The pharmaceutical giant GlaxoSmithKline is starting human trials of the first medicine, a cancer drug, that has emerged from its two-year-old collaboration with consumer genetics firm 23andMe.

The novel partnership focuses on using 23andMes massive genetic database, composed of the test results and self-reported health data from 12 million consumers who have taken its tests to learn about their ancestry and a smattering of disease-related genes, and who have said their samples could be used in research. GSK uses the database to try and validate genes and proteins that could be what researchers call targets for new drugs that is, the proteins and other molecules whose functions medicines block or otherwise change.

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SAN DIEGO, Aug. 03, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO), today announced the publication of the first study to utilize its genome imaging system, Saphyr, for the analysis of structural variants (SVs) in lung cancer and metastases. The study, published in Translational Lung Cancer Research by a team of scientists from Fudan University Shanghai Cancer Center and Shanghai Medical College, analyzed SVs using both short-read next-generation sequencing technology (NGS) and Bionanos Saphyr system on a primary lung squamous cell carcinoma sample, and on matched metastases from lymph node and pulmonary vein. The study showed that Saphyr outperformed NGS-based methods in the detection of structural variants to characterize the genetic heterogeneity between the primary tumor and the matched metastases.

Of 1026 large SVs detected on average by Saphyr in each of the tumor types, the NGS-based methods failed to detect an average of 77%. Saphyr identified 52 SVs shared between the metastases, while no shared SVs were found by NGS-based methods.

The study authors stated that Saphyr is more capable of detecting large and complex SVs, without the computational and bioinformatic challenges that come with SV calling from NGS data. They found that like with point mutations and small insertions/deletions detected with NGS, SVs make up a large part of tumor heterogeneity. The authors describe that the combination of NGS and Saphyr allowed for a more comprehensive understanding of the variation between primary tumor and metastases, with Saphyr making up for the inability of NGS to detect large SVs.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented: Researchers are increasingly becoming aware of the importance of genome-wide and unbiased detection of structural variants in cancer and of the severe limitations of NGS-based methods to do so.We are pleased to see this publication showing that Saphyr provided a comprehensive view of structural variants in lung cancer, the most commonly occurring cancer worldwide.Unlike short-read sequencing protocols which start with fragmenting the genomic DNA of the tumor, Bionanos genome imaging analyzes long, intact DNA molecules that are hundreds of thousands to millions of basepairs long, which enables Saphyrto detect structural variants that couldnt be identified before. We believe this study and the growing body of publications on Bionano data show that Saphyr is indispensable for personalized medicine and for furthering the understanding of tumorigenesis and cancer progression.

The study is available at http://tlcr.amegroups.com/article/view/40176/html.

About Bionano Genomics

Bionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. For more information, visitwww.bionanogenomics.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Saphyrs capabilities in comparison to NGS-based methods; and Saphyrs potential as an indispensable tool for personalized medicine and furthering understanding of cancer in the medical community. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Kirsten ThomasThe Ruth Group+1 (508) 280-6592kthomas@theruthgroup.com

Originally posted here:

Metastatic Lung Cancer Study Finds That Bionano's Saphyr Outperforms NGS for the Detection of Structural Variants - GlobeNewswire

MM&M first wrote about health medias COVID-19 coverage several thousand news cycles ago on February 3, to be precise. That story concluded with the following paragraph:

So it will continue to fall on health media to alternately inform, educate, soothe and de-escalate. We really need to keep thinking through how we do our jobs in an environment, like this one, where there can be misinformation. If I talk about bat soup, versus be sure to wash your hands, whats going to get more traffic? We need to do more to elevate credible information, even if it sometimes is boring.

That last quote, from WebMD chief medical officer Dr. John Whyte, feels prescient with the benefit of hindsight. Sporadic bursts of overcaution notwithstanding, health media publications and commentators embraced their elevation mission. Drowning out the deniers and grifters wasnt always easy, but nearly every health media organization attacked the task with insight and empathy. In doing so, they elevated the level of understanding and, in all likelihood, prevented people from getting sick, or sicker.

For an insider view of the continuing coverage of COVID-19, we asked leaders from a range of media-adjacent organizations to weigh in on social media follows, coverage blind spots and more. The MM&M media panel included: Jack Barrette, CEO and founder of Wego Health; Amy Conway, editor-in-chief of Health; Alexandra Gilson, director, social media at CMI/Compas; Richelle Horn, senior director, marketing at Wego Health; Craig Mait, president and chief revenue officer of Mesmerize; Andrea Palmer, president of Publicis Health Media; Georgette Pascale, founder and CEO of Pascale Communications; Dr. Judith Simmons, managing director of healthcare at Gather and founder of Lion Head Advisors; Cynthia Spitalny, senior director, integrated marketing at Outcome Health; and Whyte. Responses have been lightly edited for length and clarity.

Simmons: Good curation has been key. COVID updates at The New York Times, Johns Hopkins University of Medicine, STAT, Nature Briefing, Science, The COVID Tracking Project, The New England Journal of Medicine, Kaiser Health News and the CDC have kept up with the rapid pace of important information. Current and former officials such as Dr. Anthony Fauci, Dr. Tom Frieden and Andy Slavitt are experienced and valued voices.

Palmer: Times Up Healthcare (@timesuphc) on Twitter. Only 20% of the decision-makers in healthcare are women, which was an issue before the pandemic and will continue to be an issue if we dont advocate in this space. From a media standpoint, its been fascinating to see how brands are embracing platforms such as TikTok to spread helpful messaging, from P&Gs use of influencers to drive the #DistanceDance phenomenon to fitness and athletic companies creating at-home workout challenges.

Whyte: I focus on Twitter, because I find Instagram doesnt provide the ability to have as much dialogue. @GilBashe curates interesting scientific and policy-type articles. @JeromeAdams, the Surgeon Generals personal account, provides a personal perspective as well as succinct advice on managing the pandemic. @DrJenCaudle is an African-American physician who shares very practical advice.

Conway: On Twitter, Angela Rasmussen (@angie_rasmussen) is a Columbia virologist who shares and demystifies the latest news on COVID-19, calls out others for disinformation and promotes diversity and inclusion and manages to do it all with a dose of humor. Craig Spencer (@Craig_A_Spencer) an ER doctor and Director of Global Health at NewYork-Presbyterian/Columbia University Medical Center, has shared what it was like to be on the front lines back in March and if youre looking for guidance on masks, read his A Soliloquy on Masks. Leah Douglas (@leahjdouglas), a reporter for the Food & Environment Reporting Network, has been mapping COVID-19 outbreaks in the food system. The coverage is impressive, fascinating and terrifying.

Pascale: On Instagram, @humansofny and @wetheurban give a realistic approach to who [are] and what is really being affected.

Gilson: Governor Andrew Cuomo has been a voice of authority in this new normal, with New Yorkers being on the frontlines battling the pandemic in its early stages.

Spitalny: With multiple family members and friends working in healthcare, I am a big champion of frontline essential workers. Mask Match, a nonprofit that helps people with spare masks send them directly to healthcare workers on the front lines or donate to replenish their PPE, was something important to elevate.

Mait: We have relied on the CDC to track cases in the U.S. and for information to protect ourselves and our communities. We have also become more active on LinkedIn than ever before, seeking out leaders of similar-sized organizations to ours to see how they are responding to and dealing with the situation.

Barrette: One of my favorites on Facebook is frontline nurse and immunocompromised patient leader MarlaJan Wexler, who cuts through the politics and BS as only a nurse can do.

Whyte: Laurie McGinley at the Washington Post always provides good analysis of important issues. Shes not trying to get clicks. STAT is terrific for a daily morning update. And living in the Washington, D.C. area, I find Bob Cusack and his team at The Hill helps me understand everything happening in DC that may impact me. Its succinct and timely.

Spitalny: It has been interesting to see how mainstream journalists have been covering the innovative ways companies have addressed their business challenges during the pandemic. I have also been listening to a lot more news through podcasts, like NPRs up first and NY Times The Daily. They help prepare me for the day and keep me apprised of topics that may become important to what we message and pursue as an organization.

Palmer: COVID has shown us just how important it is to create content with a consciencecontent that works in service to the people who consume it. Lets elevate voices in the media who are dedicated to truth and facts, like Pien Huang from the Science Desk at NPR. Since the start of the outbreak, she has consistently shared thought-provoking pieces that aim to educate readers.

Conway: Olga Khazns articles for The Atlantic are engrossing and surprising, answering questions you might not even have thought to ask: Why did it take so long for therapists to start seeing clients remotely? Why does Americas sick leave policy work against its workers? Is a socially distanced pool still fun? STATs no-nonsense news reporting by Sharon Begley, Helen Branswell and Andrew Joseph goes deep into the science of COVID-19 but is always readable, engaging and enlightening.

Barrette: Overall, traditional media has pounded us with the latest hours sound bites from experts who themselves are learning real time about this disease. The result is confusion, fear, complacency and desensitized consumers

Gilson: More important than individual voices has been the collective conversation on COVID, stemming from patients and HCPs trying to navigate chronic diseases and cancer which did not let up despite the pandemic monopolizing health conversations. Those patients and their doctors are still in need of critical information, now more than ever, to keep up to date on treatments and recovery in a post-COVID world. Individual voices such as Governor Cuomo and Dr. Fauci will continue to be important in the evolving climate, but Pharma should continue to pay attention to the masses in understanding trends and sentiment within healthcare.

Pascale: Local papers and online sources are covering the news that is real and relevant to you. Sometimes its most helpful to track how things are influencing you locally, in your own backyard.

Simmons: The New York Times has stood out in providing local, national, and global views, reporting on the science, and publishing beautiful data visualizations that have helped make information clear for readers.

Mait: Unfortunately, many of us are avoiding mainstream media and news cable channels as they appear to be adding to the problem by politicizing COVID-19. Weve relied on Andrew Cuomo and Bill de Blasios daily press briefings on TV for updates on COVID-19s progress in New York. We try to listen to the medical professionals giving proper information, like the CDC, Dr. Anthony Fauci and Dr. Sanjay Gupta.

Spitalny: I am most impressed by 17-year-old Avi Schiffmann, the high school web developer who had the foresight to begin tracking COVID-19 in December when it wasnt really a news topic in the United States. His website demonstrates that ingenuity and talent can come from anywhere. Although he was offered up to $8 million from sponsors and has had numerous job offers, he declined all of it; he is adamant about protecting the integrity of the data and the site.

Simmons: Dr. Craig Smith, chair of the Department of Surgery at NewYork-Presbyterian Hospital/Columbia University Medical Center, started writing a series of daily letters that spanned a 50,000-foot overview to the ground level of his hospital. He shared important information with perspective, warmth, context and occasionally poetry. Each letter was a realistic and human assessment of the moment and collectively they have become a narrative of the pandemic.

Palmer: NPRs What Do Coronavirus Racial Disparities Look Like State By State? should be required reading. Its thorough and outlines through visuals and statistics how and why people of color are so disproportionately affected by COVID-19. We need to put this new data into action, creating points of connection and communication where they are missing or ineffective. Moving America in a healthy direction will be about more than combatting the virus effectively; itll be about advancing our society justly and inclusively.

Conway: Some Coronavirus Guidelines, a New Yorker piece by John Kenney published in March, offers helpful guidelines on how to handle the Coronavirus crisisbeginning with the simple dont panic and wash your hands and progressing to the end of the world. Its funny because it pokes fun at the very real escalation of thoughts and fears we were having at the time (and still are!).

Whyte: The reporting in March around the growing mental health epidemic was prescient. I think some people thought it was just anxiety and would go away. But we are seeing how the pandemic is exacerbating mental health issues in those persons already diagnosed, as well as creating new mental health problems in people who never exhibited problems. I give credit to Arianna Huffington and her Thrive platform, which has been sounding the alarm bell from the beginning. The medical community has only recently come around to recognizing the problem.

Spitalny: The personal impact that this pandemic has taken on HCPs has felt overlooked. My husband is a physicians assistant and works at a major hospital, so seeing his day-to-day activity and knowing that other HCPs are probably going through something similar (burnout, cut wages for longer hours, etc.) suggest there are stories that needed to be told that were grittier than just the headline.

Whyte: We dont have an adequate explanation of the data. We report the number of cases and deaths, but we dont focus enough on local infection rates and what they mean. Early on, many cases occurred in clusters in certain counties. That was relevant to know when we talked about containment. We also didnt acknowledge the uncertainty of data, that we were learning as we went along. So we made different recommendations at different times relating to masks and antibody testing. That caused confusion and eroded trust.

Mait: During the last few months, there has been a lack of leadership from the federal government, a lack of a centralized voice with clear messaging and, of course, a lack of scientific data given the novelty of the disease. This disease is something that so clearly should not be politicized, yet it has been. What we need is a real task force with a centralized voice that everyone has access to and that is not politicized. Coverage should focus on the top doctors and what they are doing and saying about COVID-19 and the reasons why.

Simmons: The unprecedented breadth of achievements in six months related to this virus and pandemic. COVID-19 is a totally new disease and when I look back on what has been accomplished in basic science, therapeutics, clinical management, vaccine development, transmission and adjustments in how people live and work in just months its amazing. It matters because we need to use the growing bank of facts and science that we have learned to guide us as we move ahead. We know a lot more now.

Horn: Having had cancer and working so closely with patient leaders, I would like to see more coverage on how people living with chronic health conditions (immunocompromised, genetic disorders, metabolic disorders) should safely, if at all, re-enter society as things begin to open up.

Pascale: People have mistakenly thought this was going to be over by now. We need to continue to put emphasis on what we are doing as we move forward. For example, with my sons basketball camp canceled, we made do by involving him with a mini-camp in the neighborhood. These kinds of things are important to talk about, as they show how people are functioning during this time. Hyperlocal pieces can be helpful, witty and smart, and get people to a better place of understanding.

Conway: The reporting is starting to catch up, but it took a while before there was substantial coverage about how discrimination and disparity play into the pandemic. Because of long-standing inequities, African-Americans, Hispanics and Latinos and American Indians/Alaskan Natives are at increased risk for getting or becoming seriously ill with COVID-19. The LGBTQ+ community already faces discrimination when seeking healthcare and may avoid getting care. Socioeconomic disparity means that children without computers or reliable Wi-Fi are not able to learn online. Workers without paid sick leave or other benefits may put themselves or others into vulnerable situations. The list goes on.

Palmer: We need to make sure that science-based solutions are not being politicized in the news. With the rise of Black Lives Matter, we are now more aware of the social determinants that have led to disproportionate COVID-19 cases in the Black community but we havent heard enough about solutions. Black Americans are 3.5 times more likely to die of COVID-19 than White Americans. That statistic should send shock waves through everyone, and inspire wide-scale behavior change. If individuals arent doing it themselves, its worth asking in our industry how media and marketing can create the impetus for broader institutional change to take place.

Whyte: 1. Data needs to be presented in terms of local infection rates. Everyone isnt a NYC or small town in Wyoming. You need to put the data in context. 2. Stop all the talk about the vaccine, because its just not realistic. Lets have a real discussion around risk and help people understand how to live with the virus. 3. Acknowledge the role of innovation. Despite some problems with testing and mixed results from therapeutics, we had nothing five months ago. The perfect cannot be the enemy of the good.

Simmons: We havent communicated a clear understanding of how the virus is transmitted, how pandemics grow and how one persons actions may affect others. Mask wearing has become politicized, rather than normalized, and that must change. Weve got to keep refreshing peoples knowledge and presenting essential information in all ways across all platforms. This virus is not going away and we will have to adapt to it.

Conway: 1. The importance of improving diversity in the fields of science and medical care. In 2018, just 5% of active doctors in the United States identified as Black or African-American, according to the Association of American Medical Colleges. According to the American Psychological Association and American Psychiatric Association, just 4% of psychologists in the U.S. and 2% of psychiatrists are Black. Having different viewpoints and voices can improve care for all. 2. What are the long-term ramifications for children in terms of socialization, education and overall health and well-being? What services have special-needs children been gettingor more importantly, not gettingduring the pandemic?

Barrette: 1. Share concrete steps that every consumer can take, and specifically how those steps will lessen the suffering caused by the virus *in their area*. For example, if 80% of Bostonians wore masks starting now, you could watch the Red Sox in August. If its just 50%, the season is canceled. 2. Check the facts before publishing anything. If theyre wrong, either dont put them out or correct them. 3. Share more stories of how [US geography here] truly flattened the curve and back it up with data.

Spitalny: Id like to see coverage of how content providers are creating compelling, unbiased information about the benefits of wearing a mask. Id also like to see a full 360-degree look at whats happening in healthcare beyond the explosion of telehealth. Id like to see journalists tackle touchy topics like, for example, if hospitals are losing money because of electives being pushed or on the personal impact of the coronavirus crisis on HCPs in terms of mental health and loan burden. Are these crises within a crisis?

Pascale: 1. Focusing on the positives a bit more would be nice. There has been some good news that hasnt received enough recognition. 2. Reiterating that we still need to be responsible. We need to find a balance in coverage about continuing to take precautions, and how to do so. Repetition builds retention! 3. Collaborating and working together to make things happen quicker, especially scientifically. With more people sharing data when developing drugs, the endpoint can be sped up safely and effectively.

Horn: I would like to see more of an emphasis on preventative care. What are the effects of skipping or delaying appointments, or discontinuing medications? As someone who had her thyroid cancer detected during a normal well visit, I want the media to encourage people to continue to seek care during this time.

Palmer: Talk about a moving target. A little while ago, we were excited about gradual reopening and outdoor dining. By late June, we were seeing around 40,000 new cases a day, with Dr. Fauci warning the sum could rise to 100,000 new cases a day. That said, the media needs to continue focusing on prevention and caution. When this started, we saw a lot of coverage around quick fixes for our stress levels and overall quarantine wellness, such as virtual fitness classes. Now, we know we are in this for the long run, and people need endurance. They need long-term solutions to the mental health challenges were mired in. Coming off COVID-19, we need the media to look at mental health with fresh eyes and future-facing insights.

From the August 01, 2020 Issue of MM&M - Medical Marketing and Media

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Health Media in the COVID-19 Era: A mid-wave report - Features - MM&M - Medical Marketing and Media

Night City isnt exactly a sprawling Metropolis that youd want to plan a vacation to. Between corporate espionage and radical trans-humanist activists hacking away at their flesh in a gruesome example of how best to remove those tattoos that you wish youd never gotten, Cyberpunk 2077s sandbox is rife with danger and intrigue.

There are some great locales to visit in Night City though! And by great, I mean differently awful. Pacifica is one such zone, a luxurious resort on the ocean that was designed to be a relaxing escape from Night Citys main hub of cyber-chaos and body-jacked maniacs. And then the the money ran out halfway during development, the developers pulled a dine and dash, and all that remains is a concrete jungle of half-baked dreams and bolt-holes for renegades looking to escape the reach of big business.

Pacifica could've been Night Citys money-making vacation resort, but once the investment dried up it became a husk left to rot. Now, instead of tourists, the district is overrun by gangs and violence, with The Voodoo Boys protecting the community forsaken by NCPD. #ConceptArt pic.twitter.com/3gjoKzHJvE

According to CD Projekt RED, Pacifica is currently controlled by the Voodoo Boys, nihilistic drug dealers who habitually terrorise people with senseless violence. Fans of magic and agents of chaos, the Voodoo Boys exploit the impressionable youth of Night City, regularly fleecing them of their chas and their lives as they war with other gangs.

This isnt the only slice of Night City that has been shown off lately. CD Projekt RED has also offered a look at the lifestyles of the rich and the famous (Theyre always complaining) in the Westbrook District, while Heywood exists as a neighbourhood of contrast: Parks and skyscrapers, lethal gangsters and cops who are in the pocket of the corporations.

Westbrook is considered by many to be the best place to live and have fun in Night City. If youve got eddies, you come here to spend them. And if you don't? Well, take out a loan and pretend youre on top of the world even for just one glorious night. #ConceptArt pic.twitter.com/gGAnMVMYWL

Heywood is a neighborhood of contrastfrom modern skyscrapers and parks in the north, to dangerous, inhospitable slums in the south. It's the biggest bedroom in Night City, where gangs like Valentinos and 6th Street get down to businesslegal and illegal alike. #ConceptArt pic.twitter.com/wc5i1sxsJB

Which zone will you choose to visit? The choice is yours, but at least you can look fashionable while getting your cyber-head cyber-kicked in by a junkie in search of a cyber-kick, while doing so.

Last Updated: July 28, 2020

Read the original:

Cyberpunk 2077 shows off the ruined dreams district of Pacifica in new concept art - Critical Hit

PizzaGate's unfounded claim emerged during the 2016 election. Later that year, a gunman appeared and fired an AR-15 inside the pizzeria, saying he was trying to rescue non-existent child sex slaves.

Now, a report from the Internet trust tool NewsGuard has found that the coronavirus pandemic is clearly helping this American ideology establish itself in Europe.

In the report, NewsGuard sees an increase in QAnon groups and social media pages in April, as the blockages caused by the new virus left millions of people practically confined to their homes.

Coronavirus conspiracies increased along with increased infections.

Such claims acted as a "gateway drug" to QAnon, providing Europeans with the "perfect way to" the online sect, Chine Labbe, managing editor for Europe at NewsGuard, told CNN.

QAnon started out as a one-time conspiracy with a cryptic anonymous post on the 4chan online forum in 2017. The person behind this, who followers would later call "Q", made the false claim that Hillary Clinton was going to be arrested. There was no such arrest.

But similar posts fueling other arrest claims and "deep state" actions continued to appear on 4chan. It is unclear who was behind the posts, or whether the same person posted the ones that followed.

QAnon supporters have compared the early posts, and the later posts, with breadcrumbs or "drops," like Hansel and Gretel, as they refer to them.

Followers of QAnon, whose online behavior has been compared by analysts to a virtual cult, spread the unfounded claims, amplifying them with manipulated or out-of-context evidence posted on social media in an attempt to back up the allegations.

Experts fear that the "dedication QAnon supporters have to their beliefs also provides an opportunity for foreign interference to use these narratives to their advantage," Aoife Gallagher, an analyst with the Institute's Digital Research Unit for CNN, told CNN the Strategic Dialogue (ISD).

The move has raised concerns about online bullying. Twitter banned more than 7,000 accounts, citing its policy of taking action on accounts with "the potential to cause harm offline."

But while QAnon has its roots in the US, supporting and disseminating unsubstantiated theories of mass shootings and elections, it has since become an amorphous ideology, appropriating conspiracies from elsewhere that sit with its anti-elite message. .

"It is such an easily translatable framework, because it is so meta," said Labbe. "It is about world elites having a Machiavellian plan, and every country in the world has elites."

This ability to assimilate old hoaxes with new conspiracies around the coronavirus outbreak has found QAnon "a broad group of supporters" beyond the US among some New Agers and the conservative right, Gallagher told CNN.

"It is tangential to the extreme right in the United States, using anti-Semitic tropes and attacking the same people as the extreme right, (but) as it spreads, we are also seeing that it is attractive to (the) left anarchist side, " she said.

QAnon's ability to evolve is not only at risk of seriously "undermining" democracy, due to its damaging narrative about individuals and institutions, but it also "undermines the disclosed official information and could hinder the effort to control the virus." Gallagher added.

QAnon has managed to incorporate the local socio-political concerns of Germany, Italy, France and the United Kingdom into its anti-elite "deep state" narrative, according to the NewsGuard report.

European QAnon groups have gained a large online presence, with the report identifying "448,760 followers or members" on the social media groups it analyzed.

Memberships began to increase in late 2019 and early 2020, particularly once the coronavirus pandemic began to take hold, according to NewsGuard.

According to the report, a French YouTube channel with videos about QAnon has amassed 21,500 subscribers since its inception in April this year. A QAnon Facebook group in the UK, created in the same month, has garnered more than 18,000 followers, according to the report.

National political complaints have found a sounding board in QAnon.

German social media accounts portray Chancellor Angela Merkel "as a 'deep-state puppet' that needs to be overthrown," the report says.

In France, President Emmanuel Macron has been dismissed as "a pawn" in QAnon's French publications.

And QAnon's Italian supporters praised former far-right interior minister Matteo Salvini, but treated the country's centrist prime minister Giuseppe Conte with contempt.

Meanwhile, debates are raging over British QAnon groups on Facebook over whether Prime Minister Boris Johnson has been "installed" by "Q" and is draining the "British swamp" along with United States President Donald Trump.

"In such panel discussions, Brexit and the British government's decision to ban Huawei from UK 5G networks are cited as evidence of Johnson's loyalty to Q," the report writes.

The report finds that QAnon is thriving in Germany. Local ideology-linked social media accounts hit the scene as early as 2018, including what is now a German-language YouTube channel of 99,600 followers and a Facebook group with 30,100 members.

German celebrities have also joined the nexus of conspiracy.

Berlin-based vegan chef Attila Hildmann, who has posted on social media about his support for theories in the QAnon constellation, implored the United States to "liberate" Germany in June 2020, according to the report. Her post, on the Telegram messaging app, falsely claimed that Merkel was working "alongside Gates, the Zionists, the Transhumanists and the Communists" to plan the "genocide of the Germans".

In a statement to CNN, Hildmann said he is not a follower of "Q", but watches the movement "and supports it." He added that "Germany is not a free country, but it is still occupied by the Americans and, therefore, only the great nation of the United States has the power to liberate the Germans from Merkel's reign of terror!"

According to the NewsGuard report, singer Xavier Naidoo has been a "driving force" behind the spread of the conspiracy in Germany, routinely sharing QAnon content with his 84,000 Telegram subscribers. CNN has seen at least five posts it has shared from QAnon groups on Telegram.

When asked to respond to allegations that Naidoo has fueled the spread of QAnon in Germany, a Naidoo spokesman said: "Xavier has nothing to do with QAnon."

A separate analysis by Gallagher at ISD found that QAnon's popularity in Germany coincides with Trump's attacks on NATO and the European Union, a sentiment that draws anti-Atlantic conspiracy groups.

"There is a good appetite for that kind of rhetoric," Gallagher said, adding that German QAnon groups on Telegram, "have seen a huge increase in membership by tens of thousands" since the beginning of 2020.

The theory remains on the fringes of European discourse, but analysts worry that adherents ally with more conventional movements.

According to the NewsGuard report, Facebook groups supporting France's yellow vest movement, or Gilet Jaune, a campaign that began protesting against rising gas prices and has since turned into a larger rally against Macron, "have been particularly interested in Q's narratives recently," the report wrote.

A group from Yellow Vest, which has 196,000 members, shared a QAnon video in July from a French QAnon site, which was created in May. "This shows how in some circles the two fights are interconnecting," Labbe said.

Social media companies have targeted the conspiracy. Three sources familiar with Facebook's work on misinformation told CNN in mid-July that the company plans to take action on QAnon. When CNN contacted this week, Facebook declined to comment.

But the jury does not know if it will stop the spread of ideology. Many say the genie may already be out of the bottle.

Labbe argues that "censorship fuels conspiracies, as soon as you remove the websites, you will find an alternative media platform."

But the opposite is also true. "QAnon flourishes because it is a community where everyone can reinforce their beliefs," said Gallagher. "Facebook groups are one of the main places" where QAnon thrives, he explained. "So it will be interesting to see the next move that Facebook is making."

CNN's Donie O & # 39; Sullivan and Paul P. Murphy contributed to this report.

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An unsupported American conspiracy theory found a foothold in Europe. New research shows how - NewsDio

The group found that the cell lines that were more resistant to radiation treatment also had higher levels of purines biological compounds that are known as the building blocks of DNA and RNA, and that can also activate signaling pathways.

This was very exciting because lots of different genetic mutations that occur in glioblastoma lead to this purine pathway being activated, Wahl says.

This suggested that they might be able to target the downstream effect of multiple genetic mutations.

We hypothesized that targeting this metabolic activity might work across tumor cells with different types of mutations instead of just whatever fraction of cells has that one particular genetic aberration you might go after with a mutation-targeting therapy.

Once the researchers discovered the correlation between high levels of purines and radiation resistance, they set out to demonstrate whether the metabolic changes actually caused the radiation to be less effective.

We gave cells more purines. It made them more resistant, Wahl says. We took away purines. It made them more sensitive to radiation. And we found it was doing this by affecting the cells ability to repair radiation-induced DNA damage.

To better understand whether targeting purine metabolism might help overcome resistance to radiation therapy in patients, the team used mouse models of glioblastoma with tumors grown from human patients cells.

They gave the mice a drug called mycophenolate mofetil, or MMF, which blocks purine biosynthesis and which has been approved for the treatment of organ transplant rejection since 2000.

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Tumor growth was moderately slowed down in mice who received radiation therapy alone or MMF alone, but almost totally halted in the mice who received both, Wahl explains. The benefits of MMF were similar whether animal tumors were grown in the brains of the mice or elsewhere in their bodies, demonstrating the drugs ability to effectively penetrate the blood-brain barrier which is critical for treating brain cancer patients.

Since the FDA has already found the drug to be safe enough to use in patients for one purpose, it makes it easier to set up a clinical trial aimed at a second disease, he says.

Ultimately, Wahl adds, the research was made possible by the collaborative, multidisciplinary environment at U-M where clinicians and researchers with expertise in glioblastoma can team up with others who specialize in cancer metabolism, data modeling and launching new clinical trials.

None of this happens without all these different teams sharing knowledge, models, methods and enthusiasm for making a difference in the lives of patients, he says.

Additional authors include Weihua Zhou, Andrew J. Scott, Kari Wilder-Romans,Joseph J. Dresser, Christian K. Werner, Hanshi Sun, Drew Pratt, Peter Sajjakulnukit, Shuang G. Zhao, Mary Davis, Meredith A. Morgan, Alnawaz Rehemtualla, Barbara S. Nelson, Christopher J. Halbrook, Li Zhang, Angela K. Walker, Maureen Kachman, Jianping Xiong, Maria G. Castro, Pedro Lowenstein, Sriram Chandrasekaran, Theodore S. Lawrence and Costas A. Lyssiotis of U-M; Yangyang Yao of U-M and First Affiliated Hospital of Nanchang University, China; Francesco Gatto of Chalmers University of Technology, Gteborg, Sweden; and Jann N. Sarkaria of the Mayo Clinic.

The research was supported by grants from the American Cancer Society, the Forbes Institute for Cancer Discovery, the National Cancer Institute (K08CA234416), the Jones Family Foundation Fund within the Chad Carr Pediatric Brain Tumor Center and U-M Taubman Emerging Scholars Program, as well as grants from the National Institutes of Health, the Michigan Institute for Clinical & Health Research, Rogel Cancer Center, an AACR NextGen Grant for Transformative Cancer Research (17-747 20-01-LYSS) and an American Cancer Society Research Scholar Grant (RSG-18-186-01).

Paper cited: Purine metabolism regulates DNA repair and therapy resistance in glioblastoma, Nature Communications. DOI: 10.1038/s41467-020-17512-x

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Study Suggests New Approach to Improve Radiation Therapy Resistance in Glioblastoma - Michigan Medicine

DURHAM, N.C., July 29, 2020 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced that it has acquired exclusive rights to a gene therapy targeting GUCY2D-associated Leber congenital amaurosis (LCA1), a genetic eye disease that affects the retina and is a leading cause of blindness in children, from Sanofi, which originally licensed it from the University of Florida. The therapy was created in the laboratory of Atsena Founder and Chief Scientific Officer Shannon Boye, Ph.D., and Founder and Chief Technology Officer Sanford Boye, M.Sc., at the University of Florida.

We are thrilled that our gene therapy for LCA1 is coming home to Atsena and that we will have the opportunity to further its development, said Shannon Boye. Atsena was founded to advance treatments for inherited retinal diseases and believes in centering patients perspectives and needs in all we do. We are honored to continue to work with LCA1 patients and their families as we strive to treat this debilitating disease.

LCA is the most common cause of blindness in children, impacting two to three per 100,000. LCA1 is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this inherited retinal disease.

Atsena has an ongoing Phase I/II clinical trial evaluating this gene therapy in LCA1 patients. The second cohort in the trial is expected to be dosed in the fall of 2020.

Atsenas gene therapy has the potential to be a major advance in treating blindness in both children and adults affected by this inherited retinal disease, said Benjamin Yerxa, Ph.D., Chief Executive Officer of the Foundation Fighting Blindness and Atsena board director. The foundation was instrumental in supporting proof of concept studies in the founders labs over the last 15 years. Now, via investment in Atsena through our Retinal Degeneration (RD) Fund, we are excited to support this potential breakthrough treatment for LCA1.

Atsena closed a Series 1 funding of $8.15 million in April 2020, led by founding investors Hatteras Venture Partners and the Foundation Fighting Blindness RD Fund with participation by Osage University Partners, PBM Capital and the University of Florida. Patrick Ritschel, M.B.A., co-founder and former President of gene therapy company StrideBio, serves as Atsenas Chief Executive Officer.

Atsena is pleased to have the support of an enthusiastic investor base that shares our dedication to bringing the life-changing power of genetic medicine to patients living with LCA1 and other forms of blindness, said Ritschel. We look forward to working closely with our investors and patients as we continue to grow, and expect to announce additional milestones later this year.

About Atsena Therapeutics

Atsena Therapeutics is a clinical-stage gene therapy company, focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness. The company has an ongoing Phase I/II clinical trial evaluating a potential therapy for one of the most common causes of blindness in children. Its additional pipeline of leading preclinical assets is powered by an adeno-associated virus (AAV) technology platform tailored to overcome the hurdles presented by inherited retinal disease, and its approach is guided by the specific needs of each patient condition. Founded by pioneers in ocular gene therapy, Atsena has a licensing, research and manufacturing collaboration with the University of Florida and is headquartered in North Carolinas Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com.

Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - BioSpace

Why was a marathon runner in his 40s stricken with a case of COVID-19 so severe it landed him in the intensive care unit? Why did a healthy 12-year-old boy lose his life to a disease that mostly harms older people? One of the most terrifying aspects of the pandemic is that the severity of the disease seems so cruelly and arbitrarily variable.

Although the SARS-CoV-2 virus is most often fatal in patients who are elderly or have chronic medical conditions such as diabetes, heart disease or high blood pressure, exceptions that bring down apparently healthy young people are commonplace. Even patients who do not die of the infection show a huge spread in their symptoms: Some never get sick; some need to be hospitalized but recover; some have lingering disabilities that last for months.

So far, scientists have been largely at a loss to explain why COVID-19 hits patients as hard as it does, though reasons surely exist. Its not just bad luck, said Helen Su, an immunologist at the National Institute of Allergy and Infectious Diseases.

One possibility under investigation is that some people harbor genes that put them at greater or lesser risk from COVID-19. The COVID Human Genetic Effort, for example, is enrolling hundreds of patients from around the globe who wound up in intensive care after infection with the SARS-CoV-2 virus. Initially, the project only enrolled patients who were under age 50 and had no underlying health conditions, though it has more recently expanded eligibility.

My hope is to understand the genetic basis of severe COVID in patients of all ages and regardless of comorbidities, said Jean-Laurent Casanova, a researcher in pediatric medicine and immunology at the Rockefeller University who co-founded the project with Su and others. And from that, to understand the mechanism that makes them vulnerable to SARS-CoV-2.

Some genetic clues may already be coming to light. Last week, a team of researchers in the Netherlands published a preliminary communication online in JAMA about four young male patients from two families who all suffered severe COVID-19 respiratory illnesses. The men, who were between the ages of 21 and 32, had no history of chronic medical problems, but DNA sequencing revealed that each of them had a rare form of a gene on his X chromosome that was linked to a deficient immune response. Much more study will be needed to determine whether similar deficiencies, possibly involving other genes, are common among COVID-19s worst cases.But in a study appearing in Nature today, researchers at the Yale University School of Medicine who followed the progression of COVID-19 in 113 hospitalized patients for two months found that greater severity of the disease was associated with maladaptive immune responses. (The causes for those immunological misfires was not determined.)

The significance of these discoveries may not be limited to COVID-19. Casanova is a champion for an idea that has been slowly gaining credence among medical researchers for many years: that genetics is always a factor in infectious diseases. Many if not all people may have very specific genetic vulnerabilities, such as weaknesses in their immune system, that go unnoticed until one particular pathogen crosses their path. That genetic trait is their Achilles heel, and that pathogen is the one thing that can take advantage of it.

The theory has emerged out of both clinical practice and scientists growing appreciation of the interconnection between genes and infectious diseases. Casanova has spent the past 25 years scanning the genomes of young people who were inexplicably debilitated by commonplace pathogens like the herpes simplex and varicella zoster viruses (which cause cold sores and chickenpox, respectively). In these children, who showed no outward symptoms of compromised immunity, he has found defects in genes that make them susceptible to severe infection with a single pathogen. In most cases, there were no clinical signs of a genetic problem until they were infected.

For many of these immune deficiencies where children or adults have very severe infections there is a genetic basis, said Trine Mogensen, a physician at Aarhus University and a member of the COVID Human Genetic Effort steering committee.

If the COVID project succeeds in finding genes relevant to the course of the infection, it could fuel interest in widening that search for other conditions. Further work on the interplay of infections, immunity and genomes could change how future gene-based medicine routinely diagnoses and treats diseases.

Infectious disease has always been one of greatest threats to humanity. Before the invention of antibiotics, infections killed half of all children by age 15. Yet as terrible as their collective toll has been, even the worst infectious diseases kill relatively few of those they infect. Tuberculosis has been a scourge, but fewer than 10% of people infected with it even get sick. Even the terrible Spanish flu pandemic that started in 1918 had a mortality rate often estimated at around 2.5%.

Variability in disease severity is usually chalked up to circumstantial factors: the virulence of different pathogen strains, the amount of pathogen exposure, the nutrition or general health of a patient. Researchers have suspected, however, that something more is lurking in the genes of the hardest-hit patients.

The idea of a genetic component to infection dates back to 1905, when an English scientist named Rowland Biffen discovered a gene responsible for a devastating fungal disease called yellow rust that was killing wheat and diminishing crop yields across England. He found that resistance to the fungus was present in some of the plants as a recessive trait passed down from parent to offspring without affecting other characteristics of the plant. The discovery was celebrated, and his method of breeding for resistant plants is still widely used today.

These types of genes were later found in other plants and animals. But genetic immunodeficiencies in humans didnt start to attract attention until the 1950s, when an immune disorder was identified in an 8-year-old boy being treated at Walter Reed Army Medical Center for recurrent blood infections. The disorder, known as X-linked agammaglobulinemia, inhibits the bodys ability to make the antibodies called gamma globulins, resulting in severe infections even from fairly innocuous pathogens.

The boy had suffered 19 bouts of pneumococcal meningitis, which were repeatedly treated with antibiotics. His condition improved more lastingly only after his physician, Ogden Bruton, discovered that the boy had almost no gamma globulins in his blood. Bruton promptly began treating him with monthly injections of gamma globulins, and the boy survived to adulthood. The discovery, which was described in Pediatrics in 1952, was later recognized as a milestone, highlighting the role of defects of the immune system in inhibiting the fight against infection. These defects were later termed inborn errors of immunity.

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Our Genes May Explain Severity of COVID-19 and Other Infections - Quanta Magazine

XconomyBoston

The promise of gene therapies and gene-editing drugs is a long-lasting treatment thats potentially a cure. But making permanent genetic changes means any accompanying problems could be long-lasting as well, says Omega Therapeutics CEO Mahesh Karande.

Omega is developing technology that takes a more nuanced approach to genomic medicine. Instead of fixing or replacing faulty genes, the company aims to harness the biological system that regulates them. If a gene is not properly translating DNA instructions into a needed protein, Omega can tune the gene expression up, Karande says. If gene expression is too high, the companys technology dials it down.

We have basically tapped into the control room of biology, says Karande, a former executive at Macrolide Pharmaceuticals and Novartis (NYSE: NVS). Our therapeutics are allowing genes to express at their native, correct level of expression. We tap into that biology.

Now the Cambridge, MA-based biotech has tapped into something more: $85 million in financing. Karande says the cash will support multiple programs, the first of which is expected to reach clinical testing in 2021.

The system that regulates genes is called the epigenome. The targets of Omegas drugs are insulated genomic domains (IGDs), three-dimensional structures that rise up from the folds of DNA. IGDs regulate the activity of a gene, similar to the way a thermostat regulates the temperature of a room, the company says. Omega has developed technology that identifies IDGs and their biological functions in states of both health and disease.

Omegas drugs are fusion proteins made up of a delivery system that takes the therapy to specific cell types, a targeting domain that binds to a specific site on the IGD, and a functional domain engineered to tweak the activity level of the IGD as needed. A single Omega drug can control the gene expression of a single gene or multiple genes, Karande says. The company can also control the length of time that a drug works, making it last days, weeks, or longer. That makes the treatment applicable for acute conditions of short duration. And unlike the permanent change made by genomic medicines, if an epigenomic Omega therapy is no longer needed, it can be turned off.

Most gene therapies and gene-editing drugs are delivered by engineered viruses. In addition to hitting the intended genetic target, these viruses can also hit other places, causing side effects, says Tom McCauley, Omegas chief scientific officer. Also, gene-editing drugs use cutting enzymes that can snip unintended spots along the genome, sparking off-target effects. By contrast, Omegas targeted approach gives its drugs the potential to more safely treat genomic disorders with a degree of control not offered by gene therapies or gene-editing drugs, McCauley says.

There are other epigenetic medicines companies. Cambridge, MA-based Epizyme (NASDAQ: EPZM) is developing drugs addressing the genetic causes of disease. In January, the FDA approved the companys small molecule drug tazemetostat (Tazverik) as a treatment for the rare cancer epithelioid sarcoma. In June, it won an an additional nod for follicular lymphoma. The most advanced drug candidate, developed by another Cambridge-based epigenetics biotech, Constellation Pharmaceuticals (NASDAQ: CNST), is a small molecule in mid-stage testing in myelofibrosis, a rare blood cancer.

Theres a reason that most of the epigenetic medicines currently available and in drug pipelines are small molecules addressing some form of cancer, McCauley says. Those drugs do hit their cancer targets but they also go elsewhere in the body, sparking side effects, he says. That risk is acceptable in rare cancers, but untenable for other diseases. Cancer is one of Omegas disease targets, but McCauley says that Omegas capability to modulate the epigenome could more safely and effectively address other diseases as well.

The IDG science that is the basis for Omegas epigenomic approach stems from the research of Richard Young and Rudolf Jaenisch, MIT biology professors and members of the Whitehead Institute for Biomedical Research. In 2016, their research was published in the journal Cell. They are both scientific advisors to Omega, which was founded in 2017 by venture capital firm Flagship Pioneering, the companys only disclosed financial backer. The firm has a track record of starting companies, incubating them, and then spinning them out to advance their research.

Omega emerged from stealth last September. Karande would not say much about the companys disease targets then, and hes saying only a little more now. Without naming specific conditions, Karande says his startup aims to treat inflammatory and immunological disorders, metabolic conditions, and rare diseases where a targeted approach to modulating the epigenome enables the company to hit disease targets previously considered undruggable. The company currently has five programs. Karande says the new financing is enough to support all five, though he leaves open the possibility that some of them could be advanced in partnership with a large pharmaceutical company.

Were on a journey right now to get five programs, in a staggered fashion, into the clinic, he says. As we make milestones in the next few months, we will be talking about them.

Image: iStock/artisteer

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan@xconomy.com.

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Omega Therapeutics Lands $85M to Tap Into Control Room of Biology - Xconomy

Editor: David L. Joffe, BSPharm, CDE, FACA

Author: ChardaeWhitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine

The EarlyBird study investigated how to predict future pre-diabetes and type 2 diabetes in children.

Years of research have shown us that there are many factors that predispose patients to type 2 diabetes. However, researchers at the University of Plymouth, in collaboration with Nestl Institute of Health Sciences, monitored children to gain more insight into the factors that predispose them to type 2 diabetes in adulthood.TheEarlyBirdstudy, which is a prospective cohort study, investigated the genetic risk markers of type 2 diabetes in healthy children, as well as the influence trajectory of insulin and glucose independently of BMI.

EarlyBirdfollowed 300 children from the ages of 5 to 16 years old to determine who would become at-risk for developing type 2 diabetes, and why.Annual clinical anthropometric and physiological measurements were taken from the children. Researchers were among the first to report an early occurrence of -cell dysfunction in children who later developed pre-diabetes.This study also showed impaired fasting glycemia in subjects by the age of 15 years; these children had previously exhibited high blood glucose levels at the age of 5. The genetic variants, puberty, and weight gain were also analyzed byEarlyBirdto see how these factors could influence insulin action and blood glucose levels at an early age.

Results from this studyproved to be signicant because they reveal the changes in insulin secretion, insulin action, and glycemia over time. Genetic linkage of the SNPs associated with adult diabetes was mirrored in the children in their association with insulin and glycemic traits. SNPs susceptibility also showed age-specic interactions in the child subjects, with some of these traits including: rs780094(GCKR), rs4457053(ZBED3), rs11257655(CDC123), rs12779790 (CDC123 and CAMK1D), rs1111875 (HHEX), rs7178572 (HMG20A), rs9787485 (NRG3), and rs1535500 (KCNK16). Many of the common genetic variants were associated with a variety of high levels of fasting blood glucose.

GCKR and ZBED3 were two intronic genetic variants that were associated with different trajectories of fasting blood glucose from an early age throughout childhood.An increased risk of developing type 2 diabetes showed some correlation from the SNP ZEBD3 through elevated WNT activity.This pathway is controlled by short-chain fatty acids produced during the digestion of dietary fiber. ZEBD3 is known to affect fiber intake, which has led to the belief that this SNP is a relevant genetic maker for children who would benefit from increased consumption of dietary intake. GCKR is believed to be associated with lower fasting blood glucose levels in adults. In this study, it was found that the GCKR genotype was negatively associated with an age-dependent course of glucose; however, children at the age of 5 years old showed a positive association with blood glucose.

One of the most pivotal discoveries in this study is that relative defects in -cell function were a determining factor for who developed pre-diabetes. HOMA-B (-cell function) carried the most genetic associations of diabetes susceptibility. SNPs in the CDC123, HHEXIDE, and KCNK16 loci, showed a negative association with HOMA-B. SNPs in the CDC123 loci may represent that there is-cell mass and can influence function throughout growth. Evidence from theEarlyBirdstudy showed that that the interactions of the SNP in HHEXIDE loci with the trajectories of SHBG, IGF-1, and 17-OHP may inuence endocrine traits and therefore the maturation of other biological processes in childhood.Through these findings, it is believed that insulin action is alsoinuenced by genetic variations in the growth hormoneIGF-1 axis and adrenal and sex steroid activity, with a negative association in both HOMA-B and SHBG (sex hormone-binding globulins). Since the HHEX IDE SNP relates to insulin secretion capacity in early life, it is believed that there are effects beyond fetal development into pubertal growth and development.

TheEarlyBirdstudy was successful in demonstrating that SNPs previously associated with diabetes in adults also can be influential in children with the course of glycemic and insulin traits, independent of BMI.

Practice Pearls:

Carayol, J. et al.(2020) Genetic Susceptibility Determines -Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird76).Diabetes Care.doi.org/10.2337/dc19-0806.

ChardaeWhitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine

See more about pre-diabetes in our condition center.

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EarlyBird Study: Early Detection of Adult-Onset Type 2 Diabetes in Youth - Diabetes In Control

Krystal Biotech Whitney Ijem was tapped to serve as the first Senior Vice President, Strategy and Business Development at Krystal Biotech. Ijem joins Krystal fromGuggenheim Securities, where she served as Managing Director and Senior Biotechnology Analyst covering genetic medicine and rare disease companies. Prior tojoining Guggenheim, Ijem was a therapeutics analyst atTourbillon Capitaland before that she was an analyst in theJ.P. Morgan Equity Research Healthcaregroup focused on biotechnology.

Viroclinics Biosciences Netherlands-based Viroclinics Bioscience B.V.named Davide Molho as its new chief executive officer. Molho succeeds Bob van Gemen, who has served as the company's CEO since 2011. This transition is part of a planned succession strategy. Molho's appointment takes effect on Aug. 1. Molho joins Viroclinics from Evolution Research Group, where he served as CEO. Prior to ERG, he worked for almost two decades at Charles River Laboratories, most recently serving as president and chief operating officer of the global organization. As CEO of Viroclinics, Molho will lead the company through its next phase of growth with a specific focus on driving revenue diversification in adjacent and novel therapeutic fields, as well as continued strategic expansion through acquisitions.

Windtree Therapeutics John Hamill has been appointed chief financial officer of Pennsylvania-based Windtree Therapeutics. In this role, Hamill will help accelerate key initiatives to advance the company's business, financial planning and shareholder value. Hamillis replacing Windtree's former CFO,John Tattorywho is leaving to pursue other opportunities.He most recently provided consulting services to various life science companies, headed up finance at Trevena, Inc., Savient Pharmaceuticals and PharmaNet.

Kronos Bio Barbara Kosacz was named chief operating officer and general counsel of California-based Kronos Bio. Kosacz joins the company with more than 25 years of experience providing strategic and legal advice to life sciences companies, and served most recently as international head of Cooley LLPs Life Sciences Practice. In her role at Kronos, she will be responsible for internal operations and legal functions within the Company. Kosacz is a member of the Board of Directors of XOMA Corporation and is on the Board of Trustees of the Keck Graduate Institute.

Akcea Therapeutics Christophe Hotermans was named senior vice president of global medical affairs at Akcea Therapeutics. In this role, he will lead and evolve the execution of medical strategies, activities and operations worldwide in collaboration with executive management. Prior to joining Akcea, Hotermans served at Biogen for more than a decade in various roles, most recently as vice president and head of U.S. medical. Before Biogen, he was chief of the neurology clinic at the University of LigeinBelgium.

ImmunoGen -- Susan Altschuller has been appointed senior vice president and CFO of ImmunoGen, Inc. Altschuller has 20 years of financial management, investor relations, and business planning experience with leading pharmaceutical and biotechnology companies. She joins ImmunoGen from Alexion Pharmaceuticals where she started as Head of Investor Relations before moving to Head of Enterprise Finance, where she led global financial reporting and provided counsel on investment prioritization to support the companys strategic imperatives. Before Alexion, Altschuller was head of Investor Relations at Bioverativ. Early in her career, Altschuller held positions at Biogen in various functions of increasing responsibility, including investor relations, corporate finance, and commercial finance.

Signifier Medical Technologies Signifier made two key appointments, Matt Sharris as vice president of Sales in North America and Steve Saunders, as head of Sales in EMEA. These appointments follow the company strategy to drive and maximize commercial footprint later into the year in their respective geographies. Sharris was most recently director of Sales and vice president of Payor relations for Regional Home Care, with prior roles within account management and sales for ResMed. Saunders joins Signifier from Philips Respironics, where he held leadership and commercial roles, and worked as a liaison to the U.K. government during the early stages of the COVID crisis. Prior roles have included Sales and Marketing positions for a range of medical technology companies including GE, Siemens, and others.

Qkine U.K.-based Qkine expanded its leadership team with the appointments of Rob Nixon as head of Commercial and Cassie Doherty, Investment Director at Parkwalk, as a new member of the board of directors. Nixon joins after having worked for both world-leading global life science reagent companies Merck Millipore and GE Healthcare Life Science, as well as emerging, fast-growing start-up Jellagen.

Adverum Biotechnologies Thomas Kochy joined the company as vice president, commercial and program strategy. In this new position, Kochywill be responsible for leading commercial planning, product strategy, and program management. Prior to joining Adverum, Kochy served as a strategy consultant in ocular disease areas. Before that, Kochy worked at Genentech from 2004 to 2019, most recently as regional sales director for Actemra and Rituxan Immunology. He also led ophthalmology pipeline strategy and worked on Lucentis.

Homology Medicines Jeff Poulton, CFO of Alnylam, was appointed to the board of directors of Homology Medicines. Poulton brings 25 years of experience to Homologys Board of Directors, including leading finance, business development and commercial operations at companies using differentiated technologies to develop treatments for patients with rare diseases. Prior to his role at Alnylam, Poulton served as CFO at Indigo Agriculture. He previously held various roles of increasing responsibility at Shire Plc, concluding his service as CFO and a member of its executive committee and board of directors.

Cradle Genomics San Diego-based Cradle Genomics expanded its executive team with the additions of Tanya Moreno, as Vice President of Development and Sue Gross, as Chief Medical Officer. Moreno has over 13 years of experience in diagnostics development and the commercialization of genomic tests.Gross has had a distinguished clinical career with roles at Montefiore Einstein, Natera where she was CMO, and most recently at Mount Sinai Hospital and Sema4 where she was the Medical Director for the Reproductive Lab and Clinical Analysis Division.

Parexel Parexel announced the addition of former regulators with significant expertise in oncology, immunotherapy and rare disease to its Regulatory and Access Consultingteam. Yajie Li recently served as Head of Compound Strategy and Pipeline Management Function at Xuanzhu Pharma. Prior to that, she served at Janssen as the Regulatory Affairs Therapeutic Area Director for Infectious Diseases & Vaccines, China Companion Diagnostic Team Leader and the China Compound Team Leader.

Jorge Camarero served at the European Medicines Agency (EMA) in The Netherlands as an alternate member of the Committee for Medicinal Products for Human Use (CHMP) and as a member the Oncology Working Party. Prior to his tenure at the EMA, he was Head of the Oncology Area for the Spanish Agency for Medicines and Medical Devices, a Pharmaceutical Inspector for the Spanish Governments Health Department delegation; and a Regulatory Clinical Assessor in Oncology for Spanish Agency for the AEMPS. Lucas Kempf held multiple positions at the FDAs Center for Drug Evaluation and Research (CDER) and the National Institutes of Health (NIH).

Replimune Group Andrea Pirzkall will assume the role of CMO on Aug. 31 at Replimune Group. Pirzkall will lead clinical development of Replimunes pipeline of next-generation oncolytic immuno-gene therapies for the treatment of cancer. Prior to joiningReplimune, Pirzkall served as Executive Director of Clinical Development at BeiGene. She served also as the global clinical development lead on the BeiGene/Celgene joint development committee. Prior to BeiGene, Pirzkall was a Principal Medical Director atGenentech.

ZIOPHARM Oncology James Huang was named to the companys board of directors. Huang is currently a Managing Partner at Kleiner Perkins Caufield & Byers (KPCB) China and has founded and financed several innovative life sciences companies, including GenScript, Legend Biotech and Zai Lab. He is also Founding Partner of Panacea Venture, which formed TriArm Therapeutics, the funding partner for Ziopharms joint venture, Eden BioCell.

Adaptate Biotherapeutics -- Adaptate Biotherapeutics formed its Scientific Advisory Board.Adrian Hayday will chair the expert team with other key appointments including Gillian Griffiths, John Haurum, Jessica Strid and Sally Ward.

Xilio Therapeutics Paul J. Clancy was named to the Xilio Therapeutics Board of Directors. He currently serves on the boards of Agios Pharmaceuticals and Incyte Corporation. Clancy was CFO for Alexion Pharmaceuticals from July 2017 to October 2019. Prior to that, Clancy was CFO of Biogen.

Cradle Genomics Cradle Genomics expanded its executive team with the additions of Tanya Moreno, as vice president of Development and Sue Gross, as CMO. Moreno has over 13 years of experience in diagnostics development and the commercialization of genomic tests. As the head of clinical sciences, in multiple clinical laboratories, she has led development programs across a broad range of advanced genomic tools to empower patients and physicians with precision medicine. Gross has had a distinguished clinical career with roles at Montefiore Einstein where she was Professor of Obstetrics and Gynecology, Pediatrics and Genetics and most recently at Mount Sinai Hospital and Sema4 where she was the Medical Director for the Reproductive Lab and Clinical Analysis Division.

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Movers & Shakers, July 24 | BioSpace - BioSpace

]]]]]]>]]]]>]]> How can genomics help tackle the Covid-19 pandemic? Credit: Shutterstock.

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In 2003, after 13 years of work and more than 2bn spent, scientists involved in the Human Genome Project mapped the first complete genetic code, or genome, of a human being. This was a huge scientific breakthrough and taught genetics researchers a lot about human genes, the genome and how they interact with health and disease.

As further genomics work was undertaken over the next decade or so, it became evident that genome sequences are most useful when combined with other data about the person who donated their sequence, such as physiological measurements and their past medical records of previous illness and prescribed medication.

By joining up these dots, genomic medicine has the potential to improve understanding about the underlying causes of genetic diseases and predict how a person could respond to certain treatments, helping to find personalised approaches for each individual patient, as well as determining what diseases people are at risk of developing in the future.

With this in mind, the UK Government created Genomics England to coordinate work in the field. Having a centralised approach also mitigates some security concerns around the storage and use of patients incredibly private health data. The UK is an excellent location to push genomics forward. Not only does the country have a strong genetics heritage two British scientists, James Watson and Francis Crick, discovered the double helix structure of DNA in the 1950s but it has a unique resource in the National Health Service (NHS), one of the worlds largest single-payer healthcare systems in the world.

Initially focused on cancer and rare diseases known to have genetic elements, Genomics England has now diversified to look at how genomics can help track the spread of infectious disease. The organisation has joined a national consortium looking to leverage genomics to better tackle the Covid-19 pandemic. The UK has been hit extremely hard by the pandemic so far according toJohn Hopkins Covid-19 map, the UK has the second-highest number of deaths globally.

Before looking at the latest project, its important to reflect on Genomics Englands foundation and mission.

Genomics England was established in 2013 by the Department of Health and Social Care to deliver the 100,000 Genomes Project, which was launched by former Prime Minister David Cameron in late 2012.

Backed by more than 300m in government funding, the 100,000 Genomes Project aimed to create a foundation for a new era of personalised medicine within the NHS by sequencing 100,000 whole genomes from 70,000 patients with rare diseases and cancers.

To support Genomics England with recruitment for the project, NHS England set up 11 Genomic Medicines Centres (GMCs); now there are 13 in England as well as a few more in Wales, Scotland and Northern Ireland as they got on board with the project in the mid-2010s. The GMCs also helped with finding the clinical information needed to inform better interpretation of each persons genome sequence.

From the outset, Genomics England was very aware that it would need to build its own technology to complete the 100,000 Genomes Project. The company decided the best way to do this was to work with innovators in the genomics and sequencing space.

Genomics Englands first partnership was signed with California-headquartered Illumina to develop a sequencing infrastructure. As part of the deal, Illumina invested 162m in this work in the UK over the next four years.

In addition, as part of its 1bn commitment to the UKs genomics industry, the Wellcome Trust agreed to spend 27m on a world-class sequencing hub just outside Cambridge to house Genomics Englands operations. This gave the 100,000 Genomes Project easy access to world leaders in the genomics space, such as the European Bioinformatics Institute and the Sanger Institute.

Within two years of the launch, ten companies moved to collaborate with Genomics England to support and further accelerate the 100,000 Genomes Project. These companies, which included GSK, AstraZeneca, UCB, AbbVie, Roche and Takeda, established the Genomics Expert Network for Enterprises (GENE) Consortium; Big Pharma had to contribute 250,000 to the project in funding to collaborate. The aim was to carry out a year-long industry trial of select whole-genome sequences to establish how industry could leverage the learnings from the 100,000 Genomes Project into drug discovery and development. This initiative was renamed the Discovery Forum in 2017.

Simultaneously, Genomics England launched its Clinical Interpretation Partnership (GeCIP) to find ways to work with clinicians and researchers to directly bring the benefit of the 100,000 Genomes Project to drive diagnosis.

As part of a pilot scheme under the 100,000 Genomes Project, Newcastle University and Hospitals used whole-genome sequencing to reveal that a patients kidney failure was due to a rare genetic variant; this explains why his father, brother and uncle had all died of the same condition.

This diagnosis using genome sequencing meant that the patient could receive personalised treatment for this specific condition. Also, his family members could be tested to find out if they were affected by the same rare genetic kidney disease, rather than face a lifetime of uncertainty.

Hot on the heels of the first patients diagnosed, two children became the first to be genetically diagnosed through the 100,000 Genomes Project via Great Ormond Street Hospital in London. Both have rare, undiagnosed and unknown medical conditions, but due to whole-genome sequencing doctors now know the genetic changes responsible for their conditions.

NHS chief scientific officer Professor Dame Sue Hill said: This is an excellent example of how whole-genome sequencing can finally provide the answers that families have been seeking out for years. This new insight sets them free to make decisions about the treatment options for their child and how they move forward with future plans for their family.

One of the biggest challenges facing delivery of the 100,000 Genomes Project early on was to create a bioinformatics pipeline to analyse and interpret the genomics data. To this end, Genomics England decided to expand its sequencing partnership with Illumina to create informatics tools for use at the NHS GMCs and GeCIP.

This was followed later in 2016 by a deal signed with Ohio-based GenomOncology to improve clinical reporting, particularly in clinical trials, for the 100,000 Genomes Project cancer programme.

In early 2018, Genomics England and the Department of Health and Social Care announced 50,000 whole genomes had been sequenced.

This put Genomics England on track to finish recruitment and scale up operations so the full project could be completed on time by the end of 2018.

As the 100,000 Genomes Project came closer to completion, the newly appointed Secretary of State for Health and Social Care Matt Hancock announced a roadmap for honouring its legacy through continuing work on genomics medicine in the NHS.

Hancock committed to sequencing five million whole genomes by 2024 and bringing access to genetic and genomic testing into mainstream clinical practice through theNHS Genomic Medicine Service. Initially it will focus on cancer and rare diseases, like the 100,000 Genomes Project, but it is expected to evolve and expand to other therapeutic areas as the technology becomes more advanced.

At the same time, Genomics England signed a research agreement with life sciences technology vendor IQVIA. This partnership involves the pair running analytics on patient-consented, de-identified data from the 100,000 Genomes Project to drive more efficient drug research and development, particularly in the field of personalised medicine. These insights could be used by IQVIAs life science customers in parallel with their clinical development programmes.

Secretary of State for Health and Social Care Matt Hancock announced in mid-December 2018 that the 100,000 Genome Project had been completed.

Genomics England chair Sir John Chisholm noted: At launch the 100,000 Genomes Project was a bold ambition to corral the UKs renowned skills in genomic science and combine them with the strengths of a truly national health service to propel the UK into a global leadership position in population genomics.

With this announcement, that ambition has been achieved. The results of this will be felt for many generations to come as the benefits of genomic medicine in the UK unfold.

This project led to one in four participants with rare diseases receiving a diagnosis for the first time, while transforming treatment for up to half of cancer patients who participated.

Although launched at the end of 2018, the NHS Genomic Medicine Service was only expected to be operational in mid-2020.

To allow the new service to hit the ground running, Genomics England expanded its sequencing partnership with Illumina to focus on the next 300,000 whole genomes. All clinical samples for the collaboration will be provided through the NHS Genomic Medicine Service.

This follows the late-2018 deal with Congenica to support clinicians to make informed medical decisions based on insights from whole-genome sequencing. Congenica had previously provided similar sequencing services to the 100,000 Genomes Project.

Although Genomics England has primarily focused on cancer and rare diseases, it is clear that insights from genomics also have a role to play in tackling infectious disease.

In the context of the ongoing Covid-19 pandemic, which has killed more than 40,000 people in the UK to date, Genomics England is carrying out a whole-genome study of 35,000 people with either severe, moderate or mild Covid-19 symptoms to try and discover why this viral disease has such a varied impact on patients.

Genomics England will read the data from entire genomes of those who have been most severely impacted by Covid-19 and compare them to those who only experienced mild symptoms; this genomics data will also be enriched by clinical insights into participants.

The company is working with the GenOMICC consortium, Illumina, the NHS and the University of Edinburgh to carry out this study. The project is backed by 28m in funding from UK Research and Innovation, the Department of Health and Social Care and the National Institute for Health Research.

The aim is for this human genomic data to be linked to the virus genome data being sequenced by the COVID-19 Genomics UK Consortium (COG-UK), which is led by the NHS and the Sanger Institute. This would help to improve insights into how the two genomes interact and affect how the patient responds to the infection, which can feed into better knowledge about promising treatments for clinical trials and practice.

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From rare diseases to Covid-19: charting the history of Genomics England - Pharmaceutical Technology

Victoria Gray, a 34-year-old mother of four in Forest, Miss., had been going to the hospital seven times a year for transfusions to help with the severe pain brought on by her sickle cell disease. In July 2019, she volunteered for a radical new technology known as gene editing. She has been free of the pain and suffering since.

I chose to participate in this trial because of hopehope that it would change my life, Gray tells Barrons. And it has already in so many ways.

Her successful treatment gives hope to the 100,000 other Americans who suffer from sickle cell. It also illuminates the enormous potential for the companies that are pioneering genetic medicine to cure diseases with a one-time treatment.

Sickle cell is among their first targets. The companies include the sponsors of Victoria Grays clinical trial Crispr Therapeutics (ticker: CRSP) and Vertex Pharmaceuticals (VRTX)as well as biotechs like bluebird bio (BLUE), whose gene therapy for sickle cell is further along in testing and could be introduced by 2022.

For these companies, genetic therapies for sickle cell could fetch annual revenue of several billion dollars apiece. A recent Bank of America Securities report predicts that new treatments for sickle cell will surpass $6 billion in sales by 2028. That is meaningful for a company of any size, but particularly so for these biotechs. Crispr doesnt yet have sales. Bluebirds revenue last year was $45 million, and Vertexs, $4 billion.

More important, the sickle cell therapies will demonstrate how such genetic technology could open the door to curing dozens of other diseases.

Investors seem persuaded. They have lifted Crispr stock threefold since March to a recent high of $97, which values the development-stage company above $6 billion. Hitting a record high of $306, Vertexs value has topped $75 billion, while bluebirdwhose investors have waited nearly a decade for their paydaytrades at a more modest market cap of $4.2 billion. Biotech valuations may be hard to rationalize these days, but that reflects the radical changes that new technologies are bringing to the health-care business. One need look only at this years fourfold rise of the messenger RNA vaccine leader Moderna (MRNA).

The focus on sickle cell is a turnaround for the pharmaceutical industry, which had long ignored the inherited disorder. Sickle cell mainly afflicts Black Americans and residents of poor African nations. It is the most commonly diagnosed genetic disorder among newborn Americans. Yet it has not had as much funding as some less-common inherited conditions. Cystic fibrosis, for example, affects one-third as many Americans, but researchers at Duke University have shown that it has historically received more than seven times the federal and foundation research funding per patient.

This year, two new sickle cell drugs came on the market. And sometime next year, bluebird will ask the U.S. Food and Drug Administration to approve its sickle cell gene therapy. Crispr and Vertex hope that they will not be not far behind.

The starting prices of the new sickle cell treatments are expected to range from $100,000 to over $1 million. It will be a challenge to make them accessible to the millions of people in poor countries who have sickle cell.

The disease is caused by a single variation in a gene for hemoglobin, the protein that carries oxygen in our red blood cells. The genetic trait is prevalent among those whose descent traces to sub-Saharan Africa, because a single copy of the sickle cell gene protects you from developing malaria. Inherit a copy from each parent, however, and you become one of 300,000 babies born in the world each year with sickle cell disease. It causes hemoglobin molecules to form long chains that warp red blood cells into sickle shapes that get stuck in blood vessels and block the flow to vital organs.

The result is terrible pain, organ damage, infections, andwhen left untreateddeath before age 5, on average. In the U.S., where the disease occurs in one of every 365 Black babies, available treatments still leave many with a life of pain, disability, and death before age 50.

The first sickle cell treatment approved by the U.S. Food and Drug Administration was hydroxyurea, in 1998. For the half of sickle cell patients with moderate disease, treatment with hydroxyurea, antibiotics, and transfusions can allow productive lives. Hydroxyurea is off-patent and costs less than a dollar a day. But even that price is beyond reach of those who live in resource-poor countries, says Russell Ware, a pediatric hematology professor at the University of Cincinnati College of Medicine. Ware is working with medical colleagues in Uganda to get more children there on hydroxyurea.

Data as of 7/22/20

Bloomberg; company filings

The beauty is that its off-patent, says Ware, but its also a curse, because no one can make money off it.

Novartis (NVS) is supporting hydroxyurea availability in collaboration with the government of Ghana. The Swiss drug giant is also planning clinical trials in Ghana and Kenya for Adakveo, a monoclonal antibody approved by the FDA last November as one of the first novel treatments in decades for sickle cell disease. Adakveo dampens the inflammatory process that makes sickle cells clog blood vessels in cases that send some 50,000 Americans to the emergency room every year.

The intravenous drugs initial sales in the years first half were $36 million, but analysts hope that by the middle of this decade, Adakveos annual sales could reach $1 billion to $2 billion in the U.S. and Europe.

Just days after approving the Novartis drug, the FDA approved another sickle cell drug called Oxbryta, from Global Blood Therapeutics (GBT). Oxbryta is a pill that prevents defective hemoglobin from forming chains within red blood cells. The product is GBTs first, and it produced $14 million in sales for the March quarter, with a loss of $73 million.

But analysts like Yatin Suneja of Guggenheim Securities say that Oxbryta can hit sales of $1.7 billion in a few years, yielding some $13 a share in earnings for GBT. That makes Suneja think that GBT stock can rise from its current level of $72 to $115.

Successful sickle cell treatments could lift a number of biotech companies.

GBT CEO Ted Love says that Oxbrytas benign safety profile gives the company confidence that it will win approval to market the product for children, and in higher doses for adults. If other sickle cell treatments in the companys pipeline pan out, he imagines that sickle cell might one day become as well managed a disease as HIV.

Love is aware of the potentially curative gene therapies being tested by others, but he thinks that patients with milder cases of sickle cell might say, Just give me a pill.

For several decades, it has been possible to cure sickle cell with a bone-marrow transplant from a related donor. But the scarcity of matched donors and the risk of serious immune reactions have limited the number of such procedures to about 1,000. Recent breakthroughs in genetic technology promise to overcome those limitations by extracting a patients own cells, manipulating the cells genetic code, and then replacing the patients marrow with the amended cells.

The Cambridge, Mass.based bluebird bio is already in Phase 3 clinical trials of its beti-cel gene therapy for another inherited disorder of red blood cells called beta-thalassemia. Less common than sickle cell, thalassemia leaves patients with so few red blood cells that they can need more than a dozen transfusions a year. At a recent online gathering of hematologists, bluebird said that 60 children and adults with thalassemia had gone through its beti-cel procedure. About 90% had gone a year without needing a single transfusion.

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With a similar treatment for sickle cell, which bluebird calls LentiGlobin, more than two dozen patients have been infused with their own modified cells. Among the 14 patients who were six months past their treatment, there has been a 99.5% decrease in the blood vessel jam-ups that the patients previously suffered.

That is fundamentally transformative, says bluebird CEO Nick Leschly, and far exceeds any and all expectations weve ever had, any of our investigators have ever had, or the patients that have been treated.

These potentially curative cell therapies are complex procedures that are expected to be priced at about $1 million a patient. The thalassemia treatment is already approved in Europe. After the patients in bluebirds U.S. trials for thalassemia and sickle cell have been followed up for 18 months, the company will seek FDA approvalhopefully next year.

RBC Capital Markets believes that the companys sickle cell treatment could reach sales of $2 billion a year and help lift bluebird stock from its recent price of $66 to $100.

It took bluebird a decade to get to this point, and its shares have sunk as low as $17 and soared as high as $236, as investors reacted to the companys dramatic successes against refractory cancers. With Buy recommendations all along Wall Street, bluebird will get the capital it needs to cross the finish line.

Hard on the heels of bluebird are companies that believe they have better genetic treatments. One of them is Crispr Therapeutics. The company takes its name from CRISPR, shorthand for a Nobel Prizewinning technology that homes in on a targeted stretch of DNA and snips the double-stranded molecular code with a kind of chemical scissors.

The way I describe it to my patients, says patient Grays doctor Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville, is that you have a book with 500 pages of thousands of words, and we are finding one word and correcting it.

Crispr Therapeutics CEO Sam Kulkarni says that CRISPR technology should provide more durable and uniform results than earlier generation treatments like bluebirds. When Crispr reported Grays healthy progress last month, it said that a second patient with sickle cell has also been treated, as well as five patients with thalassemia. Kulkarni hopes to reach the market with his treatments not too far behind bluebird.

This years surge in Crispr Therapeutics stock allowed it to raise about $450 million in a June stock offering. Jefferies analyst Maury Raycroft has estimated that a successful sickle cell treatment could contribute a third of the $5 billion in annual revenue he projects for Crispr by 2030, with earnings above $30 a share. The stock has blasted through his last price target of $82.

Behind Crispr are still other gene-editing companies working on treatments for thalassemia and sickle cell, including Sangamo Therapeutics (SGMO), Editas Medicine (EDIT), and Intellia Therapeutics (NTLA).

One of this years most successful initial public offerings was the February debut of Beam Therapeutics (BEAM), which is in preclinical testing of sickle and thalassemia treatments that would use a next-generation editing technology that CEO John Evans believes will be even more effective than CRISPR.

If these other companies sickle cell treatments pan out, they may be scrapping for market share after bluebird and Crispr have established products. Still, as the pharmaceutical giants shop for gene-editing know-how, there may be buyouts.

Sickle cell has been a long-neglected illness, but many companies are now competing with treatments that each hopes will be best-in-class. This should be a dogfight, says bluebird CEO Leschly, because thats in the interest of patients.

Write to Bill Alpert at william.alpert@barrons.com

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These Companies Are Seeking a Cure for Sickle Cell. And Its Just the Beginning for Some Gene Therapy Stocks. - Barron's

CAMBRIDGE, Mass., July 29, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report second quarter 2020 financial results after the Nasdaq Global Market closes on Wednesday, August 5, 2020. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its second quarter 2020 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 1585717. Please specify to the operator that you would like to join the "Sarepta Second Quarter 2020 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics to Announce Second Quarter 2020 Financial Results and Recent Corporate Developments on August 5, 2020 - Yahoo Finance

Compiled by Zakiyah Ebrahim | Health24

31 Jul 2020, 08:45

When two pairs of generally healthy young brothers with no immune-related disease required mechanical ventilation in the intensive care unit (ICU), doctors and researchers at Radboud University Medical Center in the Netherlands considered whether genetic factors may have played a role in compromising their immunity.

Although the new coronavirus, SARS-CoV-2, can affect people of all ages, studies have highlightedtwo groups of peoplethat are at a higher risk of getting severe Covid-19: older people, and those with underlying medical conditions.

In the case of the first pair of brothers, one of them died due to infection, while the other recovered.

Curiosity about patients' genes

This rare occurrence triggered the curiosity of a physician from the MUMC+ (Maastricht University Medical Centre+) department of clinical genetics. She alerted her colleagues in Nijmegen who then followed up with an investigation.

"In such a case, you immediately wonder whether genetic factors could play a role," said geneticist Alexander Hoischen.

"Getting sick from an infection is always an interplay between, in this case, the virus and the human immune system. It may be a mere coincidence that two brothers from the same family became so severely ill. But it is also possible that an inborn error of the immune system played an important role. We investigated this possibility, together with our multidisciplinary team at Radboudumc."

The team found that the gene TLR7 (toll-like receptor 7) played a key role in the brothers immune response to the virus a finding that potentially has huge consequences for understanding and treating Covid-19.

Their research paper is published in The Journal of the American Medical Association (JAMA).

Genes and the immune system

All genes (collectively known as the "exome") of both brothers were sequenced. The team then followed this with a search for a possible link between their genes and Covid-19.

"We mainly looked at genes that play a role in the immune system, said Cas van der Made, a PhD student and resident at the Department of Internal Medicine, adding:

We know that several of these genes are located on the X-chromosome, and with two brother pairs affected X-chromosomal genes were the most suspicious. Women carry two X-chromosomes, while men possess a Y-chromosome apart from the X. Therefore, men have only one copy of the X-chromosomal genes. In case men have a defect in such a gene, there is no second gene that can take over that role, as in women."

The role of TLR7

TLR7 is a protein of the immune system that is encoded by the TLR7 gene. There are multiple TLR-genes which belong to a family of receptors, and these play a significant role in the recognition of pathogens (such as bacteria and viruses) and the activation of the immune system.

In this case, the researchers found mutations in the gene encoding for TLR7. Hoischen explained: "A few letters were missing in the genetic code of the TLR7 gene. As a result, the code cannot be read properly and hardly any TLR7 protein is produced.

Hoischen also explained that TLR7 function has thus far never been associated with an inborn error of immunity, and that scientists now have an indication that TLR7 is actually essential for protection against the new coronavirus.

It seems that the virus can replicate undisturbed because the immune system does not get a message that the virus has invaded. Because TLR7, which must identify the intruder and subsequently activate the defence, is hardly present. That could be the reason for the severity of the disease in these brothers," said Hoischen.

Second pair of brothers infected

When the researchers came across another pair of brothers who suffered severe Covid-19 and were both put on mechanical ventilation in the ICU, the researchers wanted to dig deeper, so they proceeded to investigate the genetic code of these two brothers as well.

They found that these two men also do not make sufficient functional TLR7 protein. Suddenly we had four young people with a defect in the same gene, all of whom had fallen seriously ill from the SARS-CoV-2 virus," said Hoischen.

Van der Made explained that their results show that SARS-CoV-2 appears to have free rein in people who do not have properly functioning TLR7, because the virus is not recognised by their immune system.

Very specific abnormality

According to Frank van de Veerdonk, immunologist and infectologist, and co-author of the study, the condition seems to be a very specific abnormality, an immunodeficiency, which is mainly related to this coronavirus, and added that this is the first time scientists have been able to connect a clinical phenomenon so strongly with TLR7.

Apart from providing new insight into the intricacies behind the operation of the immune system, the teams findings may also have critical consequences for the treatment of patients with severe Covid-19. Van de Veerdonk said that the substance "interferon" is currently being investigated for treating patients with this condition.

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How genetic mutations in healthy young men made them susceptible to severe Covid-19 - Health24

Newswise A protein that is critical for retrovirus replication may select viral genetic material for packaging within the nuclei of host cells, rather than in the cytoplasm, as was previously believed. The research, led by a team at Penn State College of Medicine, could have implications for the development of therapeutics that target this protein.

Retroviruses are a type of virus that use cells asmachines to make more virus particles that are spread fromcell to cell. There are three major infectious human retroviruses, including human immunodeficiency virus-1 (HIV-1) the cause of acquired immunodeficiency syndrome (AIDS). The lab of Dr. Leslie Parent, vice dean for research and graduate studies and professor of medicine, studies the avian retrovirus Rous sarcoma virus, which replicates similarly to HIV and causes tumors in domestic fowl.

Their research focuses on the role of a special protein called Gag that acts as an escort for genetic material in viral replication. It forms a complex by binding to the viral ribonucleic acid (RNA) to package it into an infectious virus particle. According to Parent, a professor of medicine and microbiology and immunology, their latest discovery puts scientists one step closer to developing therapeutics that can stop this complex from forming.

Our primary goal has been to understand where the initial interaction between the Gag protein and viral RNA occurs, said Parent. Other drugs and approaches have targeted viral replication after these complexes form. Our hope is that if we can better understand this interaction, early intervention strategies could be developed.

For years, scientists who studied retroviruses believed that Gag protein and viral RNA interacted only in the cytoplasm of the cell. But prior work by the Parent lab revealed that Gag proteins entered the nucleus of the cell as well. Based on that finding, they hypothesized that Gag protein might select viral RNA for packaging in the nucleus, where the RNA is made.

With so much activity going on in a cell, Parent and her colleagues put fluorescent labels on the Gag protein and viral RNA so they could watch their interactions in live cells using confocal microscopy. The images and videos of this process were captured and published with their data in mBio, a journal of The American Society for Microbiology.

As they hypothesized, they observed that Gag does bind viral RNA in the nucleus, and the complex traffics out of the nucleus. They propose that the viral Gag-RNA complex ultimately travels to the outer membrane of the cell where the viral particle is released to infect new cells. According to Parent, advances in technology have made this finding possible.

Visualizing a live cell in real time allows you see the intricate dynamics of its functions, Parent said. She noted the College of Medicines core facilities, including leading-edge live-cell microscopy, were integral to carrying out this project that has been years in the making. When you observe a cell over time, you can see the start, end and speed of various processes. It allows you to witness how a live cell deals with a viral infection.

Rebecca Kaddis Maldonado and Breanna Rice, postdoctoral scholars at the College of Medicine and coauthors on the publication, said knowing that Gag protein selects viral RNA in the nucleus opens up more questions that will be explored in future studies. They want to understand more about the kinetics of the interaction between Gag protein and viral RNA in the nucleus, mechanisms for how the complex moves outside the nucleus, and what other elements of the host cell may play a role in the process.

This observation is just the first of a series of investigations we need to carry out in order to understand this interaction, Maldonado said. The more we know about the details of this process, the better suited well be to propose or develop therapeutic targets.

Coauthors include Eunice Chen, Kevin Tuffy and Estelle Chiari of Penn State College of Medicine and Kelly Fahrbach and Thomas Hope of Northwestern University. Eunice Chen is a student in the College of Medicines MD/PhD Medical Scientist Training Program.

This research was supported by grants from the Pennsylvania Department of Health using Tobacco Settlement CURE Funds and the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Pennsylvania Department of Health.

The authors declare no conflict of interest.

About Penn State College of Medicine Located on the campus of Penn State Health Milton S. Hershey Medical Center in Hershey, Pa., Penn State College of Medicine boasts a portfolio of nearly $100 million in funded research. Projects range from development of artificial organs and advanced diagnostics to groundbreaking cancer treatments and understanding the fundamental causes of disease. Enrolling its first students in 1967, the College of Medicine has more than 1,700 students and trainees in medicine, nursing, the health professions and biomedical research on its two campuses.

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Caught in the act microscopy reveals key detail in retrovirus replication - Newswise

A multi-omics, multi-algorithm approach will unleash a new wave of understanding around Alzheimers disease and diagnosis, that in time, will make precision diagnostics practical, speakers predicted at the Alzheimers Association International Conference 2020 virtual event, held July 27-31. At least a part of that understanding will be based on the biomarkers identified during this meeting.

For analytics, a multi-tool approach is moving the emphasis from determining which algorithm is better to how to put the tools together (to get the most accurate information possible), Christos Davatzilos, Ph.D., University of Pennsylvania School of Medicine, said during a live chat. That enables researchers to be less focused on the engineering aspects and thus to work as translational scientists as more is learned about the brain and neurological diseases.

There are different criteria for performance than for triaging individuals based on biomarkers, Duygu Tosun-Turgut, Ph.D., University of California San Francisco, said. We need to be very mindful of the algorithms and how they are meant to be used for clinical practice of translational trials.

Therefore, as Davatzilos said, Its difficult to say any one algorithm is the best, but you can say this is best under certain conditions or for certain problems. Ultimately, AI wont be very different from biostatistics now, in that there are many options and many criteria researchers need to consider when choosing their tools.

So far, vetting various algorithms and approaches has received a good deal of attention.

We need such a diversity of means of discovery. With a multi-omics approach, researchers have independent sources of validation they can use to verify (their results) using a separate approach, said Paul M. Thompson, Ph.D., University of Southern California.

Initially, Thompson recalled, We learned a lot from the psychiatric researchers. They advised against using physical self-maintenance (PSM) scores, as criteria during the first round of analysis because of the high percentage of false positives those scored could generate. Now that more computing power is available and machine learning can be applied to the research, that advice becomes less valid because researchers have the means of sorting through the data.

There will be a new wave of discovery when people accept machine learning, Dr. Thompson added.

Machine learning opens the door to increasingly predictive approaches. For example, Andrew Saykin, Psy.D., director of the Indiana Alzheimer Disease Center, pointed out, Were being so stringent that were filtering out things that may be important in our concern to eliminate noise.

As an example, Thompson mentioned an MRI study of 11,000 young to middle-aged people.

We didnt find apolipoprotein E (APOE), the strongest known genetic risk factor for developing Alzheimers disease. That study shows that subjects ages matter, because APOE becomes more prevalent in people after age 60. It also suggests that, as Thompson said, If you build in interactions or other conditions, such as druggable characteristics, there may be better filters than the statistical sledgehammer that is being used today.

One possibility is a better understanding of the effects of various risk factors on cognitive trajectories in early- and late-onset Alzheimers disease. A team from South Koreas Sungkyunkwan University, the Samsung Medical Center, Samsung Alzheimer Research Medical Center, and in the US, from Harvard Medical School and Indiana University found that conventional risk factors accelerated cognitive decline in late-onset Alzheimers but slowed the decline among early-onset patients.

In studying the effects of APOE4, they found that outcomes varied based upon whether the patients carried that protein. Specifically, early-onset patients who did not carry APEO4 had a more rapid cognitive decline, but not those with late-onset Alzheimers disease. Likewise, higher levels of education accelerated cognitive decline in both early- and late-onset patients, but the most pronounced effects were among those with early-onset Alzheimers disease.

This research team also found that hypertension and obesity slowed cognitive decline in early-onset Alzheimers patients, but not in late-onset patients. Not surprisingly, the team noted that additional research is needed to determine the genetic and environmental factors behind declines in early-onset patients who lack any known risk factors.

In other meeting highlights, a poster presented Tuesday by Xiaohui Yao, Ph.D., and Li Shen, PhD., both of the University of Pennsylvania, predicted tissue-specific gene targets for Alzheimers disease. The researchers combined genome-wide association studies and data from expression quantitative trait loci (eQTL) to identify several genes in various tissues that have multiple associations (pleiotrophy) between their expression levels and the diagnosis of Alzheimers disease.

Fourteen genes and 13 brain tissues showed 64 significant associations. The gene CTB-171A8.1 exhibited the highest level of associations, with log p values typically beyond 10m and, for specific tissues, often above 12.5. The highest levels were associated with the cortex, cerebellum, and caudate basal ganglia, although activity was exhibited in all 13 brain tissues. The next most active gene was CEACAM19, which was involved in 10 of the tissues. Yao and Shen plan to continue investigating these genes as targets for functional validation.

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AAIC 2020: Multi-omics and Biomarkers Emerge as Key Elements in the Future of Alzheimer's Research - BioSpace

BALA CYNWYD, Pa., July 28, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases,today announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on the companys application for orphan drug designation for CTI-1601, a potential treatment for Friedreichs ataxia (FA), a rare, progressive, multi-symptom genetic disease that affects the functioning of multiple organs and systems. CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with FA who are unable to produce enough of this essential protein. The U.S. Food and Drug Administration (FDA) previously granted Orphan Drug, Fast Track and Rare Pediatric Disease designations to CTI-1601 for the treatment of FA. Larimar expects that the European Commission, based on this positive opinion of the COMP, will formally grant the orphan drug designation for the European Union (EU) this year.

The positive opinion for orphan drug designation from the EMA COMP is an important milestone to bring a much-needed potential therapy to patients with FA, a devastating disease that currently has no approved medical treatments, said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar Therapeutics.We look forward to working closely with EMA and continuing our U.S. Phase 1 trial of CTI-1601, which has the potential to become the first frataxin replacement therapy for patients with FA. We remain on track to report topline data in the first half of 2021.

Orphan drug designation in the EU is granted by the European Commission based on a positive opinion issued by the EMA COMP. To qualify, an investigational medicine must be intended to treat a seriously debilitating or life-threatening condition that affects fewer than five in 10,000 people in the EU, and there must be sufficient non-clinical or clinical data to suggest the investigational medicine may produce clinically relevant outcomes. EMA orphan drug designation provides companies with certain benefits and incentives, including clinical protocol assistance, differentiated evaluation procedures for Health Technology Assessments in certain countries, access to a centralized marketing authorization procedure valid in all EU member states, reduced regulatory fees and 10 years of market exclusivity.

About CTI-1601 CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with Friedreichs ataxia (FA) who are unable to produce enough of this essential protein. Currently in a Phase 1 clinical trial in the U.S., CTI-1601 has been granted Rare Pediatric Disease designation, Fast Track designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA). Topline results from the Phase 1 clinical program are planned for the first half of 2021.

About Friedreichs ataxiaFriedreichs ataxia (FA) is a rare, progressive, multi-symptom genetic disease that typically presents in mid-childhood and affects the functioning of multiple organs and systems. The most common inherited ataxia, FA is a debilitating neurodegenerative disease resulting in multiple symptoms including progressive neurologic and cardiac dysfunction poor coordination of legs and arms, progressive loss of the ability to walk, generalized weakness, loss of sensation, scoliosis, diabetes and cardiomyopathy as well as impaired vision, hearing and speech. FA affects an estimated 4,000-5,000 individuals living in the United States and approximately 25,000 in the European Economic Area and United Kingdom. FA results from a deficiency of the mitochondrial protein, frataxin (FXN), which is found in cells throughout the body. To date, there are no medical treatment options approved for patients with FA.

About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq:LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. The companys lead compound, CTI-1601, is currently being evaluated in a Phase 1 clinical program in the U.S. as a potential treatment for Friedreichs ataxia, a rare and progressive genetic disease. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.

Forward-Looking StatementsThis press release contains forward-looking statements that are based on Larimars managements beliefs and assumptions and on information currently available to management. All statements contained in this release other than statements of historical fact are forward-looking statements, including but not limited to statements regarding the receipt of Orphan Drug Designation for the EU for CTI-1601 in FA from the European Commission, the expected timing for receiving Orphan Drug Designation from the European Commission, the expected incentives associated with receiving Orphan Drug Designation for CTI-1601, Larimars ability to develop and commercialize CTI-1601 and other planned product candidates, Larimars planned research and development efforts, and other matters regarding Larimars business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations.

In some cases, you can identify forward-looking statements by the words may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks, uncertainties and other factors include, among others, the that European Commission may not grant Orphan Drug Designation for the EU for CTI-1601 in FA or may do so in a longer than anticipated timeframe, the success, cost and timing of Larimars product development activities, studies and clinical trials; the ongoing impact of the COVID-19 pandemic on Larimars clinical trial timelines, ability to raise additional capital and general economic conditions; Larimars ability to optimize and scale CTI-1601s manufacturing process; Larimars ability to obtain regulatory approval for CTI-1601 and future product candidates; Larimars ability to develop sales and marketing capabilities, whether alone or with potential future collaborators, and successfully commercialize any approved product candidates; Larimars ability to raise the necessary capital to conduct its product development activities; and other risks described in the filings made by the Company with the Securities and Exchange Commission (SEC), including but not limited to Larimars periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available atwww.sec.gov. These forward-looking statements are based on a combination of facts and factors currently known by Larimar and its projections of the future, about which it cannot be certain. As a result, the forward-looking statements may not prove to be accurate. The forward-looking statements in this press release represent views as of the date hereof. Larimar undertakes no obligation to update any forward-looking statements for any reason, except as required by law.

Investor Contact:John WoolfordWestwickejohn.woolford@westwicke.com443-213-0506

Media Contact:Gina Cestari6 Degrees(917) 797-7904gcestari@6degreespr.com

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Larimar Therapeutics Announces Positive Opinion on Orphan Drug Designation Received from the European Medicines Agency for CTI-1601 for the Treatment...

WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZenecas TAGRISSO (osimertinib) has been granted Breakthrough Therapy Designation (BTD) in the US for the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent.

The Food and Drug Administrations (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging early clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

While up to 30% of patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is common in early-stage disease and nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, experience recurrence within five years.1-6

Jos Baselga, Executive Vice President, Oncology R&D said: Patients with early-stage EGFRm lung cancer often experience recurrence even after successful surgery and adjuvant chemotherapy, yet there are currently no approved targeted treatments to improve outcomes. The Phase III ADAURA trial with TAGRISSO demonstrated an unprecedented level of clinical benefit in these patients, and we are working closely with the FDA to deliver this potentially curative treatment to patients as quickly as possible.

The FDA granted the BTD based on data from the Phase III ADAURA trial, which were also recently presented during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program.

In the trial, TAGRISSO demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the adjuvant treatment of Stage IB-IIIA EGFRm NSCLC patients, reducing the risk of disease recurrence or death by 79% (HR 0.21; 95% CI 0.16-0.28; p<0.0001) in a key secondary endpoint. In April 2020, an Independent Data Monitoring Committee recommended the trial to be unblinded two years early based on its determination of overwhelming efficacy.

TAGRISSO is approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

TAGRISSO IMPORTANT SAFETY INFORMATION

INDICATIONS

Please see complete Prescribing Information, including Patient Information.

NOTES TO EDITORS

About lung cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.7 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.8 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3 A significant portion of patients with resectable NSCLC eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy. Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of tumor cells.12

About ADAURA

ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, and IIIA EGFRm NSCLC with complete tumor resection and adjuvant chemotherapy as indicated. In the experimental arm, patients were treated with TAGRISSO 80 mg once-daily oral tablets for three years or until disease recurrence. The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint is DFS in Stage II and IIIA patients and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess OS.

About TAGRISSO

TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against CNS metastases. TAGRISSO 40 mg and 80 mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm advanced NSCLC. TAGRISSO is also being developed in the Stage III, unresectable setting (LAURA), in the neoadjuvant resectable setting (NeoADAURA), in combination with chemotherapy (FLAURA2) and in combination with potential new medicines to address resistance to EGFR-TKIs (SAVANNAH, ORCHARD).

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action. AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines gefitinib and TAGRISSO, and its ongoing Phase III trials LAURA, NeoADAURA, and FLAURA2.9-11

AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD, which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Trastuzumab deruxtecan, a HER2-directed antibody drug conjugate (ADC), is in development for metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC, including trials in combination with other anticancer treatments. In addition, DS-1062, a trophoblast cell-surface antigen 2 (TROP2)-directed ADC, is in early development for advanced NSCLC where TROP2 is overexpressed in the majority of patients.13

An extensive, late-stage, Immuno-Oncology program focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.14 Durvalumab, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease including potentially curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Durvalumab is also in development in the Phase II trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline including trastuzumab deruxtecan.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focusing on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit http://www.astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

References 1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137:11911198.2. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196198.3. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123: 20962103.4. Sasaki H, et al. Prognosis of Recurrent NonSmall Cell Lung Cancer Following Complete Resection. Oncol Lett. 2014:7;1300-1304.5. Fink-Neuboeck N, et al. Hazards of Recurrence, Second Primary, or Other Tumor at Ten Years After Surgery for NonSmall-Cell Lung Cancer. Clinical Lung Cancer. Accessed February 25 2020. https://www.doi.org/10.1016/j.cllc.2020.02.011.6. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:35523559.7. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. http://www.gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed July 2020.8. LUNGevity Foundation. Types of Lung Cancer. https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed July 2020.9. Szumera-Ciekiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.10. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-2127.11. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.13. Zaman S, et al. Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther. 2019; 12: 1781-1790.14. Pakkala S, et al. Personalized Therapy for Lung Cancer: Striking a Moving Target. JCI Insight. 2018;3(15):e120858.

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TAGRISSO Granted Breakthrough Therapy Designation in the US for the Adjuvant Treatment of Patients With Stage IB-IIIA EGFR-mutated Lung Cancer -...

Prior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited.We sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center.The medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian).A total of 1666 patients met inclusion criteria (non-Hispanic Whites, 1367; Hispanics, 85, non-Hispanic Blacks, 101; Asians, 113).Demographics, patient characteristics, and referral patterns for patients who underwent genetic testing were analyzed using Kruskal-Wallis tests, chi-square test, or Fishers exact tests, stratifying by self-reported race/ethnicity. Pathogenic mutations and variants of unknown significance (VUS) were reviewed. Outcomes of patients with genetic mutations and personal history of breast and/or gynecologic malignancies were compared.Non-Hispanic Whites were more likely to be referred due to family cancer history compared to all other ethnicities while Non-Hispanic Blacks, Hispanics, and Asians were more likely to be referred due to personal history of cancer (p<0.001). Non-Hispanic Blacks and Hispanics were more likely to have advanced-stage cancer at the time of genetic testing (p<0.02). Rates of mutations did not differ by race/ethnicity when Ashkenazi Jewish patients were excluded (p=0.08). Among patients found to have a BRCA1/2 mutation, Non-Hispanic Whites were more likely to undergo cancer screening and risk-reducing surgery compared with all other ethnicities (p=0.04).Minority patients were more likely to utilize genetic services following a cancer diagnosis and less likely due to family cancer history, suggesting a missed opportunity for mutation detection and cancer prevention in this population. Efforts to eradicate racial/ethnic disparities in early access to genetic testing and guided cancer prevention strategies are essential.

PubMed

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Racial and Ethnic Disparities in Genetic Testing at a Hereditary Breast and Ovarian Cancer Center. - Physician's Weekly