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Very interesting.
GLTA,
Farrell
1U of heparin = .002mg
https://www.itwreagents.com/download_file/product_infos/A3004/en/A3004_en.pdf
Therapeutic serum level of heparin is .4U to .7U
https://pubmed.ncbi.nlm.nih.gov/8512158/
In the Caco-2 cells and the Calu 3 human cell lines the heparin effect seems to begin at about 3ug to 10ug/ml
https://www.biorxiv.org/content/10.1101/2021.11.04.467344v1.full.pdf
graph G,H and I
.7U of heparin = .0014 mg = 1.4 microgram
Therefore the upper limit of serum heparin should have no effect on Brilacidin against Covid
Good luck to all,
Farrell
Thanks for posting.
The article confirms the previous Virology paper's result that the mechanisms of action of Brilacidin is blocking viral entry and being virucidal. The study did not investigate the intracellular effect of Brilacidin against the Covid M protein as suggested in the computer model screening study.
The study did discover the molecular mechanism of action is the targeting of heparin sulfate proteoglycans both by attaching to the host cell receptor sites to block entry and by binding to the virus directly to block entry and destroy the virus.
It is pertinent this same heparin sulfate proteoglycans are found in number of viruses which means Brilaidin may be effective as an antiviral against more viral strains than previously thought.
https://ncbi.nlm.nih.gov/pmc/articles/PMC6669472/
See Table 1
The study confirmed the Brilacidin safety tests and its synergistic effect with Remdesivir.
The other good news is this MOA means viral resistance to Brilacidin is less likely. Most Coronavirus resistance is felt to be due to mutations in the spike proteins. The proposed mechanism of action against the heparin sulfate prototeoglyans is completely independent of the spike protein mutations which means viral resistance against Brilacidin is less likely to occur.
https://www.nature.com/articles/s41579-41579-021-00573-0ddh
I tried to correlate the heparin levels listed in the study Figure 5 with microgram per millimeter levels needed for therapy. I could not find a good reference as most heparin levels are not listed in ug/ml levels. I hope someone can find this.
Good luck,
Farrell
It is not false and the study report confirms the statement.
"Statistically, most will be fine and recover on their own without Molunpriavir or much help from hospitals."
Recent reports of the phase 3 interim report show 7.4% in the molunpiravir were hospitlized with zero deaths
The placebo group had 14.1 hospitalized including 8 deaths.
The results do show a very positive treatment effect,
but 85.9% of the placebo group survived without hospitalization.
https://www.pharmaceutical-technology.com/news/merck-ridgebacks-molnupiravir-covid-19/
Nice post
Mutagenic means DNA damage which can lead to birth defects as well as cancers later in life.
If you have to treat hundreds or thousands to prevent 8 deaths,how many of the living will get cancer later in life after being treated with Molunpiravirin? No one knows if it will be none or many.
Remember Molnupiravir is Ames positive. The Ames test is a screening device used to predict cancers and birth defects due to DNA damage.
Credible scientists are still concerned about the DNA damage potentially caused by Molunpiravir.
Dr Zhou studied Molunpiravir at the University of North Carolina. He made the following statements:
“There is a concern that this will cause long-term mutation effects, even cancer,” Zhou says.
Zhou says that he is certain that the drug will integrate itself into the DNA of mammalian hosts. “Biochemistry won’t lie,” he says. “This drug will be incorporated in the DNA.”
https://www.virology.ws/2021/10/14/molnupiravir-the-sars-cov-2-antiviral-is-mutagenic-for-cells/
https://www.barrons.com/articles/merck-covid-pill-risks-51633398722
GLTA,
Farrell
Agree, any investor who thinks Brilacidin has a chance to be effective against Covid needs to be fully invested Monday morning.
GLTA,Farrel
Good points...and if the news is good next week they will be the big losers.
That being said I think we will rally a bit before the close.
GLTA,
Farrel
Great Britain also approved thalidomide, but the FDA did not.
Unfortunately we live in a different time where dollars and political influence may be greater than integrity.
https://www.theguardian.com/society/2016/mar/06/thalidomide-caused-up-to-10000-miscarriages-infant-deaths-uk
Farrell
Countless numbers of affluent investors will be aware of Brilacidin and IPIX as a result of the WSJ article.
It looks like another big day for IPIX stock.
Thanks for posting,
Farrell
Looks like the look anticipated new money investors are coming in with the large orders.
Some should be very afraid; others ecstatically happy.
GLTA,
Farrell
Great summary for newbies...Please sticky at top
GLTA Farrell
Not exactly.
The article confirms Dr Degrado, IPIX science advisor, is acknowledged by his peers as a leading researcher in the field of proteins, peptides
and defensins as well as defensin based pharmaceuticals.
Brilacidin is based structurally on a defensin peptide, Magainin. Attempts to make Magainin a therapeutic failed to to the structural weakness in its peptide core.
Dr Degrado and his team used biochemical and supercomputer enhancement to produce a new pharmacologically stable compound with superior antibiotic, anti-inflammatory and now antiviral capabilities, Brilacidin.
Having Dr DeGrado give a portion of a named lecture in his field is an honor .
Having Dr Degrado as IPIX's scientific advisor gives IPIX and Brilacidin scientific and academic credibility that is priceless.
Brilacidin research is just beginning to open its multiple possible uses as a pharmacologic agent.
GLTA,Farrell
Of course if it is unblinded there would be individuals involved in the review of the data who would have a preview of the results. Of course they would be compliant with all the restrictions involved with premature discloosure and it would be impossible they could release any of the results.
But,leaks do happen,
Farrell
Run baby run! Phase 2 now unblinded???
Good luck to all,
Farrell
What good news,since we may not be a penny stock much longer!!!
GLTA,
Farrell
Moderators, sticky this post!!!
GLTA,
Farrell
There are considerable impediments to validating and reviewing the data. Different languages,medical cultures, computer systems, computer software, missing test results especially dealing with ill patients. Evaluating the two different doses in the trial and making reasonable and scientifically based decisions to evaluate these situations which arise in every trial.
It is challenging dealing with 200 different patients.
We will know the answers soon.
Glta, Farrell
"Nipah virus (NiV) is a paramyxovirus (Henipavirus genus, Paramyxovirinae subfamily, Paramyxoviridae family, order Mononegavirales), an emerging virus that can cause severe respiratory illness and deadly encephalitis in humans. It is a negative sense, single-stranded, nonsegmented, enveloped RNA virus possessing helical symmetry."
Mortality 59%
encephalitis is usual cause of death
human to human transmission has been reported
Reservoir is fruit bats in SE asia
Often spreads to pigs then humans
639 human cases since first described in 1998
survivors often have long lasting neurologic disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830995/
Good luck,
Farrell
The point is the Covid19 pandemic is an international calamity.
Ideally an antiviral medication should be a part of any treatment regimen for the moderate to severely ill covid patient.
All the previous clinical trials for covid antivirals have failed to consistently improve death rates, prevent complications or significantly reduce the length of the illness in the moderately to severely ill covid patient.
An improved outcome would be any reduction in the death rate, any reduction in comorbidities {complications} or a meaningful reduction in the length of the illness.
The improvement in any of these categories could be quite small , but it would be a success because all the other antiviral treatments have been disappointing.
Hopefully, Brilacidin will prove to be an effective treatment against this terrible disease.
We will know soon.
GLTA,Farrell
"Brilacidin only has to be 2% better than Remdesivir for it to be the antiviral drug of choice for covid."
You know that wasn't the question.
You said:
"If Brilacidin's phase 2 clinical trial shows substantial benefit in the moderate to severe covid patients it will be the only antiviral to demonstrate such efficacy and will have a virtual lock on the pathway to emergency use utilization and likely approval."
You chose to use the phrase "substantial benefit" and I asked you to define it.
If your definition is "2% better than Brilacidin" please tell me how you would measure that.
According to the CEO we are going to see results very soon. Whether they are perceived to be good or bad needs to be based on a reasonable standard and to date no one has provided one.
It seems the plan is to see the results and then set the standard. For some reason that doesn't surprise me.
Do we know how Remdesivir performs in moderate-to-severe patients in terms of the primary outcomes defined in the IPIX trial?
Ha Ha... best answer yet,
In other words in the entire cosmos using the best "science" known to man it is immeasurable like a vapor, faint smell or flash of insight.
I sure Mako wishes that was the simple truth. I am afraid the reality may prove different.
GLTA,Farrell
The good news is the bar for success is incredibly low. Brilacidin only has to be 2% better than Remdesivir for it to be the antiviral drug of choice for covid.
We should know the phase2 results very soon.
GLTA,
Farrell
That begs the question of how do you you would accurately determine naked shorts since:
A. Naked short selling is illegal. If we could measure naked shorting it seems reasonable we could prosecute and jail the offenders, but legal action seems infrequent at best.
B. The most efficient naked shorts collude with conspirators internationally to evade detection. Although Mako was recently accused of this in the Mako Research vs Abeona Therapeutics legal action, it is my understanding it is difficult to prove.
How would you suggest we measure the illegal naked shorts?
This is pertinent to IPIX since IPIX and Mako were involved in a legal action.
GLTA,Farrell
Nice thread. It is interesting to review the FDA online documents, but they can be inconsistent and confusing.
It is not confusing that the FDA has approved a number of covid treatments and vaccines for compassionate use.
We are fortunate to have a practical example of how the FDA awards compassionate use as well as extended compassionate and emergency use for a covid antiviral medication, remdesivir
Remdesivir was initially used for compassionate use in Jan of 2020.
Then in May of 2020 remdesivir was approved for emergency use after an interim review of its adaptive phase2-3 trial suggested some benefit.
"... the National Institute of Allergy and Infectious Diseases (NIAID) double-blinded placebo trial NCT04280705, reported that remdesivir was superior to placebo in speeding up the recovery time in COVID-19 patients [34]...However, from these preliminary data, the Food and Drug Administration (FDA) on 1 May 2020, approved its emergency use for patients at all ages requiring or not requiring invasive ventilation or ECMO [4]. Consequently, the European Medicines Agency (EMA) on 11 May 2020 revised the recommendations for compassionate use of remdesivir by extending the inclusion criteria with the addition of patients who do not require invasive ventilation to be treated for a period of 5 days through 10 days
https://joppp.biomedcentral.com/articles/10.1186/s40545-020-00258-8
If Brilacidin's phase 2 clinical trial shows substantial benefit in the moderate to severe covid patients it will be the only antiviral to demonstrate such efficacy and will have a virtual lock on the pathway to emergency use utilization and likely approval.
Of course the skepticism regarding Remdesivir's effectiveness proved well founded as subsequent studies by WHO and others questioned not only its efficacy, but irregularities to its path to approval.
https://www.science.org/content/article/very-very-bad-look-remdesivir-first-fda-approved-covid-19-drug
https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781959
The current NIH Covid 19 treatment guidelines from Aug 2021 state:
"Rationale for the Panel’s Assessment That There Is Insufficient Evidence to Recommend Either for or Against the Use of Remdesivir"
We should know the Brilacidin results very soon.
GLTA, Farrell
A terrific phase 2 for Brilacidin will be a career changer for many if the results are positive.
Glta,Farrell
Evonik is an international company with several production facilities in the USA:
Allentown, Pennsylvania
Function: Office, Research & Development
Birmingham, Alabama
Function: Production, Research & Development
Blair, Nebraska
Function: Production
Calvert City, Kentucky
Function: Production
Charleston, South Carolina
Function: Production
Chester, Pennsylvania
Function: Production
Deer Park, Texas
Function: Production
Etowah, Tennessee
Function: Production
Garyville, Louisiana
Function: Production
Greensboro, North Carolina
Function: Office, Production, Research & Development
Havre de Grace, Maryland
Function: Production, Research & Development
Hopewell, Virginia
Function: Production
Horsham, Pennsylvania
Function: Office, Research & Development
Janesville, Wisconsin
Function: Production
Lafayette, Indiana
Function: Production, Research & Development
Los Angeles, California
Function: Production
Mapelton, Illinois
Function: Production
Milton, Wisconsin
Function: Production
Mobile, Alabama
Function: Office, Production
Parisppany, New Jersey
Function: Regional Headquarters Evonik Region North America
Pasadena, Texas
Function: Production
Piscataway, New Jersey
Function: Research & Development
Reserve, Louisiana
Function: Production
Richmond, Virginia
Function: Office, Research & Development
Waterford, New York
Function: Production
Weston, Michigan
Function: Production
Wichita, Kansas
Function: Production
Regional Website
North America
https://corporate.evonik.com/en/company/locations/north-america
Leo is letting the interested parties know he can go it alone if he needs to. The stock options give him the ability to attract top notch administrative talent to manage Brilacidins success.
Does Leo want to go it alone or is it a negotiating strategy? We should know very soon.
Glta,
Farrell
Another excellent point.
GLTA, Farrell
It is a bit of corporate house cleaning before the well heeled visitors arrive for a profitable visit.
Expect more news soon.
I agree with your perceptive comments.
"The company is expecting stellar results. There may already be a contingent offer on the table for either partnering or full company buyout. If full buyout is on the table, then the purchasing company would want and need to know what the full outlay will be since all the shares would need to be acknowledged prior to final purchase price/payment was announced.
Just my reading of the “Setting the Table” prior to a huge announcement is my opinion. Hopefully for all the Longs on this board, we see it come to fruition."
GLTA, Farrell
Expanded access and compassionate use tab now on IPIX web-site.
http://www.ipharminc.com/expanded-access-and-compassionate-use
Good luck,
Farrell
Nice review. The only point I would add is some severe ill covid patients can not respond to the infection and have a persistent viremia. Your point about the anti-inflammatory effects of brilacidin are well taken. The antiviral and anti-inflammatory effects of Brilacidin make it unique.
Glta, Farrell
Regeneron's antibody treatment flunked its treatment for moderate to severe covid( as did every over antiviral).
Yes, it is an emergency.
Glta, Farrell
Just remember there is absolutely no evidence hedge funds are manipulating IPIX, absolutely none.
Glta,Farrell
My guess is the EUA request will be rejected. Then Merck will complete the current study plus perform additional animal studies.
The last thing the FDA and politicians want is to be a part of the next thalidomide disaster.
Glta,Farrell
Thanks for posting. Moderators, this post should be placed at the top.
GLTA,
Farrell
Mutagenic effects include DNA damage which could result in increased rates of malignancy later in life.
Birth defects can be mitigated with contraception. Unfortunately many women use contraception intermittently and do not know they are pregnant the first few weeks of pregnancy,the period where birth defects are most likely to occur.
Glta,
Farrell
Scientific report outlines the risk of gene mutations with Molnupiravir.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344773/pdf/jiab363.pdf
"This leads to the conclusion
that treatment with molnupiravir will lead to mutations in host DNA in dividing cells.
Using negative results to justify this risk as being unimportant is to create a blind
spot for potential long term harm. Until a better understanding of treatment with
molnupiravir is achieved, we would argue that its use should be limited to people
with co-factor risks for COVID who are likely to receive the greatest benefit while
being exposed to the unknown long term risks of exposure to this mutageupiravir explained"
GLTA, Farrell
"Merck isn’t simply going to get a pass on this from the FDA."
Zero hedge expressed serious concerns about Molnupiravir.
https://www.zerohedge.com/news/2021-10-01/mercks-therapeutics-waiting-wings-faucis-removal
"Today news of Merck's Molnupiravir is dominating the narrative. In dramatic fashion they are stopping the trial recruitment and plan to file an EUA. While this is fantastic news people can’t be blinded by the Merck aura and have to dig into the news to truly understand the ramifications. This is a drug with known mutagenicity. Ironically Merck’s inclusion criteria in ALL their clinical trials required participants to not have sex. This includes the clinical trial for prophylaxis. Perhaps they want to avoid the potential of birth defects so this drug is clearly not going to appeal to anyone building a family or engaging in intercourse.
The drug is using the virus’s propensity to mutate against itself by tricking the replication machinery to pump out reproduction errors until the virally infected cell collapses. The last thing the FDA wants to do is approve a drug that brings the rise of a new class of variants. It's unclear if Merck tested patients for new variants that are more likely to rise up in patients who have the longest active infections. Merck isn’t simply going to get a pass on this from the FDA. Based on the commentary in the Merck press release it's unclear if Merck even knows if their drug is safe. Essentially they talk about the incidence of drug-related adverse events as the same, but didn’t provide any color on what these events were.
"The euphoria from this news announcement isn’t looking at the fine print of the trial design of the study. Recruitment required at least one underlying medical condition like obesity, old age (>60 years), diabetes, or heart disease. Looking at this patient population was needed to obtain statistical significance because too many with no underlying conditions just get better on their own. The trial could have been a failure otherwise. Another factor contributing to Merck's success is a smaller than expected stratification of Delta variant infections. Only 40% of the clinical trial had Delta variant patients. People need to consider that a majority of the data was from the alpha variant which means that if Merck doesn't segregate the data by variant they are trying to pull the wool over our eyes to hide how weak the data really is."
GLTA,
Farrell
Thanks for posting. Interesting data which clearly outlines the deficiencies of current covid vaccines. Many studies use medicare data.
Another reason to increase the development of therapeutics like Brilacidin.
GLTA,
Farrell
Here is the whole quote with 2 additional reports.
"Based on an interim analysis of data from the phase 2, dose-finding portion (Part 1) of 2 ongoing phase 2/3 trials evaluating molnupiravir, Merck and Ridgeback Biotherapeutics have decided to halt the MOVe-IN study for hospitalized COVID-19 patients and proceed with the phase 3 portion (Part 2) of the MOVe-OUT study in outpatients with COVID-19"
https://www.empr.com/home/news/molnupiravir-merck-ridgeback-oral-antiviral-investigational-covid-19-treatment/
The pill known as molnupiravir reduced virus levels in patients during a mid-stage study but didn’t show a meaningful benefit in preventing hospitalizations and deaths, the Kenilworth, New Jersey-based company said in a statement. It decided to discontinue its development for the sickest patients, those hospitalized with the infection, after the trial showed it was unlikely to help them.
https://www.bloomberg.com/news/articles/2021-04-15/merck-setback-limits-study-of-covid-pill-to-treat-milder-disease
Merck MRK 8.37% & Co. and its partner Ridgeback Biotherapeutics LP said they are stopping a trial of their experimental Covid-19 drug after it failed to help hospitalized patients, delivering another setback to doctors seeking treatments to use for the disease.
https://www.wsj.com/articles/merck-partner-halt-covid-19-treatment-trial-for-hospitalized-patients-11618483561
This portion of the quote is incorrect.
...after the FDA asked for additional information.
Merck released the stories about MK7110 the oncoimmune anti-inflammatory drug and EIDD-2810 about the same time and the announcements were in the same articles.
Thanks for the correction.
Farrell
A scientific article also demonstrated mammalian cell DNA toxicity to molnupiravir which could induce birth defects or cancer in the host.
"SARS-CoV2 infection results in an age-related acute respiratory disease spectrum that can be life-threatening, especially in the elderly and individuals with select underlying comorbidies [14]. rNHC (initial metabolite of molnupiravir} has the potential to have therapeutic benefit in this setting. However, there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA. This risk can be inferred based on the common intermediate of the ribonucleoside diphosphate shared in the synthesis of both ribonucleoside triphosphates and 2'-deoxyribonucleoside triphosphates. The concern would be that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells. We take this as evidence that in exposing the viral population to mutagenesis in its RNA form, the host is likely to be exposed in its DNA form. It seems unlikely that a short course of therapy would spare the host from this exposure because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
GLTA,
Farrell