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Antimicrobial, endotoxine-neutralizing and anti-inflammatory agent for wound healing and treatment of bacterial skin and soft-tissue infections

Reference Number TO 14-00097

Challenge

Severe bacterial infections represent an ever-increasing threat worldwide, which is aggravated by the continued appearance of multi-resistant bacteria and the lack of efficious antidotes. This applies not only for systemic, but also non-systemic infections like COPD and severe skin and soft-tissue infections (SSTI), which are not necessarily life-threatening, but still significantly impact a patient's quality of life. Non-systemic bacterial infections causing chronic inflammations do represent a particular challenge for public health systems, emphasizing the urgent need for new therapeutic treatment options.

Antimicrobial, endotoxine-neutralizing and anti-inflammatory agent for wound healing and treatment of bacterial skin and soft-tissue infections

Healing attempt: wound before and after daily treatment w/ Pep19-2.5

Technology

Recent studies convincingly showed that Pep19-2.5 (Aspidasept), a synthetic antimicrobial, anti-inflammatory and endotoxin-neutralizing peptide, efficiently neutralizes pathogenicity factors of Gram-negative and Gram-positive bacteria and protects against sepsis. An international group of scientist led demonstrated the potential of Pep19-2.5 and the structurally related compound Pep19-4LF for their therapeutic use in wound healing, against SSTI and even atopic dermatitis (AD).

Commercial Opportunity

Proprietary peptides and compositions are available for in-licensing and/or co-development.

Development Status

Pep19-2.5 and Pep19-4LF are the result of nearly 20 years of research. Both compounds possess antimicrobial and anti-inflammatory activity and are capable of efficiently neutralizing bacterial endotoxins. Pep19-2.5 has been successfully tested (e.g. in various animal models) regarding its therapeutic use against sepsis. In this context, also the compound's general tolerability was proven.
The possible use of Pep19-2.5 and Pep19-4LF in wound healing, against SSTI and Atopic Dermantitis has been comprehensively tested in vitro, ex vivo, as well as in the context of individual healing attempts.
Both compounds inhibit the bacterial endotoxin-induced maturation and migration of monocyte-derived dendritic cells (MoDCs), thereby prevending sustained and excessive inflammatory responses, which otherwise contribute to chronic inflammation and delayed wound healing. In TLR2/6-activated keratinocytes, the peptides considerably reduced the release of IL-8, a key pro-inflammatory mediator. In a scratch assay, they markedly promoted cell migration and accelerated artificial wound closure at concentrations as low as 1 ng/ml (= equipotent to TGF-β).
Four healing attempts have been successfully conducted on patients, suffering from Atoptic Dermatitis, an open wound after radiation therapy as well as inflammations of skin or mucous membranes, using a daily topical application of Pep19-2.5 (either 0,1% or 1% in DAC base cream).

Patent Situation

The proprietary compounds are subject of patent (WO 2009/124721), which has been granted in EP, JP and US.
Particular compositions and formulations of SALPs, as well as their use for treatment of e.g. non-systemic infections are covered by separate patent application WO 2017/140770. Applications are pending in EP, JP and US.

Further Reading

Martin et al. (2015) Peptide 19-2.5 inhibits heparan sulfate-triggered Inflammation in murine cardiomyocytes stimulated with human sepsis serum. PlosOne 10:e0127584
Pfalzgraff et al. (2016) Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune repsonses in skin cells and promote keratinocyte migration. Sci Rep 6:31577
Martin et al. (2016) The synthetic antimicrobial peptide 19-2,5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis. Sci Rep 6:37277
Pfalzgraff et al. (2018) Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds. Front Pharmacol 9: 281
Kuhlmann et al. (2018) Peptide drug stability: The anti-inflammatory drugs Pep19-2.5 and Pep19-4LF in cream formulation. Eur J Pharm Sci 115: doi 10.1016