The fall in IPIX share price today was felt to be due the Merck PR today regarding its anti viral,molnupiravir.
Molnupiravir,EIDD-2801, has been studied for over 40 years ,but due to safety concerns in the past it was never developed into an antiviral drug until recently . At this point it is not a direct competitor to Brilacidin if it proves successful in treating moderate to severe covid patients.
Ridgeback's Molnupiravir failed its cliniacal trial for hospitalized patients with moderate to severe covid. The clinical was halted by Merck after the FDA asked for additional information.
https://www.empr.com/home/news/molnupiravir-m...treatment/
The current possible indications for Molnupiravir will be limited to prophylaxsis and early mild to moderate covid innon hospitalized patients.
https://www.merck.com/news/merck-and-ridgebac...r-moderat/
Brilacidin's clinical trial is for hospitalized patients with moderate to severe covid...
the trial Molnupiravir failed.
Molnupiravir has a positive Ames test which screens for genetic and fetal toxicity,
In addition concerns about safety Ridgeback has been accused of manipulating safety data as well as government safety for the advancement of Molnupiravir.
"The Bright allegation addressed by Benford's email centers on a so far unsuccessful effort by Florida-based Ridgeback Biotherapeutics to win new federal funding to develop EIDD-2801, a version of a 4-decade-old antiviral drug, into a treatment for COVID-19. Although the drug has shown potential against the coronavirus that causes the disease, Bright had opposed providing an immediate large funding boost. He argued the drug had already received substantial government support, and some earlier studies suggested EIDD-2801 could cause harmful genetic mutations. In his complaint, Bright suggests Kadlec attempted to help Ridgeback sidestep a government contracting process that is supposed to be guided by science. In one email to BARDA, a Ridgeback executive wrote that Kadlec was "personally" pushing the company "to move fast, but we can't without this authorization" for funding."
https://www.science.org/news/2020/05/emails-o...id-19-drug
https://www.washingtonpost.com/business/2020/...rapeutics/
The concern regarding Ridgeback's promotion of Molnupiravir in spite of significant safety concerns seems well documented.
Plus the shadow of birth defects as well as genetic damage hangs over this class of drug and Molnupiravir itself.
This is the controversy that led to Rick ?Bright leaving the government
" EIDD-2801 {Merck's Molnupiravir} has been viewed as a potential competitor to remdesivir, although a contentious one, because similar compounds are mutagenic in animal studies, meaning they produce birth defects. Rick Bright, who was removed from his position as head of the US Biomedical Advanced Research and Development Authority (BARDA) in April, was reluctant to provide funding for the drug for this reason, according to an 89-page whistleblower complaint Bright filed after being fired. Merck’s investment in EIDD-2801 can be seen as a vote of confidence in the compound.
Bright’s concerns began in November 2019, more than one month before China disclosed the first COVID-19 cases in Wuhan — ScienceMag has that story:
Raymond Schinazi, an Emory University chemist who has extensively studied the active ingredient in EIDD-2801 but has no connection to DRIVE, notes that his former pharmaceutical company, Pharmasset, abandoned it in 2003 after discovering its mutagenic properties. Schinazi says the small chemical tweaks made to increase the ingredient’s bioavailability and transform it into EIDD-2801 are unlikely to change its mutagenicity. “Thank goodness someone is raising the red flag,” about EIDD-2801, Schinazi says. “You don’t develop a drug that’s mutagenic. Period.”
" Merck’s Research Labs President Roger Perlmutter addressed the lingering questions about the drug’s mutagenic side-effects during the earnings call and explained what the company is doing to address safety concerns, a transcript of which is available at this link.
First of all, for the MK-4482, as you know, the compound is Ames positive. That’s, in a way, not unexpected given its mechanism of action. It is a cytosine analog so that — one could expect to see those kinds of things. The question is, does the compound have mutagenic activity that’s meaningful in mammalian cells and what do we want to do about this. Ordinarily, of course, we don’t want to take mutagens forward into clinical practice, although it has been done where the benefit/risk profile makes sense"
What does it mean to be Ames positive?:
The Ames test is a widely employed method... it is a biological assay to assess the mutagenic potential of chemical compounds.[1] A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, because cancer is often linked to mutation. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound...
THe positive Ames test and documented birth defects in similar compounds as document by Dr Bright must be thoroughly addressed.
https://bgr.com/2020/07/31/coronavirus-cure-m...ontroversy
https://en.wikipedia.org/wiki/Ames_test
A scientific article also demonstrated mammalian cell DNA toxicity which could induce birth defects or cancer in the host.
"SARS-CoV2 infection results in an age-related acute respiratory disease spectrum that can be life-threatening, especially in the elderly and individuals with select underlying comorbidies [14]. rNHC (initial metabolite of molnupiravir} has the potential to have therapeutic benefit in this setting. However, there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA. This risk can be inferred based on the common intermediate of the ribonucleoside diphosphate shared in the synthesis of both ribonucleoside triphosphates and 2′-deoxyribonucleoside triphosphates. The concern would be that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells. We take this as evidence that in exposing the viral population to mutagenesis in its RNA form, the host is likely to be exposed in its DNA form. It seems unlikely that a short course of therapy would spare the host from this exposure because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
Good luck to all,
Farrell
Molnupiravir,EIDD-2801, has been studied for over 40 years ,but due to safety concerns in the past it was never developed into an antiviral drug until recently . At this point it is not a direct competitor to Brilacidin if it proves successful in treating moderate to severe covid patients.
Ridgeback's Molnupiravir failed its cliniacal trial for hospitalized patients with moderate to severe covid. The clinical was halted by Merck after the FDA asked for additional information.
https://www.empr.com/home/news/molnupiravir-m...treatment/
The current possible indications for Molnupiravir will be limited to prophylaxsis and early mild to moderate covid innon hospitalized patients.
https://www.merck.com/news/merck-and-ridgebac...r-moderat/
Brilacidin's clinical trial is for hospitalized patients with moderate to severe covid...
the trial Molnupiravir failed.
Molnupiravir has a positive Ames test which screens for genetic and fetal toxicity,
In addition concerns about safety Ridgeback has been accused of manipulating safety data as well as government safety for the advancement of Molnupiravir.
"The Bright allegation addressed by Benford's email centers on a so far unsuccessful effort by Florida-based Ridgeback Biotherapeutics to win new federal funding to develop EIDD-2801, a version of a 4-decade-old antiviral drug, into a treatment for COVID-19. Although the drug has shown potential against the coronavirus that causes the disease, Bright had opposed providing an immediate large funding boost. He argued the drug had already received substantial government support, and some earlier studies suggested EIDD-2801 could cause harmful genetic mutations. In his complaint, Bright suggests Kadlec attempted to help Ridgeback sidestep a government contracting process that is supposed to be guided by science. In one email to BARDA, a Ridgeback executive wrote that Kadlec was "personally" pushing the company "to move fast, but we can't without this authorization" for funding."
https://www.science.org/news/2020/05/emails-o...id-19-drug
https://www.washingtonpost.com/business/2020/...rapeutics/
The concern regarding Ridgeback's promotion of Molnupiravir in spite of significant safety concerns seems well documented.
Plus the shadow of birth defects as well as genetic damage hangs over this class of drug and Molnupiravir itself.
This is the controversy that led to Rick ?Bright leaving the government
" EIDD-2801 {Merck's Molnupiravir} has been viewed as a potential competitor to remdesivir, although a contentious one, because similar compounds are mutagenic in animal studies, meaning they produce birth defects. Rick Bright, who was removed from his position as head of the US Biomedical Advanced Research and Development Authority (BARDA) in April, was reluctant to provide funding for the drug for this reason, according to an 89-page whistleblower complaint Bright filed after being fired. Merck’s investment in EIDD-2801 can be seen as a vote of confidence in the compound.
Bright’s concerns began in November 2019, more than one month before China disclosed the first COVID-19 cases in Wuhan — ScienceMag has that story:
Raymond Schinazi, an Emory University chemist who has extensively studied the active ingredient in EIDD-2801 but has no connection to DRIVE, notes that his former pharmaceutical company, Pharmasset, abandoned it in 2003 after discovering its mutagenic properties. Schinazi says the small chemical tweaks made to increase the ingredient’s bioavailability and transform it into EIDD-2801 are unlikely to change its mutagenicity. “Thank goodness someone is raising the red flag,” about EIDD-2801, Schinazi says. “You don’t develop a drug that’s mutagenic. Period.”
" Merck’s Research Labs President Roger Perlmutter addressed the lingering questions about the drug’s mutagenic side-effects during the earnings call and explained what the company is doing to address safety concerns, a transcript of which is available at this link.
First of all, for the MK-4482, as you know, the compound is Ames positive. That’s, in a way, not unexpected given its mechanism of action. It is a cytosine analog so that — one could expect to see those kinds of things. The question is, does the compound have mutagenic activity that’s meaningful in mammalian cells and what do we want to do about this. Ordinarily, of course, we don’t want to take mutagens forward into clinical practice, although it has been done where the benefit/risk profile makes sense"
What does it mean to be Ames positive?:
The Ames test is a widely employed method... it is a biological assay to assess the mutagenic potential of chemical compounds.[1] A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, because cancer is often linked to mutation. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound...
THe positive Ames test and documented birth defects in similar compounds as document by Dr Bright must be thoroughly addressed.
https://bgr.com/2020/07/31/coronavirus-cure-m...ontroversy
https://en.wikipedia.org/wiki/Ames_test
A scientific article also demonstrated mammalian cell DNA toxicity which could induce birth defects or cancer in the host.
"SARS-CoV2 infection results in an age-related acute respiratory disease spectrum that can be life-threatening, especially in the elderly and individuals with select underlying comorbidies [14]. rNHC (initial metabolite of molnupiravir} has the potential to have therapeutic benefit in this setting. However, there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA. This risk can be inferred based on the common intermediate of the ribonucleoside diphosphate shared in the synthesis of both ribonucleoside triphosphates and 2′-deoxyribonucleoside triphosphates. The concern would be that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells. We take this as evidence that in exposing the viral population to mutagenesis in its RNA form, the host is likely to be exposed in its DNA form. It seems unlikely that a short course of therapy would spare the host from this exposure because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
Good luck to all,
Farrell
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