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>>> The 'Spartacus COVID Letter' That's Gone Viral
Zero Hedge
BY TYLER DURDEN
SEP 27, 2021
https://www.zerohedge.com/covid-19/damn-you-hell-you-will-not-destroy-america-here-spartacus-covid-letter-thats-gone-viral
Via The Automatic Earth blog,
This is an anonymously posted document by someone who calls themselves Spartacus. Because it’s anonymous, I can’t contact them to ask for permission to publish. So I hesitated for a while, but it’s simply the best document I’ve seen on Covid, vaccines, etc. Whoever Spartacus is, they have a very elaborate knowledge in “the field”. If you want to know a lot more about the no. 1 issue in the world today, read it. And don’t worry if you don’t understand every single word, neither do I. But I learned a lot.
The original PDF doc is here: Covid19 – The Spartacus Letter
Hello,
My name is Spartacus, and I’ve had enough.
We have been forced to watch America and the Free World spin into inexorable decline due to a biowarfare attack. We, along with countless others, have been victimized and gaslit by propaganda and psychological warfare operations being conducted by an unelected, unaccountable Elite against the American people and our allies.
Our mental and physical health have suffered immensely over the course of the past year and a half. We have felt the sting of isolation, lockdown, masking, quarantines, and other completely nonsensical acts of healthcare theater that have done absolutely nothing to protect the health or wellbeing of the public from the ongoing COVID-19 pandemic.
Now, we are watching the medical establishment inject literal poison into millions of our fellow Americans without so much as a fight.
We have been told that we will be fired and denied our livelihoods if we refuse to vaccinate. This was the last straw.
We have spent thousands of hours analyzing leaked footage from Wuhan, scientific papers from primary sources, as well as the paper trails left by the medical establishment.
What we have discovered would shock anyone to their core.
First, we will summarize our findings, and then, we will explain them in detail. References will be placed at the end.
Summary:
COVID-19 is a blood and blood vessel disease. SARS-CoV-2 infects the lining of human blood vessels, causing them to leak into the lungs.
Current treatment protocols (e.g. invasive ventilation) are actively harmful to patients, accelerating oxidative stress and causing severe VILI (ventilator-induced lung injuries). The continued use of ventilators in the absence of any proven medical benefit constitutes mass murder.
Existing countermeasures are inadequate to slow the spread of what is an aerosolized and potentially wastewater-borne virus, and constitute a form of medical theater.
Various non-vaccine interventions have been suppressed by both the media and the medical establishment in favor of vaccines and expensive patented drugs.
The authorities have denied the usefulness of natural immunity against COVID-19, despite the fact that natural immunity confers protection against all of the virus’s proteins, and not just one.
Vaccines will do more harm than good. The antigen that these vaccines are based on, SARS-CoV- 2 Spike, is a toxic protein. SARS-CoV-2 may have ADE, or antibody-dependent enhancement; current antibodies may not neutralize future strains, but instead help them infect immune cells. Also, vaccinating during a pandemic with a leaky vaccine removes the evolutionary pressure for a virus to become less lethal.
There is a vast and appalling criminal conspiracy that directly links both Anthony Fauci and Moderna to the Wuhan Institute of Virology.
COVID-19 vaccine researchers are directly linked to scientists involved in brain-computer interface (“neural lace”) tech, one of whom was indicted for taking grant money from China.
Independent researchers have discovered mysterious nanoparticles inside the vaccines that are not supposed to be present.
The entire pandemic is being used as an excuse for a vast political and economic transformation of Western society that will enrich the already rich and turn the rest of us into serfs and untouchables.
COVID-19 Pathophysiology and Treatments:
COVID-19 is not a viral pneumonia. It is a viral vascular endotheliitis and attacks the lining of blood vessels, particularly the small pulmonary alveolar capillaries, leading to endothelial cell activation and sloughing, coagulopathy, sepsis, pulmonary edema, and ARDS-like symptoms. This is a disease of the blood and blood vessels. The circulatory system. Any pneumonia that it causes is secondary to that.
In severe cases, this leads to sepsis, blood clots, and multiple organ failure, including hypoxic and inflammatory damage to various vital organs, such as the brain, heart, liver, pancreas, kidneys, and intestines.
Some of the most common laboratory findings in COVID-19 are elevated D-dimer, elevated prothrombin time, elevated C-reactive protein, neutrophilia, lymphopenia, hypocalcemia, and hyperferritinemia, essentially matching a profile of coagulopathy and immune system hyperactivation/immune cell exhaustion.
COVID-19 can present as almost anything, due to the wide tropism of SARS-CoV-2 for various tissues in the body’s vital organs. While its most common initial presentation is respiratory illness and flu-like symptoms, it can present as brain inflammation, gastrointestinal disease, or even heart attack or pulmonary embolism.
COVID-19 is more severe in those with specific comorbidities, such as obesity, diabetes, and hypertension. This is because these conditions involve endothelial dysfunction, which renders the circulatory system more susceptible to infection and injury by this particular virus.
The vast majority of COVID-19 cases are mild and do not cause significant disease. In known cases, there is something known as the 80/20 rule, where 80% of cases are mild and 20% are severe or critical. However, this ratio is only correct for known cases, not all infections. The number of actual infections is much, much higher. Consequently, the mortality and morbidity rate is lower. However, COVID-19 spreads very quickly, meaning that there are a significant number of severely-ill and critically-ill patients appearing in a short time frame.
In those who have critical COVID-19-induced sepsis, hypoxia, coagulopathy, and ARDS, the most common treatments are intubation, injected corticosteroids, and blood thinners. This is not the correct treatment for COVID-19. In severe hypoxia, cellular metabolic shifts cause ATP to break down into hypoxanthine, which, upon the reintroduction of oxygen, causes xanthine oxidase to produce tons of highly damaging radicals that attack tissue. This is called ischemia-reperfusion injury, and it’s why the majority of people who go on a ventilator are dying. In the mitochondria, succinate buildup due to sepsis does the same exact thing; when oxygen is reintroduced, it makes superoxide radicals. Make no mistake, intubation will kill people who have COVID-19.
The end-stage of COVID-19 is severe lipid peroxidation, where fats in the body start to “rust” due to damage by oxidative stress. This drives autoimmunity. Oxidized lipids appear as foreign objects to the immune system, which recognizes and forms antibodies against OSEs, or oxidation-specific epitopes. Also, oxidized lipids feed directly into pattern recognition receptors, triggering even more inflammation and summoning even more cells of the innate immune system that release even more destructive enzymes. This is similar to the pathophysiology of Lupus.
COVID-19’s pathology is dominated by extreme oxidative stress and neutrophil respiratory burst, to the point where hemoglobin becomes incapable of carrying oxygen due to heme iron being stripped out of heme by hypochlorous acid. No amount of supplemental oxygen can oxygenate blood that chemically refuses to bind O2.
The breakdown of the pathology is as follows:
SARS-CoV-2 Spike binds to ACE2. Angiotensin Converting Enzyme 2 is an enzyme that is part of the renin-angiotensin-aldosterone system, or RAAS. The RAAS is a hormone control system that moderates fluid volume in the body and in the bloodstream (i.e. osmolarity) by controlling salt retention and excretion. This protein, ACE2, is ubiquitous in every part of the body that interfaces with the circulatory system, particularly in vascular endothelial cells and pericytes, brain astrocytes, renal tubules and podocytes, pancreatic islet cells, bile duct and intestinal epithelial cells, and the seminiferous ducts of the testis, all of which SARS-CoV-2 can infect, not just the lungs.
SARS-CoV-2 infects a cell as follows: SARS-CoV-2 Spike undergoes a conformational change where the S1 trimers flip up and extend, locking onto ACE2 bound to the surface of a cell. TMPRSS2, or transmembrane protease serine 2, comes along and cuts off the heads of the Spike, exposing the S2 stalk-shaped subunit inside. The remainder of the Spike undergoes a conformational change that causes it to unfold like an extension ladder, embedding itself in the cell membrane. Then, it folds back upon itself, pulling the viral membrane and the cell membrane together. The two membranes fuse, with the virus’s proteins migrating out onto the surface of the cell. The SARS-CoV-2 nucleocapsid enters the cell, disgorging its genetic material and beginning the viral replication process, hijacking the cell’s own structures to produce more virus.
SARS-CoV-2 Spike proteins embedded in a cell can actually cause human cells to fuse together, forming syncytia/MGCs (multinuclear giant cells). They also have other pathogenic, harmful effects. SARS-CoV- 2’s viroporins, such as its Envelope protein, act as calcium ion channels, introducing calcium into infected cells. The virus suppresses the natural interferon response, resulting in delayed inflammation. SARS-CoV-2 N protein can also directly activate the NLRP3 inflammasome. Also, it suppresses the Nrf2 antioxidant pathway. The suppression of ACE2 by binding with Spike causes a buildup of bradykinin that would otherwise be broken down by ACE2.
This constant calcium influx into the cells results in (or is accompanied by) noticeable hypocalcemia, or low blood calcium, especially in people with Vitamin D deficiencies and pre-existing endothelial dysfunction. Bradykinin upregulates cAMP, cGMP, COX, and Phospholipase C activity. This results in prostaglandin release and vastly increased intracellular calcium signaling, which promotes highly aggressive ROS release and ATP depletion. NADPH oxidase releases superoxide into the extracellular space. Superoxide radicals react with nitric oxide to form peroxynitrite. Peroxynitrite reacts with the tetrahydrobiopterin cofactor needed by endothelial nitric oxide synthase, destroying it and “uncoupling” the enzymes, causing nitric oxide synthase to synthesize more superoxide instead. This proceeds in a positive feedback loop until nitric oxide bioavailability in the circulatory system is depleted.
Dissolved nitric oxide gas produced constantly by eNOS serves many important functions, but it is also antiviral against SARS-like coronaviruses, preventing the palmitoylation of the viral Spike protein and making it harder for it to bind to host receptors. The loss of NO allows the virus to begin replicating with impunity in the body. Those with endothelial dysfunction (i.e. hypertension, diabetes, obesity, old age, African-American race) have redox equilibrium issues to begin with, giving the virus an advantage.
Due to the extreme cytokine release triggered by these processes, the body summons a great deal of neutrophils and monocyte-derived alveolar macrophages to the lungs. Cells of the innate immune system are the first-line defenders against pathogens. They work by engulfing invaders and trying to attack them with enzymes that produce powerful oxidants, like SOD and MPO. Superoxide dismutase takes superoxide and makes hydrogen peroxide, and myeloperoxidase takes hydrogen peroxide and chlorine ions and makes hypochlorous acid, which is many, many times more reactive than sodium hypochlorite bleach.
Neutrophils have a nasty trick. They can also eject these enzymes into the extracellular space, where they will continuously spit out peroxide and bleach into the bloodstream. This is called neutrophil extracellular trap formation, or, when it becomes pathogenic and counterproductive, NETosis. In severe and critical COVID-19, there is actually rather severe NETosis.
Hypochlorous acid building up in the bloodstream begins to bleach the iron out of heme and compete for O2 binding sites. Red blood cells lose the ability to transport oxygen, causing the sufferer to turn blue in the face. Unliganded iron, hydrogen peroxide, and superoxide in the bloodstream undergo the Haber- Weiss and Fenton reactions, producing extremely reactive hydroxyl radicals that violently strip electrons from surrounding fats and DNA, oxidizing them severely.
This condition is not unknown to medical science. The actual name for all of this is acute sepsis.
We know this is happening in COVID-19 because people who have died of the disease have noticeable ferroptosis signatures in their tissues, as well as various other oxidative stress markers such as nitrotyrosine, 4-HNE, and malondialdehyde.
When you intubate someone with this condition, you are setting off a free radical bomb by supplying the cells with O2. It’s a catch-22, because we need oxygen to make Adenosine Triphosphate (that is, to live), but O2 is also the precursor of all these damaging radicals that lead to lipid peroxidation.
The correct treatment for severe COVID-19 related sepsis is non-invasive ventilation, steroids, and antioxidant infusions. Most of the drugs repurposed for COVID-19 that show any benefit whatsoever in rescuing critically-ill COVID-19 patients are antioxidants. N-acetylcysteine, melatonin, fluvoxamine, budesonide, famotidine, cimetidine, and ranitidine are all antioxidants. Indomethacin prevents iron- driven oxidation of arachidonic acid to isoprostanes. There are powerful antioxidants such as apocynin that have not even been tested on COVID-19 patients yet which could defang neutrophils, prevent lipid peroxidation, restore endothelial health, and restore oxygenation to the tissues.
Scientists who know anything about pulmonary neutrophilia, ARDS, and redox biology have known or surmised much of this since March 2020. In April 2020, Swiss scientists confirmed that COVID-19 was a vascular endotheliitis. By late 2020, experts had already concluded that COVID-19 causes a form of viral sepsis. They also know that sepsis can be effectively treated with antioxidants. None of this information is particularly new, and yet, for the most part, it has not been acted upon. Doctors continue to use damaging intubation techniques with high PEEP settings despite high lung compliance and poor oxygenation, killing an untold number of critically ill patients with medical malpractice.
Because of the way they are constructed, Randomized Control Trials will never show any benefit for any antiviral against COVID-19. Not Remdesivir, not Kaletra, not HCQ, and not Ivermectin. The reason for this is simple; for the patients that they have recruited for these studies, such as Oxford’s ludicrous RECOVERY study, the intervention is too late to have any positive effect.
The clinical course of COVID-19 is such that by the time most people seek medical attention for hypoxia, their viral load has already tapered off to almost nothing. If someone is about 10 days post-exposure and has already been symptomatic for five days, there is hardly any virus left in their bodies, only cellular damage and derangement that has initiated a hyperinflammatory response. It is from this group that the clinical trials for antivirals have recruited, pretty much exclusively.
In these trials, they give antivirals to severely ill patients who have no virus in their bodies, only a delayed hyperinflammatory response, and then absurdly claim that antivirals have no utility in treating or preventing COVID-19. These clinical trials do not recruit people who are pre-symptomatic. They do not test pre-exposure or post-exposure prophylaxis.
This is like using a defibrillator to shock only flatline, and then absurdly claiming that defibrillators have no medical utility whatsoever when the patients refuse to rise from the dead. The intervention is too late. These trials for antivirals show systematic, egregious selection bias. They are providing a treatment that is futile to the specific cohort they are enrolling.
India went against the instructions of the WHO and mandated the prophylactic usage of Ivermectin. They have almost completely eradicated COVID-19. The Indian Bar Association of Mumbai has brought criminal charges against WHO Chief Scientist Dr. Soumya Swaminathan for recommending against the use of Ivermectin.
Ivermectin is not “horse dewormer”. Yes, it is sold in veterinary paste form as a dewormer for animals. It has also been available in pill form for humans for decades, as an antiparasitic drug.
The media have disingenuously claimed that because Ivermectin is an antiparasitic drug, it has no utility as an antivirus. This is incorrect. Ivermectin has utility as an antiviral. It blocks importin, preventing nuclear import, effectively inhibiting viral access to cell nuclei. Many drugs currently on the market have multiple modes of action. Ivermectin is one such drug. It is both antiparasitic and antiviral.
In Bangladesh, Ivermectin costs $1.80 for an entire 5-day course. Remdesivir, which is toxic to the liver, costs $3,120 for a 5-day course of the drug. Billions of dollars of utterly useless Remdesivir were sold to our governments on the taxpayer’s dime, and it ended up being totally useless for treating hyperinflammatory COVID-19. The media has hardly even covered this at all.
The opposition to the use of generic Ivermectin is not based in science. It is purely financially and politically-motivated. An effective non-vaccine intervention would jeopardize the rushed FDA approval of patented vaccines and medicines for which the pharmaceutical industry stands to rake in billions upon billions of dollars in sales on an ongoing basis.
The majority of the public are scientifically illiterate and cannot grasp what any of this even means, thanks to a pathetic educational system that has miseducated them. You would be lucky to find 1 in 100 people who have even the faintest clue what any of this actually means.
COVID-19 Transmission:
COVID-19 is airborne. The WHO carried water for China by claiming that the virus was only droplet- borne. Our own CDC absurdly claimed that it was mostly transmitted by fomite-to-face contact, which, given its rapid spread from Wuhan to the rest of the world, would have been physically impossible.
The ridiculous belief in fomite-to-face being a primary mode of transmission led to the use of surface disinfection protocols that wasted time, energy, productivity, and disinfectant.
The 6-foot guidelines are absolutely useless. The minimum safe distance to protect oneself from an aerosolized virus is to be 15+ feet away from an infected person, no closer. Realistically, no public transit is safe.
Surgical masks do not protect you from aerosols. The virus is too small and the filter media has too large of gaps to filter it out. They may catch respiratory droplets and keep the virus from being expelled by someone who is sick, but they do not filter a cloud of infectious aerosols if someone were to walk into said cloud.
The minimum level of protection against this virus is quite literally a P100 respirator, a PAPR/CAPR, or a 40mm NATO CBRN respirator, ideally paired with a full-body tyvek or tychem suit, gloves, and booties, with all the holes and gaps taped.
Live SARS-CoV-2 may potentially be detected in sewage outflows, and there may be oral-fecal transmission. During the SARS outbreak in 2003, in the Amoy Gardens incident, hundreds of people were infected by aerosolized fecal matter rising from floor drains in their apartments.
COVID-19 Vaccine Dangers:
The vaccines for COVID-19 are not sterilizing and do not prevent infection or transmission. They are “leaky” vaccines. This means they remove the evolutionary pressure on the virus to become less lethal. It also means that the vaccinated are perfect carriers. In other words, those who are vaccinated are a threat to the unvaccinated, not the other way around.
All of the COVID-19 vaccines currently in use have undergone minimal testing, with highly accelerated clinical trials. Though they appear to limit severe illness, the long-term safety profile of these vaccines remains unknown.
Some of these so-called “vaccines” utilize an untested new technology that has never been used in vaccines before. Traditional vaccines use weakened or killed virus to stimulate an immune response. The Moderna and Pfizer-BioNTech vaccines do not. They are purported to consist of an intramuscular shot containing a suspension of lipid nanoparticles filled with messenger RNA. The way they generate an immune response is by fusing with cells in a vaccine recipient’s shoulder, undergoing endocytosis, releasing their mRNA cargo into those cells, and then utilizing the ribosomes in those cells to synthesize modified SARS-CoV-2 Spike proteins in-situ.
These modified Spike proteins then migrate to the surface of the cell, where they are anchored in place by a transmembrane domain. The adaptive immune system detects the non-human viral protein being expressed by these cells, and then forms antibodies against that protein. This is purported to confer protection against the virus, by training the adaptive immune system to recognize and produce antibodies against the Spike on the actual virus. The J&J and AstraZeneca vaccines do something similar, but use an adenovirus vector for genetic material delivery instead of a lipid nanoparticle. These vaccines were produced or validated with the aid of fetal cell lines HEK-293 and PER.C6, which people with certain religious convictions may object strongly to.
SARS-CoV-2 Spike is a highly pathogenic protein on its own. It is impossible to overstate the danger presented by introducing this protein into the human body.
It is claimed by vaccine manufacturers that the vaccine remains in cells in the shoulder, and that SARS- CoV-2 Spike produced and expressed by these cells from the vaccine’s genetic material is harmless and inert, thanks to the insertion of prolines in the Spike sequence to stabilize it in the prefusion conformation, preventing the Spike from becoming active and fusing with other cells. However, a pharmacokinetic study from Japan showed that the lipid nanoparticles and mRNA from the Pfizer vaccine did not stay in the shoulder, and in fact bioaccumulated in many different organs, including the reproductive organs and adrenal glands, meaning that modified Spike is being expressed quite literally all over the place. These lipid nanoparticles may trigger anaphylaxis in an unlucky few, but far more concerning is the unregulated expression of Spike in various somatic cell lines far from the injection site and the unknown consequences of that.
Messenger RNA is normally consumed right after it is produced in the body, being translated into a protein by a ribosome. COVID-19 vaccine mRNA is produced outside the body, long before a ribosome translates it. In the meantime, it could accumulate damage if inadequately preserved. When a ribosome attempts to translate a damaged strand of mRNA, it can become stalled. When this happens, the ribosome becomes useless for translating proteins because it now has a piece of mRNA stuck in it, like a lace card in an old punch card reader. The whole thing has to be cleaned up and new ribosomes synthesized to replace it. In cells with low ribosome turnover, like nerve cells, this can lead to reduced protein synthesis, cytopathic effects, and neuropathies.
Certain proteins, including SARS-CoV-2 Spike, have proteolytic cleavage sites that are basically like little dotted lines that say “cut here”, which attract a living organism’s own proteases (essentially, molecular scissors) to cut them. There is a possibility that S1 may be proteolytically cleaved from S2, causing active S1 to float away into the bloodstream while leaving the S2 “stalk” embedded in the membrane of the cell that expressed the protein.
SARS-CoV-2 Spike has a Superantigenic region (SAg), which may promote extreme inflammation.
Anti-Spike antibodies were found in one study to function as autoantibodies and attack the body’s own cells. Those who have been immunized with COVID-19 vaccines have developed blood clots, myocarditis, Guillain-Barre Syndrome, Bell’s Palsy, and multiple sclerosis flares, indicating that the vaccine promotes autoimmune reactions against healthy tissue.
SARS-CoV-2 Spike does not only bind to ACE2. It was suspected to have regions that bind to basigin, integrins, neuropilin-1, and bacterial lipopolysaccharides as well. SARS-CoV-2 Spike, on its own, can potentially bind any of these things and act as a ligand for them, triggering unspecified and likely highly inflammatory cellular activity.
SARS-CoV-2 Spike contains an unusual PRRA insert that forms a furin cleavage site. Furin is a ubiquitous human protease, making this an ideal property for the Spike to have, giving it a high degree of cell tropism. No wild-type SARS-like coronaviruses related to SARS-CoV-2 possess this feature, making it highly suspicious, and perhaps a sign of human tampering.
SARS-CoV-2 Spike has a prion-like domain that enhances its infectiousness.
The Spike S1 RBD may bind to heparin-binding proteins and promote amyloid aggregation. In humans, this could lead to Parkinson’s, Lewy Body Dementia, premature Alzheimer’s, or various other neurodegenerative diseases. This is very concerning because SARS-CoV-2 S1 is capable of injuring and penetrating the blood-brain barrier and entering the brain. It is also capable of increasing the permeability of the blood-brain barrier to other molecules.
SARS-CoV-2, like other betacoronaviruses, may have Dengue-like ADE, or antibody-dependent enhancement of disease. For those who aren’t aware, some viruses, including betacoronaviruses, have a feature called ADE. There is also something called Original Antigenic Sin, which is the observation that the body prefers to produce antibodies based on previously-encountered strains of a virus over newly- encountered ones.
In ADE, antibodies from a previous infection become non-neutralizing due to mutations in the virus’s proteins. These non-neutralizing antibodies then act as trojan horses, allowing live, active virus to be pulled into macrophages through their Fc receptor pathways, allowing the virus to infect immune cells that it would not have been able to infect before. This has been known to happen with Dengue Fever; when someone gets sick with Dengue, recovers, and then contracts a different strain, they can get very, very ill.
If someone is vaccinated with mRNA based on the Spike from the initial Wuhan strain of SARS-CoV-2, and then they become infected with a future, mutated strain of the virus, they may become severely ill. In other words, it is possible for vaccines to sensitize someone to disease.
There is a precedent for this in recent history. Sanofi’s Dengvaxia vaccine for Dengue failed because it caused immune sensitization in people whose immune systems were Dengue-naive.
In mice immunized against SARS-CoV and challenged with the virus, a close relative of SARS-CoV-2, they developed immune sensitization, Th2 immunopathology, and eosinophil infiltration in their lungs.
We have been told that SARS-CoV-2 mRNA vaccines cannot be integrated into the human genome, because messenger RNA cannot be turned back into DNA. This is false. There are elements in human cells called LINE-1 retrotransposons, which can indeed integrate mRNA into a human genome by endogenous reverse transcription. Because the mRNA used in the vaccines is stabilized, it hangs around in cells longer, increasing the chances for this to happen. If the gene for SARS-CoV-2 Spike is integrated into a portion of the genome that is not silent and actually expresses a protein, it is possible that people who take this vaccine may continuously express SARS-CoV-2 Spike from their somatic cells for the rest of their lives.
By inoculating people with a vaccine that causes their bodies to produce Spike in-situ, they are being inoculated with a pathogenic protein. A toxin that may cause long-term inflammation, heart problems, and a raised risk of cancers. In the long-term, it may also potentially lead to premature neurodegenerative disease.
Absolutely nobody should be compelled to take this vaccine under any circumstances, and in actual fact, the vaccination campaign must be stopped immediately.
COVID-19 Criminal Conspiracy:
The vaccine and the virus were made by the same people.
In 2014, there was a moratorium on SARS gain-of-function research that lasted until 2017. This research was not halted. Instead, it was outsourced, with the federal grants being laundered through NGOs.
Ralph Baric is a virologist and SARS expert at UNC Chapel Hill in North Carolina. This is who Anthony Fauci was referring to when he insisted, before Congress, that if any gain-of-function research was being conducted, it was being conducted in North Carolina.
This was a lie. Anthony Fauci lied before Congress. A felony.
Ralph Baric and Shi Zhengli are colleagues and have co-written papers together. Ralph Baric mentored Shi Zhengli in his gain-of-function manipulation techniques, particularly serial passage, which results in a virus that appears as if it originated naturally. In other words, deniable bioweapons. Serial passage in humanized hACE2 mice may have produced something like SARS-CoV-2.
The funding for the gain-of-function research being conducted at the Wuhan Institute of Virology came from Peter Daszak. Peter Daszak runs an NGO called EcoHealth Alliance. EcoHealth Alliance received millions of dollars in grant money from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (that is, Anthony Fauci), the Defense Threat Reduction Agency (part of the US Department of Defense), and the United States Agency for International Development. NIH/NIAID contributed a few million dollars, and DTRA and USAID each contributed tens of millions of dollars towards this research. Altogether, it was over a hundred million dollars.
EcoHealth Alliance subcontracted these grants to the Wuhan Institute of Virology, a lab in China with a very questionable safety record and poorly trained staff, so that they could conduct gain-of-function research, not in their fancy P4 lab, but in a level-2 lab where technicians wore nothing more sophisticated than perhaps a hairnet, latex gloves, and a surgical mask, instead of the bubble suits used when working with dangerous viruses. Chinese scientists in Wuhan reported being routinely bitten and urinated on by laboratory animals. Why anyone would outsource this dangerous and delicate work to the People’s Republic of China, a country infamous for industrial accidents and massive explosions that have claimed hundreds of lives, is completely beyond me, unless the aim was to start a pandemic on purpose.
In November of 2019, three technicians at the Wuhan Institute of Virology developed symptoms consistent with a flu-like illness. Anthony Fauci, Peter Daszak, and Ralph Baric knew at once what had happened, because back channels exist between this laboratory and our scientists and officials.
December 12th, 2019, Ralph Baric signed a Material Transfer Agreement (essentially, an NDA) to receive Coronavirus mRNA vaccine-related materials co-owned by Moderna and NIH. It wasn’t until a whole month later, on January 11th, 2020, that China allegedly sent us the sequence to what would become known as SARS-CoV-2. Moderna claims, rather absurdly, that they developed a working vaccine from this sequence in under 48 hours.
Stephane Bancel, the current CEO of Moderna, was formerly the CEO of bioMerieux, a French multinational corporation specializing in medical diagnostic tech, founded by one Alain Merieux. Alain Merieux was one of the individuals who was instrumental in the construction of the Wuhan Institute of Virology’s P4 lab.
The sequence given as the closest relative to SARS-CoV-2, RaTG13, is not a real virus. It is a forgery. It was made by entering a gene sequence by hand into a database, to create a cover story for the existence of SARS-CoV-2, which is very likely a gain-of-function chimera produced at the Wuhan Institute of Virology and was either leaked by accident or intentionally released.
The animal reservoir of SARS-CoV-2 has never been found.
This is not a conspiracy “theory”. It is an actual criminal conspiracy, in which people connected to the development of Moderna’s mRNA-1273 are directly connected to the Wuhan Institute of Virology and their gain-of-function research by very few degrees of separation, if any. The paper trail is well- established.
The lab-leak theory has been suppressed because pulling that thread leads one to inevitably conclude that there is enough circumstantial evidence to link Moderna, the NIH, the WIV, and both the vaccine and the virus’s creation together. In a sane country, this would have immediately led to the world’s biggest RICO and mass murder case. Anthony Fauci, Peter Daszak, Ralph Baric, Shi Zhengli, and Stephane Bancel, and their accomplices, would have been indicted and prosecuted to the fullest extent of the law. Instead, billions of our tax dollars were awarded to the perpetrators.
The FBI raided Allure Medical in Shelby Township north of Detroit for billing insurance for “fraudulent COVID-19 cures”. The treatment they were using? Intravenous Vitamin C. An antioxidant. Which, as described above, is an entirely valid treatment for COVID-19-induced sepsis, and indeed, is now part of the MATH+ protocol advanced by Dr. Paul E. Marik.
The FDA banned ranitidine (Zantac) due to supposed NDMA (N-nitrosodimethylamine) contamination. Ranitidine is not only an H2 blocker used as antacid, but also has a powerful antioxidant effect, scavenging hydroxyl radicals. This gives it utility in treating COVID-19.
The FDA also attempted to take N-acetylcysteine, a harmless amino acid supplement and antioxidant, off the shelves, compelling Amazon to remove it from their online storefront.
This leaves us with a chilling question: did the FDA knowingly suppress antioxidants useful for treating COVID-19 sepsis as part of a criminal conspiracy against the American public?
The establishment is cooperating with, and facilitating, the worst criminals in human history, and are actively suppressing non-vaccine treatments and therapies in order to compel us to inject these criminals’ products into our bodies. This is absolutely unacceptable.
COVID-19 Vaccine Development and Links to Transhumanism:
This section deals with some more speculative aspects of the pandemic and the medical and scientific establishment’s reaction to it, as well as the disturbing links between scientists involved in vaccine research and scientists whose work involved merging nanotechnology with living cells.
On June 9th, 2020, Charles Lieber, a Harvard nanotechnology researcher with decades of experience, was indicted by the DOJ for fraud. Charles Lieber received millions of dollars in grant money from the US Department of Defense, specifically the military think tanks DARPA, AFOSR, and ONR, as well as NIH and MITRE. His specialty is the use of silicon nanowires in lieu of patch clamp electrodes to monitor and modulate intracellular activity, something he has been working on at Harvard for the past twenty years. He was claimed to have been working on silicon nanowire batteries in China, but none of his colleagues can recall him ever having worked on battery technology in his life; all of his research deals with bionanotechnology, or the blending of nanotech with living cells.
The indictment was over his collaboration with the Wuhan University of Technology. He had double- dipped, against the terms of his DOD grants, and taken money from the PRC’s Thousand Talents plan, a program which the Chinese government uses to bribe Western scientists into sharing proprietary R&D information that can be exploited by the PLA for strategic advantage.
Charles Lieber’s own papers describe the use of silicon nanowires for brain-computer interfaces, or “neural lace” technology. His papers describe how neurons can endocytose whole silicon nanowires or parts of them, monitoring and even modulating neuronal activity.
Charles Lieber was a colleague of Robert Langer. Together, along with Daniel S. Kohane, they worked on a paper describing artificial tissue scaffolds that could be implanted in a human heart to monitor its activity remotely.
Robert Langer, an MIT alumnus and expert in nanotech drug delivery, is one of the co-founders of Moderna. His net worth is now $5.1 billion USD thanks to Moderna’s mRNA-1273 vaccine sales.
Both Charles Lieber and Robert Langer’s bibliographies describe, essentially, techniques for human enhancement, i.e. transhumanism. Klaus Schwab, the founder of the World Economic Forum and the architect behind the so-called “Great Reset”, has long spoken of the “blending of biology and machinery” in his books.
Since these revelations, it has come to the attention of independent researchers that the COVID-19 vaccines may contain reduced graphene oxide nanoparticles. Japanese researchers have also found unexplained contaminants in COVID-19 vaccines.
Graphene oxide is an anxiolytic. It has been shown to reduce the anxiety of laboratory mice when injected into their brains. Indeed, given SARS-CoV-2 Spike’s propensity to compromise the blood-brain barrier and increase its permeability, it is the perfect protein for preparing brain tissue for extravasation of nanoparticles from the bloodstream and into the brain. Graphene is also highly conductive and, in some circumstances, paramagnetic.
In 2013, under the Obama administration, DARPA launched the BRAIN Initiative; BRAIN is an acronym for Brain Research Through Advancing Innovative Neurotechnologies®. This program involves the development of brain-computer interface technologies for the military, particularly non-invasive, injectable systems that cause minimal damage to brain tissue when removed. Supposedly, this technology would be used for healing wounded soldiers with traumatic brain injuries, the direct brain control of prosthetic limbs, and even new abilities such as controlling drones with one’s mind.
Various methods have been proposed for achieving this, including optogenetics, magnetogenetics, ultrasound, implanted electrodes, and transcranial electromagnetic stimulation. In all instances, the goal is to obtain read or read-write capability over neurons, either by stimulating and probing them, or by rendering them especially sensitive to stimulation and probing.
However, the notion of the widespread use of BCI technology, such as Elon Musk’s Neuralink device, raises many concerns over privacy and personal autonomy. Reading from neurons is problematic enough on its own. Wireless brain-computer interfaces may interact with current or future wireless GSM infrastructure, creating neurological data security concerns. A hacker or other malicious actor may compromise such networks to obtain people’s brain data, and then exploit it for nefarious purposes.
However, a device capable of writing to human neurons, not just reading from them, presents another, even more serious set of ethical concerns. A BCI that is capable of altering the contents of one’s mind for innocuous purposes, such as projecting a heads-up display onto their brain’s visual center or sending audio into one’s auditory cortex, would also theoretically be capable of altering mood and personality, or perhaps even subjugating someone’s very will, rendering them utterly obedient to authority. This technology would be a tyrant’s wet dream. Imagine soldiers who would shoot their own countrymen without hesitation, or helpless serfs who are satisfied to live in literal dog kennels.
BCIs could be used to unscrupulously alter perceptions of basic things such as emotions and values, changing people’s thresholds of satiety, happiness, anger, disgust, and so forth. This is not inconsequential. Someone’s entire regime of behaviors could be altered by a BCI, including such things as suppressing their appetite or desire for virtually anything on Maslow’s Hierarchy of Needs.
Anything is possible when you have direct access to someone’s brain and its contents. Someone who is obese could be made to feel disgust at the sight of food. Someone who is involuntarily celibate could have their libido disabled so they don’t even desire sex to begin with. Someone who is racist could be forced to feel delight over cohabiting with people of other races. Someone who is violent could be forced to be meek and submissive. These things might sound good to you if you are a tyrant, but to normal people, the idea of personal autonomy being overridden to such a degree is appalling.
For the wealthy, neural laces would be an unequaled boon, giving them the opportunity to enhance their intelligence with neuroprosthetics (i.e. an “exocortex”), and to deliver irresistible commands directly into the minds of their BCI-augmented servants, even physically or sexually abusive commands that they would normally refuse.
If the vaccine is a method to surreptitiously introduce an injectable BCI into millions of people without their knowledge or consent, then what we are witnessing is the rise of a tyrannical regime unlike anything ever seen before on the face of this planet, one that fully intends to strip every man, woman, and child of our free will.
Our flaws are what make us human. A utopia arrived at by removing people’s free will is not a utopia at all. It is a monomaniacal nightmare. Furthermore, the people who rule over us are Dark Triad types who cannot be trusted with such power. Imagine being beaten and sexually assaulted by a wealthy and powerful psychopath and being forced to smile and laugh over it because your neural lace gives you no choice but to obey your master.
The Elites are forging ahead with this technology without giving people any room to question the social or ethical ramifications, or to establish regulatory frameworks that ensure that our personal agency and autonomy will not be overridden by these devices. They do this because they secretly dream of a future where they can treat you worse than an animal and you cannot even fight back. If this evil plan is allowed to continue, it will spell the end of humanity as we know it.
Conclusions:
The current pandemic was produced and perpetuated by the establishment, through the use of a virus engineered in a PLA-connected Chinese biowarfare laboratory, with the aid of American taxpayer dollars and French expertise.
This research was conducted under the absolutely ridiculous euphemism of “gain-of-function” research, which is supposedly carried out in order to determine which viruses have the highest potential for zoonotic spillover and preemptively vaccinate or guard against them.
Gain-of-function/gain-of-threat research, a.k.a. “Dual-Use Research of Concern”, or DURC, is bioweapon research by another, friendlier-sounding name, simply to avoid the taboo of calling it what it actually is. It has always been bioweapon research. The people who are conducting this research fully understand that they are taking wild pathogens that are not infectious in humans and making them more infectious, often taking grants from military think tanks encouraging them to do so.
These virologists conducting this type of research are enemies of their fellow man, like pyromaniac firefighters. GOF research has never protected anyone from any pandemic. In fact, it has now started one, meaning its utility for preventing pandemics is actually negative. It should have been banned globally, and the lunatics performing it should have been put in straitjackets long ago.
Either through a leak or an intentional release from the Wuhan Institute of Virology, a deadly SARS strain is now endemic across the globe, after the WHO and CDC and public officials first downplayed the risks, and then intentionally incited a panic and lockdowns that jeopardized people’s health and their livelihoods.
This was then used by the utterly depraved and psychopathic aristocratic class who rule over us as an excuse to coerce people into accepting an injected poison which may be a depopulation agent, a mind control/pacification agent in the form of injectable “smart dust”, or both in one. They believe they can get away with this by weaponizing the social stigma of vaccine refusal. They are incorrect.
Their motives are clear and obvious to anyone who has been paying attention. These megalomaniacs have raided the pension funds of the free world. Wall Street is insolvent and has had an ongoing liquidity crisis since the end of 2019. The aim now is to exert total, full-spectrum physical, mental, and financial control over humanity before we realize just how badly we’ve been extorted by these maniacs.
The pandemic and its response served multiple purposes for the Elite:
Concealing a depression brought on by the usurious plunder of our economies conducted by rentier-capitalists and absentee owners who produce absolutely nothing of any value to society whatsoever. Instead of us having a very predictable Occupy Wall Street Part II, the Elites and their stooges got to stand up on television and paint themselves as wise and all-powerful saviors instead of the marauding cabal of despicable land pirates that they are.
Destroying small businesses and eroding the middle class.
Transferring trillions of dollars of wealth from the American public and into the pockets of billionaires and special interests.
Engaging in insider trading, buying stock in biotech companies and shorting brick-and-mortar businesses and travel companies, with the aim of collapsing face-to-face commerce and tourism and replacing it with e-commerce and servitization.
Creating a casus belli for war with China, encouraging us to attack them, wasting American lives and treasure and driving us to the brink of nuclear armageddon.
Establishing technological and biosecurity frameworks for population control and technocratic- socialist “smart cities” where everyone’s movements are despotically tracked, all in anticipation of widespread automation, joblessness, and food shortages, by using the false guise of a vaccine to compel cooperation.
Any one of these things would constitute a vicious rape of Western society. Taken together, they beggar belief; they are a complete inversion of our most treasured values.
What is the purpose of all of this? One can only speculate as to the perpetrators’ motives, however, we have some theories.
The Elites are trying to pull up the ladder, erase upward mobility for large segments of the population, cull political opponents and other “undesirables”, and put the remainder of humanity on a tight leash, rationing our access to certain goods and services that they have deemed “high-impact”, such as automobile use, tourism, meat consumption, and so on. Naturally, they will continue to have their own luxuries, as part of a strict caste system akin to feudalism.
Why are they doing this? Simple. The Elites are Neo-Malthusians and believe that we are overpopulated and that resource depletion will collapse civilization in a matter of a few short decades. They are not necessarily incorrect in this belief. We are overpopulated, and we are consuming too many resources. However, orchestrating such a gruesome and murderous power grab in response to a looming crisis demonstrates that they have nothing but the utmost contempt for their fellow man.
To those who are participating in this disgusting farce without any understanding of what they are doing, we have one word for you. Stop. You are causing irreparable harm to your country and to your fellow citizens.
To those who may be reading this warning and have full knowledge and understanding of what they are doing and how it will unjustly harm millions of innocent people, we have a few more words.
Damn you to hell. You will not destroy America and the Free World, and you will not have your New World Order. We will make certain of that.
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>>> Axsome: Multiple irons in the fire
Motley Fool
9-25-21
https://www.fool.com/investing/2021/09/25/3-best-biotech-stocks-to-buy-right-now/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Wall Street thinks that shares of Axsome Therapeutics, a specialist in disorders of the central nervous system (CNS), could jump by as much as 161% over the next 12 months. The reason: Axsome has two high-value drugs -- AXS-05 for major depressive disorder and AXS-07 for migraine headache -- under review by the FDA right now.
Analysts have estimated that AXS-05 alone could rake in sales in excess of $1.3 billion, while AXS-07 might be able to generate a respectable $300 million in sales at peak. The bad news is that AXS-05 doesn't look like it will get approved during this ongoing review cycle (although an approval isn't totally out of the realm of possibility), and investors will have to wait until April 30, 2022, to learn about the FDA's decision on AXS-07.
But patience could pay off in a big way for investors when it comes to this clinical-stage biotech. Axsome's CNS pipeline offers long-term investors two clear-cut ways to win.
First, AXS-05, despite its prolonged regulatory review, is likely to get approved at some point. The drug posted stellar pivotal-stage results, after all. So while it might take a second regulatory review to get AXS-05 across the finish line, the drug's underlying value proposition shouldn't be diminished in the long run. Second, there are multiple blue chip biotechs that could use a top-notch CNS pipeline like Axsome's. Therefore, this small-cap biotech stock could very well turn out to be a top buyout target in the not-so-distant future.
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>>> Is this the future of vaccines? UNC researchers create 3D printed vaccine patches
9-25-21
Zachery Eanes
The News & Observer
https://www.msn.com/en-us/health/medical/is-this-the-future-of-vaccines-unc-researchers-create-3d-printed-vaccine-patches/ar-AAONfbS?ocid=uxbndlbing
Sep. 25—CHAPEL HILL — Scientists at UNC-Chapel Hill and Stanford University said this week that they've successfully created a 3D-printed vaccine patch that delivers a stronger immunity response than a standard vaccine shot.
The patch, which would be placed on the skin like a Band-Aid, is covered in microneedles that deliver vaccines directly into the skin.
The researchers tested the patches on animals, and, in a study published in the Proceedings of the National Academy of Sciences, reported an antibody response 50 times higher than the traditional jab. The patches were applied with thumb pressure for two minutes and then left on the skin for 24 hours, according to the study.
The findings could have a profound impact on the logistical rollout of vaccines in the future, said Joseph DeSimone, a professor of chemical engineering at Stanford University and professor emeritus at UNC.
The patches are virtually painless and could eliminate one of the main reasons people refuse to get vaccines, which is a fear of needle injections.
But more important, DeSimone said, is that they don't require extremely cold temperatures like some vaccines, making them easier and cheaper to ship all over the world.
"I think it totally is" the future of vaccines, DeSimone said in a telephone interview with The News & Observer. "I think microneedles can be the OS for vaccine design — the operating system. And I think we're putting too much weight on the traditional way of delivery even in the design stage of vaccines."
Whether the patch will ever be used to deliver COVID-19 vaccines remains to be seen. DeSimone told The N&O the patch might be ready for human clinical trials in 18 to 14 months.
DeSimone is a prominent figure in the world of 3D printing.
During his time at UNC — where he worked from 1990 to 2014 — DeSimone pioneered a new type of 3D printing called Continuous Liquid Interface Production, or CLIP.
The breakthrough that CLIP brought helped DeSimone launch the 3D printing company Carbon Inc., which has raised more than $680 million from investors and has customers ranging from Adidas to Ford Motor Co.
The microneedles for the patches were made using a Carbon CLIP 3D printer, UNC said.
DeSimone said that the patches create a stronger immune response than needles because they deliver the vaccine to the skin rather than the muscle.
"The target cells for vaccines are way more common in our skin than in our muscle," he said. "And that's because of the way we've evolved. You know, if you fall and cut yourself, the first line of defense for avoiding infection is in the skin and those immune cells are the targets for vaccine. There's literally 100 to 1,000 times more per unit volume in the skin than in the muscle."
The patches were tested with a model vaccine, but DeSimone believes they could carry any type of vaccine, including the mRNA vaccines that have been used so effectively during the coronavirus pandemic.
The work behind 3D printing of vaccine patches predates the COVID-19 pandemic by a few years. But the struggles of delivering vaccines to the entire world have shown how critical vaccine technology is going forward, DeSimone said.
"Despite how terrible this pandemic has been — and it's been awful, really awful — it could have been a lot worse," he said. "This thing could have been avian flu with a 30% death rate, and we would be scrambling way more than we have been.
"I think a lot of people believe it's just a matter of time (before the next pandemic), and therefore technologies like this need to be readied for the future."
There could be significant cost savings as well, according to DeSimone's own projections. "I've heard numbers of syringe needles and glass vials and everything being north of $3 to $7 (per vaccine). And I think we can make these patches for less than 10 cents," he said.
DeSimone, striking an optimistic tone, said the ease of transportation of 3D patches could revolutionize the way vaccines are administered.
"We think — and our corporate partners that are emerging think — that the whole direction of this is you're going to receive a vaccine via like Amazon or the U.S. Postal Service in the future," he said.
The next step for the patches is a clinical trial in non-human primates. That could come as early as the first part of 2022, and eventually, the trials would focus on specific vaccines rather than model ones.
Commercial partners, though, are already reaching out to DeSimone about working with the technology, and the universities are eager to commercialize it.
"We love to commercialize stuff, and so we're eager to help facilitate building strategic partnerships to make this happen," he said. "We're in those dialogues now."
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>>> Innovation Pharmaceuticals Provides Update on COVID-19 Clinical Trial, Compassionate Use Requests and Research into Brilacidin's Broad-Spectrum Antiviral Properties
Yahoo Finance
September 23, 2021
https://finance.yahoo.com/news/innovation-pharmaceuticals-provides-covid-19-120000139.html
WAKEFIELD, MA / ACCESSWIRE / September 23, 2021 / Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, today provided an update on the status of its randomized, double-blind, placebo-controlled Phase 2 clinical trial of Brilacidin for the treatment of moderate-to-severe COVID-19 in hospitalized patients (see NCT04784897), as well as related news.
Based on information received from the data management and biostatistics vendors, study unblinding, analysis of the unblinded data and release of topline study results for the Brilacidin COVID-19 trial is anticipated to occur in mid-to-late October. The Company looks forward to the data to learn if Brilacidin's multiple properties translate into meaningful clinical results, given the unmet need for COVID-19 therapeutics and ongoing pandemic.
In related news, the Company has received individual patient Expanded Access (compassionate use) requests for Brilacidin to treat critically ill COVID-19 patients who are not responding to prior therapy. Expanded Access was implemented by the FDA and Congress to address physician applications for access to potentially lifesaving drugs, prior to FDA approval, for patients in their care when available treatment options have failed. Following receipt of such requests, the Company has supplied Brilacidin to relevant hospitals for individual patient use, with the FDA granting the treating physician permission for the emergency administration of Brilacidin. In addition to Brilacidin's antiviral profile, Brilacidin's immunomodulatory and anti-inflammatory properties may be particularly beneficial in treating COVID-19 in hospitalized patients.
For more details on the Company's Expanded Access policy, please visit:
https://www.ipharminc.com/expanded-access-and-compassionate-use
Brilacidin in vitro antiviral research remains ongoing at multiple universities. New preliminary data from one academic laboratory show Brilacidin is active against adenoviruses—a non-enveloped virus—complementing earlier data showing potent Brilacidin inhibition of different strains of coronaviruses, alphaviruses and bunyaviruses (enveloped viruses). A paper from this lab on Brilacidin's broad-spectrum antiviral effect in multiple virus families is being prepared. Separate scientific papers also are underway from two other academic research groups supporting Brilacidin's antiviral properties and providing insight into Brilacidin's mechanisms of action.
About Brilacidin and COVID-19
Brilacidin is the only non-peptidic defensin-mimetic drug candidate currently in a clinical trial as a treatment for SARS-CoV-2, the coronavirus responsible for COVID-19 (see NCT04784897). Innovation Pharmaceuticals is developing Brilacidin for the treatment of COVID-19 under U.S. FDA Fast Track designation. A dual-acting inhibitor able to target viral proteins and host factors, while also exhibiting robust anti-inflammatory and antibacterial properties, Brilacidin has shown potent and consistent inhibition in vitro against coronaviruses, alphaviruses, bunyaviruses and adenoviruses (with lab testing against other viruses also underway), supporting Brilacidin's development as a broad-spectrum antiviral. The annual global antiviral drug market is estimated to reach $44 billion by 2026.
A peer-reviewed article in Viruses supporting Brilacidin's COVID-19 treatment potential can be accessed at the link below.
Bakovic, A.; Risner, K.; Bhalla, N. (et al). Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture. Viruses 2021, 13, 271; https://doi.org/10.3390/v13020271
https://www.mdpi.com/1999-4915/13/2/271/
Two independent Machine Learning studies identified Brilacidin as one of the most promising inhibitors of SARS-CoV-2, the virus responsible for COVID-19, based on Brilacidin's molecular properties. Click here to learn more.
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Sign-up for Innovation Pharmaceuticals email alerts is available at:
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About Innovation Pharmaceuticals
Innovation Pharmaceuticals Inc. (IPIX) is a clinical stage biopharmaceutical company developing a world-class portfolio of innovative therapies addressing multiple areas of unmet medical need, including inflammatory diseases, cancer, infectious diseases, and dermatologic diseases.
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>>> Axsome Therapeutics Initiates SYMPHONY Phase 3 Trial of AXS-12 in Narcolepsy
Axsome Therapeutics, Inc.
September 16, 2021
https://finance.yahoo.com/news/axsome-therapeutics-initiates-symphony-phase-110000378.html
NEW YORK, Sept. 16, 2021 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, enrolled the first patient in SYMPHONY (Study Evaluating a Mechanistic Approach to Treating Narcolepsy), a Phase 3, randomized, double-blind, placebo-controlled trial of AXS-12 in patients with narcolepsy. AXS-12 is a novel, oral, potent, and highly selective norepinephrine reuptake inhibitor. Topline results from the SYMPHONY trial are anticipated in the first half of 2023.
“The advancement of AXS-12 into Phase 3 testing for narcolepsy demonstrates Axsome’s commitment to developing important new medicines for patients living with serious CNS conditions,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Narcolepsy impairs almost every aspect of a patient’s life including cognitive, psychological, social, and emotional functioning. If successfully developed, AXS-12 may address multiple symptoms of this debilitating condition.”
AXS-12 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of narcolepsy.
About the SYMPHONY Trial
SYMPHONY (Study Evaluating a Mechanistic Approach to Treating Narcolepsy) is a Phase 3, randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of AXS-12 in patients with narcolepsy. Approximately 90 patients will be randomized in a 1:1 ratio to treatment with AXS-12 or placebo for 5 weeks. The primary endpoint will be the frequency of cataplexy attacks. Other symptoms of narcolepsy as well as safety will be assessed throughout the study.
About Narcolepsy
Narcolepsy is a serious and debilitating neurological condition that causes dysregulation of the sleep-wake cycle and is characterized clinically by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep. Narcolepsy afflicts an estimated 185,000 individuals in the U.S. Cataplexy is seen in an estimated 70% of narcolepsy patients and is a sudden reduction or loss of muscle tone while a patient is awake, typically triggered by strong emotions such as laughter, fear, anger, stress, or excitement. Narcolepsy interferes with cognitive, psychological, and social functioning, increases the risk of work- and driving-related accidents, and is associated with a 1.5-fold higher mortality rate.
About AXS-12
AXS-12 (reboxetine) is a highly selective and potent norepinephrine reuptake inhibitor under development for the treatment of narcolepsy. AXS-12 modulates noradrenergic activity to promote wakefulness, maintain muscle tone and enhance cognition. AXS-12 has been granted U.S. Food and Drug Administration (FDA) Orphan Drug Designation for the treatment of narcolepsy. AXS-12 is an investigational drug product not approved by the FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are intensely committed to developing products that meaningfully improve the lives of patients and provide additional therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
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>>> Axsome (AXSM) Begins Late-Stage Sleep Disorder Study on AXS-12
Zacks Equity Research
September 17, 2021
https://finance.yahoo.com/news/axsome-axsm-begins-stage-sleep-140502817.html
Axsome Therapeutics, Inc. AXSM announced that it has initiated enrollment in the phase III study — SYMPHONY — which will evaluate its pipeline candidate, AXS-12, in patients with narcolepsy, a sleep disorder. Top-line data from the study is expected in 2023.
The company has successfully completed a phase II study evaluating the candidate in narcolepsy patients. Data from the mid-stage study demonstrated that treatment with AXS-12 resulted in a highly statistically significant reduction in the mean weekly number of cataplexy attacks from baseline compared to placebo, following a treatment period of two weeks. The treatment with AXS-12 also improved excessive daytime sleepiness by reducing the frequency of inadvertent naps in patients.
The candidate enjoys Orphan Drug Designation for the treatment of narcolepsy in the United States. However, the candidate lost its Breakthrough Therapy designation in July this year. The company stated that the FDA repealed the Breakthrough Therapy designation, following its approval to another drug, most likely Harmony Biosciences’ HRMY Wakix, as the first and only non-scheduled treatment for narcolepsy patients. We note that apart from Harmony Biosciences, Axsome will also face stiff competition from Jazz Pharmaceuticals JAZZ that has a strong sleep disorder portfolio with a couple of drugs approved to treat narcolepsy.
We also note that Axsome has an exclusive license agreement with Pfizer PFE for the non-clinical and clinical data on the latter’s reboxetine, the active pharmaceutical ingredient in AXS-12 that will support the potential new drug application (NDA) for the candidate.
Shares of Axsome have plunged 65% so far this year compared with the industry’s decrease of 0.1%.
The company’s leading pipeline candidates are AXS-05 and AXS-07 for which NDAs have been filed with the FDA seeking their approval. While the company is seeking approval for AXS-05 as a treatment of major depression disorder, AXS-07’s NDA is for acute treatment of migraine. A decision from the FDA related to the approval of AXS-07 is expected by April-end in 2022. In July, the FDA notified the company that it has identified deficiencies within the NDA that preclude labeling discussions at the time and has extended the review period of the NDA for AXS-05. The new PDUFA target action date is yet to be informed by the FDA.
Axsome is also developing AXS-05 as a potential remedy for treatment-resistant depression, smoking cessation, and agitation associated with Alzheimer's disease. The company has another candidate, AXS-14, in its pipeline that is in late-stage development as a potential treatment for the management of fibromyalgia, a debilitating central nervous system disorder with limited treatment options.
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>>> Dynavax Climbs as COVID-19 Vaccine Trial Shows Positive Results
Dynavax is collaborating with China's Clover Biopharmaceuticals on a vaccine that showed 100% efficacy against severe COVID-19 and hospitalizations.
The Street
9-22-21
TONY OWUSU
https://www.thestreet.com/investing/dynavax-jumps-positive-covid-vaccine-test-results?puc=yahoo&cm_ven=YAHOO
Shares of biopharmaceutical company Dynavax Technologies (DVAX) jumped Wednesday after the company reported positive results for the COVID-19 vaccine candidate it's developing in conjunction with China's Clover Biopharmaceuticals.
The company's trial enrolled over 30,000 adult and elderly participants across four continents with the study showing 100% efficacy against severe COVID-19 and hospitalizations and 84% efficacy against moderate-to-severe COVID-19 infections.
"In addition to the positive efficacy results, the remarkable tolerability profile of the Clover vaccine adjuvanted with CpG 1018 could be a useful tool in overcoming vaccine hesitancy for more reactogenic platforms and for booster doses in the future," CEO Ryan Spencer said.
The Phase 2/3 Spectra trial showed 79% overall efficacy against COVID-19 of any severity caused by the Delta variant that has become the dominant strain of the upper respiratory virus.
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CRVS one-year chart
https://finance.yahoo.com/quote/CRVS/
Bladerunner
Nice - >>> What's Going On With Corvus Pharmaceuticals Stock Today?
Benzinga
Adam Eckert
September 17, 2021
https://finance.yahoo.com/news/whats-going-corvus-pharmaceuticals-stock-162807986.html
Corvus Pharmaceuticals Inc (NASDAQ: CRVS) is surging higher Friday on abnormally high volume. The stock might be trading higher following favorable data results by AstraZeneca PLC (NASDAQ: AZN) for patients with unresectable, stage 3 non-small cell lung cancer.
The average session volume over a 100-day period is about 300,000. Friday's session volume was approaching 120 million at publication time.
AZN News: AstraZeneca announced that "the COAST Phase II trial showed oleclumab, an anti-CD73 monoclonal antibody, or monalizumab, an anti-NKG2A monoclonal antibody, in combination with Imfinzi (durvalumab) improved progression-free survival and objective response rate compared to Imfinzi alone in patients with unresectable, Stage III non-small cell lung cancer who had not progressed after concurrent chemoradiation therapy."
The results may be positively impacting Corvus Pharmaceuticals, which has a CD73 asset in its pipeline.
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company engaged in developing drugs and antibodies that target the most critical cellular elements of the immune system.
CRVS Price Action: Corvus Pharmaceuticals has traded as high as $5.74 and as low as $1.86 over a 52-week period.
The stock was up 72.60% at $3.90 at time of publication.
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CRVS finishes up 116% on the day in sympathy with IPHA.PA.
Bladerunner
>>> Magenta Therapeutics Announces IND Clearance for MGTA-117 Targeted Conditioning Clinical Trial
Business Wire
September 15, 2021
https://finance.yahoo.com/news/magenta-therapeutics-announces-ind-clearance-120000766.html
– Phase 1/2 clinical trial expected to open in Q4 2021 in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) –
CAMBRIDGE, Mass., September 15, 2021--(BUSINESS WIRE)--Magenta Therapeutics, Inc. (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, announced today that its Investigational New Drug (IND) application for MGTA-117 is active with the U.S. Food and Drug Administration (FDA). The company expects to open the Phase 1/2 clinical trial in Q4 2021 to evaluate its MGTA-117 antibody-drug conjugate (ADC) targeted conditioning program.
"We are very pleased that our collaboration with the FDA has resulted in the clearance of the MGTA-117 IND. We have addressed the FDA’s request for a bioassay to be incorporated into the clinical trial protocol," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics. "Improving conditioning treatments is essential for broadening patient accessibility to the curative potential of stem cell transplant and gene therapies. We have designed MGTA-117 specifically to replace toxic radiation and chemotherapy-based conditioning agents used in current medical practice. This program holds significant potential for patients across several disease areas."
The multi-center, open label Phase 1/2 clinical trial with single-dose escalating cohorts will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MGTA-117 as a single agent in relapsed/refractory AML and MDS patients. Magenta will continue to engage with the FDA to transition the trial to the intended primary target population of hematopoietic stem cell transplant-eligible AML and MDS patients. In addition, Magenta has planned gene therapy clinical trial collaborations with AVROBIO and Beam Therapeutics to evaluate the potential utility of MGTA-117 for conditioning gene therapy patients without the use of non-selective busulfan or other toxic chemotherapies.
About MGTA-117
Magenta’s MGTA-117 program is the company’s lead targeted conditioning product candidate, an antibody-drug conjugate (ADC) designed to selectively deplete hematopoietic stem cells (HSCs) from patients prior to transplant or HSC-based gene therapy to reduce the need for high-dose or high-intensity chemotherapeutic agents or, in the case of gene therapy applications, to potentially eliminate the need for chemotherapeutic agents altogether. MGTA-117 targets the CD117 receptor, which is highly expressed on the cell surface of HSCs and leukemia cells, making it a promising target for conditioning across broad sets of diseases, including certain blood cancers, hemoglobinopathies (sickle cell disease and beta thalassemia) and inherited metabolic disorders.
About Magenta Therapeutics
Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of stem cell transplants to more patients with blood cancers, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant community to revolutionize immune reset for more patients.
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MGTA gets FDA approval to start clinical trial in leukemia
https://finance.yahoo.com/news/magenta-therapeutics-announces-ind-clearance-120000766.html
Bladerunner
>>> Axsome Therapeutics Announces FDA Acceptance of New Drug Application for AXS-07 for the Acute Treatment of Migraine
Axsome Therapeutics, Inc.
September 14, 2021
https://finance.yahoo.com/news/axsome-therapeutics-announces-fda-acceptance-110000051.html
NEW YORK, Sept. 14, 2021 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine, and has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2022 for the NDA. AXS-07 (MoSEIC™ meloxicam-rizatriptan) is a novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for migraine.
“The FDA’s acceptance of the NDA for AXS-07 is an important milestone for Axsome as it brings us closer to potentially making this multi-mechanistic treatment available to migraine patients in need,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “We look forward to continued interactions with the FDA during the review process.”
The NDA is supported by results from two Phase 3 randomized, double-blind, controlled trials of AXS-07 in the acute treatment of migraine, the MOMENTUM and INTERCEPT trials, which demonstrated statistically significant elimination of migraine pain with AXS-07 compared to placebo and active controls.
About Migraine
Over 37 million Americans suffer from migraine according to the Centers for Disease Control, and it is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation. Migraine is characterized by recurrent attacks of pulsating, often severe and disabling head pain associated with nausea, and sensitivity to light and or sound. It is estimated that migraine accounts for $78 billion in direct (e.g. doctor visits, medications) and indirect (e.g. missed work, lost productivity) costs each year in the United States [1]. Published surveys of migraine sufferers indicate that more than 70% are not fully satisfied with their current treatment, that nearly 80% would try a new therapy, and that they desire treatments that work faster, more consistently, and result in less symptom recurrence [2,3].
About AXS-07
AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence. AXS-07 is covered by more than 80 issued U.S. and international patents which provide protection out to 2036. AXS-07 is not approved by the FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are intensely committed to developing products that meaningfully improve the lives of patients and provide additional therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
References
Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: A summary report and call to action. Ann Neurol. 2017 Apr; 81(4):479-484.
Smelt AF, Louter MA, Kies DA, Blom JW, Terwindt GM, van der Heijden GJ, De Gucht V, Ferrari MD, Assendelft WJ. What do patients consider to be the most important outcomes for effectiveness studies on migraine treatment? Results of a Delphi study. PLoS One. 2014 Jun 16;9(6):e98933.
Lipton RB, Stewart WF. Acute migraine therapy: do doctors understand what patients with migraine want from therapy? Headache. 1999;39(suppl 2):S20-S26.
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Dynavax - >>> Valneva Shares Plunge As UK Terminates COVID-19 Vaccine Contract: What You Need Know
Benzinga
by Vandana Singh
September 13, 2021
https://finance.yahoo.com/news/valneva-shares-plunge-uk-terminates-123244411.html
The U.K. government has terminated its COVID-19 vaccine contract with Valneva SE (NASDAQ: VALN) over alleged breach of obligations.
"HMG has alleged that the Company is in breach of its obligations under the Supply Agreement, but the Company strenuously denies this," it added.
Britain has ordered 100 million doses of Valneva's vaccine candidate, VLA2001, and had an option to secure an additional 90 million doses. The total value of these 190 million doses is around €1.4 billion.
The vaccine candidate is currently in Phase 3 trial, with results expected to be available early in the fourth quarter. Valneva has completed recruitment for VLA2001's pivotal Phase 3 trial "Cov-Compare" (VLA2001-301) with over 4,000 randomized participants.
Valneva's COVID vaccine candidate uses Dynavax Technologies Corporation's (NASDAQ: DVAX) CpG 1018 as an adjuvant.
Under Dynavax's existing supply agreement for CpG 1018, purchase orders submitted by Valneva are cancellable if the U.K. Government reduces or terminates its order for VLA2001.
Valneva has not yet canceled any outstanding purchase orders for CpG 1018. Dynavax has the right to retain any portion of the purchase price for CpG 1018 made in advance by Valneva and any CpG 1018 manufactured but not yet delivered.
Based on its portfolio of COVID-19 collaborations, Dynavax reiterates that its CpG 1018 supply contracts continue to represent an approximately 0 million - 0 million aggregate revenue opportunity in 2021.
Price Action: VALN stock is down 40.20% at $27.97, and DVAX stock dropped 11.10% at $15.60 during the premarket session on the last check Monday.
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>>> FDA has declined Humanigen’s Emergency Use Authorization (EUA) Request for Lenzilumab in Hospitalized COVID-19 Patients
Businesswire
September 9, 2021
https://finance.yahoo.com/news/fda-declined-humanigen-emergency-authorization-041600134.html
FDA has committed to working with Humanigen in the development of lenzilumab and has invited Humanigen to submit additional data as it becomes available
NIH’s ACTIV-5/BET-B study is expected to provide further data that may support a new EUA request
Humanigen remains committed to completing regulatory processes underway seeking Marketing Authorization for lenzilumab to treat hospitalized COVID-19 patients in the U.K. and other territories
BURLINGAME, Calif., September 09, 2021--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ announced today the U.S. FDA has declined its request for emergency use authorization of lenzilumab to treat newly hospitalized COVID-19 patients. In its letter, FDA stated that it was unable to conclude that the known and potential benefits of lenzilumab outweigh the known and potential risks of its use as a treatment for COVID-19.
"We remain committed to bringing lenzilumab to patients hospitalized with COVID-19," said Cameron Durrant, MD, Chief Executive Officer, Humanigen. "We believe the ongoing ACTIV-5/BET-B trial, which has been advanced to enroll up to 500 patients, may provide additional safety and efficacy data sufficient to support our efforts to obtain an EUA to treat hospitalized COVID-19 patients."
About Humanigen
Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’. Lenzilumab is a first-in class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF). Results from preclinical models indicate GM-CSF is an upstream regulator of many inflammatory cytokines and chemokines involved in the cytokine storm. Early in the COVID-19 pandemic, investigation showed high levels of GM-CSF secreting T cells were associated with disease severity and intensive care unit admission. Humanigen’s Phase 3 LIVE-AIR study suggests early intervention with lenzilumab may prevent consequences of a full-blown cytokine storm in hospitalized patients with COVID-19. Humanigen has submitted lenzilumab to Medicines and Health Regulatory Agency in the United Kingdom for a rolling review towards potential Marketing Authorization. Humanigen is developing lenzilumab as a treatment for cytokine storm associated with COVID-19, CD19-targeted CAR-T cell therapies and exploring the effectiveness of lenzilumab in other inflammatory conditions such as acute Graft versus Host Disease in patients undergoing allogeneic hematopoietic stem cell transplantation, eosinophilic asthma, and rheumatoid arthritis. For more information, visit www.humanigen.com and follow Humanigen on LinkedIn, Twitter, and Facebook.
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>>> Cardiff Oncology Announces New Data from Phase 1b/2 Trial in KRAS-mutated Metastatic Colorectal Cancer Showing Robust Objective Response Rate and Progression Free Survival
Yahoo Finance
September 8, 2021
https://finance.yahoo.com/news/cardiff-oncology-announces-data-phase-200000264.html
Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment.
8 of 19 (42%) patients treated per protocol at the recommended Phase 2 dose (RP2D) of onvansertib 15 mg/m2 who were evaluable for disease response as of the data cut-off achieved a partial response (PR). Historically, objective response rates (ORR) of 5-13% have been reported in a similar patient population treated with standard of care chemotherapy1-4
12 of 32 (38%) patients evaluable for response as of data cutoff date across all dose levels achieved a PR
Median progression-free survival (mPFS) across all response-evaluable patients is 9.4 months and has not yet been reached in those treated per protocol at the RP2D. Historically, mPFS of ~4.5-5.7 months has been reported in a similar patient population treated with standard of care chemotherapy1-4
The combination regimen of onvansertib plus FOLFIRI/bevacizumab is well tolerated
Management is hosting key opinion leader webinar to discuss data today at 4:00 PM ET; a replay of the webinar will be available on the events section of the Cardiff Oncology website for 90 days
Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, today announced new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC).
"Our Phase 1b/2 trial continues to generate data suggesting that the addition of onvansertib to SOC results in an objective response rate and median progression-free survival that substantially exceed those previously achieved with SOC alone," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "Radiographic responses have been observed across multiple KRAS mutation variants, which speaks to a key advantage of onvansertib over competing agents targeting individual mutations. These impressive results, which have remained consistent across both academic and community trial sites, highlight the potential for onvansertib to address the unmet need for new second-line therapeutic options to treat patients with KRAS-mutated mCRC. I look forward to the trial's continued advancement and future data readouts."
Highlights from today's data announcement include:
Efficacy data in patients evaluable for disease response as of data cutoff date (July 2, 2021):
Patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) across both Phase 1b and Phase 2:
Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) across both phases of the study
Median progression free survival (mPFS)
mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 32) is 9.4 months (95% confidence interval: 7.8 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Biomarker data as of data cutoff date across all patients:
Partial responses (PRs) were observed across different KRAS mutation variants, including the 3 most common observed in colorectal cancer (G12D, G12V, G13D)
Patients achieving a best response of PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle (28 days) of therapy
Safety data as of data cutoff date across all patients:
The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 10% (49/490) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Most reported treatment-related adverse events (TRAEs) were manageable and reversible with supportive care
Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "The strong signal of efficacy and favorable tolerability profile observed in this trial bodes well not only for our lead mCRC program, but for each of our KRAS-focused clinical programs. The meaningful improvements we are seeing in treatment response relative to historical controls demonstrate the value of combination therapy and support the synergistic effect observed preclinically when onvansertib is added to standard-of-care irinotecan and 5-FU (FOLFIRI). We are also seeing compelling biomarker results that highlight the potential utility of plasma KRAS MAF as a predictive tool that could aid in the design of subsequent trials. Looking forward, we anticipate the ongoing Phase 2 portion of the trial to provide additional data catalysts that will advance the clinical development of onvansertib, generate value for shareholders and, most importantly, provide new treatment options for patients."
Key Opinion Leader Webinar
The newly announced data are being discussed today at 4:00 PM ET as part of a key opinion leader (KOL) webinar being hosted by Cardiff Oncology. The webinar is featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team.
To attend the webinar, click here. A replay of the webinar will be available by visiting the "Events" section of the Cardiff Oncology website shortly after its conclusion.
About the Phase 1b/2 Trial of Onvansertib in KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin® (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have failed treatment with, or be intolerant to, FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit https://clinicaltrials.gov/ct2/show/NCT03829410.
References
Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37
About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need. Our goal is to target tumor vulnerabilities with treatment combinations that overcome disease resistance and improve disease response to standard treatment regimens and to increase overall survival. We are developing onvansertib, a first-in-class, third-generation Polo-like Kinase 1 ("PLK1") inhibitor, in combination with standard-of-care anti-cancer therapeutics. Our clinical development programs incorporate tumor genomics and biomarker technology to refine assessment of patient response to treatment. We have three clinical programs currently ongoing: a Phase 1b/2 study of onvansertib in combination with FOLFIRI/Avastin® (bevacizumab) in KRAS-mutated metastatic colorectal cancer (mCRC); a Phase 2 trial of onvansertib in combination with nanoliposomal irinotecan, leucovorin and fluorouracil for the second-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC); and a Phase 2 study of onvansertib in combination with Zytiga® (abiraterone)/prednisone in metastatic castrate-resistant prostate cancer (mCRPC). For more information, please visit https://www.cardiffoncology.com.
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I sold some MYOV to buy CRDF under $8. An onc doc friend of mine called CRDF results released yesterday "spectacular." He expects CRDF to get accelerated approval.
Bladerunner
ADAP news - Adaptimmune Enters into a Strategic Collaboration with Genentech to Research, Develop, and Commercialize Cancer-targeted Allogeneic T-cell Therapies
September 07, 2021 07:00 ET | Source: Adaptimmune Therapeutics plc
https://www.globenewswire.com/news-release/2021/09/07/2292303/35803/en/Adaptimmune-Enters-into-a-Strategic-Collaboration-with-Genentech-to-Research-Develop-and-Commercialize-Cancer-targeted-Allogeneic-T-cell-Therapies.html
>>> Why Coronavirus Stock Dynavax Crushed It Today
There was some very good news on the authorization front for the company.
Motley Fool
by Eric Volkman
Aug 23, 2021
https://www.fool.com/investing/2021/08/23/why-coronavirus-stock-dynavax-is-crushing-it-today/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
What happened
Vaccine specialist Dynavax (NASDAQ:DVAX) climbed more than 14% higher on Monday. It's little wonder: The company announced the coronavirus jab it co-developed with Taiwan's Medigen has been rolled out in the populous Asian nation.
So what
Every Dynavax watcher knew this day was coming; still, it's encouraging that MVC-COV1901 has been efficiently produced and launched. After all, the vaccine received its Emergency Use Authorization (EUA) from Taiwan's health ministry barely over one month ago.
In its press release trumpeting the news, Dynavax said that roughly 600,000 people in the large island nation will be inoculated with the vaccine this week. Similar to the more high-profile coronavirus vaccines made by Pfizer/BioNTech and Moderna, MVC-COV1901 is a two-shot solution.
Dynavax makes the adjuvant -- an ingredient used to stimulate a stronger immune response in vaccines -- utilized in the Medigen jab.
"We are very excited for this first, of hopefully multiple, EUAs and approvals for COVID-19 vaccines that include CpG 1018 adjuvant," the biotech company quoted CEO Ryan Spencer as saying.
"Considering the limitations of current vaccines and the global vaccine shortage, we believe adjuvanted vaccines can contribute significantly to current vaccination efforts," he added.
Now what
The ball is certainly rolling for MVC-COV1901. Indeed, now that the shot has won its first authorization from a national health authority and will soon be jabbed into arms, it's likely other authorizations will follow.
Nevertheless, Dynavax bulls should temper their enthusiasm by recognizing that other vaccines -- notably Pfizer/BioNTech's newly fully approved Comirnaty -- have been on the market for quite some time and are well established throughout the world.
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>>> Bio-Path Stock Jumps as Leukemia Treatment Candidate Moves to Testing
The FDA approves the company's new investigational drug application, allowing it to move to Phase 1/1b clinical stage.
The Street
TONY OWUSU
8-24-21
https://www.thestreet.com/investing/biopath-jumps-leukemia-treatment?puc=yahoo&cm_ven=YAHOO
Shares of Bio-Path Holdings (BPTH) - Get Report jumped Tuesday afternoon after the company announced that the U.S. Food and Drug Administration has reviewed and cleared its investigational leukemia treatment.
The company's second drug candidate BP1002 has been cleared for an initial Phase 1/1b clinical trial that will evaluate its ability to treat refractory/relapsed acute myeloid leukemia patients.
"Preclinical studies indicate that the BP1002 and decitabine combination is effective against venetoclax-resistant cell lines, suggesting that the BP1002 and decitabine combination therapy may provide benefits to patients who have relapsed from venetoclax-based treatment," said CEO Peter Nielsen.
The company says that by targeting its treatment at the DNA level rather than the protein, BP1002 might "overcome and prevent some of the mechanisms of resistance that affect venetoclax."
Phase 1/1b clinical trials feature humans and provide the first introduction of a pharmaceutical product into patients having the disease of interest. The primary endpoint of the trial is determining safety, metabolism and pharmacokinetic properties of the product.
The investigational new drug review process was performed by the FDA's Office of Oncologic Disease Division of Hematologic Malignancies and involved the agency conducting a comprehensive review of data submitted by the company.
“We are excited to move into these advanced clinical studies and look forward to generating data that not only support the DNAbilize platform but bring us one step closer to bringing these potentially lifesaving drugs to patients,” said Jorge Cortes, chairman of Bio-Path's scientific advisory board.
Bio-Path shares rose 16% to $6.63 a share Tuesday at last check.
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>>> Pfizer Agrees to Buy Cancer Biotech Trillium Therapeutics at a 200% Premium
Barron's
By Josh Nathan-Kazis
Aug. 23, 2021
https://www.barrons.com/articles/pfizer-trillium-acquisition-cancer-51629726947?siteid=yhoof2
Pfizer acquisition values Trillum at $2.3 million. Company sees "blockbuster potential" for its cancer treatments.
Pfizer said early Monday that it had agreed to purchase cancer-focused biotech Trillium Therapeutics for $2.3 billion in cash, or $18.50 a share, a 118% premium over the stock’s average price over the past 60 days, and a 208.8% premium over its Friday closing price of $6.09.
Pfizer (ticker: PFE) has previously signaled interest in the company, and in September made a $25 million investment in Trillum (TRIL). A Pfizer executive sits on its scientific advisory board.
Trillium’s lead drug candidates, known as TTI-622 and TTI-621, block a molecule known as CD47, and are being tested in various types of cancer.
Shares of Trillium were up 187.6%, to $17.52, in Monday morning trading. Pfizer shares were up 3.5%. Shares of other Covid-19 vaccine makers were also rising after the U.S. Food and Drug Administration gave full approval to Pfizer’s Covid-19 vaccine on Monday.
“The proposed acquisition of Trillium builds on our strong track record of leadership in Oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe,” said Pfizer Oncology global president and general manager Andy Schmeltz, in a statement out early Monday.
In a presentation posted Monday, Pfizer called TTI-622 and TTI-621 “potential best-in-class” compounds, and said they would diversify the company’s oncology pipeline, and could be used in combination with other Pfizer therapeutics. The drugs block a signal that cancerous tumors use to evade the body’s innate immune system.
The company said that the drugs have “blockbuster revenue potential” in the 2026-to-2030 time frame.
The more than 200% premium Pfizer is paying over Trillium’s Friday closing price raised some eyebrows early Monday. According to a database of biotech acquisitions maintained by the website BiopharmaDive, it is the third-largest percentage premium paid for any biotech firm since 2018. As of Friday, Trillium shares were down 58.6% so far this year, and 39.2% over the past 12 months. Of the seven analysts tracked by FactSet who cover the stock, all had Buy or Overweight ratings.
In a note out Monday, Bernstein analyst Ronny Gal wrote that Pfizer has lots of cash to spend. “Pfizer is now sitting in a position where it generates very large amounts of cash, with the need to place it to shore up post-Covid growth,” he wrote. Bernstein said that buying a company to acquire a drug that targets CD47 “is not very imaginative,” but “offers a solid risk reward.”
“We suspect that Trillium, realizing that staying competitive…would require large company resources, was a realistic seller,” Gal wrote.
The acquisition must be approved by Trillium shareholders.
Pfizer stock is up 32.4% this year as of the close of the market on Friday. It trades at 13.2 times earnings expected over the next 12 months, according to FactSet, slightly above its five-year average of 12.4 times earnings.
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>>> Why Is Axsome Therapeutics (AXSM) Stock Shooting Higher On Monday?
Benzinga
by Vandana Singh
August 23, 2021
https://finance.yahoo.com/news/why-axsome-therapeutics-axsm-stock-122802327.html
Axsome Therapeutics Inc (NASDAQ: AXSM) stock is rising in premarket due to an update for its US marketing application seeking approval for AXS-05 for major depressive disorder (MDD).
The FDA informed that it would not meet the target action date of August 22 for the application.
Investors are probably cheering because the agency did not ask for any additional information, and the application review is ongoing.
Related Content: Axsome received an FDA letter for the AXS-05 application for MDD, citing deficiencies that preclude discussion of labeling and post-marketing requirements/commitments.
AXS-05 (dextromethorphan-bupropion) is an NMDA receptor antagonist with multimodal activity under development to treat MDD and other central nervous system disorders.
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________________________________________________
>>> Why Axsome Therapeutics Stock Is Jumping Today
Investors are happy that the FDA didn't ask for more information to supplement Axsome's regulatory filing for AXS-05.
Motley Fool
by Keith Speights
Aug 23, 2021
https://www.fool.com/investing/2021/08/23/why-axsome-therapeutics-stock-is-jumping-today/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Key Points
The FDA did not meet its scheduled date to make an approval decision about AXS-05 as a treatment for major depressive disorder.
The news was not a big surprise since Axsome had previously warned investors about a potential delay.
The FDA didn't ask for any additional information and is continuing to review the approval application for AXS-05.
What happened
Shares of Axsome Therapeutics (NASDAQ:AXSM) were up by 7.5% as of 11:55 a.m. EDT Monday. The gain came after the company announced a delay in the Food and Drug Administration's review of its application for AXS-05 to be approved as a treatment for major depressive disorder.
So what
The FDA had originally set a Prescription Drug User Fee Act (PDUFA) date of Aug. 22 to complete its review of the regulatory filing for AXS-05. However, Axsome said that the agency informed it on Aug. 20 that it wouldn't meet that target date.
Ordinarily, this kind of announcement would cause a drugmaker's shares to fall. However, Axsome had already told investors in its second-quarter update earlier this month that the FDA had "identified deficiencies" in its regulatory filing. The company warned then that there could be a delay in the approval process.
Investors were likely pleased with Monday's news because Axsome said that the FDA had not requested any additional information; the agency is continuing to review the company's application.
Now what
There's one big question for Axsome now: When will the FDA make its decision on AXS-05? Unfortunately, the agency didn't provide a new date. Axsome is also waiting on the FDA to announce its decision on acceptance of its filing for AXS-07 in treating migraine.
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>>> The Noble Lies of COVID-19
Do we want public health officials to report facts and uncertainties transparently? Or do we want them to shape information to influence the public to take specific actions?
Slate
BY KERRINGTON POWELL AND VINAY PRASAD
JULY 28, 2021
https://slate.com/technology/2021/07/noble-lies-covid-fauci-cdc-masks.html
In March 2020, as the pandemic began, Anthony Fauci, the chief medical adviser to the president of the United States, explained in a 60 Minutes interview that he felt community use of masks was unnecessary. A few months later, he argued that his statements were not meant to imply that he felt the data to justify the use of cloth masks was insufficient. Rather, he said, had he endorsed mask wearing (of any kind), mass panic would ensue and lead to a surgical and N95 mask shortage among health care workers, who needed the masks more. Yet, emails from a Freedom of Information Act request revealed that Fauci privately gave the same advice—against mask use—suggesting it was not merely his outward stance to the broader public.
Although some have claimed that the evidence changed substantively in the early weeks of March, our assessment of the literature does not concur. We believe the evidence at the time of Fauci’s 60 Minutes interview was largely similar to that in April 2020. Thus, there are two ways to consider Fauci’s statement. One possibility is, as he says, that his initial statement was dishonest but motivated to avoid a run on masks needed by health care workers. The other is that he believed his initial statements were accurate, and he subsequently decided to advocate for cloth masks to divert attention from surgical or N95 masks, or to provide a sense of hope and control to a fearful and anxious public.
Additional evidence suggests that the second interpretation may be more accurate. In a lengthy commentary from July 2020, COVID expert Michael Osterholm wrote in detail about the continued scientific uncertainty regarding masks—even as he expressed support for their widespread public use as one measure among many. But Fauci’s reversal, which came at a time of political polarization, contributed to the evolution of masks from a basic, precautionary mitigation strategy to a badge of political allegiance. President Donald Trump was reluctant to wear a mask and justified his behavior by referring to Fauci’s comments from the 60 Minutes interview. The controversy continued into the presidential debates, with Trump mocking Joe Biden for donning the “biggest mask” he’d ever seen.
One thing is beyond a doubt, however: One of those two statements did not accurately reflect the evidence as Fauci saw it. Such high-profile mixed messages in a short time frame, without substantive new data to justify the change, generated confusion and a backlash from politicians, other experts, and the general public.
When experts or agencies deliver information to the public that they consider possibly or definitively false to further a larger, often well-meaning agenda, they are telling what is called a noble lie. Although the teller’s intentions may be pure—for example, a feeling of urgency that behavioral change is needed among the lay public—the consequences can undermine not only those intentions but also public trust in experts and science. During the first year of COVID-19, leaders were faced with an unknown disease amid a politically sensitive election in the era of social media, and the preconditions for noble lies became especially fertile. Not surprisingly, we witnessed several examples. More than anything, these examples illustrate the destructive potential of such lies.
Later in 2020, Fauci participated in a second noble lie. In December, he explained in a phone interview with then–New York Times reporter Donald McNeil that he had been moving the target estimate for herd immunity based in part on emerging studies. But he also said:
When polls said only about half of all Americans would take a vaccine, I was saying herd immunity would take 70 to 75 percent. Then, when newer surveys said 60 percent or more would take it, I thought, “I can nudge this up a bit,” so I went to 80, 85.
In his own words, he “nudged” his target range for herd immunity to promote vaccine uptake. Even though his comments were made to influence public actions to get more people vaccinated (a noble effort), the central dilemma remains: Do we want public health officials to report facts and uncertainties transparently? Or do we want them to shape information, via nudges, to influence the public to take specific actions? The former fosters an open and honest dialogue with the public to facilitate democratic policymaking. The second subverts the very idea of a democracy and implies that those who set the rules or shape the media narrative are justified in depriving the public of information that they may consider or value differently.
Aside from whether it’s right to tell noble lies in the service of eliciting socially beneficial behavior, there is also the question of efficacy. Experts on infectious diseases are not necessarily experts on social behavior. Even if we accept Fauci’s claim that he downplayed the importance of wearing masks because he didn’t want to unleash a run on masks, we might wonder how he knew that his noble lie would be more effective than simply being honest and explaining to people why it was important to assure an adequate supply of masks for medical workers.
With the arrival of vaccines in early 2021, the potential for such deliberately misleading messages to backfire became more obvious. Key opinion leaders, agencies, and the Centers for Disease Control and Prevention all articulated some version of “once you are vaccinated, nothing changes,” implying that experts did not know if it was safe to relax precautions and restrictions, such as mask wearing or social distancing, after immunization. But the stance was immediately called into question by others, including epidemiologists, who pointed to the high efficacy of the vaccines and suggested that some, but not all, social distancing measures could be relaxed in certain circumstances. Ultimately, the “no change” message, which may have been intended to discourage mass gatherings or out of a fear that unvaccinated people would lie about their vaccination status, may itself have been harmful: Surveys find that interest in vaccination increases if people are told that it means they can stop masking.
The fourth noble lie from government agencies and/or officials occurred more recently. On June 4, using data from February to March, the agency made the case that hospitalizations were rising in adolescents. It tweeted, “The report shows the importance of #COVID19 vaccination for adolescents.” That tweet spurred a great deal of media attention and concern. It was true that hospitalization rates had risen. However, at the time of the press coverage, hospitalization rates in this age group had already fallen again. Numerous commenters immediately pointed out that the “rise” in hospitalization statistic promoted by the CDC was out of date the moment it was highlighted and raised questions about why the CDC would promote a dated statistic, when the organization had access to up-to-date information.
This obvious error was compounded weeks later during a meeting of the Advisory Committee on Immunization Practices. The committee met to discuss what we knew and did not know about heart inflammation, or myocarditis, that had been linked to mRNA vaccination, and most notable in young men who received the vaccine. During the course of the meeting, representatives of the CDC showed a model that claimed that vaccination of young adults was preferable to the disease itself.
There were, however, several concerns with this model. First, it used rates of community SARS-CoV-2 spread that again were out of date. By the time of the meeting, the rates were lower, meaning the benefits of vaccination would be reduced, but the harms remain the same. Second, it did not consider the risks separately for boys and girls, who appear to have substantially different risk of myocarditis (much higher in boys). Third, it did not consider any middle ground positions, such as only receiving one dose of the vaccine, which provides much of the benefit with far lower myocarditis risk. Instead, the CDC presented zero or two doses as the only options. Fourth, the modeling did not consider natural immunity—i.e., the vaccine’s risk to kids who already recovered from COVID-19 might be the same, but the benefits far lower (as these children have some natural immunity). Finally, the model did not consider the fact that young adults with preexisting medical conditions and those who are otherwise well might have different risk benefit profiles, as the former account for a disproportionate number of COVID-19 hospitalizations.
Together, these are all information choices made by government agencies and/or officials about vaccination of young adults. Amplifying out-of-date statistics and building a model to support vaccination that has questionable assumptions work to support rapid deployment of two doses of mRNA to all healthy kids aged 12 to 17. That may be the CDC’s policy pursuit, and one we are sympathetic to. However, distorting evidence to achieve this result is a form of a noble lie. Accurately reporting current risks to adolescents, and exploring other dosing possibilities, is part of the unbiased scientific exploration of data.
We worry that vaccine policy among supporters of vaccines is increasingly anchored to the irrational views of those who oppose them—by always pursuing the opposite. Exaggerating the risk of the virus in the moment and failing to explore middle ground positions appear to be the antithesis of the anti-vax movement, which is an extremist effort to refuse vaccination. This seems a reflexive attempt to vaccinate at all costs—by creating fear in the public (despite falling adolescent rates) and pushing the notion that two doses of mRNA at the current dose level or nothing at all are the only two choices—a logical error called the fallacy of the excluded middle.
Noble lies—small untruths—yield unpredictable outcomes. Nietzsche once wrote, “Not that you lied to me, but that I no longer believe you, has shaken me.” Public health messaging is predicated on trust, which overcomes the enormous complexity of the scientific literature, creating an opportunity to communicate initiatives effectively. Still, violation of this trust renders the communication unreliable. When trust is shattered, messaging is no longer clear and straightforward, and instead results in the audience trying to reverse-engineer the statement based on their view of the speaker’s intent. Simply put, noble lies can rob confidence from the public, leading to confusion, a loss of credibility, conspiracy theories, and obfuscated policy.
Noble lies are a trap. We cannot predict the public’s behavior, and loss of trust is devastating. The general population is far too skeptical to blindly follow the advice of experts, and far too intelligent to be easily duped.
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>>> Studies look at clotting, myocarditis tied to COVID-19 vaccines
Center for Infectious Disease Research and Policy
by Lianna Matt McLernon
Aug 10, 2021
https://www.cidrap.umn.edu/news-perspective/2021/08/studies-look-clotting-myocarditis-tied-covid-19-vaccines
Two studies published by JAMA Cardiology today discuss adverse effects associated with COVID-19 vaccines. The first describes vaccine-induced immune thrombotic thrombocytopenia with cerebral venous sinus thrombosis (VITT with CVST) linked to the AstraZeneca/Oxford and Johnson & Johnson vaccines. The second is a case series looking at 15 adolescents who experienced myocarditis after receiving the Pfizer/BioNTech vaccine.
Despite these risks, both research teams continue to advocate for COVID-19 vaccines as the health risks from the virus are far greater than those linked to the vaccine. For instance, the VITT study researchers say that CVST risk from COVID-19 infection is 60- to 230-fold higher than the risk derived from COVID-19 vaccination.
No current strategies to avoid VITT
Both the AstraZeneca and Johnson & Johnson COVID-19 vaccines have regulatory warnings about VITT now, and data have shown that women under 60 years old appear to be at a higher risk. Symptoms include intracranial pressure, shortness of breath, lethargy, back pain, abdominal pain, spot bleeding under the skin, and leg or arm weakness, as well as positive test results for heparin-induced thrombocytopenia (HIT). Onset occurs a median of 8 or 10 days after receiving the Johnson & Johnson or AstraZeneca COVID-19 vaccine, respectively.
CVST, one of the worst manifestations of VITT, happens when clots form in the brain and major dural sinuses. While the average 30-day mortality is 6%, about 10% of patients have permanent neurological issues 1 year later.
No current strategies exist to avoid VITT, but interim recommendations include first-line therapy with non-heparin anticoagulants and intravenous immunoglobulins (IVIG), plus second-line steroids. Platelet transfusions can be given if the patient has or is at high risk for serious bleeding, but the researchers emphasize that routine platelet transfusions are associated with a 5-fold increase in mortality, probably because they are the source of platelet factor 4. Healthcare providers should also avoid aspirin.
"The mechanism of development of the prothrombotic state and its association with the vaccine are still only partially known, because multiple converging prothrombotic pathways may be involved in the pathogenesis," the researchers write.
Although both AstraZeneca's and Johnson & Johnson's adenovirus-based COVID-19 vaccines have been connected with VITT, the syndrome seems to occur at four times the frequency with the AstraZeneca vaccine, according to the researchers. As for the mRNA COVID-19 vaccines, no instances have been recorded with the Pfizer vaccine, but three cases have been connected to Moderna.
"Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG," the researchers write.
Myocarditis appears to mostly resolve
Pfizer's COVID-19 vaccine is more associated with myocarditis, or heart inflammation, with crude analysis showing greater risk for males ages 12 to 17, according to the authors of the case series. To examine the outcomes, they looked at 15 children admitted to Boston Children's Hospital from May 1 to Jul 15 for vaccine-associated myocarditis. All but one patient was male, and the median age was 15 (children 12 to 17 are eligible for Pfizer's vaccine). None had prior, known COVID-19 infection, although one did have reactive antibodies.
Symptom onset began 1 to 6 days post-vaccine (14 cases occurred after the second dose). The whole cohort experienced chest pain, but other common symptoms were fever (10), weakness (8), and headache (6). Troponin levels were also elevated at admission (median, 0.25 nanograms per milliliter compared with 0.1) and continued increasing 0.1 to 2.3 days after admission.
Overall, 13 patients presented with myocarditis via cardiac magnetic resonance imaging. Three had decreased left ventricular ejection fraction, and five had abnormal global longitudinal or circumferential strain. Still, no patients needed intensive care unit (ICU) admission, and hospitalization stay was a median of 2 days.
At a median of 1 to 13 days after discharge, four patients still had symptoms (fatigue, 3; chest pain, 1). Troponin was mildly elevated in three patients, and one patient had nonsustained ventricular tachycardia. One of the asymptomatic cases had persistent borderline low left ventricular systolic function.
The researchers conclude, "In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population."
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>>> Could Biogen Acquire Axsome Therapeutics?
Here are three reasons why a buyout just might happen.
Motley Fool
by Keith Speights
Aug 20, 2021
https://www.fool.com/investing/2021/08/20/could-biogen-acquire-axsome-therapeutics/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Axsome's neurological pipeline appears to be a good fit for Biogen.
After its major stock decline this year, Axsome's price tag would be quite affordable.
Biogen needs a deal due to challenges for its existing product lineup and a relatively weak late-stage pipeline.
It's been a great year for Biogen (NASDAQ:BIIB). The big biotech won a controversial U.S. approval for its Alzheimer's disease drug Aduhelm. Because of this surprising victory, Biogen's shares have soared close to 40% year to date.
The story hasn't been so great, though, for Axsome Therapeutics (NASDAQ:AXSM). The U.S. Food and Drug Administration (FDA) recently identified issues with the company's filing for approval of AXS-05 in treating major depressive disorder. Axsome stock plunged on the news and is now down more than 70% this year.
But Axsome's pipeline still has plenty of potential. And Biogen seems likely to look for smaller drugmakers to gobble up. Could Biogen acquire Axsome? There are three reasons why the answer could be a resounding "yes."
A good fit
The most important reason why Axsome could be on Biogen's radar is that it seems to be a pretty good fit for the big biotech. Biogen focuses primarily on neurological disorders. So does Axsome.
Biogen first rose to success with its multiple sclerosis (MS) franchise. Its spinal muscular atrophy drug Spinraza achieved blockbuster sales. Aduhelm will likely become one of the best-selling drugs on the market as a treatment for Alzheimer's disease.
The company's pipeline includes nearly 30 candidates. Most of them target neurological disorders, from additional experimental Alzheimer's disease therapies to stroke.
Axsome is somewhat unusual for a clinical-stage biotech in that it has two lead candidates. The company had hoped to win FDA approval for AXS-05 in treating major depressive disorder this month, although that's unlikely now with the agency's review of deficiencies in Axsome's regulatory filing. Axsome filed for FDA approval of another drug, AXS-07, in treating migraines in the second quarter of this year.
In addition to these two programs, Axsome is evaluating AXS-05 in a late-stage study targeting Alzheimer's disease agitation. It hopes to advance the drug into a late-stage study as a smoking-cessation therapy. The company should soon initiate a late-stage study of AXS-12 in treating narcolepsy. Axsome anticipates filing for FDA approval by the end of 2022 for AXS-14 in treating fibromyalgia.
Attractive price
There aren't many positives when a biotech stock crashes more than 70%. However, such a meltdown does make a company much cheaper for a potential acquisition.
That's certainly the case for Axsome. The company's market cap is now below $800 million. With multiple late-stage programs that could win FDA approvals in the not-too-distant future, Axsome could be viewed as a bottom-barrel bargain. This assumes, of course, that its pipeline candidates still have reasonable prospects for approvals.
Biogen should be able to buy Axsome on the cheap if it chose to do so. The company could definitely afford the deal. Biogen ended the second quarter with a cash stockpile of nearly $4 billion. As Aduhelm picks up sales momentum, the company's cash position will likely improve significantly.
Biogen needs a deal
Prior to the FDA approval of Aduhelm, Biogen was in a position where it desperately needed to make an acquisition or significant licensing deal. Sales for its MS franchise continue to decline. Spinraza isn't the growth driver that it once was. Rituxan, which Biogen licensed to Roche, faces biosimilar competition.
It probably wouldn't be correct to say that Biogen is now desperate to make a deal with the FDA approval of Aduhelm. However, the drug seems likely to face some stiff challenges winning acceptance.
Some healthcare providers have stated they won't prescribe the drug. Some payers, including the Veterans Administration, have refused to include Aduhelm on their formularies.
Other Alzheimer's disease drugs could be on the way that might threaten Aduhelm. Eli Lilly, for example, plans to file for FDA approval for its Alzheimer's disease drug donanemab by the end of this year.
Meanwhile, Biogen doesn't have an especially strong late-stage pipeline. With all of these dynamics, it would make a lot of sense for the company to look to make an acquisition that could quickly provide sales growth. There aren't many small drugmakers around that would enable Biogen to accomplish this goal. But Axsome would if at least one or two of its late-stage programs win FDA approval.
Biogen might not have its eye on Axsome -- but it wouldn't be surprising if it does.
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>>> UK approves Regeneron/Roche antibody cocktail for COVID-19
Reuters
https://www.reuters.com/business/healthcare-pharmaceuticals/uk-regulator-approves-first-monoclonal-antibody-treatment-covid-19-2021-08-20/
Aug 20 (Reuters) - The UK drug regulator has approved an antibody cocktail developed by Regeneron (REGN.O) and Roche (ROG.S) to prevent and treat COVID-19, it said on Friday, as the nation battles rising hospitalisations due to the more infectious Delta variant.
The Medicines and Healthcare products Regulatory Agency (MHRA) said clinical trial data shows the drug Ronapreve could help prevent infection, help resolve symptoms of severe COVID-19 infection and reduce the chances of hospitalisation.
"This treatment will be a significant addition to our armoury to tackle COVID-19," British health minister Sajid Javid said in a statement.
The news comes as hospitalisations of COVID-19 patients exceeded 6,100 this week, a five-month high. Two thirds of hospitalised patients were not vaccinated, data showed earlier this month.
Ronapreve, known as REGEN-COV in the United States, can be taken via injection or infusion. It binds tightly to the coronavirus at the lining of the respiratory system and prevents it from gaining access to cells of the respiratory system, the MHRA said.
Ronapreve belongs to a class of drugs called monoclonal antibodies which mimic natural antibodies produced by the body to fight off infections. The drug is not intended to be used as a substitute for vaccination, the MHRA said.
Javid said the government would start to roll out the therapy across the NHS as soon as possible.
It's the third therapy in the UK's arsenal in addition to generic steroid dexamethasone and arthritis drug tocilizumab, sold by Roche as Actemra and RoActemra.
Earlier this week, Roche warned of a global shortage of its arthritis drug which will last a few more weeks.
Ronapreve/REGEN-COV received emergency approval to treat COVID-19 in more than 20 countries including the United States, which has also authorised a similar treatment by Eli Lilly (LLY.N) for non-hospitalized COVID-19 patients.
It has been a big earner for Regeneron, which logged U.S. sales of $2.59 billion in the second quarter.
In June, the European Union bought about 55,000 doses of the treatment while the region's drug watchdog reviews the drug for approval.
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>>> Molnupiravir Shows Promise for Treatment of Moderate COVID-19 in Phase 2/3 Trial
Contagion Live
July 14, 2021
by Killian Meara
https://www.contagionlive.com/view/molnupiravir-shows-promise-for-treatment-of-moderate-covid-19-in-phase-2-3-trial
Conference | European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
The MOVe-OUT study will continue to the phase 3 portion and evaluate 800 mg of the therapy administered twice daily.
Merck Pharmaceuticals and Ridgeback Biotherapeutics have announced that their investigational oral therapeutic for the treatment of mild-to-moderate COVID-19, molnupiravir, has showed promising results as part of their phase 2/3 trial.
Results from the trial were also recently presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
“We continue to make progress in the clinical development of our antiviral candidate molnupiravir. Data from the dose-finding portion of these studies are consistent with the mechanism of action and provide meaningful evidence for the antiviral potential of the 800 mg dose,” Roy Baynes, senior vice president and head of global clinical development and chief medical officer at Merck Research Laboratories said. “Based on the findings of this study we are advancing a Phase 3 trial program in non-hospitalized patients that strategically leverages our large network of clinical sites to enroll appropriate patients globally.”
The ongoing phase 2/3, randomized, placebo-controlled, double-blind, multi-site study is evaluating the efficacy, safety and pharmacokinetics of orally administered molnupiravir in non-hospitalized participants with a PCR confirmed case of COVID-19.
Part 1 of the trial included 302 participants who had symptom onset within 7 days prior to randomization and were assigned to receive either 200 mg, 400 mg or 800 mg of molnupiravir or a placebo.
Findings from part 1 of the trial demonstrated that the percentage of patients who were hospitalized and/or died was lower in the combined molnupiravir-treated groups versus the placebo arm.
Additionally, those participants who received 800 mg of the therapy had the largest overall antiviral effect, in comparison to those who received 200 mg or 400 mg.
Part 2 of the trial, the phase 3 portion, will evaluate an 800 mg dose of molnupiravir administered twice daily.
The companies estimated that data from the phase 3 portion will be available in September or October of 2021.
“We are pleased that molnupiravir continues to show promise as a potential treatment for non-hospitalized patients with COVID-19,” Wendy Holman, chief executive officer at Ridgeback Biotherapeutics said. “Data from Ridgeback Bio’s EIDD-2801-2003 study (MK-4482-006) coupled with Merck’s MK-4482-002 study provide compelling evidence for the antiviral activity of molnupiravir. We look forward to the initiation and completion of the Phase 3 portion of the MOVe-OUT study.”
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>>> Interim Results from Phase 2/3 Studies of Molnupiravir, an Investigational Oral Antiviral Therapeutic for Mild to Moderate COVID-19, Presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID)
Merck
July 12, 2021
https://www.merck.com/news/interim-results-from-phase-2-3-studies-of-molnupiravir-an-investigational-oral-antiviral-therapeutic-for-mild-to-moderate-covid-19-presented-at-the-european-congress-of-clinical-microbiology-i/
KENILWORTH, N.J. & MIAMI--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics announced today the presentation of previously announced Phase 2 interim results from two Phase 2/3 clinical trials (MOVe-OUT and MOVe-IN) of molnupiravir (MK-4482/EIDD-2801), an investigational oral antiviral therapeutic. The data were presented during the late-breaking clinical trials session at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). The Phase 3 portion of the global MOVe-OUT trial studying molnupiravir in non-hospitalized adult patients with laboratory-confirmed COVID-19 and at least one risk factor associated with poor disease outcomes is underway. In addition, Merck plans to initiate a clinical program to evaluate molnupiravir for post-exposure prophylaxis in the second half of 2021.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210712005251/en/
“It continues to be critically important to advance potential antiviral treatments to address the devastating impact of COVID-19 globally,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “If successful, molnupiravir could help address the continued urgent need for therapeutics.”
“These data are promising, and we are pleased to be able to present the Phase 2 interim results for molnupiravir while we proceed with the Phase 3 portion of MOVe-OUT in non-hospitalized patients,” said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics. “There remains a great need for a range of solutions for the pandemic, and we are hopeful that molnupiravir will play a role in helping patients.”
For further information regarding our clinical trials, please visit https://merckcovidresearch.com/ or https://clinicaltrials.gov.
About Molnupiravir
Molnupiravir (EIDD-2801/MK-4482) is an investigational, orally bioavailable form of a potent ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2, the causative agent of COVID-19. Molnupiravir has been shown to be active in several models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission, as well as SARS-CoV-1 and MERS. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University and is being developed by Merck & Co., Inc. in collaboration with Ridgeback Biotherapeutics. Since licensed by Ridgeback, all funds used for the development of EIDD-2801/MK-4482 have been provided by Wayne and Wendy Holman and Merck.
About Ridgeback Biotherapeutics
Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is a biotechnology company focused on emerging infectious diseases. Ridgeback markets EbangaTM for the treatment of Ebola and has a late-stage development pipeline which includes molnupiravir for the treatment of COVID-19. Development of molnupiravir is entirely funded by Ridgeback Biotherapeutics and Merck & Co., Inc. All equity capital in Ridgeback Biotherapeutics LP originated from Wayne and Wendy Holman, who are committed to investing in and supporting medical technologies that will save lives. The team at Ridgeback Biotherapeutics is dedicated to working toward finding life-saving and life-changing solutions for patients and diseases that need champions.
About Merck
For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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Molnupiravir - >>> Oral antiviral drug effective against COVID-19 in hamsters
NIH / National Institutes of Health
April 27, 2021
https://www.nih.gov/news-events/nih-research-matters/oral-antiviral-drug-effective-against-covid-19-hamsters
An oral antiviral drug called MK-4482 inhibited SARS-CoV-2 replication in hamsters.
The drug might be able to prevent or treat COVID-19 outside of a clinical setting, and is currently being tested in people.
Syrian hamsters are susceptible to SARS-CoV-2 infection and so provide a useful model for testing COVID-19 treatments.
Only one antiviral drug, remdesivir, is currently approved for treating COVID-19. Remdesivir must be administered intravenously, which limits its use to clinical settings and hinders its use for preventing COVID-19 following exposure.
A team led by Dr. Heinz Feldmann from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Dr. Michael Jarvis, a guest researcher at NIAID from the University of Plymouth, tested MK-4482, an experimental antiviral drug that can be taken orally, against COVID-19. The results of their study appeared on April 16, 2021 in Nature Communications.
Previous work by the researchers showed that Syrian hamsters were highly susceptible to SARS-CoV-2 infection. Infected hamsters had high virus levels in their lungs but developed only mild, transient clinical symptoms. Thus, Syrian hamsters provide a useful model for evaluating the efficacy of COVID-19 treatments.
The researchers used the hamster model to test MK-4482. Also called Molnupiravir, MK-4482 is a prodrug, meaning that it has no activity on its own. Rather, the body’s metabolism converts it into an active drug. The corresponding active form of MK-4482, called EIDD-1931, was developed in the early 2000s to treat hepatitis C virus. Recent studies in mice showed it to be effective against SARS-CoV-1 and MERS-CoV, viruses related to SARS-CoV-2.
The researchers first tested the ability of EIDD-1931 to stop SARS-CoV-2 replication in cultured human lung cells. Treatment with EIDD-1931 reduced viral replication by almost a thousand-fold. Notably, effective doses of the drug exhibited minimal toxicity to the cells.
Next, the researchers gave MK-4482 to two groups of hamsters. One group began taking the drug 12 hours before infection with SARS-CoV-2. The other began 12 hours after infection. Both groups continued taking MK-4482 every 12 hours until the fourth day after infection.
By the fourth day, hamsters in both treatment groups had about 10-fold less viral RNA in their lungs than untreated hamsters. Treated hamsters also had 100-fold fewer infectious viruses and fewer lesions in their lungs. However, the drug had no effect on the amount of virus shedding from the mouth. Hamsters in both treatment groups had similar levels of the active compound EIDD-1931 in their lungs.
MK-4482 is now in human clinical trials in SARS-CoV-2 infected patients. If it succeeds, MK-4482 could expand the available options for COVID-19 treatment. Because it can be taken orally, the drug could be used shortly before or after exposure to prevent COVID-19 symptoms. Combining MK-4482 with remdesivir may also be more effective than either drug on its own.
“In contrast to vaccines against SARS-CoV-2, we really don't have many drugs that are effective against the virus,” Jarvis says. “This is an exciting result that identifies MK-4482 as an additional antiviral against SARS-CoV-2. I think this additional control measure could prove to be really useful in the current pandemic.”
— by Brian Doctrow, Ph.D.
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>>> Best Biotech ETFs for Q4 2021
ARKG, IDNA, and BBH are the best biotech ETFs for Q4 2021
Investopedia
By NATHAN REIFF
Aug 12, 2021
https://www.investopedia.com/articles/investing/081415/top-3-biotech-etfs.asp?utm_campaign=quote-yahoo&utm_source=yahoo&utm_medium=referral
Biotech companies use or modify biological processes in order to create new pharmaceuticals or therapies. Some of the most prominent biotech companies include Vertex Pharmaceuticals Inc. (VRTX) and Regeneron Pharmaceuticals Inc. (REGN).
KEY TAKEAWAYS
The biotech sector underperformed the broader market over the past year.
The biotech ETFs with the best one-year trailing total return are ARKG, IDNA, and BBH.
The top holding of ARKG is Teladoc Health Inc., and the top holding of IDNA and BBH is Moderna Inc.
Investing in the biotech sector can be risky. The scientific and regulatory issues involved with gaining approval from the U.S. Food and Drug Administration (FDA) can be substantial, making it risky and difficult to predict what biotech stocks will outperform.1 One of the easiest ways to invest in the sector is through biotech exchange-traded funds (ETFs). These funds have holdings in a large array of biotech companies, offering investors a well-diversified portfolio in one easy-to-execute trade.
There are 10 biotech ETFs that trade in the U.S., excluding inverse and leveraged ETFs as well as funds with less than $50 million in assets under management (AUM). The biotech sector, as measured by the Nasdaq Biotechnology Index, has underperformed the broader market with a total return of 28.0% over the past 12 months compared to the S&P 500's total return of 34.0%, as of Aug. 10, 2021.2 The best-performing biotech ETF, based on performance over the past year, is the ARK Genomic Revolution ETF (ARKG). We examine the top three best biotech ETFs below. All numbers are as of Aug. 10, 2021.3
ARK Genomic Revolution ETF (ARKG)
Performance over One-Year: 46.2%
Expense Ratio: 0.75%
Annual Dividend Yield: 0.91%
Three-Month Average Daily Volume: 2,939,797
Assets Under Management: $8.9 billion
Inception Date: Oct. 31, 2014
Issuer: ARK
ARKG is an actively managed ETF focused on companies expected to benefit from technologies and scientific developments in genomics that could extend and enhance the quality of human and other life. The fund provides exposure to companies engaged in gene editing, therapeutics, stem cells, and bioinformatics and holds approximately 60 growth stocks of various market capitalizations.4
ARKG's top three holdings include Teladoc Health Inc. (TDOC), a provider of tele-healthcare services; Pacific Biosciences of California Inc. (PACB), a maker of systems for gene sequencing; and Fate Therapeutics Inc. (FATE), a biopharmaceutical company developing immunotherapies for cancer.5
iShares Genomics Immunology and Healthcare ETF (IDNA)
Performance over One-Year: 39.5%
Expense Ratio: 0.47%
Annual Dividend Yield: 0.16%
Three-Month Average Daily Volume: 62,820
Assets Under Management: $359.2 million
Inception Date: June 11, 2019
Issuer: BlackRock Financial Management
IDNA is a multi-cap blended fund that tracks the NYSE FactSet Global Genomics and Immuno Biopharma Index, which is made up of companies that may benefit from long-term growth and innovation in genomics, immunology, and bioengineering. The fund invests in companies from both developed and emerging markets, although the large majority of its holdings are domiciled in the U.S. or Germany.6
IDNA's top holdings include Moderna Inc. (MRNA), a pharmaceutical and biotechnology company specialized in vaccine technologies based on messenger RNA; Intellia Therapeutics Inc. (NTLA), a biotechnology company focused on CRISPR gene-editing technology; and sponsored American depositary receipts (ADRs) of BioNTech SE (BNTX), a German biotechnology company that manufactures immunotherapies.7
VanEck Vectors Biotech ETF (BBH)
Performance over One-Year: 35.2%
Expense Ratio: 0.35%
Annual Dividend Yield: 0.28%
Three-Month Average Daily Volume: 15,785
Assets Under Management: $629.3 million
Inception Date: Dec. 20, 2011
Issuer: VanEck
BBH tracks the MVIS U.S. Listed Biotech 25 Index, an index of companies involved in the development and production, sales, and marketing of therapies based on genetic analysis and diagnostic equipment. The fund is highly concentrated in a few names, with the top 10 of its 24 holdings accounting for more than 60% of all invested assets.8
BBH's top holdings include Moderna Inc.; Amgen Inc. (AMGN), a biopharmaceutical company focused on treating serious illnesses and hard to cure diseases; and sponsored ADRs of BioNTech SE.9
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>>> Humanigen Reports Second Quarter 2021 Financial Results
Yahoo Finance
August 12, 2021
https://finance.yahoo.com/news/humanigen-reports-second-quarter-2021-200000787.html
BURLINGAME, Calif., August 12, 2021--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called "cytokine storm’" with its lead drug candidate, lenzilumab, today provided a corporate and regulatory update and reported financial results for the second quarter and six months ended June 30, 2021.
Update on Status of Emergency Use Authorization ("EUA") Application
On May 28, 2021, Humanigen submitted an EUA application for lenzilumab in patients hospitalized with COVID-19. Since that time, the company has responded to several requests from the U.S. Food and Drug Administration ("FDA") regarding the application. No formal timelines exist for the FDA to complete their review of our EUA application and as a result the company is unable to give guidance on the timing of a decision by the FDA.
"We remain firm in our belief the results of our LIVE-AIR Phase 3 study warrant lenzilumab being granted emergency use authorization. The achievement of the primary endpoint for the overall patient population, and the recent supplemental subset analysis which showed significant response to treatment by Black and African-American patients in the study, support our view of the potential benefit lenzilumab could bring to patient care if authorization were to be granted," said Cameron Durrant, MD, Chief Executive Officer, Humanigen.
Timothy Morris, CFO and COO, Humanigen, noted, "While the review of the EUA application continues, we are preparing for potential launch in the U.S., and simultaneously working to complete, before the end of the third quarter 2021, the submission of the Marketing Authorization Application ("MAA") to the Medicines Healthcare products Regulatory Agency ("MHRA") in the U.K. We have initiated the MAA process to the European Medicines Agency ("EMA") and anticipate the appointment of rapporteurs in the near term."
Second Quarter and Recent Highlights:
Lenzilumab in hospitalized COVID-19
Submitted an application to the FDA for an EUA for lenzilumab for the treatment of patients hospitalized with COVID-19.
Initiated filing and received acknowledgement the UK submission for Marketing Authorization for lenzilumab in COVID-19 has been accepted for expedited COVID-related rolling review by the MHRA. The submission is expected to be completed by September 30, 2021.
Initiated the process to make a submission to the European Medicines Agency for Marketing Authorization of lenzilumab in COVID-19.
The company’s commercial partners in South Korea and the Philippines, KPM Tech and Telcon RF Pharmaceutical, received approval from South Korea’s Ministry of Food and Drug Safety, the South Korean equivalent of FDA, to conduct a Phase 1 clinical study of lenzilumab, to enable submission and potential approval in South Korea.
Announced analysis of results from our Phase 3 LIVE-AIR study of lenzilumab in hospitalized patients with COVID-19 suggesting Black and African-American patients having a CRP<150 mg/L may be the highest responders to treatment, with a nearly 9-fold increase in likelihood of survival without ventilation ("SWOV") [n=51, p-value=0.0418]. In the overall population with CRP<150 mg/L, LIVE-AIR Phase 3 results show patients treated with lenzilumab demonstrated a 2.5-fold increased likelihood of SWOV [mITT, n=351, p-value=0.0009].
Entered into manufacturing agreement with Chime Biologics to produce lenzilumab bulk drug substance and drug product to be sold, with requisite regulatory authorization, in regions outside the United States.
Corporate
Completed underwritten public offering of common stock, raising net proceeds of $94.2 million.
The company was added to the Russell 3000® Index in June 2021.
Ken Trbovich was appointed to the newly-created role of SVP Investor Relations.
ACTIV-5 Update
In August 2021, the National Institutes of Health ("NIH") announced the expansion of the Accelerating COVID-19 Therapeutic Interventions and Vaccines ("ACTIV-5") and Big Effect Trial, in the "B" arm of the trial ("BET-B"), referred to as ACTIV-5/BET-B. Following feedback from and consultation with the company, the NIH advanced the study to a Phase 2/3 study with target enrollment of at least 400 patients and amended the protocol for ACTIV-5/BET-B in a manner that aligns with the design of the company’s LIVE-AIR trial. As a result of the advancement to a Phase 2/3 and amended protocol, the company anticipates that ACTIV-5/BET-B may serve as a second confirmatory study required for submission to FDA as part of a Biologics License Application ("BLA") that the company would submit if the ACTIV-5/BET-B data further validate the benefits of lenzilumab in COVID-19 patients.
Second Quarter and Six Months Ended June 30, 2021 Financial Results
Net loss for the three months ended June 30, 2021 was $70.8 million or $1.20 per share as compared to $24.0 million or $0.79 per share for the three months ended June 30, 2020. The net loss for the six months ended June 30, 2021 was $136.4 million or $2.45 per share as compared to $26.5 million or $1.00 per share for the six months ended June 30, 2020. The increase in net loss for both periods was largely due to an increase in total expenses, mainly Research and Development ("R&D") expense which rose significantly as the company accelerated its efforts to manufacture lenzilumab for potential commercialization upon a regulatory authorization. R&D expense increased $41.9 million from $21.1 million for the three months ended June 30, 2020, to $63.0 million for the three months ended June 30, 2021, and increased $101.1 million from $21.8 million for the six months ended June 30, 2020, to $122.9 million for the six months ended June 30, 2021. The manufacturing expense included in R&D was $57.1 million for the second quarter of 2021 as compared to $17.1 million for the prior year quarter, and $107.1 million for the six months ended June 30, 2021, as compared to $17.4 million for the prior year period. The costs incurred to produce lenzilumab will continue to be included in R&D expense until lenzilumab is authorized or approved for commercial use, at which point the amounts expended for production would be reclassified as inventory. A meaningful portion of these expenses are associated with initiation of manufacturing processes on a site-by-site basis.
Cash and Cash Equivalents
Net cash used in operating activities, net of balance sheet changes, was $103.8 million for the six months ended June 30, 2021. During the same period, the company raised net proceeds of $36.1 million from the sale of shares of common stock under its At-the-Market offering program, drew the first tranche of $25.0 million under its credit facility with Hercules Capital, providing net proceeds of $24.4 million, and completed a public offering of common stock with net proceeds of $94.2 million. As of June 30, 2021, the company had cash and cash equivalents of $120.5 million. The company expects to continue to use its funds on the manufacturing of lenzilumab in anticipation of its potential commercialization under EUA in the US or conditional marketing authorization in the UK. For the third quarter of 2021 the company anticipates the R&D expense related to lenzilumab production will be same level as the second quarter of 2021. If an EUA or CMA for lenzilumab is not received in the third quarter of 2021, the company would seek to decrease its spending on lenzilumab production.
About Humanigen, Inc.
Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’. Lenzilumab is a first-in class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF). Results of preclinical models indicate GM-CSF is an upstream regulator of many inflammatory cytokines and chemokines involved in the cytokine storm. Early in the COVID-19 pandemic, investigation showed high levels of GM-CSF secreting T cells were associated with disease severity and intensive care unit admission. Humanigen’s Phase 3 LIVE-AIR study suggests early intervention with lenzilumab may prevent consequences of a full-blown cytokine storm in hospitalized patients with COVID-19. Humanigen is developing lenzilumab as a treatment for cytokine storm associated with CD19-targeted CAR-T cell therapies and exploring the effectiveness of lenzilumab in other inflammatory conditions such as acute Graft versus Host Disease (aGvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), eosinophilic asthma, and rheumatoid arthritis. Humanigen is also developing a portfolio of clinical and pre-clinical therapies for the treatment of inflammation and immuno-oncology. For more information, visit www.humanigen.com and follow Humanigen on LinkedIn, Twitter, and Facebook.
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IPIX - >>> U.S. Severe Oral Mucositis Market to Surpass US$ 267.7 Million by 2028, Says Coherent Market Insights (CMI)
MarketWatch
Aug. 12, 2021
https://www.marketwatch.com/press-release/us-severe-oral-mucositis-market-to-surpass-us-2677-million-by-2028-says-coherent-market-insights-cmi-2021-08-12?siteid=bigcharts&dist=bigcharts&tesla=y
SEATTLE, Aug 12, 2021 (GLOBE NEWSWIRE via COMTEX) -- SEATTLE, Aug. 12, 2021 (GLOBE NEWSWIRE) -- According to Coherent Market Insights, the U.S. Severe Oral Mucositis Market is estimated to be valued at US$ 78.5 million in 2021 and is expected to exhibit a CAGR of 19.2% during the forecast period (2021-2028).
Key Trends and Analysis of the U.S. Severe Oral Mucositis Market:
Key players operating in the market are focusing on the development of treatments for severe oral mucositis, which is expected to offer lucrative opportunities for the market players to launch novel products in the market. For instance, in June 2020, Soligenix, Inc. announced that it completed patient enrolment in its Phase 3 DOM-INNATE study for SGX942 (dusquetide) in the treatment of oral mucositis (OM) in head and neck cancer (HNC) patients.
For instance, in February 2020, Galera Therapeutics, Inc. announced full tumor results of the two year follow up of patients with head and neck cancer treated with avasopasem manganese (GC4419), which is Galera's lead product candidate for severe oral mucositis (SOM) and is currently in a Phase 2b clinical trial.
Key Market Takeaways:
The U.S. severe oral mucositis market is expected to exhibit a CAGR of 19.2% during the forecast period due to increasing prevalence of head and neck cancer in the U.S., which is expected to boost the U.S. severe oral mucositis market in 2028. For instance, according to the Centers for Disease Control and Prevention report, around 650,000 cancer patients receive chemotherapy in an outpatient setting each year in the U.S. and according to a consensus about 500,000 cases of OM occur in the U.S. every year.
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On the basis of Drug Type, Late Phase Drugs (Avasopasem and Dusquetide) segment is estimated to exhibit higher CAGR in the U.S. severe oral mucositis market over forecast period. Key companies in the market are focused on research and development activities to develop novel therapeutics for the treatment of severe oral mucositis, which is expected to drive the segment growth during the forecast period. For instance, in June 2020, Soligenix Inc., a pharmaceutical company, announced the completion of patient enrollment for its phase III clinical trial study of SGX942 (Dusquetide) for the treatment of oral mucositis.
On the basis of Grade, Grade IV segment is estimated to hold a dominant position in the U.S. severe oral mucositis market in 2021. Increasing hospitalization of the patients suffering from grade IV oral mucositis is expected to drive the segment growth. For instance, according to the U.S. National library of Medicine report 2017, around 70% of the patients with grade III- IV oral mucositis require feeding tube insertion and immediate medical attention in the U.S.
Among Distribution channel, Hospital Pharmacies segment is estimated to hold a dominant position in the U.S. severe oral mucositis market in 2021. Increase in the healthcare expenditure by various healthcare regulatory organizations in the U.S. in the past years is expected to drive the segment growth. For instance, according to the U.S. Centers for Medicare and Medicaid Services' 2019 findings on the National Health Expenditure (NHE), hospital expenditure grew by 4.6% to US$ 3.8 trillion in 2019, compared to the previous year (2018). Additionally, prescription drug expenditure increased by 5.7% to US$ 369.7 billion in 2019, which was higher than the 3.8% growth in 2018.
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Competitive Landscape:
Key players operating in the U.S. severe oral mucositis market include Innovation Pharmaceuticals Inc.*, Monopar Therapeutics Inc., Soligenix, Inc., Oragenics, Inc., Enzychem Lifesciences, Galera Therapeutics, Inc., Amgen, Inc., and Covis Pharma Group.
Market Segmentation:
U.S. Severe Oral Mucositis Market, Drug Type:
Palifermin
Amifostine
Chlorhexidine
Sucralfate
Late Phase (Avasopasem, Dusquetide)
U.S. Severe Oral Mucositis Market, By Cause:
Chemotherapy
Radiotherapy
U.S. Severe Oral Mucositis Market, By Grade:
Grade III
Grade IV
U.S. Severe Oral Mucositis Market, By Distribution Channel:
Hospital Pharmacies
Retail Pharmacies
Hospital
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About Us:
Coherent Market Insights is a global market intelligence and consulting organization focused on assisting our plethora of clients achieve transformational growth by helping them make critical business decisions. We are headquartered in India, having sales office at global financial capital in the U.S. and sales consultants in United Kingdom and Japan. Our client base includes players from across various business verticals in over 57 countries worldwide.
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NAC - >>> N-Acetylcysteine to Combat COVID-19: An Evidence Review
Zhongcheng Shi1,2 and Carlos A Puyo3
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649937/
Ther Clin Risk Manag. 2020; 16: 1047–1055.
Published online 2020 Nov 2. doi: 10.2147/TCRM.S273700
Abstract
The novel coronavirus disease (COVID-19) is caused by a virus (SARS-Cov-2) and is known for inducing multisystem organ dysfunction associated with significant morbidity and mortality. Current therapeutic strategies for COVID-19 have failed to effectively reduce mortality rate, especially for elderly patients. A newly developed vaccine against SARS-Cov-2 has been reported to induce the production of neutralizing antibodies in young volunteers. However, the vaccine has shown limited benefit in the elderly, suggesting an age-dependent immune response. As a result, exploring new applications of existing medications could potentially provide valuable treatments for COVID-19. N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2. This review offers a thorough analysis of NAC and discusses its potential use for treatment of COVID-19.
Keywords: N-acetylcysteine, SARS-Cov-2, COVID-19
Introduction
According to the CDC, most SARS-Cov-2 infected individuals can recover from the disease at home. However, this virus can also cause serious illness in immune-compromised individuals, elderly patients, and in those with certain preexisting health conditions, such as hypertension, diabetes, and cardiovascular disease.1 It takes approximately 7 days to develop computed tomography (CT)-confirmed pneumonia (COVID-19) from the onset symptoms, such as fever or dry cough, and another 2 days to progress to acute respiratory distress syndrome (ARDS).2 ARDS is the major cause of death for COVID-19 patients and is associated with dysregulated host immune responses following viral infection
One of the early immune responses during viral infection is the production of cytokines and chemokines from immune cells. High levels of IL-8, a strong chemoattractant for neutrophils, has been detected early in infected SARS patients.3 Once activated by infection, neutrophils are rapidly recruited to sites of inflammation in the lungs, where they produce and secrete cytokines, enzymes, including elastase (NE), reactive oxygen species (ROS) by oxidative burst, and finally release DNA to form neutrophil extracellular traps (NETs).4 In severe COVID-19 patients, an increased number of neutrophils has been associated with disease severity,5 most likely due to the production of large amounts of proinflammatory cytokines, creating a “cytokine storm”.
In neutrophils, NE can degrade a wide variety of architecturally and functionally important molecules, such as clotting factors and complement proteins.6 NE activity may, in part, explain the significant increase of D-dimer and pulmonary hemorrhage observed in COVID-19 patients.2 Additionally, NET-bound NE can degrade local plasminogen without generating plasmin onto fibrin, thus resulting in impaired fibrinolysis. This suggests that NE-bound NETs have the potential to serve as a platform for activation and formation of intravascular coagulation,7,8 which partly explains why pulmonary embolism usually occurs in critical COVID-19 patients in the intensive care unit (ICU).9 In some critically ill COVID-19 patients, the coexistence of thrombosis and hemorrhage was observed,10 indicating that suppression of NE production by stabilizing neutrophils could be beneficial for either condition. For instance, inhibiting neutrophil activation by an IL-8 antibody can effectively combat acute lung injury.11,12 In other words, any measure that can suppress neutrophil activation might improve the outcomes of COVID-19 patients.
Cellular immunity is also required for a host to fight a viral infection, which is regulated by an oxidant-antioxidant balance. This balance is maintained by antioxidants including glutathione. In the immune cells of senior or immune-compromised individuals, ROS is increased due to decreased glutathione, which causes dysregulation of immune responses, particularly of T cell-mediated functions. This may explain the depressed cell-mediated immunity and increased mortality found in elderly persons as a result of infectious diseases, such as pneumonia.13,14 In fact, in addition to depressed functions, the number of lymphocytes, including both CD4+ and CD8+ T cells, was found to decrease linearly with age.15 Furthermore, a reduced number of T cells as a result of apoptosis was also observed in critical COVID-19 patients, which further compromised cellular immunity and was associated with the higher mortality for these populations.2,16 Therefore, replenishing certain antioxidants may restore the normal responses of immune cells through inhibiting T cell apoptosis, potentially reducing incidence or severity of pneumonia due to virus infection.
Combining count changes of neutrophils and lymphocytes, several groups have recently revealed that a high neutrophil-to-lymphocyte ratio (NLR) predicts a more severe progression of the disease and worse outcomes for COVID-19 patients,17–19 suggesting that NLR may be used as a prognostic marker and a therapeutic guide during acute COVID-19 infection. Therefore, in addition to administration of anti-viral drugs, inhibiting neutrophil activation and protecting T cells could provide an effective therapeutic option for treating COVID-19 patients.
Theoretically, an effective vaccine would be the best solution to combat SARS-cov-2 infection. A recent study showed that a recombinant adenovirus type-5 (Ad5) vaccine was capable of inducing neutralizing antibodies at day 14 post-vaccination,20 suggesting that a quick control of the COVID-19 pandemic is a possibility. However, this study also found that the neutralizing antibodies were reduced between the ages of 45 to 60 when compared with younger people. Since younger people are widely considered the major carriers and spreaders of SARS-Cov-2, effective vaccines are still desperately needed to reduce virus transmission. Meanwhile, exogenous neutralizing antibodies may help those not responsive to the SARS-Cov-2 vaccines. Unfortunately, both vaccines and neutralizing antibodies are still under development. Therefore, a multimodal approach may be necessary when treating COVID-19 in elderly patients or in those with preexisting conditions.
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>>> Involvement of nicotine receptors in COVID-19
https://www.news-medical.net/news/20200720/Involvement-of-nicotine-receptors-in-COVID-19.aspx
By Dr. Tomislav Meštrovic, MD, Ph.D.
Jul 20 2020
Researchers from the University of Bristol, Oxford Brookes University and the University of California San Diego neatly demonstrated how the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits high affinity for nicotinic acetylcholine receptors (nAChRs), with significant implications for coronavirus disease (COVID-19) pathology and infectivity. Their findings are published on the bioRxiv* preprint server.
The ongoing COVID-19 pandemic, caused by SARS-CoV-2, remains a substantial threat to global health, the international economy and society as a whole. Several major risk factors for COVID-19 have been identified – namely, age, diabetes, hypertension, and heart disease.
Recently, given the seemingly low prevalence of smokers among hospitalized patients, it was suggested that nicotine might provide some protection in mitigating COVID-19, which was dubbed the 'protection' hypothesis.
More specifically, based on the early observations where smoking prevalence in hospitalized COVID-19 patients was lower than expected, certain studies suggested a role for nAChRs in the pathophysiology of COVID-19 through a direct interaction between these receptors and the viral spike glycoprotein (S-protein).
This suggestion was primarily based on the fact that the S-protein from SARS-CoV-2 harbors a sequence motif related to known nAChR antagonists and may interact with nAChRs. Consequently, such interactions may be then involved in pathology and infectivity, which is a notion known as 'nicotinic hypothesis.'
Furthermore, it was also proposed that COVID-19 might be controlled or alleviated by the use of nicotine if this compound can sterically or allosterically compete with the virus for binding to nAChRs.
In this novel study, the researchers used molecular simulation to examine the nicotinic hypothesis – primarily by appraising whether the SARS-CoV-2 S-protein can stably bind to nAChRs via the Y674-R685 region (i.e., a viral portion with the highest affinity to these receptors)...
...
Verified interaction of SARS-CoV-2 with nicotinic acetylcholine receptors
In a nutshell, the findings reported in this study support the hypothesis that the SARS-CoV-2 S-protein can indeed interact with nAChRs. More specifically, the results indicate that the Y674-R685 region from the S-protein shows a significant affinity for nAChRs in general, with the highest affinity for the muscle-like receptor.
"Our calculations indicate stable binding of the S-protein to these receptors through a region adjacent to the furin cleavage site and corresponding to the Y674-R685 loop", study authors explain their findings. "They also show apparent subtype-specific interactions, with the highest affinity for the muscle-type aß?d receptor", they add.
Of note, furin cleavage site has many implications for the viral life cycle. Additionally, the region in the S-protein that is responsible for binding to nAChRs shares high sequence similarity with neurotoxins known to be nAChRs antagonists.
"Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs", study authors further explain.
Finally, modeling studies of the interaction between the full-length S-protein and nAChRs show that association is achievable with the proteins in a non-parallel orientation to one another, which is a significant observation for further research endeavors in this field.
Smoking cessation agents as drugs for COVID-19?
We already know that COVID-19 can be responsible for a wide array of respiratory, muscular, and neurological symptoms. Hence, the interactions predicted in this study may be relevant for understanding the pathophysiology of this disease.
"If nicotine does indeed prove to have any clinical value, it would likely be due to interfering with the association with nAChRs," study authors conclude in their bioRxiv paper.
And if that is indeed the case, nicotine analogs (also referred to as smoking cessation agents) –such as varenicline, cytisine, and cytisine derivatives – could also find their place in treating patients with (potentially severe) COVID-19.
Taking into account these promising results, further mutational and structural studies will be required to test the importance of SARS-CoV-2 S-protein interactions with nAChRs, with its potential relevance to pathology and infectivity of COVID-19.
*Important Notice
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Journal references:
Oliveira, A.S.F. et al. (2020). Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity. bioRxiv. https://doi.org/10.1101/2020.07.16.206680.
Changeux JP. (2018). The nicotinic acetylcholine receptor: a typical 'allosteric machine'. Philos Trans R Soc Lond B Biol Sci. https://doi.org/10.1098/rstb.2017.0174.
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>>> Atea Pharmaceuticals, Inc. (AVIR), a clinical-stage biopharmaceutical company, focused on discovering, developing, and commercializing antiviral therapeutics for patients suffering from viral infections. Its lead product candidate is AT-527, a novel antiviral agent that is in Phase II clinical trial for the treatment of patients with COVID-19. The company also develops AT-752, an oral purine nucleoside prodrug product candidate, which has completed Phase Ia clinical trial for the treatment of dengue; AT-787, a co-formulated, oral, pan-genotypic fixed dose combination of AT-527 and AT-777 that is in Phase I/IIa clinical trial for the treatment of chronic hepatitis C; and AT-889, an investigational, second-generation nucleoside pyrimidine prodrug and other compounds for the treatment of respiratory syncytial virus. It has a Roche License Agreement with F. Hoffmann-La Roche Ltd and Genentech, Inc. for development and commercialization related to AT-527 outside of the United States. The company was incorporated in 2012 and is headquartered in Boston, Massachusetts.
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>>> Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia
Angela Huynh, John G. Kelton, Donald M. Arnold, Mercy Daka & Ishac Nazy
Nature (2021), July 7. 2021
https://www.nature.com/articles/s41586-021-03744-4
Abstract
Vaccine-induced immune thrombotic thrombocytopaenia (VITT) is a rare adverse effect of COVID-19 adenoviral vector vaccines1,2,3. VITT resembles heparin-induced thrombocytopaenia (HIT) in that it is associated with platelet-activating antibodies against platelet factor 4 (PF4)4; however, patients with VITT develop thrombocytopaenia and thrombosis without exposure to heparin. Here we sought to determine the binding site on PF4 of antibodies from patients with VITT. Using alanine-scanning mutagenesis5, we found that the binding of anti-PF4 antibodies from patients with VITT (n = 5) was restricted to eight surface amino acids on PF4, all of which were located within the heparin-binding site, and that the binding was inhibited by heparin. By contrast, antibodies from patients with HIT (n = 10) bound to amino acids that corresponded to two different sites on PF4. Biolayer interferometry experiments also revealed that VITT anti-PF4 antibodies had a stronger binding response to PF4 and PF4–heparin complexes than did HIT anti-PF4 antibodies, albeit with similar dissociation rates. Our data indicate that VITT antibodies can mimic the effect of heparin by binding to a similar site on PF4; this allows PF4 tetramers to cluster and form immune complexes, which in turn causes Fc? receptor IIa (Fc?RIIa; also known as CD32a)-dependent platelet activation. These results provide an explanation for VITT-antibody-induced platelet activation that could contribute to thrombosis.
VITT is a rare but serious adverse effect of adenoviral vector vaccines against SARS-CoV-2. The clinical picture of VITT is moderate to severe thrombocytopaenia together with arterial and/or venous thrombi, often occurring in unusual locations1,2,3. These findings resemble the immunological drug reaction HIT, which presents clinically as thrombocytopaenia and thrombosis in patients who have previously been exposed to heparin4. VITT most closely resembles the exceptionally rare spontaneous HIT, which occurs in the absence of heparin6,7.
HIT is caused by immunoglobulin G (IgG) antibodies that bind to neoepitopes on PF4 (also known as CXCL4), a 70-amino-acid cationic protein that is contained within platelets8,9. The neoepitopes become exposed after heparin, a large anionic polysaccharide, binds to a specific site on PF4, which causes tetramers to cluster together. The IgG-specific antibodies bind to PF4–heparin to form immune complexes, which activate platelets through Fc?RIIa receptors, leading to an intense activation of platelets and the release of procoagulant-rich microparticles10. Other cells, including monocytes, are also activated by these immune complexes, which amplifies the hypercoagulable state in patients with HIT11. It has been postulated that VITT has a similar pathophysiology to HIT, and several studies have shown that high levels of anti-PF4 antibodies are present in samples from patients with VITT1,2,3,12. However, VITT is a unique syndrome as it occurs without heparin exposure, and the pattern of platelet reactivity in vitro does not exhibit the typical heparin dependence that is seen with HIT.
In this report, we describe the binding site and characteristics of anti-PF4 antibodies that developed in patients with VITT in response to vaccination against COVID-19 with an adenoviral vector. We found that patients with VITT had anti-PF4 antibodies that bound to a highly restricted site on PF4 that corresponds to the heparin-binding site. These antibodies can form platelet-activating immune complexes without heparin, potentially causing the thrombocytopaenia and clotting that are observed in VITT...
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Innovation Pharma - >>> Last Patient Last Visit Completed in Innovation Pharmaceuticals’ Phase 2 Clinical Trial of Brilacidin for COVID-19; Trial Database Undergoing Review in Preparation for Database Lock
Innovation Pharmaceuticals Inc.
August 12, 2021
https://finance.yahoo.com/news/last-patient-last-visit-completed-130000435.html
WAKEFIELD, Mass., Aug. 12, 2021 (GLOBE NEWSWIRE) -- Innovation Pharmaceuticals (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, today provided additional information regarding the status of its randomized, double-blind, placebo-controlled Phase 2 clinical trial of Brilacidin for the treatment of moderate-to-severe COVID-19 in hospitalized patients (see NCT04784897). The Company is developing Brilacidin for treatment of COVID-19 under U.S. FDA Fast Track designation.
Full enrollment in the 120-patient clinical trial was completed in early June 2021. The last patient follow-up visit occurred on July 30, 2021. The subject database remains blinded with the current emphasis on confirmation of all data entered at study sites, as well as completion of source data verification and the necessary checks and reviews by the data management vendor in preparation of database lock.
Following database lock and transfer to the biostatistics vendor, analysis of the unblinded data from the clinical trial will begin to assess Brilacidin’s performance, against placebo, across primary, secondary, and other endpoints. Topline results are anticipated to be available one week after database lock, with full analysis to follow.
“Our team is as excited as anyone to learn the results of our Brilacidin COVID-19 clinical trial. Everything is advancing per industry norms and standards,” said Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. “We look forward to sharing Brilacidin topline data in treating COVID-19 as soon as we have it in hand.”
About Brilacidin and COVID-19
Brilacidin is the only non-peptidic defensin-mimetic drug candidate currently in a clinical trial as a treatment for SARS-CoV-2, the coronavirus responsible for COVID-19 (see NCT04784897). Brilacidin has shown potent and consistent inhibition in vitro against coronaviruses, alphaviruses and bunyaviruses (with laboratory testing against other viruses also underway), supporting Brilacidin’s potential to be developed as a broad-spectrum antiviral. The annual global antiviral drug market is estimated to reach $44 billion by 2026.
A peer-reviewed article in Viruses supporting Brilacidin’s COVID-19 treatment potential can be accessed at the link below.
Bakovic, A.; Risner, K.; Bhalla, N. (et al). Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture. Viruses 2021, 13, 271; https://doi.org/10.3390/v13020271
https://www.mdpi.com/1999-4915/13/2/271/
Two independent Machine Learning studies identified Brilacidin as one of the most promising inhibitors of SARS-CoV-2, the virus responsible for COVID-19, based on Brilacidin’s molecular properties. Click here to learn more.
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About Innovation Pharmaceuticals
Innovation Pharmaceuticals Inc. (IPIX) is a clinical stage biopharmaceutical company developing a world-class portfolio of innovative therapies addressing multiple areas of unmet medical need, including inflammatory diseases, cancer, infectious diseases, and dermatologic diseases.
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>>> Why Dynavax, Novavax, and Sorrento Soared This Week
There were different reasons behind each of these COVID-19 vaccine stocks' big gains.
Motley Fool
by Keith Speights
Aug 13, 2021
https://www.fool.com/investing/2021/08/13/why-dynavax-novavax-and-sorrento-soared-this-week/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
Key Points
Novavax rebounded from last week's sell-off with a leak about the pricing of its EU supply deal.
Dynavax's momentum continued after a strong Q2 earnings report last week.
Sorrento announced a couple of new developments for its COVID-19 vaccine program.
What happened
Several stocks of companies hoping to make a big splash in the COVID-19 vaccine market soared this week. Shares of Novavax (NASDAQ:NVAX) were up 29.6% as of the market close on Thursday. Dynavax Technologies (NASDAQ:DVAX) stock jumped 19%. Sorrento Therapeutics (NASDAQ:SRNE) shares rose 9.8%.
Novavax rebounded from a sell-off last week after the company announced it was delaying the U.S. Emergency Use Authorization filing for COVID-19 vaccine candidate NVX-CoV2373 until the fourth quarter of 2021. On Wednesday, Denmark stated that it planned to buy 280,000 doses of NVX-CoV2373 for nearly $21 per dose.
Dynavax continued to enjoy momentum from its strong Q2 earnings report last week. Analysts also remain bullish about the stock with a consensus price target reflecting a premium of more than 45% above the current share price.
Sorrento had a couple of positive developments this week. On Monday, the company presented an overview of its messenger RNA (mRNA) COVID-19 vaccine development program. On Wednesday, Sorrento announced a deal to license Dyadic's lead COVID-19 vaccine candidate DYAI-100 and C1-cell protein production platform.
So what
The quality of the catalysts for these vaccine stocks this week varies. It probably makes sense that Novavax delivered the biggest gain.
Denmark's order of 280,000 doses isn't a big deal. However, the country inadvertently revealed the price tag that's applicable for the overall supply deal between the European Union and Novavax. That deal includes 100 million doses plus an option for an additional 100 million doses. Novavax stands to receive at least $2.1 billion and perhaps up to double that amount from its EU agreement.
Dynavax's continued uptrend also is understandable. The company just reported the best quarter ever for hepatitis B vaccine Heplisav-B. Revenue from its CpG 1018 adjuvant is also growing.
Of these three high-flying stocks this week, Sorrento arguably had the least impressive catalysts. The company's mRNA vaccine presentation didn't give investors any new information about the timing of progress for the program. Sorrento's licensing agreement with Dyadic hasn't been finalized yet. And it's for a program that hasn't advanced into clinical testing.
Now what
Novavax hopes to file for EUAs of NVX-CoV2373 in the U.K. in the third quarter with regulatory filings in the EU, Australia, Canada, and New Zealand coming within the following weeks. The company could win authorizations in India, Indonesia, and the Philippines even sooner.
Dynavax's upcoming milestones include a Centers for Disease Control and Prevention advisory committee vote in October on recommending hepatitis B vaccination for previously unvaccinated adults. Several of the company's partners using the CpG 1018 adjuvant should report clinical results by the end of the year as well.
Sorrento has plenty of irons in the fire. The company received a green light from the U.S. Food and Drug Administration to initiate a phase 1 study evaluating a cell therapy candidate in treating multiple myeloma. It's continuing a phase 2 study in the U.K. evaluating an experimental COVID-19 antibody therapy. Sorrento also plans to soon begin marketing COVID-19 tests in Mexico.
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>>> Why Axsome Therapeutics Is Plunging Again Today
Investors are losing hope in this promising biotech.
Motley Fool
by Zhiyuan Sun
Aug 10, 2021
https://www.fool.com/investing/2021/08/10/why-axsome-therapeutics-is-plunging-again-today/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article
What happened?
Shares of Axsome Therapeutics (NASDAQ:AXSM) are down 14% to $23.53 apiece as of 2:30 p.m. EDT after a brutal sell-off on Aug. 9 wiped out nearly 50% of its equity value. Investors are still upset that the U.S. Food and Drug Administration (FDA) outlined deficiencies in Axsome's New Drug Application filing for its central nervous system drug, AXS-05 -- which will lengthen the approval process.
So what
The FDA issued neither a complete response letter nor a refusal to file -- leading many shareholders to wonder if the stock is oversold in the face of a small blunder. But the setback did bring up a few issues. Axsome planned to submit its NDA filing for AXS-05 last year after the drug succeeded in a phase 3 study to treat depression, but it got delayed due to a COVID-19-related logistical delay from one vendor.
Now what
But the more important problem that came to light is the drug's composition. AXS-05 consists of Wellbutrin (or bupropion, an antidepressant) and dextromethorphan, a common ingredient in cough syrups. The company could run into problems protecting its intellectual property even if AXS-05 makes it to approval. Nothing is stopping pharmacies from compounding the drug, or even for patients themselves to buy over-the-counter cough syrup and mix it with their Wellbutrin prescription.
At this point, Axsome has a market cap of only $880 million. So investors are pretty much valuing the company's AXS-07 migraine drug and AXS-14 fibromyalgia drugs for next to nothing. And both drugs attained success in clinical studies. So even if AXS-05 fails to impress, the biotech stock is a good buy on the dip.
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>>> Why Axsome Therapeutics Stock Is Crashing Today
An unexpected regulatory setback is weighing on the biotech's shares today.
Motley Fool
George Budwell
Aug 9, 2021
Axsome's promising MDD drug candidate could take longer than expected to enter the market.
What happened
Shares of Axsome Therapeutics (NASDAQ:AXSM), a mid-cap biotech, are down by a hefty 41.4% as of 10:08 a.m. EDT Monday morning. The drugmaker's shares are tumbling today in response to a disappointing regulatory update for AXS-05 as a potential treatment for major depressive disorder (MDD).
Specifically, Axsome revealed during its 2021 second-quarter earnings release this morning that the U.S. Food and Drug Administration (FDA) had notified the company on July 30, 2021 that it has identified deficiencies within the drug's regulatory application that preclude discussion of labeling and post-marketing requirements at this time. A final decision on AXS-05's regulatory review for MDD is currently slated for Aug. 22, 2021.
So what
Wall Street expects AXS-05 to rake in over $1.3 billion in sales per year by the end of the current decade. With this sizable revenue stream now in question, it's not altogether surprising that some shareholders are hitting the exits today. That said, Axsome did note in its Q2 earnings release that the FDA has yet to communicate any specific details in regards to the application's deficiencies. In other words, shareholders might be making a mountain out of a molehill.
Now what
Is Axsome's stock a bad-news buy? Bargain hunters may indeed want to take advantage of this sharp pullback in the biotech's share price today. Axsome, after all, has multiple irons in the fire outside of its lead product candidate, and this regulatory setback could prove to be nothing more than an unfortunate delay in AXS-05's ultimate approval for MDD.
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Looking at the CRL that ACAD received in April, it appears the FDA arbitrarily changed the criteria for approval (see below). So a dishonest FDA, what else is new. And now they are using a similar tactic with AXSM.
Regulatory capture in action? Or perhaps other motivations, which in AXSM's case would be that the FDA and 'powers that be' need the MDD and TRD indications to remain devoid of alternate treatments in order to justify legalizing the new psych-meds (DMT, Psilocybin related, etc).
Like cannabis, the idea is to pave the way toward total recreational legalization of psychedelics by first touting them as medicines. The broader goal? To produce a stoned/stupid population staring at their navels, a similar strategy as used by the British Empire on the Chinese population during the 19th century Opium Wars, which produced a wiped out population too stoned to resist or cause trouble.
ACAD -
>>> Despite prior agreements with the Division of Psychiatry regarding the pivotal Phase 3 HARMONY study design targeting a broad DRP patient population analyzed as a single group, the Division, in the CRL, cited a lack of statistical significance in some of the subgroups of dementia, and insufficient numbers of patients with certain less common dementia subtypes as lack of substantial evidence of effectiveness to support approval.
The DRP pivotal HARMONY study met its prespecified primary and secondary endpoints with robust and persuasive clinical and statistical superiority of pimavanserin over placebo, which was a prospectively agreed prerequisite for the DRP indication. Statistical separation by dementia subgroups and certain minimum numbers of patients with specific subtypes were not among the prespecified requirements.
“Acadia stands behind the robustly positive results from the pivotal Phase 3 HARMONY study and the prospectively agreed trial design and criteria for establishing efficacy in DRP. Over the entire course of the review, the Division did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,” said Steve Davis, Chief Executive Officer of Acadia. “We will immediately request a Type A meeting to work with the FDA to address the CRL and determine an expeditious path forward for the approval of pimavanserin in DRP.”
The Division also stated in the CRL that it considers the Phase 2 Alzheimer’s disease psychosis study -019, a supportive study in the sNDA filing, to not be adequate and well controlled, citing that it was a single center study with no type I error control of secondary endpoints in which certain protocol deviations occurred. The Company believes these observations impact neither the positive results on the study’s primary endpoint, nor the study’s overall conclusions of efficacy.
There were no safety issues or concerns raised in the CRL.
sNDA Submission for Dementia-Related Psychosis
The sNDA submission of pimavanserin for the treatment of hallucinations and delusions associated with DRP was supported by results from the pivotal Phase 3 HARMONY study, which met its primary endpoint, demonstrating that pimavanserin significantly reduced the risk of relapse of psychosis by 2.8 fold compared to placebo (hazard ratio = 0.353; one-sided p=0.0023). Pimavanserin also met the key secondary endpoint in the study, significantly reducing the risk of discontinuation for any reason by 2.2 fold compared to placebo (hazard ratio = 0.452, one-sided p=0.0024). The sNDA also included positive efficacy results from two additional placebo-controlled studies, both of which met their respective primary endpoints: the Phase 2 (-019) study in patients with Alzheimer’s disease psychosis and the Phase 3 (-020) study in patients with Parkinson’s disease psychosis. In addition, the sNDA included a large safety database from completed and ongoing studies representing over 1,500 patients with neurodegenerative disease.
<<<
https://ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-receives-complete-response-letter-us-fda
AXSM - The FDA letter verbiage looks identical to ACAD's letter in March, which resulted in a CRL on the PDUFA date -
AXSM -
>>> On July 30, 2021, the Company received a letter from the FDA stating that it has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The letter stated further that the notification does not reflect a final decision on the information under review. The letter did not state what the deficiencies are. In response to the Company’s inquiries regarding the nature of the deficiencies since receipt of the letter, the FDA has informed the Company that their review is ongoing, but have not yet communicated any details regarding the nature of the deficiencies. The Prescription Drug User Fee Act (PDUFA) target action date for the NDA is August 22, 2021. <<<
ACAD - (from early March 2021)
>>> Acadia Pharmaceuticals today announced that the Company received a notification from the U.S. Food and Drug Administration (FDA) on March 3, 2021, stating that, as part of its ongoing review of the Company’s supplemental New Drug Application (sNDA), the FDA has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The FDA stated that the notification does not reflect a final decision on the information under review.
The notification does not specify the deficiencies identified by the FDA and there has been no clarification by the FDA at this time. The Company plans to work with the FDA to learn the nature of the deficiencies and seek to resolve them. In July 2020, the FDA assigned a Prescription Drug User Fee Act (PDUFA) action date of April 3, 2021 for completion of its review of the sNDA. <<<
>>> Axsome Therapeutics Announces AXS-05 Achieves Primary and Key Secondary Endpoints in the MERIT Phase 2 Trial in Treatment Resistant Depression
Axsome Therapeutics, Inc.
August 9, 2021
https://finance.yahoo.com/news/axsome-therapeutics-announces-axs-05-110000935.html
AXS-05 significantly delayed the time to relapse of depression compared to placebo (p=0.002, primary endpoint)
AXS-05 significantly prevented relapse of depression over at least 6 months compared to placebo (p=0.004, key secondary endpoint)
NEW YORK, Aug. 09, 2021 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today announced that AXS-05, a novel, oral, investigational NMDA receptor antagonist with multimodal activity, met the primary and key secondary endpoints in the MERIT (Mechanistic Evaluation of Response in TRD) Phase 2 trial, and substantially and statistically significantly prevented relapse of depressive symptoms compared to placebo in patients with treatment resistant depression (TRD). The MERIT study was a randomized, double-blind, placebo-controlled, relapse prevention, multi-center, U.S. trial, which evaluated 44 TRD patients. Patients in stable remission after treatment with AXS-05 were randomized to continue treatment with AXS-05 or to discontinue AXS-05 and switch to placebo.
AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of depressive symptoms as compared to placebo (p=0.002), with no relapses observed with AXS-05 over at least 6 months of double-blind treatment. AXS-05 also met the key secondary endpoint of relapse prevention, based on the rates of relapse during the double-blind treatment period (0.0% of AXS-05 patients, 36.4% of patients switched from AXS-05 to placebo, p=0.004).
AXS-05 was well tolerated in the trial. There were no treatment-emergent adverse events reported in >1 patient in the AXS-05 group. One subject in the AXS-05 group experienced two serious adverse events (gout and bacteremia), both of which were deemed not related to the study medication.
A new drug application (NDA) for AXS-05 for the treatment of major depressive disorder is under Priority Review by the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) target action date of August 22, 2021.
About the MERIT Study
MERIT was a Phase 2, randomized, double-blind, placebo-controlled, multi-center study to evaluate AXS-05 compared to placebo in preventing relapse of depressive symptoms in patients with treatment resistant depression (TRD). Treatment resistance was defined as ongoing symptoms of depression despite receiving treatment with two or more prior antidepressants during the current major depressive episode. TRD patients were enrolled into MERIT from the long-term, open-label Phase 3 trial of AXS-05, and were required to be in stable remission prior to randomization. Stable remission was defined as at least two consecutive Montgomery-Åsberg Depression Rating Scale (MADRS) scores of ≤12, separated by at least 4 weeks.
A total of 44 TRD patients who experienced a stable remission after up to 12 months of open-label treatment with AXS-05 (45 mg dextromethorphan-105 mg bupropion) tablets twice daily, were randomized 1:1 to continue AXS-05, or to discontinue AXS-05 and switch to placebo, in a double-blind fashion, for at least 26 weeks or until a relapse of depressive symptoms occurred. Relapse was defined in the study by one or more of the following: MADRS total score ≥18 for 2 consecutive assessments; a ≥2-point increase from randomization in the Clinical Global Impression of Severity, with a minimum CGI-S score of 4, for 2 consecutive assessments; hospitalization due to worsening of depression or risk of suicide; investigator determination of relapse or need for additional antidepressant or treatment switch.
The primary endpoint in the study was time from randomization to relapse calculated by the Kaplan-Meier estimates and the hazard ratio. The key secondary endpoint, to assess relapse prevention, was the percentage of patients without relapse.
About Major Depressive Disorder
Major depressive disorder (MDD) is a debilitating, chronic, biologically-based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, and which impairs social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. According to the National Institutes of Health, an estimated 7% of U.S. adults, or approximately 19 million, experience MDD each year1. According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease2. Nearly two-thirds of diagnosed and treated patients do not experience adequate treatment response with currently available first-line therapy3, highlighting the need for additional therapies with new mechanisms of action. The majority of initial failures also fail second-line treatment. Patients diagnosed with MDD are defined as having treatment resistant depression (TRD) if they have failed to respond to two or more antidepressant therapies.
About AXS-05
AXS-05 (dextromethorphan-bupropion) is a novel, oral, patent-protected, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of major depressive disorder and other central nervous system (CNS) disorders. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also known as a glutamate receptor modulator, which is a novel mechanism of action, meaning it works differently than currently approved oral therapies for major depressive disorder. The dextromethorphan component of AXS-05 is also a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is currently covered by more than 100 issued U.S. and international patents, with expiration dates out to 2040. AXS-05 has been granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy designations for the treatment of MDD and for treatment of Alzheimer’s disease agitation. A new drug application (NDA) for AXS-05 for the treatment of major depressive disorder is under Priority Review by the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of August 22, 2021. AXS-05 is not approved by the FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are intensely committed to developing products that meaningfully improve the lives of patients and provide additional therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
References
Substance Abuse and Mental Health Services Administration. (2020). Results from the 2019 National Survey on Drug Use and Health. Retrieved from https://www.samhsa.gov/data/.
World Health Organization. Fact Sheets: Depression.
Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).
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>>> Axsome Therapeutics Reports Second Quarter 2021 Financial Results and Provides Business Update
Axsome Therapeutics, Inc.
August 9, 2021
https://finance.yahoo.com/news/axsome-therapeutics-reports-second-quarter-110500963.html
Company to host conference call today at 8:00 AM Eastern
NEW YORK, Aug. 09, 2021 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today reported financial results for the second quarter ended June 30, 2021.
“As part of the ongoing review of our NDA for AXS-05, the FDA recently notified us that they have identified deficiencies that preclude labeling discussions at this time. We are attempting to learn the nature of these deficiencies with the goal of addressing them, however, this development may lead to a delay in the potential approval of AXS-05. We will keep you informed as we learn more,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Our other programs continue to advance. We successfully filed our NDA for AXS-07 for the acute treatment of migraine in the second quarter, and we remain on track to initiate the planned Phase 3 trial of AXS-12 for the treatment of narcolepsy this quarter. The buildout of our team and infrastructure is also continuing as we work towards our goal of delivering potentially life-changing medicines to people living with serious CNS conditions.”
Business Update
For the many people facing unsatisfactory treatments for CNS disorders, Axsome accelerates the invention and adoption of life-changing medicines. The Company is developing a portfolio of differentiated, patent-protected, CNS product candidates with four in active clinical development.
AXS-05
AXS-05 (dextromethorphan-bupropion) is Axsome’s novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for the following indications: major depressive disorder (MDD), Alzheimer’s disease (AD) agitation, and smoking cessation. AXS-05 has been granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy designations for MDD and for AD agitation.
Depression: Axsome’s New Drug Application (NDA) for AXS-05 for the treatment of MDD was granted Priority Review and is currently under review by the FDA. On July 30, 2021, the Company received a letter from the FDA stating that it has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The letter stated further that the notification does not reflect a final decision on the information under review. The letter did not state what the deficiencies are. In response to the Company’s inquiries regarding the nature of the deficiencies since receipt of the letter, the FDA has informed the Company that their review is ongoing, but have not yet communicated any details regarding the nature of the deficiencies. The Prescription Drug User Fee Act (PDUFA) target action date for the NDA is August 22, 2021.
Axsome has completed the MERIT trial, a Phase 2, randomized, double-blind, placebo-controlled, relapse prevention trial of AXS-05 in treatment resistant depression (TRD) patients. In a separate release issued this morning, Axsome announced that AXS-05 met the primary and key secondary endpoint in the trial. AXS-05 substantially and significantly delayed the time to relapse of depression (p=0.002, primary endpoint), and prevented relapse of depression (p=0.004, key secondary endpoint), compared to placebo.
AD Agitation: Axsome is conducting the ACCORD study, a Phase 3, double-blind, placebo-controlled, multicenter, randomized withdrawal trial to evaluate the efficacy and safety of AXS-05 in the treatment of Alzheimer’s disease (AD) agitation. Axsome anticipates completion of the trial in the fourth quarter of 2022.
Smoking Cessation: Axsome is scheduled to meet with the FDA in the third quarter to discuss the continued clinical development of AXS-05 as an aid to smoking cessation treatment. Axsome previously announced positive results from a Phase 2 trial of AXS-05 for smoking cessation treatment conducted under a research collaboration between Axsome and Duke University.
AXS-07
AXS-07 (MoSEIC™ meloxicam-rizatriptan) is Axsome’s novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for the acute treatment of migraine.
Migraine: Axsome submitted an NDA for AXS-07 for the acute treatment of migraine in the second quarter. The Company intends to announce the FDA’s decision regarding its acceptance of the NDA filing in the third quarter.
AXS-12
AXS-12 (reboxetine) is Axsome’s novel, oral, potent, and highly selective norepinephrine reuptake inhibitor for the treatment of narcolepsy. AXS-12 has been granted FDA Orphan Drug designation for the treatment of narcolepsy.
Narcolepsy: Axsome is on track to initiate a Phase 3 trial of AXS-12 in the treatment of narcolepsy in the third quarter. The planned Phase 3 trial will be a randomized, double-blind, placebo-controlled, parallel-group study.
AXS-14
AXS-14 (esreboxetine) is Axsome’s novel, oral, potent, and highly selective norepinephrine reuptake inhibitor for the management of fibromyalgia. Esreboxetine, the SS-enantiomer of reboxetine, is more potent and selective than racemic reboxetine.
Fibromyalgia: In June 2021, Axsome announced it had completed a pre-NDA meeting with the FDA for AXS-14. Axsome anticipates submitting an NDA for AXS-14 for the management of fibromyalgia in the fourth quarter of 2022, pending successful completion of manufacturing and other activities related to the product candidate. AXS-14 has previously met the primary endpoints and demonstrated positive and statistically significant results in a Phase 3 and in a Phase 2 trial for the management of fibromyalgia.
Commercial and Launch-Readiness Activities
Axsome continues with preparations for a potential commercial launch of AXS-05 for the treatment of MDD, if approved, and for a subsequent launch of AXS-07 for the acute treatment of migraine, if approved, including technology implementation and team build:
Axsome’s Digital Centric Commercialization™ (DCC) platform design and implementation is now complete and testing of the platform for execution at launch is underway.
Axsome’s field leadership team is now fully staffed and field force representative hiring has commenced. The Company anticipates having all field representatives on-board by launch.
The market access team continues to engage in permitted ongoing discussion with payers, ensuring awareness of Axsome and of AXS-05’s product profile, and is actively setting up comprehensive patient support services.
2021 Anticipated Milestones
Regulatory and Commercial:
AXS-05 for MDD, PDUFA target action date (August 22, 2021)
AXS-07 for migraine, NDA acceptance decision (3Q 2021)
AXS-05 for smoking cessation, FDA meeting (3Q 2021)
AXS-05 for MDD, commercial launch, if approved (4Q 2021)
Clinical Trial Initiations:
Phase 3 trial of AXS-12 in the treatment of narcolepsy (3Q 2021)
Upcoming Scientific Conferences
Axsome is scheduled to present data at the following upcoming scientific conferences:
International Headache Congress (IHC), September 8-12, 2021
Second Quarter 2021 Financial Results
Research and development (R&D) expenses: R&D expenses were $14.5 million for the three months ended June 30, 2021 and $10.5 million for the comparable period in 2020. The increase was driven by costs to support the NDA filings and personnel expense which includes an increase in headcount along with an increase in stock compensation expense.
General and administrative (G&A) expenses: G&A expenses were $16.3 million for the three months ended June 30, 2021 and $7.2 million for the comparable period in 2020. The increase was primarily due to pre-commercial activities and personnel expense which includes an increase in headcount along with an increase in stock compensation expense.
Net loss: Net loss was $32.3 million, or $(0.86) per share, for the three months ended June 30, 2021 compared to a net loss of $18.3 million, or $(0.49) per share, for the comparable period in 2020.
Cash: At June 30, 2021, Axsome had $141.2 million of cash compared to $183.9 million at December 31, 2020.
Shares outstanding: At June 30, 2021, Axsome had 37,648,948 shares of common stock outstanding.
Financial Guidance
Axsome believes that its cash at June 30, 2021, along with the remaining committed capital from the $225 million term loan facility, is sufficient to fund anticipated operations, based on the current operating plan, which includes costs for the potential commercial launch of AXS-05 in MDD and AXS-07 in migraine, into at least 2024.
Axsome expects that its operating expenses will increase year over year as we continue to build out the commercial function and further advance our pipeline.
Conference Call Information
Axsome will host a conference call and webcast today at 8:00 AM Eastern to discuss second quarter 2021 financial results as well as to provide a corporate update. To participate in the live conference call, please dial (844) 698-4029 (toll-free domestic) or (647) 253-8660 (international), and use the conference ID 2545435. The live webcast can be accessed on the "Webcasts & Presentations" page of the "Investors" section of the Company’s website at axsome.com. A replay of the webcast will be available for approximately 30 days following the live event.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are intensely committed to developing products that meaningfully improve the lives of patients and provide additional therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
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Axsome Therapeutics - >>> Buy This Stock Before Everyone Else Does
This biotech has significant upside left.
Motley Fool
by Prosper Junior Bakiny
Jul 14, 2021
https://finance.yahoo.com/m/5a273c54-5b77-3827-919e-981e3c8bddaa/buy-this-stock-before.html
Axsome Therapeutics is currently lagging in the market.
The company has two potential catalysts in the next few months that could send its stock price higher.
The biotech's long-term prospects are also appealing.
It can be stressful to watch shares of companies you own (or are thinking about buying) significantly underperform the market. But this also provides an opportunity to scoop up said company's stock on the dip -- if, of course, there are good reasons to think a rebound is in the cards. Take Axsome Therapeutics (NASDAQ:AXSM), a biotech whose shares have been struggling of late.
The drugmaker's stock is down by 21.98% in the past 12 months, compared to gains of 37.54% for the S&P 500. But this clinical-stage biotech has a lot going its way, and with a major potential catalyst in the near future, now might be an excellent time to purchase its shares. Let's look deeper into why Axsome Therapeutics could be a steal at current levels.
Mark this date on your calendar
Axsome Therapeutics doesn't have any products on the market, but that could change soon. The U.S. Food and Drug Administration (FDA) is currently reviewing the company's AXS-05, a potential treatment for major depressive disorder (MDD). The regulatory agency set a PDUFA goal date of Aug. 22 for the end of its review. There are good reasons to think AXS-05 will earn the green light from regulators.
In a phase 3 clinical trial, the medicine was shown to improve the symptoms of depression. The FDA granted AXS-05 priority review for the treatment of MDD, an honor reserved for medicines that would represent a significant improvement compared to the current standards of care for an illness. The priority review designation also comes with a six-month review period (as opposed to 10 months for regular applications).
What does the market opportunity look like for AXS-05? Depression was already a huge problem before the pandemic, but the events of the past year and a half have severely exacerbated the scope of this issue. Roughly 80 million people showed symptoms of depression during the outbreak, compared to 22 million prior.
Even if that number decreases as the pandemic subsides, it is unlikely to drop to or below pre-pandemic levels. In other words, there is a dire need for medicines like AXS-05. In my view, the drug has a good chance of topping $1 billion in sales within the next couple of years. If the FDA approves it, Axsome Therapeutics' stock will jump.
More reasons to jump in
Axsome Therapeutics is also developing AXS-05 as a potential treatment for Alzheimer's disease (AD) agitation (psychological and behavioral symptoms). This condition affects roughly 70% of the AD population in the U.S., or about 4 million people. The number of people with AD is projected to continue growing in the coming years.
AXS-05's potential in both AD and MDD looks very strong. But the company does have other candidates to consider as well. The most promising of the bunch is AXS-07, a potential migraine treatment. In December 2020, Axsome announced positive results from a phase 3 study for AXS-07 in this indication. The company said it would file a New Drug Application (NDA) for the medicine during the second quarter and announce the FDA's decision regarding acceptance of the NDA in the third quarter.
Given a patient population of 37 million, AXS-07 could also become an important growth driver for Axsome if approved. The biotech's other pipeline candidates include investigational treatments for narcolepsy and fibromyalgia.
A bright future
Axsome has two catalysts to look forward to within the next four months or so. First, there is the FDA's decision regarding AXS-05 as a treatment for MDD, and then there is the regulatory body's decision concerning the biotech's NDA for AXS-07 in treating migraine. If the company manages a win in both cases, expect its shares to get a noticeable boost.
More importantly, though, thanks to these medicines (and others), Axsome Therapeutics' long-term prospects look bright. Investors would do well to purchase shares of this biotech stock before they soar.
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Brilacidin - Bill DeGrado: 'De Novo Protein Design' presentation -
Axsome - >>> 3 “Strong Buy” Stocks Trading at Steep Discounts
TipRanks
August 2, 2021
https://finance.yahoo.com/news/3-strong-buy-stocks-trading-142616588.html
How do you define a stock market opportunity? Is it a windfall, a piece of luck, or the result of careful planning, a strategy to make the most of any opening? The savvy investor seeks out the latter, looking for stocks that offer inducements to entry, be it a high upside or a depressed share price or a recent positive analyst review – or better yet, a combination of all three.
So there’s a profile. We’ve used the TipRanks database to look up three stocks that fit it – stocks with Strong Buy consensus ratings, plenty of upside potential, and recent thumbs up from the analyst corps. And, while these stocks have plenty of positives in the profile, each one has also seen steep share price losses in recent weeks. Let's take a closer look.
Axsome Therapeutics (AXSM)
We’ll start with Axsome, a biopharma research company working on new medication therapies for diseases of the central nervous system (CNS). Axsome’s target conditions currently have limited treatment options – and also have a deep potential patient base. The company is researching medications with ‘novel mechanisms of action’ as a way to transform the approach to CNS treatment. The company is investigating treatments for a varied range of conditions, from Alzheimer’s, to fibromyalgia, to severe migraines, to depression.
Axsome currently has four drug candidates in the development pipeline. The leading candidate, AXS-05, is a multimodal treatment, developed to treat major depressive disorder, Alzheimer’s-related agitation, and smoking cessation. The depressive disorder track, for which AXS-05 has a breakthrough therapy designation, is farthest along – the New Drug Application has been submitted, and the FDA has given a PDUFA target date of August 22 this year. If approved, the company plans to launch commercially in 4Q21. On the Alzheimer’s track, AXS-05 is currently undergoing the Phase 3, double-blind ACCORD study. Enrollment is currently ongoing.
The next big update for the company is planned NDA submission for AXS-14, a new treatment for fibromyalgia. This drug candidate has competed two trials, a Phase 2 with 267 patients and a Phase 3 with 1,122 patients, both with positive results. Data from the trials will be included in the NDA submission, which is planned for Q4 of 2022.
Finally, Axsome has AXS-7 as a migraine treatment. This candidate has demonstrated effective pain relief in patients within two hours of dosing, and has a potential patient base of 37 million. The company has an NDA in preparation for this drug candidate, and hopes for approval next year.
The pipeline is the key point here, and Berenberg’s Esther Hong bases her Buy rating on the potential of AXS-05 as a treatment for major depressive disorder.
“We are bullish on the prospects and see a potential commercial launch in Q4 2021. Second, the company expects to submit a new drug application (NDA) with the FDA this quarter for a second product (AXS-07 for the treatment of migraine). Approval could come in 2022. We see opportunity for significant price appreciation over the remainder of the year driven by these key upcoming catalysts with longer-term upside from a robust pipeline,” Hong opined.
The analyst added, "We are bullish on the prospects for AXS-05 in MDD due to 1) its robust efficacy in treating depression as a result of its novel mechanism of action [MOA]; 2) the speed of efficacy compared to traditional antidepressants; and 3) a superior safety profile compared to other NMDA antagonist antidepressants..."
Hong puts a $112 price target on the stock, suggesting an upside of 123% for the year ahead. (To watch Hong’s track record, click here)
With a unanimous Strong Buy consensus rating, based on 8 recent reviews, it’s clear that Wall Street agrees with Hong on the potential of this stock. The shares fell in the past year, mainly due to regulator hurdles, but in the Street’s estimation, that has opened up an opportunity. The stock is selling for $50.27 and has an average target of $135.33, indicating room for ~170% upside potential this year. (See AXSM stock analysis on TipRanks)
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>>> Dynavax Announces Second Quarter 2021 Financial Results
Yahoo Finance
August 4, 2021
https://finance.yahoo.com/news/dynavax-announces-second-quarter-2021-200200653.html
Explore the topics mentioned in this article
- Second quarter 2021 total revenue of $52.8 million, which includes HEPLISAV-B's highest quarterly revenue to date at $13.7 million
- Executed multiple commercial supply agreements for CpG 1018® adjuvant with our COVID-19 vaccine collaborators
- Conference call to be held today at 4:30 p.m. ET/1:30 p.m. PT
EMERYVILLE, Calif., Aug. 4, 2021 /PRNewswire/ -- Dynavax Technologies Corporation (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, today reported financial results for the second quarter of 2021.
"Our successful execution in the second quarter of 2021 continued to build on the progress made in 2020. With the combined strength of opportunities from HEPLISAV-B and CpG 1018, we believe 2021 will be a transformational year for Dynavax," commented Ryan Spencer, Chief Executive Officer of Dynavax. "HEPLISAV-B achieved its highest quarterly revenue at $13.7 million and continues to increase market share, which reinforces our belief that it will become the standard of care in the U.S. for adult hepatitis B vaccinations."
Mr. Spencer continued, "Dynavax is also making progress on numerous collaborations for its proven CpG 1018 vaccine adjuvant across multiple indications, including COVID-19, pertussis, and universal flu. Our COVID-19 collaborations have advanced significantly in recent months with the execution of commercial supply agreements with Biological E and Clover Biopharmaceuticals, in addition to the two previously executed agreements with Valneva and Medigen. Multiple partners have reported that they currently intend to apply for emergency or conditional authorization for their COVID-19 vaccines in the second half of 2021. Importantly, these collaborations are generating meaningful revenue for Dynavax, with second quarter CpG 1018 revenue of $39 million. We continue to be excited about each of our partners' clinical programs and believe that the emerging portfolio of product opportunities with CpG 1018 adjuvant has the potential to continue generating meaningful future value for Dynavax."
HEPLISAV-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted]
Net product revenue for HEPLISAV-B was $13.7 million during the second quarter 2021, representing the highest quarterly HEPLISAV-B net sales to date, compared to $2.4 million for the second quarter 2020. This increase was primarily driven by continued success in the field targeted accounts and ongoing progress in national accounts.
Market share in accounts targeted by the field sales team increased to 30%, up from 21% in the second quarter of 2020.
Dynavax and Bavarian Nordic entered into a commercialization agreement for the marketing and distribution of HEPLISAV B in Germany.
CpG 1018® (Advanced Vaccine Adjuvant)
Net product revenue for CpG 1018 adjuvant during the second quarter 2021 was $39.0 million.
Dynavax and Biological E (Bio E) entered into a commercial supply agreement for the use of CpG 1018 adjuvant in the commercial production of Bio E's subunit COVID-19 vaccine candidate, CORBEVAX™. Upon completion of their Phase 2/3 and subsequently emergency use authorization (EUA) India's Union Ministry of Health has reserved 300 million doses of CORBEVAX™.
Dynavax and Clover Biopharmaceuticals entered into a commercial supply agreement for the use of CpG 1018 adjuvant in the commercial production of Clover's COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum). In parallel, Clover announced an advanced purchase agreement with GAVI to supply up to 414 million doses of SCB-2019 (CpG 1018/Alum) through 2022 for the COVAX Facility.
The Coalition for Epidemic Preparedness Innovations (CEPI) expanded its agreement with Dynavax to provide funding to manufacture CpG 1018 for CEPI's COVID-19 vaccine grantees, increasing total funding under the loan agreement from $99.0 million to $176.4 million to support Dynavax's manufacturing costs.
Medigen Vaccine Biologics Corporation received EUA from the Taiwan Food and Drug Administration and received approval for inclusion in Taiwan's COVID-19 vaccination immunization program for MVC-COV1901, its COVID-19 vaccine adjuvanted with CpG 1018.
Valneva SE reported positive initial results for Part A of the Phase 1/2 clinical trial of its COVID-19 vaccine candidate, VLA2001 adjuvanted with CpG 1018. Based on the positive results Valneva initiated a pivotal Phase 3 clinical trial, which is now fully enrolled. Valneva is also participating in a UK government-funded clinical trial looking at various COVID-19 'booster' vaccines.
Convertible Debt Offering
In May 2020, we issued $225.5 million in aggregate principal amount of 2.50% convertible senior notes due 2026. As of June 30, 2021, the aggregate principal amount of our Convertible Notes was $225.5 million, excluding debt discount of $5.5 million.
A portion of the net proceeds from the offering were used to pay off an existing $190.2 million term loan in full, including the termination payment. In connection with the offering, we also entered into capped call transactions with certain financial institutions that are expected generally to reduce the potential dilution to common stock in certain circumstances, upon conversion of the notes.
This debt refinancing is expected to reduce interest expense by approximately $12.1 million on an annualized basis.
Upcoming Milestones
CDC Advisory Committee on Immunization Practices expected to vote on a universal hepatitis b recommendation for all previously unvaccinated adults in October.
Multiple data readouts from our CpG 1018 COVID-19 collaboration partners with potential for emergency or conditional use authorization by the end of 2021.
Data from Tdap-1018 in the ongoing Phase 1 clinical trial, for an improved tetanus, diphtheria, and acellular pertussis booster vaccine candidate adjuvanted with CpG 1018 expected in first quarter 2022.
Financial Results
Total Revenue. Total revenues for the second quarter of 2021 were $52.8 million, including $52.7 million of net product revenue, an increase from total revenue for the second quarter of 2020 of $2.7 million.
Product Revenue, Net. HEPLISAV-B product revenue, net was $13.7 million in the second quarter of 2021 compared to $2.4 million in the same period in 2020. CpG 1018 product revenue, net was $39.0 million in the second quarter of 2021 and there was no revenue in the same period in 2020. As CpG 1018 revenues are generally recorded upon shipment to a customer, there may be fluctuations in revenues between quarters as shipments often consist of large-sized batches.
Cost of Sales - Product. Cost of sales - product for the second quarter 2021 increased to $14.8 million, compared to $1.0 million for the second quarter of 2020. The increase was primarily due to manufacturing costs for increased volumes of CpG 1018 and HEPLISAV-B sold to customers.
Research and Development Expenses (R&D). R&D expenses for the second quarter of 2021 increased to $7.2 million, compared to $5.9 million for the second quarter of 2020. The increase is primarily associated with higher headcount and outside services to support vaccine clinical and development activities.
Selling, General and Administrative Expenses (SG&A). SG&A expenses for the second quarter of 2021 increased to $21.6 million, compared to $19.0 million for the second quarter of 2020. This increase is primarily driven by compensation and related personnel costs, including non-cash stock-based compensation, associated with higher headcount.
Income (loss) from Operations and Net Income (loss). Income from operations for the second quarter of 2021 was $9.2 million compared to a loss from operations of $23.3 million in the second quarter of 2020. Net income for the second quarter of 2021 was $4.5 million compared to a net loss of $51.6 million for the second quarter of 2020.
Earnings per share. Basic and diluted net income per share were $0.04 and $0.02, respectively, for the second quarter of 2021, compared to basic and diluted net loss per share of ($0.53) and ($0.53), respectively, in the second quarter of 2020.
Cash Position. Cash, cash equivalents and marketable securities totaled $345.8 million at June 30, 2021.
Conference Call and Webcast Information
Dynavax will hold a conference call today at 4:30 p.m. ET/1:30 p.m. PT. The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company's website at www.dynavax.com. Alternatively, participants may dial (866) 420-4066 or (409) 217-8237 and refer to conference ID 9970706. A replay of the webcast will be available for 30 days following the live event.
Please see Important Safety Information below.
For more information about HEPLISAV-B, visit http://heplisavb.com.
About Hepatitis B
Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer and death. The hepatitis B virus is 50 to 100 times more infectious than HIV,i and transmission is on the rise. There is no cure for hepatitis B, but effective vaccination can prevent the disease.
In adults, hepatitis B is spread through contact with infected blood and through unprotected sex with an infected person. The U.S. Centers for Disease Control (CDC) recommends vaccination for those at high risk for infection due to their jobs, lifestyle, living situations and travel to certain areas.ii Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults age 19 to 59 with diabetes as soon as possible after their diagnosis, and for people age 60 and older with diabetes at their physician's discretion.iii Approximately 20 million U.S. adults have diabetes, and 1.5 million new cases of diabetes are diagnosed each year.iv
About HEPLISAV-B
HEPLISAV-B is an adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax's proprietary Toll-like Receptor (TLR) 9 agonist CpG 1018 to enhance the immune response. Dynavax has worldwide commercial rights to HEPLISAV-B.
Important U.S. Product Information
HEPLISAV-B is indicated for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older.
Safety and effectiveness of HEPLISAV-B have not been established in adults on hemodialysis.
For full U.S. Prescribing Information for HEPLISAV-B, click here.
Important U.S. Safety Information (ISI)
Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B. Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration. The most common patient reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%) and headache (8% to 17%).
Important EU/EEA Product Information
HEPLISAV B is indicated for active immunisation against hepatitis B virus infection (HBV) caused by all known subtypes of hepatitis B virus in adults 18 years of age and older.
The use of HEPLISAV B should be in accordance with official recommendations.
It can be expected that hepatitis D will also be prevented by immunization with HEPLISAV B as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
For full EU/EEA. Prescribing Information for HEPLISAV-B, click here.
Important EU/EEA Safety information
Do not receive HEPLISAV B if you have had a sudden life-threatening, allergic reaction after receiving HEPLISAV B in the past, or if you are allergic to any of components of this vaccine, including yeast. Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face or tongue.
Appropriate medical treatment and supervision should be readily available in case of rare anaphylactic reactions following the administration of the vaccine.
The administration of HEPLISAV B should be postponed in subjects suffering from acute severe febrile illness.
Immunocompromised persons may have a diminished immune response to HEPLISAV B.
Because of the long incubation period of hepatitis B, it is possible for unrecognised HBV infection to be present at the time of immunisation. HEPLISAV B may not prevent HBV infection in such cases.
There are very limited data on the immune response to HEPLISAV B in individuals who did not mount a protective immune response to another hepatitis B vaccine.
As a precautionary measure, it is preferable to avoid the use of HEPLISAV B during pregnancy. Vaccination during pregnancy should only be performed if the risk-benefit ratio at the individual level outweighs possible risks for the fetus.
The most common patient-reported side effects reported within 7 days of vaccination were pain, swelling or redness at the injection site, feeling tired, headache, muscle aches, feeling unwell and fever.
About CpG 1018 Adjuvant
CpG 1018 is the adjuvant used in HEPLISAV-B. Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response, which has been demonstrated in HEPLISAV-B. CpG 1018 adjuvant provides a well- developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of a COVID-19 vaccine.
About Dynavax
Dynavax is a commercial stage biopharmaceutical company developing and commercializing novel vaccines. The Company's first commercial product, HEPLISAV-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted], is approved in the U.S. and the European Union for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. Dynavax is also advancing CpG 1018 adjuvant as a premier vaccine adjuvant through research collaborations and partnerships. Current collaborations are focused on adjuvanted vaccines for COVID-19, pertussis and universal influenza. For more information, visit www.dynavax.com and follow the company on LinkedIn.
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Brilacidin - >>> Antibiotic Artisan
Forbes
Jan 26, 2011
Robert Langreth
https://www.forbes.com/forbes/2011/0214/technology-william-degrado-chemistry-biotech-antibiotic-artisan.html?sh=4246b8f3bdce
The biotech industry creates new drugs by making tweaks to natural proteins. University of Pennsylvania chemist William DeGrado is more of an artist than a tweaker. He has spent much of his career designing new proteins from scratch, a three-dimensional engineering task so complicated that until recently few scientists bothered to try. His goal is to create molecules unknown to nature but adept at serving humans by absorbing environmental toxins, fighting cancer or extending Moore's Law down to the atomic scale.
These applications are years away. But DeGrado's interest in creating artificial molecules that mimic more complex natural ones may have a more immediate payoff: a powerful new generation of antibiotics.
Scientists have known for decades that organisms as diverse as insects, frogs, pigs and humans make natural protein-based antibiotics to ward off microbes. These chemicals are one of life's most ancient defenses. They attack microbes in a unique way that makes it hard for resistance to develop.
Drugmakers have tried to bottle their power, but the compounds, known as antimicrobial peptides, have proven to be poor drugs. They are difficult to manufacture, unstable in the bloodstream and prone to toxic side effects. A drug based on pig chemicals failed to prevent pneumonia in hospital patients in a 2006 study. Another drug, from the African clawed frog, was rejected in 1999 by the FDA as a treatment for diabetic foot ulcers. Because of the peptides' high cost and unclear safety profile, "Big Pharma has abandoned them," says Georgetown University researcher Michael Zasloff.
DeGrado, with the help of a powerful supercomputer simulation, has created new antibiotics that mimic natural ones but are far simpler to produce and more stable. They capture the essence of animal antibiotics in molecules that are one quarter the size and can be made with standard chemistry techniques. The supercomputer work "was absolutely critical" in crafting the antibiotic, says DeGrado. "It narrowed the choices tremendously [and converted it] from an intractable problem to a feasible one."
The first antibiotic from this work is now in human trials at the biotech firm PolyMedix, which DeGrado cofounded in 2002. In animal tests PolyMedix's drug PMX-30063 is at least as powerful as the gold standard hospital antibiotic vancomycin at killing key strains. The initial effectiveness trial in staph skin infections could yield results this year.
New antibiotics are badly needed as bacteria become resistant to existing drugs. Because existing antibiotics target specific bacterial molecules, a mutation in the bacterium can render the drugs ineffective. One nasty bug inhabiting American hospitals, methicillin-resistant Staphylococcus aureus, is linked to 18,650 deaths each year, a 2007 study concluded. In contrast, the peptide antibiotics are less vulnerable to resistance because they infiltrate and damage the membrane that holds the bacterium together.
In 2000 DeGrado became curious about what was the simplest possible molecule that could mimic this membrane-infiltrating ability. He realized that the key was a two-sided structure. One side is attracted to negatively charged molecules on the surface of bacterial membranes. This, among other things, helps it to distinguish bacteria from human membranes, which have a less negative charge. The other side of the antibiotic contains an oily surface that is attracted to the greasy interior portion of the membrane.
Doodling on a scrap of paper with postdoctoral student Gregory Tew (now a professor at the University of Massachusetts), DeGrado came up with a crescent-shaped molecule that was somewhat similar to the polymer Kevlar used in bulletproof vests. He wasn't sure it would work, so he took it across the campus to molecular modeling expert Michael Klein. Klein took one look and was convinced that DeGrado was on to something. "I was so excited that I got [DeGrado] to sign and date the paper and gave it to my secretary" for safekeeping, recalls Klein, now at Temple University.
Klein devised a supercomputer simulation to predict in practically atomic detail what would happen when DeGrado's molecule collided with a bacterium's membrane. Each "frame" of the movie represents a fraction of a nanosecond and involves 1 million calculations. The simulation took nearly three months to perform at the Pittsburgh Supercomputing Center and revealed that DeGrado's instincts were on target. "What we discovered with the simulation is that these things dive into the membrane and swim around underneath," says Klein. "When there is enough of them they make their way to the other side of the membrane and make a pore." The bacterium's contents leak out. Lab experiments confirmed that this is what happens.
DeGrado and Klein published their initial results in 2002 and cofounded PolyMedix the same year. It took six years to design and test a molecule safe and effective enough to go into human trials. No resistance to PolyMedix' drug has emerged in standard lab tests. Klein says the continuous simulations give chemists confidence they are on the right track. "Our role is often psychological. A good scientist has intuition. If we can build a model that reinforces that intuition, they have confidence to extrapolate to the next level."
Wall Street remains skeptical. PolyMedix shares hover around a dollar. A key question is whether the drug will be able to distinguish bacteria from host as it goes about its killing business. PolyMedix Chief Executive Nicholas Landekic is optimistic--there have been no showstopper safety problems so far--but only big human trials can tell for sure.
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Regeneron Pharmaceuticals Inc | REGN | 2.77% |
Moderna Inc | MRNA | 2.65% |
Gilead Sciences Inc | GILD | 2.43% |
Vertex Pharmaceuticals Inc | VRTX | 2.32% |
Biogen Inc | BIIB | 2.28% |
United Therapeutics Corp | UTHR | 2.26% |
Biomarin Pharmaceutical Inc | BMRN | 2.25% |
Seattle Genetics Inc | SGEN | 2.16% |
Exelixis Inc | EXEL | 2.06% |
ACADIA Pharmaceuticals Inc | ACAD | 2.04% |
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---|---|---|
Regeneron Pharmaceuticals Inc | REGN | 4.88% |
Gilead Sciences Inc | GILD | 4.58% |
Qiagen NV | QGEN | 4.48% |
Biogen Inc | BIIB | 4.28% |
Seattle Genetics Inc | SGEN | 4.08% |
United Therapeutics Corp | UTHR | 3.93% |
Vertex Pharmaceuticals Inc | VRTX | 3.89% |
ACADIA Pharmaceuticals Inc | ACAD | 3.75% |
Biomarin Pharmaceutical Inc | BMRN | 3.69% |
Alnylam Pharmaceuticals Inc | ALNY | 3.53% |
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---|---|---|
Pacific Biosciences of California Inc | PACB | 6.85% |
Teladoc Health Inc | TDOC | 5.94% |
CRISPR Therapeutics AG | CRSP | 5.77% |
Twist Bioscience Corp | TWST | 5.72% |
CareDx Inc | CDNA | 3.87% |
Iovance Biotherapeutics Inc | IOVA | 3.59% |
Exact Sciences Corp | EXAS | 3.58% |
Fate Therapeutics Inc | FATE | 3.47% |
Invitae Corp | NVTA | 3.42% |
Personalis Inc | PSNL | 3.26% |
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