Innovation Pharmaceuticals Inc (IPIX)

[slcimmuno]

Polymedix Supercomputing Backstory

Have posted on this before (e.g., the Landekic intvw)—how Polymedix came up with Brilacidin and related compounds via Uber-Supercomputing. The first two articles below, though, reveal just much brain (and processing) power--the Gee-Whiz factor--not to mention time (the years and years of development) and money (tens of millions I'd think though someone once posted it was north of $100m), went into what CTIX now has. DeGrado, Klein et al were simply far ahead of their times, by about a decade, with other researchers—IBM Research Labs, U of MD, Ohio State, U of Michigan—now playing catch-up (and w/o perhaps, well most probably, the equivalent brain/computer power).

I also added a WSJ article from 2005 that I hadn’t seen before. Some relevant stuff, including PolyCide applications.

NEW WEAPONS FOR THE GERM WARS: Inexpensive Polymers Can Extend the Range of Nature's Germ Fighter Arsenal (2002)
http://www.psc.edu/science/2002/klein/new_weapons_for_the_germ_wars.pdf
Excerpt
To solve this problem, Klein's team carried out a series of demanding quantum computations, an approach called density functional theory, to systematically derive accurate readings of the rotational resistance of the arylamide backbone. With about 60,000 hours of computing time using 128 LeMieux processors, they derived the force fields they needed.

SCALABILITY/TECHNICAL COMPUTING (2003)
Pittsburgh Supercomputing Center
Pittsburgh, PA
United States
Year: 2003
Status: Finalist
Category: Science
Nominating Company: Hewlett-Packard Company
Summary: Massive computing power accelerates the search for inexpensive polymers that would function the same way as simple but difficult-to-manufacture peptides that are known to be powerful anti-bacterials and that can reduce the incidence of in hospital infection.
http://www.cwhonors.org/Search/his_4a_detail.asp?id=4849

Excerpt
Prior to LeMieux becoming available (early 2002), there was no similarly powerful system available to researchers in the United States outside of a few installations at classified government laboratory facilities. LeMieux thus filled a large gap in United States research capability -- highlighted in a 1999 report to President Clinton (The President’s Information Technology Advisory Committee report). When installed, LeMieux’s 3,000 parallel processors, capable of six teraflops peak performance (six trillion calculations a second), provided more than five times more computing capability than the next most powerful system available to researchers through the National Science Foundation. It has facilitated, and will continue to facilitate, progress in many areas of significant social impact, such as the structure and dynamics of proteins useful in drug design, storm-scale weather forecasting, earthquake modeling, and modeling of global climate change.

WSJ: START-UP COOKS UP A BACTERIA SLAYER (JAN 2005)
http://www.wsj.com/articles/SB110487454326216811
Full Story
A young Philadelphia company is aiming to develop an antibiotic drug that would kill bacteria once and for all. Researchers fight a continuing battle with bacteria, which adapt and eventually develop resistance to new antibiotics. Many of the world's bacterial infections become resistant to the drugs prescribed to fight them, and public-health advocates warn of a weakening pipeline of potentially life-saving antibiotics.

PolyMedix Inc., co-founded by University of Pennsylvania researchers, is targeting bacteria with synthetic molecules that mimic the activity of antimicrobial proteins that have a natural ability to prevent bacteria from developing resistance. "We believe that our antibiotic is unique," said PolyMedix President and Chief Executive Nick Landekic. The company believes it is the only one developing an antibiotic that uses synthetic molecules to mimic the mechanism of these "host defense proteins," which work by rupturing the skin of bacterial cells. "Our antibiotic 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 this," said Mr. Landekic, a pharmaceutical-industry veteran who helped form PolyMedix about 2½ years ago.

Conventional antibiotics must get inside the bacterial cell and target an enzyme, he explained. Bacteria develop resistance to such drugs by changing the target or simply pumping the antibiotic out of the bacterium, he said. PolyMedix says test-tube experiments demonstrate that bacteria don't develop resistance to the company's antibiotic, which works on infections in lab mice. The company believes it can start human clinical trials in a year if it secures the necessary financing.

PolyMedix says it identified its lead drug candidate in less than 18 months for less than $2 million. The company believes it can have its first antibiotic drug on the market in five to six years, for about $100 million. It has created 12 classes of antibiotics and selected several of them as candidates for human trials, Mr. Landekic said. "We've shown that they kill 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," Mr. Landekic said. The compounds have been effective on the biowarfare pathogens black plague, tularemia and 12 strains of anthrax, he said.

PolyMedix has raised more than $6 million from so-called angel investors -- wealthy individuals who advise start-up companies at their earliest stage -- and plans to seek $20 million to $25 million more from institutional investors this spring, with Legg Mason Inc. acting as its financial adviser, Mr. Landekic said. The university and the founding researchers have equity stakes in the business.

Assuming it gains the financing, the company hopes to file an investigative-new-drug application for its lead antibiotic with the Food and Drug Administration in December 2005 and would start clinical trials soon thereafter. The company, which says the world-wide market for antimicrobial drugs exceeds $30 billion, plans to first develop its antibiotic as an intravenous treatment, followed by oral and topical formulations. "This drug has multibillion-dollar sales potential and the opportunity to become the standard of care for hospital infections," the company says in an investor presentation. "Oral formulations have the potential to become the agent of choice in outpatient care of infections."

PolyMedix also will seek FDA approval for a sanitizing polymer hand lotion for doctors and nurses that it expects will prevent bacterial resistance, using the same protein-mimicking mechanism.
The U.S. Centers for Disease Control and Prevention in Atlanta has launched a campaign against antimicrobial resistance in hospitals, where, it says, nearly two million patients contract infections each year, and roughly 90,000 die as a result. More than 70% of bacteria that cause hospital-acquired infections are resistant to at least one of the drugs commonly used to treat them, the CDC says.

PolyMedix is weighing other polymer-based antimicrobial products, such as additives that could give paints, plastics and fabrics self-sterilizing surfaces. The company envisions licensing the technology for use in such products as bandages, catheters, food-preparation surfaces, toilet seats and uniforms, and is talking with many companies, Mr. Landekic said. For the drugs, PolyMedix aims to retain North American rights and license rights for the rest of the world to others. It has spoken with some pharmaceutical companies, he said.

Other researchers have developed drugs directly from proteins or smaller peptides -- chains of amino acids, the building blocks of life -- but protein-based drugs can be difficult and expensive to make and can't be taken orally. "We attempted to understand the molecular and biophysical basis for the action and then made molecules that are much smaller and much easier and cheaper to prepare," said William DeGrado, a professor of biochemistry and biophysics at the University of Pennsylvania's medical school, who is a PolyMedix co-founder and a member of its scientific advisory board.

Michael Zasloff, senior life-sciences analyst for Ferris Baker Watts and a professor at Georgetown University School of Medicine, said the implications of PolyMedix's technology are broad. "They've created a new class of antimicrobial substances, merging the design principles of polymers with the antibiotic or antimicrobial killing properties of some of nature's most potent anti-infectives," said Mr. Zasloff, who discovered an antimicrobial peptide he named magainin, from the Hebrew for shield, in the skin of a frog.

It is the mechanism of magainin-like proteins that PolyMedix is mimicking through synthetic molecules. If PolyMedix's antibiotics prove effective in oral form, "then they would have enormous potential," said Mr. Zasloff, who isn't involved with the company. Even if there were problems with the drugs, he said, PolyMedix may find broad applications for its synthetic antimicrobial molecules in other products.