Private Markets to Double to $18.3 Trillion by 2027, Preqin Says

 Private capital strategies are set to double assets under management over the next five years, according to data provider Preqin, even as the fast-growing industry adjusts to a new macro environment.

Private capital markets, encompassing private equity and private capital, have been booming over the last decade as investors chased yield during an era of fiscal stimulus and ample liquidity. Despite this year’s market routs and challenging outlook, with borrowing costs surging and economies cooling, demand for private capital “continues to show resilience,” Preqin said in a report Wednesday.

https://www.iqstock.news/n/private-markets-double-18-trillion-2027-preqin-4702919/

Holiday Covid Flareups Spark Travel Chaos Before China Congress

 China’s Covid-19 cases climbed to the highest in more than two weeks as outbreaks during a week-long holiday dash hopes of keeping a tight lid on the virus ahead of the politically significant Party Congress.

Nationwide, there were 909 infections for Tuesday, with 273 reported in Inner Mongolia. Residents in parts of the provincial capital Hohhot, as well as other cities, were ordered to stay at home or within their residential compounds. Manzhouli city and Linxi county were locked down after each detecting one infection.

The region’s party chief, Sun Shaocheng, said in a briefing on Saturday that authorities would stamp out transmissions by “killing chickens using a knife for killing cows”, a phrase meaning to use excessive efforts for a small task. Infections must be contained and especially cannot spread to Beijing, he said.  

The rise during this week’s National Day holiday is stoking concerns about whether tough Covid curbs may be deployed more widely in the lead up to the Party Congress, which begins mid-October and is expected to see President Xi Jinping secure a precedent-breaking third term in power. Xi has made Covid Zero a cornerstone of his leadership, and Beijing views the measures as key in averting the death tolls seen in other parts of the world despite its growing social and economic costs.

The flareups also indicate many people didn’t heed advice from authorities to not travel during the holiday and raises the risk of residents carrying infections back home with them. Beijing posted three cases for Tuesday, including one visitor from Inner Mongolia, though all were detected in quarantine. 

Many places around the country have stepped up control measures to minimize infection risks, leading to travel chaos as tourists become stranded or have their plans disrupted due to quarantine or testing requirements.

Xinjiang’s capital Urumqi banned people from leaving the city on Tuesday, while passenger train services and long-distance coaches have been suspended. In Yunnan province, hundreds of tourists were stranded in the airport in Xishuangbanna after the prefecture went into lockdown on Tuesday. Unverified videos posted on social media showed people arguing with workers dressed in personal protective gear in the airport, as well as officers with guns and shields.

https://www.bloomberg.com/news/articles/2022-10-05/holiday-covid-flareups-spark-travel-chaos-before-china-congress

Theranos founder gets hearing on new trial

 Sentencing of former Theranos boss Elizabeth Holmes has been delayed as a judge considers whether the testimony of a key witness in her high-profile trial was truthful.

Holmes requested a new trial after claiming that federal prosecutors presented misleading evidence.

She was convicted in January on four of 11 counts of defrauding investors in the blood-testing firm.

The decision marks the latest twist in a case that has gripped Silicon Valley.

Holmes entered the "motion for a new trial based on newly discovered evidence" regarding former Theranos laboratory director Adam Rosendorff, court papers showed.

Holmes' lawyers said that Mr Rosendorff appeared at her home in August to express regret over his testimony in the trial.

This latest development comes after her lawyers last month failed in an attempt to get the conviction overturned.

Holmes, who is currently free on bail, had been due to be sentenced on 17 October.

In January, a jury found Holmes guilty of defrauding investors after a months-long landmark trial in California.

Jurors found her guilty of conspiracy to commit fraud against investors and three charges of wire fraud. She denied the charges.

Prosecutors said Holmes knowingly lied about technology that she said could detect diseases such as cancer and diabetes with a few drops of blood. The firm promised that it would revolutionise the healthcare industry with the test.

But these claims began to unravel in 2015 after a Wall Street Journal investigation reported that its core blood-testing technology did not work.

Her ex-boyfriend and former Theranos President Ramesh "Sunny" Balwani was found guilty in July on similar counts, as well as defrauding patients. He is scheduled to be sentenced next month.

Theranos was once the darling of biotech and Silicon Valley, valued at $9bn (£7.9bn) at its peak.

Holmes was able to raise more than $900m from billionaires, including media magnate Rupert Murdoch and technology mogul Larry Ellison.

https://www.bbc.com/news/business-63140536

Bankruptcy Judge Pauses New Mexico, Mississippi Lawsuits Over J&J Talc Products

 A New Jersey bankruptcy judge on Tuesday paused consumer-protection lawsuits brought by New Mexico and Mississippi linking Johnson & Johnson's talc-based products to cancer.

Judge Michael Kaplan of the U.S. Bankruptcy Court in Trenton agreed to extend the legal stay protecting J&J's bankrupt talc unit to the parent company, even though it isn't in chapter 11.

Judge Kaplan ruled the talc subsidiary, LTL Management LLC, and its chapter 11 case would be irreparably harmed if the state attorneys general were allowed to move ahead with their lawsuits against J&J during the bankruptcy.

The state lawsuits allege that J&J was aware that its talc-based products contained cancer-causing asbestos but refused to post a warning on its products, which the company denies.

The accusations raised by New Mexico and Mississippi concern the central dispute in LTL's bankruptcy case and would disrupt it if they were allowed to move forward, Judge Kaplan said.

The judge also indicated he wouldn't put the state lawsuits on hold indefinitely and would revisit his ruling in December.

Although the pause will benefit J&J, Judge Kaplan said the benefits to the company are relatively small compared to the potential harm to LTL and its prospect for settling all talc-related claims against it in chapter 11.

https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/Bankruptcy-Judge-Pauses-New-Mexico-Mississippi-Lawsuits-Over-J-J-Talc-Products-41928712/

Novavax No Longer Expected To Become Profitable This Year

 Novavax (NVAX) cut its full-year guidance in half in early August after reporting a wide second-quarter sales miss, and NVAX stock plunged.

For the year, the biotech company now expects $2 billion to $2.3 billion in sales, down from its prior guidance for $4 billion to $5 billion in sales. Novavax remained confident in its Covid shot, though, saying it has shipped more than 23 million doses since the beginning of July.

Authorizations have been rampant and continuous, however. Officials in multiple countries, including the U.S., have signed off on Novavax's Covid shot for adolescents age 12-17. Regulators in New Zealand, Switzerland and Europe recently allowed Novavax's Covid booster.

The company is also testing a pediatric vaccine in children as young as 6 months old, and just asked the Food and Drug Administration to sign off on its booster shot.

But pressure remains for NVAX stock. The FDA has warned against the risk of heart inflammation in recipients of the shot, echoing warnings for Moderna's (MRNA) and Pfizer's (PFE) shots in boys and young men. Officials in Europe have also added a warning for several allergic reactions to the shot, following two cases.

Novavax also is working on two methods of blocking omicron subvariants. It doesn't expect to have an updated Covid booster shot until the fourth quarter, however. Preliminary data suggest its BA.1-blocking booster can also handle BA.4 and BA.5 subvariants of omicron.

The company is mired in annual losses, a trend that continued last year. In 2021, Novavax lost $23.44 per share, widening from a per-share loss of $7.27 in 2020 and missing expectations. This year, analysts expect Novavax to lose 34 cents a share.

It's important to note, losses are common for newly commercial biotech companies — which are usually investing in research and development — but it's not desirable from a CAN SLIM perspective.

Last year, revenue was nearly $1.15 billion, below expectations for $1.26 billion. Still, revenue surged 141%. This year, NVAX stock analysts project $2.06 billion in revenue. The company just slashed its outlook and now expects $2 billion to $2.3 billion in sales.

During the second quarter, Novavax unexpectedly lost $6.53 per share and reported $185.9 million in sales. Both measures widely missed expectations. Analysts called for a gain of $5.54 per share and $1.02 billion in sales. Losses also widened year over year and sales fell 38%.

For the third quarter, analysts predict adjusted earnings of $1.45 per share and $591 million in sales. Earnings would swing from a $4.31 per-share loss in the same three months last year. Sales would grow about 230%.

Savvy investors should look for companies reporting recent quarterly revenue and earnings growth of at least 20%-25%. Novavax's earnings are shaky with a gain in the first quarter and a loss in the second. Stocks with a record like Novavax's are speculative for growth investors and carry a higher risk. Further, analysts' estimates for the third quarter and full year have come down recently.

Novavax has launched its Covid shot in the U.S. The vaccine is also used in a number of countries and has an emergency use listing from the World Health Organization.

But the FDA warned against the risk of myocarditis and pericarditis in recipients of the Novavax shot. The same warnings apply to the Pfizer and Moderna vaccines.

These incidents of heart inflammation have occurred mostly in boys and young men. In Novavax's study, six cases occurred in vaccine recipients and one took place in the placebo group. Of those six, five took place in males. Four were in people younger than age 30.

Overall, the vaccine proved about 90% effective in preventing mild, moderate or severe cases of Covid. In people age 65 and older, it was nearly 79% protective. The most common side effects were injection site pain or tenderness, fatigue, muscle pain, headache, joint pain, nausea/vomiting and fever.

NVAX stock has a Composite Rating of 12 out of a best-possible 99. The Composite Rating is a 1-99 measure of a stock's technical and fundamental growth metrics. On this measure, NVAX stock outranks 12% of all stocks.

Shares also have a low EPS Rating of 36. The EPS Rating is a measure of profitability and, on that bar, NVAX stock is weak. (Keep tabs on IBD Digital for more on stock ratings.)

Mutual funds hold a good chunk of the biotech stock. As of June, 496 funds owned 28% of Novavax stock. Institutional support is a good sign.

Novavax uses insect cells to develop molecules for vaccine development at a faster pace than the historical process, which relies on chicken eggs. Although government agencies have seen promise in that technology, NVAX stock is plagued by some high-profile disappointments.

In 2011, the U.S. Department of Health and Human Services' Biomedical Advanced Research and Development Authority gave Novavax $179 million to develop a flu vaccine. Nine years later, that flu vaccine succeeded in the final-phase test. The next day, Novavax stock popped 4%.

But its vaccine to treat respiratory syncytial virus hasn't had the same luck. The biotech company received $89 million from the Bill & Melinda Gates Foundation in 2015 to develop the vaccine. A year later, the vaccine didn't meet its primary or secondary goals in older adults and Novavax laid off nearly a third of its staff.

Novavax stock ended 2016 with a spectacular downfall. Shares plummeted 85% that year.

In 2019, the respiratory syncytial virus vaccine failed in pregnant women and Novavax announced a reverse stock split to avoid delisting from the Nasdaq. The biotech company also sold some manufacturing facilities to Catalent (CTLT) to raise $18 million in cash.

That year, NVAX stock plunged 89%.

Novavax has received funding from the Coalition for Epidemic Preparedness, a global alliance to stop epidemics. The Gates Foundation and the U.S. government also gave Novavax money to help speed its Covid vaccine efforts.

Variant news has impacted Novavax stock.

Novavax stock has a worst-possible Relative Strength Rating of 1. The RS Rating pits all stocks, regardless of industry group, against one another in terms of 12-month price performance. On this measure, NVAX stock ranks in the bottom 1% of all stocks. Leading stocks tend to have RS Ratings of at least 80.

NVAX stock isn't currently forming a definitive chart pattern, MarketSmith.com shows. On Oct. 4, shares were below their 50-day line and 200-day moving average.

On Oct. 4, Novavax stock wasn't a buy. Shares were a sell on Aug. 9 when they tumbled below their 50-day line in high volume following the disappointing second-quarter report and guidance cut — a bearish sign. Previously, NVAX stock had mostly closed above or in line with that key mark since late June.

On a fundamental level, NVAX stock is plagued by years of losses and its revenue remains low. It will be important to see how sales perform as Novavax plays catch-up with its Covid vaccine and booster shot. It's also important to keep an eye on earlier-stage programs from Novavax.

https://www.investors.com/news/technology/nvax-stock-buy-now/

Clinical trial of phage therapy for cystic fibrosis begins

 Enrollment has begun in an early-stage clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry Pseudomonas aeruginosa (P. aeruginosa) in their lungs. The trial is evaluating whether the bacteriophage, or "phage," therapy is safe and able to reduce the amount of bacteria in the lungs of volunteers. The trial is being conducted by the Antibacterial Resistance Leadership Group (ARLG), funded by the National Institute of Allergy and Infectious Diseases. Investigators aim to enroll up to 72 adults at 16 CF centers across the United States.

Phages are viruses that can kill or neutralize specific bacteria while leaving non-target bacteria and human cells unharmed. For more than a century, researchers have considered the potential use of phages as therapeutics, theorizing that mixtures of bacteriophages might be used on their own, or in conjunction with antibiotics, to treat bacterial infections -- especially those resistant to antibiotics.

P. aeruginosa, a serious and sometimes deadly bacterium frequently acquired in healthcare settings, is the most common bacterial cause of CF exacerbations. P. aeruginosa can take advantage of the tissue damage caused by CF changes in mucus to infect and colonize the lungs. Multidrug-resistant P. aeruginosa infections are becoming increasingly common, and in recent years, only a handful of new antibiotics have been approved to treat them.

"The prevalence of antibiotic resistance is concerning, and the need for more effective therapeutics for vulnerable populations, such as people with cystic fibrosis, is especially urgent," said NIAID Director Anthony S. Fauci, M.D. "Although research on bacteriophage therapy may still be in its infancy in the United States, we hope that this study, and others like it, could open the doors to a new type of therapy for difficult-to-treat bacterial infections."

The experimental phage therapeutic, WRAIR-PAM-CF1, is manufactured by Adaptive Phage Therapeutics, Gaithersburg, Maryland. It contains a cocktail of four bacteriophage species that naturally infect P. aeruginosa and take over its cellular processes, killing the bacterium in the process. The phages in the cocktail are highly specific and do not attack human cells. They have been cultivated, purified, and extensively studied in a lab setting. Genetic analyses of these phages have determined that they do not carry harmful genes that could accidentally be transferred to the bacteria they infect, such as genes that could confer antibiotic resistance.

The trial will enroll CF patients who chronically harbor P. aeruginosa in their respiratory tracts. Participants will receive the phage cocktail as a single IV infusion at one of three dosage levels. Researchers will gather data on safety and microbiological activity; how the phages function in the body; how the cocktail affects the participants' lung function; whether the therapy works differently on P. aeruginosa from different geographical regions; and whether the therapy changes participants' overall quality of life.

The trial will begin as a Phase 1b trial and will expand to a Phase 2 trial. First, two participants per dosage level will receive an unblinded infusion of the therapeutic and will be closely monitored for four days thereafter. If no serious safety issues are identified, researchers will begin enrolling additional participants, who will be randomly assigned to receive a single infusion of the therapeutic at one of the three dosage levels, or a placebo infusion. This part of the trial will be double-blinded, so neither the participants nor the investigators will know who is receiving placebo. An assessment of the therapeutic's safety and microbiological impact will be conducted after eight participants have completed each dosage. The results of this assessment will determine which dosage will be given in the next stage of the trial. The Phase 2 trial will enroll up to 50 participants who will be randomly assigned to receive the selected dose of the phage cocktail or a placebo. Each volunteer will make multiple follow-up visits to monitor their health and reaction to the experimental therapeutic.

The ARLG is a clinical research consortium supported by NIAID which works to combat the antibacterial resistance crisis and improve patient care. ARLG's mission is to prioritize, design, and execute clinical research that will impact the prevention, diagnosis, and treatment of infections caused by antibiotic-resistant bacteria.

NIAID conducts and supports research -- at NIH, throughout the United States, and worldwide -- to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

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Story Source:

Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2022/10/221004134330.htm

Decreased proteins, not amyloid plaques, tied to Alzheimer's disease

 New research from the University of Cincinnati bolsters a hypothesis that Alzheimer's disease is caused by a decline in levels of a specific protein, contrary to a prevailing theory that has been recently called into question.

UC researchers led by Alberto Espay, MD, and Andrea Sturchio, MD, in collaboration with the Karolinska Institute in Sweden, published the research on Oct. 4 in the Journal of Alzheimer's Disease.

Questioning the dominant hypothesis

The research is focused on a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, meaning dissolvable in water, but it sometimes hardens into clumps, known as amyloid plaques.

The conventional wisdom in the field of Alzheimer's research for more than 100 years stated that Alzheimer's was caused by the buildup of amyloid plaques in the brain. But Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic or infectious stress, transform into the abnormal amyloid plaques.

"The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia," said Espay, professor of neurology in the UC College of Medicine, director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders at the UC Gardner Neuroscience Institute and a UC Health physician. "Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies."

Sturchio noted that many research studies and clinical trials over the years have aimed at reducing amyloid plaques in the brain, and some have lessened plaques, but until the September 27 announcement of a positive trial by Biogen and Eisai (lecanemab), none slowed the progression of Alzheimer's disease. More importantly, in support of their hypothesis, in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.

"I think this is probably the best proof that reducing the level of the soluble form of the protein can be toxic," said Sturchio, first author of the report and adjunct research instructor at UC's College of Medicine. "When done, patients have gotten worse."

Research results

Previous research from the team found that regardless of the buildup of plaques in the brain, people with high levels of soluble amyloid-beta were cognitively normal, while those with low levels of the protein were more likely to have cognitive impairment.

In the current study, the team analyzed the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer's disease.

"One of the strongest supports to the hypothesis of amyloid toxicity was based on these mutations," Sturchio said. "We studied that population because it offers the most important data."

Even in this group of patients thought to have the highest risk of Alzheimer's disease, the researchers found similar results as the study of the general population.

"What we found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span," Espay said.

The research found that with a baseline level of soluble amyloid-beta in the brain above 270 picograms per milliliter, people can remain cognitively normal regardless of the amount of amyloid plaques in their brains.

"It's only too logical, if you are detached from the biases that we've created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques," Espay said. "Degeneration is a process of loss, and what we lose turns out to be much more important."

Next steps

Sturchio said the research is moving forward to study if increasing the levels of soluble amyloid-beta in the brain is a beneficial therapy for patients with Alzheimer's.

Espay said it will be important to ensure that the elevated levels of the protein introduced into the brain do not then turn into amyloid plaques, since the soluble version of the protein is needed for normal function to make an impact in the brain.

On a larger scale, the researchers said they believe a similar hypothesis of what causes neurodegeneration can be applied to other diseases including Parkinson's and Creutzfeldt-Jakob disease, with research ongoing in these areas as well.

For example, in Parkinson's disease, a normal soluble protein in the brain called alpha-synuclein can harden into a deposit called a Lewy body. The researchers hypothesize that Parkinson's is not caused by Lewy bodies aggregating in the brain, but rather by a decrease in levels of normal, soluble alpha-synuclein.

"We're advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins," Espay said. "The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress."

Espay said he envisions a future with two approaches to treating neurodegenerative diseases: rescue medicine and precision medicine.

Rescue medicine looks like the current work, studying if boosting levels of key proteins like amyloid-beta leads to better outcomes.

"Interestingly, lecanemab, the anti-amyloid drug recently reported as beneficial, does something that most other anti-amyloid treatments don't do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta," Espay said.

Alternatively, precision medicine entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle or a biological or genetic process. If the root cause is addressed, the levels of the protein wouldn't need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.

Espay said precision medicine would take into account the fact that no two patients are alike, providing more personalized treatments. The researchers are making progress in precision medicine through the Cincinnati Cohort Biomarker Program, a project aiming to divide neurodegenerative diseases by biological subtypes in order to match therapies based on biomarkers to those most likely to benefit from them.

"The Cincinnati Cohort Biomarker Program is dedicated to working toward deploying the first success in precision medicine in this decade," Espay said. "By recognizing biological, infectious and toxic subtypes of Parkinson's and Alzheimer's, we will have specific treatments that can slow the progression of those affected."

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Story Source:

Materials provided by University of Cincinnati. Original written by Tim Tedeschi. Note: Content may be edited for style and length.

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Journal Reference:

1. Andrea Sturchio, Alok K. Dwivedi, Tarja Malm, Matthew J.A. Wood, Roberto Cilia, Jennifer S. Sharma, Emily J. Hill, Lon S. Schneider, Neill R. Graff-Radford, Hiroshi Mori, Georg Nübling, Samir El Andaloussi, Per Svenningsson, Kariem Ezzat, Alberto J. Espay. High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations. Journal of Alzheimer's Disease, 2022; 1 DOI: 10.3233/JAD-220808

https://www.sciencedaily.com/releases/2022/10/221004151217.htm