Innovation Pharmaceuticals Inc (IPIX)

[slcimmuno]

THE BRILACIDIN BACK STORY

might cause eyes to glaze over, but thought there might be folks who hadn't seen, or might want to re-read, how we got to here from there, and why we should all be excited with what we have...the Polymedix backstory: the depth and quality of the clinical work that went into developing Brilacidin and the larger Defensin Mimetics platform (solid science)---again we have a good shot of becoming the next novel bad bug killer (First In Class, possibly best among all classes). its a compilation of past posts---tried to put most of it all in one place for ez-ier ref.

long short of it, polymedix was way-Way ahead of everyone else, supercomputing their way to novel ABXs, improving upon Mother Nature (less stable, less specific natural defensins). i also included below links to various other def-mimetic research groups playing catch-up (a few DeGrado/PYMX tie-ins). maybe this is the type of info that could be fwd'd to someone - if that someone could be identified - in advance of Copenhagen. or maybe to an eventual sci reporter who wants to break/revisit the story (recall Polymedix landed in places like WSJ, Scient American etc).

i divided the info into three main areas-- I) Polymedix Brain Trust and Approach; II) Former Polymedix Staff--Where Are They Now (again, hoping we can nab some as part of an adv board, esp DeGrado); III) Other Defensin-Mimetic Research (labs playing catchup)

I. THE POLYMEDIX BRAIN TRUST AND APPROACH

ARTICLES

The Genius Chemist and His Assault on Mutant Killer Bacteria (2011)
http://www.forbes.com/sites/robertlangreth/2011/01/28/the-genius-chemist-and-his-assault-on-mutant-killer-bacteria/

Nicholas Landekic Interview (2003)
http://www.twst.com/interview/16845

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.html
http://www.cwhonors.org/Search/his_4a_detail.asp?id=4849

Dock This: In Silico Drug Design Feeds Drug Development (2007)
http://biomedicalcomputationreview.org/content/dock-silico-drug-design-feeds-drug-development

Man-Made Defensin Rips Resistant Bacteria Apart (2008)
http://www.newscientist.com/article/dn13924-manmade-defensin-rips-resistant-bacteria-apart.html#.VOtPJS7QOMJ

Start-Up Cooks Up a Bacteria Slayer (WSJ) (2005)
http://www.wsj.com/articles/SB110487454326216811

SLIDE DECK/PUBLISHED RESEARCH

2012 PYMX Slide Deck on Defensin-Mimetics
http://files.shareholder.com/downloads/ABEA-4ITCYZ/0x0x598955/c3e5a236-e44a-4e85-80c8-25fe7733ec65/Host_Defense_Antimicrobial_Peptides.pdf

De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications (2010)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808429/

Antibacterial Mechanism of Action of Arylamide Foldamer (2011)
http://aac.asm.org/content/55/11/5043.long

New Bactericidal Surgical Suture Coating (2012)
http://1drv.ms/1vpe0Q8

POSTERS/PRESENTATIONS (hopefully in Copenhagen we'll get some updates)

A Phase 2 Randomized, Double-Blinded, Dose-Ranging, Active Controlled Efficacy and Safety Evaluation of Brilacidin (PMX-30063) for the Treatment of ABSSSI Caused by Staphylococcus Aureus
http://bit.ly/1zE7qgm

Activity of Brilacidin (PMX-30063) Against Drug Resistance Staphylcocci
http://bit.ly/1zE7o87

Metabolism and Excretion of Brilacidin (PMX-30063): A Novel Class of Antibiotics
http://bit.ly/1zE7o8d

Small, Nonpeptidic Mimics of Host Defense Proteins Exhibit Potent Killing Activity Against Gram-Positive and Gram-negative biofilm cultures
http://bit.ly/1zE7qgt

Nonpeptidic Mimics of Host Defense Proteins as Antimicrobial Agents for E Coli, Campylobacter and Other Foodborne Pathogens
http://bit.ly/1zE7qwJ

Nonpepditic Mimics of Host Defense Proteins as Antimicrobial Agents for Category A and B Biowarfare Pathogens
http://bit.ly/1zE7o8n

Slide Deck for PMX 10070/72, 2009 Presentation at Am Soc of Micro-B (just found this... hadnt seen before, E. Coli)
http://files.shareholder.com/downloads/ABEA-4ITCYZ/1410277423x0x502487/6f7e3b34-918c-477c-a3cf-59b3ce9c91fa/ASMGeneral2009.pdf

Below is an overview on Bioinformatics... a State of the Nation type overview... Polymedix research is cited (Ref # 66)--- EXCERPT
"Lastly, synthetic biology (Way et al., 2014) promises to extend biological systems well beyond what is naturally observed [IE MIMICKING DEFENSINS] and its integration with computational drug design (Marchisio and Stelling, 2009; Tew et al., 2010) and structural bioinformatics will open new and exciting possibilities."
Achievements and challenges in structural bioinformatics and computational biophysics (Jan 2015)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271151/

A few more overviews, informative reads:

Antimicrobial Peptides Stage a Comeback: Better understanding of the MOA, modification and synthesis of antimicrobial peptides is reigniting commercial development (May 2013)
http://amit1b.files.wordpress.com/2008/03/fox-2013-antimicrobial-peptides-stage-a-comeback.pdf

Antimicrobial peptidomimetics: reinterpreting nature to deliver innovative therapeutics (2012) [note see Brilacidin reference, PMX-30063, and PMX 10070/PMX 10072)
http://journal.frontiersin.org/article/10.3389/fimmu.2012.00171/full

II. FORMER POLYMEDIX STAFF--WHERE ARE THEY NOW?

1) William DeGrado, now at UCSF - DeGrado Lab (PYMX chem genius)
http://pharm.ucsf.edu/degrado
Protein Society Award
http://www.proteinsociety.org/protein-society-awards/the-stein-and-moore-award/

2) Michael Klein now at Temple University - Michael Klein Group (PYMX quant genius)
https://icms.cst.temple.edu/

3) Richard Scott (Fox Chase Chemical Diversity Center) (working w CTIX on gram-neg, anti-fungals)
http://www.fc-cdci.com/documents/FCCDC_Service_Offering.pdf

4) Gregory Tew - Tew Research Group (U Mass Amherst) (suture study)
http://www.pse.umass.edu/faculty/researchgroup/tew

5) Nicholas Landekic - Karunix Inc
http://www.rxpcci.com/archives/2014/karunix.htm
https://www.linkedin.com/pub/nick-landekic/5/119/aab
http://atgsites.com/KARUNIX_INC

how he summarizes time at PYMX
President & C.E.O. PolyMedix Inc. 2002 – 2013 (11 years)
PolyMedix is a public biotechnology company focused on transforming the treatment of infectious diseases with a novel class of antibiotic drugs: defensin-mimetics. The company created its own drugs and polymer biomaterials using a proprietary computational drug design platform developed at and licensed from the University of Pennsylvania. I was the Founder of PolyMedix, and started the company completely from the ground up:
• Raised $120 million in total financing, including reverse merger public offering.
• Secured >$18 million in 16 non-dilutive grant and research contract financings, which supports
1/2 of headcount and overhead, and research operations.
• Led drug discovery of two completely novel therapeutic agents with unprecedented efficiency
and productivity, starting from scratch with software computational design.
• Defensin-mimetic antibiotic (brilacidin) – the world’s first and only small molecule defensin-mimetic antibiotic to which bacterial resistance is unlikely to develop.
- Starting with software, to 4 clinical trials completed and Phase 2 clinical proof of
concept for <$30 million, plus platform of >1,700 active compounds
• Identified clinical IND lead candidate antibiotic compounds and initiated additional pipeline programs in less than 18 months and spending under $2,000,000 from company start-up.
• Managed company extremely efficiently, 28 total employees (up to 14 supported by grants).

III. OTHER DEFENSIN MIMETIC RESEARCH

N8 Medical
http://www.twst.com/interview/16845
Eccmid Poster
http://eccmid.meetingexpert.net/ECCMID_546/poster_120899/program.aspx

Ohio State - Kudryashov Group
http://news.osu.edu/news/2015/01/07/the-best-offense-against-bacteria-is-a-good-defense/
https://research.chemistry.ohio-state.edu/kudryashov/

U of Michigan - Kuroda Lab
In 2003, prior to joining the faculty at the University of Michigan School of Dentistry in 2006, he was a postdoctoral researcher in Prof. William DeGrado's group at University of Pennsylvania School of Medicine and developed antimicrobials based on polymeric materials. His current research interests include the development of biologically active polymers Designing Antimicrobial Polymers as Synthetic Mimics of Host-defense Peptides
http://www.cheme.washington.edu/files/news/imgs/4-22-13%20Kuroda%20Seminar%20Announcement.pdf
https://sites.google.com/a/umich.edu/kurodalab/research

U of Maryland - Erik De Leeuw, Alexander MacKerell (U of Md version of computational whiz Michael Klein when he was at U Penn/PYMX-affiliated)
Turning Defense into Offense: Defensin Mimetics as Novel Antibiotics Targeting Lipid II (2014)
Lead compound (BAS00127538)
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003732
List of full compounds... BAS00127538 on pg 15 of PDF
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004611
Note it is potent against A. buamanni: Efficacy of the small molecule inhibitor of Lipid II BAS00127538 against Acinetobacter baumannii.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134019/
Patent Application
http://www.google.com/patents/US20130331413
Researcher profiles (Erik De Leeuw, Mackerrel)
http://medschool.umaryland.edu/facultyresearchprofile/viewprofile.aspx?id=20093
http://mackerell.umaryland.edu/
Mackerrel's computational company
http://www.silcsbio.com/#/products
Investment Solicitation
http://www.umventures.org/technologies/defensin-molecules-novel-antimicrobial-agents

U of Copenhagen - Paul Hansen
http://forskning.ku.dk/find-en-forsker/?pure=da/persons/116652
See Abstract pg 50 - From Host-Defense Peptides to New Antibiotics
http://lifescienceevents.com/wp-content/uploads/AntibioticAlternatives5-7thNovABSTRACTS2014.pdf

IBM Research Labs / Ninja Polymers (a former DeGrado student is one of their scientists)
http://www.research.ibm.com/featured/ninjas/images/Ninjas-Infographic_12.03.2013.pdf
http://www.research.ibm.com/articles/nanomedicine.shtml#fbid=OMLbUqBG9Rp
http://youtu.be/1_4PmriHmuM