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Thanks for posting .Nice summary of defensin's pharmacologic properties.The good news is the properties attributed to natural defensins have been found in Brilacidin. The graphs in the article demonstrate many of the properties proven to be in Brilacidin:
antibiotic, antiviral, immune modulation, immune stimulation of T cells and B cells to fight infection, intracellular interruption of viral DNA and halt of viral protein synthesis,blocks viral entry.
"Defensin acts on the membrane or envelopes wall by its amphipathic nature"
Interesting to note natural defensins have been shown to block viral binding site for not only Coronavirus,but influenza, Ebola and Lassa viruses.
The George Mason RBL has done a number of studies regarding defensins prior to the Covid 19 epidemic. They are aware of their properties and have already found Brilacidin to have activity against Alpha Viruses {including Encephalitis} bunyaviruses as well as Coronavirus.
I am looking forward to the July American Society of Virology presentation to see what new properties of Brilacidin have been discovered.
GLTA,Farrell
https://www.globenewswire.com/news-release/2021/06/18/2249692/0/en/Innovation-Pharma-Announces-New-Brilacidin-Antiviral-Research-on-Non-SARS-CoV-2-Endemic-Viral-Diseases-to-be-Presented-at-the-2021-Military-Health-System-Research-Symposium.html
https://science.gmu.edu/news/innovation-pharmaceuticals-and-george-mason-university-release-laboratory-testing-results
https://science.gmu.edu/news/innovation-pharmaceuticals-and-george-mason-university-release-laboratory-testing-results
https://www.globenewswire.com/en/news-release/2021/04/14/2210088/0/en/Innovation-Pharma-s-Broad-Spectrum-Antiviral-Drug-Candidate-Brilacidin-Highlighted-in-Biodefense-and-Infectious-Diseases-COVID-19-Presentation.html
Brilacidin was tested against the Washington and Italian virus strains in the RBL in vitro studies.
"This assay was performed using two different strains of SARS-CoV-2 (Washington strain-nCoV/USA-WA1/2020 and Italy strain-Italy-INMI1)"
https://www.mdpi.com/1999-4915/13/2/271/htm
In the Phase 2 study no mention is made of testing for different strains or variants. Basically anyone testing postive for Covid19 that met the study inclusion guidelines is eligible for treatment.
Russia reported last week the Covid 19 delta variant is producing a third wave of infection and accounts for 90% of the new cases.It would seem likely some of the treated cases would be the delta variant.
https://www.dw.com/en/covid-19-russia-battles-delta-variant-in-deadly-3rd-wave/av-58072948
I will send an email to IPIX to see if testing and treatment of variants is a part of the study.
GLTA, Farrell
Lilly's Covid 19 drugs, bamlanivimab and etesevimab, paused due to poor activity against Beta and Gamma Covid19 variants. Its EUA was previously revoked.
Bamlanivimab and etesevimab were approved for use only in high risk patients with mild to moderate Covid19
"Due to the presence of variants, the US said Friday that it’s pausing shipments of Eli Lilly’s monoclonal antibody combo for the treatment of Covid-19 on a national basis until further notice.
The pause, which could amount to the loss of about $375 million in sales according to one biotech analyst, is another blow to Lilly’s efforts to treat Covid-19 outside of the hospital, as the company previously had its EUA for bamlanivimab revoked.
“The CDC identified that the combined frequencies of the SARS-CoV-2 P.1/Gamma variant (first identified in Brazil) and the B.1.351/Beta variant (first identified in South Africa) throughout the United States now exceed 11% and are trending upward,” John Redd, CMO of the Office of the Assistant Secretary for Preparedness and Response, said in a letter obtained by Endpoints News.
“Results from in vitro assays that are used to assess the susceptibility of viral variants to particular monoclonal antibodies suggest that bamlanivimab and etesevimab administered together are not active against either the P.1 or B.1.351 variants,” Redd wrote."
https://endpts.com/us-pauses-use-of-eli-lillys-covid-19-treatment-nationwide-due-to-variants/
GLTA Farrell
CDC states Covid vaccines likely related to myocarditis.
"There have been more than 1,200 cases of a myocarditis or pericarditis mostly in people 30 and under who received Pfizer’s or Moderna’s Covid-19 vaccine, according to CDC data."
JMO this risk balanced against the small benefit from Covid vaccination for young people is unacceptable. The M RNA vaccines should be limited to older individuals.
GLTA Farrell
https://www.cnbc.com/2021/06/23/cdc-reports-more-than-1200-cases-of-rare-heart-inflammation-after-covid-vaccine-shots.html
I do not think it is untenable for countries outside of N America and Europe to pay for Brilacidin for Covid19. Covid has and will ruin economies and overwhelm healthcare systems. The logic for treatment is simple...it will save them money and preserve their economies.
Glta, Farrell
White Square's closing may be due to a more fundamental change...their backers are backing out.
"In the investor letter announcing the fund’s closure, White Square said that last year, despite that year’s strong performance, two large investors had opted to withdraw their cash and put it in cheap passive funds or private equity. “We experienced first-hand the shift in trend away from hedge fund investing to cheaper alternatives,” it added."
https://www.ft.com/content/397bdbe9-f257-4ca6-b600-1756804517b6
GLTA, Farrell
If the Brilacidin phase 2 study confirms efficacy against Covid there will be intensive research to develop alternate delivery systems.
IPIX has already announce its interest in developing an inhaler for Covid. Small peptides are already available for clinical use eg insulin inhaler
Other possible options include depo intramuscular injections
eg DepoMedrol DepoProvera
Trans dermal eg nitrate patches
Developing oral medications from IV pharmaceuticals has become an area of research and development. The article below summarizes some of this research:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471246/
"To meet the increasing demand for biopharmaceutical oral products, research has been focused on developing devices for oral delivery. While still at an early stage, recent devices include intestinal patch systems, microneedle capsules and particulate systems [51]. The intestinal patch systems are based on a unidirectional drug release depot, which is similar to a microdevice adhered to the intestinal wall [52]. The microneedle capsule increases the penetration rate of drug molecules by piercing the mucosa directly with microneedles. A recent study developed a method to inflate a microneedle into the mucosa by responding to the change in pH [53]. Particulate devices are the most common oral vehicles, which have been investigated for the encapsulation and targeting of a vast variety of therapeutics. In general, the current technologies are still at the preclinical stage. Therefore, more research efforts should be directed to solve the existing technical challenges of oral drug delivery systems and prove the feasibility in clinical use."
GLTA Farrell
Good point. The military stock piles pharmaceuticals. A DOD, Department of Defense,contract would be very lucrative.
Why would that be of interest to the military?
Because infectious diseases around the world interfere with military preparedness.
An army can not move if the soldiers are in the infirmary.
GLTA,
Farrell
Wow 10 million for Brilacidin phase 3 and 2.99 million Brilacidin EUA doses @ 1000 a dose.
Good to see Biden planning ahead.
GLTA Farrel
It's just so quiet....but is it?
Good luck to all,
Farrell
There are a number of examples of the FDA issuing EUA's after smaller studies.
The most recent was Sotrovimab
Sotrovimab study was stopped before it was completed due to the interim analysis. We do not know how many were treated , but 583 were approved for treatment before the trial was stopped.
"The data supporting this EUA for sotrovimab are based on an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result."
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19
GLTA, Farrell
I have reviewed the viruses article again. I do not understand your concerns.
The in vitro tests are just for a few hours, but Brilacidin will be dosed over 5 days which should result in virtual elimination of Covid 19 very quickly. Its virucidal property will be accentuated by its direct antiviral action in the plasma since Brilacidin is not a prodrug.
Brilacidins half life is long, not short, and has been reported to be up to 23 hours with "consistent and linear pharmacokinetics in plasma"
Remember in ABSSI one IV dose of Brilacidin was equivalent to 1 week of Daptomycin.
https://static1.squarespace.com/static/5715352e20c647639137f992/t/583f8286d2b85731b8713a36/1480557192947/A-Randomized-Double-Blind-Study-Comparing-Single-Dose-and-Short-Course-Brilacidin-to-Daptomycin-in-the-Treatment-of-Acute-Bacterial-Skin-Skin-Structure-Infections-ABSSSI1.pdf
The IC 50 dose is .565 um; IC 90 was 2.63 um while the maximum serum level in ABBSI was 7.67 um at .6mg/kg
Brilacidin's serum level is 13.5 greater than the IC50 and 3 times greater than the IC90 which should give a nice margin of effectiveness against Covid19 with Brilacidin's long half life . In addition the peak and trough levels should increase with each IV dose.
Fortunately safety is not a concern with Brilacidin.The paresthesias were all transient and the BP would be easily treatable if it became elevated to significant levels.Neither should play a significant role when treating a life threatening disease like Covid19.
Of course all of this is a guess at this point since we do not know the dose given in the phase 2 clinical trial.
It is possible the most important attribute of Brilacidin for Covid19 could prove to be its anti-inflammatory properties.
We will find out when the Phase 2 results are available.
GLTA,Farrell
What we know is Remdesivir has been studied in multiple clinical trials leading many experts to conclude it just does not work well on the mild,moderate, or severely ill Covid 19 patients.
The articles I posted demonstrate Remdesivir's in vitro promise could not be fulfilled due to its pharmacologic short comings which limit its effective dose.
Brilacidin's studies to date suggest it will be able to treat Covid19 due to the properties discovered in the RBL and reported in the Viruses article.
Fortunately Brilacidin is demonstrating tremendous promise.
"Its virucidal mechanism of action means it kills Covid19 on contact. It does not have to be converted to an active form so with infusion it kills the virus at first in the serum. With its good pharmcokinetics and high SI number it is well distributed throughout the body and kills the virus in the extracellular spaces as well as inside the cells. It was shown in the Viruses publication to block entry of Covid19 in the cells. And, computer modeling suggests it can disrupts the viral M-protein of Covid19 to prevent viral replication.
These multiple mechanisms of action, high SI number and safety all should make Brilacidin a superior antiviral, but also be active against Covid variants. It should make viral resistance much less likely."
Of course many promising drugs have failed in clinical trials.
Time will tell if Brilacidin will prove effective in its clinical trials against Covid19
GLTA,
Farrell
Fortunately Brilacidin is not limited by these factors.
Its virucidal mechanism of action means it kills Covid19 on contact. It does not have to be converted to an active form so with infusion it kills the virus at first in the serum. With its good pharmcokinetics and high SI number it is well distributed throughout the body and kills the virus in the extracellular spaces as well as inside the cells. It was shown in the Viruses publication to block entry of Covid19 in the cells. And, computer modeling suggests it can disrupts the viral M-protein of Covid19 to prevent viral replication.
These multiple mechanisms of action, high SI number and safety all should make Brilacidin a superior antiviral, but also be active against Covid variants. It should make viral resistance much less likely.
We will know for sure soon.
GLTA, Farrell
Remdesivirs in vitro studies were one of the reasons it was quickly studied for Covid 19. Unfotunately further studies showed it lack efficay against Covid 19. Why?
Redesivir's poor clinical showing in spite of relative good in vitro studies is due to its hepatic toxicity which limits higher dosing and its relatively complicated conversion to its active metabolite requires an intracellular conversion.
https://www.statnews.com/2020/05/14/gilead-should-ditch-remdesivir-and-focus-on-its-simpler-safer-ancestor/
"Remdesivir’s lackluster results in patients with advanced Covid-19 in the NIAID-sponsored trial and the finding that it provided no statistically significant benefit in a clinical trial conducted in China among patients with severe Covid-19 symptoms are likely due to the suboptimal level of active GS-441524 triphosphate in the lungs. Patients with advanced or severe Covid-19 generally have a high viral load in their lungs and would need a high concentration of GS-441524 triphosphate to combat it. The benefit of using GS-441524 over remdesivir is that GS-441524 can almost certainly be given at much higher doses due to its lower toxicity. This would result in more conversion to the active compound, GS-441524 triphosphate, in the lungs."
Remdesivir IC 50 in vitro is .77um, but it has to enter the host cells to prevent intracellular viral reproduction. Remdesivir is a prodrug and is converted inside the cell to its active metabolite which is estimated to have an IC 50 of 38um to 231um or 7.7um in other studies, well below that of Brilacidin's IC 50 of .565um.
Its pharmacology explains Remdesivir's poor clinical performance in spite of a relatively good in vitro IC 50.
In addition Remdesivir's hepatotoxicity limits higher dosing.
"Assuming similar distribution and accumulation ratios of remdesivir and Nuc-TP in the lung between humans and monkeys, an optimistic estimation of Nuc-TP in the human lung tissues is 2 to 3-fold higher at a steady state than that observed in the monkey lung tissues [1]. This suggests that an IV dose of 200 mg remdesivir in a human may only achieve a suboptimal concentration of active form of Nuc-TP of <?2–5 µM in the human lung tissues (TableIII). Given that the intracellular volume (0.54 l) is 46% of the total volume of the lung (1.17 l) [17], the intracellular concentration of Nuc-TP in the human lung may be only at 4–10 µM (TableIII), which may be below the estimated intracellular IC50 and IC90 of Nuc-TP. Unfortunately, systemic adverse effects such as hepatotoxicity preclude escalation of the remdesivir dose to more than 200 mg/day."
The following article demonstrates these findings in great detail.
https://link.springer.com/article/10.1208/s12248-020-00459-8
GLTA,Farrell
Alfasigma planning clinical trial of Brilacidin for Ulcerative Proctitis
from 10Q May2021
...in the pipeline, Alfasigma S.p.A. (“Alfasigma”)—the licensee of worldwide rights to develop, manufacture and commercialize rectally-administered Brilacidin for treatment of Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS)—notified the Company, in April, of its intentions to commence, in 2021, a Phase 2 multinational clinical trial of Brilacidin for UP/UPS. Alfasigma has placed an order with the Company for Brilacidin drug substance needed for the trial, which the Company is in the process of supplying. Per the licensing agreement, Innovation Pharma is eligible to receive $24 million in upfront and milestone payments, and a 6 percent royalty (net sales), upon the successful marketing of Brilacidin for UP/UPS."
"Ehrlich continued: “Elsewhere, it was exciting to learn that Alfasigma is planning to commence a Phase 2 trial of Brilacidin for treatment of UP/UPS this year, which complements our goal to develop oral Brilacidin in Inflammatory Bowel Diseases. That Alfasigma is investing substantial resources and monies in the clinical development of Brilacidin is a reassuring sign they continue to see therapeutic promise and commercial merit in Brilacidin in the area of IBD, as do we. Development work related to the formulation and manufacture of Brilacidin in capsule form is underway to support our Phase 2 trial in Ulcerative Colitis planned to commence this year. Additional work tied to starting, in 2022, a planned Phase 3 study of Brilacidin in Oral Mucositis is also in progress. We aim to maintain momentum across our clinical programs.”
Every positive result takes Brilacidin another step forward and lowers the risk of my investment
GLTA,Farrel
Agree very well written.
Glta,Farrell
"In studies with serious outcomes, all parties would wish that any major treatment advance be identified and made available as soon as possible. It is critical, however, that the study yield a valid and definitive result. Thus, tensions between ethical and scientific considerations may arise. Consider, for example, a placebo-controlled trial of a new product for a serious illness or condition for which there is no standard treatment. If the emerging data suggest that those receiving the treatment are doing better, one might expect that a DMC would consider whether the study should be terminated earlier than planned. Estimates of treatment effect, however, will be unstable at early points in a study, and the chance is substantial of observing a nominally statistically significant benefit (e.g., p<0.05) at one of multiple interim analyses during a study of an ineffective product (see Section 4.4.2). A DMC, guided by a pre-specified statistical monitoring plan acceptable to both the DMC and the study leadership, will generally be charged with recommending early termination on the basis of a positive result only when the data are truly compelling and the risk of a false positive conclusion is acceptably low."
https://www.fda.gov/media/75398/download
GLTA, Farrell
.49 cent shares {$4.9 post split} I bought in March are looking better every day.
GLTA Farrell
I hope you are right. I would be delighted if the Brilacidin for Covid 19 results are so positive it would get an immediate pass to an EUA.
Pfizer on the other hand may be hesitant to submit another drug for an early EUA after Merck's experience.
Merck partnered with Oncoimmune for their graft vs host drug for Covid 19 and surprisingly got rejected. Then,in spite of a good Covid 19 anti-inflammatory study; they pulled the drug.
Then you couple that with Cytodyn's experience it appears the FDA is becoming less welcoming.
GLTA,
Farrell
https://www.fiercebiotech.com/biotech/fda-tells-merck-told-to-show-more-data-for-its-oncoimmune-covid-drug-as-eua-pushed-back
https://www.merck.com/news/merck-to-discontinue-development-of-mk-7110-for-covid-19/
https://www.biospace.com/article/releases/oncoimmune-s-saccovid-cd24fc-exhibits-superb-therapeutic-efficacy-a-potential-breakthrough-in-treating-severe-and-critical-covid-19/
Kevetrin is a P53 drug. Unless the tumor genetic profile testing also showed a P53 mutation it is unlikely to be effective.
Many cancers have multiple genetic mutations. P53 mutations are not uncommon in non small cell lung cancer.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-019-0910-2
Hopefully IPIX will have the resources to study Kevetrin completely some day.
GLTA Farrell
It will be interesting to see if Sotrvimab is the first monoclonal antibody approved for mild to moderate Covid19. Most of the other monoclonals are now seeking approval for prophylaxisis in high risk patients since they were unable to show efficacy in the mild,moderate or severely ill Covid 19 patients.
Sotrovimab had some very positive attributes. It was effective at a low dose,it appears to be reasonably safe with good pharmocokinetics.
You can look at statistics in different ways. The authors summary showed statistical validity:
... interim study results demonstrated an 85% (p=0.002) reduction in hospitalization for more than 24 hours or death in those receiving sotrovimab compared to placebo.
Another way to look at the results was they treated 583 high risk patients to prevent 1 death and 18 hospitalizations {21-3}.
While that would probably warrant approval in the US, Japan or EU. I am not sure that other countries would find that calculation enough of a value to extend treatment to the high risk individuals.
The other monoclonal antiboies for Covid failed to show good results when large numbers of patients were treated.
We will have to wait until Sotrovimab completes its studies.
GLTA Farrell
The employees of the CDC should be the best informed group in the world to decide the value of Covid vaccination.
Why isn't their vaccination rate a 100%?
During the hearings one of the panel discussed the efforts of the CDC to increase the vaccination rates. Do they believe they can further educate this group? Why is that necessary?
Some of the answers are there are real concerns about the value of the vaccine especially to the young and healthy.There are concerns the vaccine was rushed through testing.Concerns regarding the long term side effects. Concerns that previous MRNA vaccines not only failed animal testing ,but result in the deaths of most of the animals.
That being said I took the vaccine because I felt my exposure to the the public and other factors put me and my family at a higher risk of infection.
Everyone's situation is different and many very well informed and educated individuals have made the decision to not take the vaccine.
GLTA,
Farrell
Sotrovimab is a monoclonal antibody which attaches to the Spike protein of the Coronavirus.
This is the same site of attachment as the other Covid 19 monoclonal antibodies, baricitinib, bamlanivimab,as well as Regeneron's antibiotic cocktail of casirivimab and imdevimab; all have been given an EUAs but have not approved as Covid 19 therapeutics.
The other monoclonal antibodies for Covid all block viral entry into the human cells to prevent infection. Sotrovimab also blocks viral cell entry, but its mechanism is defined in a more detailed manner:
"Sotrovimab inhibits an undefined step that occurs after virus attachment and prior to fusion of the viral and cell membranes."
"Sotrovimab is a recombinant human IgG1-kappa mAb that binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2 with a dissociation constant KD = 0.21 nM) but does not compete with human ACE2 receptor binding (IC50 value >33.6 nM [5 µg/mL]). Sotrovimab inhibits an undefined step that occurs after virus attachment and prior to fusion of the viral and cell membranes. The Fc domain of sotrovimab includes M428L and N434S amino acid substitutions (LS modification) that extend antibody half-life, but do not impact wild-type Fc-mediated effector functions in cell culture."
The FDA seems concerned Sotrovimab will share so of the other Covid 19 monoclonal antibody side effects and listed them in the physicians insert as a warning to doctors treating Covid19 patients.
"5.2 Clinical Worsening After SARS-CoV-2 Monoclonal Antibody AdministrationClinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of
Covid19"
GLTA, Farrell
Sotrovimab FDA letter to providers:
1. Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.
2.Sotrovimab is not authorized for use in patients: owho are hospitalized due to COVID-19, OR owho require oxygen therapy due to COVID-19, OR owho require an increase in baseline oxygen flow rate due to COVID-19 (in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity).
3. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions, occurring during theinfusion andup to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening. Signs and symptoms of infusion-related reactions may include: ?fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (e.g., pre-syncope, syncope), dizziness, and diaphoresis.Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.
4.Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19.
https://www.fda.gov/media/149534/download
GLTA Farrell
I believe you are on the right path. The normal course would be to wait until all the data is completely reviewed,but these are not normal times, here or abroad.
According to the CDC 438 individuals died from Covid last week in the US. 50% of the population is vaccinated,but the vaccination rates are dropping sharply. Tens of thousands are dying abroad.
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html
I think the Remdeivir model and timeline still applies since another Covid antiviral has not been approved and additional experience with Remdesivir has not confirmed the early enthusiasm.
Remdesivir was given on a compassionate use basis at the very beginning of the US infections in January 2020. This is before any of the clinical trials were finished, but based on studies done for Ebola, SARS and MERs.
https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
In March of 2020 Gilead began an expanded compassionate use program. The first Redesivir Covid 19 trial was begun in China , but suspended. The adaptive phase 2-3 trial was begun on 2/21/2020 and first results posted on 9/25/2020
EUA was granted on May 1,2020 and approval by the FDA was given on 10/25/2020.
IMO that gives a timeline on how Brilacidin may progress.
If the phase 2 Brilacidin trial is very positive. I believe expanded compassionate use could be begin soon. To be quickly followed by an announcement of a phase 3 study with grants and possible partnership. If the phase 3 study shows promise at the first interim report we could see an EUA. Formal FDA approval would be given after the phase 3 trial is completed.
If the phase 2 trial shows modest results, ie better than Remdesivir, we could still see the course accelerated.
Time will tell.
Good luck to all,
Farrell
In addition to being unemployed and open to endless law suits the CEO could receive up to 5 years for lying to Congress.
Too bad they can not get to their overseers eg Citadel and others.
GLTA,
Farrell
Another great post
Thanks
GLTA,
Farrell
I think you are close for the 120. They seem to want to complete a few extra just in case they are needed.
GLTA, Farrell
Precision vaccinations provides a good summary of Covid medicines as well as updates.
Thanks for the reminder.
https://www.precisionvaccinations.com/vaccines/brilacidin-covid-19-therapeutic
GLTA,Farrell
One additional PR should have been added:
"data from a leading Public Health Research Institute (PHRI) showing Brilacidin inhibits SARS-CoV-2, the novel coronavirus responsible for COVID-19, in a human cell line. Brilacidin, in comparison to vehicle control, exhibited an inhibitory effect on SARS-CoV-2 in a dose-dependent manner—an average 29 percent inhibition at 0.1ug/ml (the lowest concentration) to an 85 percent inhibition at 100ug/ml (the highest concentration)."
http://www.ipharminc.com/press-release/2020/5/26/innovation-pharmaceuticals-receives-data-from-public-health-research-institute-showing-brilacidin-inhibits-sars-cov-2-covid-19-in-a-human-cell-line
GLTA Farrell
This PR I believe is the first mention of the PHRI and its plans to research Brilacidin.
http://www.ipharminc.com/press-release/2020/5/5/inhibitory-effect-of-innovation-pharmaceuticals-brilacidin-on-sars-cov-2-covid-19-in-primary-human-immune-cells-to-be-studied-at-leading-public-health-research-institute
"This new research is separate from the previously announced antiviral studies being conducted at a U.S. Regional Biocontainment Laboratory (RBL), which over the weekend informed us that the next phase of Brilacidin testing has commenced.
Scientists at the Public Health Research Institute plan to evaluate Brilacidin’s inhibitory effect on SARS-CoV-2 viral replication in primary immune mediators (peripheral blood mononuclear cells, T cells, B cells, monocytes, macrophages) obtained from both young and old donors to assess age-dependent host responses to the novel coronavirus. Brilacidin drug substance has been received by the Institute and is now available for testing."
The PHRI was founded in New York City as a research health center. It later became affiliated with Rutger University.
https://phri.njms.rutgers.edu/
The PHRI has a relationship with the " Bio-Safety Level 3 (BSL3) vivarium and laboratory spaces dedicated to study infectious diseases and highly transmissible pathogenic agents".
https://phri.njms.rutgers.edu/programs-and-resources/bls3-vivarium-facility/
The Rutgers BSL3 lab is one of the national NIH affiliated Biodefense labs.
https://phri.njms.rutgers.edu/programs-and-resources/rutgers-biocontainment-laboratory/
Thersa Chang PHD from the Rutgers PHRI contributed to the article published in Viuses which outlined Brilacidin's anti Covid research
https://phri.njms.rutgers.edu/faculty-and-research/faculty/theresa-chang/
Thersa Chang has published research outling defensins immune modulation attributes.
https://pubmed.ncbi.nlm.nih.gov/29501617/
Ding, J.; Chou, Y.Y.; Chang, T.L. Defensins in viral infections.J. Innate Immun.2009,1, 413–420.
Klotman, M.E.; Chang, T.L. Defensins in innate antiviral immunity.Nat. Rev. Immunol.2006,6, 447–456. [CrossRef] [PubMe
She is also credited with being an important contributor to the Viruses article including performing some of the experiments T.L.C.
Author Contributions:Conceptualization, A.B., A.N., T.L.C., W.K.W., and J.A.H.; Methodology,A.B., W.K.W., J.A.H.; A.B., K.R., N.B., F.A., and T.L.C. conducted experiments; Visualization, Formalanalysis, Data curation, A.B., A.N., W.K.W., T.L.C., and J.A.H.; Writing—original draft preparation,A.B., A.N., W.K.W., and J.A.H.; Writing—review and editing, A.B., A.N., W.K.W., and J.A.H.; Projectadministration, A.N., W.K.W., and J.A.H.; Funding acquisition, A.N., W.K.W., and J.A.H. All authorshave read and agreed to the published version of the manuscript.
GLTA, Farrell
Here's TD Ameritrade list by sticker. ERHE trading is restricted to sales only,no buys.
Late buying kicking in. It is now green.
Which brokerages allow unrestricted trading?
https://www.tdameritrade.com/retail-en_us/resources/pdf/cesecuritylist.pdf
TD Ameritrade began the same restriction today.
GTA Farrell
Spoken like a clairyoant, prophet or seer showing us the future.
If the Phase 2 study shows Brilacidin is effective my bet that is exactly what will happen not only in India, but Brazil,Japan and wherever the mutations devastate and ravage .
"A prophet is a teacher of known truth; a seer is a perceiver of hidden truth, a revelator is a bearer of new truth. In the widest sense, the one most commonly used, the title 'prophet' includes the other titles and makes of the prophet, a teacher, perceiver, and bearer of truth."
"I'm sure IPIX is on the horn right now with Indian Health Ministry and all the top Indian Pharmas"
GLTA,
Farrell
The Indian variant represents a mutation on the Corona virus S protein which attaches the virus to human cells. This is of great concern because A number of Covid treatments,eg Lilly's Bamlanivimab and Regeneron's antibody as well as convalescent serum, mechanism of action is to bind to the S protein to prevent attachment to the cells.
This may reduce the effectiveness not only of therapeutics but also vaccines
Pfizer or Moderna shots. In these studies, the antibodies could still neutralize the B.1.617 variant, but the potency of the antibodies dropped by about sevenfold on average, the authors reported.Although early studies show they can still prevent infection.
The Astra Zenica vaccine is less likely to prevent infection but
"preliminary evidence suggests this vaccine will also be able to prevent severe cases and deaths, said Rakesh Mishra, adviser to the Centre for Cellular & Molecular Biology in Hyderabad, India.
https://www.npr.org/sections/goatsandsoda/2021/05/12/995855343/will-covid-19-vaccines-still-work-against-the-variant-from-india
"B.1.617.1 has been called the “Indian double mutant”, but this term is misleading as it has around 15 mutations compared with older variants. “Double mutant” refers to the fact that it has two mutations of particular concern in the outer spike protein of the virus. These two mutations, known as L452R and E484Q, might make antibodies to older variants or existing vaccines less effective..."
"Some B.1.617.1 viruses have an additional mutation called V382L in the spike protein. This is what is meant by the term “triple mutant”."
https://www.newscientist.com/definition/indian-covid-19-variant-b-1-617/
Thanks for posting the WHO update on the Indian variant.
Alarming points:
1."Earlier this week, the WHO declared B.1.617-which counts three so-called sub-lineages with slightly different mutations and characteristics-a "variant of concern"."
2. " it appears to be transmitting more easily than the original virus, pointing to the "rapid increases in prevalence in multiple countries".
3 "the variant was more resistant to treatment with the monoclonal antibody Bamlanivimab, and also highlighted early lab studies indicating "limited reduction in neutralization by antibodies".
4" "real-world impacts" on the effectiveness of vaccines against the variant "may be limited".
5.The World Health Organization said on Wednesday a variant of COVID-19 behind the acceleration of India's explosive outbreak has been found in dozens of countries all over the world.
Brilacidin's potential triple mechanism of action would provide additional protection against Corona virus mutations if it is proven effective.
GLTA,
Farrell
Its the catch 22 of government regulations and FDA oversight. IPIX is not to blame in the study design.
Remdesivir does not work to lower Covid19 mortality or complications.
In spite of this Remdesivir was the only antiviral approved by the FDA for Covid19 and is a part of virtually every Covid 19 study{which was one of the best arguments against approving it}.
Remdesivir is considered the "standard of care" at many hospitals.
It is unethical not to provide the standard of care in Covid19 studies.
As a result Covid 19 antiviral studies in the US are currently using Remdesivir and not a placebo in clinical trials.
How can one tell if another antiviral eg Brilacidin is superior to Remdesiviir without a placebo?
Well if the Brilacidin treatment arm substantially lowers mortality or complications then one could reasonably assume Brilacidin is effective against Covid19 {remember Remdesivir does not work}.
At this point there has been no definition of the SOC in the Brilacidin phase 2 study except as defined in the local facility. It is possible Remdesivir will only be used in the US hospitals, and it appears those numbers may be small.
So that will add to the mystery.
It will be up to the wisdom of the FDA to design the phase 3 study. Will the phase 3 study include a placebo control arm without Remdesivir...
We will have to wait and see. My guess is it will not be necessary, but who knows?
GLTA, Farrell
In contrast Brilacidin may have 3 antiviral mechanisms of action. In addition it is a proven broad spectrum antibiotic and it has anti-inflammatory properties.
Brilacidin starts killing Covid 19 in the serum shortly after infusion. It does not require conversion to an active form like Remdesivir and Pfizers PF 07321332..Brilacidin is the only antiviral being studied which is viruidal. It attaches to the viral coat and destroys the virus shortly after contact.
The Pfizer drug is a prodrug, like Remdesivir, and has to be activated to its effective form.
In addition testing at the RBL demonstrated that Brilacidin prevents viral attachment to the cells.Computer simulations showed it may deactivate the virus's main protease.
Bliacidin has a number of anti-inflammatory properties which may limit the Covid 19 inflammatory cascade which leads to many complications including pulmonary failure.
It broad spectrum antibiotic may reduce the secondary infection rate in hospitalized patients which has been reported as high as 8%
Brilacidin has been successful in all of its previous studies. The Phase 2 study is soon to be fully enrolled.
GLTA,Farrell
The Pfizer Covid19 drug is a protease inhibitor. All the protease inhibitors tested to date have failed to show efficacy against Covid19.
These include the antiviral drugs. lopinavir, ritonavir, darunavir andcobicistat have been shown in clinical trials to not be effective against Covid19.
The current FDA recommendation is to not use any protease inhibitor against Covid19 in any patient:
"Recommendations
The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of lopinavir/ritonavir and other HIV protease inhibitors for the treatment of COVID-19 in hospitalized patients (AI).
The Panel recommends against the use of lopinavir/ritonavir and other HIV protease inhibitors for the treatment of COVID-19 in nonhospitalized patients (AIII)."
https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/lopinavir-ritonavir-and-other-hiv-protease-inhibitors/
In addition lopinavir and ritonavir have significant cardiac and hepatotoxicity
The Pfiizer study is a phase 1 ascending dose trial in 60 healthy volunteers. This is the first time the drug has been used in humans.
https://clinicaltrials.gov/ct2/show/study/NCT04756531#contacts