omiganan (CLS001) / Maruho - LARVOL DELTA

A first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy. (PubMed, Cell Rep Med) - "A first-in-human investigator-initiated clinical study of a corneal endothelial cell substitute (CLS001) derived from a clinical-grade induced pluripotent stem cell (iPSC) line shows improvement of visual acuity and corneal stromal edema, with no adverse events for up to 1 year after surgery for the treatment of bullous keratopathy...Our study demonstrates the feasibility of using iPSC-derived cells to replace donor transplant for bullous keratopathy, while shedding light on risk management of gene mutation in cell products. Further follow-up is required for long-term analysis of clinical safety and efficacy."

Journal • P1 data • Oncology • Ophthalmology • Transplantation • EP300

Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis. (PubMed, ACS Biomater Sci Eng) - "Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis."

Journal • Hematological Disorders • Infectious Disease • Ocular Infections • Ocular Inflammation • Ophthalmology

Antibacterial and Hemolytic Activity of Antimicrobial Hydrogels Utilizing Immobilized Antimicrobial Peptides. (PubMed, Int J Mol Sci) - "Two previously well-studied AMPs, Piscidin 1 and Omiganan, were also included as comparisons...Additionally, all the AMPs showed varying degrees of hemolytic activity when in solution. This activity was entirely diminished, and all the AMPs were non-hemolytic when attached to the hydrogels."

Journal • Infectious Disease

The Study of Antistaphylococcal Potential of Omiganan and Retro-Omiganan Under Flow Conditions. (PubMed, Probiotics Antimicrob Proteins) - "We found out that retro-omiganan trifluoroacetate had the highest biofilm inhibitory properties, however, acetates of both compounds exhibited the highest activity against planktonic and biofilm cultures. Moreover, the developed methodology of investigation under flow conditions allows the implementation of the studies under flow conditions to other compounds."

Journal • Infectious Disease

An infection-microenvironment-targeted and responsive peptide-drug nanosystem for sepsis emergency by suppressing infection and inflammation. (PubMed, Asian J Pharm Sci) - "The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid (HA). In multiple tissue infection and sepsis animal models, Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction, thereby preventing subsequent fatal complications and significantly improving survival outcomes. The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies."

Journal • Infectious Disease • Inflammation • Septic Shock • ICAM1

Ceragenins exhibit bactericidal properties that are independent of the ionic strength in the environment mimicking cystic fibrosis sputum. (PubMed, Front Microbiol) - "CF-associated bacterial (Pseudomonas aeruginosa, Ochrobactrum spp., and Staphylococcus aureus), and fungal pathogens (Candida albicans, and Candida tropicalis) were used as target organisms for ceragenins (CSA-13 and CSA-131) and AMPs (LL-37 and omiganan). Our results demonstrated that ceragenins exhibit potent antimicrobial activity in CF sputum regardless of the NaCl concentration when compared to LL-37 and omiganan. Given the broad-spectrum antimicrobial activity of ceragenins in the microenvironments mimicking the airways of CF patients, ceragenins might be promising agents in managing CF disease."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial. (PubMed, Int J Mol Sci) - "Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action."

Journal • Dermatitis • Dermatology • Immunology • Inflammation • Seborrheic Dermatitis

Rational design of stapled antimicrobial peptides. (PubMed, Amino Acids) - P3 | "Antimicrobial peptides under clinical trial: Pexiganan (NCT01594762, 2012-05-07). Omiganan (NCT02576847, 2015-10-13)."

Journal • Review • Infectious Disease

"Cellusion and Minaris Regenerative Medicine, a member of Showa Denko Materials, Enter into Business Alliance for the Manufacturing of CLS001 for a Corneal Endothelial Cell Regenerative Therapy https://t.co/da19h63Y1Q" (@NewsFromBW)

Liposomes encapsulating novel antimicrobial peptide Omiganan: characterization and its pharmacodynamic evaluation in atopic dermatitis and psoriasis mice model. (PubMed, Int J Pharm) - "A substantial reduction in levels of pro-inflammatory cytokines and improvement in AD and psoriatic lesions were achieved by Omiganan liposomal gel compared to Omiganan gel and lotion-based formulations. The present study confirms that Omiganan liposomal formulation can be an effective, safe, and novel alternative treatment approach in atopic dermatitis and psoriasis."

Journal • PK/PD data • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Psoriasis

Cellusion Inc. (BIO 2022) - "The investigator-initiated clinical study of CLS001 is about to start in Keio university hospital soon. Besides, Cellusion has several pipelines focusing on not only ophthalmologic diseases, but also beyond ophthalmologic diseases."

Ophthalmology • Transplantation

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections. (PubMed, Antibiotics (Basel)) - "Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy."

Journal • Candidiasis • Infectious Disease • Vaginitis

Anticandidal Activity of Omiganan and Its Retro Analog Alone and in Combination with Fluconazole. (PubMed, Probiotics Antimicrob Proteins) - "The AMPs appeared to be effective against C. albicans biofilm, and the reversion of the sequence generally led to an improved antimicrobial activity. Furthermore, confocal and scanning electron microscopic visualizations revealed the effectiveness of AMPs-fluconazole combinations also against fluconazole-resistant strains."

Combination therapy • Journal • Candidiasis • Vaginitis

Topical anti-microbial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild-to-moderate atopic dermatitis in a phase 2 randomized controlled trial. (PubMed, J Am Acad Dermatol) - "Topical administration of omiganan twice daily for up to 28 days in patients with mild-to-moderate AD led to a recovery of dysbiosis, but without clinical improvement. Therefore, a mono-treatment that selectively targets the microbiome does not appear to be a successful treatment strategy in mild-to-moderate AD."

Clinical • Journal • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Host genetics and tumor environment determine the functional impact of neutrophils in mouse tumor models. (PubMed, J Immunother Cancer) - "Neutrophil functionality differs strongly between mouse strains and tumor types, with consequences for tumor progression and therapy."

Journal • Oncology

Study to Evaluate the Safety and Efficacy of a Once-Daily CLS001 Topical Gel Versus Vehicle (clinicaltrials.gov) - P3; N=263; Completed; Sponsor: Cutanea Life Sciences, Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar

Pharmacodynamics, Safety and Efficacy of Topical Omiganan in Patients With External Genital Warts (clinicaltrials.gov) - P2; N=24; Completed; Sponsor: Cutanea Life Sciences, Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar

Safety and Efficacy Study of CLS001Topical Gel Compared to Vehicle in Subjects With Inflammatory Acne Vulgaris (clinicaltrials.gov) - P2; N=327; Completed; Sponsor: Cutanea Life Sciences, Inc.; Active, not recruiting -> Completed

Trial completion • Biosimilar • Immunology • Inflammation

Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll-Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells. (PubMed, Clin Transl Sci) - "Based on this type I interferon-enhancing effect, omiganan may qualify as potential treatment modality for virus-driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated."

Journal • Immune Modulation • Immunology • Inflammation

Pharmacodynamic effects of topical omiganan in patients with mild to moderate atopic dermatitis in a randomized placebo-controlled phase II trial. (PubMed, Clin Transl Sci) - "In conclusion, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis and small but statistically significant improvement of clinical scores were detected. Our findings warrant further exploration in future clinical trials."

Clinical • Journal • P2 data • PK/PD data • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Inflammation

Omiganan enhances imiquimod-induced inflammatory responses in skin of healthy volunteers. (PubMed, Clin Transl Sci) - "IRF- and NFκB-driven responses following TLR7 stimulation were enhanced by omiganan (increases in IL-6, IL-10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+ and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/omiganan combination therapy in HPV-induced skin diseases."

Clinical • Journal • CD14 • IL10 • IL6

From pathogenesis of acne vulgaris to anti-acne agents. (PubMed, Arch Dermatol Res) - "Commonly used anti-acne agents include retinoids, benzoyl peroxide, antibiotics and hormonal agents (e.g. spironolactone, combination oral contraceptive and flutamide). New approaches including peroxisome proliferator-activated receptor γ modifier, melanocortin receptor antagonists, epigallocatechin-3-gallate, metformin, olumacostat glasaretil, stearoyl-CoA desaturase inhibitor omiganan pentahydrochloride, KPT, afamelanotide, apremilast and biologics have been developed as promising treatments for acne vulgaris. Although these anti-acne agents have various pharmacological effects against the diverse pathogenesis of acne, all of them have a synergistic mode of action, the attenuation of Akt/mTORC1 signaling and enhancement of p53 signal transduction. In addition to drug therapy, diet with no hyperglycemic carbohydrates, no milk and dairy products is also beneficial for treatment of acne."

Journal • Review

Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions. (PubMed, Br J Clin Pharmacol) - "Topical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced HPV load after 12 weeks of treatment in AGW patients."

Clinical • Journal • P2 data

Antimicrobial Activity of Selected Antimicrobial Peptides Against Planktonic Culture and Biofilm of Acinetobacter baumannii. (PubMed, Probiotics Antimicrob Proteins) - "In this study, eight AMPs, namely aurein 1.2, CAMEL, citropin 1.1., LL-37, omiganan, r-omiganan, pexiganan, and temporin A, were tested for their antimicrobial activity. Considering the fact that the majority of A. baumannii infections are associated with mechanical ventilation and the use of indwelling devices, the activity against biofilm was assessed on both a polystyrene surface and tracheal tube fragments. In addition, cytotoxicity (HaCaT) was determined and in vitro selectivity index was calculated."

Journal • Preclinical

Omiganan Twice a Day (BID) in Patients With Facial Seborrheic Dermatitis (clinicaltrials.gov) - P2; N=36; Recruiting; Sponsor: Cutanea Life Sciences, Inc.; Trial completion date: Jun 2019 ➔ Dec 2019; Trial primary completion date: May 2019 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date