RNA-based immunizing agents have enriched the repertoire of technologies used for vaccine development. An analysis of the active clinical trials in early…
RNA-based immunizing agents have enriched the repertoire of technologies used for vaccine development. An analysis of the active clinical trials in early Phase I and Phase I during the year of 2023 illustrates this point. A total of 161 active vaccine trials were registered at clinicaltrials.gov. Information from these trials was used to plot (Chart 1) and (Chart 2) SARS-CoV-2/COVID-19 trials were excluded to give more evidence to other disease targets.
Chart 1. Targets for Vaccines in Early Stages of Clinical Development. Early Phase I and Phase I clinical trials were grouped according to the diseases (cancer or Alzheimer) or type of infectious agents (viruses, bacteria, protozoa, helminth, and yeast). One-hundred-sixty-one trials were identified using vaccine as keyword and filters for active trials and therapeutic intervention during the period of 01/01/2023 to 1/7/2024. COVID 19/SARS-CoV-2 related trials were excluded. [clinicaltrials.gov]The highest number of trials were against viral infections (67 trials). Most have influenza, Herpes zoster, RSV (Respiratory Syncytial virus), and HIV as targets. The commercially available flu vaccines do need improvement and RNA technologies provide hope for better products. Different companies are exploring this space, including Moderna, Sanofi, Pfizer, Arcturus, Seqirus, and GSK.
The commercial success of Shingrix®, the GSK vaccine against Herpes zoster, has led to five companies in China to follow suit with their own products. Moderna is also pursuing the shingles market with an mRNA-based candidate, while Immorna (China) is testing a self-replicating RNA vaccine. Another competitive market is vaccines for respiratory tract infections. RSV is the leading causative agent for lower track respiratory diseases, causing 3.4 million hospitalizations and 950,00–150,000 deaths every year.
Until recently, no vaccines against the virus were commercially available, but two were approved by the FDA in 2023. Arexvy® from GSK, was approved for older adults, and Abrysvo® from Pfizer, for adults and pregnant women (to protect infants from birth to six months). Four other companies are developing vaccines against RSV.
Blue Lake Biotechnology (U.S.) and Codagenix (U.S.) are testing pediatric vaccines. The former is working on an intranasal recombinant parainfluenza virus type 5 for infants and children, and the latter, also developing an intranasal pediatric vaccine, but based on a live-attenuated engineered virus. Sanofi has two trials, one for infants (intranasal) based on live attenuated virus and one for adults (intramuscular) against both RSV and hMPV (human metapneumovirus).
Targeting both these viruses in one jab is also in Moderna’s and AstraZeneca’s pipeline. While Moderna is developing an mRNA-based formulation for infants, AstraZeneca, through the acquisition of Icosavax, has a VLP (Virus-Like Particle) platform technology with a lead program targeting both viruses[1].
Decades of difficulties in the development of vaccines against HIV resulted in many companies dropping their research programs targeting the virus. Of the eight ongoing trials, seven are sponsored by research institutions and only one is sponsored by a company, Vir Biotechnology.
Second largest target
The second largest target in number of trials is cancer (56 trials). The vast majority involve the development of immunotherapies and a recurrent approach are therapeutic vaccines using dendritic cells loaded with personalized neoantigens. Ten out of the 56 cancer trials are based on RNA technologies. Nature’s publication from June 2023[2], showing promising results of a personalized neoantigen mRNA immunotherapy for pancreatic cancer, indicated the feasibility of this complex approach.
The number of companies as sponsors of early-stage trials for vaccines for cancer is smaller than that for viral infections (many cancer trials are sponsored by research/academic institutions). Nevertheless, a good proportion of the company-sponsored trials are for cancers associated with viruses, such as is the case for the HPV vaccines. The vast majority of cervical cancers is associated with the presence of the HPV virus and immunization programs almost eliminated cervical cancer in women born in England since 1995[3].
It is reasonable to hope that the vaccines being developed for EBV (Epstein–Barr virus) or CMV (Cytomegalovirus) associated cancers (hematological malignancies and glioblastomas, respectively) can be successful as well. Immunomic Therapeutics has a DNA formulation based on its UNITE® proprietary technology that explores the CMV-GBM association.
The twelve trials in the protozoa group (Chart 1) are all against just one protozoan, Plasmodium, the causative agent of malaria. Six are sponsored by the University of Oxford. R21, the vaccine developed by Oxford University and the Serum Institute of India, is based on a recombinant protein. It is the second vaccine recommended by the WHO for malaria, a fusion recombinant product which is part circumsporozoite protein of Plasmodium falciparum and part Hepatitis B surface protein antigen.
Recombinant construct
Expressed in yeast, this recombinant construct is more immunogenic and cheaper to manufacture than Mosquirix® (the first malaria vaccine recommended by WHO, developed by GSK)[4]. It is worthy to note that all formulations in University of Oxford’s trials employ the Matrix-MTM adjuvant, which was developed by Novavax and is made with compounds from the bark of the Chilean tree Quillaja saponaria[5].
Twenty trials are registered against bacterial infections: tetanus, diphtheria, Shigellosis, pneumococcal, streptococcal, and meningococcal infections, tuberculosis, and Lyme Disease are the targets. Old unmet medical needs, such as Lyme disease and tuberculosis, are being addressed (also) by mRNA technologies. The Austrian company Eveliqure has a new approach for attenuating genetically engineered bacteria and is testing its oral ShigETEC against Shigellosis. In Australia, GPN Vaccines innovated on inactivation of whole organisms and is using its technology against pneumococcal infections.
Chart 2. Technologies Used for Vaccine Development. [Golgher and Rodrigues]Lastly are the trials that comprise a low percentage of the pipeline, which is unfortunate since they address unmet medical needs of millions. There is just one trial against helminths, against schistosomiasis, a disease that affects 240 million people. Sponsored by the International Vaccine Institute, it has Seattle-based PAI Life Sciences as a collaborator.
Two trials are against Alzheimer disease, both sponsored by research institutions. One is a DNA based vaccine that aims to elicit antibodies against amyloid-β.The other, interestingly, is testing if the BCG vaccine (Bacillus Calmette–Guérin) has an effect on reducing biomarkers for the disease. BCG vaccines are based on attenuated forms of the bacterium Mycobacterium bovis.
The only trial against a fungal infection targets yeast. The goal is to generate protection for women who experience recurrent vulvovaginal candidiasis, and the trial is sponsored by the Swiss company LimmaTech Biologics, in collaboration with GSK. There are no available vaccines against fungal infections, which are responsible for an annual global death rate of approximately 1.5 million[6].
More input needed from South America
Interesting points could be drawn from the analysis of the ongoing early Phase I and Phase I clinical trials on vaccines. There were more European biotechnology companies (11) (Austria, Denmark, France, Germany, Switzerland, Sweden) plus one in the U.K., than there were American companies (10).
By adding the Australian and Asian companies in early stages clinical trials, there were 30 biotechs dedicated to the development of interesting immunizing agents. By mix and matching old approaches (inactivated or attenuated) with more modern ones (recombinant proteins, fusion constructs, VLPs, RNA, DNA), using systems biology, genetic engineering, AI), innovation in vaccines is flourishing. See Figure 1.
Figure 1. Novel, and not so novel, technologies incrementing the vaccine pipeline. [Golgher and Rodrigues]Some of the diseases studied by the companies developing these early-stage clinical trials are predominantly health problems of low- and middle-income countries. It is disappointing to note the absence of companies from South America among the sponsors or collaborators in these trials. According to IQVIA, the global vaccine market (excluding COVID-19) reached $39 billion in 2022, with a growth rate of seven percent CAGR between 2017–2022[7]. The market is mostly driven by innovative vaccines and is bound to grow. South American countries must work to have a better share of it.
Brazil has an admirable vaccination program and internationally recognized governmental vaccine factories (Butantan and Biomanguinhos), but a poor track record on innovation in this area[8]. It is senseless to invest so much in the training of excellent immunologists, vaccinologists, and infectious disease experts and not translate this into novel products. A lot more can be done.
If it depends on the initiative, CTVacinas (soon to be CN Vaccines, CN for National Center), coordinated by the researcher Ricardo Gazzinelli, DSc, DVM, Oswaldo Cruz Foundation and Universidade Federal de Minas Gerais (UFMG), it will be done.
For those who know Gazzinelli, it is easy to bet that the enterprise under his leadership, which includes the collaboration of several other researchers from UFMG, will thrive. When it comes to partnerships, CTVacinas is open and agnostic; what matters is that meaningful projects move forward, and partners can come from private, public, international or national institutions. An important part of their mission is to be an institute good at translating academic research into novel immunizing formulations. The aim is to generate more businesses, products, and startups.
CTVacinas has a history: part of its revenues come from royalties from a vaccine for dogs against visceral leishmaniasis, developed by Gazzinelli and his business partner, Ana Paula Fernandes.
Figure 2. Ricardo Gazzinelli, pictured on the right and the CTVacinas team on the left. CTVacinas is located at UFMG’s technology park, it is a leading organization in developing vaccine projects that can become innovative products and businesses. The initiative has secured funds for expansion. [CTVacinas]In CTVacinas pipeline is SpiN-Tec, a vaccine against SARS-CoV-2, now in Phase II trials. It is the first 100% Brazilian vaccine. SpiN-Tec is a made of a recombinant fusion product of the S and N proteins of the virus, and the hope is that it will confer protection irrespective of the strain.
Helton Santiago, MD, PhD, a professor at UFMG who works with Gazzinelli, is responsible for SpiN-Tec’s clinical program, among others. He is an enthusiastic member of the CTVacinas vaccine team and is optimistic about the future of Brazil in the vaccine field. According to Santiago, the COVID-19 pandemic stimulated the national players to move at a faster pace toward innovation.
If some needed a pandemic to shake them out of a sluggish mode, others have started out going as fast as possible. It is the case, for example, of Luana Raposo, Bruna Porchia, and Mariana Diniz, founders of ImunoTera, a spinoff from the University of São Paulo (Figure 3). With proprietary technology developed during their PhDs, they have succeeded in securing funds for their company’s first steps.
Figure 3. Founders of ImunoTera, Luana Raposo (left) and Bruna Porchia (right) at the Albert Einstein Hospital. ImunoTera was one of the startups selected for the hospital’s biotechnology program. [Tauan Sousa]ImunoTera is dedicated to developing immunotherapies against infectious diseases and cancer and has been selected for competitive preincubation and incubation programs in the country. The founders have chosen wisely and, with the support of the best programs and partners to develop their pipeline, are advancing. Their first product has been tested in patients with HPV-induced high grade cervical neoplasia, with promising results. ImunoTera may be the one to develop the next 100% Brazilian vaccine.
Denise Golgher, PhD (d.golgher@gmail.com) is a life sciences consultant based in São Paulo, Brazil. Rob Rodrigues, LLM, Stanford Law School, is a partner at Licks Attorneys. Many thanks to our interviewees, Luana Raposo from Imunotera, Walderez Dutra from UFMG, Ricardo Gazzinelli and Helton Santiago from CT vacinas, Eduardo Levi from DASA, Jorge Kalil from USP and Constantino Lopez from Instituto Mexicano del Seguro Social.
LOS ANGELES — A clinical trial from Keck Medicine of USC will test the feasibility of treating non-small cell lung cancer with immunotherapy provided at home.
Credit: Ricardo Carrasco III
LOS ANGELES — A clinical trial from Keck Medicine of USC will test the feasibility of treating non-small cell lung cancer with immunotherapy provided at home.
Immunotherapy, medicines that use the body’s immune system to eliminate or control cancer cells, are effective for many cancer patients, but are currently only administered intravenously (into the vein) in a doctor’s office or hospital.
The study will examine if a new formulation of atezolizumab, an immunotherapy approved for treating certain types of non-small cell lung cancer, can instead be safely and effectively administered subcutaneously, meaning it is injected under the patient’s skin, by a nurse at the patient’s home, along with telemedicine appointments and remote monitoring through wearable trackers.
This will be the first clinical trial to test at-home administration of subcutaneous immunotherapy and could potentially lay the foundation for the future of at-home cancer care.
“Many types of drugs are now being delivered subcutaneously at home for several conditions, and we hypothesize that this method of drug delivery can also be successful for cancer patients,” said Jorge Nieva, MD, a medical oncologist and lung cancer specialist with Keck Medicine, a member of USC Norris Comprehensive Cancer Center and lead investigator of the clinical trial. “Additionally, since COVID-19, we’ve learned that physicians have the digital tools to provide patients with excellent remote care.”
The benefits of at-home treatment
Lung cancer is the second most diagnosed cancer in the world and the leading cause of cancer deaths for both men and women worldwide. Non-small cell lung cancer accounts for 81% of all lung cancer cases in the United States.
Immunotherapy is a relatively new treatment option that has been approved to treat many cancer types both on its own or in combination with other therapies, such as radiation and chemotherapy.
Nieva believes that moving immunotherapy from a medical setting to the home will benefit patients. Patients will save time and energy traveling to a clinic or doctor’s office, which can be especially difficult for those who are very sick, and they may feel more relaxed in their own homes. This could also potentially expand access to cancer treatment to patients who live in more remote areas or lack reliable access to transportation.
Delivering the drug under the skin rather than through an intravenous line (IV) has advantages as well.
“The procedure is easier and faster to administer and less likely to cause infection or complications, and patients avoid the potential discomfort of being stuck with a needle several times in the attempt to find a suitable vein for the IV,” said Nieva.
Nieva was motivated to research at-home cancer treatments during the COVID-19 pandemic when a patient who was afraid of catching the virus died after he stopped going into the hospital for his cancer treatments.
“I realized we had to change the delivery of cancer care,” said Nieva.
Clinical trial will use an immunotherapy consisting of monoclonal antibodies
The drug used in the clinical trial, atezolizumab, consists of a monoclonal antibody, a man-made protein that triggers the immune system to attack cancer cells. It was approved by the Food and Drug Administration in 2016 for late-stage lung cancer and more recently in 2021, for early stage, non-small cell lung cancer.
Investigators aim to enroll 37 patients with non-small cell lung cancer who are deemed eligible to receive immunotherapy as treatment. Patients will receive treatments administered by a nurse who will visit their home every three weeks for one to two years.
Additionally, Nieva and his colleagues will use the latest digital tools to track patients’ vital signs, physical activity and other markers of health remotely and monitor patients with telehealth visits.
The study will not only examine the feasibility of home administration of the medication, but how well patients comply with the program and how satisfied they are with being treated remotely and through telehealth appointments.
Nivea hopes that the clinical trial will not only benefit patients with non-small cell lung cancer, but other cancer patients as well.
“Increasingly, health care is moving in a direction where instead of patients going to us for services, we are able to come to them, increasing access to care and potentially addressing existing health care disparities,” said Nieva. “If this study can show that at-home cancer immunotherapy is safe and feasible for non-small cell lung cancer, it will open the door for more home treatments for other types of cancers in the future.”
To learn more about the criteria to participate in the clinical trial, click here. Those who are interested in participating in the trial may contact Sandy Tran at (323) 865-3935 or sandy.tran@med.usc.edu.
The sponsors of the clinical trial are the National Cancer Institute (NCI), grant number ML43326, and Genentech, Inc.
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For more information about Keck Medicine of USC, please visit news.KeckMedicine.org.
Walgreens Incurs $5.8Bn Charge on VillageMD Amid Cost-Cutting
Under the leadership of CEO Rosalind Brewer, the company sought to enhance its healthcare offerings by investing heavily in VillageMD, a network of doctors’…
Under the leadership of CEO Rosalind Brewer, the company sought to enhance its healthcare offerings by investing heavily in VillageMD, a network of doctors’ clinics known for consuming substantial cash flows.
Over recent years, Walgreens has poured more than $6 billion into acquiring a majority stake in VillageMD, further bolstering its healthcare footprint with a $3.5 billion investment in Summit Health in 2022.
However, a strategic pivot occurred with Timothy Wentworth stepping in as the new CEO, bringing a sharpened focus on bolstering profitability. This included unveiling a comprehensive plan to trim costs by $1 billion in October as part of a broader effort to realign the company’s financial strategies.
This quarter, the repercussions of these investments became starkly evident as Walgreens reported a net loss of $5.9 billion for the quarter ending February 29, primarily due to the significant impairment charge. Concurrently, the company adjusted its profit outlook for the 2024 fiscal year downwards, reflecting the ongoing economic pressures impacting its retail segment.
This revision sets a more conservative benchmark for growth expectations in the 2025 fiscal year, as Leerink Partners analyst Michael Cherny noted. This amplifies concerns about Walgreens’ fundamental earning capabilities.
Amid these challenges, Walgreens also contends with diminished consumer spending on personal care and beauty items, a trend exacerbated by inflation and a decline in demand for COVID-19 vaccines and testing services. This broader consumer reticence has further strained the company’s financial performance, evidenced by a 1.4% drop in premarket shares.
Despite these hurdles, Walgreens managed to surpass analyst expectations on an adjusted basis, posting earnings of $1.20 per share for the quarter against the consensus forecast of 82 cents per share from LSEG data.
The company has revised its adjusted earnings projection for the fiscal year ending August 31 to between $3.20 and $3.35 per share. It maintains the lower end of its initial January forecast while narrowing the upper limit from the previously stated $3.50 per share.
The EU never enforced its Growth and Stability Pact or Maastricht Treaty rules. The crisis is coming to a head with France and Italy in the spotlight. The first casualty will be Green policy.
Deficit rule: a country is compliant if (i) the budget balance of general government is equal or larger than -3% of GDP or, (ii) in case the -3% of GDP threshold is breached, the deviation remains small (max 0.5% of GDP) and limited to one year.
Debt rule: a country is compliant if the general government debt-to-GDP ratio is below 60% of GDP or if the excess above 60% of GDP has been declining by 1/20 on average over the past three years.
Structural balance rule: a country is compliant if (i) the structural budget balance of general government is at or above the medium-term objective (MTO) or, (ii) in case the MTO has not been reached yet, the annual improvement of the structural balance is equal or higher than 0.5% of GDP, or the remaining distance to the MTO is smaller than 0.5% of GDP.
Expenditure rule: a country is complaint if the annual rate of growth of primary government expenditure, net of discretionary revenue measures and one-offs, is at or below the 10-year average of the nominal rate of potential output growth minus the convergence margin necessary to ensure an adjustment of the structural budget deficit in line with the structural balance rule.
Deficit Disaster Zones
France and Italy are major disasters right now on the budget deficit rule. France has a budget deficit of 7 percent and Italy 5 percent.
France needs to reduce its deficit by a whopping 4 percent of GDP!
Neither Italy nor Greece should never have been allowed in the EMU (European Monetary Union – Eurozone) in the first place.
Greece has a debt-to-GDP ratio of 170 percent. The target is 60 percent.
But the lead chart tells the picture. Only the Scandinavian countries are in compliance.
The latest revamp of two-decades-old rules known as the Stability and Growth Pact came after some EU countries racked up record high debt as they increased spending to help their economies recover from the pandemic, and as the bloc announced ambitious green, industrial and defense goals.
The revised rules allow countries with excessive borrowing to reduce their debt on average by 1% per year if it is above 90% of gross domestic product (GDP), and by 0.5% per year on average if the debt pile is between 60% and 90% of GDP.
Countries with a deficit above 3% of GDP are required to halve this to 1.5% during periods of growth, creating a safety buffer for tough times ahead.
Defense spending will be taken into account when the Commission assesses a country’s high deficit, a consideration triggered by Russia’s invasion of Ukraine.
The new rules give countries seven years, up from four previously, to cut debt and deficit starting from 2025.
Note that the EU can tweak enforcement but not the baseline Stability and Growth Pact targets themselves without unanimous agreement, and a new treaty.
With that background, let’s look ahead to the crisis that looms as described by Eurointelligence.
Europe’s Next Financial Crisis
We would like to alert our readers to a theme that has been preoccupying us for a while – the possibility of another financial crisis in Europe. We have generally been restrained in our warning of financial crises. The main exception was the global financial crisis and its cousin, the euro area’s sovereign debt crisis. Fifteen or so years later, we see another financial crisis ahead here in Europe: a crisis of the European social and political model with deep consequences for fiscal and financial stability.
The canary in the coalmine is the overshooting budget deficits in France and Italy, at over 7% and over 5% for 2024 respectively. These numbers are a symptom, not a cause. Behind them lies a lack of economic growth needed to sustain Europe’s social model. Germany’s fiscal policy could not be more different than that of France or Italy, and yet Germany is afflicted by the exact same problem.
The European model was powered by oligopolistic industrial companies, which were heavily supported by the state through regulation that tilted the level-playing field in their favor. The German car industry is a classic example, but everybody did this.
What is killing this model now is a shift in technology and geopolitical fragmentation. Of the two, we would argue the first is the more important. More and more functions in our lives that were previously the realm of purely mechanical processes are nowadays wholly or partially digitalized. Barriers of entry have collapsed. China went from zero to the world leader in electric cars.
European companies no longer generate sufficient profits to fuel the social model – and to fund long-term research. It is no surprise that Europe has only very few tech companies. In short, Europe’s oligopolistic old-tech model no longer works in a digital world. We have been reporting on the attempts by the EU to stem against technological developments through regulation. But this is a way of addressing symptoms, not causes.
After the multiple global shocks of this decade, the consequences of Europe’s technological decline translate into lower potential growth rates. Italy came first. Its productivity growth has been near zero since it joined the euro. The UK’s productivity growth slumped after the global financial crisis, and never recovered since. Germany’s productivity growth is unlikely to recover, even if the economic cycle does. The German Council of Economic Experts see a potential growth of around 0.5% until the end of the decade. With productivity growth that low, Europe’s model has become financially unsustainable. It is unsurprising that the political system is fragmenting everywhere. The argument for sustained deficits, in France for example, is that you need them to keep Marine Le Pen out of power. This means they will persist.
We have a fiscal crisis ahead, caused by a combination of falling productivity growth and political gridlock. Technology is the main cause of the decline. Geopolitics is what accelerated it. The solutions we have been advocating over the years – a joint fiscal capacity, a capital markets union, joint defense procurement to neutralize the rise in defense spending – are further away than ever. Unless one of these parameters change, a financial crisis is a very plausible scenario.
Spotlight France
France has a budget deficit of 7 percent but wants to fund a European army to fight Russia.
How is that supposed to work?
Spotlight Green Fantasies
The EU has adopted ambitious Green policies that will cost much more money than has been budgeted.
How is that supposed to work?
Targets Won’t Be Met
You can take those Green targets and throw then into the ashcan of ideas that never should have been set in the first place.
Even if you give France 7 years to be deficit compliant, how is France supposed to cut back a whopping 4 percent of GDP?
What’s the Basic Problem?
Eurointelligence says “Technology is the main cause of the decline. Geopolitics is what accelerated it.”
Technology is not the problem. The Maastricht treaty that created the Eurozone is flawed. And it cannot be fixed without unanimous agreement.
Given productivity and work rule differences, one interest rate set by the ECB cannot serve Italy, France, Greece, and Germany.
Add to that, EU nannycrat rules. The EU is more interested in cracking down on Google (Now Alphabet GOOG), Apple (AAPL), Facebook (now Meta Platforms META), and Microsoft (MSFT) for alleged monopolies than developing anything.
The EU Is Dysfunctional
In a single word, the EU is dysfunctional. That’s the problem, not technology. The Maastricht treaty itself is a big part of the reason the EU is dysfunctional. The Euro itself, with one common interest rate, is fundamentally flawed.
Companies like Alphabet, Meta, Microsoft, and Apple could not exist in the EU because in the name of competition and diversity, the EU would kill them before they ever got big enough to matter.
EU rules make it impossible to fix the basic problem. So the EU has resorted to nannycrat rules to regulate US and Chinese companies instead of fixing anything.
Technology, including AI, and geopolitics is now accelerating the basic problem, the EU is dysfunctional by treaty. It’s showing up in polls everywhere.
European Parliament Polls in France
EP France Polls from Wikipedia
Marine Le Pen’s National Rally is clobbering Renew/Modem by a whopping 12 percentage points, 30-18.
This chart is for France only, not the entire parliament, but it reflects on French President Emmanuel Macron’s sinking popularity and the sinking centrists in general.
A War Economy
As a way to create jobs, EC President Charles Michel promotes a war economy.
I have a suggestion. Let US senator Lindsey Graham and EC president Charles Michel lead the charge.
Instead of fixing Germany’s aging infrastructure, attempting to compete with the US on AI, or competing with China on anything, EC President Charles Michel promotes war as growth.
It’s Time for a New Strategy
Please note German Chancellor Olaf Scholz is refusing to send Taurus cruise missiles to Ukraine.
Poll after poll shows support for Ukraine. Every one of then is flawed because they fail to ask “how much are you willing to pay.”
There’s solidarity in the EU, but it stops with wheat and weapons. In the US, Biden is desperate for the war to go on. But he still has no goal. Is Biden’s goal the same as Zelensky’s: “The war will not be over as long as Crimea is occupied.”
We don’t know because Biden won’t say. Biden also will not say how much he is willing to commit. Is it another $150 billion or is it $1 trillion or more?
Meanwhile, prepare for carnage of the center, Greens, and warmongers in the next European Parliament elections.
A fiscal crisis awaits. The first casualty will be Green energy policies.
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