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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
Good point.
Farrell
No facts currently support the notion that this represents toxic financing.
We know very little about the deal. It is interesting the number of shares owned by Kips bay is an odd lot,20,978,229. Usually odd lots are the result of retail buying. I have never seen a company release an odd lot in a financing deal.
IPIX is sure to enlighten us soon about the deal if it includes warrants or other enticements, but we are 10 days from the Kips bay announcement. If the event were material an 8K should have been released within 4 days.
GLTA,Farrell
How do you know that? They just purchased 20 million shares; may be they want 20 million more.
GLTA Farrell
IPIX could release an after hours PR which is always welcome.
GLTA Farrell
I think Biopa is correct. The transaction is a stock purchase or acquisition without restriction. My understanding is Kips Bay has the right to buy and sell IPIX stock without restriction until they get to 5% then they have to report the 13G which they did.They also have the right to form groups to acquire stock.
They are in because they think the stock price is going up.
The new owner is called a Beneficial owner:
"“Beneficial Ownership” has two components: voting power and investment power. Voting power includes the power to vote, or to direct the voting of, the security. Investment power includes the power to dispose of, or to direct the disposition of, the security. Beneficial ownership can be shared by security holders (including through any contracts or arrangements) and can arise directly or indirectly. In addition, when calculating the number of securities beneficially owned, a person must include that person’s right to acquire beneficial ownership of that class of securities within 60 days (through, for example, the exercise of an option or a warrant)."
https://www.lexology.com/library/detail.aspx?g=41a16a1b-a159-409c-98ad-39051b7f4753
The SEC report calls this a rule 13D-1c transaction:
"Rule 13d-1(c) is the “Passive Investor” exemption and provides that holders who (1) have not acquired the securities with any purpose, or with the effect, of changing or influencing the control of the issuer (or in connection with or as a participant in any transaction having that purpose or effect), (2) are not an “Institutional Investor” defined in the “Institutional Investor” exemption and (3) are not directly or indirectly the beneficial owner of 20 percent or more of the class may file a Schedule 13G in lieu of a Schedule 13D. The determination of whether an investor is a “passive investor” is based on the specific facts and circumstances of the investment"
The 13d-1{c] excludes institutional investors who must file under 13d-1{b]
“Institutional Investors” include certain (1) broker dealers; (2) banks; (3) insurance companies; (4) registered investment companies; (5) registered investment advisers; (6) ERISA plans; (7) parent holding companies or control persons, provided the aggregate amount held directly by the parents or control persons, and directly and indirectly by their subsidiaries or affiliates that are not persons specified in this list of individuals, does not exceed 1 percent of the securities of the subject class; (8) savings associations; (9) church plans excluded from the definition of investment company; (10) a non-US institution that is the functional equivalent of any of the institutions listed above that is subject to a regulatory scheme that is substantially comparable to the regulatory scheme applicable to an equivalent US institution; and (11) any group whose members are all persons enumerated in this list."
https://www.lexology.com/library/detail.aspx?g=41a16a1b-a159-409c-98ad-39051b7f4753
So our Kips bay investor could be an individual or group of individual investors.
The previous financing in December was more complex and involved the issuance of Warrants and preferred stock. Due to the requirements on the company,IPIX, it had to be reported in an 8K as a material event.
Many posters here have a greater understanding of the SEC requirements than I do. Feel free to comment or correct the above
http://www.edgarmaster.com/Inet/main/DataFeedHtml1.jsp
GLTA,
Farrell
50mg/ml is the concentration as supplied to the pharmacy, not the dose. The dose would be how many total milligrams were given, eg 5ml at 50 mg/ml would be a dose of 250mg.
As Keltoi stated this is often diluted in IV solution in varying amounts to give the final concentration, eg 250mg in .1 liter {100ml} of IV fluids would give a final concentration of 2.5mg per ml.
The last variable is the rate of delivery eg 50 ml per hour {often listed as cc}; for the above example the infusion time would be 2 hours
These details will be listed in the human trial protocol.
Farrell
Biodocs comments were supportive of the importance of the antiviral being administered during the proper window before the immune cascade and end organ damage becomes irreversible.
Hopefully Brilacidin's antiviral, anti-inflammatory and antibiotic attributes will prove to be part of the answer to this horrible plague.
The human clinical trials will soon provide the answer.If the human trials are successful the next phase of testing will be Brilacidin combined with other drugs, anti-inflammatory, antiviral and others looking for synergy.
If Brilacidin is effective my guess is Brilacidin will be developed as a prophylactic inhaler to be given at the time of diagnosis.
GLTA, Farrell
post 342729
"Though the anti-viral window may be small the effect may be profound in reducing viral load and limiting the cytokine cascade. The anti-inflammatory and anti-microbial properties of brilacidin complement the anti-viral properties and the relative importance of each will depend on the stage of disease.
I like Brilacidin's multiple mechanisms of action to fight the disease and limit tissue damage. As always, I fret over dosing and trial design.
Hoping for the best."
post 342733
"we don't know if B will help and I am always concerned about trial design and dosing.
Yes, in the ER it's almost all respiratory and the vast majority of ICU admissions are respiratory. Down the road, however, it's multisystem with damage from the inflammatory response. Renal failure and myocarditis are common. Neurological impairment is the norm and these patients have brain fog for months after recovery when they survive which is not about hypoxic brain injury.
How many patients have you seen who were extubated and appeared to be doing ok only to be admitted a few days later with heart failure only to die a few days later?
The multi-system problems are all secondary to inflammation. Did you see the articles about asymptomatic young male football players with myocarditis? 10% after 30 days if I recall correctly.
The anti-microbial properties of brilacidin are an added benefit and not a liability. ICU patients on ventilators frequently develop secondary infections. An anti-bacterial with a reasonable coverage spectrum, imo, is a good thing. We simply won't know if it makes a difference until trials are completed if any of this makes a difference in outcome.
Seems to me that if we reduce the viral load as early as possible while tempering the inflammatory response, patients stand a chance of doing ok. Critically ill patients who present at death's door are unlikely to do well no matter what we do."
What is most interesting you and others have focused on 1 chart and ignored the whole body of the research. In addition you and others have attributed efficacy to Remdesivir which it does not possess.
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 strainof 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—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 reposting and sharing your expertise.
If phase 2 is positive I believe the lack of good Covid19 treatment options as well as the focus on better treatment options will result in a course similar to Remdesivir.
Expanded compassionate use before stage 3 trial. Large expedited stage 3 trial with EUA after interim analysis. Followed by multiple new trials looking for synergy with other antivirals and anti-inflammatory medications. Then final approval after stage 3 trial analysis is finished.
Remdesivir was able to accomplish this in 7months. With FDA assistance plus Barda and other grants I think this would be possible for Brilacidin.
It is all contingent on successful trials to demonstrate superiority to Remdesivir in terms of safety and efficacy. Then Brilacidin needs financial and regulatory assistance the rest of the way.
If Brilacidin can lower mortality and complications it will be an absolute blessing for all.
Glta,
Farrell
Plus, that does not include a short squeeze, market hysteria,a bidding war or Reddit subscribers piling on.
Brilacidin is looking good going into an important week.
GLTA, Farrell
Well lets do the math.
Assume Brilacidin is successful and becomes the worldwide Covid19 antiviral drug of choice.
If Remdeivir can make 2 billion a quarter a superior drug could make at least 2.5 billion a quarter
2.5 billion x 4 quarters=10 billion/yr / number of shares 355.96 million per Yahoo financial
equals $29.76 dollars per share earnings x market multiple 20 P/E =
a share price of...
$595.308
Any way you look at it that is a lot of money.A very big bargaining chip for Leo and IPIX.
GLTA,
Farrell
I agree this could be a template for a future deal. If Brilacidin does become the Covid19 antiviral drug of choice it will be worth much more than OncoImmune's CD24Fc and Gilead's Remdesivir.
Remdesivir brought in almost 2 billion dollars last quarter. A lot of money for a drug many clinicians and the WHO says doesn't work or at best is mildly effective.
"Remdesivir, which is sold under the brand name Veklury, brought in $1.9 billion in the fourth quarter ended Dec. 31, above analysts’ estimates of $1.34 billion. Excluding Veklury, Gilead said its quarterly sales fell 7%."
"For 2021, the California-based company projected an adjusted earnings range with a midpoint of $7.10 per share, on product sales with a midpoint of $24.4 billion, ahead of respective Wall Street estimates of $6.85 per share and $24.27 billion, according to IBES data from Refinitiv."
https://www.reuters.com/article/us-gilead-sciences-results/gilead-forecasts-2021-growth-strong-remdesivir-covid-19-sales-idUSKBN2A42V7
https://www.bmj.com/content/371/bmj.m4057
There are creative ways of insuring the selling company can capture future growth and maintain the rest of its assets. For example:
Oncoimmune sold their GVH drug to Merck. The drug,
CD24Fc, was shown to be very effective in treating the severe immunologic complications of Covid in very ill patents
$425 million plus milestone and sales related payments to shareholders to place the drug in a new subsidiary owned by Merck.
In addition Oncimmune spun certain right and assets to current shareholders into a new company and received 50 million dollars
" Under the agreement, prior to the completion of the acquisition, OncoImmune will spin-out certain rights and assets unrelated to the CD24Fc program to a new entity to be owned by the existing shareholders of OncoImmune. In connection with the closing of the acquisition, Merck will invest $50 million, and become a minority shareholder, in the new entity."
" Merck (NYSE: MRK), known as MSD outside the United States and Canada, and OncoImmune, a privately-held, clinical-stage biopharmaceutical company, today announced that the companies have entered into a definitive agreement pursuant to which Merck, through a subsidiary, will acquire all outstanding shares of OncoImmune for an upfront payment of $425 million in cash. In addition, OncoImmune shareholders will be eligible to receive sales-based payments and payments contingent on the successful achievement of certain regulatory milestones. OncoImmune recently announced positive top-line findings from an interim efficacy analysis of a Phase 3 study evaluating its lead therapeutic candidate CD24Fc for the treatment of patients with severe and critical COVID-19.
Under the agreement, prior to the completion of the acquisition, OncoImmune will spin-out certain rights and assets unrelated to the CD24Fc program to a new entity to be owned by the existing shareholders of OncoImmune. Under the agreement, prior to the completion of the acquisition, OncoImmune will spin-out certain rights and assets unrelated to the CD24Fc program to a new entity to be owned by the existing shareholders of OncoImmune. In connection with the closing of the acquisition, Merck will invest $50 million, and become a minority shareholder, in the new entity.
https://www.merck.com/news/merck-to-acquire-oncoimmune/
GLTA,
Farrell
A Friday after the close, terrific PR would be welcomed.
GLTA,
Farrell
I think you hit the nail squarely on the head. IPIX has its hands full executing the trials and working with the FDA. This has resulted in fewer PRs.
My bet is the next PR will be substantial with many updates and maybe a few surprises.
BWDIK
GLTA,Farrell
Meanwhile Covid marches on:
"The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data."
We need Brilacidin...soon.
https://www.medscape.com/viewarticle/945490?src=mkm_covid_update_210208_MSCPEDIT&uac=144876AG&impID=3180029&faf=1
GLTA,
Farrell
2/5/2021 FDA limits convalescent antibody treatment after review of data shows disappointing results in very ill patients and patients with adequate antibodies.
"The revision states that only high-titer COVID-19 convalescent plasma can be used and only in hospitalized patients who are early in the disease course and those with impaired humoral immunity who cannot produce an adequate antibody response.
The revisions stem from new clinical trial data analyzed or reported since the original EUA was issued in August 2020. The original EUA did not have these restrictions."
https://www.medscape.com/viewarticle/945396
If Brilacidin proves to be widely effective it will have limited competition.
GLTA,
Farrell
I agree completely;the Phase2 trial will have limitations due to its size. We can expect the phase 3 trial to be much larger and more statistically accurate.
One undeniable factor in Brilacidin's favor is how mediocre the Covid19 antiviral competitors have been. Below is listed some of the concerns with Remdesivir, Regeneron's antibody therapy and Bamlanivimab.
Remdesivir is the Covid19 antiviral of choice at many hospitals in spite of its widely criticized early trial.Its "adaptive trial" was changed in mid course when it became obvious it did not improve mortality. Its only treatment benefit was a shorter hospital stay which was not an initial end point of the trial.The control group was eliminated.
"The study found that on day 11, patients in the five-day remdesivir arm were 65% more likely to achieve better clinical scores than the standard care arm. Using the same yardstick, there was no benefit with 10 days of remdesivir. Also, there was no reduction in hospitalisation, mortality or reduced duration of oxygen requirement. They concluded that patients receiving five days of remdesivir had a significantly different clinical status than those receiving standard therapy, with uncertain clinical importance.
As with previous COVID-19 related clinical trials, there are several red flags we need to address before interpreting the results. Of note: the sponsor of the trial is Gilead Sciences Inc., a major manufacturer of remdesivir. Additionally, the end-point is an unimpressive one: odds of a better clinical status is quite vague relative to other, more clinically meaningful measurements like mortality, hospital stay, duration of oxygen requirement, etc. None of the authors’ own exploratory end-points, such as time to recovery or time to improvement in clinical status (by 1, 2 or 3 points) were significantly different with remdesivir.
Of the patients included, 80-85% had a clinical score of 5 (hospitalised, not requiring supplemental oxygen but requiring ongoing medical care). It is unclear how the same end-point – change in clinical status – that was used by the trial group for their previous trials involving severe COVID-19 patients can be applied to patients with moderate disease.
At the outset, the premise of this trial is questionable at the least. Remdesivir costs Rs 5,000 per dose, implying a cost of Rs 30,000 or Rs 60,000 for a five- or 10-day course respectively. In people with moderate COVID-19, where the mortality was 1%, it is impossible to justify remdesivir’s use without evidence of concrete clinical benefit. There is nothing objectionable about negative trials – which are those trials that fail to achieve their desired end-point. However, the fact that this trial was allowed to report its result as positive, in favour of remdesivir, is highly suspect.
Also read: Remdesivir – a Drug in Search of a Disease
In a nutshell, this trial encapsulates the issues with trials funded by the pharmaceutical industry in the context of the COVID-19 pandemic. By applying an ambiguous end-point to a patient population that may not have needed any treatment other than supportive care or supplemental oxygen, this trial bears all the hallmarks of bad science. Another difficult concept to grasp is why patients receiving 10 days of remdesivir had no difference in clinical status compared to standard treatment, while those receiving five days of treatment did. Considering that all three arms had comparable characteristics and were randomised, the benefit from remdesivir should have been apparent in both arms, not just one.
By consistently allowing poorly designed trials to make their way in to prestigious journals – JAMA is the third highest rated medicine journal in the world – the medical fraternity is doing itself a great disservice. Research can only be considered reliable when it is scientifically sound and can withstand the scrutiny of rigorous peer review. Once trust in science is eroded, the after effects will be felt long after the pandemic has abated."
https://science.thewire.in/the-sciences/remdesivir-clinical-trial-jama-gilead-bad-science/
https://jamanetwork.com/journals/jama/fullarticle/2769870
https://jamanetwork.com/journals/jama/fullarticle/2768397
Regeneron's antibody treatment is still under review. Regeneron has tightly controlled the little data that has been released. Regeneron claims treatment given early can reduce the viral load and reduce "medically supervised visits". I can find no data on mortality, complications, reduced ventilator or oxygen usage.
The best summary I could find of the data is below describing both Regeneron's antibody and Lily's Bamlanivimab.
".. the monoclonal antibody products I'll be discussing have had studies that have not shown benefit or have been associated with worse outcomes for hospitalized patients, especially those on high-flow oxygen or in the intensive care unit (ICU)."
"This kind of strategy for early treatment is going to be a minor contribution from a prevention standpoint before we have widespread, effective vaccines. Studies remain in progress where it might have a larger role (although a very expensive one) in preventing disease in patients who might be at [higher] risk — especially, for example, in congregate living facilities or nursing facilities. Unfortunately, we will need to wait for data to see if this is effective.
So, we have some newer therapies. Nothing is a home run... "
https://www.medscape.com/viewarticle/941830
New data released suggested a use for monoclonal antibodies and Remdesivir for preventative care.
https://www.medscape.com/viewarticle/945136#vp_2
GLTA Farrell
That is definitely true. It is obvious IPIX has attracted new investors and their money. Any PR which brings more credibility to the trials and a positive outcome will make this rocket fly higher.
GLTA Farrell
My prayer is IPIX can blast past 2 dollars and leave OTC land behind.
Some day soon...maybe
GLTA,Farrell
Having a disciplined plan is essential to good investing.
Good luck,
Farrell