Replies to post #283658 on Innovation Pharmaceuticals Inc (IPIX)

[farrell90]

I am sure you have discovered much of Polymedix research on the viral effects of its compounds is not available.Many of past Polymedix presentations are no longer available on line. They did extensive research on bacterial, tb, and malaria.They have done invitro studies on the anti viral effects of their Definsin mimetics but not much is available online. I suspect Mr Ehrlich contacted Drs DeGrado, Tew,Scott, and Klein for input for yesterdays blog post.

The diagram on pg 8 of yesterdays blog post shows a diagram with a link to coronavirus and "direct antimicrobial activity" This diagram is from an earlier Polymedix presentation which I have been unable to locate on line.

The diagram can be interpreted a number of ways,but to me it means Polymedix studied Brilacidin and Defensin mimetics against Coronavirus and it had some "antimicrobial effects"

This is the only link I have found to Coronavirus and IPIX until yesterdays blog post.

I did find one archived presentation where they reviewed their early research. The only antiviral compound mentioned was PMX10098.

https://www.sec.gov/Archives/edgar/data/1341843/000136231008008026

William DeGrado synthesized Brilacidin based on the structure and polarity of Manginin. His goal was to develop a pharmaceutical which was effective, evolutionary based, small,safe and easily manufactured.The design was aided by computer aided design.Even though DeGrado used a computer, the initial design was sketched on paper.

"On a bright summer day in June 2000, William DeGrado sketched a ribbon-like molecule on a piece of scrap paper.

It may not have looked like much, but it so excited the biochemist and his team of fellow researchers at the University of Pennsylvania in Philadelphia that they all signed the sketch and set to work building the molecule in a laboratory.

The source of their excitement was the molecule’s resemblance to antimicrobial peptides, or AMPs. These tiny proteins are produced by the body’s own tissues as a first line of defense against all sorts of infections. AMPs don’t have to enter a pathogen to kill it — they literally punch holes through bacteria cell walls. That means they can kill both Gram-positive and thick-skinned Gram-negative bugs.

Scientists have long recognized the potential of AMPs. But previous efforts to turn the proteins into effective drugs failed: The products were too costly, too toxic or too chemically unstable. DeGrado’s sketch suggested it was possible to create a synthetic version of an AMP without those drawbacks.

“I thought, if it works, we’ve got a simple drug that would be cheap to make that could go to the developing world and cure all sorts of things,” said Michael Klein, a computational chemist who was tasked with creating computer models of the molecule.

Within two years, they had formed a company, called PolyMedix, and raised a few million dollars in funding from NIH grants and private investors. Soon after, they obtained patents and published their first scientific paper on the potential of their new drug, eventually called Brilacidin.


https://www.forbes.com/forbes/2011/0214/technology-william-degrado-chemistry-biotech-antibiotic-artisan.html#35307087bdce
https://www.reuters.com/article/us-usa-uncounted-drugs-specialreport/special-report-stronger-superbugs-and-no-new-drugs-to-fight-them-idUSKBN1441SO
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135847/
http://www.polymedix.com/pdf/PFQPolymedixarticle.PDF

Good article linking Magainin and Brilacidin. The article is about polymerization of defensin mimetics but the first 2 paragraphs show the association.

https://www.pnas.org/content/99/8/5110.full

Good review of Polymedix's research. No mention of viruses but one of the few reviews I have seen which mentions Brilacidin against C diffe and Shigella

http://www.polymedix.com/pdf/AntibioticInformationPackage_0110.pdf

Evidently C diffe was a funded study
http://www.polymedix.com/pdf/2009annualmeeting-Hardcopy.pdf

Article outling Michael Zasloff's discovery of Magainin 2nd article reviews why HDP are so important

https://www.embopress.org/doi/full/10.1038/sj.embor.embor748
https://pdfs.semanticscholar.org/aa96/c669649b4fb0dd4ea6b45b6b86ea7f7d08f2.pdf

Magainins antiviral effects on Herpes simplex

https://www.sciencedirect.com/science/article/abs/pii/S0924857999000941

Yesterday blog post stated the following:

This is exactly where Brilacidin fits in into the emerging Coronavirus
threat—a promising small molecule in late-phase development worthy of further
evaluation as to its antiviral properties.

Brilacidin already has demonstrated broad and robust antibacterial,
anti-inflammatory and immunomodulatory properties in multiple FDA clinical
trials. Pre-clinical research also supports Brilacidin’s antiviral properties
based on work by conducted by Dr. William DeGrado (UCSF) and Dr. Richard Scott
(Fox Chase).

Brilacidin and other defensin mimetics similar in structure to Brilacidin have
been tested against enveloped viruses with moderate activity noted from the
outset. To date, Brilacidin has not been tested specifically against
Coronavirus (an enveloped positive stranded RNA virus). But the scientists who
conducted preliminary research are optimistic about the multi-tiered
advantages of Brilacidin to elicit a response when accompanied by drug
optimization, formulation and delivery work.

GLTA,Farrell

[farrell90]

Todays PR again suggest Brilacidin's mechanism of action is the same for viruses as bacteria, it attaches to the "pathogens" cell wall and disrupts it.

It also answers a confusing question about vaccines. The last PR suggested Brilacidin has a vaccine. Todays PR suggests disrupting the virus cell wall could enhance the development of new drugs and vaccines , presumably by exposing more antigens.



"Brilacidin is a compelling investigational drug for COVID-19 due to its unique qualities to mimic the human innate immune system and Mechanism of Action that includes disruption of the membrane of pathogens, leading to cell death. Throughout laboratory and clinical studies, Brilacidin has demonstrated potent activity against Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), and coverage against Gram-negative bacteria. Research supports the ability of Brilacidin to swiftly penetrate a peptidoglycan layer in these difficult bacteria, which is key to rapid pathogen destruction and decreases the likelihood of drug resistance emerging.

The ability to penetrate cell walls engenders confidence in this opportunity to meet an urgent medical need in treating coronaviruses like COVID-19. COVID-19 is an “enveloped” virus, meaning it has a glycoprotein envelope surrounding its nucleocapsid. More succinctly, it has a lipid envelope derived from the host cell membranes studded with crown-like projections from which it is named."
"
"Penetrating the COVID-19 envelope could prove beneficial in designing a new drug or vaccine against the virus, although this would have to be confirmed through extensive laboratory and clinical research."

GLTA Farrell