-19 but are unlikely to become seriously ill.

Be concerned about omicron but dont be alarmed. But if youre unvaccinated, you have some reason to be alarmed, he said.

Read more here.

A MESSAGE FROM ASTRAZENECA AND FRIENDS OF CANCER RESEARCH

The Battle Against Cancer: Setting the Next Agenda

To mark 50 years since the passage of the National Cancer Act of 1971, a select group of thought leaders working at the intersection of public health and oncology participated in a roundtable discussion, hosted by The Hill in partnership with Friends of Cancer Research and AstraZenecas YOUR Cancer Program, on expanding access to oncology precision medicine. Learn more.

RELATED: BIDEN ALSO CALLED FOR SCHOOLS TO STAY OPEN

President Bidenon Tuesday reiterated his belief that schools in the United States should remain physically open despite the wave of coronavirus cases driven largely by the omicron variant.

Biden noted during remarks at the White House that his $1.9 trillion coronavirus relief plan included billions of dollars to help support schoolreopeningsduring the coronavirus pandemic.

We have no reason to think at this point that omicron is worse for children than previous variants. We know that our kids can be safe when in school by the way. Thats why I believe schools should remain open. They have what they need, Biden said before a briefing with his COVID-19 response team.

Political issue:Republicans have tried to make schoolreopeningsa political issue, arguing that Democrats are siding withteachersunions and support closing schools during the pandemic.

Some schools have decided to revert to remote learning for periods of time as cases surge around the country, including districts in Wisconsin, Michigan and Ohio.

Read more here.

More Pfizer pills on the way...but is it enough?

The United States is purchasing an additional10 million courses of Pfizer's COVID-19 treatmentPaxlovid, the company said Tuesday, bringing the total U.S. order to 20 million.

The move comes as the Biden administration seeks to ramp up the treatments available as another tool to battle the virus.

Pfizer also said Tuesday that the delivery of the first 10 million courses has been accelerated to June, with the following 10 million coming by September.

Calls formore: Experts have been pushing the White House to do more to ramp up production of the treatment given that it can play a major role in defanging the virus, but it is expected to be in shortage in the near term.

The White House previously said that just 265,000 courses of the treatment would be available in January, amid a major surge of COVID-19.

Officials have pointed to a complex manufacturing process as posing hurdles to getting doses sooner.

"Its still way too small and too late to meet the anticipated needs," Eric Topol, professor of molecular medicine at Scripps Research, wrote in an email after the announcement of the new order.

Read more here.

CDC: Omicron now 95 percent of all cases

The new data shows how quicklythe highly transmissible variant has taken over, displacing the previously dominant delta variant.Just two weeks earlier, in the week ending Dec. 18, omicron accounted for only 38 percent of U.S.cases, the CDC said.

The omicron variant has fueled a massive spike in cases, to over 400,000 per day nationwide, but there is mounting evidence that the variant, on average, causes less severe disease than previous variants.

Key is hospitalizations:Still, while most people will have mild cases, even a smallpercentagegetting hospitalized poses a risk to the hospital system given the massive numberof total infections.

About 100,000 people are hospitalized with COVID-19,according to a New York Times tracker, aboutthe same asthe peak from the deltawave over the summer, and the number is climbing quickly.

The CDClast monthsignificantlyrevised down its estimatesfor omicron's prevalence. But the range of the latest estimate is smaller, indicating a higher level of confidence.

Read more here.

CDC RECOMMENDS PFIZER RECIPIENTS GET BOOSTER AFTER 5 MONTHS

The Centers for Disease Control and Prevention (CDC) recommended on Tuesday that Pfizer-BioNTech COVID-19 vaccine recipients get a booster dose five months after their second shot instead of the previously approved six months.

The agency endorsed the shorter period after the Food and Drug Administration (FDA) authorized the reduced timeline on Monday for those who received the Pfizer-BioNTech vaccine.

The CDC also suggested moderately and severely immunocompromised 5- to 11-year-olds get an additional dose about a month after their second shot, aligning their recommendations for the age group with immunocompromised adults.

The CDCs advisory panel is slated to meet Wednesday to discuss whether to recommend boosters for 12- to 15-year-olds after the FDA expanded access to the extra doses among young teens.

For other vaccines:The CDC still suggests that Johnson & Johnson and Moderna recipients receive their boosters two months and six months, respectively, after completing the primary series.

Read more here.

WHAT WERE READING

A MESSAGE FROM ASTRAZENECA AND FRIENDS OF CANCER RESEARCH

The Battle Against Cancer: Setting the Next Agenda

To mark 50 years since the passage of the National Cancer Act of 1971, a select group of thought leaders working at the intersection of public health and oncology participated in a roundtable discussion, hosted by The Hill in partnership with Friends of Cancer Research and AstraZenecas YOUR Cancer Program, on expanding access to oncology precision medicine. Learn more.

STATE BY STATE

OP-EDS IN THE HILL

That's it for today, thanks for reading. Check out The Hill's healthcarepage for the latest news and coverage. See you tomorrow.

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Overnight Health Care Presented by AstraZeneca and Friends of Cancer Research Biden seeks to alleviate omicron concerns | TheHill - The Hill

An at-home COVID-19 testing method that is spreading like wildfire on social media claims that people should swab their throat instead of their nose in order to get a more accurate test result.NewsCenter 5 interviewed three different doctors about the throat swab method, and each of them said at-home COVID-19 tests were developed, studied and approved by the U.S. Food and Drug Administration to be used a certain way by swabbing the nose."I think any recommendation to swab your throat would be premature, and I think it's important to follow the directions on the tests as they are written," said Dr. Helen Boucher, an infectious disease specialist at Tufts Medical Center and the interim dean of the Tufts University School of Medicine."Right now, these kinds of reports are just that just reports and rumors that are kind of going around," said Dr. Nate Hafer, an assistant professor of molecular medicine at UMass Chan Medical School. "We don't have any hard data yet showing that swabbing the throat versus the nasal area is any better.""People are not going to like it. It's probably going to cause a little bit of a gag reflex," said Dr. Brian Cruz, regional director for PhysicianOne Urgent Care.More at-home COVID-19 test FAQsWhen it comes to efficacy, Boucher said she is not aware of any data that suggests any brands of authorized, at-home COVID-19 test perform better than others."I think, really, the best thing to do is to use the test that you have available," Boucher said. "Most of them have very good directions with diagrams to help you. So using them as directed is another layer of protection that can be added to the other measures that we have."In order to ensure that negative results from at-home COVID-19 tests are accurate, Cruz recommends that people who are asymptomatic test multiple times over multiple days."To do serial testing is more beneficial to try to pick up the virus than just one test and think: 'Hey, I'm OK to go,'" Cruz said.At-home COVID-19 test kits, however, can be expensive. According to the Internal Revenue Service, those kits can be paid for or reimbursed with a health savings account.

An at-home COVID-19 testing method that is spreading like wildfire on social media claims that people should swab their throat instead of their nose in order to get a more accurate test result.

NewsCenter 5 interviewed three different doctors about the throat swab method, and each of them said at-home COVID-19 tests were developed, studied and approved by the U.S. Food and Drug Administration to be used a certain way by swabbing the nose.

"I think any recommendation to swab your throat would be premature, and I think it's important to follow the directions on the tests as they are written," said Dr. Helen Boucher, an infectious disease specialist at Tufts Medical Center and the interim dean of the Tufts University School of Medicine.

"Right now, these kinds of reports are just that just reports and rumors that are kind of going around," said Dr. Nate Hafer, an assistant professor of molecular medicine at UMass Chan Medical School. "We don't have any hard data yet showing that swabbing the throat versus the nasal area is any better."

"People are not going to like it. It's probably going to cause a little bit of a gag reflex," said Dr. Brian Cruz, regional director for PhysicianOne Urgent Care.

When it comes to efficacy, Boucher said she is not aware of any data that suggests any brands of authorized, at-home COVID-19 test perform better than others.

"I think, really, the best thing to do is to use the test that you have available," Boucher said. "Most of them have very good directions with diagrams to help you. So using them as directed is another layer of protection that can be added to the other measures that we have."

In order to ensure that negative results from at-home COVID-19 tests are accurate, Cruz recommends that people who are asymptomatic test multiple times over multiple days.

"To do serial testing is more beneficial to try to pick up the virus than just one test and think: 'Hey, I'm OK to go,'" Cruz said.

At-home COVID-19 test kits, however, can be expensive. According to the Internal Revenue Service, those kits can be paid for or reimbursed with a health savings account.

Read more:
Is throat swab more effective? Massachusetts doctors weigh in on at-home COVID-19 testing method - WCVB Boston

image:E. Sally Ward, Ph.D., at UT Southwestern in 2004 view more

Credit: UT Southwestern Medical Center

A first-in-kind immune-modulating drug that arose from decades of basic research at UTSouthwestern Medical Center has received approval from the U.S. Food and Drug Administration as a new treatment for adults with a form of myasthenia gravis. This rare and chronic autoimmune disease is characterized by debilitating and potentially life-threatening muscle weakness.

The new drug, efgartigimod alfa-fcab, is an engineered fragment of a human antibody that binds to a cell surface receptor known as the neonatal Fc receptor, or FcRn. Between 1990 and 2015, former UTSW Professor ofImmunologyE. Sally Ward, Ph.D., led work that characterized this receptors role in regulating the levels and persistence of immunoglobulin G (IgG) antibodies. In 2005, her laboratory described an approach to lower antibody levels by blocking FcRn activity, and subsequently demonstrated preclinical proof-of-concept to treat antibody-mediated autoimmune disease. The global immunology company argenx has licensed exclusive patent rights related to this drug from UTSW.

The development of this FcRn inhibitor came out of the fundamental work on FcRn biology that my group had worked on during the decades that I was on the UTSW faculty, said Dr. Ward, now a Professor of Molecular Immunology and Director of Translational Immunology at the University of Southampton in England. Working out the molecular and cell biological processes involved in FcRn biology and its regulation and transport of antibody molecules was a major focus of our work at UTSW over more than two decades, starting when I was an assistant professor there.

Clinical trials that led to the recent FDA approval found that 68% percent of patients with anti-acetylcholine receptor antibody positive myasthenia gravis responded to efgartigimod, compared to 30% of those taking a placebo. The company is exploring possible uses for the agent in other conditions mediated by IgG.

Efgartigimod represents Dr. Wards second commercial success based on fundamental research conducted at UTSW. That work also led to technology that can extend the half-life of therapeutic antibodies and currently is used in the FDA-approved drug ravulizumab and two antibody therapies against COVID-19, as well as another antibody in development to treat respiratory syncytial virus (RSV).

It is also the second first-in-kind drug developed from basic research at UTSW to be approved by the FDA in the past year. Less than six months ago, belzutifan, aHIF-2 inhibitor, received approval as a treatment for familial kidney cancer.

Considered together, these approvals mark UTSW as one of the major sources of breakthrough medicines for previously untreatable diseases. We are indeed a center for biotechnology, saidMichael Brown, M.D., Professor of Molecular Genetics and Internal Medicine and joint recipient of the 1985 Nobel Prize in Physiology or Medicine with research partner UTSW colleagueJoseph Goldstein, M.D.Dr. Brown helped recruit Dr. Ward to UTSW in 1990.

UTSouthwestern receives financial compensation from argenx for the newly approved drugs foundational intellectual property. Dr. Ward also receives compensation related to the licensing of the technology and research funding from the company.

Both Drs. Goldstein and Brown are Regental Professors.

Dr. Brown holds The W. A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research and the Paul J. Thomas Chair in Medicine.

Dr. Goldstein holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research and the Paul J. Thomas Chair in Medicine.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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More than two decades of UTSW research paves way for first-in-kind drug - EurekAlert

Responses among those treated with Brutons tyrosine kinase (BTK) inhibitors differ across subtypes of diffuse large B-cell lymphoma (DLBCL), according to Mark Roschewski, MD.

Although the combination of ibrutinib (Imbruvica) and rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) does improve survival in patients, the benefit is limited by the toxicity of the regimen. Similarly, acalabrutinib (Calquence) has activity in DLBCL, according to research.

However, what remains unknown is how patients with DLBCL who have varying molecular profiles will respond to the therapy. Investigators sought to provide a better understanding of acalabrutinib treatment for DLBCL by administering the agent 14 days before frontline therapy.

In a recent study, a total of 34 patients were enrolled, and complete responses (CRs) to acalabrutinib were observed in 27. Two patients relapsed after the achievement of a CR. The estimated progression-free survival rate observed after a median follow-up of 9.2 months was 84.9% (95% CI, 58-95). Fifty percent and 35% of patients, respectively, experienced grade 3 or 4 neutropenia. Grade 3 thrombocytopenia occurred in 22%, and the events were grade 4 for 12% of patients. There were no increases in infections, atrial fibrillation, or bleeding in the patients treated with acalabrutinib in the study.

In an interview with Targeted Oncology, Roschewski, senior clinician, Lymphoid Malignancies Branch, Center of Cancer Research, National Cancer Institute, discussed precision medicine in DLBCL and using acalabrutinib in a pre-chemotherapy window to better understand its potential benefit.

TARGETED ONCOLOGY: Can you explain the differences between the DLBCL subtypes?

Roschewski: During ASH 2021, we talked a little bit about precision medicine and large B-cell lymphoma. What we know is that our preclinical models suggest that there are certain subtypes of large cell lymphoma that will preferentially respond to targeted agents. We've seen that in clinical studies, most of those clinical studies have been in the relapse setting. And so those are slightly different patient populations. In the untreated patient population. We do have randomized studies that don't show much difference with the use of targeted agents. But recently, our group did show that there were specific genetic subtypes of diffuse large B cell lymphoma that seem and in younger patients that seemed to have a benefit when a Bruton it was added to our job. So, we don't know yet enough about the individual response to targeted agents within subtypes of lymphoma.

What efficacy and safety findings have been reported so far with the combination of ibrutinib and R-CHOP in DLBCL?

In untreated large B-cell lymphoma, the most important study has been a randomized study known as the PHOENIX trial. The primary end point of that study was negative, meaning we could not see a benefit of ibrutinib with our R-CHOP across diffuse large B-cell lymphoma. But what was very interesting is that younger patients under 16 did seem to have a benefit, according to a subgroup analysis. More recently, our group published that there were 2 genetic subtypes of large B-cell lymphoma in that younger patient population, these are known as N1 and MCD that did seem to have a benefit. So, 1 of the problems we have is the heterogeneity of large cell lymphoma. But at this point, it's unclear who should get those medicines just because the data isn't sufficient.

What makes acalabrutinib a good treatment candidate for certain DLBCL subgroups?

The BTK inhibitors do seem like they have a role and they work very quickly. There are many patients that benefit from them, which we can see in the relapse setting. Acalabrutinib is very similar to ibrutinib, but it has more specificity. So, it binds to te similar epitope of the receptor. But it gets higher concentrations because it's given twice a day. So, the BTK occupancy is higher. Because of that selectivity, there is this theoretical benefit that it will have fewer off-target effects. So that will limit potentially some of the toxicity that is seen, and there is some evidence that that's true.

What were the key goals of your phase 2 study of acalabrutinib prior to frontline therapy in untreated patients with aggressive b-cell lymphoma?

It is important understand that we have a very unique study design. So, since we're interested in understanding, primarily, the role of the calibrated what we did was we implemented a window design. What happens is we first give the acalabrutinib by itself to all comers for up to 14 days. Because the medicine works very quickly, when patients benefit from it, we can see reductions in tumors very fast. The main focus in research is what are the types of patients that benefit from this acalabrutinib and we're going to be doing molecular profiling of these tumors, and we're going to be comparing tumors that respond to acalabrutinib of compared to those that don't. So, that's the primary goal.

Now, from a clinical perspective, what happens is, if we see a response, and we define that as only a 25% reduction, so that's less than we might think about in conventional response criteria. But if there's only a 20%, at least a 25% reduction, then we take that to mean the tumor is at least somewhat responsive to acalabrutinib, and then they get that acalabrutinib with their chemotherapy. But if there is no response in the window, then they get treated with chemotherapy alone. So, it also has a response adaptive design, and in that way, we can justify giving acalabrutinib to patients because we know they have a benefit, and we don't have to take the risk of the toxicity in patients that we don't see any benefit in the window.

Can you discuss the results you recently presented during the ASH Annual Meeting?

This was an interim analysis, and overall, we're going to enroll up to 100 patients. So far, we've enrolled 40. What we've seen so far is that in the 39 patients that have completed the window, 18 of them have responded to acalabrutinib, while 21 have not. So, it's about half and half. Then, we will look very closely at the genetic profile of these tumors both by cell of origin, as well as Han's criteria, and genetic subtypes. Now, we take all subtypes of large cell lymphoma on this study, except for primary mediastinal B-cell lymphoma. So, we took an agnostic approach. In other words, a preceding hypothesis would be that the patients with ABC large cell lymphoma or non-GCB lymphoma would be the ones that are most likely to respond. But that's not what we've observed. So far, what we've seen is that our responders have been enriched for patients with GCB. And this has been confirmed by cell of origin testing by RNA sequencing.

Then we've also looked closely at the genetic subtype. As I mentioned, 1 of our preceding hypotheses would be that patients with MCD or N1 genetic subtypes would respond. But none of our responders have had those genetic subtypes. So, we do see that the responses to acalabrutinib are broader than we may have thought before this study.

Another important aspect of this study is we're interested in developing and understanding the role of circulating tumor DNA [ctDNA]. So, this is an analyte that may help us predict responses much quicker than imaging. In this 14-day window, we're actually sampling ctDNA every 7 days to see if early changes in ctDNA, we can predict response that we see on CT scan. So far, on the first patients that we've looked at, that's been very true, there's been a very tight correlation with how quickly the ctDNA goes down and CT scan response. What's really interesting is that we saw that we could predict CT response after 14 days, as early as only 7 days by ctDNA. So, it does suggest that changes or decreases are actually a sign that the patient is responding to the tumor. It's a pretty good correlation between that and kind of overall tumor burden. So, those are the main findings. And of course, our patients have done very well. The safety has been good on this study. We've only had a few events, and our survival right now is over 90%. So, I think it looks in a randomized way and uncontrolled way that our patients are benefiting.

In your opinion, what would a randomized phase 3 study for this strategy look like?

I think we have a little bit more to learn. One of the focuses, of course, is to try to home in very tightly on which patients benefit from acalabrutinib. If we can identify a group of patients that do not benefit from acalabrutinib, we could design a study where we just don't enroll those patients, so we don't take the risk of acalabrutinib in those patients. So, both of those are key objectives. And so, I think what we're focused on here is who's the right patient population.

So, if we had the ideal patient population if we knew how to identify them, and then we would only enroll those patients and then do a randomized study, probably acalabrutinib or not with conventional chemotherapy that would be one way to go. Now the ctDNA adds in a whole other aspect. The question then becomes, can we do a different type of randomized study where we're looking at responses early on with ctDNA to be the reason to randomize from there? So that's another potential study. I think we're already discussing these types of options, but it's a little early to know for sure, just because our data aren't quite mature enough. But we're starting to get a signal for the right way to move forward.

How would you explain the importance of doing gene expression profiling for these patients?

It's important to recognize that gene expression profiling is distinguishing that these are truly different tumors. So, we have to have an understanding of the underlying molecular biology of these tumors. Now, does that currently help us in the clinic select which treatment to use? No, not yet. Part of the reason it doesn't is that the story is much more complex than just gene expression profiling. So, we've been interested in this question for a long time. And the most recent papers we've done show us that these genetic subtypes sort of cross over with the gene expression profiling subgroups. There are also some tight correlations, and there are some that aren't. So, I do think it's really important with therapy, particularly new therapies to know which groups of patients benefit the most, so they can be prioritized. We have all these targeted agents and immunotherapy agents. The disease is so heterogeneous, that if we don't have a nuanced understanding of which patients benefit, then we're going to be guessing in the clinic, or we're going to be relegated to only answering important questions with randomized studies. Now, randomized studies are important. But we also have to have a better understanding of how we approach individual patients. It takes a long time to get there. But I think every study that tests new agents should be also reporting how it responds within these subgroups of patients and genetic subtypes. I think that's the future.

Reference:

Roschewski M, Phelan JD, Pittaluga S, et al.Phase 2 study of acalabrutinib window prior to frontline therapy in untreated aggressive b-cell lymphoma: preliminary results and correlatives of response to acalabrutinib. Presented 2021 American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 524.

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Determining the Molecular Profile of BTK Inhibitor Responsive DLBCL Tumors - Targeted Oncology

A global proteomics approach to study the influence of COVID-19 on host signaling pathways. One resource to bring all the structural databases together. A new way to automate and optimize proteinprotein studies. Read about papers on these topics recently published in the journal Molecular & Cellular Proteomics.

NIAID-RML

This scanning electron microscope image shows SARS-CoV-2 (round blue objects)emerging from the surface of cells cultured in the lab. SARS-CoV-2 is the virus thatcauses COVID-19.

COVID-19 has taken over the world as the largest global pandemic of our time. While the inflammatory implications of SARS-CoV-2 have been well studied, researchers do not yet understand the effect of the virus on signaling pathways. This is crucial, since COVID-19 manifests in severities ranging from asymptomatic infection to multiorgan failure. Immune response to a viral antigen is wide-ranging, from an interferon-mediated antiviral response to downstream events that activate transcription factors. This eventually leads to an inhibition of replication, transcription and translation of the viral genome, followed by its degradation and recruitment of immune cells.

In a recent study in the journal Molecular & Cellular Proteomics, Patrick M.Vanderboom and colleagues at the Mayo Clinic compared SARS-CoV-2 negative and positive patient samples to analyze molecular features of the host response. A global proteomics approach was used to characterize the influence of this infection, and samples were obtained from the nasopharynx due to the proximity to the lungs, where this COVID-19 most often progresses to severity.

When they subjected these samples to mass spectrometry, the researchers found 7,582 proteins, of which 143 were upregulated and 80 were downregulated in patients who had COVID-19. The upregulated proteins were involved mostly in interferon signaling. In particular, the authors monitored two specific molecules, RIG-1 and STAT1, involved in interferon signaling and found that the levels of these proteins correlate with viral loads.

The authors state that while these studies provide definitive information about the signaling pathways that are affected by SARS-CoV-2 infections, they will need to do more research to understand completely the pathogenesis of the virus and its potential outcomes in individual patients.

A popular technique used to validate direct interactions in protein complexes is cross-linking mass spectrometry, or XL-MS, which typically will detect linked residues while integrating these networks with structural techniques to generate accurate models of high-level molecular processes. XL-MS can overcome ambiguity in modest-resolution cryo-EM density maps and add more information to extrapolate X-ray maps into more accurate models.

In a recent paper in the journal Molecular & Cellular Proteomics, Daniel S. Ziemianowicz and colleagues at the University of California, San Francisco, and the University of Calgary, Canada, describe a new tool known as IMProv that can integrate cryo-EM densities, existing structures and cross-linking data. This addresses the effect of underlying protein dynamics on cross-linking. To use this resource, a user provides the sequence information for each protein building block and available partial or homologous structures. IMProv generates models using four steps: building a Python modeling interface, creating corresponding directories, using a SLURM bash script to model on a high-performance cluster and combining all of the above to generate the final model.

The authors show how IMProv could fill some gaps in the current model of the polycomb repressive complex 2. Overall, this resource will serve as an effective tool to develop existing data repositories and enable the use of cross-linking data to interpret and model structural data with greater precision.

When protein interactions occur in intrinsically disordered regions, its often through short linear motifs, known as SLiMs, which are both tedious and challenging to study. Researchers must incubate individual peptide spots with the protein extract on a cellulose membrane and then retrieve them for further analysis. This time-consuming procedure limits the number of samples that can be analyzed at a time.

To overcome these shortcomings, Evelyn Ramberger, Lorena SuarezArtiles, Daniel PerezHernandez and colleagues at Max Delbrck Center for Molecular Medicine in the Helmholtz Association, Germany, have developed an optimized method for using protein interaction screen on a peptide matrix, or PRISMA, in combination with quantitative mass spectrometry.

PRISMA is a new way to study point mutations and post-translational modifications within protein interaction motifs and to map these motifs.

In a recent paper in the journal Molecular & Cellular Proteomics, the authors write that PRISMA can be automated and allow the detection of phosphorylation-dependent interactors of certain proteins or mutation-dependent interactions of certain peptides. The authors propose that the transfer of this method from manual low-throughput procedures to an automated, microwell format with a high-throughput output retrieval will enable researchers to use PRISMA to explore disordered protein functions more efficiently. This method could contribute to deciphering the protein networks dependent on these short motifs that are involved in signaling processes and diseases.

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From the journals: MCP - American Society for Biochemistry and Molecular Biology

SILICON VALLEY, Calif., Jan. 4, 2022 /PRNewswire/ -- Predicine, a global molecular insights company, announced today that it has appointed Dennis Merkle, PhD, MBA, as its new Chief Executive Officer (CEO) for Predicine Europe as well as its Global Head of Biopharma Business. Dr. Merkle moves into the role after leading the oncology development strategy, alliance management and biorepository teams at Invitae, which he joined as part of the acquisition of ArcherDx, where he was Senior Vice President of corporate development.

Dr. Dennis Merkle

Known for his strategic leadership across commercial and R&D organizations, Dr. Merkle has extensive experience building high performing teams and novel functions in both the biopharma and in vitro diagnostic (IVD) industries. Based in Germany, Dr. Merkle's primary role will be to build, scale and manage Predicine's European business strategy, operations, and organization, while growing, synergizing and strengthening its partnerships with biopharma clients globally.

Dr. Merkle has over 20 years' experience in cancer biology, molecular and companion diagnostics and drug development. Prior to joining ArcherDx and Invitae, Dr. Merkle built and lead the global companion diagnostics group at Merck KGaA, leading to that organization's first ever drug-companion diagnostic co-approvals. Dr. Merkle has also held senior positions in marketing and R&D at Merck KGaA, Abbott Laboratories and Philips building extensive experience in the development and launch of novel drug and diagnostic products, as well as the lifecycle management and marketing of mature products.

"Predicine Europe is one step closer to our grand mission - to empower the global healthcare ecosystem through innovation. Dr. Merkle is an accomplished industrial leader with a proven track record of product development and launch in the diagnostics and biopharma space. In the last six years, Predicine has made significant progress in precision medicine in both the biopharma and patient testing businesses. We welcome strong leaders, such as Dr. Merkle, to drive our next-phase business growth in global oncology and infectious diseases." said Dr. Shidong Jia, Predicine's Founder and Global CEO.

Story continues

Dennis Merkle, new CEO of Predicine Europe, said:

"Predicine offers a best-in-class genomic platform that enables minimally-invasive diagnostics and molecular analysis for patients, healthcare providers and the biopharmaceutical industry. Through its unique portfolio of blood-, urine- and tissue-based diagnostic solutions, I am confident Predicine will be a market leader in precision medicine for years to come.

I am excited to be joining Predicine's world-class global team and establishing its European business operations, while also continuing to strengthen collaborations with our very important pharmaceutical partners. Complementing our presence in Silicon Valley, Tustin, Shanghai, Singapore, Houston and Boston, the European affiliate will make Predicine a truly global player in personalized healthcare. So, stay tuned for more announcements from this very important region!"

About Predicine

Predicine is a global molecular insights company that is committed to advancing precision medicine in oncology and infectious diseases. Predicine has developed a breakthrough cell-free DNA- and cell-free RNA-based liquid biopsy technology enabling minimally invasive molecular diagnosis for treatment selection, therapy monitoring, and minimal residual disease and early cancer detection. The company has launched a portfolio of blood-, urine- and tissue-based diagnostic assays for oncology and infectious diseases, including COVID-19. Through its business operations in Silicon Valley, Tustin, Houston, Shanghai, Singapore, Berlin and Boston, Predicine partners with leading biopharma companies, institutions and governments to support personalized healthcare on a global scale. Further information is available on the company's website, http://www.predicine.com. Stay in touch on LinkedIn or @Predicine on Twitter.

Contact Information:

Sushmasri TakkilapatiPredicine Inc.(857) 756-3469 326820@email4pr.com

Cision

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SOURCE Predicine Inc

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Predicine Appoints Dr. Dennis Merkle as Chief Executive Officer of Predicine Europe and Global Head of Biopharma Business - Yahoo Finance

Goodbye, 2021. We wont focus on the way you left us dealing with a new COVID-19 variant anduncertain about the future. No, we at Washington University in St. Louis will focus on the good bold new discoveries, hopeful new students and a promising new direction for the university.

Here, the Source shares some of the years most-read stories that highlight the great strides of the WashU community.

Supporting students; expanding opportunities

With an unprecedented endowment return of 65%, Washington University made a bold $1 billion investment in student success. The initiative, which the university is calling Gateway to Success, includes a $800 million in endowed funding to support need-blind undergraduate admissions long a top goal for the university. As a need-blind institution, the university will not consider an applicants financial situation when making admissions decisions while still meeting 100% of demonstrated financial need for admitted undergraduates. An additional $200 million will be designated for financial aid for graduate and professional students in the Brown School, the School of Law and the School of Medicine, as well as in business, engineering, art and architecture, and Arts & Sciences.

Since I became chancellor nearly two years ago, becoming need-blind has been a top priority. Building on the momentum that began with our previous administration, were finally making it happen, Chancellor Andrew D. Martin said upon announcing Gateway to Success in October. This is a proud moment for us as an institution and Im grateful to all who have contributed along the way, including generous donors who have provided scholarships and other financial support for our students.

The university also announced other major gifts to support students. Alumnus and emeritus trustee Arnold B. Zetcher and his wife, Ellen, made a commitment of at least $8 million in outright and estate gifts to establish an endowed scholarship for undergraduate students. Alumnus and emeritus trustee John Dains donated $8 million to support an undergraduate student success fund to help cover emergency and educational enrichment expenses. And P. Roy Vagelos, MD, founder of the Division of Biology & Biomedical Sciences (DBBS), and his wife, Diana Vagelos, made a $15 million gift to undergraduate programs and graduate student fellowships in the life sciences.

Studying COVID-19; seeking solutions

Washington University scientists committed 2021 to studying the deadly COVID-19 pandemic. Readers were especially intrigued by the following stories:

Research from Ziyad Al-Aly, MD, assistant professor of medicine, found that COVID-19 survivors including those not sick enough to be hospitalized have an increased risk of death in the six months following diagnosis with the virus.

Research published in August co-led by Ali Ellebedy, associate professor of pathology and immunology, of medicine and of molecular microbiology, found that the delta variant of the virus that causes COVID-19 is largely unable to evade antibodies elicited by vaccination.

Research from the lab of Ryan Bogdan, associate professor of psychological and brain sciences in Arts & Sciences, suggests cannabis use disorder (CUD) should be added to the list of COVID-19 risk factors because the genetic predisposition to CUD is overrepresented in people with poor COVID-19 outcomes.

And research from Jeannie Kelly, MD, assistant professor of obstetrics and gynecology, suggests nursing mothers who receive a COVID-19 vaccine may pass protective antibodies to their babies through breast milk for at least 80 days following vaccination.

Saying hello, bidding farewell to amazing students

During an exceptional admissions cycle, Undergraduate Admissions reviewed 33,634 applications a 20% increase from 2020. In August, 1,994 of those students moved onto the South 40, made new friends at the Bear Beginnings tailgate party and celebrated Convocation in Brookings Quadrangle. The Class of 2025 is the largest and most diverse in university history 17% are Pell Grant-eligible, 12% are the first in their families to attend college, 5% are international and 49% identify as students of color.

Washington University celebrated the Commencement of the Class of 2021 in its new home, Francis Olympic Field. Basketball legend and activist Kareem Abdul-Jabbar served as speaker. The Class of 2020 also was welcomed home for an in-person ceremony featuring Julie L. Gerberding, MD, the first woman to serve as director of the Centers for Disease Control and Prevention.

Among those who left their mark at Washington University are the School of Medicines graduating physicians; a Maryland man who graduated 67 years after he started his education at Washington University; and baseball Bears Caleb Durbin and Ryan Loutos, who signed deals with Major League Baseball teams Durbin as a 14th-round draft pick to the Atlanta Braves and Loutos as an undrafted free agent to the St. Louis Cardinals.

Digging for clues; overcoming obstacles

Despite the pandemic, Washington University researchers persisted in their research, making groundbreaking discoveries in archeology, medicine, engineering and other disciplines.

Two archeological studies especially fascinated readers. In one, Tristram T.R. Kidder, the Edward S. and Tedi Macias Professor of Anthropology in Arts & Sciences, found evidence that suggests Americas first civilization was made up of sophisticated engineers capable of building massive earthen structures in a matter of months possibly even weeks that withstood the test of time. In the other, Caitlin Rankin, who conducted her graduate studies at Washington University, found there is little evidence to support the prevailing theory that wood overuse led to the collapse of Cahokia, the pre-Columbian Native American city in present-day Illinois.

Other top stories include:

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2021 in review: New direction, new discoveries - The Source - Washington University in St. Louis - Washington University in St. Louis Newsroom