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Host Defence Peptides

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Bacterial resistance to antibiotics is a major and fast-growing health concern

  • Pharma Holdings is addressing the problem with its drugs derived from host defence peptides through Structure-activity-relationship studies on Lactoferricin.
  • Pharma Holdings’ infection drug candidate degrades the membranes of microorganisms
  • Pharma Holdings’ current focus is on topical treatment of infections and nasal eradication of staphylococci pre-operatively
  • Pharma Holdings’ infection drug candidate has proven efficacy against a broad range of resistant organisms
About Lytixar™ (LTX-109)

LTX-109 is an investigational antimicrobial drug with a novel membrane-lysing mechanism of action, based on the biological principle of innate immune effectors, lytic peptides. The drug has a rapid bactericidal lytic activity. The drug has been tested in vitro and in vivo models and has undergone a comprehensive nonclinical safety and toxicology program and been studied in man in a Phase I study, and two phase I/IIa studies. The drug is in development as a treatment for bacterial skin infections, fungal infections and nasal decolonisation of MRSA.

LTX-109 structure

LTX-109 highlights:

  • A synthetic protein fragment; a peptidomimetic
  • High stability against degradation
  • Produced in large scale

Mechanism of Action

The antimicrobial mode of action of LTX-109 represents a highly beneficial strategy for killing bacteria and other microorganisms. The diagram below demonstrates the mechanism of action for LTX-109 lysis of bacterial membranes.
The mechanism of action on a more detailed level can be represented by the Shai-Matsuzaki-Huang mode of action of an antimicrobial peptide:

Antimicrobial peptides of multicellular organisms

Mechanism of lysing action. Illustration by Michael Zasloff, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA

Lack of resistance development
In general, compounds acting on the cell membrane have low propensity for developing resistance. The occurrence of spontaneous resistance towards LTX-109 was studied by plating a heterogeneous mixture of bacteria. Neither in wild type, MRSA nor glycol peptide resistant Staphylococcus aureus was any spontaneous resistance observed. No signs of resistance development have been observed in 5 different Staphylococcus aureus strains after 14 passages
LTX-109 kills MRSA better than ‘Gold Standard’ drugs
  • Murine skin infection model (tape-stripping, ATCC 33591
  • Read-out: bact growth +9 hours after the first of 3 doses

Outstanding efficiency in animal models

In vivo efficacy has been investigated at Statens Serum Institut (SSI) in Copenhagen, Denmark, and NAEJA, Canada, using a well-documented skin infection model.
A skin lesion is infected on day one, and the infection allowed to develop for 24 hours. The drug and comparators are applied 3 times in a single day. LTX-109 is strongly bactericidal against all strains of Staphylococci tested, including both hospital-acquired and community-acquired MRSA (USA300).
Highly effective on MRSA wound biofilm​

Green indicate living cells and red indicate dead cells

LTX-109 demonstrates a significant effect on MRSA round biofilm
LTX-109 reduces CA-MRSA (USA300) significantly faster than Mupirocin
  • Tape-stripping and scalpel blade cut injury
  • TID treatment (every 3 hours)
  • Bacterial tissue load determined by CFU from skin biopsies
LTX-109 is as fungicidal as Amphotericin B

LTX-109 is rapidly bactericidal
The onset of LTX-109 activity is rapid and dependent on concentration.

Rapid Killing Of Pathogens
LTX-109 acting on Staphylococcus aureus bacteria; Live (green) and dead (red). Time lapsing in minutes