Note that included in today's PR there is a link t
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Posted On: 04/20/2020 12:42:53 PM
Note that included in today's PR there is a link to a 45 page PDF updated 4/20/20 that is accessible on the IPIX web site discussing the following:
Brilacidin First-in-Class Defensin-Mimetic Drug Candidate
Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment
https://static1.squarespace.com/static/571535....20.20.pdf
This 45 page PDF has updated information summarizing mechanism of action, pre/clinical data and academic literature supporting the development of Brilacidin as a potential novel COVID-19 therapeutic. This document builds on a previous version released at the beginning of March.
From page 2:
Brilacidin (PMX-30063) is Innovation Pharmaceutical’s lead Host Defense Protein (HDP)/Defensin-Mimetic drug candidate targeting SARS-CoV-2, the virus responsible for COVID-19. Laboratory testing conducted at a U.S.-based Regional Biocontainment Laboratory (RBL) supports Brilacidin’s antiviral activity in directly inhibit ing SARS-CoV-2 in cell-based assays. Additional pre-clinical and clinical data support Brilacidin’s therapeutic potential to inhibit the production of IL-6, IL-1, TNF-and other pro-inflammatory cytokines and chemokines (e.g., MCP-1), identified as central drivers in the worsening prognoses of COVID-19 patients. Brilacidin’s antimicrobial properties might also help in fighting secondary bacterial infections, which can co-present in up to 20 percent of COVID-19 patients. Collectively, these data support Brilacidin as a promising and unique— 3 in 1 combination: antiviral, immune/anti-inflammatory, and antimicrobial —anti-COVID-19 drug candidate. Additional drug delivery work (e.g., developed as an inhalant) might complement Brilacidin’s anti-COVID-19 therapeutic potential. Brilacidin has been tested in multiple Phase 2 human trials for other clinical indications, providing an established safety and efficacy profile, thereby potentially enabling it to help confront the worldwide coronavirus crisis.
From page 6:
In cooperation with Dr. DeGrado (UCSF)
- MOA for optimized arylamides
- Advantages of Mimetic Approach
From page 11:
Up to date info on RBL testing.
From page 12:
Immuno/Anti-Inflammatory
An excessive immune response to fight the novel coronavirus (triggering a “cytokine storm”) is theorized to play an important role in COVID-19 disease severity, which can lead to Acute Respiratory Distress Syndrome (ARDS)—a serious respiratory complication necessitating mechanical ventilation and leading cause of death among COVID-19 patients . Scientists at the University of Science and Technology of China (USCT) have identified interleukin 6 (IL-6), a pro-inflammatory cytokine, as the “main culprit” in the body’s overreaction when trying to fend off the virus.
Brilacidin, through its modulation of the cyclic adenosine monophosphate (cAMP) pathway, has been shown to be a potent regulator of immune response. Brilacidin has been shown to inhibit IL-6, as well as other pro-inflammatory cytokines and chemokines (e.g., TNF-α, IL-1β, IL-6, IL-8, MIP2-α, MCP-1, MMP-9, and CINC-3), thereby positioning the drug as a potential promising treatment for COVID-19 patients.
From page 16:
Antimicrobial
Even though a vast majority of COVID-19 patients are administered IV antibiotics, bacterial infections can co-present, in up to 15 percent of patients according to one study (even as high as 20 percent according to another study), with 50 percent of those who have died having had a secondary infection.
From page 20:
Vaccine
Vaccines containing defensins as adjuvants have been shown, in vivo and in vitro, to activate the primary innate antiviral immune response and mediate other immunomodulatory activities against a number of viruses, including coronaviruses. A vaccine based on Brilacidin, a defensin-mimetic, is another potential clinical development pathway, though developing Brilacidin as a vaccine would involve a longer process (12-18 months) than advancing it as a COVID-19 drug candidate. Legislative and regulatory authorities, however, have indicated (pdf) a willingness to expedite vaccine development, including eliminating the need for animal studies, assigning promising vaccines Breakthrough Therapy status and making COVID19 vaccines eligible for Priority Review Vouchers , etc. Information below and posted to the Company website includes links to literature detailing the potential of defensins developed as antiviral vaccines.
From page 24:
Next Steps
The Company is engaged in discussions within government, the pharmaceutical industry, and among health care provider networks and hospitals both in the United States and Europe, toward rapidly advancing Brilacidin testing into human trials to evaluate its potential as a novel coronavirus (COVID-19) therapeutic. Their interest in Brilacidin as a treatment for COVID-19 and associated complications is based on the drug’s promising antiviral activity against SARS-CoV-2, as supported in preliminary testing conducted in a monkey epithelial cell line (with testing planned to continue), and the drug’s established anti-inflammatory and antimicrobial properties—a 3-in-1 treatment combination. In advance of potential clinical testing, the Company is investigating procurement of appropriate drug supply (i.e., manufacture of intravenous drug product), and preparing for engagement with regulatory authorities . While there can be no assurance that a Brilacidin for COVID-19 clinical trial will commence, though that is the goal of the Company, a recent announcement by the National Institutes of Health (NIH) to launch a public-private partnership to speed COVID-19 therapeutics is a hopeful sign—that promising drugs, such as Brilacidin, might be rapidly developed to help address the COVID-19 pandemic.
From page 44:
Secondary Infections
Bacterial infections (10-20%) can often co-present in COVID-19 patients. In one retrospective study of 191 patients in China, 95 percent received antibiotics, compared to 21 percent of patients receiving antiviral treatment, 30 percent corticosteroids, and 24 IV immunoglobulin. Half of non-survivors experienced a secondary infection, and ventilator-associated pneumonia occurred in ten (31%) of 32 patients requiring invasive mechanical ventilation . The duration of antibiotic treatment in another study of 99 cases in Wuhan China was between 3 and 17 days, with a median duration of 5 days.
Brilacidin First-in-Class Defensin-Mimetic Drug Candidate
Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment
https://static1.squarespace.com/static/571535....20.20.pdf
This 45 page PDF has updated information summarizing mechanism of action, pre/clinical data and academic literature supporting the development of Brilacidin as a potential novel COVID-19 therapeutic. This document builds on a previous version released at the beginning of March.
From page 2:
Brilacidin (PMX-30063) is Innovation Pharmaceutical’s lead Host Defense Protein (HDP)/Defensin-Mimetic drug candidate targeting SARS-CoV-2, the virus responsible for COVID-19. Laboratory testing conducted at a U.S.-based Regional Biocontainment Laboratory (RBL) supports Brilacidin’s antiviral activity in directly inhibit ing SARS-CoV-2 in cell-based assays. Additional pre-clinical and clinical data support Brilacidin’s therapeutic potential to inhibit the production of IL-6, IL-1, TNF-and other pro-inflammatory cytokines and chemokines (e.g., MCP-1), identified as central drivers in the worsening prognoses of COVID-19 patients. Brilacidin’s antimicrobial properties might also help in fighting secondary bacterial infections, which can co-present in up to 20 percent of COVID-19 patients. Collectively, these data support Brilacidin as a promising and unique— 3 in 1 combination: antiviral, immune/anti-inflammatory, and antimicrobial —anti-COVID-19 drug candidate. Additional drug delivery work (e.g., developed as an inhalant) might complement Brilacidin’s anti-COVID-19 therapeutic potential. Brilacidin has been tested in multiple Phase 2 human trials for other clinical indications, providing an established safety and efficacy profile, thereby potentially enabling it to help confront the worldwide coronavirus crisis.
From page 6:
In cooperation with Dr. DeGrado (UCSF)
- MOA for optimized arylamides
- Advantages of Mimetic Approach
From page 11:
Up to date info on RBL testing.
From page 12:
Immuno/Anti-Inflammatory
An excessive immune response to fight the novel coronavirus (triggering a “cytokine storm”) is theorized to play an important role in COVID-19 disease severity, which can lead to Acute Respiratory Distress Syndrome (ARDS)—a serious respiratory complication necessitating mechanical ventilation and leading cause of death among COVID-19 patients . Scientists at the University of Science and Technology of China (USCT) have identified interleukin 6 (IL-6), a pro-inflammatory cytokine, as the “main culprit” in the body’s overreaction when trying to fend off the virus.
Brilacidin, through its modulation of the cyclic adenosine monophosphate (cAMP) pathway, has been shown to be a potent regulator of immune response. Brilacidin has been shown to inhibit IL-6, as well as other pro-inflammatory cytokines and chemokines (e.g., TNF-α, IL-1β, IL-6, IL-8, MIP2-α, MCP-1, MMP-9, and CINC-3), thereby positioning the drug as a potential promising treatment for COVID-19 patients.
From page 16:
Antimicrobial
Even though a vast majority of COVID-19 patients are administered IV antibiotics, bacterial infections can co-present, in up to 15 percent of patients according to one study (even as high as 20 percent according to another study), with 50 percent of those who have died having had a secondary infection.
From page 20:
Vaccine
Vaccines containing defensins as adjuvants have been shown, in vivo and in vitro, to activate the primary innate antiviral immune response and mediate other immunomodulatory activities against a number of viruses, including coronaviruses. A vaccine based on Brilacidin, a defensin-mimetic, is another potential clinical development pathway, though developing Brilacidin as a vaccine would involve a longer process (12-18 months) than advancing it as a COVID-19 drug candidate. Legislative and regulatory authorities, however, have indicated (pdf) a willingness to expedite vaccine development, including eliminating the need for animal studies, assigning promising vaccines Breakthrough Therapy status and making COVID19 vaccines eligible for Priority Review Vouchers , etc. Information below and posted to the Company website includes links to literature detailing the potential of defensins developed as antiviral vaccines.
From page 24:
Next Steps
The Company is engaged in discussions within government, the pharmaceutical industry, and among health care provider networks and hospitals both in the United States and Europe, toward rapidly advancing Brilacidin testing into human trials to evaluate its potential as a novel coronavirus (COVID-19) therapeutic. Their interest in Brilacidin as a treatment for COVID-19 and associated complications is based on the drug’s promising antiviral activity against SARS-CoV-2, as supported in preliminary testing conducted in a monkey epithelial cell line (with testing planned to continue), and the drug’s established anti-inflammatory and antimicrobial properties—a 3-in-1 treatment combination. In advance of potential clinical testing, the Company is investigating procurement of appropriate drug supply (i.e., manufacture of intravenous drug product), and preparing for engagement with regulatory authorities . While there can be no assurance that a Brilacidin for COVID-19 clinical trial will commence, though that is the goal of the Company, a recent announcement by the National Institutes of Health (NIH) to launch a public-private partnership to speed COVID-19 therapeutics is a hopeful sign—that promising drugs, such as Brilacidin, might be rapidly developed to help address the COVID-19 pandemic.
From page 44:
Secondary Infections
Bacterial infections (10-20%) can often co-present in COVID-19 patients. In one retrospective study of 191 patients in China, 95 percent received antibiotics, compared to 21 percent of patients receiving antiviral treatment, 30 percent corticosteroids, and 24 IV immunoglobulin. Half of non-survivors experienced a secondary infection, and ventilator-associated pneumonia occurred in ten (31%) of 32 patients requiring invasive mechanical ventilation . The duration of antibiotic treatment in another study of 99 cases in Wuhan China was between 3 and 17 days, with a median duration of 5 days.
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