REPRINT FROM FEBRUARY 23, 2015

EMERGING COMPANY PROFILE

EYEING NEW ANTIBIOTICS

BY STEPHEN PARMLEY, SENIOR WRITER

Traditional antibiotics kill bacteria by inhibiting protein,

DNA, or cell wall synthesis but require multiplying cells to
be effective. SinSa Laboratories Inc.s peptide antibiotics kill
slow- and fast-growing bacteria by direct disruption of the
cell membrane, and could have reduced risk of susceptibility
to resistance mechanisms compared with existing antibiotics
for antibiotic-resistant eye infections.
SinSas antimicrobial peptides were created with its
SpearHead technology, which incorporates positively
charged amino acids and lipophilic groups to specifically
disrupt negatively charged bacterial cell membranes
regardless of their growth state.
According to CSO Roger Beuerman, It doesnt make any
difference whether the cells are in log or stationary phase, we
see rapid killing. Beuerman also is senior scientific director
of the Singapore Eye Research Institute (SERI), from which
SinSa has exclusive rights to the SpearHead technology, plus
antimicrobial compounds AM218 and B2088.
Beuerman said another benefit of the compounds
mechanism is a low likelihood of resistance emerging quickly
because the compounds target polymers in the cell wall and
cell membrane, not proteins.
Our drugs target the membrane in several different ways,
and they dont depend on one biosynthetic step, he said.
Since these polymers do not mutate, bacteria cannot
acquire resistance by simply mutating the target.
Beuerman said his group synthesized the SpearHead
antimicrobials by modeling them after natural antimicrobial
peptides, like polymyxin B and human defensins, but he
added that the compounds should have better drug-like
properties.
The group screened for compounds that disrupted
bacterial cell membranes but did not affect mammalian cell
membranes.
According to Beuerman, while compounds like polymyxin B
work directly on bacterial membranes, they lack therapeutic
potential because the concentration required to kill bacteria

SINSA LABORATORIES INC.

Montreal, Quebec
Technology: Synthetic peptide antimicrobials that
target pathogen membranes
Disease focus: Infectious
Clinical status: Preclinical
Founded: 2014 by Roger Beuerman, Magnus Precht
and Urban Olson
University collaborators: Singapore Eye Research
Institute (SERI)
Corporate partners: None
Number of employees: 2
Funds raised: Not disclosed
Investors: Not disclosed
CEO: Magnus Precht
Patents: 5 issued covering small molecules, peptides
and pharmaceutical antimicrobial compositions

in an active infection is too high. At a therapeutic dose you

see a terrible amount of inflammation, he said.
In 2012 the SERI team reported preclinical data for B2088
in the Journal of Biological Chemistry. The SpearHead
antimicrobial is a dimeric cationic peptide that was
synthesized based on the human beta defensin 3 C-terminus.
B2088 killed Gram-negative bacteria, Pseudomonas aeruginosa,
Escherichia coli and Klebsiella pneumonia with a minimum
inhibitory concentration (MIC) of 2.75 g/mL. It did not
lyse red blood cells at concentrations as high as 2 mg/mL.
The selectivity for bacterial cells versus mammalian cells was
significantly higher than reported values for Lytix Biopharma
A/Ss Lytixar (LTX-109), a synthetic antimicrobial peptide
in Phase II testing for skin infections, and Dipexium
Pharmaceuticals Inc.s Locilex pexiganan acetate, a linear
peptide in Phase III for infections of diabetic foot ulcers.
B2088 killed more than 99.99% of gentamicin-resistant P.
aeruginosa in 10 minutes at 2x MIC. The study also showed
it was possible to passage P. aeruginosa more than 17 times

in B2088 with no resistance. Resistance emerged with gentamicin or

norfloxacin by passage 15.
The combination of B2088 with gatifloxacin was more effective than
gatifloxacin alone at treating an existing P. aeruginosa corneal infection in
mice. In a rabbit corneal wound-healing model, topical application of B2088
did not interfere with wound closure and showed no clinical signs of toxicity.
President and CEO Magnus Precht said SinSa has started manufacturing
B2088 and will combine it with fixed doses of gentamicin a combination
the company calls Dorzidin to treat antibiotic-resistant Pseudomonas eye
infections that lead to keratitis in contact lens wearers.
The companys second candidate is AM218, a SpearHead antimicrobial
that was synthesized by modifying a hydrophobic xanthone core with
cationic arginine and lipophilic isoprenyl groups. Data published in the
Journal of Medicinal Chemistry last month showed AM218 killed a wide
range of Gram-positive bacteria. In studies similar to those performed on
B2088, AM218 killed Staphylococcus aureus with a MIC of 0.5 g/mL, lysed
red blood cells with an EC50 of 277 g/mL and showed less resistance
than generic gatifloxacin or norfloxacin.

SinSa plans to begin Phase I testing of Dorzidin within a year and a half of
series A funding. It is seeking a $10 million in series A.
The company plans to start Phase I testing of AM218 for Gram-positive
eye infections after obtaining clinical proof of concept with B2088.
COMPANIES AND INSTITUTIONS MENTIONED
Dipexium Pharmaceuticals Inc. (NASDAQ:DPRX), New York, N.Y.
Lytix Biopharma A/S, Tromso, Norway
Singapore Eye Research Institute, Singapore
SinSa Laboratories Inc., Montreal, Quebec

REFERENCES
Bai, Y. et al. Progressive structuring of a branched antimicrobial peptide on the path to the inner
membrane target. Journal of Biological Chemistry (2012)
Koh, J.-J. et al. Amino acid modified xanthone derivatives: novel, highly promising membrane-active
antimicrobials for multidrug-resistant Gram-positive bacterial infections. Journal of Medicinal Chemistry
(2015)

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reprint from February 23, 2015

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