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Friday, July 30, 2021

Omega Therapeutics Announces Pricing of IPO

 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a development-stage biotechnology company leveraging its OMEGA Epigenomic Programming™ platform to harness the power of epigenetics to develop a new class of DNA-sequence-targeting, mRNA-encoded programmable epigenetic medicines, today announced the pricing of its initial public offering of 7,400,000 shares of its common stock at a price to the public of $17.00 per share. All of the shares of common stock are being offered by Omega. The gross proceeds from the offering, before deducting underwriting discounts and commissions and estimated offering expenses payable by Omega, are expected to be approximately $125.8 million, excluding any exercise of the underwriters' option to purchase additional shares. Omega's common stock is expected to begin trading on the Nasdaq Global Select Market under the ticker symbol "OMGA" on July 30, 2021. The offering is expected to close on August 3, 2021, subject to satisfaction of customary closing conditions. In addition, Omega has granted the underwriters a 30-day option to purchase up to an additional 1,110,000 shares of common stock at the initial public offering price less underwriting discounts and commissions.

Goldman Sachs & Co. LLC, Jefferies LLC and Piper Sandler are acting as joint book-running managers of the offering. Wedbush PacGrow is acting as lead manager.

https://www.prnewswire.com/news-releases/omega-therapeutics-announces-pricing-of-initial-public-offering-301344870.html

Fed's Powell bets economy will navigate new coronavirus surge

 Federal Reserve Chair Jerome Powell’s belief that the U.S. economy has “learned to handle” the coronavirus and won’t be swamped in a fresh wave of infections or by rising inflation may get tested in coming weeks as schools reopen, supply chains remain clogged, and federal unemployment benefits wane.

Data released on Thursday showed the risk ahead as the country navigates the transition from an economy dependent for the last year on federal government benefits to one where those emergency programs expire and private incomes take over.

The economy returned to its pre-pandemic level of output in the second quarter, according to gross domestic product data released by the Commerce Department on Thursday, a rebound that came earlier than many expected. But the report also showed personal income dropping alongside a decline in federal transfer payments and the economy growing at an annual rate of 6.5%, slightly below the 7% expected by the U.S. central bank.

It was massive federal stimulus, unemployment benefits and other payments that led to the “better-than-anyone-expected” outcomes during a coronavirus surge last summer, which Powell cited on Wednesday as evidence that each COVID-19 wave has had successively less economic impact.

Those government payments are disappearing just as concerns rise around the spread of the more infectious Delta variant of the virus, putting a new note of caution around the U.S. growth outlook.

Despite second-quarter GDP being slightly lower than expected and the Delta variant “a key downside risk,” Lydia Boussour, lead U.S. economist for Oxford Economics, said she continued to anticipate 7% growth for the full year as supply-chain problems ease, goods get onto shelves, and consumers continue spending.

“We still expect the economy to maintain strong momentum,” she wrote in a note.

By contrast, Paul Ashworth, chief North America economist at Capitol Economics, painted a dour economic picture in which the Delta variant becomes a drag and rising prices cut into household purchasing power. Inflation measures in Thursday’s GDP report, at greater than 6%, are the highest since the early 1980s when the Fed was battling entrenched price increases.

Ashworth said economic growth may slow to just 3.5% in the second half of the year, “with the impact from the fiscal stimulus waning, surging prices weakening purchasing power, the Delta variant running amok in the South.”

‘DEFIANTLY UPBEAT’

Powell issued his blunt assessment of COVID-19’s threat to the economy during a news conference on Wednesday to discuss the Fed’s latest policy meeting. In their statement, policymakers said the economic recovery appeared on track, that the impact of the virus on the economy continued to wane, and that the economy was making progress toward the day when the Fed could reduce some of the emergency steps taken in 2020 to nurse the economy through the pandemic.

Coupled with earlier changes, the Fed’s actions this week continued the central bank’s steady divorce between the ongoing pandemic and the outlook for the economy.

Epidemiologists have warned from early on that the coronavirus would not disappear - with true herd immunity a stretch goal in a country with high levels of vaccine hesitancy - but rather be a part of the social and economic background for years to come.

The Fed, in successive steps, has seemed to adopt to that view. Since April it has stopped referring to the pandemic as a factor weighing on the economy, emphasized the impact of vaccinations, and this week said, in effect, that the virus would remain as a future risk, but not a significant one.

“We’ve kind of learned to live with it,” Powell told reporters. Even with the Delta variant filling hospitals in some parts of the country, “with a reasonably high percentage of the country vaccinated and the vaccine apparently being effective ... the effects will probably be less. There probably won’t be significant lockdowns and things like that.”

Whether that remains the case will be seen through the late summer and fall. Some companies already have delayed the planned return of their workforces to offices, potentially pushing out the day when downtown retail stores and restaurants see their weekday traffic return.

Powell acknowledged that, at the margins and for a while at least, the Delta surge could lead to further complications if school districts delay the reopening of in-person learning, or if sidelined workers wait a few more weeks to return to their jobs.

But for now, and absent a clear darkening of the economic outlook, it won’t derail Fed planning that anticipates continued job growth, and needs to manage the risks of potentially higher inflation as well.

Diane Swonk, chief economist at Grant Thornton, called Powell’s commentary this week “defiantly upbeat,” and listed the hurdles his outlook faces - from the Delta variant to the slow, ongoing efforts of millions of unemployed workers to match themselves with new jobs.

The new infection surge “has already delayed the return to offices for some companies to later this year,” Swonk wrote. “We are becoming accustomed to spending during outbreaks, as Powell noted ... That spending has been supported by fiscal stimulus. That will wane as we enter 2022.”

https://www.reuters.com/article/usa-economy-fed/feds-powell-bets-economy-will-navigate-new-coronavirus-surge-idUSL1N2P51JW

Thursday, July 29, 2021

Empagliflozin to be probed as possible treatment for COVID-19 in RECOVERY trial

 Empagliflozin – a routine treatment for type 2 diabetes – will be investigated in the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial. This is the world’s largest clinical trial of treatments for patients hospitalised with COVID-19, taking place in 185 hospitals in the UK, Nepal and Indonesia and with over 41,000 patients recruited so far.

Empagliflozin is regularly used to treat type 2 diabetes, and has also been shown to have benefits for patients with chronic kidney disease or heart failure. The drug works by reversibly blocking the action of a sodium-glucose co-transporter (SGLT) in the kidney. This reduces the amount of glucose absorbed by the body, causing it to be excreted into the urine instead. It is thought that sodium-glucose co-transporters may help stabilise metabolic pathways that become dysregulated during viral infection, reduce inflammation, improve heart and blood vessel function, and increase blood oxygen transport. Together, these actions may protect against organ damage and improve the chance of recovery for patients with COVID-19.

A similar sodium-glucose co-transporter inhibitor, dapagliflozin, was compared to a placebo among 1250 hospitalised COVID-19 patients by the DARE-19 trial. In patients treated with the drug, there was a non-significant reduction in the risk of organ failure or death of one-fifth and there were no major safety concerns with its use.

Professor Sir Peter Horby, from the Nuffield Department of Medicine at the University of Oxford, UK, Co-Chief Investigator of the RECOVERY trial, said ‘The COVID-19 pandemic still has a long way to run, and whilst COVID-19 continues to claim lives, we will continue our quest to find new, affordable treatments that are accessible to all. I’m delighted that we are adding empagliflozin, since this will test a new treatment strategy using a class of drugs that are widely available and relatively inexpensive.’

Professor Sir Martin Landray, from the Nuffield Department of Population Health at the University of Oxford, who co-leads the RECOVERY trial said ‘Empagliflozin and similar SGLT2-inhibitor drugs have been shown to have significant benefits on the heart and kidney in patients with or without diabetes. The recent DARE-19 trial provided encouraging but inconclusive evidence that these drugs may reduce the risk of lung, heart, and kidney damage or death in patients hospitalised with COVID-19. By including empagliflozin in a much larger comparison within the RECOVERY trial, we will be able to determine whether this early promise turns into a reality.’

It is anticipated that at least 2500 patients recruited to the RECOVERY trial will be randomly allocated to receive empagliflozin plus usual standard-of-care, and results will be compared with at least 2500 patients who receive usual standard-of-care on its own. The dosage of empagliflozin used will be a 10mg tablet once daily. The main aim is to assess whether empagliflozin reduces the risk of death among patients admitted to hospital with COVID-19. The trial will also investigate whether the treatment shortens the length of hospital stay or reduces the need for a mechanical ventilator. It is likely to be several months before the results are available.

Sodium-glucose co-transporter inhibitors are not considered to be safe in pregnancy and breastfeeding, so these women will not be included in this comparison.

The decision to add empagliflozin to the trial was made by the University of Oxford researchers and trial steering committee leading the trial in conjunction with the Chief Medical Officer, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel.

The other treatments currently being investigated in the RECOVERY trial are:

  • baricitinib (an immunomodulatory drug used in rheumatoid arthritis)
  • dimethyl fumarate (an immunomodulatory drug used in psoriasis and multiple sclerosis)
  • high-dose vs standard corticosteroids.

Antibody Evolution after SARS-CoV-2 mRNA Vaccination

 Alice Cho, Frauke Muecksch, Dennis Schaefer-Babajew, Zijun Wang, Shlomo Finkin, Christian Gaebler, Victor Ramos, Melissa Cipolla, Marianna Agudelo, Eva Bednarski, Justin DaSilva, Irina Shimeliovich, Juan Dizon, Mridushi Daga, Katrina Millard, Martina Turroja, Fabian Schmidt, Fengwen Zhang, Tarek Ben Tanfous, Mila Jankovic, Thiago Oliveira, Anna Gazumyan, Marina Caskey, Paul D Bieniasz, Theodora Hatziioannou, Michel C. Nussenzweig

SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration

 DanishIdreesa     ijayKumar

DOI: https://doi.org/10.1016/j.bbrc.2021.03.100

Abstract

The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Moreover, heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. In this paper, we have shown that the SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. These interactions suggests that the heparin-binding site on the S1 protein might assist the binding of amyloid proteins to the viral surface and thus could initiate aggregation of these proteins and finally leads to neurodegeneration in brain. The results will help us to prevent future outcomes of neurodegeneration by targeting this binding and aggregation process.

https://www.sciencedirect.com/science/article/abs/pii/S0006291X2100499X

No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing

 NathanSmits110JayRasmussen210Gabriela O.Bodea1210Alberto A.Amarilla310PatriciaGerdes1Francisco J.Sanchez-Luque45PrabhaAjjikuttira2NaphakModhiran3BenjaminLiang3JamilaFaivre6Ira W.Deveson78Alexander A.Khromykh39DanielWatterson39Adam D.Ewing1Geoffrey J.Faulkner1211