BEDFORD, Mass.--(BUSINESS WIRE)--Stoke Therapeutics, Inc., (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of genetic diseases by precisely upregulating protein expression, today announced the appointment of Julie Anne Smith to its Board of Directors. Ms. Smith has also been appointed to the Compensation Committee of the Board of Directors. Ms. Smith will replace Samuel Hall, Ph.D., whose term on the Board of Directors expired.

Julie brings more than two decades of experience in the life sciences industry, with a strong track record of successfully developing and commercializing medicines for rare and inherited diseases. Her expertise in drug development for neurodegenerative diseases will be particularly valued as we advance STK-001 for Dravet syndrome into the clinic later this year, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. We thank Sam for his many important contributions to Stoke from our inception and as we matured through our successful IPO to become a public company prepared to enter the clinic with STK-001, the first potential medicine developed using our TANGO platform. We welcome Julie to the Board and look forward to her insights and contributions.

This is an exciting time for Stoke as it transitions to a clinical stage company and looks to the future, said Ms. Smith. I am pleased to work with the Board members and the executive leadership team as they advance their work in Dravet and expand the pipeline to help people who are living with severe genetic diseases and realize the potential of the TANGO platform.

Ms. Smith currently serves as President and CEO of ESCAPE Bio, Inc., a biotechnology company developing precisely targeted therapeutics for genetic forms of neurodegenerative disease. She previously served as President and CEO of Nuredis, Inc., a biotechnology company developing small-molecule therapies for nucleotide repeat disorders such as Huntingtons disease. In 2014, Ms. Smith was appointed President and CEO at Raptor Pharmaceuticals, a public biotechnology company with two commercial medicines for orphan diseases, where she served until its acquisition in 2016 (by Horizon Pharmaceuticals, Inc.). Prior to joining Raptor, Ms. Smith served as the Chief Commercial Officer at Enobia Pharmaceuticals (acquired by Alexion Pharmaceuticals, Inc.). Earlier in her career, she held positions of increasing responsibility at Jazz Pharmaceuticals plc, Genzyme, Novazyme and Bristol-Myers Squibb Company.

Ms. Smith previously served on the board of directors of Audentes Therapeutics, Inc., a genetic medicines company, and as a director on the Health and Emerging Companies Section Governing Boards of the Biotechnology Industry Organization (BIO). She currently serves on the board of directors of Exelixis, Inc., a public genomics-based drug discovery company. Ms. Smith holds a B.S. in biological and nutritional sciences from Cornell University.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Stokes expectation about timing and execution of anticipated milestones with respect to STK-001, including advancement of STK-001 to the clinical stage, and expansion of the Companys pipeline. Statements including words such as plan, continue, expect, or ongoing and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause Stokes actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Stokes ability to develop, obtain regulatory approval for and commercialize STK-001 and its future product candidates, the timing and results of preclinical studies and clinical trials, Stokes ability to protect intellectual property; and other risks set forth in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These forward-looking statements are based on our current believes and expectations and speak only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking statements.

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HOUSTON, June 4, 2020 /PRNewswire/ -- The Golden Helix Foundation and the Pharmacogenomics Access & Reimbursement Coalition (PARC) will co-present the inaugural Pharmacogenomics Access & Reimbursement Symposium (PARS) at the National Academy of Sciences Building on October 8, 2020 in Washington D.C. to define opportunities to expand patient access to personalized medicine. Public- and private- sector members across healthcare will assemble to develop a path forward through discussions of best practices, improved economic evaluation and strategic alignment.

"Since genetic variation impacts medication responses, it is important to leverage technologies that can translate genetic information into care tailored for each patient.Market access is a critical step in achieving widespread adoption of personalized medicine." Sara Rogers, PARC Co-Chairman and Director at the American Society of Pharmacovigilance.

The symposium program includes speakers from industry, government agencies, payer organizations, health systems and health policy organizations. Thought leaders will explore the newest developments in health technology assessment, health economics and value-based payment strategies for pharmacogenomics. In addition to convening decision-makers from around the world, the symposium will develop solutions that identify actionable ways that stakeholders can work together to democratize personalized medicine.

"Defining the value of personalized medicine interventions is of utmost importance to expedite the incorporation of these innovative healthcare solutions in routine clinical practice that would directly impact patient care and quality of life." Christina Mitropoulou, The Golden Helix Foundation Managing Director, Executive Board member and Principal Investigator of the Ubiquitous Pharmacogenomics Consortium.

Organizations across health care have partnered to support the symposium, including Intermountain Precision Genomics, Medical Device Innovation Consortium (MDIC) and Pharmacogenomics Research Network (PGRN). Stakeholders are encouraged to join the discussion by registering to participate athttp://www.parcoalition.org/symposium. A live webcast will be provided to accommodate attendees who prefer to participate remotely.

About the Golden Helix Foundation The Golden Helix Foundation is an international non-profit research organization (registered London-based UK charity) aiming to advance research and education in the area of genome and personalized medicine. The Golden Helix Foundation aims to promote the development of research and the transfer and communication of knowledge from researchers and scientists in the wider scientific community through collaborative projects and conferences in the field of pharmacogenomicsand personalized medicine.

About the Pharmacogenomics Access & Reimbursement Coalition (PARC)PARC seeks to address barriers to patient access and payer coverage of Pharmacogenomics (PGx) testing by sharing resources and leveraging shared expertise in PGx. For more information, please contact [emailprotected] and follow @PGxARC

American Society of PharmacovigilanceP.O. Box 20433Houston, TX 77225www.stopADR.org

Contact: Geneva MorelDirector of Communications Email: [emailprotected] phone: 469-939-8475

SOURCE American Society of Pharmacovigilance

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The Golden Helix Foundation and PARC Co-Present International Meeting to Expand Patient Access to Personalized Medicine - PRNewswire

Mark Williams The Columbus Dispatch

TuesdayJun2,2020at5:11PM

A Massachusetts-based biopharmaceutical company plans to create 100 jobs as part of an expansion of its Columbus operations.

Sarepta Therapeutics will open an 85,000-square-foot building at 3435 Stelzer Rd. as part of its Gene Therapy Center of Excellence.

The company says it will invest more than $30 million, and that hiring for research, technician and general operations positions will begin immediately.

Employees currently working out of the companys offices in Dublin will move to the new building over time.

Sarepta, based in Cambridge, focuses on gene therapy programs to treat rare diseases.

It has two approved drugs for Duchenne muscular dystrophy and more than 40 treatments in development.

Duchenne slowly steals muscle, making children weaker and weaker as they grow older. Many died by their mid-20s. The disease afflicts mostly boys.

We are confident that gene therapy will revolutionize genetic medicine, and we chose Ohio for our Gene Therapy Center of Excellence because we believe Columbus will become a hub for genetic medicine innovation, the companys president and CEO, Doug Ingram, said in a statement.

mawilliams@dispatch.com

@BizMarkWilliams

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Sarepta to expand Columbus operations, add 100 jobs - The Columbus Dispatch

CARLSBAD, Calif., June 2, 2020 /PRNewswire/ --Prescient Medical, a subsidiary of Prescient Medicine Holdings, Inc., announced today a research collaborationwith the Harvard Chan Microbiome in Public Health Center (HCMPH Center), a group at Harvard T.H. Chan School of Public Health dedicated to expanding research on the microbiome to improve public health. The aim of the collaboration is tostudy microbial biomarkers to identify the presence of precancerous adenomas and carcinomas in the colon. The initial collaboration will investigate prevalent gut microbial biomarkers for colorectal cancer (CRC) by analyzing known, recent CRC cases across populations with which the HCMPH Center works and applying cutting-edge statistical and bioinformatic techniques for microbiome meta-analysis.

"The ongoing research collaboration will further enhance diagnostic screening for colon cancer," said Keri Donaldson, M.D, chief executive officer at Prescient Medicine. "Offering a non-invasive alternative to colonoscopies that screen for colorectal adenomas and carcinomas could represent a paradigm shift in CRC screening driven by the microbiome. Therefore, research to better understand the microbiome's role in CRC is needed at this time."

Curtis Huttenhower, Ph.D., professor of computational biology at Harvard Chan School and co-director of the HCMPH Center, said, "The mission of the HCMPH Center is to improve population health via microbiome science, and there are few chronic disease conditions as well-positioned to benefit from microbiome screening as colorectal cancer. It is one of the most common causes of cancer deaths, but also one of the most preventable cancers if detected early. It's exciting to embark on this collaboration to advance the latest science and, I hope, eventually deploy our findings to the clinic."

The past decade has seen a dramatic expansion of research on the human microbiome, including investigation into the role of microbes and microbiota in the gastrointestinal track in the origin and development of CRC. The advancements in this field parallel the preceding decade's growth in personalized genetic medicine, with the microbiome offering opportunities for both therapeutic and diagnostic biomarker discovery.

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in both men and in women. The U.S. spends approximately $14 billion each year for the diagnosis and treatment of CRC with costs largely due to delayed detection. There is a lack of non-invasive screening tests that can accurately detect precancerous polyps as effectively as a colonoscopy, the current standard of care. Screening recommendations currently suggest acolonoscopy for average-risk patients starting at age 45 every 10 years and earlier for high-risk patients, but approximately one in three patients are not in compliance with these recommendations.Research indicates that early detection of precancerous adenomas and carcinomas could lead to significantly better patient outcomes.

About Prescient Metabiomics Prescient Metabiomics LLC, a privately held company and subsidiary of Prescient Medicine Holdings, Inc., is an early stage molecular diagnostics company developing in-vitro diagnostics that leverage breakthroughs in next-generation DNA sequencing, computational systems biology, and human microbiome sciences. To learn more, visit http://www.metabiomics.com.

About Prescient Medicine HoldingsPrescient Medicine Holdings, Inc. is a privately held company focused on developing diagnostic tools that advance the precision healthcare movement.Prescient Medicine's mission is to accelerate the development, commercialization and deployment of advanced clinical diagnostics to address the most pressing public health issues in the U.S. Prescient Medicine designs powerful tests and analytic solutions to offer deep predictive insights so doctors and patients have the data they need to make more informed clinical decisions and achieve the best possible patient outcomes. Prescient Medicine technologies include LifeKitPrevent designed to detect colon cancer and precancerous adenomas and LifeKitPredict, an in vitro diagnostic test commercialized in partnership with its subsidiary AutoGenomics, used for the identification of patients who may be at risk for opioid dependency. To learn more, visit http://www.prescientmedicine.com.

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SOURCE Prescient Medicine; Prescient Metabiomics

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Prescient Metabiomics and the Harvard Chan Microbiome in Public Health Center Collaborate to Advance Research in Colon Cancer Screening - BioSpace

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Chemical compound restores tetracycline's effectiveness by blocking bacterial resistance

Shown above are two different 3D views of TetX7 (green), a tetracycline-destroying enzyme that causes resistance to all tetracycline antibiotics (the small multicolored molecule in the center). Researchers at Washington University in St. Louis and the National Institutes of Health (NIH) have found that genes that confer the power to destroy tetracyclines are widespread in bacteria that live in the soil and on people.

The latest generation of tetracyclines a class of powerful, first-line antibiotics was designed to thwart the two most common ways bacteria resist such drugs. But a new study from researchers at Washington University in St. Louis and the National Institutes of Health (NIH) has found that genes representing yet another method of resistance are widespread in bacteria that live in the soil and on people. Some of these genes confer the power to destroy all tetracyclines, including the latest generation of these antibiotics.

However, the researchers have created a chemical compound that shields tetracyclines from destruction. When the chemical compound was given in combination with tetracyclines as part of the new study, the antibiotics lethal effects were restored.

The findings, available online in Communications Biology, indicate an emerging threat to one of the most widely used classes of antibiotics but also a promising way to protect against that threat.

We first found tetracycline-destroying genes five years ago in harmless environmental bacteria, and we said at the time that there was a risk the genes could get into bacteria that cause disease, leading to infections that would be very difficult to treat, said co-senior author Gautam Dantas, PhD, a professor of pathology and immunology and of molecular microbiology at Washington University School of Medicine in St. Louis. Once we started looking for these genes in clinical samples, we found them immediately. The fact that we were able to find them so rapidly tells me that these genes are more widespread than we thought. Its no longer a theoretical risk that this will be a problem in the clinic. Its already a problem.

In 2015, Dantas, also a professor of biomedical engineering, and Timothy Wencewicz, PhD, an associate professor of chemistry in Arts & Sciences at Washington University, discovered 10 different genes that each gave bacteria the ability to dice up the toxic part of the tetracycline molecule, thereby inactivating the drug. These genes code for proteins the researchers dubbed tetracycline destructases.

But they didnt know how widespread such genes were. To find out, Dantas and first author Andrew Gasparrini, PhD then a graduate student in Dantas lab screened 53 soil, 176 human stool, two animal feces, and 13 latrine samples for genes similar to the 10 theyd already found. The survey yielded 69 additional possible tetracycline-destructase genes.

Then they cloned some of the genes into E. coli bacteria that had no resistance to tetracyclines and tested whether the genetically modified bacteria survived exposure to the drugs. E. coli that had received supposed destructase genes from soil bacteria inactivated some of the tetracyclines. E. coli that had received genes from bacteria associated with people destroyed all 11 tetracyclines.

The scary thing is that one of the tetracycline destructases we found in human-associated bacteria Tet(X7) may have evolved from an ancestral destructase in soil bacteria, but it has a broader range and enhanced efficiency, said Wencewicz, who is a co-senior author on the new study. Usually theres a trade-off between how broad an enzyme is and how efficient it is. But Tet(X7) manages to be broad and efficient, and thats a potentially deadly combination.

In the first screen, the researchers had found tetracycline-destructase genes only in bacteria not known to cause disease in people. To find out whether disease-causing species also carried such genes, the scientists scanned the genetic sequences of clinical samples Dantas had collected over the years. They found Tet(X7) in a bacterium that had caused a lung infection and sent a man to intensive care in Pakistan in 2016.

Tetracyclines have been around since the 1940s. They are one of the most widely used classes of antibiotics, used for diseases ranging from pneumonia, to skin or urinary tract infections, to stomach ulcers, as well as in agriculture and aquaculture. In recent decades, mounting antibiotic resistance has driven pharmaceutical companies to spend hundreds of millions of dollars developing a new generation of tetracyclines that is impervious to the two most common resistance strategies: expelling drugs from the bacterial cell before they can do harm, and fortifying vulnerable parts of the bacterial cell.

The emergence of a third method of antibiotic resistance in disease-causing bacteria could be disastrous for public health. To better understand how Tet(X7) works, co-senior author Niraj Tolia, PhD, a senior investigator at the National Institute of Allergy and Infectious Diseases at the NIH, and co-author Hirdesh Kumar, PhD, a postdoctoral researcher in Tolias lab, solved the structure of the protein.

I established that Tet(X7) is very similar to known structures but way more active, and we dont really know why because the part that interacts with the tetracycline rings is the same, Kumar said. Im now taking a molecular dynamics approach so we can see the protein in action. If we can understand why it is so efficient, we can design even better inhibitors.

Wencewicz and colleagues previously designed a chemical compound that preserves the potency of tetracyclines by preventing destructases from chewing up the antibiotics. In the most recent study, co-author Jana L. Markley, PhD, a postdoctoral researcher in Wencewiczs lab, evaluated that inhibitor against the bacterium from the patient in Pakistan and its powerful Tet(X7) destructase. Adding the compound made the bacteria two to four times more sensitive to all three of the latest generation of tetracyclines.

Our team has a motto extending the wise words of Benjamin Franklin: In this world nothing can be said to be certain, except death, taxes and antibiotic resistance, Wencewicz said. Antibiotic resistance is going to happen. We need to get ahead of it and design inhibitors now to protect our antibiotics, because if we wait until it becomes a crisis, its too late.

Gasparrini AJ, Markley JL, Kumar H, Wang B, Fang L, Irum S, Symister C, Wallace M, Burnham CAD, Andleeb S, Tolia NH, Wencewicz TA, Dantas G. Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance. Communications Biology. May 15, 2020. DOI: 10.1038/s42003-020-0966-5

This work is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), grant number R01 AI123394; the National Institute of General Medical Sciences, training grant number T32 GM007067; the National Institute of Diabetes and Digestive and Kidney Diseases, training grant number T32 DK077653; and Washington University, W.M. Keck Postdoctoral Program in Molecular Medicine and the Chancellors Graduate Fellowship Program.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Antibiotic-destroying genes widespread in bacteria in soil and on people - Washington University School of Medicine in St. Louis

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

After Italy saw its first case of COVID-19 in late February 2020, the country quickly became a global hubfor the virus. With over 233,000 cases and more than 33,000 deaths to date, the virus was more fatal in Italy than in China. To slow the spread, the government ordered everyone to stay home. Now, infection rates are finally falling.

And as the country begins to reopen, a handful of Italian doctors say the deadly virus is losing steam.

"In March and April, patients reached the emergency room very sick. They had acute respiratory distress syndrome, multi-organ failure. They needed immediate oxygen, ventilation, and in two to three days, we had patients that died," says Matteo Bassetti, MD, director of the Infectious Diseases Clinic at the San Martino Hospital in Genoa. "But now, in the past four to five weeks, it's been totally different. Patients of a similar age as the ones before, even very elderly patients, are not as sick as patients were just four to six weeks before."

In stark opposition to Bassetti's and other doctors' statements, Italian public health officials and the World Health Organization (WHO) warn there's no evidence to support these claims. They urge health care providers and the public to continue to take the virus extremely seriously. Meanwhile, Bassetti says proof is on the way.

"One of the golden rules of virology," says Mark Cameron, PhD, an associate professor of population and quantitative health sciences at Case Western Reserve University School of Medicine, "is that viruses that circulate in the community do change and mutate."

They do this, he says, to survive. A virus that's deadly enough to kill all of its hosts will die out as soon as the last infected person dies. A weaker form of the virus -- one that doesn't make people quite as sick -- can continue to travel from person to person.

"A virus is interested in its own survival," says Cameron. "It needs to maintain high viral fitness and not kill its host -- us. COVID-19 has already struck that perfect balance."

It could take generations for enough genetic change to take place to substantially weaken a coronavirus -- both the one that causes COVID-19 and other forms that were around before it. Human coronaviruses are known to be extremely stable in their genetic makeup. They change very little over time. Early tracking of SARS-CoV-2, the coronavirus that causes COVID-19, suggests that it is behaving like its relatives, changing slowly and subtly over time.

That's not to say that the virus isn't changing at all. When researchers at Arizona State University analyzed coronavirus samples collected from nasal swabs, they found one individual sample that had a major genetic difference from other samples.

But it's unknown whether this particular variation of the virus results in more or less severe illness or any difference in symptoms at all. To confirm a theory like that will require much more research. Scientists will need to align the various genetic sequences of numerous nasal swabs with patient symptoms.

Still, Cameron says, this single mutated sample won't prevent other strains from continuing to spread and cause illness. Viral strains survive independently of each other. That's why, for example, several flu strains circulate every season.

With so many people infected with SARS-CoV-2, a mutation in a single sample is unlikely to change the course of the outbreak, Cameron says.

Though researchers say it's unlikely that the virus has mutated enough to make major differences in how severe an illness will be, that's not all bad news. That makes the virus a stable target for researchers working on a vaccine. The flu, for example, changes so quickly that vaccine developers have to come up with a new shot every year.

Public health officials stress there's no scientific proof that the virus is now weaker. Until that proof is found, health authorities warn that the public cannot lower its defenses against the spread of the virus. But Bassetti promises the evidence is coming. He cites studies in progress in the northern Italian cities of Milan and Brescia that will show that people are carrying lower viral loads than before -- a sign of less severe disease -- and that genetic mutations in the virus have made it less deadly.

One of the golden rules of virology is that viruses that circulate in the community do change and mutate. Dr Mark Cameron

"We are not here to say that the virus is gone," Bassetti says. "We are here to say that it is different." He attributes these differences to a potential combination of things, including biological changes in the virus, and the success of the lockdown, social distancing, mask use, and hand-washing. Flattening the curve, Cameron adds, allows testing to catch up and makes medical care available to those who need it without delay.

In response to the WHO's rebuttal of his claims, Bassetti says, "The WHO does not take care of patients. They are seated at a table in Geneva. These are the impressions of the majority of doctors on the ground. We have admitted more than 500 [COVID-19] patients at San Martino hospital since the beginning of the epidemic, and I have seen a dramatic reduction in the severity of the disease."

It could be that the work of on-the-ground health care providers is responsible for this dramatic change, Cameron says.

"I would lay the credit for the consistently improving patient outcomes in Italy right at the doctors' and health care workers' feet," he says. "It's a testament to their heroics that they've broken this virus's back without much, if any, help from the virus itself. We will have to wait for virus sequencing studies and clinical studies to resolve the issue."

Originally posted here:
Claims of a Weaker COVID-19 Virus Disputed - Medscape

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, using the next-generation sequencing panel MSK-IMPACT.

This testing identified 2043 patients (17.1%) with variants in cancer predisposition genes, including 849 patients (7.1%) who had targetable genes by strict criteria and 1003 patients (8.6%) by less strict criteria.

"Of course, these numbers are not static," commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. "And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

"Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer," she added.

Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology (ASCO) 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9% to 11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

"The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment," said Erin Wysong Hofstatter, MD, from the Yale School of Medicine, New Haven, Connecticut, in a Highlights of the Day session.

Now, more than ever before, germline testing is indicated for the selection of cancer treatment. Dr Erin Wysong Hofstatter

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. "And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing."

For their study, Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

"Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed," she said. "Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service."

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Hofstatter noted that, using strict criteria, 7.1% of patients were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6%.

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a PARP inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. "There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated," she said. "But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1."

Some questions remain unanswered, she noted, such as, "What percentage of patients undergoing tumor-normal testing signed a germline protocol?" and, "Does the population introduce a bias such as younger patients, family history, and so on?"

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. "What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

"But to be fair, it is not easy to seek the germline mutations," Meric-Bernstam continued. "These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results."

An infrastructure is needed to return/counsel/offer cascade testing, and "analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion," she added.

The study was supported by MSKCC internal funding. Stadler reports relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Meric-Bernstram reports relationships with numerous pharmaceutical companies.

American Society of Clinical Oncology (ASCO) 2020: Abstract 1500, presented May 30, 2020.

Follow Medscape Oncology on Twitter for more cancer news: @MedscapeOnc.

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Germline Testing In Advanced Cancer Can Lead to Targeted Tx - Medscape

What happened

Shares of Intellia Therapeutics (NASDAQ:NTLA) rose as much as 18% today after the company announced an expansion of its partnership with Regeneron Pharmaceuticals (NASDAQ:REGN).

The pair will jointly develop drug candidates to treat hereditary blood disorders hemophilia A and hemophilia B. Additionally, Regeneron Pharmaceuticals will gain rights to develop drug candidates using both in vivo (inside the body) and ex vivo (outside the body) drug candidates and delivery tools developed by Intellia Therapeutics.

The gene editing pioneer will earn a combined up-front payment of $100 million in cash and equity. It ended March 2020 with roughly $250 million in cash. As of 11:05 a.m. EDT, the pharma stock had settled to a 12.1% gain.

Image source: Getty Images.

Investors have punished Intellia Therapeutics for falling behind peers CRISPR Therapeutics and Editas Medicine in clinical development. The company will be the last of the trio of CRISPR gene editing companies to enter clinical trials. While it told investors the delay was largely due to work on delivery technologies -- one of the most important components of a genetic medicine -- Wall Street didn't have much patience.

As a result, Intellia Therapeutics boasts a market valuation of $1 billion, which is far behind the $3.9 billion valuation of CRISPR Therapeutics and the $1.5 billion market cap of Editas Medicine.

Today's news might not completely remove doubt from the minds of investors, but it serves as a reminder that Regeneron Pharmaceuticals remains a committed development partner. If other CRISPR gene editing platforms stumble in the clinic because of a lack of attention to delivery technologies, Intellia Therapeutics might be rewarded for its slow-and-steady approach.

Things are finally heating up for Intellia Therapeutics. In addition to the expanded partnership with Regeneron Pharmaceuticals announced today, the gene editing pioneer announced in March that a sickle cell disease drug candidate being developed with Novartis had earned the green light for clinical trials from regulators.

Meanwhile, the company's lead drug candidate is expected to begin a phase 1 clinical trial in the second half of 2020. Multiple other drug candidates are expected to earn regulatory permission in 2021 for clinical trials. There's a long way to go for Intellia Therapeutics, but investors will finally have tangible milestones to look forward to in the coming quarters.

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Here's Why Intellia Therapeutics Gained as Much as 18.0% Today - Motley Fool

The Forest Service is proposing to remove the prohibition against logging trees larger than 21 inches that grow in national forests on the eastside of the Cascades in Oregon. The probation was put into place when ecological studies demonstrated the critical importance of large-diameter old-growth trees to overall forest ecosystem function.

The Forest Service argues that it needs the flexibility to cut larger fir and other tree species competing with ponderosa pine to restore forest health. The agency suggests thinning the forests will enhance the resilience of the forest against the ravages of wildfire, bark beetles, and other sources of tree mortality.

The so-called need for restoration to what ails the forest by chainsaws medicine reflects the agencys Industrial Forestry Paradigm. By happy coincidence, such restoration happens to provide wood fiber to the timber industry, and typically at a loss to taxpayers.

One might assume that green and fast-growing trees are more desirable than dead or slow-growing trees. What the agency doesnt acknowledge due to its inherent Industrial Forestry bias is that healthy forest ecosystems require significant sources of tree mortality. The healthy forest that the Forest Service promotes is a degraded forest ecosystem.

Dead trees provide food and shelter to many plants and animals. By some estimates, more species depend on dead trees than live trees. These species live in mortal fear of green forests, which is the ultimate expression of the Industrial Forestry Paradigm.

Indeed, the second-highest biodiversity in forest ecosystems occurs after high severity wildfires kill most of all living trees.

However, due to the Industrial Forestry worldview bias of foresters and the Forest Service, that views any source of tree mortality as antithetical to forest health. Forest health is not the same as forest ecosystem health.

Logging does not restore forest ecosystems. It removes the snags and down wood that is critical wildlife habitat for many species of animals and plants. It removes carbon that is stored in those trees. It compacts soils and spread weeds. Logging roads fragment forest habitat and provide access for ORVs, hunters, and just more human disturbance for wildlife.

Worse for our forest ecosystems, thinning/logging can reduce the genetic diversity of our forest, eliminating, rather than enhancing, forest resilience. We know that some individual trees possess genetic traits that allow them to endure drought or resist bark beetles, and even some ability to survive some wildfires.

If foresters were concerned about forest ecosystem health, not just whether trees remained green until they were cut for lumber, they would welcome the wildfires, bark beetles, drought, and all the other sources of mortality that maintain healthy functioning forest ecosystems.

Yet the Forest Service continuously justifies timber cutting to restore forest health and resilience to the forest by trying to limit or exclude the very ecological processes like high severity wildfire, bark beetles, mistletoe, and other agents that sustain healthy forest ecosystems.

Allowing natural processes to thin the forest or select which trees have the best attributes to survive is how you preserve healthy forest ecosystems. Chainsaw medicine, the favored response of the timber industry for restoration, is not the solution; it is the problem.

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The Problem With Chainsaw Medicine: the Forest Service's Move to Cut Oregon's Big Trees - CounterPunch

Based on market cap,CRISPR Therapeutics (NASDAQ:CRSP)ranks as the top biotech focused on developing CRISPR gene-editing therapies. It's more than 2 1/2 times the size ofEditas Medicine (NASDAQ:EDIT) and nearly four times larger thanIntellia Therapeutics (NASDAQ:NTLA).

But based on stock performance so far in 2020, Intellia wins the prize as the hottest CRISPR biotech stock. Its shares have soared more than 40%, thanks in large part to the expansion of its partnership with Regeneron.

While CRISPR Therapeutics and Intellia have captured investors' attention lately, Editas Medicine could now be the CRISPR stock to really watch. There are both near-term and long-term reasons why investors should keep their eyes on this company.

Image source: Getty Images.

In March, Editas and its partner Allerganannounced the dosing of the first patient in a phase 1/2 clinical study evaluating EDIT-101 in treating Leber congenital amaurosis type 10 (LCA10), an inherited form of blindness. Editas CEO Cynthia Collins called it "a truly historic event," as it wasthe world's first human study of anin vivo (inside the body) CRISPR gene-editing therapy.

Editas' Chief Scientific Officer Charlie Albright stated in the company's Q1 conference calllast month that the study "has been cleared to continue based on a review of safety data on the first patient." That's great news, especially considering the pioneering nature of the LCA10 therapy.

I don't necessarily look for this clinical trial to provide a big catalyst for Editas over the next few months, at least not directly. But it could give the biotech an indirect catalyst.

Editas Medicine's experience with EDIT-101 in targeting LCA10 has enabled it to move forward with EDIT-102, a CRISPR therapy targeting another genetic eye disease, Usher syndrome 2A. Allergan is currently reviewing a preclinical data package for the potential licensing of EDIT-102. Editas expects a decision from Allergan on exercising its option for EDIT-102 by the third quarter of 2020.

My hunch is that Allergan will decide to license EDIT-102 unless some safety issue emerges in the phase 1/2 study for EDIT-101. A positive decision would likely cause Editas' shares to jump.

CRISPR Therapeutics is the leader in developing a CRISPR therapy for treating rare blood diseases sickle cell disease and beta-thalassemia. The company and its partner, Vertex Pharmaceuticals, expect to report additional data from two phase 1/2 studies in progress evaluating CRISPR/Cas9 gene-editing therapy CTX001 later this year.

Editas is behind CRISPR Therapeutics right now. But I won't be surprised if Editas emerges as a winner in sickle cell disease and beta-thalassemia over the long term.

The company plans to file for FDA approval by the end of 2020 to begin clinical testing of EDIT-301 in treating sickle cell disease. EDIT-301 uses its proprietary enzyme Cas12a (also known as Cpf1) instead of Cas9, the enzyme most commonly used in CRISPR gene-editing therapies.

Editas thinks that EDIT-301 could be the best-in-class CRISPR therapy for treating both sickle cell disease and beta-thalassemia. One reason behind the biotech's confidence is that the therapy edits the HBG1 and HBG2 genes rather than theBCL11Ae gene targeted by CRISPR Therapeutics' CTX001. Editas believes that this difference will give EDIT-301 a better safety profile than CTX001 will have. The company also thinks that using Cas12a will lead to sustained higher fetal hemoglobin levels than using the Cas9 enzyme will.

There's another intriguing possibility for Editas Medicine. Its partner on EDIT-101, Allergan, was recently acquired by AbbVie (NYSE:ABBV). The primary reason for this deal was for AbbVie to reduce its dependence on Humira, which faces biosimilar competition in the U.S. beginning in 2023.

AbbVie has other arrows in its quiver for offsetting the inevitable loss of revenue from Humira -- notably including its new immunology drugs Rinvoq and Skyrizi. However, the closer the date approaches for Humira's U.S. sales decline, the more I suspect that AbbVie will be interested in making additional smaller deals to boost its top line.

If EDIT-101 is successful in phase 1 testing and advances to phase 2, Editas Medicine could very well be on AbbVie's acquisition radar. The biotech wouldn't be so expensive that it would require AbbVie to take on a lot of additional debt. Buying Editas could also boost AbbVie's oncology program since Editas has several preclinical programs that use CRISPR gene editing in cancer cell therapies.

To be sure, Editas Medicine is a speculative play. For that matter, so are CRISPR Therapeutics and Intellia Therapeutics. All of these biotech stocks face significant risks that their gene-editing therapies won't work or won't be safe. But the possibility of near-term catalysts and the tremendous long-term potential for Editas make this CRISPR biotech one for investors to closely watch.

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Why Editas Medicine Is Now the CRISPR Stock to Really Watch - Motley Fool