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It has been my observation the hedge fund managers are never shy.
Of course, it reflected badly on him and Ridgeback when Dr Bright stood up to him when his political contacts tried to help him score funds from Barda.
Even though Merck bought a position in Ridgeback, it is Ridgeback controlling the phase 1 and 2 trials, not Merck. How much credibility does Ridgeback have?
Stuart Varney"s and Dr Siegel"s phones must be ringing constantly to tell them the rest of the story. Mr Hedge fund has made a lot of enemies.
Remember. Dr Rick Bright is now on the Biden Coronavirus Advisory Committee
The other point is Dr Rick Bright spent several years early in his career at Emory then the CDC which works closely with Emory. I doubt many at Emory were happy to see Molnupiravir sold to a hedge fund.
Which brings up the question,why the hell would they do that?
The truth is often stranger than fiction.
GLTA Farrell
I have a better question. The oil bull market is on the up slope.
Many credible sources are projecting $80 a barrel oil by this summer.
When is ERHE going to participate?
ERHE's JDZ assets are increasing in value daily. Is anyone home to answer the phone?
Best wishes to all,
Farrell
Love the FDA pictures. Reminiscent of Sienfeld's Kramer going to the taking vet medicine for a cough.
Who said the stiffs at the FDA had no sense of humor?
https://www.google.com/search?client=firefox-b-1-d&q=you+tube+Kramer+taking+vet+medicine
GLTA, Farrell
Additional background about Molnupiravir:
- its mechanism of action is similar to Remdesivir and Favipiravir as a nucleoside analogue
- it has only completed a phase 1 study in healthy volunteers
- its large phase 2 trials are still recruiting patients
-it is was purchased from Emory University by a hedge fund
- the hedge fund owner,Rick Holman, is listed as an author of the Phase 1 study publication
-The hedge fund company's Ridgeback Biotherapeutics has been accused of improper influence in seeking Barda funds
-Former Barda chief Dr Rick Bright stated, "similar experimental drugs in this class had been shown to cause reproductive toxicity in animals, and offspring from treated animals had been born without teeth and without parts of their skulls."
-Bright also stated,"illegally retaliated against him for objecting to what he saw as improper and unscientific efforts to steer taxpayer dollars to certain firms run by "cronies" or "for political purposes"
-in the end Dr Bright filed a whistleblower lawsuit which result in his removal from Barda.
- Dr Rick Bright is now a Biden Transition COVID-19 Advisory Board member
-Ridgeback has licensed Molnupipiravir to Merck,but still has a substantial interest in the drug including being responsible for the Phase 1 and 2 clinical trials.
"Ridgeback will continue to fund and conduct multiple Ridgeback-sponsored Phase 1 and 2 trials and fund manufacturing campaigns for clinical supply. Going forward, the parties will collaborate on clinical development for COVID-19 and manufacturing..."
https://www.businesswire.com/news/home/20200701005928/en/Merck-and-Ridgeback-Bio-Announce-Closing-of-Collaboration-and-Licensing-Transaction
From Wikipedia
"In his complaint, Bright also noted the dangers in pursuing EIDD-2801, an oral antiviral candidate previously supported by NIAID led by Dr. Anthony Fauci and DOD...In February, 2021, Bright co-authored an opinion editorial in the Washington Post claiming "efforts to develop a therapeutics were slow and limited.]"
https://www.businesswire.com/news/home/20200701005928/en/Merck-and-Ridgeback-Bio-Announce-Closing-of-Collaboration-and-Licensing-Transaction
https://www.washingtonpost.com/business/2020/06/11/coronavirus-drug-
ridgeback-biotherapeutics/
https://pulitzercenter.org/stories/emails-offer-look-whistleblower-charges-cronyism-behind-potential-covid-19-drug
https://aac.asm.org/content/aac/early/2021/02/24/AAC.02428-20.full.pdf
https://www.clinicaltrials.gov/ct2/results?recrs=&cond=&term=Molnupiravir&cntry=&state=&city=&dist=
https://en.wikipedia.org/wiki/Rick_Bright
Glta,Farrell
© 2021 InvestorsHub.com, Inc.
There are many things DR Siegal left out about Molnupiravir:
- its mechanism of action is similar to Remdesivir and Favipiravir as a nucleoside analogue
- it has only completed a phase 1 study in healthy volunteers
- its large phase 2 trials are still recruiting patients
-it is was purchased from Emory University by a hedge fund
- the hedge fund owner,Rick Holman, is listed as an author of the Phase 1 study publication
-The hedge fund company's Ridgeback Biotherapeutics has been accused of improper influence in seeking Barda funds
-Former Barda chief Dr Rick Bright stated, "similar experimental drugs in this class had been shown to cause reproductive toxicity in animals, and offspring from treated animals had been born without teeth and without parts of their skulls."
-Bright also stated,"illegally retaliated against him for objecting to what he saw as improper and unscientific efforts to steer taxpayer dollars to certain firms run by "cronies" or "for political purposes"
-in the end Dr Bright filed a whistleblower lawsuit which result in his removal from Barda.
- Dr Rick Bright is now a Biden Transition COVID-19 Advisory Board member
-Ridgeback has licensed Molnupipiravir to Merck,but still has a substantial interest in the drug including being responsible for the Phase 1 and 2 clinical trials.
"Ridgeback will continue to fund and conduct multiple Ridgeback-sponsored Phase 1 and 2 trials and fund manufacturing campaigns for clinical supply. Going forward, the parties will collaborate on clinical development for COVID-19 and manufacturing..."
https://www.businesswire.com/news/home/20200701005928/en/Merck-and-Ridgeback-Bio-Announce-Closing-of-Collaboration-and-Licensing-Transaction
From Wikipedia
"In his complaint, Bright also noted the dangers in pursuing EIDD-2801, an oral antiviral candidate previously supported by NIAID led by Dr. Anthony Fauci and DOD...In February, 2021, Bright co-authored an opinion editorial in the Washington Post claiming "efforts to develop a therapeutics were slow and limited.]"
https://www.businesswire.com/news/home/20200701005928/en/Merck-and-Ridgeback-Bio-Announce-Closing-of-Collaboration-and-Licensing-Transaction
https://www.washingtonpost.com/business/2020/06/11/coronavirus-drug-
ridgeback-biotherapeutics/
https://pulitzercenter.org/stories/emails-offer-look-whistleblower-charges-cronyism-behind-potential-covid-19-drug
https://aac.asm.org/content/aac/early/2021/02/24/AAC.02428-20.full.pdf
https://www.clinicaltrials.gov/ct2/results?recrs=&cond=&term=Molnupiravir&cntry=&state=&city=&dist=
https://en.wikipedia.org/wiki/Rick_Bright
Glta,Farrell
Great post.
In the NHS dexamethasone trial its anti-inflammatory effect was judged by the clinical response. Inflammatory markers are only briefly mentioned.
https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
Now we have Brilacidin with 3 possible antiviral MOA's plus being a proven broad spectrum antibiotic and with anti-inflammatory properties.
It seems it would be difficult to tell which MOA was primarily improving clinical response except as you outlined by correlating the time from the first infectious symptoms and following inflammatory markers serially.
The other question I have is the 3 or 5 day dosing. Obviously the current planned dosing is for the antiviral effect. The long half life of Brilacidin will extend its biologic effects several days.
If the Brilacidin's primary MOA is anti inflammatory and not anti viral should the dosing be adjusted for that effect? In the NHS study Dexamethasone was given for up to 10 days. Will monitoring inflammatory markers as planned be helpful in adjusting the Brilacidin treatment course from 3 to 5 days?
In this short Phase 2 trial it is not likely additional adjustments will be made in the trial parameters. If the inflammatory markers show a response to Brilacidin, how would you design the Phase 3 trial?
TIA
GLTA Farrell
You are correct it is not clear. It is clear the DMC will review the results after its interim analysis safety review. So about half of the patients will receive the 3 day treatment, whatever dose that is.
The other half could receive the 3 day or the 5 day course. It is possible sub groups or even individual patients could receive different treatment lengths based on their response to treatment ,but I think that would complicate the statistical analysis and make the"quadruple blinding" more complex.
I had the same thought that it was a compromise between IPIX and the FDA.
Hopefully the interim report will be more revealing.
Good luck,Farrell
Leronlimab is an anti-inflammatory medication; its primary competitor for Covid 19 is Dexamethasone.
If Brilacidin proves to be an effective antiviral for Covid 19 its primary competitor will be Remdesivir.
Even if Leronolib becomes the primary Covid19 anti-inflammatory drug it does not, "raise the bar" for Brilacidin one millimeter.
Dexamethasone has become widely used for Covid19. It has a long history as an inexpensive synthetic corticosteroid with multiple indications.
Dexamethasone was shown to significantly reduce mortality against Covid19 in an extremely well done 11,000 patient British study published in the NEJM.
https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
"Dexamethasone reduced deaths by one-third in ventilated patients and by one fifth in other patients receiving oxygen only.There was no benefit among those patients who did not require respiratory support."
https://www.gmmh.nhs.uk/download.cfm?doc=docm93jijm4n7645.pdf&ver=10221
It is Leronlimab, even with its potentially promising study, which still has a significant bar to overcome.
GLTA, Farrell
Ridgeback Biotherapeutics has an interesting as well as colorful history in its efforts to profit from Molnupiravir :
https://www.washingtonpost.com/business/2020/06/11/coronavirus-drug-
ridgeback-biotherapeutics/
https://pulitzercenter.org/stories/emails-offer-look-whistleblower-charges-cronyism-behind-potential-covid-19-drug
Molnupiravir is an oral drug with a mechanism of action similar to Remedesivir and Favipiravir. The phase 1 study is linked below:
https://aac.asm.org/content/aac/early/2021/02/24/AAC.02428-20.full.pdf
Interesting the hedge fund manager,Wayne Holman, is listed as a lead author of the Phase1 report.
Glta,Farrell
I agree since it was found to be safe in the ABSSSI trial, it makes sense to use the .6mg/kg Brilacidin dose even if it later proves to be effective at a lower dose. The lower possible dose was suggested in the RBL studies and was reported in the Virus journal article:
"Recently released in vitro data showed Brilacidin exhibited a potent inhibitory effect on SARS-CoV-2, the novel coronavirus responsible for COVID-19, in a human lung epithelial cell line—reducing viral load by 95 percent and 97 percent at two efficacious concentrations tested, compared to control (DMSO)."
"The new data, using the same assay method, reveal Brilacidin exhibited a similarly potent inhibitory effect against SARS-CoV-2 at an even lower concentration in the same human lung epithelial cell line. Brilacidin achieved approximately 90 percent inhibition of SARS-CoV-2 at a drug concentration that was one-half lower than previously tested. The lowest concentration of Brilacidin used in RBL testing to date is well below the clinically-achievable concentration based on the pharmacokinetics observed in the Company’s Phase 2b clinical trial of Brilacidin in Acute Bacterial Skin and Skin Structure Infections"
http://www.ipharminc.com/press-release/2020/7/20/innovation-pharmaceuticals-brilacidin-inhibits-novel-coronavirus-covid-19-by-almost-90-at-the-lowest-concentration-tested-to-date-in-a-human-lung-cell-line
The journal article also gave some additional information regarding Brilacidin dosing which I summarized in post 346149 It also allows comparison with Remdesivir:
The Discussion on page 10 outlines the results of the study:
1. "All experiments conducted in Vero and Calu-3 cell line models were supportive of an early inhibition exerted by brilacidin on SARS-CoV-2, indicating the drug’s impact on viral integrity. The idea that brilacidin directly interferes with the integrity of the virion is further supported by the observation that when drug treatment was limited to the virus alone (Figure 2E), with no treatment of host cells, a robust decrease of viral load was still observed in both the Washington strain and the Italian strain of SARS-CoV-2."
This is consistent with claims Brilacidin is virucidal. It quickly attacks the virus before it enters the cell.
2. "The high CC50 (a measure of cytotoxicity) and low IC50 (a measure of potency) values observed for brilacidin in Calu-3 cells—{ human lung epithelial cells}yielding a Selectivity Index (SI) for brilacidin of 426 (CC50 = 241µM/IC50 = 0.565µM)—strongly support brilacidin’s treatment potential to possibly achieve positive antiviral outcomes in humans clinical trials."
This statement reflects the low toxicity and high potency of Brilacidin against Covid 19. The high SI number supports positive outcomes in human clinical trials
3. In the combination studies Brilacidin and Remdesivir 2.5 um demonstrated synergy in vitro
https://www.mdpi.com/1999-4915/13/2/271
The reality is the 2.5 um dose is easiy achievable in vivo by Brilacidin which obtained a median C-max in the ABSSSI study of 7.67 um and is well above its IC 50 of .565um.
https://www.biorxiv.org/content/10.1101/2020.10.29.352450v1.full
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, Nuc-TP, 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
Thanks for sharing your insight and experience.
How do you expect the SOC drugs will be used? If SOC includes Remdesivir do you expect it will be used in either the control or treatment arm?
If Redesivir is used in the treatment arm it may make it difficult to determine Brilacidin's effect in such a small trial.
In Russia it seems Favipiravir will be used as the SOC.
I was surprised the Brilacidin for Covid phase 2 clinical trial did not include any dosage information. The best guess seems to be it will follow the .6mg/kg x first day then .3mg/kg the final 2 days as in the ABSSSI trial followed by IV placebo x 3 days:
" Subjects randomized to brilacidin will receive either a single intravenous infusion (0.6 mg/kg or 0.8 mg/kg) followed by six days of once daily placebo, or a three day regimen (0.6 mg/kg on Day 1 followed by 0.3 mg/kg on Days 2 and 3) followed by 4 days of once daily placebo. Subjects randomized to daptomycin will receive 7 days of treatment. Subjects will be assessed for both clinical and microbiologic efficacy 48-72 hours after the first dose of study drug. After an assessment at Day 7-8, subjects will be again be evaluated for efficacy at Day 10-14 and via a phone contact at Day 21-28."
https://clinicaltrials.gov/ct2/show/NCT02052388
Thanks again,
Farrell
Experts fear a new surge of coronavirus infections in the US due to new mutations.
"The fear is that just as humanity appears to be finally turning the corner in the battle against the virus, the variants could give the pathogen the upper hand once again. They could trigger a new surge. And new, even more worrisome variants could emerge because the virus is still spreading so widely."
New therapeutics are more important than ever before.
GLTA,
Farrell
https://www.npr.org/sections/health-shots/2021/03/03/971327204/worried-about-coronavirus-variants-heres-what-you-need-to-know
I reviewed the Brilacidin clinical trials .gov site again this AM and found this:
"The study will start with 3 days of study drug administration. After an interim analysis safety review, by an independent Data Monitoring Committee (DMC), dosing may be extended to 5 days."
My interpretation is if the drug is working well they will maintain the 3 day dosing. If after the interim review ,which should be mid trial, they can increase the dosing to 5 days if they feel additional benefit can be safely achieved from 2 additional days of treatment.
So that answers a lot of questions. The DMC will only raise the dose for the whole trial based on the analysis at the interim review. Individual patients will not be given 2 extra days based on their individual responses.
Sorry for the oversight.
GLTA Farrell
That is a good question which brings up more questions:
What criteria will the DMC use to extend treatment, will the 5 day course be given to patients who are struggling; patients with more risk factors who are otherwise improving; will the doctors have to request the extension; how will the extension affect the data interpretation as well as the "blinding of the trial"?
Another good point: the DMC must be working around the clock in order to be able to make the call to extend a patient from 3 day to 5 day.
DMC responsibilities and meetings can vary. Below are some reviews of DMCs.
https://www.ctti-clinicaltrials.org/files/recommendations/dmc-recommendations.pdf
https://www.jclinepi.com/article/S0895-4356(20)30612-0/pdf
GLTA Farrell
The trial is not adaptive as I thought it might be. The only variation allowed is the possible extension of dosing to 5 days as previously PRed.
Ordinal scale for staging at onset and quantifying results as previously reported.
I read it twice and could not find the dosing.
Nothing surprising on the exclusions.
The primary and secondary outcomes were well explained and reasonable. I thought they were more challenging than other therapeutic trials.
Bottom line if it works it works. We should know soon.
With the slow roll out I hope theywill do an interim report as mentioned previously.
GLTA Farrell
Agree...Excellent review:
Thanks for posting, Farrell
Brilacidin COVID-19 Antiviral News
March 2, 2021 - Innovation Pharmaceuticals announced the publication of a peer-reviewed scientific article—Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture—in the journal Viruses. Leo Ehrlich, Chief Executive Officer of Innovation Pharmaceuticals, commented, “Infectious disease experts have noted the next phase in the global fight against COVID-19 will be in developing potent antivirals that directly act on the SARS-CoV-2 virus—which is what Brilacidin has been shown to do in pre-clinical studies.
February 26, 2021 - Innovation Pharmaceuticals provided additional study details for its ongoing Phase 2 clinical trial assessing Brilacidin as a novel therapeutic in hospitalized patients with COVID-19. Patients are being treated, with recruitment and enrollment progressing at trial sites.
January 14, 2021 - Innovation Pharmaceuticals’ Brilacidin for the Treatment of COVID-19 Receives FDA Fast Track Designation. Laboratory testing at independent laboratories supports Brilacidin’s antiviral ability to safely and potently inhibit SARS-CoV-2 and multiple strains of human coronaviruses. In a human lung cell line against SARS-CoV-2, Brilacidin achieved a Selectivity Index of 426. A molecular screening study of 11,552 compounds also supports Brilacidin as a promising novel coronavirus treatment. Brilacidin antiviral research to date has been limited to laboratory-based experiments.
December 21, 2020 - The U.S. FDA Granted IND Approval for Phase 2 Clinical Trial of Innovation Pharmaceuticals’ Brilacidin for Treating COVID-19. Brilacidin’s potent in vitro inhibition of the Washington and Italian strains of SARS-CoV-2 supports its potential to inhibit emerging coronavirus mutations (variants), such as those in the United Kingdom, Denmark, and South Africa.
November 30, 2020 - Innovation Pharmaceuticals COVID-19 Clinical Trial to Support Additional Development of Brilacidin as a “Pan-Coronavirus” Therapeutic. Additional independent preliminary laboratory research suggests Brilacidin, the Company’s flagship defensin mimetic, can treat other endemic human coronaviruses (H-CoVs), such as those causing common colds, and not just SARS-CoV-2, the novel coronavirus responsible for the ongoing global COVID-19 pandemic.
November 16, 2020 - Innovation Pharmaceuticals announced that an overseas Clinical Trial Application (CTA) had been submitted to the governing health agency, with a U.S. Investigational New Drug (IND) application also to be submitted this week to the FDA. Both these submissions are part of final preparations for the Company’s multinational Phase 2 clinical trial of Brilacidin for COVID-19, which is on track to commence in 2020 upon gaining required approvals.
October 30, 2020 - Innovation Pharmaceuticals and George Mason University’s (Mason’s) National Center for Biodefense and Infectious Diseases (NCBID) jointly announced the completion of extensive laboratory testing supporting the anti-SARS-CoV-2 activity of Brilacidin, a defensin-mimetic drug candidate, which is being developed as a potential COVID-19 treatment. “In testing at GMU’s BSL-3 lab, we showed that Brilacidin potently inhibits SARS-CoV-2 in vitro against the live virus. Beyond exhibiting treatment potential for those already infected by COVID-19, Brilacidin’s ability to disrupt viral integrity and block viral entry indicates it has the added potential to prevent infection, upon appropriate formulation, as a prophylactic. I look forward to working with Innovation to investigate further Brilacidin’s antiviral properties,” said Aarthi Narayanan, Ph.D., Associate Professor of Systems Biology in Mason’s College of Science.
Brilacidin COVID-19 Antiviral Clinical Trial
The Phase 2 clinical trial will be a randomized, double-blind, placebo-controlled, multi-national, multi-center study that is expected to enroll approximately 120 patients with moderate-to-severe COVID-19. The trial’s primary endpoint is time to sustained recovery through Day 29 based on the National Institute of Allergy and Infectious Diseases Adaptive COVID-19 Treatment Trial clinical status ordinal scale.
Related Articles
reserach lab
Fact checked by Robert Carlson, MD
3 in 1 Combination COVID-19 Therapeutic Launches Late-Stage Study
Innovation Pharmaceuticals Brilacidin is a combination antiviral, immuno/anti-inflammatory, and antimicrobial COVID-19 therapeutic candidate
https://www.precisionvaccinations.com/vaccines/brilacidin-covid-19-therapeutic
Vaccine Data
Condition:
COVID-19
Drug Class:
Antiviral
Name
Brand:
Brilacidin
Generic:
PMX-30063
Manufacturer
Innovation Pharmaceuticals Inc
Country ID:
US
Code
ChEMBL ID:
25023695
Accession Number:
DB12997
UNII:
I1679X069H
Status
Status:
Candidate
FDA First In Class:
Yes
Availability:
Pending
Clinical Trials
Clinical Trial Phase II:
Study of the Effects of Brilacidin Oral Rinse on Radiation-induced Oral Mucositis in Patients With Head and Neck Cancer (Brilaci
External Data
VIS:
PDF
New Vax Data
VIR-7831 Antibody
Janssen COVID-19 Vaccine (Ad26.COV2-S)
Herpes Vaccine Candidates
Plaquenil Antiviral Medication
Pfizer-BioNTech COVID-19 Vaccine
Moderna COVID-19 Vaccine
Sputnik V Vaccine
Sci-B-Vac Hepatitis B Vaccine
Brilacidin COVID-19 Therapeutic
VBI-1901 Glioblastoma (GBM) Cancer Vaccine
VBI-2601 Hepatitis B Vaccine
VGX-3100 HPV Cancer Vaccine
Thanks for pointing that out. I should have said it is likely to be an adaptive trial as I explained in the post below:
"We will not know for sure until the Brilacidin for Covid19 protocol is released {? tomorrow} but the last PR is suggestive of a plan similar to NIAID's ACTT plan which tested Remdesivir and other Covid drugs.
Plus the most of the recent Covid therapeutic studies have been done through one of the 6 ACTT plans.
https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6
"After an interim review, by an independent Data Monitoring Committee (DMC), dosing may be extended to 5 days.
The trial’s primary endpoint is time to sustained recovery through Day 29, using a clinical status ordinal scale based on that used in the series of National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trials (ACTTs). Additional endpoints include: in-hospital outcomes (e.g., duration of hospitalization, time to discharge), all-cause mortality, measurement of disease biomarkers (e.g., CRP, ferritin) and inflammation-related biomarkers (e.g., IL-1ß, IL-6, IL-10, total IL-18, TNF-a), changes to SARS-CoV-2 viral load, as well as other key measures."
http://www.ipharminc.com/press-release/2021/2/26/innovation-pharma-provides-study-details-for-ongoing-phase-2-clinical-trial-of-brilacidin-in-hospitalized-covid-19-patients"
Glta, Farrell
Good luck, Farrell
We will not know for sure until the Brilacidin for Covid19 protocol is released {? tomorrow} but the last PR is suggestive of a plan similar to NIAID's ACTT plan which tested Remdesivir and other Covid drugs.
Plus the most of the recent Covid therapeutic studies have been done through one of the 6 ACTT plans.
https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6
"After an interim review, by an independent Data Monitoring Committee (DMC), dosing may be extended to 5 days.
The trial’s primary endpoint is time to sustained recovery through Day 29, using a clinical status ordinal scale based on that used in the series of National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trials (ACTTs). Additional endpoints include: in-hospital outcomes (e.g., duration of hospitalization, time to discharge), all-cause mortality, measurement of disease biomarkers (e.g., CRP, ferritin) and inflammation-related biomarkers (e.g., IL-1ß, IL-6, IL-10, total IL-18, TNF-a), changes to SARS-CoV-2 viral load, as well as other key measures."
http://www.ipharminc.com/press-release/2021/2/26/innovation-pharma-provides-study-details-for-ongoing-phase-2-clinical-trial-of-brilacidin-in-hospitalized-covid-19-patients
Glta, Farrell
Some of key points:
-The Merck/Oncoimmune drug, CD24Fc now MK-7710, is an immunmomodulating drug developed for treatment of Graft vs Host disease seen as a complication of bone marrow transplants.
-Its phase 3 clinical trial for Covid19 showed good results even in the sickest patients.
-As an anti-inflammatory it will compete against dexamethasone. If I was advising the FDA what I would want to know is this really better than dexamethasone and would require a head to head trial.
-Neither Dexamethosone or CD24Fc now MK-7710 will compete directly against Brilacidin which is being studied as an antiviral.
Unless ,of course, Brilacidin immmunomodulating effects are so effective it makes anti-inflammatory medications unnecessary.
GLTA, Farrell
Most of what concerns you and Mr Locke about the Brilacidin Phase 2 trials ignores the fact that this is an adaptive trial and has the ability to add additional patients and even extend the trial to a Phase 3 seamlessly if Brilacidin is found to be safe and effective.
Below the FDA describes different scenarios describing current clinical trials for Covid 19. Brilacidin's protocol will likely have elements of these trials
From the FDA update:
https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials
"The Adaptive COVID-19 Treatment Trial (ACTT) is evaluating the safety and efficacy of the investigational antiviral Veklury® (remdesivir), developed by Gilead Sciences Inc., alone and in combination with other therapeutics. The patient population is hospitalized adults with COVID-19 and evidence of lung involvement, including rattling sounds when breathing (rales) with a need for supplemental oxygen or abnormal chest X-rays, or illness requiring mechanical ventilation."
"The ACTIV-2 master protocol(link is external) is designed as a Phase 2 trial that can expand seamlessly to Phase 3. The trial will enroll adults with COVID-19 who are not hospitalized and aims to evaluate safety, to understand if the investigational treatment can reduce the duration of symptoms, and to test if the treatment can increase the proportion of participants with undetectable virus. It will perform testing using nasopharyngeal swabs at specific time points. Multiple therapies, beginning with a monoclonal antibody but including other types of therapeutics, will be tested in ACTIV-2."
"Working in an unprecedented timeframe, the ACTIV public-private partnership has evaluated hundreds of available therapeutic agents with potential application for COVID-19, prioritized the most promising candidates, designed and harmonized five adaptive master protocols for ACTIV clinical trials, and selected numerous NIH-supported networks to launch these clinical trials to test prioritized therapeutic candidates.
"Master protocols allow coordinated and efficient evaluation of multiple investigational agents as they become available, but within the same clinical trial structure, across multiple study sites. Adaptive protocols swiftly weed out experimental drugs that do not demonstrate effectiveness and identify those that do. Adaptive master protocols reduce administrative burden and cost, provide a flexible framework to rapidly identify drugs that work, and rapidly move additional experimental agents into the trial."
GLTA Farrell
Why GSK? If phase 2 Brilacidin for Covid 19 is solidly positive IPIX should have its choice of suitors.
Good luck to all,
Farrell
When clinicaltrials.gov is released we should receive a better definition of what SOC means for this trial.
Many institutions routinely use an anti-inflamtory (usually dexamethasone) ;anticoagulants are routinely added especially if cardiac involvement develops such as arrhythmias,myocarditis,or ischemia. Others often use other treatments such as convalescent plasma even azithromycin and other treatments which have marginal scientific basis. These are just examples because the treatments will vary at different institutions which makes it impossible to predict the SOC.
Any co existing or developing medical problems will be treated
In the treatment arm all 60 patients will receive Brilacidin.
In the control arm my feeling is some of the patients will receive Remdesivir others, primarily, in Russia, will receive Favipiravir.
The above is just my best guess from reading the PRs and literature, we will have a better idea when the protocols are outlined in clinicaltrials.gov.
Glta,
Farrell
You are exactly right.
My bet is once today's new information sinks in the share price will respond.
GLTA Farrell
Do you remember IPIX in a better position then right now?
14 milly in the bank.
B in patients from East to West in a multinational trial.
Fast Tracked
Peer reviewed journal article printed.
Can’t believe we get to continue to accumulate while we wait and debate. Got to love a sleeper pick.
With todays PR much of the mystery of the clinical trials is solved. IMO this is the buy of the decade. I bought more today and look to pick up additional shares as I expect the price to run next week.
Look for a run up in the last hour today.
JMO
GLTA
ACTT developed by the NIAID seems to be the outline Brilacidin will be following for Brilacidin for Covid19 Phase2. Until the study guidelines are published on Clinicaltrials.gov it is useful to review the ACTT.
GLTA,Farrell
From todays PR:
" The trial’s primary endpoint is time to sustained recovery through Day 29, using a clinical status ordinal scale based on that used in the series of National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trials (ACTTs). Additional endpoints include: in-hospital outcomes (e.g., duration of hospitalization, time to discharge), all-cause mortality, measurement of disease biomarkers (e.g., CRP, ferritin) and inflammation-related biomarkers (e.g., IL-1ß, IL-6, IL-10, total IL-18, TNF-a), changes to SARS-CoV-2 viral load, as well as other key measures.
8 point ordinal scale:
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant
Brilacidin will follow some of the the NIAID Adaptive Treatment Trial guidelines for Covid 19 studies as outlined in the links below:
https://clinicaltrials.gov/ct2/show/NCT04280705 ACTT1}
https://clinicaltrials.gov/ct2/show/NCT04401579 {ACTT2}
https://clinicaltrials.gov/ct2/show/NCT04492475 {ACTT3}
In addition to the study parameters outlined in the PR the following are included in the ACTT 3 and most likely many of these will be incorporated in the Brilacidin for Covid19 protocol when it is released on clinicaltrials.gov:
1 "There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms."
2 "Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. "
3. "All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized)."
4." The primary outcome is time to recovery by Day 29 for patients with baseline ordinal score 4, 5 and 6. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. Each stage may prioritize different secondary endpoints for the purpose of multiple comparison analyses."
5.Primary Outcome Measures :
" Time to recovery for patients with baseline ordinal score 4, 5, and 6 [ Time Frame: Day 1 through Day 29 ]
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care."
6. Secondary Outcome Measures :
Change from baseline in alanine aminotransferase (ALT) [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in aspartate aminotransferase (AST) [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in C-reactive protein (CRP) [ Time Frame: Day 1 through Day 29 ]
Change from baseline in creatinine [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in d-dimer concentration [ Time Frame: Day 1 through Day 29 ]
Change from baseline in hemoglobin [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in international normalized ratio (INR) [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in platelets [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in total bilirubin [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change from baseline in white blood cell count (WBC) with differential [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Change in National Early Warning Score (NEWS) from baseline [ Time Frame: Day 1 through Day 29 ]
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6). Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Cumulative incidence of serious adverse events (SAEs) [ Time Frame: Day 1 through Day 29 ]
Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6). An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Duration of hospitalization [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of invasive mechanical ventilation [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of new oxygen use [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of non invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 29 ]
Measured in days.
Duration of oxygen use [ Time Frame: Day 1 through Day 29 ]
Measured in days
Incidence of discontinuation or temporary suspension of study product administration [ Time Frame: Day 1 through Day 10 ]
For any reason. Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).
Incidence of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 29 ]
Incidence of new oxygen use [ Time Frame: Day 1 through Day 29 ]
Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 29 ]
Mean change from baseline in the ordinal scale [ Time Frame: Day 1 through Day 29 ]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Participant's clinical status at Day 15 by ordinal scale for patients with baseline ordinal score 4 and 5 [ Time Frame: Day 15 ]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Percentage of subjects reporting each severity rating on an 8 point ordinal scale [ Time Frame: Days 3, 5, 8, 11, 22, and 29 ]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Subject 14-day mortality [ Time Frame: Day 1 through Day 15 ]
Date and cause of death (if applicable).
Subject 28-day mortality [ Time Frame: Day 1 through Day 29 ]
Date and cause of death (if applicable).
Time to an improvement of one category using an ordinal scale [ Time Frame: Day 1 through Day 29 ]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time to an improvement of two categories using an ordinal scale [ Time Frame: Day 1 through Day 29 ]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Time to discharge or to a National Early Warning Score (NEWS) of </= 2 and maintained for 24 hours, whichever occurs first [ Time Frame: Day 1 through Day 29 ]
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Time to recovery for patients with a baseline ordinal score of 4 and 5 [ Time Frame: Day 1 through Day 29 ]
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.
Thanks, post of the month. Mods please sticky to top.
Good luck, Farrell
IPIX simply lucked out that Brilacidin is showing promise and is in the running as a potential covid therapeutic.
Fighting COVID-19-Related Financial Fraud
https://www.sec.gov/fighting-covid-19-related-financial-fraud
SEC Coronavirus (COVID-19) Response
https://www.sec.gov/sec-coronavirus-covid-19-response
Click to open Enforcement, Examinations and Investor Education tab for list of problem companies.
You won't find IPIX since they have independent research from two US Regional Biocontainment labs showing promise of Brilacidin against Covid. And, the company has had FDA had meetings with FDA and is in midst of a covid trial.
Agree, "it won’t be long before we hear something."
Clinical trials .gov listing required by 21 days after initiation of study treatments.
Listing could begin at any time.
From 1/29/2021
"Innovation Pharmaceuticals’ Phase 2 Clinical Trial of Brilacidin for Treating COVID-19 Scheduled to Begin Next Week"
One week from 1/29 was 2/5...+21 is this coming Friday 2/26.
Glta,Farrell
Do you have a link for that? No mention of change in 10Q.
Good luck,
Farrell
"My point of the above is to show this 10Q extension request is unusual and the explanation seemingly unprecedented under Leo's reign. I expect the "significant change" to be significantly positive."
For many reasons and after extensive review and parsing the 10q extention, I have decided it is likely to be positive too.
We should know for sure tomorrow.
GLTA Farrell
If Brilacidin is only marginally better than Remdesivir it will be a roaring success.
GLTA,Farrell
Unfortunately there are too many "no ways" in your argument.
I think IPIX will clarify the situation soon.
I will not be upset if it is shown you are right and I am wrong, but I am certain with the information we have been given neither of us can conclusively predict how this will turn out.
And, that's why I am not discussing it any more until the company issues its clarification.
GLTA,Farrell
Unfortunately there are too many "no ways" in your argument.
I think IPIX will clarify the situation soon.
I will not be upset if it is shown you are right and I am wrong, but I am certain with the information we have been given neither of us can conclusively predict how this will turn out.
And, that's why I am not discussing it any more until the company issues its clarification.
GLTA,Farrell
Your premise just does not follow. Kips Bay did not own the preferred shares therefore it had nothing to convert.Kips Bay and Leviston are different legal entities
Kips Bay only had common shares reported on the 13G.
If Lewiston somehow became Kip's Bay or transferred the IPIX shares that should be a material event for IPIX since the transfer would include warrants and preferred shares which could impact IPIX financially.
Stay tuned.
Good luck,Farrell
So maybe the last week or 2?I do not remember seeing it before.
That would correlate with the rumors last week.
GLTA Farrell
Expanded Access and Compassionate Use
Is this new?
http://www.ipharminc.com/expanded-access-and-compassionate-use
My guess is the FDA would require it since it appears Covid19 resistance to drugs and vaccines is going to be an issue.
GLTA Farrell
You could be right, but they are separate agreements.
An 8K was released after the Leviston deal, but none after the Kips Bay.
The Leviston deal involved warrants and preferred stock whereas the Kips bay deal only common stock was reported.
It is my understanding the Kips bay deal has 60 days to announce additional terms, but IPIX should have had to issued an 8K in 4 days if it was more than a stock deal if I understand the SEC requirements properly.
IPIX should clarify the Kips Bay deal soon.
Good look ,Farrell
Thanks for posting. There have been reports of clusters of elderly and ill patients dying after vaccination; most of these have received the Pfizer vaccine.
Norway; 23 dead after Pfizer vaccine
https://www.bmj.com/content/372/bmj.n149
Spain: 7 nursing home patients died in Spanish nursing homes and 78 came down with Covid 19 after Pfizer caccine
https://www.globaltimes.cn/page/202102/1214761.shtml
Germany:10 dead after Pfizer vaccine
https://health.economictimes.indiatimes.com/news/diagnostics/german-specialists-probing-10-deaths-of-people-vaccinated-against-covid-19/80278306
Many "fact checkers" claim deaths not related to vaccines:
https://www.dw.com/en/fact-check-are-covid-19-vaccines-causing-deaths/a-56458746
These associations always occur when treatments are given quickly to millions of people. People become ill and die every day. People who are elderly, frail and ill die at a faster rate. Whether they are related to the vaccinations or not will take years of study.
After the reports of Gillian Barre autoimmune disorder occurring after flu vaccinations decades ago years of intensive study suggested a consensus that they "could" be related.
The fact is we may never know.
If the current studies prove Brilacidin is effective against Covid19,it will be tested as a prophylactic treatment; that is, given after exposure or at the onset of Covid19 in high risk individuals, but before they are clinically ill to prevent complications in high risk individuals.
Animalstudies have already been done for Remdesivir used in this way which suggest a benefit.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32021-3/fulltext
I believe a Brilacidin inhaler will soon be developed for prophylaxis if the current studies prove efficacy against Covid19.
Some day Brilacidin prophylaxis may be proved to be superior to vaccinations in some individuals.
GLTA,Farrell
Great point. We will see if that is addressed in the clinical trials.gov when it is posted . Some covid trials have checked for mutation/variants and others have not.
Hopefully this trial will since it is becoming more prevalent.
GLTA, Farrell
I agree the high number of sites is a surprise. We know from the US experience how regional Covid19 can be.I expect some of the sites will have 15-20 patients in the study while others will have 3 or 4 or may be even none due to the hot spots which can develop with Covid 19.
An excellent plan to quickly complete the study.
GLTA,
Farrell