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Cancer Immunotherapy Developers in Asia Explore Diverse Approaches

How might one gauge the contributions of selected geographical regions to cancer immunotherapy? Initially, one might assess cancer incidence and prevalence…

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How might one gauge the contributions of selected geographical regions to cancer immunotherapy? Initially, one might assess cancer incidence and prevalence numbers, research and development expenditures, papers published in peer-reviewed journals, etc. By consulting such proxy figures, one might at least get a rough idea of how much attention one should devote to developments in different regions.

For example, market research figures suggest that roughly equal attention should be paid to developments in North America, Europe, and the Asia-Pacific regions. By 2027, the market sizes for these regions—according to Market Data Forecast—will be about $50 billion, $42 billion, and $33 billion, respectively. (The Asia-Pacific region’s market size is somewhat smaller, but this region’s growth rate is the highest, at 13.2%.)

Such broad figures tell us only so much. To learn more, we need to shift from high-level to low-level views. For example, we could get a feel for cancer immunotherapy developments in Asia by looking at the interesting things individual companies are doing. That’s what we’ll do in this article, which focuses on the advances that are being made by just a few commercially oriented institutions, all of which are located in Asia—in East Asia and Southeast Asia, to be slightly more precise. Each exemplifies creativity, drive, and humanity. Together, they make for a story that is more compelling than any high-level summation.

Drugs targeting intracellular oncoproteins

Qi Zeng, PhD
Research Director, A*STAR

Most antibody-based cancer drugs target molecules that appear on the outer surfaces of cancer cells or are secreted by cancer cells. “Antibodies are generally believed to be too large to enter cells,” says Qi Zeng, PhD, research director at A*STAR’s Institute of Molecular and Cell Biology. “What this means is there is a large untapped pool of intracellular therapeutic targets, such as phosphatases, kinases, and transcription factors.”

For the last 20 years, Zeng has been studying the intracellular PRL3 protein that is overexpressed in many tumors but undetectable in most normal tissues for tumor-specific novel cancer immunotherapy. “In 2008,” she recalls, “we demonstrated that PRL3 antibody could specifically inhibit tumors expressing intracellular PRL3 oncoproteins.”

“We found that when cancer cells are stressed or are dying, PRL3 could be found on their surfaces or in the tumor microenvironment, enabling antibody binding and therapy,” she continues. “When PRL3-zumab was tested in multiple mouse models of cancer, we found that the antibody could bind to PRL3 to trigger an immune response against tumors, causing tumor shrinkage by as much as 90%.”

In 2015, Zeng founded an A*STAR spinoff company, Singapore-based Intra-ImmuSG (IISG), to develop PRL3-zumab, a first-in-class humanized antibody, to treat multiple PRL3-positive cancers. “The main advantage of this system,” she points out, “is that compared to the use of small chemical inhibitors in chemotherapy, antibody therapy like PRL3-zumab is more target specific, which helps to minimize off-target side effects.”

Since its inception, IISG has reached several milestones. In 2019, PRL3-zumab commenced Phase II trials for gastric and hepatocellular carcinoma in Singapore. A year later, Phase II trials were also approved by the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration for all solid tumors.

“We are hoping to accelerate our process to recruit patients for clinical trials,” Zeng states. “Patients eligible for PRL3-zumab treatment typically have run out of all standard-of-care treatments. By then, the patients’ immune system is very weak and their response to treatment may not be as strong as we would hope.

“Targeting intracellular cancer-specific antigens would significantly enhance antibody immunotherapy [by opening] doors to a wide range of targets, including tumor-specific mutated intracellular proteins and intracellular mediators of cancer cell survival. We look forward to pioneering a new era of cancer immunotherapy.”

Light-activated tumor-targeting moieties

Many cancer therapies lack specificity and are associated with adverse side effects. “We have developed an investigational platform that makes use of photoimmunotherapy for cancer treatment,” says Takashi Toraishi, PhD, president of Rakuten Medical, a global biotechnology firm with offices in San Diego, Tokyo, Taipei City, and elsewhere. The company’s platform, which is called Alluminox, consists of a drug, a device, and other related components.

“The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding,” Toraishi details. “The device component consists of a light source that locally illuminates the targeted cells with nonthermal light to activate the drug.

“Research is being done on therapies developed on the Alluminox platform to determine if local and systemic innate and adaptive immune activation occur due to immunogenic cell death of the targeted cells and/or the removal of immunosuppressive elements within the tumor microenvironment. In September of 2020, we received the first approval of our lead asset (ASP-1929) in Japan, and in January of 2021, we started marketing products including a device for illumination. Currently, our new treatment is provided by a growing number of sites and doctors across Japan.”

Alluminox photoimmunotherapies proceed as follows: Patients are administered a drug that binds to targeted cancer cells. After about 24 hours, a nonthermal light dose is applied, activating the drug so that it induces rapid and selective necrosis with minimal side effects on surrounding tissues.

“[Our] longer-term vision … is to generate a ‘palette’ of Alluminox conjugates targeting a variety of cancer antigens,” Toraishi declares. “Alluminox Palette is a drug discovery program that develops drugs using various tumor-targeting moieties such as antibodies, peptides, proteins, and small molecules.

“The first Alluminox Palette programs under clinical development consist of monoclonal antibody-IRDye 700DX conjugates targeting various tumor and immune cell antigens. These include ASP-1929, an antibody dye conjugate consisting of cetuximab (an anti-EGFR antibody) and RM-1995 (a conjugate of an anti-CD25 antibody targeting CD25-positive regulatory T cells).”

Toraishi notes that RM-1995 is Rakuten Medical’s second pipeline asset to reach clinical trials. He adds that the company aims to “combine multiple conjugates from the Alluminox Palette” and to “expand therapies based on the Alluminox platform for the treatment of a range of solid tumors.”

Engineered T cells targeting liver cancer

Hepatitis B virus (HBV) and hepatitis C virus (HCV) can establish persistent infections that cause chronic hepatic inflammation, leading to the development of hepatocellular carcinoma (HCC). Although antiviral therapies for HCV have delivered remarkable cure rates, curative therapies for HBV remain unavailable.

To develop new therapies against HBV—and to eliminate HBV-related HCC—the scientists at Singapore-based Lion TCR decided to conduct research into “new and more radical therapies designed to eliminate or at least stably maintain low levels of HBV replication under the control of a functional anti-host response.”

The quote above comes from a journal article (Cytotherapy 2017; 19: 1317–1324) written by Antonio Bertoletti, MD, Anthony Tan, PhD, and Sarene Koh, PhD—the scientific founder and chairman, a scientific advisor, and the director of technology and manufacturing at Lion TCR, respectively. In their work at Lion TCR, the scientists have focused on the development of T-cell therapies for HBV.

Lion TCR illustration
Lion TCR, a spinoff company from Singapore’s A*STAR, specializes in the development and commercialization of engineered T-cell receptor (TCR) products against infectious disease and its associated cancers. For example, the company engineers hepatitis B virus (HBV)-specific T cells that can recognize HBV-expressing tumor cells and achieve targeted killing.

Even before Lion TCR was founded in 2015, the company’s scientists had amassed considerable experience characterizing HBV T-cell responses and T-cell receptors (TCRs) in HBV-related diseases, says Tina Wang, MD, PhD, chief operating officer and chief medical officer of Lion TCR. She adds that the scientists also provided—first in xenograft mice and then in patients—the proof of concept that HBV-specific TCR T cells can recognize HBV antigen expressed in HCC and thus treat HBV-related HCC.

“A few years later,” she declares, “the technology was demonstrated to have clinical efficacy in humans.” Moreover, Lion TCR has established the world’s largest HBV-specific TCR library, covering about 80% of the population in China, East Asia, and Southeast Asia. Finally, the company has developed LioCyx-M, an autologous T-cell product transiently modified with in vitro–transcribed mRNA encoding HBV-specific TCR.

“The advantage of our product is that the expression of the HBV-specific TCR wanes within a week after the mRNA introduced to the cells via electroporation is translated,” Wang explains. “This safety feature makes LioCyx-M suitable for use in advanced cancer patients to reduce primary tumor burden and metastases and potentially also in HBV chronic infection.”

Wang remarks that another advantage of LioCyx-M treatment is that its therapeutic efficacy is independent of tumor heterogeneity. “HBV-DNA integrations are presented in 80–90% of HBV-related HCC cells,” she elaborates. “Epitopes encoded by these HBV-DNA integrations that assemble with MHC class I molecules on cell surfaces thus serve as ideal targets for T cells as HBV-specific TCR T-cell-mediated tumor killing is independent of oncogenic status of HCC tumor cells.”

Last September, Lion TCR received clearance from the FDA for its Investigational New Drug (IND) application to assess LioCyx-M as a treatment for HBV-related HCC. At the time, the company indicated that it intended to start a Phase Ib/II multicenter study to analyze LioCyx-M as a monotherapy as well as a combination therapy with lenvatinib, a tyrosine kinase inhibitor. Since then, the company has received Fast Track Designation from the FDA for LioCyx-M for the treatment of HBV-related HCC.

Stem cell–based modeling and screening systems

“In recent years, stem cell research has made remarkable advances,” says Pengtao Liu, PhD, professor of biomedical sciences at the University of Hong Kong and director of the Center for Translational Stem Cell Biology (CTSCB). “At CTSCB, we are deriving Expanded Potential Stem Cells (EPSCs) from patients to study immune disorders and develop personalized ‘assays’ for evaluating immune responses and assessing drug candidates.”

Conventional embryonic stem cells are derived from the blastocyst, a pre-embryonic structure of about 70–100 cells that forms about five days after fertilization. In contrast, EPSCs are established from much younger pre-embryonic structures that consist of as few as four cells. Accordingly, EPSCs are more primitive than embryonic stem cells and have higher developmental potential.

“The advantages of using human EPSCs are that they are robust in culture and genetically and epigenetically stable,” Liu maintains. “They also permit efficient precision genome editing and can generate all types of cells examined so far—including engineered immune cells that may provide a new cell source for cell-based cancer immunotherapy.”

CTSCB researchers are engineering and differentiating EPSCs into genetically defined stem cell–based immune cell and tissue organoid models to study crosstalk phenomena. “At CTSCB,” Liu declares, “we strive to translate scientific discoveries into both commercial successes and healthcare benefits, and we are expecting a spinoff this year.”

PD-1-based DNA vaccines

Cancer vaccines can prevent cancer by relying on the ability of dendritic cells to induce antigen-specific immune responses. Unfortunately, this antigen process pathway is usually inefficient, resulting in low vaccine efficacy.

Determined to overcome this problem, Zhiwei Chen, PhD, DVM, professor of microbiology at the University of Hong Kong, began focusing on the development of PD-1-based DNA vaccine technology. To help commercialize the technology, Chen co-founded Immuno Cure BioTech in 2015.

“In our patented technology, the DNA vaccine encodes a PD-1-fused antigen,” says Michael Wong, PhD, Immuno Cure’s research and development director. “The unique design of the PD-1-fused antigen allows effective antigen targeting toward the PD-1 ligands expressed on dendritic cells for antigen capture and presentation.

Michael Wong
Michael Wong, PhD
R&D Director
Immuno Cure BioTech

“At the same time, the PD-1-fused antigens also enhance dendritic cell activation. These two effects facilitate a potent induction of protective immune responses against cancers, allowing substantial improvement of prevention and treatment outcomes.”

Immuno Cure’s PD-1-based DNA vaccine platform can be used in combination with immune checkpoint inhibitors to treat mesothelioma and breast cancer in preclinical animal models synergistically. In particular, PD-1-based DNA vaccination has also been shown to significantly enhance antitumor T-cell immunity, providing sustained therapeutic effect against established mesothelioma when combined with CTLA-4 blockade in mice.

Headquartered in Hong Kong, Immuno Cure maintains satellite offices in Shenzhen and Beijing. According to Wong, the company is “aiming to provide quick responses to emerging infectious diseases, cancers, and inflammatory diseases using our technology platforms at reasonably low cost for the benefit of mankind.” It is currently conducting a Phase I trial of a COVID-19 vaccine.

CAR T cells and host T cells working in tandem

Although chimeric antigen receptor (CAR) T cells are generally effective against so-called liquid cancers, they are usually defeated by solid tumors. “This is because solid tumors are a mass of cells and CAR T cells need to be able to infiltrate inside them,” says Koji Tamada, MD, PhD, professor of immunology at Yamaguchi University and president and CEO of Noile-Immune Biotech. “Furthermore, solid tumors are highly heterogeneous, and most CAR T-cell products recognize only one cancer antigen target.”

“When I started my professorship at Yamaguchi University in 2011,” Tamada relates, “I knew I had to find strategies to enhance accumulation of CAR T cells and to enhance polyclonal T-cell response.” In 2015, Tamada established Noile-Immune Biotech in Tokyo. In 2018, Tamada led a team of Yamaguchi- and company-affiliated scientists that engineered CAR T cells to express interleukin-7 (IL-7) and CCL19. The scientists reported (Adachi et al. Nature Biotechnology 2018; 36: 346–351) that in mice, these CAR T cells “achieved complete regression of preestablished solid tumors and prolonged mouse survival, with superior antitumor activity compared with conventional CAR-T cells.”

“Our choice of IL-7 and CCL19 stems from our understanding that T-zone fibroblastic reticular cells in the lymph nodes produce these biomolecules to recruit T cells,” Tamada details. “We wanted to exploit a natural way to make our CAR T cells more powerful. This is the basis of our Proliferating-Inducing and Migration-Enhancing (PRIME) technology.”

In addition to the efficacy from administered CAR T cells, PRIME technology also boosts endogenous T-cell and dendritic cell responses, with the potential to convert “cold” tumors to “hot” tumors. This is a powerful approach to induce host T-cell responses against target-negative cancer cells and to generate long-term memory T-cell responses.

Noile-Immune Biotech currently has three products in Phase I trials—two are licensed exclusively to Takeda Pharmaceuticals, and one is under development in-house. The company is also collaborating with other companies working on autologous immune cell derivation and gene editing.

“Our five-year vision for the company,” Tamada declares, “is to combine and expand PRIME technology with other promising technologies such as induced pluripotent stem cell–derived T cells and natural killer cells to improve care for
cancer patients.”

The post Cancer Immunotherapy Developers in Asia Explore Diverse Approaches appeared first on GEN - Genetic Engineering and Biotechnology News.

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Four Years Ago This Week, Freedom Was Torched

Four Years Ago This Week, Freedom Was Torched

Authored by Jeffrey Tucker via The Brownstone Institute,

"Beware the Ides of March,” Shakespeare…

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Four Years Ago This Week, Freedom Was Torched

Authored by Jeffrey Tucker via The Brownstone Institute,

"Beware the Ides of March,” Shakespeare quotes the soothsayer’s warning Julius Caesar about what turned out to be an impending assassination on March 15. The death of American liberty happened around the same time four years ago, when the orders went out from all levels of government to close all indoor and outdoor venues where people gather. 

It was not quite a law and it was never voted on by anyone. Seemingly out of nowhere, people who the public had largely ignored, the public health bureaucrats, all united to tell the executives in charge – mayors, governors, and the president – that the only way to deal with a respiratory virus was to scrap freedom and the Bill of Rights. 

And they did, not only in the US but all over the world. 

The forced closures in the US began on March 6 when the mayor of Austin, Texas, announced the shutdown of the technology and arts festival South by Southwest. Hundreds of thousands of contracts, of attendees and vendors, were instantly scrapped. The mayor said he was acting on the advice of his health experts and they in turn pointed to the CDC, which in turn pointed to the World Health Organization, which in turn pointed to member states and so on. 

There was no record of Covid in Austin, Texas, that day but they were sure they were doing their part to stop the spread. It was the first deployment of the “Zero Covid” strategy that became, for a time, official US policy, just as in China. 

It was never clear precisely who to blame or who would take responsibility, legal or otherwise. 

This Friday evening press conference in Austin was just the beginning. By the next Thursday evening, the lockdown mania reached a full crescendo. Donald Trump went on nationwide television to announce that everything was under control but that he was stopping all travel in and out of US borders, from Europe, the UK, Australia, and New Zealand. American citizens would need to return by Monday or be stuck. 

Americans abroad panicked while spending on tickets home and crowded into international airports with waits up to 8 hours standing shoulder to shoulder. It was the first clear sign: there would be no consistency in the deployment of these edicts. 

There is no historical record of any American president ever issuing global travel restrictions like this without a declaration of war. Until then, and since the age of travel began, every American had taken it for granted that he could buy a ticket and board a plane. That was no longer possible. Very quickly it became even difficult to travel state to state, as most states eventually implemented a two-week quarantine rule. 

The next day, Friday March 13, Broadway closed and New York City began to empty out as any residents who could went to summer homes or out of state. 

On that day, the Trump administration declared the national emergency by invoking the Stafford Act which triggers new powers and resources to the Federal Emergency Management Administration. 

In addition, the Department of Health and Human Services issued a classified document, only to be released to the public months later. The document initiated the lockdowns. It still does not exist on any government website.

The White House Coronavirus Response Task Force, led by the Vice President, will coordinate a whole-of-government approach, including governors, state and local officials, and members of Congress, to develop the best options for the safety, well-being, and health of the American people. HHS is the LFA [Lead Federal Agency] for coordinating the federal response to COVID-19.

Closures were guaranteed:

Recommend significantly limiting public gatherings and cancellation of almost all sporting events, performances, and public and private meetings that cannot be convened by phone. Consider school closures. Issue widespread ‘stay at home’ directives for public and private organizations, with nearly 100% telework for some, although critical public services and infrastructure may need to retain skeleton crews. Law enforcement could shift to focus more on crime prevention, as routine monitoring of storefronts could be important.

In this vision of turnkey totalitarian control of society, the vaccine was pre-approved: “Partner with pharmaceutical industry to produce anti-virals and vaccine.”

The National Security Council was put in charge of policy making. The CDC was just the marketing operation. That’s why it felt like martial law. Without using those words, that’s what was being declared. It even urged information management, with censorship strongly implied.

The timing here is fascinating. This document came out on a Friday. But according to every autobiographical account – from Mike Pence and Scott Gottlieb to Deborah Birx and Jared Kushner – the gathered team did not meet with Trump himself until the weekend of the 14th and 15th, Saturday and Sunday. 

According to their account, this was his first real encounter with the urge that he lock down the whole country. He reluctantly agreed to 15 days to flatten the curve. He announced this on Monday the 16th with the famous line: “All public and private venues where people gather should be closed.”

This makes no sense. The decision had already been made and all enabling documents were already in circulation. 

There are only two possibilities. 

One: the Department of Homeland Security issued this March 13 HHS document without Trump’s knowledge or authority. That seems unlikely. 

Two: Kushner, Birx, Pence, and Gottlieb are lying. They decided on a story and they are sticking to it. 

Trump himself has never explained the timeline or precisely when he decided to greenlight the lockdowns. To this day, he avoids the issue beyond his constant claim that he doesn’t get enough credit for his handling of the pandemic.

With Nixon, the famous question was always what did he know and when did he know it? When it comes to Trump and insofar as concerns Covid lockdowns – unlike the fake allegations of collusion with Russia – we have no investigations. To this day, no one in the corporate media seems even slightly interested in why, how, or when human rights got abolished by bureaucratic edict. 

As part of the lockdowns, the Cybersecurity and Infrastructure Security Agency, which was and is part of the Department of Homeland Security, as set up in 2018, broke the entire American labor force into essential and nonessential.

They also set up and enforced censorship protocols, which is why it seemed like so few objected. In addition, CISA was tasked with overseeing mail-in ballots. 

Only 8 days into the 15, Trump announced that he wanted to open the country by Easter, which was on April 12. His announcement on March 24 was treated as outrageous and irresponsible by the national press but keep in mind: Easter would already take us beyond the initial two-week lockdown. What seemed to be an opening was an extension of closing. 

This announcement by Trump encouraged Birx and Fauci to ask for an additional 30 days of lockdown, which Trump granted. Even on April 23, Trump told Georgia and Florida, which had made noises about reopening, that “It’s too soon.” He publicly fought with the governor of Georgia, who was first to open his state. 

Before the 15 days was over, Congress passed and the president signed the 880-page CARES Act, which authorized the distribution of $2 trillion to states, businesses, and individuals, thus guaranteeing that lockdowns would continue for the duration. 

There was never a stated exit plan beyond Birx’s public statements that she wanted zero cases of Covid in the country. That was never going to happen. It is very likely that the virus had already been circulating in the US and Canada from October 2019. A famous seroprevalence study by Jay Bhattacharya came out in May 2020 discerning that infections and immunity were already widespread in the California county they examined. 

What that implied was two crucial points: there was zero hope for the Zero Covid mission and this pandemic would end as they all did, through endemicity via exposure, not from a vaccine as such. That was certainly not the message that was being broadcast from Washington. The growing sense at the time was that we all had to sit tight and just wait for the inoculation on which pharmaceutical companies were working. 

By summer 2020, you recall what happened. A restless generation of kids fed up with this stay-at-home nonsense seized on the opportunity to protest racial injustice in the killing of George Floyd. Public health officials approved of these gatherings – unlike protests against lockdowns – on grounds that racism was a virus even more serious than Covid. Some of these protests got out of hand and became violent and destructive. 

Meanwhile, substance abuse rage – the liquor and weed stores never closed – and immune systems were being degraded by lack of normal exposure, exactly as the Bakersfield doctors had predicted. Millions of small businesses had closed. The learning losses from school closures were mounting, as it turned out that Zoom school was near worthless. 

It was about this time that Trump seemed to figure out – thanks to the wise council of Dr. Scott Atlas – that he had been played and started urging states to reopen. But it was strange: he seemed to be less in the position of being a president in charge and more of a public pundit, Tweeting out his wishes until his account was banned. He was unable to put the worms back in the can that he had approved opening. 

By that time, and by all accounts, Trump was convinced that the whole effort was a mistake, that he had been trolled into wrecking the country he promised to make great. It was too late. Mail-in ballots had been widely approved, the country was in shambles, the media and public health bureaucrats were ruling the airwaves, and his final months of the campaign failed even to come to grips with the reality on the ground. 

At the time, many people had predicted that once Biden took office and the vaccine was released, Covid would be declared to have been beaten. But that didn’t happen and mainly for one reason: resistance to the vaccine was more intense than anyone had predicted. The Biden administration attempted to impose mandates on the entire US workforce. Thanks to a Supreme Court ruling, that effort was thwarted but not before HR departments around the country had already implemented them. 

As the months rolled on – and four major cities closed all public accommodations to the unvaccinated, who were being demonized for prolonging the pandemic – it became clear that the vaccine could not and would not stop infection or transmission, which means that this shot could not be classified as a public health benefit. Even as a private benefit, the evidence was mixed. Any protection it provided was short-lived and reports of vaccine injury began to mount. Even now, we cannot gain full clarity on the scale of the problem because essential data and documentation remains classified. 

After four years, we find ourselves in a strange position. We still do not know precisely what unfolded in mid-March 2020: who made what decisions, when, and why. There has been no serious attempt at any high level to provide a clear accounting much less assign blame. 

Not even Tucker Carlson, who reportedly played a crucial role in getting Trump to panic over the virus, will tell us the source of his own information or what his source told him. There have been a series of valuable hearings in the House and Senate but they have received little to no press attention, and none have focus on the lockdown orders themselves. 

The prevailing attitude in public life is just to forget the whole thing. And yet we live now in a country very different from the one we inhabited five years ago. Our media is captured. Social media is widely censored in violation of the First Amendment, a problem being taken up by the Supreme Court this month with no certainty of the outcome. The administrative state that seized control has not given up power. Crime has been normalized. Art and music institutions are on the rocks. Public trust in all official institutions is at rock bottom. We don’t even know if we can trust the elections anymore. 

In the early days of lockdown, Henry Kissinger warned that if the mitigation plan does not go well, the world will find itself set “on fire.” He died in 2023. Meanwhile, the world is indeed on fire. The essential struggle in every country on earth today concerns the battle between the authority and power of permanent administration apparatus of the state – the very one that took total control in lockdowns – and the enlightenment ideal of a government that is responsible to the will of the people and the moral demand for freedom and rights. 

How this struggle turns out is the essential story of our times. 

CODA: I’m embedding a copy of PanCAP Adapted, as annotated by Debbie Lerman. You might need to download the whole thing to see the annotations. If you can help with research, please do.

*  *  *

Jeffrey Tucker is the author of the excellent new book 'Life After Lock-Down'

Tyler Durden Mon, 03/11/2024 - 23:40

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Red Candle In The Wind

Red Candle In The Wind

By Benjamin PIcton of Rabobank

February non-farm payrolls superficially exceeded market expectations on Friday by…

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Red Candle In The Wind

By Benjamin PIcton of Rabobank

February non-farm payrolls superficially exceeded market expectations on Friday by printing at 275,000 against a consensus call of 200,000. We say superficially, because the downward revisions to prior months totalled 167,000 for December and January, taking the total change in employed persons well below the implied forecast, and helping the unemployment rate to pop two-ticks to 3.9%. The U6 underemployment rate also rose from 7.2% to 7.3%, while average hourly earnings growth fell to 0.2% m-o-m and average weekly hours worked languished at 34.3, equalling pre-pandemic lows.

Undeterred by the devil in the detail, the algos sprang into action once exchanges opened. Market darling NVIDIA hit a new intraday high of $974 before (presumably) the humans took over and sold the stock down more than 10% to close at $875.28. If our suspicions are correct that it was the AIs buying before the humans started selling (no doubt triggering trailing stops on the way down), the irony is not lost on us.

The 1-day chart for NVIDIA now makes for interesting viewing, because the red candle posted on Friday presents quite a strong bearish engulfing signal. Volume traded on the day was almost double the 15-day simple moving average, and similar price action is observable on the 1-day charts for both Intel and AMD. Regular readers will be aware that we have expressed incredulity in the past about the durability the AI thematic melt-up, so it will be interesting to see whether Friday’s sell off is just a profit-taking blip, or a genuine trend reversal.

AI equities aside, this week ought to be important for markets because the BTFP program expires today. That means that the Fed will no longer be loaning cash to the banking system in exchange for collateral pledged at-par. The KBW Regional Banking index has so far taken this in its stride and is trading 30% above the lows established during the mini banking crisis of this time last year, but the Fed’s liquidity facility was effectively an exercise in can-kicking that makes regional banks a sector of the market worth paying attention to in the weeks ahead. Even here in Sydney, regulators are warning of external risks posed to the banking sector from scheduled refinancing of commercial real estate loans following sharp falls in valuations.

Markets are sending signals in other sectors, too. Gold closed at a new record-high of $2178/oz on Friday after trading above $2200/oz briefly. Gold has been going ballistic since the Friday before last, posting gains even on days where 2-year Treasury yields have risen. Gold bugs are buying as real yields fall from the October highs and inflation breakevens creep higher. This is particularly interesting as gold ETFs have been recording net outflows; suggesting that price gains aren’t being driven by a retail pile-in. Are gold buyers now betting on a stagflationary outcome where the Fed cuts without inflation being anchored at the 2% target? The price action around the US CPI release tomorrow ought to be illuminating.

Leaving the day-to-day movements to one side, we are also seeing further signs of structural change at the macro level. The UK budget last week included a provision for the creation of a British ISA. That is, an Individual Savings Account that provides tax breaks to savers who invest their money in the stock of British companies. This follows moves last year to encourage pension funds to head up the risk curve by allocating 5% of their capital to unlisted investments.

As a Hail Mary option for a government cruising toward an electoral drubbing it’s a curious choice, but it’s worth highlighting as cash-strapped governments increasingly see private savings pools as a funding solution for their spending priorities.

Of course, the UK is not alone in making creeping moves towards financial repression. In contrast to announcements today of increased trade liberalisation, Australian Treasurer Jim Chalmers has in the recent past flagged his interest in tapping private pension savings to fund state spending priorities, including defence, public housing and renewable energy projects. Both the UK and Australia appear intent on finding ways to open up the lungs of their economies, but government wants more say in directing private capital flows for state goals.

So, how far is the blurring of the lines between free markets and state planning likely to go? Given the immense and varied budgetary (and security) pressures that governments are facing, could we see a re-up of WWII-era Victory bonds, where private investors are encouraged to do their patriotic duty by directly financing government at negative real rates?

That would really light a fire under the gold market.

Tyler Durden Mon, 03/11/2024 - 19:00

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Trump “Clearly Hasn’t Learned From His COVID-Era Mistakes”, RFK Jr. Says

Trump "Clearly Hasn’t Learned From His COVID-Era Mistakes", RFK Jr. Says

Authored by Jeff Louderback via The Epoch Times (emphasis ours),

President…

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Trump "Clearly Hasn't Learned From His COVID-Era Mistakes", RFK Jr. Says

Authored by Jeff Louderback via The Epoch Times (emphasis ours),

President Joe Biden claimed that COVID vaccines are now helping cancer patients during his State of the Union address on March 7, but it was a response on Truth Social from former President Donald Trump that drew the ire of independent presidential candidate Robert F. Kennedy Jr.

Robert F. Kennedy Jr. holds a voter rally in Grand Rapids, Mich., on Feb. 10, 2024. (Mitch Ranger for The Epoch Times)

During the address, President Biden said: “The pandemic no longer controls our lives. The vaccines that saved us from COVID are now being used to help beat cancer, turning setback into comeback. That’s what America does.”

President Trump wrote: “The Pandemic no longer controls our lives. The VACCINES that saved us from COVID are now being used to help beat cancer—turning setback into comeback. YOU’RE WELCOME JOE. NINE-MONTH APPROVAL TIME VS. 12 YEARS THAT IT WOULD HAVE TAKEN YOU.”

An outspoken critic of President Trump’s COVID response, and the Operation Warp Speed program that escalated the availability of COVID vaccines, Mr. Kennedy said on X, formerly known as Twitter, that “Donald Trump clearly hasn’t learned from his COVID-era mistakes.”

“He fails to recognize how ineffective his warp speed vaccine is as the ninth shot is being recommended to seniors. Even more troubling is the documented harm being caused by the shot to so many innocent children and adults who are suffering myocarditis, pericarditis, and brain inflammation,” Mr. Kennedy remarked.

“This has been confirmed by a CDC-funded study of 99 million people. Instead of bragging about its speedy approval, we should be honestly and transparently debating the abundant evidence that this vaccine may have caused more harm than good.

“I look forward to debating both Trump and Biden on Sept. 16 in San Marcos, Texas.”

Mr. Kennedy announced in April 2023 that he would challenge President Biden for the 2024 Democratic Party presidential nomination before declaring his run as an independent last October, claiming that the Democrat National Committee was “rigging the primary.”

Since the early stages of his campaign, Mr. Kennedy has generated more support than pundits expected from conservatives, moderates, and independents resulting in speculation that he could take votes away from President Trump.

Many Republicans continue to seek a reckoning over the government-imposed pandemic lockdowns and vaccine mandates.

President Trump’s defense of Operation Warp Speed, the program he rolled out in May 2020 to spur the development and distribution of COVID-19 vaccines amid the pandemic, remains a sticking point for some of his supporters.

Vice President Mike Pence (L) and President Donald Trump deliver an update on Operation Warp Speed in the Rose Garden of the White House in Washington on Nov. 13, 2020. (Mandel Ngan/AFP via Getty Images)

Operation Warp Speed featured a partnership between the government, the military, and the private sector, with the government paying for millions of vaccine doses to be produced.

President Trump released a statement in March 2021 saying: “I hope everyone remembers when they’re getting the COVID-19 Vaccine, that if I wasn’t President, you wouldn’t be getting that beautiful ‘shot’ for 5 years, at best, and probably wouldn’t be getting it at all. I hope everyone remembers!”

President Trump said about the COVID-19 vaccine in an interview on Fox News in March 2021: “It works incredibly well. Ninety-five percent, maybe even more than that. I would recommend it, and I would recommend it to a lot of people that don’t want to get it and a lot of those people voted for me, frankly.

“But again, we have our freedoms and we have to live by that and I agree with that also. But it’s a great vaccine, it’s a safe vaccine, and it’s something that works.”

On many occasions, President Trump has said that he is not in favor of vaccine mandates.

An environmental attorney, Mr. Kennedy founded Children’s Health Defense, a nonprofit that aims to end childhood health epidemics by promoting vaccine safeguards, among other initiatives.

Last year, Mr. Kennedy told podcaster Joe Rogan that ivermectin was suppressed by the FDA so that the COVID-19 vaccines could be granted emergency use authorization.

He has criticized Big Pharma, vaccine safety, and government mandates for years.

Since launching his presidential campaign, Mr. Kennedy has made his stances on the COVID-19 vaccines, and vaccines in general, a frequent talking point.

“I would argue that the science is very clear right now that they [vaccines] caused a lot more problems than they averted,” Mr. Kennedy said on Piers Morgan Uncensored last April.

“And if you look at the countries that did not vaccinate, they had the lowest death rates, they had the lowest COVID and infection rates.”

Additional data show a “direct correlation” between excess deaths and high vaccination rates in developed countries, he said.

President Trump and Mr. Kennedy have similar views on topics like protecting the U.S.-Mexico border and ending the Russia-Ukraine war.

COVID-19 is the topic where Mr. Kennedy and President Trump seem to differ the most.

Former President Donald Trump intended to “drain the swamp” when he took office in 2017, but he was “intimidated by bureaucrats” at federal agencies and did not accomplish that objective, Mr. Kennedy said on Feb. 5.

Speaking at a voter rally in Tucson, where he collected signatures to get on the Arizona ballot, the independent presidential candidate said President Trump was “earnest” when he vowed to “drain the swamp,” but it was “business as usual” during his term.

John Bolton, who President Trump appointed as a national security adviser, is “the template for a swamp creature,” Mr. Kennedy said.

Scott Gottlieb, who President Trump named to run the FDA, “was Pfizer’s business partner” and eventually returned to Pfizer, Mr. Kennedy said.

Mr. Kennedy said that President Trump had more lobbyists running federal agencies than any president in U.S. history.

“You can’t reform them when you’ve got the swamp creatures running them, and I’m not going to do that. I’m going to do something different,” Mr. Kennedy said.

During the COVID-19 pandemic, President Trump “did not ask the questions that he should have,” he believes.

President Trump “knew that lockdowns were wrong” and then “agreed to lockdowns,” Mr. Kennedy said.

He also “knew that hydroxychloroquine worked, he said it,” Mr. Kennedy explained, adding that he was eventually “rolled over” by Dr. Anthony Fauci and his advisers.

President Donald Trump greets the crowd before he leaves at the Operation Warp Speed Vaccine Summit in Washington on Dec. 8, 2020. (Tasos Katopodis/Getty Images)

MaryJo Perry, a longtime advocate for vaccine choice and a Trump supporter, thinks votes will be at a premium come Election Day, particularly because the independent and third-party field is becoming more competitive.

Ms. Perry, president of Mississippi Parents for Vaccine Rights, believes advocates for medical freedom could determine who is ultimately president.

She believes that Mr. Kennedy is “pulling votes from Trump” because of the former president’s stance on the vaccines.

“People care about medical freedom. It’s an important issue here in Mississippi, and across the country,” Ms. Perry told The Epoch Times.

“Trump should admit he was wrong about Operation Warp Speed and that COVID vaccines have been dangerous. That would make a difference among people he has offended.”

President Trump won’t lose enough votes to Mr. Kennedy about Operation Warp Speed and COVID vaccines to have a significant impact on the election, Ohio Republican strategist Wes Farno told The Epoch Times.

President Trump won in Ohio by eight percentage points in both 2016 and 2020. The Ohio Republican Party endorsed President Trump for the nomination in 2024.

“The positives of a Trump presidency far outweigh the negatives,” Mr. Farno said. “People are more concerned about their wallet and the economy.

“They are asking themselves if they were better off during President Trump’s term compared to since President Biden took office. The answer to that question is obvious because many Americans are struggling to afford groceries, gas, mortgages, and rent payments.

“America needs President Trump.”

Multiple national polls back Mr. Farno’s view.

As of March 6, the RealClearPolitics average of polls indicates that President Trump has 41.8 percent support in a five-way race that includes President Biden (38.4 percent), Mr. Kennedy (12.7 percent), independent Cornel West (2.6 percent), and Green Party nominee Jill Stein (1.7 percent).

A Pew Research Center study conducted among 10,133 U.S. adults from Feb. 7 to Feb. 11 showed that Democrats and Democrat-leaning independents (42 percent) are more likely than Republicans and GOP-leaning independents (15 percent) to say they have received an updated COVID vaccine.

The poll also reported that just 28 percent of adults say they have received the updated COVID inoculation.

The peer-reviewed multinational study of more than 99 million vaccinated people that Mr. Kennedy referenced in his X post on March 7 was published in the Vaccine journal on Feb. 12.

It aimed to evaluate the risk of 13 adverse events of special interest (AESI) following COVID-19 vaccination. The AESIs spanned three categories—neurological, hematologic (blood), and cardiovascular.

The study reviewed data collected from more than 99 million vaccinated people from eight nations—Argentina, Australia, Canada, Denmark, Finland, France, New Zealand, and Scotland—looking at risks up to 42 days after getting the shots.

Three vaccines—Pfizer and Moderna’s mRNA vaccines as well as AstraZeneca’s viral vector jab—were examined in the study.

Researchers found higher-than-expected cases that they deemed met the threshold to be potential safety signals for multiple AESIs, including for Guillain-Barre syndrome (GBS), cerebral venous sinus thrombosis (CVST), myocarditis, and pericarditis.

A safety signal refers to information that could suggest a potential risk or harm that may be associated with a medical product.

The study identified higher incidences of neurological, cardiovascular, and blood disorder complications than what the researchers expected.

President Trump’s role in Operation Warp Speed, and his continued praise of the COVID vaccine, remains a concern for some voters, including those who still support him.

Krista Cobb is a 40-year-old mother in western Ohio. She voted for President Trump in 2020 and said she would cast her vote for him this November, but she was stunned when she saw his response to President Biden about the COVID-19 vaccine during the State of the Union address.

I love President Trump and support his policies, but at this point, he has to know they [advisers and health officials] lied about the shot,” Ms. Cobb told The Epoch Times.

“If he continues to promote it, especially after all of the hearings they’ve had about it in Congress, the side effects, and cover-ups on Capitol Hill, at what point does he become the same as the people who have lied?” Ms. Cobb added.

“I think he should distance himself from talk about Operation Warp Speed and even admit that he was wrong—that the vaccines have not had the impact he was told they would have. If he did that, people would respect him even more.”

Tyler Durden Mon, 03/11/2024 - 17:00

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