XZ-700 / Micreos - LARVOL DELTA

Phage-derived endolysin prevents dissemination of methicillin resistant Staphylococcus aureus during oral co-infection with Candida albicans. (PubMed, Antimicrob Agents Chemother) - "Taken together, the results presented here indicate that selective removal of MRSA from the oral cavity of mice with XZ.700 during co-infection with C. albicans is effective in preventing dissemination. Further studies need to show clinical applicability of XZ.700 and related compounds in prevention of sepsis in at-risk patients."

Journal • Infectious Disease • Septic Shock

S. aureus colonization and clinical symptoms remain stable upon topical XZ.700 treatment: Results of a double-blind randomized clinical trial in patients with mild to moderate atopic dermatitis. (PubMed, Br J Clin Pharmacol) - "Tolerability and safety of short-term topical administration of XZ.700 100 μg/g for 14 days were acceptable in most participants; however, some local application-site events occurred, and one hypersensitivity reaction led to discontinuation. XZ.700 did not demonstrate target engagement or clinical benefit vs. vehicle under the tested conditions."

Clinical • First-in-human • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Effect of endolysin XZ.700 on monocyte differentiation into osteoclasts and foreign body giant cells. (PubMed, Biochem Biophys Res Commun) - "Endolysin XZ.700 downregulated differentiation-related gene expression, but upregulated cytokine-related gene expression in monocytes differentiating into osteoclasts or foreign body giant cells. In conclusion, the biofilm-reducing agent endolysin XZ.700 decreases the formation of immunomodulatory cells, i.e. foreign body giant cells and osteoclasts, indicating that it might be highly promising as a novel antimicrobial, with short term administration as the safest mode of treatment."

Journal • Infectious Disease • Orthopedics • CD14

Selective depletion of S. aureus restores the skin microbiome and accelerates tissue repair following injury. (PubMed, J Invest Dermatol) - "Here we provide important data on the selectivity and efficacy of an S. aureus-targeted endolysin (XZ.700) within the complex living skin/wound microbiome...Subsequent mechanistic studies confirmed the importance of this microbiome modulation for effective healing in human skin. Taken together, these findings strongly support further development of S. aureus-targeted endolysins for future clinical management of skin and wound infections."

Journal • Infectious Disease

Staphylococcus aureus induce drug resistance in cancer T cells in Sézary Syndrome. (PubMed, Blood) - "Supernatant from patient-derived, SE-producing S. aureus and recombinant SE significantly inhibit cell death induced by HDAC inhibitor romidepsin in primary malignant T-cells from SS patients. Bacterial killing by engineered, bacteriophage-derived, S. aureus-specific endolysin (XZ.700) abrogates the effect of S. aureus supernatant...Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide)...Inversely, SE cannot rescue from cell death induced by proteasome/NFB inhibitor bortezomib...In conclusion, we show that S. aureus enterotoxins induce drug-resistance in primary malignant T-cells. These findings suggest that S. aureus enterotoxins cause clinical treatment-resistance in SS patients and that anti-bacterial measures may improve the outcome of cancer-directed therapy in patients harboring S. aureus."

Journal • Cutaneous T-cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma. (PubMed, J Invest Dermatol) - "Whereas patient-derived S. aureus stimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving non-malignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and STAT5 phosphorylation) and proliferation (reduced Ki67) of malignant T cells and cell lines in the presence of non-malignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureus, and blocks their potential tumor-promoting effects on malignant T cells."

Journal • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CXCL10 • IFNG • IL2RA • STAT5

Linker-Improved Chimeric Endolysin Selectively Kills Staphylococcus aureus In Vitro, on Reconstituted Human Epidermis, and in a Murine Model of Skin Infection. (PubMed, Antimicrob Agents Chemother) - "Furthermore, XZ.700 did not induce resistance in S. aureus during repeated rounds of exposure to sublethal concentrations. Finally, we demonstrated that XZ.700 formulated as a cream is effective at killing S. aureus on reconstituted human epidermis and that an XZ.700-containing gel significantly reduces bacterial numbers compared to an untreated control in a mouse model of S. aureus-induced skin infection."

Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Inflammation

The novel endolysin XZ.700 effectively treats MRSA biofilms in two biofilm models without showing toxicity on human bone cells in vitro. (PubMed, Biofouling) - "In comparison, PVP-I and gentamicin showed slower biofilm killing, with no apparent biofilm removal. In conclusion, XZ.700 reduced MRSA biofilms, especially under flow condition, without toxicity for surrounding bone cells."

Journal • Preclinical • Orthopedics

Phase update (PRNewswire) - P1➔P2, Atopic Dermatitis

Phase shift • Atopic Dermatitis

Micreos initiates clinical trial to evaluate world's first endolysin-drug as a therapy for Atopic Dermatitis (PRNewswire) - "Dutch biotech company Micreos Human Health has enrolled the first patients in a Phase I/IIa...study to assess the safety and efficacy of XZ.700 in patients with mild to moderate atopic dermatitis. The study marks the world's first evaluation of a pharmaceutical endolysin for topical use in humans."

Trial status • Atopic Dermatitis • Dermatology