Investigational study provides evidence that recombinant endolysin XZ.700* is a promising novel non-antibiotic treatment strategy aimed at controlling Staphylococcus aureus (S. aureus) colonization of lesional skin in Cutaneous T-cell lymphoma (CTCL).
(Adnkronos) - Research shows XZ.700* could block tumor promoting effects of S. aureus on malignant T cells, potentially delaying tumor progression.
Findings strengthen potential of Micreos' endolysin technology to address unmet patient needs in treating CTCL in the wake of devastating antimicrobial resistance.
ZUG, Switzerland, March 7, 2023 /PRNewswire/ -- Micreos is pleased to share the positive results of an investigational study: Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma, published in the Journal of Infectious Disease, 2023 (https://doi.org/10.1016/j.jid.2023.01.039). The study, led by Prof Niels Ødum, University of Copenhagen's Skin Immunology Research Centre, was undertaken to investigate the effect of endolysin (XZ.700*) on skin colonization, chemokine expression, proliferation of pathogenic S. aureus and possible tumor-blocking effects on malignant T cells.
Cutaneous T-cell lymphoma (CTCL) is a rare, debilitating form of skin cancer affecting T cells that are part of the immune system. S. aureus and staphylococcal enterotoxins (SE) have been suspected to fuel disease activity and cancer progression in CTCL through a direct stimulation of the malignant T cells1- 3. It has a profound impact on patients' quality of life due to its chronic nature and the fact that a considerable proportion of patients either have a poor response or no sustained response to current treatments4,5. CTCL is a rare disease with less than 200,000 patients in the US meaning that the indication qualifies for an Orphan Drug Designation6,7.
Niels Ødum, Professor at University of Copenhagen's Skin Immunology Research Centre, who has been working with Micreos to validate the approach of endolysin treatment in CTCL from a pre-clinical perspective said, "The results of this study are significant as they show the endolysin XZ.700* has the potential to improve outcomes for patients by targeting bacteria that are associated with CTCL disease activity and progression. Treating S. aureus with antibiotics is discouraged due to the associated risk of antibiotic resistance induction. Thus, there is an important medical need for new, specific, anti-staphylococcal alternatives such as XZ.700* that show no signs of resistance induction. This study showed that the endolysin XZ.700* profoundly inhibited skin colonization by S. aureus of both healthy skin and lesional CTCL skin. Importantly, we saw that this endolysin killed S. aureus after the S. aureus colonization had been established. This suggests that XZ.700* has potential in both an acute treatment-setting and as a prophylactic treatment."
XZ.700* has been developed by Micreos, a world-class endolysin platform company, as a topical treatment of the inflammatory skin symptoms associated with CTCL and for the reduction of disease activity in adult patients with CTCL. Studies have shown that aggressive antibiotic treatment inhibits proliferation of malignant T-cells and disease activity1. However, antibiotics are not a viable option for chronic use due to resistance development and the impact on the skin microbiome8. Research and development have been progressing swiftly and based on pre-clinical models Micreos has moved the development program from XZ.700* to the next generation endolysin namely, MEndoC.
"Micreos is committed to achieving a 'medical paradigm shift' in successfully treating life-threatening and disabling bacterial pathogen associated diseases where antibiotics cannot be used or are ineffective. XZ.700* was the first of many innovative endolysins in our development portfolio." Said Matt Regan, CEO of Micreos. "Prof Ødum's work has been incredibly important. Given the highly encouraging results, we are moving forward our research and development programme in CTCL with our 'next generation' endolysin MEndoC that has significantly higher intrinsic activity levels. This is extremely positive news as we move closer to our clinical trial program. We are working to make engineered endolysin-based treatments a clinical reality giving physicians the ability to specifically & selectively target harmful bacteria which play a significant role in diseases like CTCL, while preserving the rest of the Microbiome. This can provide an important & potentially viable solution to the global AMR crisis."
About Micreos
Micreos is a clinical-stage pharmaceutical biotech developing medicinal solutions to combat antimicrobial resistance and make a profound difference to humanity. With its unique capability in modular engineering to optimize enzyme therapeutics, Micreos is pioneering the development of antimicrobials that selectively kill only harmful bacteria whilst preserving the rest of the health-enhancing microbiome.
Micreos is focused on the challenges facing modern medicine in the 21st century by selecting and engineering biological alternatives to current antibiotics which are increasingly powerless to combat bacterial infections that play a significant role in disease, often beyond the primary infection. Current investigational treatments are being evaluated in three therapeutic areas that are caused or aggravated by pathogenic bacteria and where burgeoning antibiotic resistance is leaving patients with increasingly limited options: Cutaneous T-cell Lymphoma (CTCL), Atopic Dermatitis (AD) and Bacterial Bloodstream Infection (BBI).
www.micreos.com
About XZ.700
*About MEndoC
Based on pre-clinical models and increased intrinsic activity, Micreos has moved the development program in CTCL from XZ.700 to the next generation endolysin, namely MEndoC.
Endolysins and Micreos Technology
Endolysins are small organic structures originally used by bacteria-killing viruses, called bacteriophages. Endolysins work by attaching themselves to the outside of the bacteria. Once attached they break down bonds within the bacterial cell wall causing the bacteria to burst and die. Both of these steps require structures that are unique to both the endolysin and the target bacteria meaning that endolysins only attack and kill one type of bacteria.
Micreos employs a unique science-driven approach to engineer endolysins and bacteriophages into targeted antibacterial treatments, leveraging the high potential of both technologies for its proprietary products. Its molecules selectively target harmful bacteria - including antibiotic resistant strains - which cause and exacerbate acute and chronic illnesses. The natural bacteria of the microbiome, beneficial for our health, remain unaffected. Due to the unique mode of action of endolysins, the emergence of resistance is extremely unlikely.
Forward looking statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding expectations surrounding the potential of our product candidates, including our lead candidate XZ.700 (MEndoC) and expectations regarding our pipeline, including trial design, initiation of preclinical studies and advancement of multiple preclinical development programs. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future result. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
References
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