Replies to post #314451 on Innovation Pharmaceuticals Inc (IPIX)

[xoc]

Do we still owe Penn 3% out of the 6% we will get from Fccc for the antifungal?

[LilyGDog]

Awesome post!

Go Leo & IPIX!

Another glitch in the memory bank - PolyMedix did not use the U of Penn Super Computer, they used "Big Ben" at the Pittsburgh SuperComputer Center to do the numbers crunching for the formulation of Brilacidin.

Here is the latest PR from that facility, dtd 9June2020, stating that they received a $5MM grant from the Natl. Science Foundation to build NeoCortex, a unique AI system, to speed AI research.

https://www.psc.edu/

From data acquired from IHUB post 92313, dtd 2/23/15, written by slcimmuno which give TONS of background with references attached, he made the follow ascertains given by PolyMedix founder (and a recognized genius in many fields) Nicholas Landekic.

1) CONNECTION TO U OF PENN - The company (PolyMedix) created its own drugs and polymer biomaterials using a proprietary computational drug design platform developed at and licensed from the University of Pennsylvania.

2)SUPER COMPUTER USE - This comes from justfactsmam per the post attached dtd sometime around Mar of this year.
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Nothing wrong with repeating old news here...many here have never read about the $30M/60,000 super computing time used in formulation Brilacidin, no less the $10's of millions in testing Brilacidin in lab and human trials.

1. Brilacidin was formulated and co-developed by University of Pennsylvania and its Researchers. (not in Leo's garage)

2. The University of Pennsylvania and its Researchers (Founders) formed an entity Polymedix, the original patent filer, which patent was bought by and now owned by IPIX.

3. Among Founders and Originally Advisory Members were, William F. DeGrado PhD., Dr. and Richard Scott, Henry Heine, Phd., Gregory Tew PhD., Henry S. Heine, Ph.D. and others..(see below...and see where they are now!)

4. Founders spent $30M and in 2005 used 60,000 hours of the then NEW Pittsburgh Supercomputer Center's (PSC) "Big Ben",

5. "Big Ben" was built, in part, "to design of new materials, protein dynamics studies that lead to new therapeutic drugs" through which Brilacidin was formulated.

6. Brilacidin is a synthetic molecule targeting bacteria which mimics the activity of antimicrobial proteins that have a natural ability to prevent bacteria from developing resistance.

7. Brilacidin..uses synthetic molecules to mimic the mechanism of these "host defense proteins," which work by rupturing the skin of bacterial cells.

8. Brilacidin, is an ANTIBIOTIC... that directly breaks the bacteria cell membrane very much like a needle going into a balloon...and because of that there's a very low chance the bacteria can develop resistance to it

9. PolyMedix has "... shown that Brilacidin kills more than 80 different strains of bacteria. Actually, we haven't found any strain of bacteria that we haven't been able to kill with these compounds," ... The compounds have been effective on the bio warfare pathogens black plague, tularemia and 12 strains of anthrax. (FUNNY THING...Brilacidin HAS NEVER FAILED A CLINICAL TRIAL UNDER IPIX/CTIX!)

KEY NOW...will Covid-19 "treatment" test show that Brilacidin "breaks the Covid-19 (and maybe many virus's) cell membrane very much like a needle going into a balloon????



Key players in the development of Brilacidin:

William F. "Bill" DeGrado, Ph.D., is the Professor of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF) where he is the Director of DeGrado Lab research Laboratory and a member of the National Academy of Sciences.

He received a B.S. (chemistry) from Kalamazoo College and a Ph.D. (Chemistry) from the University of Chicago in 1977 working with Emil T. Kaiser and F. Kezdy. His graduate work focused on the design of the oxime resin for solid-phase synthesis, which was used for synthesis of protected peptides and is still in use for various types of combinatorial chemistry today. He also used peptide design to demonstrate that melittin adopts an amphiphilic helical structure, which is responsible for its membrane-disrupting activity.

He first held an industrial position at DuPont Central Research & Development (later DuPont Merck Pharmaceutical Company). He transitioned to academia in 1996, joining the University of Pennsylvania as the George W. Raiziss professor of biochemistry and biophysics and then moved to UCSF in 2011.

Dr. DeGrado was one of the original scientists involved, while at the University of Pennsylvania, in the discovery and subsequent development (see recent mechanistic studies) of Brilacidin and the larger Innovation Pharmaceuticals’ (patent successor to PolyMedix) Host Defense Protein (HDP)-mimetic platform.

Dr. DeGrado’s work laid the foundations for PolyMedix’s core lead drug development programs and product candidates. Both PMX-30063 antibiotic, the world’s first small molecule mimetic of host defense proteins intended for systemic use, and PMX-60056 heptagonist, a new reversing agent for heparin and Low Molecular Weight Heparins, are based on pioneering discoveries originally made by Dr. DeGrado.

He was the scientific founder of and Chief Scientific Advisor for PolyMedix, an emerging biotechnology company at the time developing new therapeutic drugs for serious, life-threatening acute cardiovascular and infectious disease. He was a Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine in Philadelphia, PA, and a member of the National Acad

Based on his work at PolyMedix, he was named the 2008 recipient of the prestigious Ralph F. Hirschmann Award in Peptide Chemistry. The award recognizes a person who has made outstanding contributions in the chemistry, biochemistry, or biophysics of peptides.

His published research includes contributions to the fields of protein design, synthesis of peptidomimetics, and characterization of membrane-active peptides and proteins, most notably the M2 protein.

The M2 proton channel from Influenza A virus. DeGrado’s early work with the groups of Robert Lamb and Larry Pinto established the overall structure and mechanism of the M2 proton channel, which is the target of the anti-influenza drugs, amantadine and rimantadine. A decade later their crystallographic, and NMR structures defined the fine details of the binding site for these drugs and explained the mechanism of the growing problem of amantadine-resistance. With Michael Klein, Robert Lamb and Larry Pinto, DeGrado extensively characterized the physiological properties of many drug-resistant mutants of the channel, identified those most likely to lead to resistance, and designed new drugs to address the problem of drug-resistant forms of influenza A virus.


Dr. DeGrado was one of the original scientists involved, while at the University of Pennsylvania, in the discovery and subsequent development (see recent mechanistic studies) of Brilacidin and the larger Innovation Pharmaceuticals’ (patent successor to PolyMedix) Host Defense Protein (HDP)-mimetic platform.

In 2017, at a lecture, Dr DeGrado has referred to Brilacidin, a promising immunomodulatory drug candidate currently being evaluated in mid-stage clinical trials. Brilacidin, based on insights gleaned from frog peptides, is a successful example of de novo protein design, described as: "the process of using peptide sequences that are not existent in, but inspired by nature" to build molecules as potential innovative therapeutics with novel attributes and applications. As to drug development, such novel synthetic design strategies of proteins ("the workhorses of all living creatures" allow for improved pharmacokinetic properties and enhanced target specificity.

Dr. DeGrado has co-authored over 370 articles (list of publications), holds more than 25 patents, and is a member of the National Academy of Sciences, elected in 1999. In 2003, he was presented (pdf) with the Merrifield Award by the American Peptide Society. He received The Protein Society's Stein and Moore Award in 2015 and, most recently, was presented with the 2017 Biopolymers Murray Goodman Memorial Prize.

Michael L. Klein, is Laura H. Carnell Professor of Science, Director of the Institute for Computational Molecular Science, and Dean of the College of Science and Technology at Temple University in Philadelphia, USA.

He was previously the Hepburn Professor of Physical Science in the Center for Molecular Modeling at the University of Pennsylvania and worked with PolyMedix and instrumental in PolyMedix obtaining the patent titled, "Facially Amphiphilic Polymers as Anti-infective Agents" (developed into Brilacidin) allows compositions of matter and uses for a number of series of antimicrobial compounds for antibiotic and other anti-infective applications. to develop acute care products for drug resistant bacteria and acute cardiovascular disorders based on biomimetics - novel non-peptide small molecule drugs that mimic the activity of proteins. PolyMedix’s compounds are designed with a proprietary computational drug design technology licensed from the University of Pennsylvania, and are based on the work of Drs. William DeGrado, Michael Klein, and Gregory Tew.

PolyMedix has developed novel small molecule antibiotic drug candidates by mimicking the activity of the host defense proteins, one of the oldest and most effective antimicrobial defense systems present in virtually all living creatures. Unlike many antibiotic drugs which act on biochemical targets and to which bacterial resistance readily develops, PolyMedix’s antimicrobial compounds have the potential to be rapid acting broad-spectrum antibiotic drugs because they appear to work biophysically by a novel mechanism that targets and disrupts bacterial cell membranes. These new antibiotics compounds are active against Gram-positive, Gram-negative and drug-resistant bacteria, as well as have antifungal and antiviral properties. Laboratory testing has shown their mechanism of action is associated with a low incidence for the development of resistance.

I have deleted backgrounds on the other founders as though they were important they are not that germane to this post.

[george h]

I wonder if William F. "Bill" DeGrado, is an IPIX shareholder. Does anyone here know him?
gh

[Hungry_Ghost]

This should B posted EVERY day...eom

[loanranger]

In an exhibit to the 10-K filed on 9/30/13 the Company lists the "Intellectual Property Acquired from Polymedix", one of which was a patent application entitled "Compounds and Methods for Treating Candidiasis and Aspergillus Infections", described this way: "The application relates to compositions and use of anti-fungal compounds."
That was the first ever use of the term "antifungal" by Cellecutix in a filing. There is no question that CTIX acquired that application from Polymedix.

A review of the history of the application of that patent (I'm sure you can find it....start at USPTO.gov) shows that there were 4 inventors and that 3 of those inventors, including Dr. Scott now of Fox, assigned their rights to CTIX prior to the issuance of the patent itself and the fourth, Dr. Gil Diamond, University of Medicine and Dentistry of New Jersey, who had led the presentations at PM's anti-fungal exhibitions, assigned his interest to Rutgers.
The PolyMedix anti-fungal compound was identified as PMX-10098, as distinguished from PMX-30063 which we know as Brilacidin.

In a 9/16/13 CTIX PR updating investors on the acquisition entitled Cellceutix Completes Acquisition of PolyMedix Assets, Immediately Plans Brilacidin(TM) Phase 2b Clinical Trial for Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Phase 2 Clinical Trial for Oral Mucositis the Company said this:
"The Company has also started reviewing other newly acquired compounds and, in particular, sees strong possibilities in PMX-10098 for fungal infections."


Those are some of the reasons that I felt that it is appropriate to ask "What does the University of Pennsylvania have to do with anti-fungals and what do anti-fungals have to do with Brilacidin?"

An IPIX press release was linked that talked about the properties of CTIX-1502 (referred to as C4). It had the term "Brilacidin" floating by itself below the headline but didn't mention it anywhere in the text...
http://www.ipharminc.com/new-blog/2017/9/25/innovation-anti-fungal-compound-shows-potent-activity-against-multi-drug-resistant-candida-and-new-fungal-superbug
Can you connect CTIX-1502 to the PolyMedix acquisition?

The next 10-K filing said this and it's the basis for my initial questions:
"As research at the Company is now focused on supporting its clinical trials, we have reduced costs associated with the licensing of intellectual property for gram-negative bacteria and anti-fungal compounds by returning our patent portfolio titled “Compounds and Methods for Treating Candidiasis and Aspergillus Infections” back to the university co-licensor. The Company at this time does not have any active gram-negative or anti-fungal programs and therefore has decided not to pay for the maintenance of these patent rights."

There have been a number of discussions about just what was being returned but they have all centered around the assumption that the patent "portfolio" was being returned to the University of Pennsylvania and it turns out that the co-licensor for the patent entitled “Compounds and Methods for Treating Candidiasis and Aspergillus Infections” is Rutgers. No wonder it wasn't easily resolved.


The footnotes in the IPIX IP table in the 2015 10-K for the patent in question showed "Patent family co-owned with Rutgers, The State University of New Jersey." (Obviously that doesn't describe the Brilacidin patent family). The 10-Ks issued since then have not shown that footnote and continue to merely describe the unnamed Rutgers as "the university co-licensor".


So what, one might ask? It's the same issue I tried to raise earlier.
If, as they say in the most recent 10Ks, "The Company at this time does not have any active gram-negative or anti-fungal programs and therefore has decided not to pay for the maintenance of these patent rights", then what programs were they talking about a few days ago when they conveyed SOMETHING that was described as "all discovery, intellectual property and commercialization rights related to its share of their joint antifungal drug program." And if that program involved the patent entitled Compounds and Methods for Treating Candidiasis and Aspergillus Infections, does Fox know that IPIX sent that patent back to RUTGERS and that the USPTO has designated it as Abandoned?

All of this could be resolved by a simple filing or two. The original agreement with Fox which would describe "their joint antifungal drug program" and the amendment to that program that the parties just agreed to.