Medical Application

Our drug candidate "HY-133" has been specifically designed to meet previously unachievable requirements for a therapeutic for decolonization.

Applications

Our drug candidate "HY-133" has been specifically designed to meet previously unachievable requirements for a therapeutic for decolonization.

Clinical studies indicate that nosocomial infections caused by Staphylococcus aureus (S. aureus) such as respiratory related pneumonia, bacteremia and sepsis or wound and implant infections are triggered by those bacterial strains that colonize the nose of the patient temporarily or permanently. For this reason, it is necessary to provide appropriate risk persons e.g. under multi-day use of antibiotics-containing creams to decolonize from those bacterial strains. Our drug candidate „HY-133“ has been specifically designed to meet previously unachievable requirements for a therapeutic for decolonization: a) High efficiency and rapid bactericidal action in less than 24 hours, b) Efficacy against resistant strains and even no resistance building, c) High specificity for S. aureus (both methicillin-sensitive and methicillin-resistant strains) without affecting the physiological bacterial flora.

The content and purpose of a collaboration with academic partners is the GMP-compliant production of gram-range HY-133.

The subsequent formulation as a hydrogel for use in the human nose via applicator, and the control of the tolerability, immunogenicity and efficacy of HY-133 in healthy volunteers with known S. aureus colonization. As part of the project, efficacy studies with phage lysine are carried out both in vitro and in vivo in order to evaluate efficacy in dependence of time and dose.

What HYpharm already has achieved together with its collaboration partners: After optimizing the drug concentration in vitro, two different treatment regimens were tested in the animal model.As an alternative to the animal model, experiments were carried out with human skin models, which gave excellent results. The concentration of 1 mg / ml HY-133 resulted in complete elimination of S. aureus within 30 min in all cases. The concentration of 0.1 mg / ml showed small numbers of surviving bacteria in individual samples of the test series both after 30 min and after 2 h. From these data, it can be outlined that a concentration above 0.1 mg / ml should be efficient for complete eradication of S. aureus within 30 min. Optimization on the formulation of the hydrogel in terms of stability were carried out by varying the storage buffer. In the existing formulation, the drug is released with delay in order to allow a longer term decolonization.

The development of highly selective decolonizing lysine represents a major advance in drug development. The goal is the selective removal of pathobionts without affecting the normal flora.

  • HYpharm_iconHYpharm_icon
    Pipeline Prevention: Use as prophylaxis to reduce S. aureus infections in patients receiving haemodialysis or continuous ambulatory peritoneal dialysis treatment.
  • HYpharm_iconHYpharm_icon
    Product: Nasal ointment for the elimination of nasal carriage of staphylococci, including methicillin resistant Staphylococcus aureus (MRSA).
  • HYpharm_iconHYpharm_icon
    Publications

Publications

The Advantages and Challenges of Using Endolysins in a Clinical Setting.
Ellen Murray,Lorraine A. Draper,R. Paul Ross and Colin Hill Viruses 2021, 13(4), 680; https://doi.org/10.3390/v13040680

Exploration of Bacterial Re-Growth as In Vitro Phenomenon Affecting Methods for Analysis of the Antimicrobial Activity of Chimeric Bacteriophage Endolysins.
Kaspar U, Schleimer N, Idelevich EA ,Molinaro S, Becker K Microorganisms. 2022 Feb 15;10(2):445. doi: 10.3390/microorganisms10020445.

Comparative in vitro activity of bacteriophage endolysin HY-133 against Staphylococcus aureus attached to vascular graft surface.
Idelevich EA, Knaack D, Nugroho NT, Peters G, Bisdas T, Molinaro S, Torsello GB, Becker K, Herten M. Med Microbiol Immunol. 2019 Oct 17. doi: 10.1007/s00430-019-00638-1.

Bactericidal activity of bacteriophage endolysin HY-133 against Staphylococcus aureus in comparison to other antibiotics as determined by minimum bactericidal concentrations and time-kill analysis.
Knaack D, Idelevich EA, Schleimer N, Molinaro S, Kriegeskorte A, Peters G, Becker K.
Diagn Microbiol Infect Dis. 2019 Apr;93(4):362-368. doi: 10.1016/j.diagmicrobio.2018.11.005. Epub 2018 Nov 20.

In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types.
Schleimer N, Kaspar U, Knaack D, von Eiff C, Molinaro S, Grallert H, Idelevich EA, Becker K. Int J Mol Sci. 2019 Feb 7;20(3). pii: E716. doi: 10.3390/ijms20030716.

The Novel Phage-Derived Antimicrobial Agent HY-133 Is Active against Livestock-Associated Methicillin-Resistant Staphylococcus aureus.
Kaspar U, de Haro Sautto JA, Molinaro S, Peters G, Idelevich EA, Becker K. Antimicrob Agents Chemother. 2018 Jun 26;62(7). pii: e00385-18. doi: 10.1128/AAC.00385-18. Pr

Combination of endolysins and high pressure to inactivate Listeria monocytogenes.
van Nassau TJ, Lenz CA, Scherzinger AS, Vogel RF. Food Microbiol. 2017 Dec;68:81-88. doi: 10.1016/j.fm.2017.06.005. Epub 2017 Jun 8.

Vascular Graft Impregnation with Antibiotics: The Influence of High Concentrations of Rifampin, Vancomycin, Daptomycin, and Bacteriophage Endolysin HY-133 on Viability of Vascular Cells.
Herten M, Idelevich EA, Sielker S, Becker K, Scherzinger AS, Osada N, Torsello GB, Bisdas T. Med Sci Monit Basic Res. 2017 Jun 27;23:250-257.

The Recombinant Bacteriophage Endolysin HY-133 Exhibits In Vitro Activity against Different African Clonal Lineages of the Staphylococcus aureus Complex, Including Staphylococcus schweitzeri.
Idelevich EA, Schaumburg F, Knaack D, Scherzinger AS, Mutter W, Peters G, Peschel A, Becker K. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2551-3. doi: 10.1128/AAC.02859-15. Print 2016 Apr.

In vitro activity against Staphylococcus aureus of a novel antimicrobial agent, PRF-119, a recombinant chimeric bacteriophage endolysin.
Idelevich EA, von Eiff C, Friedrich AW, Iannelli D, Xia G, Peters G, Peschel A, Wanninger I, Becker K. Antimicrob Agents Chemother. 2011 Sep;55(9):4416-9. doi: 10.1128/AAC.00217-11. Epub 2011 Jul 11.

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